[Acute failure of the gastric mucosa and duodenum: treatment and prevention].
In article last given literatures, concerning the basic aspects of acute lesions of a mucosa of a stomach and a duodenum are analysed: the reasons of occurrence, features of clinical implications, treatment and preventive maintenance questions are surveyed.


Functional organization of the simian virus 40 origin of DNA replication.
To define the sequence elements involved in initiation of DNA synthesis at the simian virus 40 origin of replication, we determined the relative replication efficiencies in vitro and in vivo of templates containing a variety of mutations within the origin region. Replication of the mutants in vitro was assayed by the cell-free DNA replication system that we recently described (J.J. Li and T.J. Kelly, Proc. Natl. Acad. Sci. USA 81:6973-6977, 1984; J.J. Li and T.J. Kelly, Mol. Cell. Biol. 5:1238-1246, 1985), and replication in vivo was assayed after transfection of the mutant templates into COS-1 cells. The minimal origin of replication defined by both assays included a 15-base-pair (bp) imperfect inverted repeat, a 27-bp perfect inverted repeat, and a 17-bp A/T-rich region. T-antigen binding site I was not required for DNA replication, but its presence increased replication efficiency severalfold both in vitro and in vivo. Although SP1 binding sites and enhancers had little or no effect on replication in vitro, the presence of either element markedly increased replication in vivo. Thus, the biological role of these elements is not restricted to stimulating transcription but may be more general.


Recommendations for the Management of Rare Kidney Cancers.
The European Association of Urology Renal Cell Carcinoma Guideline Panel recently conducted a systematic review of treatment options for patients with advanced non-clear-cell renal cell carcinomas (RCCs), which showed a substantial lack of evidence for management recommendations. To improve the outcomes of patients with rare kidney cancers (RKCs), we performed a subsequent unstructured review to determine current treatment strategies and druggable pathways, involving key stakeholders with a global perspective to generate recommendations. Based on the systematic review, literature was queried in Pubmed, Medline, and abstracts from proceedings of European Society for Medical Oncology and American Society of Clinical Oncology, in addition to consulting key opinion leaders and stakeholders. A conventional narrative review strategy was adopted to summarize the data. The systematic review showed an absence of evidence for treating RKCs, with data only supporting sunitinib or MET inhibitors for some specific subtypes. However, a growing body of evidence implicates druggable pathways in specific RKC subtypes. To test hypotheses, the small patient numbers in each subtype require coordinated multicenter efforts. Many RKC patients are currently excluded from studies or are not analyzed using subtype-specific parameters, despite their unmet medical need. We recognize the need for additional multicenter studies and subtype-specific analyses; however, we present management recommendations based on the data available. Web-based tools facilitating subtype-specific global registries and shared translational research resources will help generate sufficient data to formulate evidence-based recommendations for guidelines. Patients confronted with rare kidney cancers are often treated the same way as clear-cell renal cell carcinoma patients, despite little evidence from randomized trials. Molecular characterization of tumors to stratify patients may improve outcomes. Availability of potential agents and trials remain a problem. Collaboration among medical centers is important to pool scarce data.


Positron emission tomography in the evaluation of the negative neck in patients with oral cavity cancer.
Proper management of the clinically negative neck (N0) in patients with squamous cell carcinoma (SCC) of the oral cavity (OC) is controversial. Detecting cervical metastasis in these patients is important, because cervical lymph node metastasis is associated with an unfavourable prognosis. Conventional radiographic studies, such as computerized tomography (CT) and magnetic resonance imaging (MRI), may augment physical examination. However, there are still limitations of these modalities in detecting the presence of metastatic cervical disease. Positron emission tomography (PET) is a functional imaging modality that has recently been used in patients to detect head and neck neoplasms. We report using PET in the evaluation of the N0 neck in 11 consecutive patients with SCC of the OC who underwent neck dissection. The results of PET scans were correlated with the pathologic findings of 19 neck dissections. Four patients (36%) undergoing 7 neck dissections (37%) had pathologic evidence of disease. Positron emission tomography scans were positive in all of these patients and in all pathologically confirmed cervical metastasis. Seven patients (64%) undergoing 12 neck dissections (63%) had no pathologic evidence of cervical metastasis. Positron emission tomography scans were negative for malignancy in all of these seven patients. In the patient with SCC of the OC with a clinically N0 neck, we found PET to have an overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%. Computerized tomography demonstrated 40%, 88%, 67%, 70%, 69%, respectively. In all statistical categories except specificity (p = .1), PET demonstrated statistical significance (p < .05) over CT. Positron emission tomography appears to be a promising diagnostic aid that may be applied when evaluating the N0 neck for patients with SCC of the OC.


Fear of missing out (FoMO) and internet use: A comprehensive systematic review and meta-analysis.
FoMO has been considered a predisposing factor toward excessive internet use, and a great deal of literature has investigated the link between FoMO and internet use. However, there is still a lack of cohesion in the literature. The current study have been conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In the current systematic review and meta-analysis of 86 effect-sizes, representative of 55,134 participants (Mean age = 22.07, SD = 6.15, females = 58.37%), we found that the strength of the trait FoMO- internet use association significantly varies from r = 0.11 to r = 0.63. In some populations, FoMO appears to increase with age and it is reverse in other populations. Facebook use was unrelated to FoMO in some populations, and higher FoMO was linked with stopping Instagram use for some individuals. The FoMO- internet use association was independent of their severity, as the interaction was not significant, and this association was neither linear nor curvilinear. The FoMO-internet use association does not appear to be associated with depressive, anxiety, and stress symptoms or level of life satisfaction. The COVID-19 pandemic was the only significant moderator of the FoMO-internet use association, strengthening this relationship. FoMO demonstrates a considerable role in internet use; however, there is no evidence of interaction or bi-directional association between the mentioned. Overall, we still don't know what factors contribute to individuals exhibiting distinct patterns in the FoMO-internet use association.


