Socioeconomic and Other Demographic Disparities Predicting Survival among Head and Neck Cancer Patients.
The Institute of Medicine (IOM) report, "Unequal Treatment," which defines disparities as racially based, indicates that disparities in cancer diagnosis and treatment are less clear. While a number of studies have acknowledged cancer disparities, they have limitations of retrospective nature, small sample sizes, inability to control for covariates, and measurement errors. The purpose of this study was to examine disparities as predictors of survival among newly diagnosed head and neck cancer patients recruited from 3 hospitals in Michigan, USA, while controlling for a number of covariates (health behaviors, medical comorbidities, and treatment modality). Longitudinal data were collected from newly diagnosed head and neck cancer patients (N = 634). The independent variables were median household income, education, race, age, sex, and marital status. The outcome variables were overall, cancer-specific, and disease-free survival censored at 5 years. Kaplan-Meier curves and univariate and multivariate Cox proportional hazards models were performed to examine demographic disparities in relation to survival. Five-year overall, cancer-specific, and disease-free survival were 65.4% (407/622), 76.4% (487/622), and 67.0% (427/622), respectively. Lower income (HR, 1.5; 95% CI, 1.1-2.0 for overall survival; HR, 1.4; 95% CI, 1.0-1.9 for cancer-specific survival), high school education or less (HR, 1.4; 95% CI, 1.1-1.9 for overall survival; HR, 1.4; 95% CI, 1.1-1.9 for cancer-specific survival), and older age in decades (HR, 1.4; 95% CI, 1.2-1.7 for overall survival; HR, 1.2; 95% CI, 1.1-1.4 for cancer-specific survival) decreased both overall and disease-free survival rates. A high school education or less (HR, 1.4; 95% CI, 1.0-2.1) and advanced age (HR, 1.3; 95% CI, 1.1-1.6) were significant independent predictors of poor cancer-specific survival. Low income, low education, and advanced age predicted poor survival while controlling for a number of covariates (health behaviors, medical comorbidities, and treatment modality). Recommendations from the Institute of Medicine's Report to reduce disparities need to be implemented in treating head and neck cancer patients.


Vascular anatomy of the spinal cord.
Knowledge of spinal cord vascular anatomy is essential to the neurosurgeon planning and undertaking procedures on vascular lesions of the spinal cord. This article relates general concepts and nomenclature regarding this unique circulation and describes the regional and segmental arterial and venous anatomy of the spinal cord. The article concludes with surgical considerations and recommendations based on this anatomy.


High throughput purification of combinatorial libraries.
This article summarizes recent advances at MDS Panlabs which provide for the high-throughput preparative HPLC purification of our Optiverse screening library. Topics covered include unique methods for the preparation, purification, characterization, and plating of purified screening compounds. Also discussed are procedures for data tracking as samples proceed through the purification process.


Control of the pars intermedia of the lizard, Anolis carolinensis. II. Ultrastructure of the intact intermediate lobe.
The ultrastructure of the intermediate lobe of the hypophysis was studied in Anolis carolinensis with the use of a threefold aldehyde fixative. Lizards with a brown skin were selected. The possibility of two types of secretory cells is discussed; neither cell type is innervated. Type I cells are rarely found and contain dense granules approximately 0.3 micron in diameter; Type II cells vary widely in secretory activity. Most of the Type II cells contain a large number of dense secretory granules (up to about 1.3 micron in diameter) almost filling the cytoplasm. Rough endoplasmic reticulum (RER), Golgi apparatus and mitochondria are poorly developed. Only some of these cells show signs suggesting a high secretory activity, namely a well developed RER, Golgi apparatus and numerous mitochondria. In these cells the RER sometimes forms large intracisternal droplets (up to 7 micron in diameter). Two of the animals exhibited a more uniform, high secretory activity. Large (about 2 micron in diameter), pale vacuoles, probably of extracellular character, were found mostly in the vicinity of the perivascular septum. Their role in the release of MSH is discussed. The present data, which are discussed with reference to earlier findings (Forbes, 1972), form the morphological basis for an experimental study on regulation of MSH release (Larsson et al., 1979).


Scaffold protein enigma homolog activates CREB whereas a short splice variant prevents CREB activation in cardiomyocytes.
Enigma Homolog (ENH1 or Pdlim5) is a scaffold protein composed of an N-terminal PDZ domain and three LIM domains at the C-terminal end. The enh gene encodes for several splice variants with opposing functions. ENH1 promotes cardiomyocytes hypertrophy whereas ENH splice variants lacking LIM domains prevent it. ENH1 interacts with various Protein Kinase C (PKC) isozymes and Protein Kinase D1 (PKD1). In addition, the binding of ENH1's LIM domains to PKC is sufficient to activate the kinase without stimulation. The downstream events of the ENH1-PKC/PKD1 complex remain unknown. PKC and PKD1 are known to phosphorylate the transcription factor cAMP-response element binding protein (CREB). We tested whether ENH1 could play a role in the activation of CREB. We found that, in neonatal rat ventricular cardiomyocytes, ENH1 interacts with CREB, is necessary for the phosphorylation of CREB at ser133, and the activation of CREB-dependent transcription. On the contrary, the overexpression of ENH3, a LIM-less splice variant, inhibited the phosphorylation of CREB. ENH3 overexpression or shRNA knockdown of ENH1 prevented the CREB-dependent transcription. Our results thus suggest that ENH1 plays an essential role in CREB's activation and dependent transcription in cardiomyocytes. At the opposite, ENH3 prevents the CREB transcriptional activity. In conclusion, these results provide a first molecular explanation to the opposing functions of ENH splice variants.


[Palatine clefts following puncture of the amniotic sac in the rat].
1) Amniotic sac puncture is a reliable procedure for induction of a cleft palate in rat foetuses 15 days old. 2) This possibility persists during the first hours of day 16. 3) When applied to rats after 16 days 12 hours of pregnancy, amniocentesis does't induce a cleft palate. 4) Treatment during this critical stage of pregnancy with substances able to reduce the amniotic fluid volume, such as acetazolamide and hydrocortisone, doesn't produce cleft palate.


Improved health-related quality of life in patients 6 and 12 months after surgical aortic valve replacement.
Objectives. Quality of life (QoL) is possibly the most important variable for the patient when subjective results of heart procedures are evaluated. The purpose of this study was to analyze the change in the quality of life 1 year after surgical aortic valve replacement (SAVR). Design. A Finnish single-center prospective cohort intervention study was performed from 2013 to 2018. QoL was assessed with the EQ-5D-3L VAS questionnaire before surgery and 6 and 12 months after surgery. We used univariate analysis to assess the change in the number of people experiencing problems and logistic regression analysis to assess the patients' characteristics on the change in QoL. Results. At one year follow-up, patients' quality of life improved in all EQ-5D dimensions. The greatest decreases in patients experiencing problems 12 months after surgery occurred in the dimension "mobility" (-24.1% change in reporting problems, p < .01), "self-care" (-32.9%, p < .01), and "pain or discomfort" (-25.7%, p < .01). Before surgery mean of EQ visual analogue scale (VAS, from 0 to 100) was 63.0 (SD 17.7, n = 604), and 12 months after surgery 81.2 (SD 13.8, n = 367, p < .001). In multivariable analysis, preoperative obesity was associated with better quality of life (OR 3.39, 95% CI 1.007-11.439) in "daily activities" and patients' higher operative risk was associated with better "self-care" after surgery. Conclusions. SAVR can improve the 1-year quality of life in all dimensions of EQ-5D and self-rated overall health (VAS).


[Changes in glutamate dehydrogenase activity in the neurons of the motor cortexof the cerebral hemispheres during light deprivation].
It has been shown that early light deprivation (keeping the rats for eight weeks from birth in a dark chamber) produces compensatory changes in the majority of pyramidal neurones in layers III and V of the brain motor area: significant enhancement of glutamatdehydrogenase activity activity in the bodies and processes of the neurones, increase of their volumes, augmentation of the number of neuroglial satellites with a high ferment activity. The revealed morphochemical changes, more pronounced in the layer V, are considered as a manifestation of enhanced functional activity of the coritcal end of the motor analyser, resulting from visual dereceptation.


Responses of atrial mechanoreceptors to pulsation of atrial volume.
1. Firing patterns of single atrial fibres were monitored in order to study their sensitivity to rate of change of atrial volume and their dependence on receptor location in the atria.2. To that effect, sinusoidal fluctuations of volume (+/-1 ml.; 60/min) were superimposed on the natural pulsations of the heart of spontaneously breathing anaesthetized cats.3. Stimulus-response histograms revealed that maximal firing frequency of B-impulses preceded maximal volume change by 10-80 degrees (average 48+/-7 degrees (S.E.), thirteen right and left atrial receptors) indicating that sensitivity to rate of change of atrial volume at least equalled volume sensitivity.4. The rate sensitive component of B-firing increased with respect to the volume sensitive component when atrial filling diminished and was larger for high threshold receptors than for low threshold receptors (P<0.001).5. The A-bursts were not affected by atrial pulsing in eight out of nine anatomically localized receptors; inspiration prolonged the A-bursts of three receptors and advanced the timing of A-bursts with respect to the a-wave (10-50 msec) of all nine receptors.6. About half of all anatomically localized receptors were traced to the interatrial septum. These septal receptors differed from right and left atrial receptors as follows: (a) they were exclusively of the AB-type (fired during atrial a- and v-wave); (b) their B-firing rates were significantly lower (P<0.05); (c) A-firing patterns remained largely unaffected by respiration or by atrial pulsing; (d) they signalled volume changes of either atria; (e) no association of rate sensitivity with threshold was detected (P>0.95). The physiological role of septal receptors remains to be elucidated.7. It was concluded that B-fibres were sensitive to both change and rate of change of atrial volume; their role as sensors of venous return is suggested strongly. Results further suggested that A- and B-firing are determined largely by the location of atrial stretch receptors.


Shared and distinct factors driving attention and temporal processing across modalities.
In addition to the classic finding that "sounds are judged longer than lights," the timing of auditory stimuli is often more precise and accurate than is the timing of visual stimuli. In cognitive models of temporal processing, these modality differences are explained by positing that auditory stimuli more automatically capture and hold attention, more efficiently closing an attentional switch that allows the accumulation of pulses marking the passage of time (Penney, Gibbon, & Meck, 2000). However, attention is a multifaceted construct, and there has been little attempt to determine which aspects of attention may be related to modality effects. We used visual and auditory versions of the Continuous Temporal Expectancy Task (CTET; O'Connell et al., 2009) a timing task previously linked to behavioral and electrophysiological measures of mind-wandering and attention lapses, and tested participants with or without the presence of a video distractor. Performance in the auditory condition was generally superior to that in the visual condition, replicating standard results in the timing literature. The auditory modality was also less affected by declines in sustained attention indexed by declines in performance over time. In contrast, distraction had an equivalent impact on performance in the two modalities. Analysis of individual differences in performance revealed further differences between the two modalities: Poor performance in the auditory condition was primarily related to boredom whereas poor performance in the visual condition was primarily related to distractibility. These results suggest that: 1) challenges to different aspects of attention reveal both modality-specific and nonspecific effects on temporal processing, and 2) different factors drive individual differences when testing across modalities.


[Vein surgery, functional investigation, surveying equipment (author's transl)].
The different physical screening tests (ultrasound-Doppler technique, plethysmography, phlebodynamometry) are easily documented and provide a less dangerous, less expensive, and more comprehensive statement about the venous hemodynamics of the lower extremity. The number of diagnostic errors can be minimized, and the indication for operation is reliable.


[Cell wall permeability and export of proteins into the culture broth of Saccharomyces cerevisiae].
The upper limit of Saccharomyces cerevisiae cell wall permeability is such that only molecules with a mass not greater than 2-3 kDa can pass across the cell wall. However, proteins with a much higher molecular mass are exported into the cultural broth when the organism is cultivated in a liquid medium with peptone. Under certain conditions, exogenous proteins interact with the cytoplasmic membrane. These as well as some other findings imply that the cell wall may have microplots with an anomalous permeability, via which the regulated exchange of macromolecules is realized between the intracellular and outer media.


The KTR and MNN1 mannosyltransferase families of Saccharomyces cerevisiae.
Glycosylation constitutes one of the most important of all the post-translational modifications and may have numerous effects on the function, structure, physical properties and targeting of particular proteins. Eukaryotic glycan structures are progressively elaborated in the secretory pathway. Following the addition of a core N-linked carbohydrate in the endoplasmic reticulum, glycoproteins move to the Golgi complex where the elongation of O-linked sugar chains and processing of complex N-linked oligosaccharide structures take place. In order to better define how such post-translational modifications occur, we have been studying the yeast KTR and MNN1 mannosyltransferase gene families. The KTR family contains nine members: KRE2, YUR1, KTR1, KTR2, KTR3, KTR4, KTR5, KTR6 and KTR7. The MNN1 family contains six members: MNN1, TTP1, YGL257c, YNR059w, YIL014w and YJL86w. In this review, we address protein structure, sequence similarities and enzymatic activity in the context of each gene family. In addition, a description of the known function of many family members in O- and N-linked glycosylation is included. Finally, the genetic interactions and functional redundancies within a gene family are also discussed.


Regulation of follistatin messenger ribonucleic acid in cultured rat granulosa cells.
The regulation of the follistatin mRNA by hormones and endocrine manipulations was examined in granulosa cell cultures. The follistatin mRNA accumulation was stimulated in a dose-dependent manner by follicle-stimulating hormone (FSH) with a maximal response twice as great as in control cultures at a dose of 100 ng/ml FSH. The time course of the FSH effect on follistatin mRNA had a biphasic effect in which FSH increased follistatin mRNA within 2 h, and subsequently reduced it to below the control level. 8-Br-8 brom-adenosine 3,5-cyclic monophosphate (cAMP) (2 mM) and phorbol 12-myristate 13-acetate (PMA) (10 nm) induced a time-dependent increase in follistatin mRNA levels, with the maximal response at 6 h and 2 h, respectively. Co-treatment of the granulosa cells with cAMP and PMA demonstrated that 0.2 mM of 8-Br-cAMP suppressed the follistatin mRNA of the control and the samples with a small amount of PMA in the granulosa cells. Follistatin expression is therefore regulated by protein kinase A and protein kinase C pathways in rat granulosa cells. A more dramatic stimulation of follistatin mRNA was observed when this culture was treated with activin, and follistatin also blocked the effect of activin on the follistatin mRNA.


Spinal dural arteriovenous fistula adjacent to a spinal neurofibroma--a misleading coexistence. Case report.
The authors report the case of a patient harbouring a spinal dural arteriovenous fistula adjacent to an intradural neurofibroma. Only the latter could be demonstrated by the diagnostic modalities employed. Such a coexistence proved misleading and two interventions were needed to cure both lesions. Only one report has appeared in the literature dealing with such a condition. The possibility of such a coexistence is stressed and mechanisms are discussed.


Exploring doctors' trade-offs between management, research and clinical training in the medical curriculum: a protocol for a discrete choice experiment in Southern Africa.
Medical curricula should prepare doctors for roles that extend beyond that of a clinician. But the formal inclusion of both management and research training still appear to be neglected. It is important to understand what the profession would be willing to give up in terms of clinical training time for management and research content teaching prior to making any changes in a medical curriculum. A discrete choice experiment will elicit the preferences and trade-offs that medical doctors in Southern Africa are prepared to make about the management, research and clinical training. Attention will also be given to the teaching method and placement of the content. DCE data will be collected using an online survey with an estimated sample size of 368 medical doctors. Data regarding participants' preference for a traditional or revised curriculum will be assessed using the Resistance to Change-Beliefs (RC-B) scale and demographic information will also be collected to assess preference heterogeneity.Analysis of the DCE data will be based on the Random Utility Maximisation framework using variants of the multinomial logit model. Data quality will be assessed. Value will be estimated in terms of clinical time, that is, how much clinical training time medical doctors are willing to give up to have research and management training within a curriculum that has a maximum of 40 hours per week. Observed preference heterogeneity will be assessed using the RC-B scale data and characteristics of respondents. Latent class models will be used to test for unobserved heterogeneity. The research ethics and institutional committees of the sites have approved the study. The survey includes an informed consent section. Study findings will be reported to the medical schools and papers will be submitted to peer-reviewed, accredited journals and higher education and health economic conferences.


Acid-mediated ring-expansion reaction of N-aryl-2-vinylazetidines: synthesis and unanticipated reactivity of tetrahydrobenzazocines.
The aza-Clasen rearrangement of N-aryl-2-vinylazetidines has been explored. N-Aryl-2-vinylazetidines were transformed to corresponding tetrahydrobenzazocines in good yields. Unexpectedly, the tetrahydrobenzazocine was unstable and readily isomerized to vinyltetrahydroquinoline in the presence of acid. The mechanism of this ring contraction was studied in detail.


Effect of education based on the "4A Model" on the Iranian nurses' moral distress in CCU wards.
Complexity of health care has caused ethical dilemmas and moral distress to be quite unavoidable for nurses. Moral distress is a major, highly prevalent problem in the nursing profession. The study aims to investigate the effect of education based on the "4A model" on the rate of moral distress among the nurses working in Cardiac Care Units (CCU). The participants consisted of 60 nurses working in Cardiac Care Units (CCU), 30 in the control and 30 in the intervention group. Those in the intervention group took part in the educational workshop about "moral distress" and "4A model". The moral distress questionnaire was completed by both study groups 1 and 2 months after the intervention. After the intervention, the results of repeated measures analysis of variance revealed a significant difference in the moral distress mean scores between the intervention and the control groups (P<0.001) and within the two groups (P<0.001). Moreover, a significant difference was found between the two study groups regarding the mean score of moral distress 1 and 2 months after the intervention. The findings of the current study revealed a decreasing trend in the moral distress mean score in the intervention group, while there was an increasing trend in the control group after the intervention. It can be concluded that the "4A model" can be used for reducing moral distress and educational interventions can reduce the rate of moral distress among nurses. Authors of this study recommend that more studies with larger sample sizes be conducted in different hospital wards as well.


Traditional Chinese medicine formula Xiaoqinglong decoction for cough caused by COVID-19: A protocol for a systematic review and meta-analysis.
Assessing the effectiveness and safety of Traditional Chinese medicine formula Xiaoqinglong decoction for cough caused by COVID-19 is the main purpose of this systematic review protocol. The following electronic databases will be searched from their respective inception dates to October 1, 2020: PubMed, MEDLINE, the Cochrane Library, Embase, WorldSciNet, Ovid, the Allied and Complementary Medicine Database, the Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database (VIP), the Wanfang Database, and the China Biology Medicine Disc. All published randomized controlled trials in English or Chinese related to Traditional Chinese medicine formula Xiaoqinglong decoction for cough caused by COVID-19 will be included. The primary outcome is the time and rate of appearance of coughing. The secondary outcomes are the length of hospital stay. Two reviewers will conduct the study selection, data extraction, and assessment independently. The assessment of risk of bias and data synthesis will be conducted with RevMan V.5.2. The results will provide a high-quality synthesis of current evidence for researchers in this subject area. The conclusion of our study will provide an evidence to judge whether traditional Chinese medicine formula Xiaoqinglong decoction is an effective intervention for patients with cough caused by COVID-19. Formal ethical approval is not necessary as the data cannot be individualized. The results of this protocol will be disseminated in a peer-reviewed journal or presented at relevant conferences. CRD42020202079.


Collagen modifications.
Collagen, the major structural protein found in all animal tissues, has a variety of uses in the armamentarium of the plastic surgeon. This article discusses the biologic characteristics of collagen that determine its behavior as an implant material. Clinical applications discussed include hemostatic collagen fleece, collagen sponge wound dressing, composite tissue tendon allografts, injectable collagen, and manipulation of scar collagen.


Androgen deprivation therapy and the risk of death from prostate cancer among men with favorable or unfavorable intermediate-risk disease.
Radiotherapy (RT), short-course androgen deprivation therapy (ADT), and brachytherapy in various combinations are treatment options for patients with intermediate-risk prostate cancer (PC), but the question of which combination if any is necessary to minimize PC-specific mortality (PCSM) risk in patients with favorable or unfavorable intermediate-risk PC is unknown. The authors assessed PCSM risk after commonly used treatments. The cohort consisted of 2510 men with favorable (1902 men; 75.78%) or unfavorable (608 men; 24.22%) intermediate-risk PC who were treated from 1997 to 2013. Treatment included brachytherapy with or without neoadjuvant ADT among men with favorable disease and brachytherapy with neoadjuvant RT or ADT among men with unfavorable disease. Fine and Gray's competing-risks regression model was used to assess whether ADT among men with favorable disease or RT or ADT among men with unfavorable disease decreased PCSM risk after adjusting for treatment propensity score, year of brachytherapy, and PC prognostic factors. After a median follow-up of 7.78 years, 366 deaths (14.58%) were observed, 29 of which (7.92%) were from PC. There was a significant reduction in PCSM risk in men with unfavorable disease who were treated with ADT versus RT (adjusted hazard ratio, 0.34; 95% confidence interval, 0.13-0.91 [P = .03]), but no significant difference in PCSM risk in men with favorable disease who received ADT and brachytherapy versus brachytherapy (adjusted hazard ratio, 0.67; 95% confidence interval, 0.18-2.57 [P =.56]). Neoadjuvant ADT does not appear to reduce PCSM risk in men undergoing brachytherapy for favorable intermediate-risk PC and should not be considered a standard; however, it appears superior to neoadjuvant RT in men with unfavorable intermediate-risk PC undergoing brachytherapy, making neoadjuvant ADT and brachytherapy a preferred option in these men.