Adherence to disease-modifying antirheumatic drugs and the effects of exposure misclassification on the risk of hospital admission.
To describe the effect of different exposure classification strategies for disease-modifying antirheumatic drugs (DMARDs) on drug-outcome associations. We studied the association between DMARD initiation and all-cause hospitalizations in patients with rheumatoid arthritis (RA), 1995-2005. Initiators of DMARDs and oral glucocorticoids were followed for < or =180 days. We compared 2 strategies for exposure classification: a persistent exposure required (PER) approach, in which followup stopped when the regimen changed; and a persistent exposure ignored (PEI) approach, in which followup continued despite regimen changes. For PEI, adherence was assessed using the medication possession ratio. All-cause hospitalization risk was compared among RA regimen initiators using Cox models and methotrexate as the reference. We identified 28,906 episodes of medication initiation. In PER analyses, tumor necrosis factor alpha antagonists did not increase hospitalization risk compared with methotrexate, whereas leflunomide did (hazard ratio [HR] 1.36, 95% confidence interval [95% CI] 1.1-1.67). Glucocorticoids increased hospitalization risk (HR 1.29, 1.54, and 2.03 for low, medium, and high doses, respectively). PEI results were similar to PER except that infliximab initiation increased the risk of hospitalization compared with methotrexate (HR 1.46, 95% CI 1.19-1.8), and most other effects were closer to the null. In PEI, adherence ranged from 73% for etanercept to 6% for glucocorticoids and adherence to methotrexate was 59%. Compared with methotrexate initiation, leflunomide or glucocorticoid initiation consistently increased all-cause hospitalizations in the first 180 days of use. Most PER and PEI estimates were similar; observed differences in risk between these methods were likely due to differences in adherence.


Kinematics of a total arthroplasty of the ankle: comparison to normal ankle motion.
Although the concept of a total ankle arthroplasty has been advanced as a method for treating severe ankle arthritis, the clinical experience with all of the models developed has been discouraging. Both the constrained designs, which maximize joint contact area by restricting the available motion, and the unconstrained designs, which allow more normal motion at the expense of higher contact stresses, uniformly result in implant loosening, pain, and clinical failure in 2 to 7 years. This has led to the recommendation against the use of a total ankle arthroplasty except in very low-demand patients. Failure of ankle implants can be ascribed to either anatomic considerations (e.g.--the talus is too small to accommodate the stress transfers of a prosthesis), or mechanical etiologies. Abnormal 3-dimensional motion of the ankle following arthroplasty would fall into the latter category. This study examined the motion that occurs after implantation of an unconstrained-type total ankle arthroplasty. Using previously validated methodology, axially loaded ankle specimens were cycled through an arc of plantarflex/dorsiflexion while measuring the resulting coupled internal/external and varus/valgus rotations. The average coupled motions in prosthetic ankles were not significantly different than their intact controls. There was, however, a significantly increased amount of hysteresis (defined as the difference between the upper and lower pathways of coupled motion at any given sagittal position) that occurred as the ankle was dorsiflexed and plantar flexed. The increased hysteresis was seen in both the axial and coronal planes. This indicates that there was a greater permitted envelop of motion in the prosthetic ankles compared to normal ankles. It is hypothesized that this subtle change in ankle kinematics caused by the arthroplasty leads to abnormal stress transfer at the prosthesis-bone interface, thereby promoting early implant failure.


Spontaneous contractions in elasmobranch vessels in vitro.
Isolated vessels from four elasmobranchs, yellow stingray (Urolophus jamaicensis), clearnose skate (Raja eglanteria), ghost shark (Hydrolagus novaezelandiae), and spiny dogfish (Squalus acanthias), were examined for the presence of spontaneous contractions (SC). SC were observed in otherwise unstimulated dorsal aortas (DA) from stingray and ghost shark, but not in skate DA. Unstimulated ventral aortas (VA) did not exhibit SC. After treatment of VA with a contractile agonist, SC appeared in stingray and skate but not ghost shark or dogfish. SC in stingray VA were subsequently inhibited by either epinephrine (10(-5) M) or indomethacin (10(-4) M). Agonist contraction also elicited strong SC in ductus Cuvier from stingray, but not from ghost shark or dogfish. SC in dogfish hepatic portal veins (HPV) produced a rhythmical oscillation in tension. The frequency of HPV SC was highest (approximately 1 min(-1)) in intact veins and lower (approximately 3 min(-1)) in vein segments, indicative of a dominant pacemaker in the intact vessel. SC in HPV were depressed during the first 30 min of hypoxia, but there was substantial recovery over an additional 30 min of hypoxia and complete recovery upon return to normoxia. Addition of 80 mM KCl completely inhibited HPV SC and lowered resting tone. These results show that SC are a common feature of elasmobranch vessels and there appears to be a correlation between swimming behavior and the propensity for SC. KCl inhibition of SC and tonus in HPV is highly unusual for vascular smooth muscle.


Spectrum of thoracic outlet syndrome presentation in adolescents.
To study the outcomes of children with thoracic outlet syndrome (TOS) treated surgically with transaxillary first-rib resection and scalenectomy (FRRS). A retrospective database review. The Johns Hopkins Medical Institutions. Patients 18 years or younger who had undergone FRRS. All patients underwent FRRS. Patients with venous TOS underwent venography 2 weeks postoperatively. Main Outcomes Measures For patients with venous TOS, good outcomes included patent subclavian veins. For patients with neurogenic and arterial TOS, good outcomes included relief of pain and discomfort. Thirty-five adolescents, including 14 male and 21 female patients, presented with TOS. Of these, 18 had venous symptoms, 9 had neurogenic symptoms, and 8 had arterial symptoms. Seventeen of the 18 patients with venous TOS had thrombosis. At postoperative venography, 13 patients required dilation of a stenotic vein, 2 had patent veins, and 2 had chronically occluded veins. All 18 patients had patent veins, but 1 had persistent ipsilateral neurogenic symptoms. Physical therapy before FRRS had failed in all 9 patients with neurogenic TOS. Five of the 8 patients with arterial TOS presented with abnormal ribs. Two had episodes of embolization, and 1 had an occluded radial artery. None had an axillosubclavian aneurysm. All 8 patients underwent FRRS; 3 also required removal of the fused cervical rib. All 35 patients had a favorable follow-up period. Adolescents present more frequently with venous and arterial TOS than do adults. However, in nearly all adolescent patients, treatment with FRRS leads to a rapid return to full activity.