Antigen-specific IgE in sinus mucosa of allergic fungal rhinosinusitis patients.
Local tissue production of antigen-specific immunoglobulin E (IgE) has been shown in patients with allergic rhinitis and in patients with chronic rhinosinusitis (CRS) with nasal polyps. In allergic fungal rhinosinusitis (AFRS), specific IgE has been established in nasal lavage fluid and eosinophilic mucin. In this study, local production of antigen-specific IgE within sinus mucosa of AFRS patients was evaluated. Sinus mucosa homogenates from 11 AFRS patients, 8 patients with CRS without nasal polyps (CRSsNP), and 9 nonrhinosinusitis control patients were assessed for IgE localization by immunohistochemistry. AFRS and control tissue homogenates were also evaluated for antigen-specific IgE to 14 common antigens by ImmunoCAP testing (Phadia AB, Portage, MI). There was a significant increase in IgE staining in AFRS sinus epithelium and subepithelium compared with controls and with patients with CRSsNP (p <or= 0.012 for all group differences). AFRS patients showed increased IgE staining in the subepithelium when compared with epithelium (p < 0.001). AFRS sinus tissue had significantly more IgE measured by ImmunoCAP when compared with control sinus tissue for 7 of 14 specific antigens (p < 0.05) and for total IgE (p = 0.004). Antigens with a significant difference on ImmunoCAP included Cladosporium, Aspergillus, Timothy grass, red maple, cockroach, ragweed, and cocklebur. AFRS patients showed significantly more IgE in sinus mucosa tissue specimens, with increased IgE in subepithelial sites when compared with epithelium. The increased expression of antigen-specific IgE is not limited to fungal antigens. These findings support the role of type I hypersensitivity and local manifestations of allergy in AFRS patients.


Amino acids content and electrophoretic profile of camel milk casein from different camel breeds in Saudi Arabia.
This study aimed to evaluate amino acids content and the electrophoretic profile of camel milk casein from different camel breeds. Milk from three different camel breeds (Majaheim, Wadah and Safrah) as well as cow milk were used in this study. Results showed that ash and moisture contents were significantly higher in camel milk casein of all breeds compared to that of cow milk. On the other hand, casein protein of cow milk was significantly higher compared to that of all camel milk breeds. Molecular weights of casein patterns of camel milk breeds were higher compared to that of cow milk. Essential (Phe, Lys and His) and non-essential amino acids content was significantly higher in cow milk casein compared to the casein of all camel milk breeds. However, there was no significant difference for the other essential amino acids between cow casein and the casein of Safrah breed and their quantities in cow and Safrah casein were significantly higher compared to the other two breeds. Non-essential amino acids except Arg and the essential amino acids (Met, Ile, Lue and Phe) were also significantly higher in cow milk α-casein compared to α-casein from all camel breeds. Moreover, essential amino acids (Val, Phe and His) and the non-essential amino acids (Gly and Ser) content was significantly higher in cow milk β-casein compared to the β-casein of all camel milk breeds and the opposite was true for Lys, Thr, Met and Ile. However, Met, Ile, Phe and His were significantly higher for β-casein of Majaheim compared to the other two milk breeds. The non-essential amino acids (Gly, Tyr, Ala and Asp) and the essential amino acids (Thr, Val and Ile) were significantly higher in cow milk κ-casein compared to that for all camel milk breeds. There was no significant difference among all camel milk breeds in their κ-casein content of most essential amino acids. Relative migration of casein bands of camel milk casein was not identical. The relative migration of αs-, β- and κ-casein of camel casein was slower than those of cow casein. The molecular weights of αs-, β- and κ-casein of camel caseins were 27.6, 23.8 and 22.4 KDa, respectively. More studies are needed to elucidate the structure of camel milk.


The Effects of Imaging Enhancement Tools in the Detection of Horizontal Root Fractures.
Detection of root fracture is challenging both clinically and radiographically. Root fractures occur in different planes with unpredictable presentations. The aim of the study was to evaluate the diagnostic accuracy of selected digital image enhancement tools in the detection of horizontal Root Fracture (RF). Fifty three roots, of single and multi-rooted teeth, in eight dentate human cadaver mandibles were selected for this study. Following minimally traumatic extraction of the teeth, horizontal fractures were induced in 23 roots and remounted in the empty sockets of their respective human dry mandibles. The remaining teeth with no fractures were used as the control group. Twenty two periapical radiographs were obtained by using the paralleling technique and using Complementary Metal Oxide Semiconductor (CMOS). Image J software was used to enhance the original images with the Inversion (IN), Histogram-Equalization (EQ) and Polynomial (Poly) tools. A total of 88 periapical images (original and three enhanced images) were reviewed independently by three Oral and Maxillofacial Radiologists and two Endodontists. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the accuracy of fracture detection and the kappa statistic was used to assess agreement among reviewers. The diagnostic accuracy for one of the observers was significantly different in detection of RF with only EQ enhancement tool. Sensitivity and specificity were not significantly different. Interobserver agreement showed no significant difference between imaging methods. Intra-observer agreement was high to moderate. There was no significant difference between the different imaging modalities. No statistical difference for the agreement was found among or between the endodontists and radiologists in this study.


A Review of Normal Intestinal Healing, Intestinal Anastomosis, and the Pathophysiology and Treatment of Intestinal Dehiscence in Foreign Body Obstructions in Dogs.
Small intestinal anastomoses are commonly performed in veterinary medicine following resection of diseased or devitalized intestinal tissue. Traditionally, suture has been employed to anastomose intestinal ends. However, use of intestinal staplers has become increasingly popular due to the ability to produce a rapid anastomosis with purported superior healing properties. Under normal conditions, intestinal healing occurs in three phases: inflammatory, proliferative, and maturation. Dehiscence, a devastating consequence of intestinal anastomosis surgery, most often occurs during the inflammatory phase of healing where the biomechanical strength of the anastomosis is almost entirely dependent on the anastomotic technique (suture or staple line). The resulting septic peritonitis is associated with a staggering morbidity rate upwards of 85% secondary to the severe systemic aberrations and financial burden induced by septic peritonitis and requirement of a second surgery, respectively. Intraoperative and postoperative consideration of the multifactorial nature of dehiscence is required for successful patient management to mitigate recurrence. Moreover, intensive postoperative critical care management is necessitated and includes antibiotic and fluid therapy, vasopressor or colloidal support, and monitoring of the patient's fluid balance and cardiovascular status. An understanding of anastomotic techniques and their relation to intestinal healing will facilitate intraoperative decision-making and may minimize the occurrence of postoperative dehiscence.


Decreased physical performance despite objective and subjective maximal exhaustion in post-COVID-19 individuals with fatigue.
Fatigue is a common symptom in post-COVID-19 patients. Individuals with fatigue often perform less well compared to healthy peers or without fatigue. It is not yet clear to what extent fatigue is related to the inability to reach maximum exhaustion during physical exercise. A symptom-based questionnaire based on the Carruthers guidelines (2003) was used for reporting the presence of fatigue and further symptoms related to COVID-19 from 85 participants (60.0% male, 33.5 ± 11.9 years). Cardiopulmonary exercise testing (CPET) and lactate measurement at the end of the test were conducted. Objective and subjective exhaustion criteria according to Wasserman of physically active individuals with fatigue (FS) were compared to those without fatigue (NFS). Differences between FS and NFS were found in Peak V̇O2/BM (p < 0.001) and Max Power/BM (p < 0.001). FS were more likely to suffer from further persistent symptoms (p < 0.05). The exhaustion criterion Max. lactate was reached significantly more often by NFS individuals. Although the aerobic performance (Max Power/BM) and the metabolic rate (Peak V̇O2/BM and Max. lactate) of FS were lower compared to NFS, they were equally able to reach objective exhaustion criteria. The decreased number of FS who reached the lactate criteria and the decreased V̇O2 peak indicates a change in metabolism. Other persistent post-COVID-19 symptoms besides fatigue may also impair performance, trainability and the ability to reach objective exhaustion. Trial registration Trial registration: DRKS00023717; date of registration: 15.06.2021 (retrospectively registered).


An angular compounding technique using displacement projection for noninvasive ultrasound strain imaging of vessel cross-sections.
Strain is considered to be a useful indicator of atherosclerotic plaque vulnerability. This study introduces an alternative for a recently introduced strain imaging method that combined beam steered ultrasound acquisitions to construct radial strain images of transverse cross-sections of superficial arteries. In that study, axial strains were projected in the radial direction. Using the alternative method introduced in this study, axial displacements are projected radially, followed by a least squares estimation of radial strains. This enables the use of a larger projection angle. Consequently, fewer acquisitions at smaller beam steering angles are required to construct radial strain images. Simulated and experimentally obtained radio-frequency data of radially expanding vessel phantoms were used to compare the two methods. Using only three beam steering angles (-30°, 0° and 30°), the new method outperformed the older method that used seven different angles and up to 45° of beam steering: the root mean squared error was reduced by 38% and the elastographic signal- and contrast-to-noise ratios increased by 1.8 dB and 4.9 dB, respectively. The new method was also superior for homogeneous and heterogeneous phantoms with eccentric lumens. To conclude, an improved noninvasive method was developed for radial strain imaging in transverse cross-sections of superficial arteries.