The red blood cell deformability alterations under desfluran anesthesia in rats.
General anesthesia, either with inhalation or through nonvolatile anesthetics, is known to affect the overall cardiovascular function as well as the microcirculatory hemodynamics. In this study, the effects of desfluran anesthesia on the red blood cell deformability of young and old rats are investigated. 33 male rats were used in the study and the rats were divided into two groups according to their age (young and old) comprising of two subgroups in each. First group was the young control (n = 5), the second was the young group treated with desfluran (n = 7), the third group was the old control (n = 7) and the last group was the old group treated with desfluran (n = 7). %6 of desfluran was applied to the rats with inhalation in an adjustable cage for one hour. The elongation indexes of the erythrocytes were measured by a laser diffractometer (Myrenne Rheodyne SSD). Deformability indexes of red blood cells were significantly increased with desfluran in young rats (p = 0.042) whereas they were significantly decreased in old rats (p = 0.004) with desfluran application compared with their controls. When we compared the young and old control groups, the deformability indexes were significantly higher in old ones (p < 0.001). However, there was no significant difference between the old and the young desfluran applied groups. The volatile anesthetic agent desfluran impairs the deformability of erythrocytes in old rats compared to their controls, whereas it has the opposite effects on young ones. This may be due to the alterations in membrane structure with age. These results reveal that the inhalation of anesthetics like desfluran may cause more serious problems in the elder people during the surgery and may influence their hemodynamic parameters.


Stewardship to tackle global phosphorus inefficiency: The case of Europe.
The inefficient use of phosphorus (P) in the food chain is a threat to the global aquatic environment and the health and well-being of citizens, and it is depleting an essential finite natural resource critical for future food security and ecosystem function. We outline a strategic framework of 5R stewardship (Re-align P inputs, Reduce P losses, Recycle P in bioresources, Recover P in wastes, and Redefine P in food systems) to help identify and deliver a range of integrated, cost-effective, and feasible technological innovations to improve P use efficiency in society and reduce Europe's dependence on P imports. Their combined adoption facilitated by interactive policies, co-operation between upstream and downstream stakeholders (researchers, investors, producers, distributors, and consumers), and more harmonized approaches to P accounting would maximize the resource and environmental benefits and help deliver a more competitive, circular, and sustainable European economy. The case of Europe provides a blueprint for global P stewardship.


Instability of digoxin in digoxin-amorphous silicon dioxide triturates prepared by solvent deposition and ball milling.
Digoxin underwent hydrolytic degradation to its molecular components when solvent deposited on or ball milled with various commercial grades of amorphous silicon dioxide. The degradation was greater during ball milling than after solvent deposition, and increased with a longer ball milling. By itself digoxin was also degraded by ball milling, but not as much as when a silicon dioxide was present. The extent of the degradation appeared to depend on the acidity, surface area and pore size of the silicon dioxide used. A similar degradative behavior was observed for the related glycoside digitoxin.


Risk factors for the development of PTSD and depression among child and adolescent victims following a 7.4 magnitude earthquake.
Objective. PTSD and major depression occur frequently following traumatic exposure, both as separate disorders and concurrently. Although much of Turkey is under threat of severe earthquakes, risk factors for developing psychiatric disorders among Turkish children have not yet been studied. The aim of the study was to examine risk factors for PTSD and depression develpoment in children. Method. A total of 160 survivors (102 girls and 58 boys) severely impacted by Turkey's 7.4-magnitude quake participated in a psychiatric interview 6-20 weeks after the disaster. The mean age was 14.43. Logistic regression was used to test effects of pre-disaster, disaster-related and post-disaster factors on diagnoses, yielding odds ratios (OR). Results. CAPS indicated that 96 (60%) had PTSD, and psychiatric interview found 49 (31%) with depression. Children diagnosed with PTSD were more likely to have witnessed death (OR=2.47) and experienced an extreme parental reaction (OR=3.45). Children with depression were more likely to be male (OR=4.48), have a higher trait anxiety score (OR=1.12 for every additional point), sustain injury (OR=4.29), and have lost a family member in the quake (OR=10.96). Focusing on the 96 children with PTSD, those with comorbid depression were more likely male, have a higher trait anxiety score, and have lost of family member. Conclusions. Mental health professionals should offer support to children witnessing death or losing a family member in a disaster. The ability of the family to remain calm and reassuring also may be a key factor in preventing PTSD.


Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications.
There is evidence for increased levels of circulating reactive oxygen species (ROS) in diabetics, as indirectly inferred by the findings of increased lipid peroxidation and decreased antioxidant status. Direct measurements of intracellular generation of ROS using fluorescent dyes also demonstrate an association of oxidative stress with diabetes. Although phenolic compounds attenuate oxidative stress-related tissue damage, there are concerns over toxicity of synthetic phenolic antioxidants and this has considerably stimulated interest in investigating the role of natural phenolics in medicinal applications. Curcumin (the primary active principle in turmeric, Curcuma longa Linn.) has been claimed to represent a potential antioxidant and antiinflammatory agent with phytonutrient and bioprotective properties. However there are lack of molecular studies to demonstrate its cellular action and potential molecular targets. In this study the antioxidant effect of curcumin as a function of changes in cellular ROS generation was tested. Our results clearly demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and thapsigargin-induced ROS generation in cells from control and diabetic subjects. The pattern of these ROS inhibitory effects as a function of dose-dependency suggests that curcumin mechanistically interferes with protein kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca2+ influx suggest that a rise in cytosolic Ca2+ may be a trigger for increased ROS generation. We suggest that the antioxidant and antiangeogenic actions of curcumin, as a mechanism of inhibition of Ca2+ entry and PKC activity, should be further exploited to develop suitable and novel drugs for the treatment of diabetic retinopathy and other diabetic complications.