Diagnostic value of a questionnaire for term assessment among women seeking abortion.
Since 2020 in France, at-home medical abortion (AHMA) has been authorised for up to nine weeks of gestation. All consultations can be performed via teleconsultation. The determination of gestational age (GA) by interrogation avoids a systematic ultrasound and facilitates the care pathway. The main objective of this study was to evaluate the diagnostic value of a questionnaire to determine a GA lower than seven or nine weeks of gestation (WG). This was a prospective study carried out on patients requesting an abortion in the Gynaecology Department of the North and Conception hospitals (Hôpital Nord and la Conception), AP-HM (Assistance Publique des Hôpitaux de Marseille), from 2 November 2021 to 1 September 2022. A modified translated questionnaire was evaluated. The questionnaire was published in June 2020 by the Royal College of Obstetricians and Gynaecologists (RCOG) to ensure access to abortion in England. All patients included in the study completed the questionnaire and received an ultrasound. We assessed the diagnostic value of the questionnaire for determining GA below seven or nine WG. Seven hundred and forty-eight patients were included in the study. The sensitivity of the questionnaire for determining patients with a GA of less than seven and nine WG was 84% and 93%, with a positive predictive value of 71.4% and 91.8% respectively. The study showed that the questionnaire had good diagnostic value for the selection of patients of under nine WG. Thus, women with limited access to ultrasounds could avoid them.


Clinical characteristics and predictors for in-hospital mortality in adult COVID-19 patients: A retrospective single center cohort study in Vilnius, Lithuania.
The COVID-19 infection had spread worldwide causing many deaths. Mortality rates and patients' characteristics varied within and between countries, making it important to understand the peculiarities of different populations. The aim of this study was to identify the main predictors associated with in-hospital mortality due to COVID-19 in Vilnius, Lithuania. This was a retrospective observational cohort study conducted at Vilnius University Hospital Santaros Clinics, Lithuania. The study included SARS-CoV-2 positive patients aged over 18 years and hospitalized between March 2020 and May 2021. Depersonalized data were retrieved from electronic medical records. The predictive values of laboratory parameters were evaluated using ROC analysis. Multivariable binary logistic regression was performed to reveal predictors of in-hospital mortality due to COVID-19. Among 2794 patients, 54.4% were male, the age median was 59 years (IQR 48-70), 47.4% had at least one comorbidity. The most common comorbidities were arterial hypertension (36.9%) and diabetes mellitus (13.7%). Overall, 12.7% of patients died. Multivariable regression revealed that age (OR 1.04, 95%CI 1.02-1.06), congestive heart failure (OR 3.06, 95%CI 1.96-4.77), obesity (OR 3.90, 95%CI 2.12-7.16), COPD (OR 2.92, 95%CI 1.12-7.60), previous stroke (OR 5.80, 95%CI 2.07-16.21), urea >7.01 mmol/l (OR 2.32, 95%CI 1.47-3.67), AST/ALT >1.49 (OR 1.54, 95%CI 1.08-2.21), LDH >452.5 U/l (OR 2.60, 95%CI 1.74-3.88), CRP >92.68 mg/l (OR 1.58, 95%CI 1.06-2.35), IL-6 >69.55 ng/l (OR 1.62, 95%CI 1.10-2.40), and troponin I >18.95 ng/l (OR 2.04, 95%CI 1.38-3.02), were associated with increased risk for in-hospital mortality in COVID-19 patients. Age, congestive heart failure, obesity, COPD, prior stroke, and increased concentration of urea, LDH, CRP, IL-6, troponin I, ALT to AST ratio were identified to be the predictors for in-hospital mortality of COVID-19 patients.


Significance of NSAID serum to response relationships.
NSAIDs are given to patients to obtain a therapeutic benefit, and a "therapeutic serum concentration range" would be useful. To define the therapeutic range requires a specific assay, knowledge of the active moiety, confidence that the action of the drug is rapid and reversible, examination of the relationship at kinetic equilibrium, careful and innovative ways to measure clinical response, and elimination of as many potential interfering interactions as possible. When defined, the therapeutic range can help clinicians develop dosing aimed at a usual concentration for response, help define toxicity, and help determine compliance.


Exceptional lexical skills but executive language deficits in school starters and young adults with Turners syndrome: implications for X chromosome effects on brain function.
TS school starters had enhanced receptive and expressive language on standardised assessment (CELF-P) and enhanced rhyme judgements, spoonerisms, and lexical decision, indicating enhanced phonological skills and word representations. There was marginal but consistent advantage across lexico-semantic tasks. On executive tasks, speeded naming of numbers was impaired but not pictures. Young TS adults had enhanced naming and receptive vocabulary, indicating enhanced semantic skills. There were consistent deficits in executive language: phonemic oral fluency, rhyme fluency, speeded naming of pictures, numbers and colours; sentence completion requiring supression of prepotent responses. Haploinsufficiency of X-chromosome drives mechanisms that affect the anatomical and neurochemical development of the brain, resulting in enhanced temporal lobe aspects of language. These strengths co-exist with impaired development of frontal lobe executive language systems. This means not only that these elements of language can decouple in development but that their very independence is driven by mechanisms linked to the X-chromosome.


Studies of mutual neutralization in collisions involving Mg+/H-, Na+/H-, Li+/H- and Li+/Cl.
The Landau-Zener model is used to systematically compute mutual neutralization cross sections for collisions between M g + / H - , N a + / H - , L i + / H - and L i + / C l - . Potential energy curves for electronic states that are relevant for mutual neutralization are taken from available literature. Where non-adiabatic couplings are available, they are utilized to compute the diabatic potential energy curves, crossing distance and electronic couplings. In cases where non-adiabatic couplings are not available, they are approximated using a Lorentzian function. The reaction cross sections are computed for the energy range 0.001 eV to 1000 eV. The results are compared with other available experimental and theoretical results and are found to be very comparable. There is an observable trend in the reaction cross section involving ions of metals and hydrogen at collision energies below 10 eV, with the heaviest metal showing the largest reaction cross section and the lightest metal with the lowest cross section. At collision energies below 10 eV, isotope effect is also found to have an effect on the reaction cross section for L i + / C l - .


[Spontaneous chromosome aberrations in the lymphocytes of human peripheral blood].
The authors carried out cytogenetic studies on lymphocytes from human peripheral blood of 105 persons--49 women and 56 men in order to examine spontaneous frequency of the structural chromosomal abberations in the somatic cells. There were 191 cells with abberations (1,17%), out of 16,267 analyzed metaphasic plates. They found 0,39% of chromatid fragments, 0,71% of chromosomal fragments, 0,06% dicentricets, 0,01% of symetric and asymetric chromatid exchanges and 0,006% of rings. There were no statistically significant differences in the discovery of the spontaneous abberations in the examined persons at various age and sex.


Repair of pig dura in vivo using temperature controlled CO(2) laser soldering.
The purpose of this study was to demonstrate that laser soldering might be successfully used for closing holes or cuts in the dura layer, which encapsulates the brain. A temperature controlled fiberoptic CO(2) laser system and albumin solder were used for spot soldering of fascia patches to holes in the dura of farm pigs, in vitro and in vivo. The mean burst pressure of the soldered patches in the in vitro experiments was 190 +/- 88 mm Hg-significantly higher than typical maximum CSF pressure of 15 mm Hg. In the in vivo experiments the pigs showed no postoperative complications. Histopathological studies exhibited an accepted level of inflammatory reaction and showed no thermal damage to the underlying brain tissue. It has been clearly demonstrated that temperature controlled laser soldering is a very useful technique for the repair of the dura. It provides significant advantages over standard closure techniques: it is easy to apply, the bond is strong and watertight and the procedure is likely to be much faster than suturing. This research work will lead to clinical trials.


Post-intubation acute laryngeal injuries in infants and children: A new classification system.
To compare the Classification of Acute Laryngeal Injuries (CALI) with other classifications to determine which of these offers the greatest sensitivity and specificity in predicting the development of subglottic stenosis. All children intubated for the first time in the pediatric intensive care unit were included and subjected to flexible fiber-optic laryngoscopy (FFL) within 8 h of extubation. Their injuries were categorized using the CALI, as well as adapted classifications from Lindholm, Colice and Benjamin. The children were followed up to determine who developed subglottic stenosis. This study included 194 children, with a median age of 2.67 months. The sensitivity and specificity of the CALI were 90% and 73%, respectively. The CALI showed greater specificity than the adapted classifications from Colice and Benjamin (p < 0.001 for both), and greater sensitivity than the adapted classification from Lindholm (p < 0.001). Based on the CALI, 90% of children who developed subglottic stenosis had moderate to severe injuries on the initial FFL. The CALI includes all injury types described by Benjamin, as well as a proposed severity scale for these lesions, and was predictive of the development of chronic laryngeal injury.


Efficacy of vitrectomy and inner limiting membrane peeling in age-related macular degeneration resistant to anti-vascular endothelial growth factor therapy, with vitreomacular traction or epiretinal membrane.
We assessed the efficacy of vitrectomy and inner limiting membrane (ILM) peeling, followed by anti-vascular endothelial growth factor (VEGF) therapy, anti-VEGF-resistant age-related macular degeneration (AMD) due to vitreomacular traction (VMT) or epiretinal membrane (ERM). We identified six patients with anti-VEGF-resistant AMD due to VMT or ERM amongst a total of 588 patients with AMD (821 eyes) referred to Okayama University Hospital between February 2012 and May 2014. These patients underwent vitrectomy to release the VMT (4 cases) or remove the ERM (2 cases), along with ILM peeling. The regimen used for intravitreal injections of anti-VEGF reagents after surgery was based on the severity of exudative changes in each patient. Preoperative and postoperative best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measurements were compared. After vitrectomy and ILM peeling, all six patients responded to anti-VEGF therapy, which was then able to maintain dry retinas. Mean BCVA did not improve significantly (0.49 ± 0.28 before vs. 0.43 ± 0.38 after surgery, P = 0.538). However, mean CR was significantly decreased after surgery, from 423 ± 83.5 μm to 257 ± 75.8 μm (P = 0.0078). Vitrectomy and ILM peeling followed by anti-VEGF therapy may be a useful therapeutic option for anti-VEGF-resistant AMD with VMT or ERM.


Irradiation-induced exosomal HMGB1 to confer radioresistance via the PI3K/AKT/FOXO3A signaling pathway in ESCC.
Radioresistance is a major cause of treatment failure in esophageal squamous cell carcinoma (ESCC) radiotherapy, and the underlying mechanisms of radioresistance are still unclear. Irradiation (IR) stimulates changes in tumor-derived exosome contents, which can be taken up by recipient cells, playing an important role in the proliferation, cell cycle and apoptosis of recipient cells. This study investigated the effect of IR-induced exosomal high mobility group box 1 (HMGB1) on radioresistance in ESCC cells. Plasma exosomes were isolated from 21 ESCC patients and 24 healthy volunteers, and the expression of HMGB1 was examined. Then, the therapeutic effect of radiotherapy was analyzed according to the different expression levels of plasma exosomal HMGB1 in ESCC patients. The uptake of exosomes by recipient cells was verified by immunofluorescence staining, and the localization of exosomes and HMGB1 in cells before and after IR was evaluated. The effects of IR-induced exosomes on cell proliferation, invasion, apoptosis, cell cycle distribution and radioresistance after HMGB1 knockdown were verified. Moreover, western blotting was used to measure changes in the expression of cyclin B1, CDK1, Bax, Bcl2, phosphorylated histone H2AX and the PI3K/AKT/FOXO3A pathway in the HMGB1-knockdown exosome group and the negative control group. The expression of HMGB1 in ESCC plasma exosomes was significantly increased compared with that in healthy volunteers, and high expression of HMGB1 in plasma exosomes was associated with radioresistance (P = 0.016). IR-induced the release of exosomal HMGB1 and promoted proliferation and radioresistance in recipient cells, with a sensitization enhancement ratio (SER) of 0.906 and 0.919, respectively. In addition, IR-induced exosomal HMGB1 promotes G2/M phase arrest by regulating the proteins cyclin B1 and CDK1, cooperating with the proteins Bax and Bcl2 to reduce the apoptosis rate through the PI3K/AKT/FOXO3A signaling pathway, and participated in IR-induced DNA damage repair through γH2AX. These findings indicate that high expression of plasma exosomal HMGB1 is associated with an adverse radiotherapy response. IR-induced exosomal HMGB1 enhances the radioresistance of ESCC cells.


The impact of age on utilization of intensive care resources.
The impact of age on admission practices and pattern of care were examined in 599 admissions to a medical intensive care unit (MICU) and 290 patients on the conventional medical care divisions of the same hospital. Four age groups were compared: under 55, 55 to 64, 65 to 74, and 75 years of age and over. Severity of illness and prior health were assessed using the Acute Physiology Score (APS) and the Chronic Health Evaluation (CHE) instruments. Resource utilization was assessed using the Therapeutic Intervention Scoring System (TISS) and hospital charges. Patients 65 years of age and over comprised 48% of the MICU sample. The distribution of CHE was different among the four groups. Twenty-one percent of patients under 55 years of age had no prior chronic illness, as compared to less than 8% of older patients. The APS at admission was similar for all age groups, as was admission, daily, and total TISS. Hospital survival declined with age from 85% to 70%, while the likelihood of being designated do not resuscitate (DNR) increased from 10% to 24%. Differences in hospital survival disappeared when controlling for severity of illness and prior health, but differences in DNR status did not. Still, elderly DNR patients received as much resources as younger DNR patients and this was more than non-DNR patients. The sample of patients treated on conventional medical divisions had age distribution similar to the MICU sample. There was some evidence that admission APS (median, 5, 5, 6, 6, respectively, P = .055) and maximum APS (median, 5, 5, 7, 8, respectively, P = .023) differed slightly across age groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of estrogen on the expression of GnRH and kisspeptin in the hypothalamus of rats during puberty.
The aim of this study was to assess whether changes in kisspeptin and GnRH levels could be attributed to sex steroids at puberty onset. We used the ovariectomy (OVX) model in rats treated with 17β-estradiol (E2; OVX + E2), or oil (OVX + oil), and in intact rats treated with E2 (intact + E2) or oil only (intact + oil) to determine gene expression changes of Kiss1 and Gnrh1 in the hypothalamus and protein expression of kisspeptin and GnRH in the different areas of the hypothalamus. In the intact + E2 and OVX + E2 rats on the day of the onset of puberty, GnRH-immunoreactive (ir) cell numbers decreased (P < 0.05) in the arcuate nucleus but were increased in the preoptic area; Kisspeptin-ir cells increased (P < 0.05) in the arcuate nucleus, periventricular nucleus, and preoptic area; no difference (P > 0.05) was found in the paraventricularis nucleus for GnRH-ir or kisspeptin-ir cells. Additionally, levels of Kiss1 and Gnrh1 messenger RNA in the hypothalamus were significantly higher (P < 0.05) in the OVX + E2 or intact + E2 rats than in the OVX + oil or intact + oil animals, respectively. In the OVX + oil rats, OVX significantly increased (P < 0.05) levels of Gnrh1 and Kiss1 messenger RNA and the expression of GnRH and kisspeptin in the hypothalamus compared to intact + oil animals. These results suggest that kisspeptin and GnRH play major roles in modulating the activity of estrogen circuits at the onset of puberty.


Classifying Autism Spectrum Disorders by ADI-R: Subtypes or Severity Gradient?
To reduce phenotypic heterogeneity of Autism spectrum disorders (ASD) and add to the current diagnostic discussion this study aimed at identifying clinically meaningful ASD subgroups. Cluster analyses were used to describe empirically derived groups based on the Autism Diagnostic Interview-revised (ADI-R) in a large sample of n = 463 individuals with ASD aged 3-21. Three clusters were observed. Most severely affected individuals regarding all core symptoms were allocated to cluster 2. Cluster 3 comprised moderate symptom severity of social communication impairments (SCI) and less stereotyped repetitive behavior (RRB). Minor SCI and relatively more RRB characterized cluster 1. This study offers support for both, a symptom profile, and a gradient model of ASD within the spectrum due to the sample included.


Sustainable, economical and rapid treatment of multiple lung diseases using therapeutic potential of curcumin nanoparticles.
The study was designed to prepare pure curcumin nanoparticles in rapid and simple way for target specific drug delivery to kill bacteria lying deep down within the alveoli of lungs via inhaler. Three different methods including evaporation precipitation of nanosuspension (ENP), solid dispersion (SD) and anti-solvent precipitation (ASP) were selected to prepare nanocurcumin in pure form in very simple way. This was done to compare their efficiency in terms of particle size obtained and water solubility and bacterial toxicity of as prepared curcumin nanoparticles. In this comparative study, curcumin NPs obtained from three different methods having particles size 65.3 nm, 98.7 nm and 47.4 nm respectively. The NPs were characterized using various techniques like SEM, XRD, UV-Visible and FTIR for their particle size determination and solubility evaluation. These particles were screened off against five bacterial strains causing lung diseases. AB3 prepared by ASP method, being smallest sized nanostructures, showed maximum solubility in water. These nanoparticles can be used as drug directly via inhaler to the target area without using any support or nano-carrier. In this way minimum dose formulation is required to target bacteria.


Branched chain amino acid enriched parenteral nutrition in surgical intensive care patients.
The metabolic responses to branched chain amino acid enriched total parenteral nutrition were studied in surgical intensive care patients with documented severe catabolism. Twenty-four patients were randomised to receive total parenteral nutrition with either 50% (BCAA) or 15% (CONTROL) of its amino acid content as branched chain amino acids. The daily intake of nitrogen was 0.24 g per kg b. wt and that of energy, at steady state, 45 kcal per kg b. wt. Total parenteral nutrition resulted in similar nitrogen balances (Day 1 BCAA: -0.07 +/- 0.09, CONTROL: -0.05 +/- 0.10; Day 4 BCAA: -0.12 +/- 0.07, CONTROL: -0.06 +/- 0.09; Day 5 BCAA: -0.07 +/- 0.08, CONTROL: -0.05 +/- 0.08 g/kg b. wt day; mean +/- S.D.) in both treatment groups throughout the study. The urinary excretion of 3-methylhistidine was higher before feeding in the control group but the rates were similar during total parenteral nutrition in both groups. There were no differences between the groups in the decrease of serum prealbumin during the study. We conclude that the proposed benefits, if any, from enriching nutritional regimens with branched chain amino acids are unlikely to be of major therapeutic relevance in severe catabolism.


Voltage-mediated mechanism for calcium wave synchronization and arrhythmogenesis in atrial tissue.
A wide range of atrial arrythmias are caused by molecular defects in proteins that regulate calcium (Ca) cycling. In many cases, these defects promote the propagation of subcellular Ca waves in the cell, which can perturb the voltage time course and induce dangerous perturbations of the action potential (AP). However, subcellular Ca waves occur randomly in cells and, therefore, electrical coupling between cells substantially decreases their effect on the AP. In this study, we present evidence that Ca waves in atrial tissue can synchronize in-phase owing to an order-disorder phase transition. In particular, we show that, below a critical pacing rate, Ca waves are desynchronized and therefore do not induce substantial AP fluctuations in tissue. However, above this critical pacing rate, Ca waves gradually synchronize over millions of cells, which leads to a dramatic amplification of AP fluctuations. We exploit an underlying Ising symmetry of paced cardiac tissue to show that this transition exhibits universal properties common to a wide range of physical systems in nature. Finally, we show that in the heart, phase synchronization induces spatially out-of-phase AP duration alternans which drives wave break and reentry. These results suggest that cardiac tissue exhibits a phase transition that is required for subcellular Ca cycling defects to induce a life-threatening arrhythmia.


Have urinary function outcomes after radical prostatectomy improved over the past decade?
Changes in surgical technique and postoperative care that target improvements in functional outcomes are widespread in the literature. Radical prostatectomy (RP) is one such procedure that has seen multiple advances over the past decade. The objective of this study was to leverage RP as an index case to determine whether practice changes over time produced observable improvements in patient-reported outcomes. This study analyzed patients undergoing RP by experienced surgeons at a tertiary care center with prospectively maintained patient-reported outcome data from 2008 to 2019. Four patient-reported urinary function outcomes at 6 and 12 months after RP were defined with a validated instrument: good urinary function (domain score ≥ 17), no incontinence (0 pads per day), social continence (≤1 pad per day), and severe incontinence (≥3 pads per day). Multivariable logistic regressions evaluated changes in outcomes based on the surgical date. Among 3945 patients meeting the inclusion criteria, excellent urinary outcomes were reported throughout the decade but without consistent observable improvements over time. Specifically, there were no improvements in good urinary function at 12 months (P = .087) based on the surgical date, and there were countervailing effects on no incontinence (worsening; P = .005) versus severe incontinence (improving; P = .003). Neither approach (open, laparoscopic, or robotic), nor nerve sparing, nor membranous urethral length mediated changes in outcomes. In a decade with multiple advances in surgical and postoperative care, there was evidence of improvements in severe incontinence, but no measurable improvements across 3 other urinary outcomes. Although worsening disease factors could contribute to the stable observed outcomes, a more systematic approach to evaluating techniques and implementing patient selection and postoperative care advances is needed. Although there have been advances in radical prostatectomy over the past decade, consistent observable improvements in postoperative incontinence were not reported by patients. To improve urinary function outcomes beyond the current high standard, the approach to studying innovations in surgical technique needs to be changed, and further development of other aspects of prostatectomy care is needed.