Subjective well-being and mortality revisited: differential effects of cognitive and emotional facets of well-being on mortality.
Subjective well-being (SWB) is an important predictor of mortality. To date, surprisingly little is known about whether cognitive and emotional facets of SWB independently predict mortality, and whether such effects vary by age. This study examined differential effects of life satisfaction (LS), positive affect (PA), and negative affect (NA) on mortality in a conjoint analysis using data of German adults between the ages of 40 to 85 years (N = 3,124). Effects of SWB facets were analyzed using Cox Proportional Hazards Models. LS and PA predicted mortality over and above sociodemographic factors and physical health (HRLS = .89, 95% CI = .79-1.00, p < .05, HRPA = .81, 95% CI = .70-.93, p < .05). However, this effect diminished when including self-rated health and physical activity. NA was not associated with mortality. Age group comparative analyses revealed that PA predicted mortality in older adults (65+) even after controlling for self-rated health and physical activity (HRPA = .82, 95% CI = .70-.97, p < .05). In middle-aged participants, no SWB indicator predicted mortality when controlling for covariates. These findings suggest a differential impact of cognitive and emotional well-being on mortality and suggest that in middle-aged adults the effects of SWB on mortality are attenuated by self-rated health and physical activity. The study underscores the importance of SWB for health and longevity, particularly for older adults.


Long-term studies of hantavirus reservoir populations in the southwestern United States: rationale, potential, and methods.
Hantaviruses are rodent-borne zoonotic agents that cause hemorrhagic fever with renal syndrome in Asia and Europe and hantavirus pulmonary syndrome (HPS) in North and South America. The epidemiology of human diseases caused by these viruses is tied to the ecology of the rodent hosts, and effective control and prevention relies on a through understanding of host ecology. After the 1993 HPS outbreak in the southwestern United States, the Centers for Disease Control and Prevention initiated long-term studies of the temporal dynamics of hantavirus infection in host populations. These studies, which used mark-recapture techniques on 24 trapping webs at nine sites in the southwestern United States, were designed to monitor changes in reservoir population densities and in the prevalence and incidence of infection; quantify environmental factors associated with these changes; and when linked to surveillance databases for HPS, lead to predictive models of human risk to be used in the design and implementation of control and prevention measures for human hantavirus disease.


Loss of expression of the DRR 1 gene at chromosomal segment 3p21.1 in renal cell carcinoma.
Consistent deletion of DNA sequences in chromosomal band 3p21 observed in a variety of human tumors suggests the presence of one or more tumor suppressor genes within this region. Previously, we reported on the construction of two distinct cosmid contigs and our identification of several new genes within 3p21.1. In our search for tumor suppressor genes from this region, we have cloned a gene that we have called DRR 1 (downregulated in renal cell carcinoma). The gene was first mapped to 3p21.1 by fluorescence in situ hybridization analysis. Further analysis of yeast artificial chromosome clones in 3p14.2-p21.1 refined its localization. DRR 1 spans about 10 Kb of genomic DNA with a 3.5-Kb mature transcript. The putative protein encoded by this gene is 144 amino acids and includes a nuclear localization signal and a coiled domain. The gene showed loss of expression in eight of eight renal cell carcinoma cell lines, one of seven ovarian cancer cell lines, one of one cervical cancer cell line, one of one gastric cancer cell line, and one of one non-small-cell lung cancer cell line. Southern blot analysis did not show any altered bands, indicating that gross structural changes or deletions did not cause the loss of expression. This gene was also found to have reduced expression in 23 of 34 paired primary renal cell carcinomas. Mutational analysis detected three polymorphic sites within the gene, but no point mutations were identified in the 34 primary tumors. However, we did detect base substitutions in 4 of 12 cell lines that had undetectable expression of the gene. We also transfected the gene into DRR 1-negative cell lines and observed clear growth retardation. Our results suggest that loss of expression of the DRR 1 gene may play an important role in the development of renal cell carcinoma and possibly other tumors. Genes Chromosomes Cancer 27:1-10, 2000.


Renal transplantation 2004: where do we stand today?
In spite of considerable progress in immunosuppressive and supportive treatment, numerous problems persist which interfere with the success of renal transplantation. Before transplantation has been performed, factors impacting on outcome include the donor (living vs cadaver, age and HLA system) as well as the recipient (age, immunological reactivity, potential sensitization and duration of dialysis). These are the main factors that affect the outcome of the transplant, particularly in the long-term. After transplantation a number of events may put graft function at risk: potential recurrence of the primary renal disease in the allograft; 'de novo' renal disease triggered by infections, drugs or autoimmunity; and non-specific progression promoters, such as diabetes, hypertension, proteinuria, nephrotoxic agents and/or viral infections. The two most frequent causes of chronic allograft dysfunction are (i) chronic rejection (often triggered by preceding acute rejection, delayed graft function or poor compliance) and (ii) calcineurin-inhibitor nephrotoxicity (more likely to develop in kidneys of older donors or in marginal kidneys). The differential diagnosis between these two entities is generally difficult, but some histological clues (reduplication of glomerular basement membrane, obliterating vasculopathy and C4d deposits) as well as the demonstration of humoral antibodies are pointers suggesting rejection. Treatment of chronic graft dysfunction is difficult, whatever the cause, particularly in cases with advanced renal lesions. Therefore, early diagnosis is of paramount importance. In this regard, graft biopsy can be of great help. In spite of many problems and complications, not only short-term but also long-term results of renal transplantation are improving progressively, as documented by CTS data showing that in Europe for transplants performed between 1982 and 1984 the mean graft half-life was 7 years, while for transplants performed between 1997 and 1999 it was 20 years.