Outcomes of intracytoplasmic sperm injection using the zona pellucida-bound sperm or manually selected sperm.
Zona pellucida (ZP)-bound sperm used for intracytoplasmic sperm injection (ICSI) enhances embryo quality, implantation, and clinical pregnancy rates. This study aimed to assess the pregnancy outcomes and clinical significance of ICSI with ZP-bound sperm. A total of 84 infertile couples who underwent cycles of ICSI following failed in vitro fertilization between June 2012 and February 2014 were enrolled and randomized (1:1): in the treatment group, ICSI was performed using ZP-bound sperm; in the control group, ICSI was performed in a standard manner. Rates of fertilization, cleavage, high-quality embryos, and clinical pregnancy were compared between the two groups. There were no significant differences in age, infertile period, gonadotrophin dose, number of metaphase II oocytes, and number of embryo transfers between the two groups (P > 0.05). The clinical pregnancy rate was higher in the treatment group than in the control group, but without statistical significance (60.5 vs. 47.6 %, P > 0.05). No significant differences in the rates of fertilization and cleavage were observed (83.0 vs. 81.6 %, and 96.3 vs. 96.5 %, both P > 0.05), but higher rates of high-quality embryos and useable embryos were observed with ZP-bound sperm compared with controls (66.1 vs. 50.8 % and 76.0 vs. 66.3 %, both P < 0.05). ICSI using ZP-bound sperm might increase the embryo quality and number of useable embryos, possibly improving the clinical pregnancy outcome of ICSI.


Behavioural sensitivity of a key Southern Ocean species (Antarctic krill, Euphausia superba) to p,p'-DDE exposure.
Persistent organic pollutants (POPs) have been frequently measured throughout the Southern Ocean food web for which little information is available to assess the potential risks of POP exposure. The current study evaluated the toxicological sensitivity of a key Southern Ocean species, Antarctic krill, to aqueous exposure of p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE). Behavioural endpoints were used as indicators of sublethal toxicity. Immediate behavioural responses (partial immobility and tail flicking) most likely reflect neurotoxicity, while the p,p'-DDE body residue causing a median level of sublethal toxicity in Antarctic krill following 96h exposure (IEC50(sublethal toxicity)=3.9±0.21mmol/kg lipid weight) is comparable to those known to cause sublethal narcosis in temperate aquatic species. Critical body residues (CBRs) were more reproducible across tests than effective seawater concentrations. These findings support the concept of the CBR approach, that effective tissue residues are comparable across species and geographical ranges despite differences in environmental factors.


Renal considerations in cardiovascular drug therapy.
The increasing number of patients with both cardiac and renal disease makes it important for the clinician to bear in mind the effect of both renal failure and peritoneal or hemodialysis on the handling of drugs. Guidelines are available for specific medications; however, they must be used in the light of the patient's individual response and metabolism.


Non-destructive method for detecting Aphanomyces astaci, the causative agent of crayfish plague, on the individual level.
The pathogenic oomycete Aphanomyces astaci, transmitted mainly by invasive North American crayfish, causes the crayfish plague, a disease mostly lethal for native European crayfish. Due to its decimating effects on native crayfish populations in the last century, A. astaci has been listed among the 100 worst invasive species. Importantly, detecting the pathogen in endangered native crayfish populations before a disease outbreak would provide a starting point in the development of effective control measures. However, current A. astaci-detection protocols either rely on degradation-prone eDNA isolated from large volumes of water or, if focused on individual animals, include killing the crayfish. We developed a non-destructive method that detects A. astaci DNA in the microbial biofilm associated with the cuticle of individual crayfish, without the need for destructive sampling. Efficiency of the new method was confirmed by PCR and qPCR and the obtained results were congruent with the traditional destructive sampling method. Additionally, we demonstrated the applicability of the method for A. astaci monitoring in natural populations. We propose that the new method should be used in future monitoring of A. astaci presence in endangered European native crayfish individuals as an alternative to eDNA-based monitoring.


Chemical ecology of astigmatid mites LXXXVII. S-(+)-isopiperitenone: re-identification of the alarm pheromone as the female sex pheromone in Tyrophagus similis (Acari: Acaridae).
Behavioral analysis revealed that S-(+)-isopiperitenone [(S)-3-methyl-6-isopropenyl-2-cyclohexen-1-one], previously identified as an alarm pheromone, is also the female sex pheromone of Tyrophagus similis (Astigmata: Acaridae), showing maximum male attraction at a dose of 0.1 female equivalent. Although the antipode, R-(-)-isopiperitenone, was not detectable in the mite extract, this synthetic optical isomer (80% e.e.) also induced activity at a dose of 100 ng, a response indicative of S-(+)-isopiperitenone being the active compound. The average content was determined to be 38.5 ng per female and 19.8 ng per male. This is the first example of an astigmatid mite species possessing a compound that functions as an alarm as well as a sex pheromone.


Marital transitions during earlier adulthood and subsequent health and well-being in mid- to late-life among female nurses: An outcome-wide analysis.
Comparing outcomes for individuals remaining married to those for single or divorced individuals might overstate the positive effects of the decision to marry, since marriage carries an inherent risk of divorce and its associated negative outcomes. While a growing literature has examined marital transitions, confounding by past marital history remains a concern and only a limited set of outcomes have been examined. To address these issues, this study examined incident first-time marriage and incident divorce/separation in relation to multiple subsequent physical health, health behavior, psychological distress, and psychosocial well-being outcomes in a large sample of female nurses in the U.S.. Data from the Nurses' Health Study II were studied (1993 to 2015/2017 questionnaire wave, Nmarriage analyses = 11,830, Ndivorce/separation analyses = 73,018, interquartile range of baseline age = 35 to 42 years). A set of regression models were used to regress each outcome on marital transition status, adjusting for a wide range of initial health and wellbeing status in addition to other covariates. Bonferroni correction was performed to account for multiple testing. Among the initially never married, those who became married had lower mortality (RR = 0.65, 95%CI = 0.50, 0.84), lower risks of cardiovascular diseases (e.g., RRstroke = 0.64, 95%CI = 0.50, 0.82), greater psychological wellbeing and less psychological distress (e.g., ßdepressive symptoms = -0.10, 95%CI = -0.15, -0.06). Among the initially married, those who became divorced/separated had lower social integration (β = -0.15, 95%CI = -0.19, -0.11), greater psychosocial distress (e.g., RRdepression = 1.23, 95%CI = 1.10, 1.37), and possibly greater risks of mortality, cardiovascular diseases, and smoking. Future research could study similar questions using data from more recent cohorts, examine potential mechanisms and heterogeneity, and also examine alternative social relationship types.


Modulation of glycine-induced currents by zinc and other metal cations in neurons acutely dissociated from the dorsal motor nucleus of the vagus of the rat.
Effects of Zn2+ and other polyvalent cations on glycine-induced currents in the freshly dissociated rat dorsal motor nucleus of the vagus neurons were investigated under voltage-clamp conditions by the use of the nystatin-perforated patch recording configuration. Glycine evoked a Cl- current in a concentration-dependent manner with a half-maximum effective concentration (EC50) of 3.3x10-5 M. Strychnine inhibited the 3x10-5 M glycine-induced current in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of 6.8x10-7 M. At low concentrations (3x10-8 M-3x10-6 M), Zn2+ potentiated the current elicited by 3x10-5 M glycine. On the other hand, at concentrations higher than 10-5 M, Zn2+ inhibited the glycine response. The biphasic action of Zn2+ was mimicked by Ni2+, but La3+ and Co2+ had only potentiating effect. Zn2+ shifted the concentration-response curve for the glycine-induced current without changing the maximum response, and the EC50 values for the glycine response in the absence and presence of 10-6 M and 10-4 M Zn2+ were 3.3x10-5 M, 1.3x10-5 M and 1.3x10-4 M, respectively. These results suggest that the biphasic modulation of glycine response by Zn2+ results from changes in apparent glycine affinity.


Evaluating fetomaternal hemorrhage by alphafetoprotein and Kleihauer following therapeutic abortions.
In a survey of 75 patients at 6-11 weeks gestation, fetomaternal hemorrhage (FMH) was detected by significant rises (greater than 2 S.D.) in maternal alphafetoprotein (AFP) levels in 57% of patients, while increased fetal cells were detected by the Kleihauer test in 24% of patients. With increasing gestation, FMH was detected more readily by both tests; however, in evaluating FMH at less than 10 weeks gestation. AFP was found to be a more sensitive and reliable marker than the Kleihauer test. We suggest that there is a gray zone for the Kleihauer test in early gestation, when erythroblasts containing embryonic hemoglobins are gradually replaced in the fetal circulation by erythrocytes containing fetal hemoglobin.


Fast evolutionary genetic differentiation during experimental colonizations.
Founder effects during colonization of a novel environment are expected to change the genetic composition of populations, leading to differentiation between the colonizer population and its source population. Another expected outcome is differentiation among populations derived from repeated independent colonizations starting from the same source. We have previously detected significant founder effects affecting rate of laboratory adaptation among Drosophila subobscura laboratory populations derived from the wild. We also showed that during the first generations in the laboratory, considerable genetic differentiation occurs between foundations. The present study deepens that analysis, taking into account the natural sampling hierarchy of six foundations, derived from different locations, different years and from two samples in one of the years. We show that striking stochastic effects occur in the first two generations of laboratory culture, effects that produce immediate differentiation between foundations, independent of the source of origin and despite similarity among all founders. This divergence is probably due to powerful genetic sampling effects during the first few generations of culture in the novel laboratory environment, as a result of a significant drop in Ne. Changes in demography as well as high variance in reproductive success in the novel environment may contribute to the low values of Ne. This study shows that estimates of genetic differentiation between natural populations may be accurate when based on the initial samples collected in the wild, though considerable genetic differentiation may occur in the very first generations of evolution in a new, confined environment. Rapid and significant evolutionary changes can thus occur during the early generations of a founding event, both in the wild and under domestication, effects of interest for both scientific and conservation purposes.