Studies of renal cell function using cell culture techniques.
Cell culture, a powerful tool for the study of cell biology, offers advantages for the study of renal cell function. Epithelial cells derived from a variety of organs, including the kidney, form oriented epithelial sheets in culture that have many structural characteristics (microvilli, tight junctions) of epithelia in situ. There is evidence of transepithelial transport of salt and water by cells of two lines (MDCK and LLC-PK1) derived from mammalian kidney. LLC-PK1 cells may also manifest the glucose transport system of the proximal tubule. Cells of both lines have adenylate cyclase activity sensitive to hormones. Two lines of cells derived from toad urinary bladder form epithelia with a high transepithelial resistance and transport sodium actively from apical to basolateral surface. The rate of sodium transport in both lines is stimulated by cyclic AMP and by aldosterone. There are important differences in the characteristics of the response of the two lines to aldosterone as well as in their sensitivity to inhibition of sodium transport by amiloride. These differences may lead to new insights regarding the molecular events in the response to aldosterone and in the inhibitory action of amiloride. Cultures of kidney cells have also been used effectively to study the biosynthesis of the hormonal derivative of vitamin D and to study prostaglandin production. In addition, cell culture is ideally suited for study of the developmental biology of the kidney.


Matrix metalloproteinases-2, -3, and -9 secreted by explants of benign and malignant lesions of the uterine cervix.
Elevated expression of matrix metalloproteinases (MMPs) plays a critical role in extracellular matrix (EM) degradation in tumor development and prognosis of different human carcinomas. In cervical carcinoma (Ce Ca), the role of these proteinases in the biological development of this neoplasm is controversial. In the present study, we compared the secretion of MMP-2, MMP-3 and MMP-9 among 29 benign and premalignant cervical lesions (cervicitis and cervical intraepithelial neoplasias) and 46 tumoral explants of Ce Ca. The explants were cultured for 48 h. The gelatinases secreted into conditioned medium were revealed by zymography and quantified by densitometry. The results showed high levels of MMP-3 and MMP-9 in tumoral explants. In contrast, only the pro-MMP-2 was higher in benign cervical lesions, although both active and inactive MMP-2 species are associated with advanced clinical stages in tumoral samples, and only the secretion of MMP-3 was associated with unresponsiveness to radiotherapy. We can conclude that the expression of MMPs is related to the invasive process in Ce Ca and suggest that they may play a role in degradation of the EM during local invasion. In addition, MMP-3 secretion could be a marker of poor prognosis in Ce Ca.


A risk prediction model based on machine learning for postoperative cognitive dysfunction in elderly patients with non-cardiac surgery.
Early identification of elderly patients undergoing non-cardiac surgery who may be at high risk for postoperative cognitive dysfunction (POCD) can increase the chances of prevention for them, as extra attention and limited resources can be allocated more to these patients. We performed this analysis with the aim of developing a simple, clinically useful machine learning (ML) model to predict the probability of POCD at 3 months in elderly patients after non-cardiac surgery. We collected information on patients who received surgical treatment at Nanjing First Hospital from May 2020 to May 2021. We used LASSO regression to select key features and built 5 ML models to assess the risk of POCD at 3 months in elderly patients after non-cardiac surgery. The Shapley Additive exPlanations (SHAP) and methods were introduced to interpret the best model. A total of 415 patients with non-cardiac surgery were included. The support vector machine (SVM) was the best-performing model of the five ML models. The model showed excellent performance compared to the other four models. The SHAP results showed that VAS score, age, intraoperative hypotension, and preoperative hemoglobin were the four most important features, indicating that the SVM model had good interpretability and reliability. The website of the web-based calculator was https://modricreagan-non-3-pocd-9w2q78.streamlit.app/ . Based on six important perioperative variables, we successfully established a series of ML models for predicting POCD occurrence at 3 months after surgery in elderly non-cardiac patients, with SVM model being the best-performing model. Our models are expected to serve as decision aids for clinicians to monitor screened high-risk patients more closely or to consider further interventions.


The tobacco mosaic virus resistance gene, N.
Summary In this mini review we discuss recent advances in the understanding of the N gene-mediated resistance to tobacco mosaic virus (TMV). The tobacco N gene belongs to toll-interleukin-1 receptor homology/nucleotide binding/leucine rich repeat (TIR-NB-LRR) class of resistance genes. It encodes two transcripts, N(S) and N(L), by alternative splicing, both of which are required to confer resistance to TMV. The structure-function analysis of the N gene indicates that the TIR, NB and LRR domains are indispensable for its function. The N gene response is elicited by the C-terminal helicase domain of the 126 kDa TMV replicase protein. Tobacco N gene can also confer resistance to TMV in heterologous plants like tomato and Nicotiana benthamiana. Recent studies on N-mediated signalling suggest that EDS1, Rar1 and NPR1 genes play an important role in TMV resistance. Finally, we discuss current status of the N-mediated signal transduction and speculate directions for future work to understand N-TMV interaction.


Solving Complex Biologics Truncation Problems by Top-Down Mass Spectrometry.
With increasing protein therapeutics being designed as non-mAb (non-monoclonal antibody) modalities, additional efforts and resources are required to develop and characterize such therapeutic proteins. Truncation is an emerging issue for manufacturing of non-mAb drug substances and requires sophisticated methods to investigate. In this paper, we describe two cases with complex truncation problems where traditional methods such as intact mass spectrometry led to inclusive or wrong identifications. Therefore, we developed an online top-down LC-MS (liquid chromatography-mass spectrometry) based workflow to study truncated drug substances, and we successfully identified the clipping locations. Compared to other orthogonal methods, this method provides a unique capability of solving protein clipping problems. The successful identification of truncated species and the high compatibility to routine intact MS make it a very valuable tool for resolving truncation problems during protein production in the pharmaceutical industry.


[Co-author and keyword networks and their clustering appearance in preventive medicine fields in Korea: analysis of papers in the Journal of Preventive Medicine and Public Health, 1991~2006].
This study evaluated knowledge structure and its effect factor by analysis of co-author and keyword networks in Korea's preventive medicine sector. The data was extracted from 873 papers listed in the Journal of Preventive Medicine and Public Health, and was transformed into a co-author and keyword matrix where the existence of a 'link' was judged by impact factors calculated by the weight value of the role and rate of author participation. Research achievement was dependent upon the author's status and networking index, as analyzed by neighborhood degree, multidimensional scaling, correspondence analysis, and multiple regression. Co-author networks developed as randomness network in the center of a few high-productivity researchers. In particular, closeness centrality was more developed than degree centrality. Also, power law distribution was discovered in impact factor and research productivity by college affiliation. In multiple regression, the effect of the author's role was significant in both the impact factor calculated by the participatory rate and the number of listed articles. However, the number of listed articles varied by sex. This study shows that the small world phenomenon exists in co-author and keyword networks in a journal, as in citation networks. However, the differentiation of knowledge structure in the field of preventive medicine was relatively restricted by specialization.


Down-Regulation of Rice Glutelin by CRISPR-Cas9 Gene Editing Decreases Carbohydrate Content and Grain Weight and Modulates Synthesis of Seed Storage Proteins during Seed Maturation.
The glutelins are a family of abundant plant proteins comprised of four glutelin subfamilies (GluA, GluB, GluC, and GluD) encoded by 15 genes. In this study, expression of subsets of rice glutelins were suppressed using CRISPR-Cas9 gene-editing technology to generate three transgenic rice variant lines, GluA1, GluB2, and GluC1. Suppression of the targeted glutelin genes was confirmed by SDS-PAGE, Western blot, and q-RT-PCR. Transgenic rice variants GluA1, GluB2, and GluC1 showed reduced amylose and starch content, increased prolamine content, reduced grain weight, and irregularly shaped protein aggregates/protein bodies in mature seeds. Targeted transcriptional profiling of immature seeds was performed with a focus on genes associated with grain quality, starch content, and grain weight, and the results were analyzed using the Pearson correlation test (requiring correlation coefficient absolute value ≥ 0.7 for significance). Significantly up- or down-regulated genes were associated with gene ontology (GO) and KEGG pathway functional annotations related to RNA processing (spliceosomal RNAs, group II catalytic introns, small nucleolar RNAs, microRNAs), as well as protein translation (transfer RNA, ribosomal RNA and other ribosome and translation factors). These results suggest that rice glutelin genes may interact during seed development with genes that regulate synthesis of starch and seed storage proteins and modulate their expression via post-transcriptional and translational mechanisms.


Responses to norepinephrine resistant to inhibition by alpha and beta adrenoceptor antagonists.
The mode of action of clonidine and norepinephrine (NE) has been investigated in the isolated transmurally stimulated guinea-pig ileum preparation using rauwolscine, idazoxan and benextramine as antagonists. Both clonidine and NE produced concentration-dependent inhibition of the cholinergically induced twitch response and were antagonized by rauwolscine and idazoxan, but only clonidine was antagonized in a truly competitive fashion. Benextramine, an irreversible alpha adrenoceptor antagonist, in a concentration of 10(-5) M, inhibited the effect of clonidine completely but only partially antagonized the inhibitory action of NE. The antagonism of NE by rauwolscine and benextramine was most pronounced after reserpine pretreatment and blockade of neuronal and extraneuronal uptake. Under these conditions, the concentration-effect curve to NE remaining after treatment with benextramine showed an IC50 of about 3 X 10(-7) M and an intrinsic activity of 0.6. This curve was resistant to further inhibition by clonidine (10(-5) M), phentolamine (3 X 10(-6) M), rauwolscine (3 X 10(-6) M), prazosin (10(-6) M) and propranolol (1.2 X 10(-5) M). Thus, alpha and beta adrenergic receptors do not appear to be involved. It is postulated that NE-induced inhibition of the guinea-pig ileum twitch response is mediated by two distinct sites: one is the classical alpha-2 adrenoceptor (the site of action of clonidine and the alpha adrenoceptor antagonists) whereas the other is a site seemingly unrelated to the alpha and beta subtypes.


Does endometrial thickness affect pregnancy outcomes in isolated male infertility IVF cycles? A retrospective cohort study.
In our retrospective cohort study, we aimed to determine the role of endometrial thickness (ET) in isolated male factor infertile women in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo cycles. The patients were classified as having an endometrial thickness of <7 mm (n: 80), 7-9.9 mm (n: 335), 10-14 mm (n: 579) and >14 mm (n: 50) according to their ETs on the human chorionic gonadotropin (hCG) day. The overall clinical pregnancy rate was 37.4%, and no significant difference was found between the groups (p = .262). There was no significant difference between live birth rates (p = .094), but the highest pregnancy (46%) and live birth (34%) rates were found in the group with >14 mm ET. The increase in ET in IVF cycles increases pregnancy rates, albeit partially. When it is desired to determine a cut-off value, it can be said that pregnancy rates increase significantly in thicknesses of 14 mm and above.Impact StatementWhat is already known on this subject? When the literature is examined, many studies conclude that clinical pregnancy rates increase with the increase in endometrial thickness (ET) in IVF cycles, but there are also studies that argue the opposite. There is no study in the literature investigating the effect of ET on clinical pregnancy rates in patients with isolated male factor infertility.What do the results of this study add? In support of the literature, an increase in ET was found to be associated with an increase in clinical pregnancy rates, regardless of male and female factors. Although pregnancy occurs in thin endometriums, abortion rates are undesirably high.What are the implications of these findings for clinical practice and/or further research? Although the risk of abortion is high in thin endometriums, live birth rates are satisfactory. As a result, thin endometrium does not require cycle cancellation.