Prognostic and clinicopathological significance of CapG in various cancers: Evidence from a meta-analysis.
The gelsolin-like actin-capping protein (CapG) is an actin-binding protein in the gelsolin superfamily. Increasing evidence indicates that CapG is highly expressed in various types of cancer. However, the role of CapG in malignant tumors is still controversial. Therefore, we conducted a meta-analysis to assess the prognostic value and clinicopathological significance of CapG in malignant tumors. We searched for eligible studies in the PubMed, Web of Science, Embase, and Cochrane databases. Stata SE12.0 software was used for quantitative meta-analysis. The hazard ratios (HRs) and odds ratios (ORs) with 95% CI were pooled to assess the relationship between CapG expression and overall survival (OS), as well as clinicopathological parameters. Sixteen studies with a total of 1987 cancer patients were included in this meta-analysis. The results showed that higher CapG expression was statistically correlated with shorter OS (HR 1.70, 95% CI 1.43-1.97, P < 0.001), positive lymph node metastasis (OR 1.91, 95% CI 1.19-3.09, P = 0.008), advanced TNM stage (OR 1.87, 95% CI 1.17-3.00, P = 0.009), advanced T-primary stage (OR 2.54, 95% CI 1.08-6.00, P = 0.033) and male sex (OR 1.77, 95% CI 1.23-2.56, P = 0.002). However, no significant correlation was observed between increased CapG expression and advanced age, larger tumor size, differentiation, or advanced histopathologic grading (P > 0.05). High CapG expression is associated with a poor prognosis and worse clinicopathological parameters in various cancers. CapG is a potential prognostic biomarker and a possible clinicopathological predictive factor for various cancers.


A new pattern of pulmonary graft vs host disease in a hematopoietic stem cell transplant patient.
The primary pulmonary manifestation of chronic graft vs host disease (GvHD) is the development of bronchiolitis obliterans. Other pulmonary manifestations of chronic GvHD that have been reported include diffuse alveolar damage, lymphocytic interstitial pneumonia, bronchiolitis organising pneumonia and lymphocytic bronchiolitis/bronchitis. We report an unusual case of a 34-year-old patient with acute myeloid leukaemia, status post-allogenic hematopoietic stem cell transplantation who subsequently developed GvHD with skin involvement. He presented to our hospital with new onset respiratory failure and on subsequent surgical lung biopsy was found to have non-specific interstitial pneumonia (NSIP). This is the third case of a patient with biopsy-proven GvHD who had NSIP pattern on surgical lung biopsy. We believe this may represent a rare manifestation of pulmonary GvHD.


Further comparative studies on chemical properties of carcinoembryonic antigen in tumor tissues and closely related antigens in adult feces and meconium.
The chemical structure of carcinoembryonic antigen (CEA) and two closely related antigens, normal fecal antigen-2 (NFA-2) in normal adult feces and nonspecific cross-reacting antigen-2 (NCA-2) in the meconium, were further analyzed comparatively. The NH2-terminal amino acid sequence of NCA-2 was newly determined to position 18 and found to be identical to that so far determined for CEA- and NFA-2. After proteolytic digestion with chymotrypsin or protease V8, the digests of these antigens showed two groups of fragments upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. One consisted of the sharply banded fragments which were identical in all antigens and stained only with Coomassie brilliant blue (CBB) (five bands in the range 2500-10,000 daltons for chymotrypsin and 11 bands in the range 8000-35,000 daltons for protease V8, respectively), and the other consisted of the dispersed fragments which had variable mol. wts in the range 10,000-100,000 and were stainable with both CBB and periodic acid-Schiff reagent. Elution profiles of CEA, NFA-2, and NCA-2 from lectin columns, especially from concanavalin A-Sepharose columns, suggested some differences in oligosaccharide chains between them. These results indicate that the fundamental chemical structure of these antigens seems to be very similar to one another and is divided into two parts; an homologous portion(s) which is common to all three antigens and contains no sialylated sugar components, and a heterogeneous portion(s) which is variable among these antigens and contains sialylated sugar components.


The ubiquitin ligase CHIP regulates c-Myc stability and transcriptional activity.
c-Myc is a proto-oncogenic transcription factor and its rapid turnover mediated by the ubiquitin-proteasome system is critical for maintaining normal cellular homeostasis. Multiple ubiquitin ligases have been assigned for c-Myc regulation till date. However, the available data suggest for the possible existence of additional E3 ligase(s). Here, we report a new E3 ligase for c-Myc, the carboxyl terminus of Hsc70-interacting protein or CHIP, which is a chaperone-associated Ubox-containing E3 ligase. In this report, we show that CHIP interacts and ubiquitinates c-Myc, thus targeting it for proteasome-mediated degradation. Overexpression of CHIP could accelerate the turnover rate of c-Myc protein. Conversely, knockdown of CHIP by RNAi stabilizes endogenous c-Myc. The interaction between CHIP and c-Myc depends on the N-terminally located tetratricopeptide repeats of CHIP, which has been implicated as a chaperone-binding motif. Inhibition of Hsp90 chaperone activity by 17-N-allylamino-17-demethoxygeldanamycin reduces c-Myc protein level. We found that the association between CHIP and c-Myc is dependent on the chaperones; particularly Hsp70. CHIP antagonizes the transcriptional activity of c-Myc and decreases the abundance of the transcripts of its target genes. Overall, CHIP-knockdown increases malignant behavior of C6 glioma cells. To the best of our knowledge, this is the first report of c-Myc being regulated by a bona-fide chaperone-associated E3 ligase in HEK293 as well as glioma cells. Because CHIP has been reported earlier to be negatively regulating Akt1, BCR-ABL and hTERT, and now c-Myc, the present study may strengthen the view that CHIP acts as a tumor suppressor.


[Troubles felt in the central surgery suite of an hospital in Marseilles: what relevant factor?].
In August 2005, a series of complaints, with a strong media coverage, occurred among the staff of the surgery suite of an hospital in Marseilles during a maintenance work period. A study realized during this period of time concluded that the complaints were due to a collective phenomenon provoked by a << self-amplified >> acute discomfort among the staff. No triggering mechanism was identified till then. In order to found a relevant factor that could explain the complaints, we performed a retrospective investigation some time after the events with the aim of reducing the auto-suggestive phenomenon. Six months after the events, a questionnaire was submitted to each person of the 109 medical and paramedic staff working at central surgery suite during the maintenance work period. Subjects were asked about age, gender, disorder description, medical history, work place and work conditions during the event period. The study counted 98 persons with 31 physicians and 67 paramedic staff having replied to the questionnaire. Sixty-nine persons (70,4%) plead showing up symptoms. Multifactorial analysis found that female gender (OR=4,21; IC=1,23-14,38) and perception of particular odours (OR=8,81: IC=2,52-30,78) increased the probability of the occurrence of symptoms. A significant increase (p=0,03) of felt disorders was evidenced among the staff working in the sanitizing room. Disorders were less frequent for persons working in the operating room (p=0,04) and were strongly decreased for smokers (OR=0,25; IC=0,07-0,89). No complaint was recorded six months after the events. Considering the work places and conditions, peracetic acid appears as the most plausible etiologic agent of the reported disorders. As a consequence, hospitals, especially during maintenance work periods, must be sensitized to the involvement of the occupational physician in order to avoid the social and financial cost of such crisis.


Use of novel structural features to identify urinary biomarkers during acute kidney injury that predict progression to chronic kidney disease.
A significant barrier to biomarker development in the field of acute kidney injury (AKI) is the use of kidney function to identify candidates. Progress in imaging technology makes it possible to detect early structural changes prior to a decline in kidney function. Early identification of those who will advance to chronic kidney disease (CKD) would allow for the initiation of interventions to halt progression. The goal of this study was to use a structural phenotype defined by magnetic resonance imaging and histology to advance biomarker discovery during the transition from AKI to CKD. Urine was collected and analyzed from adult C57Bl/6 male mice at four days and 12 weeks after folic acid-induced AKI. Mice were euthanized 12 weeks after AKI and structural metrics were obtained from cationic ferritin-enhanced-MRI (CFE-MRI) and histologic assessment. The fraction of proximal tubules, number of atubular glomeruli (ATG), and area of scarring were measured histologically. The correlation between the urinary biomarkers at the AKI or CKD and CFE-MRI derived features was determined, alone or in combination with the histologic features, using principal components. Using principal components derived from structural features, twelve urinary proteins were identified at the time of AKI that predicted structural changes 12 weeks after injury. The raw and normalized urinary concentrations of IGFBP-3 and TNFRII strongly correlated to the structural findings from histology and CFE-MRI. Urinary fractalkine concentration at the time of CKD correlated with structural findings of CKD. We have used structural features to identify several candidate urinary proteins that predict whole kidney pathologic features during the transition from AKI to CKD, including IGFBP-3, TNFRII, and fractalkine. In future work, these biomarkers must be corroborated in patient cohorts to determine their suitability to predict CKD after AKI.


C-4-Modified Isotetrones Prevent Biofilm Growth and Persister Cell Resuscitation in Mycobacterium smegmatis.
Hyperphosphorylated nucleotide (p)ppGpp, synthesized by Rel protein, regulates the stringent response pathway responsible for biofilm and persister cell growth in mycobacteria. The discovery of vitamin C as an inhibitor of Rel protein activities raises the prospect of tetrone lactones to prevent such pathways. The closely related isotetrone lactone derivatives are identified herein as inhibitors of the above processes in a mycobacterium. Synthesis and biochemical evaluations show that an isotetrone possessing phenyl substituent at C-4 inhibit the biofilm formation at 400 μg mL-1, 84 h post-exposure, followed by moderate inhibition by the isotetrone possessing the p-hydroxyphenyl substituent. The latter isotetrone inhibits the growth of persister cells at 400 μg mL-1 f.c. when monitored for 2 weeks, under PBS starvation. Isotetrones also potentiate the inhibition of antibiotic-tolerant regrowth of cells by ciprofloxacin (0.75 μg mL-1) and thus act as bioenhancers. Molecular dynamics studies show that isotetrone derivatives bind to the RelMsm protein more efficiently than vitamin C at a binding site possessing serine, threonine, lysine, and arginine.


First colombian interlaboratory study for the determination of aflatoxin B1 in yellow corn.
An interlaboratory study for the determination of aflatoxin B1 in yellow corn was conducted with 16 laboratories that analyze for aflatoxins in Colombia. Naturally contaminated ground yellow corn (Monsanto DK 4004) with an assigned reference value of 26.3 μg/kg aflatoxin B1 was distributed as double blind duplicates in sachets of 55 g. z-Scores were computed for each of the results; repeatability of the two replicate analysis was also calculated. Four of the participating laboratories used HPLC, seven used TLC, one used fluorometry, one ELISA and three a semi quantitative analytical technique (Aflacard®). Only 10 of the 26 quantitative results (39%) had satisfactory z-scores, two scores were questionable (8%) and 14 of the 26 results had unsatisfactory z-scores (54%). A total of 8 laboratories had satisfactory repeatability (62%), and 5 had unsatisfactory repeatability (39%). The present study indicates that only about one third of the results for aflatoxin reported by Colombian laboratories have good accuracy (as measured by the z-score of the result), although satisfactory precision (measured as repeatability) is achieved by about two thirds of the laboratories. These results indicate that an improvement in quality assurance is needed in Colombian laboratories. The routine use of reference standards and reference materials is highly recommended.


Paternal Migration and Children's Educational Attainment and Work Activity: The Case of Mexico.
Most of the research evaluating the import of paternal migration for children's outcomes has taken "left-behind children" as a single group. Such an approach does not take into account how family processes may intersect with migration processes. Taking a life course perspective, this paper distinguishes fathers' short-term and long-term migrations, as well as return migration, as they affect children's productive activities. Using the Mexican Family Life Survey (2002-2009), we followed school-aged children from two-parent households in 2002 and observed their activities as they transitioned into adulthood from 2005 through 2009. We found that fathers' short-term migration is negatively associated with children's labor force participation, especially for 12- to 18-year-old boys, suggesting that paternal migration may interrupt adolescent boys' labor market transition in the short-term. Fathers' long-term migration and return migration does not significantly alter children's activities. However, the negative role of fathers' long-term absence and benefits brought by the paternal migration trip are important mechanisms for educational persistence and the labor force entrance of 12- to 18-year-old girls, highlighting the conditions under which certain mechanisms may work. This suggests that migration is a family process, with the outcomes lying in the interplay of the stages of migration, children's life stages, and how gender is treated within cultural and familial contexts.


Clinical Course and Outcome Patterns of Acute-on-chronic Liver Failure: A Multicenter Retrospective Cohort Study.
Acute-on-chronic liver failure (ACLF) is acute decompensation of liver function in the setting of chronic liver disease, and characterized by high short-term mortality. In this study, we sought to investigate the clinical course of patients at specific time points, and to propose dynamic prognostic criteria. We assessed the clinical course of 453 patients with ACLF during a 12-week follow-up period in this retrospective multicenter study. The clinical course of patients was defined as disease recovery, improvement, worsening or steady patterns based on the variation tendency in prothrombin activity (PTA) and total bilirubin (TB) at different time points. Resolution of PTA was observed in 231 patients (51%) at 12 weeks after the diagnosis of ACLF. Among the remaining patients, 66 (14.6%) showed improvement and 156 (34.4%) showed a steady or worsening course. In patients with resolved PTA, the clinical course of TB exhibited resolved pattern in 95.2%, improved in 3.9%, and steady or worse in 0.8%. Correspondingly, in patients with improved PTA, these values for TB were 28.8%, 27.3%, and 43.9%, respectively. In patients with steady or worsening PTA, these values for TB were 5.7%, 32.3%, and 65.6%, respectively. Dynamic prognostic criteria were developed by combining the clinical course of PTA/TB and the clinical outcomes at 4 and 12 weeks after diagnosis in ACLF patients. We propose the following dynamic prognostic criteria: rapid progression, slow progression, rapid recovery, slow recovery, and slow persistence, which lay the foundation for precise prediction of prognosis and the improvement of ACLF therapy.


Influence of composite insertion technique on gap formation.
To compare newer bulk-fill composites with an incrementally filled composite for adaptability and subsequent gap formation at the pulpal floor. Class I cavities were prepared in 60 intact molars, with a shallow depression in the center of the pulpal floor. The samples were divided into four groups (n = 15), according to the material used; smart dentine replacement (SDR), SonicFill, Ever X Flow and Z350 XT, restored to a depth of 4 mm. Following thermocycling, samples were sectioned buccolingually and examined under a stereomicroscope. Seven samples from each group were coated with nail varnish except for approximately 1 mm around the tooth restoration junction. These samples were examined under stereomicroscope after staining with 2% buffered methylene blue dye. The remaining samples were examined under a scanning electron microscope for gap formation. The data were statistically analyzed using one-way ANOVA and post-hoc Bonferroni test. SDR showed the significantly best adaptability as compared to both SonicFill and Ever X Flow (comparable). However, significantly least adaptive capacity was seen in the incrementally filled group (Z350 XT). Bulk-fill composites performed better than incremental composites, demonstrating better adaptability and less gap formation at the pulpal floor.


Power spectra reveal distinct BOLD resting-state time courses in white matter.
Accurate characterization of the time courses of blood-oxygen-level-dependent (BOLD) signal changes is crucial for the analysis and interpretation of functional MRI data. While several studies have shown that white matter (WM) exhibits distinct BOLD responses evoked by tasks, there have been no comprehensive investigations into the time courses of spontaneous signal fluctuations in WM. We measured the power spectra of the resting-state time courses in a set of regions within WM identified as showing synchronous signals using independent components analysis. In each component, a clear separation between voxels into two categories was evident, based on their power spectra: one group exhibited a single peak, and the other had an additional peak at a higher frequency. Their groupings are location specific, and their distributions reflect unique neurovascular and anatomical configurations. Importantly, the two categories of voxels differed in their engagement in functional integration, revealed by differences in the number of interregional connections based on the two categories separately. Taken together, these findings suggest WM signals are heterogeneous in nature and depend on local structural-vascular-functional associations.


A human-food web-animal interface on the prevalence of food-borne pathogens (Clostridia and Enterococcus) in mixed veterinary farms.
In the present work, we addressed the impact of a human-food web-animal interface on the prevalence of food-borne pathogens in mixed farms of Tamil Nadu, India. We have isolated and identified six strains of Clostridium sp. and five strains of Enterococcus sp. from food and animal sources disposed near to the veterinary and poultry farms. Phylogenetic relationships of these strains were inferred from their homologies in 16S rDNA sequences and rRNA secondary structures. The strain PCP07 was taxonomically equivalent to C. botulinum confirmed by neurotoxin-specific PCR primers, followed by mouse bioassay. Other Clostridial and Enterococcal isolates have shown a phylogenetic similarity to the C. bifermentans and E. durans isolated from veterinary farms, respectively. Results of our study revealed that a human-food web-animal interface has influenced the disease incidence and prevalence of these isolates in the poultry to veterinary farms, where human food acted as a likely transmittance vehicle for their infections.


Effect of chemical and biological degumming on the adsorption of heavy metal by cellulose xanthogenates prepared from Eichhornia crassipes.
Cellulose xanthogenates, derived from the straw of Eichhornia crassipes, were prepared as adsorbents for heavy metals by CS(2) sulfonation and magnesium substitution after degumming with alkali, self-isolated A(1) strain and pectase, respectively. The effects of three degumming treatments were compared by functional groups analysis, surface morphology and surface element composition and heavy metal (Pb(2+)) adsorption studies. The results demonstrate that bio-degumming treatments by A(1) strain and pectase have weaker degumming effects than alkali treatment. However, the surface characteristics of the bio-degumming products, especially the pectase degumming product, are more beneficial to heavy metal adsorption. In comparison to that of the raw plant materials, the Pb(2+) adsorption performances of the three xanthogenates improved significantly, although no obvious differences being observed among themselves. From an environmental point of view, the two bio-degumming treatments, especially the pectase degumming treatment, are more beneficial to prepare heavy metal adsorbents than the alkali degumming treatment.


The juvenile hormone epoxide hydrolase homolog in Penaeus vannamei plays immune-related functions.
Juvenile hormone epoxide hydrolase (JHEH) participates in the degradation of juvenile hormone and also involved in the development and molting process in insects. Here, the JHEH homolog in Pennaus vannamei was cloned and found to consist of a full-length cDNA of 2543 bp and an open reading frame (ORF) of 1386 bp. Transcripts of PvJHEH1 were expressed in most tissues of healthy shrimp with the highest found in the hepatopancreas and lowest in hemocytes. Both Gram-negative (Vibrio parahaemolyticus) and Gram-positive (Streptococcus iniae) bacteria induced PvJHEH1 expression in shrimp hemocytes and hepatopancreas, suggesting the involvement of PvJHEH1 in P. vannamei immune responses. Moreover, the mRNA levels of ecdysone inducible nuclear transcription factor PvE75 and crustacean hyperglycemic hormone (PvCHH), two endocrine-related genes with roles in shrimp innate immune response, decreased significantly in shrimp hemocytes after PvJHEH1 knockdown. Shrimp survival was also affected after PvJHEH1 knockdown followed by V. parahaemolyticus challenge, indicating that JHEH1 plays an essential role in shrimp survival during bacterial infection.


Incidence and predictive risk factors for ophthalmological complications in children with nephrotic syndrome receiving long-term oral corticosteroids: a cohort study.
There is a paucity of data from India on ophthalmological complications in children on long-term oral corticosteroids for idiopathic nephrotic syndrome. All children aged 4-18 years with idiopathic nephrotic syndrome who had received long-term oral steroids for >6 months and who attended the paediatric nephrology clinic between January 2019 and January 2021 were included. The majority of them (95/110) were being followed up in the paediatric nephrology clinic which was functioning from 2010. The children were screened for ophthalmological complications at 6-month intervals. Overall, 110 children with nephrotic syndrome were enrolled. Their median (IQR) age was 9.4 (7.0-12.8) years, and the median (range) duration of follow-up following onset of nephrotic syndrome was 5 years (1.0-16). The incidence of cataract was 18.1% (20 of 110 cases). Visual acuity was impaired in seven (35%) of the children with cataract. Children with cataract were younger as compared to those without cataract [Median (IQR) age at onset of nephrotic syndrome [2.5 (2.0-4.0) yrs vs 4 (2.1-6.0) yrs] (p=0.03)]. Children with cataract also had higher cumulative dose of prednisolone intake (mg/m2) [28,669 (21,329-33,500) vs 14,995 (10,492-19,687)] (p<0.01)] and greater cumulative duration of prednisolone intake [4.3 (3.1-5.2) vs 2.25 (1.3-3.7) yrs] (p<0.01). The incidence of raised IOP was 9.1% (10 of 110 cases). The incidence of cataract and raised IOP was high. The risk factors for the development of cataract were age at onset of nephrotic syndrome, cumulative dose and cumulative duration of steroid intake.


C-5 modified nucleosides: direct insertion of alkynyl-thio functionality in pyrimidines.
A route is presented to append, in a single step, alkynyl thioesters to the 5-position of a pyrimidine ring of a nucleoside that is unprotected. These products should be useful to support in vitro selection experiments with functionalized DNA.