Risk of cardiovascular events and rofecoxib: cumulative meta-analysis.
The cyclo-oxygenase 2 inhibitor rofecoxib was recently withdrawn because of cardiovascular adverse effects. An increased risk of myocardial infarction had been observed in 2000 in the Vioxx Gastrointestinal Outcomes Research study (VIGOR), but was attributed to cardioprotection of naproxen rather than a cardiotoxic effect of rofecoxib. We used standard and cumulative random-effects meta-analyses of randomised controlled trials and observational studies to establish whether robust evidence on the adverse effects of rofecoxib was available before September, 2004. We searched bibliographic databases and relevant files of the US Food and Drug Administration. We included all randomised controlled trials in patients with chronic musculoskeletal disorders that compared rofecoxib with other non-steroidal anti-inflammatory drugs (NSAIDs) or placebo, and cohort and case-control studies of cardiovascular risk and naproxen. Myocardial infarction was the primary endpoint. We identified 18 randomised controlled trials and 11 observational studies. By the end of 2000 (52 myocardial infarctions, 20742 patients) the relative risk from randomised controlled trials was 2.30 (95% CI 1.22-4.33, p=0.010), and 1 year later (64 events, 21432 patients) it was 2.24 (1.24-4.02, p=0.007). There was little evidence that the relative risk differed depending on the control group (placebo, non-naproxen NSAID, or naproxen; p=0.41) or trial duration (p=0.82). In observational studies, the cardioprotective effect of naproxen was small (combined estimate 0.86 [95% CI 0.75-0.99]) and could not have explained the findings of the VIGOR trial. Our findings indicate that rofecoxib should have been withdrawn several years earlier. The reasons why manufacturer and drug licensing authorities did not continuously monitor and summarise the accumulating evidence need to be clarified.


Blood pentobarbital concentrations during thiopental therapy.
The desulfuration of thiopental to pentobarbital has previously been shown to be a relatively minor pathway of thiopental metabolism. In two cases, we observed significant conversion, resulting in blood pentobarbital concentrations up to 50 percent of total blood barbiturate (thiopental and pentobarbital) concentrations. Both patients received continuous infusions of thiopental and had present a condition (hypothermia) or drug (cimetidine) known to inhibit hepatic microsomal enzyme activity. It is suggested that inhibition of hepatic microsomal enzyme activity may prevent thiopental's metabolism to its major metabolite, a carboxylic acid analogue, and increase the amount of thiopental desulfurated to pentobarbital. Inhibition of hepatic microsomal metabolism also decreases the metabolism of pentobarbital. Until further elucidation of the causes of altered thiopental metabolism is available to identify patients more likely to have elevated concentrations of pentobarbital, monitoring of blood drug concentrations in patients receiving thiopental should include determination of both thiopental and pentobarbital concentrations.


New Yes/No Recognition Memory Analysis on the California Verbal Learning Test-3: Clinical Utility in Alzheimer's and Huntington's Disease.
The third edition of the California Verbal Learning Test (CVLT-3) includes a new index termed List A versus Novel/Unrelated recognition discriminability (RD) on the Yes/No Recognition trial. Whereas the Total RD index incorporates false positive (FP) errors associated with all distractors (including List B and semantically related items), the new List A versus Novel/Unrelated RD index incorporates only FP errors associated with novel, semantically unrelated distractors. Thus, in minimizing levels of source and semantic interference, the List A versus Novel/Unrelated RD index may yield purer assessments of yes/no recognition memory independent of vulnerability to source memory difficulties or semantic confusion, both of which are often seen in individuals with primarily frontal-system dysfunction (e.g., early Huntington's disease [HD]). We compared the performance of individuals with Alzheimer's disease (AD) and HD in mild and moderate stages of dementia on CVLT-3 indices of Total RD and List A versus Novel/Unrelated RD. Although AD and HD subgroups exhibited deficits on both RD indices relative to healthy comparison groups, those with HD generally outperformed those with AD, and group differences were more robust on List A versus Novel/Unrelated RD than on Total RD. Our findings highlight the clinical utility of the new CVLT-3 List A versus Novel/Unrelated RD index, which (a) maximally assesses yes/no recognition memory independent of source and semantic interference; and (b) provides a greater differentiation between individuals whose memory disorder is primarily at the encoding/storage level (e.g., as in AD) versus at the retrieval level (e.g., as in early HD). (JINS, 2018, 24, 833-841).


Streptomyces aqsuensis sp. nov., isolated from ditch sediment in Xinjiang, China.
A novel actinobacterium, designated TRM46399T, was isolated from ditch sediment in Xinjiang Province, Northwest China. Phylogenetic, physiological, chemotaxonomic and morphological analyses demonstrated that strain TRM46399T belonged to the genus Streptomyces. The strain was aerobic, Gram-stain-positive, had aerial mycelia that branched monopodially and formed chains of arthrospores. The spores were oval to cylindrical with smooth surfaces. The strain had an optimum NaCl concentration for growth of 5 % (w/v). The whole-cell sugar pattern of TRM46399T consisted of ribose, xylose, mannose and galactose. The predominant menaquinones were MK-9(H6), MK-9(H8) and MK-9(H10). The polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides. Major fatty acids were iso-C16 : 0 (47.8 %), iso-C14 : 0 (13.5 %), C16 : 0 (8.9 %), anteiso-C15 : 0 (8.4 %), anteiso-C17 : 0 (4.2 %) and C17 : 0cyclo (2.7 %). The G+C content of the genomic DNA was 68.7 mol%. Comparative 16S rRNA gene sequence analysis indicated that strain TRM46399T (KY688182) was phylogenetically most closely related to Streptomyces xinghaiensis S187T (99.13 % sequence similarity); however, DNA-DNA hybridization studies between stain TRM46399T and S. xinhaiensis S187T showed only 65.32 % relatedness. Based on the evidence from this polyphasic study, strain TRM46399T represents a novel species of the genus Streptomyces, for which the name Streptomyces aqsuensis sp. nov. is proposed. The type strain is TRM46399T (=KCTC 39610 T=CCTCC AA 2015009T).


Evaluation of Botulinum Toxin A as an Optional Treatment for Atopic Dermatitis.
OBJECTIVE: Botulinum toxin (BTX) A has different biological activities, including anti-inflammatory and antipruritic behavior. Studies on humans and animals have shown that BTX is efficient in treating itch caused by histamine, lichen simplex chronicus, psoriasis, rosacea, allergic rhinitis, and scar avoidance. OBJECTIVE: This study sought to assess the impact of BTX-A in patients with atopic dermatitis using scores of SCORAD and to identify parameters linked to greater improvements. METHODS: This was a prospective, intrapatient, left-to-right, randomized, placebo-controlled study of BTX-A for the treatment of atopic dermatitis. The study included 26 patients with atopic dermatitis (12 males and 14 females) with an average age of 37.8 years. Responses to therapy were assessed using SCORAD, Dermatology Quality of Life Index (DLQI), and the worldwide clinical reaction score evaluation. RESULTS: Mean SCORAD values dropped from 50.5 to 11 points (p<0.001); meanwhile, 64.1 percent of patients reported an excellent response, including 78.9 percent of patients with severe AD. The DLQI score fell by 10.15 points (43.5%) in patients treated with BTX-A. A statistically significant reduction in SCORAD and DLQI scores occurred relative to in the placebo group (p<0.001). CONCLUSION: Based on the results of this study, BTX-A appears to be a safe and effective therapy for atopic dermatitis of all grades (mild, moderate, and severe). However, BTX-A appears to be best suited for patients with severe atopic dermatitis.


Dependence of asbestos- and mineral dust-induced transformation of mammalian cells in culture on fiber dimension.
The abilities of chrysotile and crocidolite asbestos, glass fibers of differing dimensions, and nonfibrous mineral particulates to induce morphological transformation of Syrian hamster embryo cells in culture were compared. Chrysotile and crocidolite asbestos induced morphologically transformed colonies which were indistinguishable from transformed colonies observed following treatment with known chemical carcinogens. A linear, dose-dependent increase in the frequency of transformed colonies was observed. The slope of the dose-response curve on a log-log scale was approximately 1, which is consistent with a one-hit mechanism for their induction. The transforming potency of chrysotile asbestos was decreased by milling of the fibers but not by extraction with an organic solvent. Chrysotile asbestos was nearly twice as potent in inducing morphological transformation as crocidolite asbestos. Glass fibers were also very active in this assay. Thin glass fibers with an average diameter of 0.1 to 0.2 micrometer were as active as asbestos. In contrast, two nonfibrous particulates, alpha-quartz and Min-U-Sil, were inactive over the same concentration range used for the fibrous dusts; however, both were active at higher doses. The effect of varying fiber dimension on induction of morphological transformation was examined with glass fibers. When compared on a per-weight basis, thick glass fibers [average diameter, 0.8 plus/minus 0.06 micrometer (S.E.)] were 20-fold less potent than thin fibers [average diameter, 0.13 plus/minus 0.005 micrometer] in inducing cell transformation. When the average fiber length of thin glass fibers was reduced from 9.5 to 1.7 micrometer by milling the fibers in a mortar and pestle, a 10-fold decrease in transforming activity resulted. When the average fiber length was reduced to 0.95 micrometer, transforming ability was totally absent. The cytotoxic potencies of the various mineral dusts correlated with their transforming potencies. The varying abilities of the mineral dusts to induce cell transformation in vitro are similar to their abilities to induce mesotheliomas in vivo. Thus, this system provides a unique model for studying the mechanism of mineral fiber tumorigenesis and for comparing the relative risks of mineral dusts.


Role of AMP-activated protein kinase in the regulation by glucose of islet beta cell gene expression.
Elevated glucose concentrations stimulate the transcription of the pre-proinsulin (PPI), L-type pyruvate kinase (L-PK), and other genes in islet beta cells. In liver cells, pharmacological activation by 5-amino-4-imidazolecarboxamide riboside (AICAR) of AMP-activated protein kinase (AMPK), the mammalian homologue of the yeast SNF1 kinase complex, inhibits the effects of glucose, suggesting a key signaling role for this kinase. Here, we demonstrate that AMPK activity is inhibited by elevated glucose concentrations in MIN6 beta cells and that activation of the enzyme with AICAR prevents the activation of the L-PK gene by elevated glucose. Furthermore, microinjection of antibodies to the alpha2- (catalytic) or beta2-subunits of AMPK complex, but not to the alpha1-subunit or extracellular stimulus-regulated kinase, mimics the effects of elevated glucose on the L-PK and PPI promoter activities as assessed by single-cell imaging of promoter luciferase constructs. In each case, injection of antibodies into the nucleus and cytosol, but not the nucleus alone, was necessary, indicating the importance of either a cytosolic phosphorylation event or the subcellular localization of the alpha2-subunits. Incubation with AICAR diminished, but did not abolish, the effect of glucose on PPI transcription. These data suggest that glucose-induced changes in AMPK activity are necessary and sufficient for the regulation of the L-PK gene by the sugar and also play an important role in the regulation of the PPI promoter.


Ethical challenges in designing and conducting medicine quality surveys.
In this paper we discuss the main ethical challenges related to the conduct of medicine quality surveys and make suggestions on how to address them. Most evidence-based information regarding medicine quality derives from surveys. However, existing research ethical guidelines do not provide specific guidance for medicine quality surveys. Hence, those conducting surveys are often left wondering how to judge what counts as best practice. A list of the main ethical challenges in the design and conduct of surveys is presented. It is vital that the design and conduct of medicine quality surveys uphold moral and ethical obligations and analyse the ethical implications and consequences of such work. These aspects include the impact on the local availability of and access to medicines; the confidentiality and privacy of the surveyors and the surveyed; questions as to whether outlet staff personnel should be told they are part of a survey; the need of ethical and regulatory approvals; and how the findings should be disseminated. Medicine quality surveys should ideally be conducted in partnership with the relevant national Medicine Regulatory Authorities. An international, but contextually sensitive, model of good ethical practice for such surveys is needed.


Supported imprinted nanospheres for the selective recognition of cholesterol.
The preparation of innovative polymeric systems using molecular imprinting technology for application in extracorporeal blood purification is described. Membranes based on a methylmethacrylate-co-acrylic acid copolymer, produced through the phase inversion method, were modified introducing into their structure specific binding sites for cholesterol molecule by adding molecularly imprinted nanoparticles in the membrane matrix. Membranes prepared are intended to selectively remove cholesterol from the blood by using interactions at a molecular level, between the membrane/nanoparticles devices and the template, created during the preparation of polymers. Three polymeric systems in form of nanoparticles were prepared differing in the polymerisation solvent (a mixture of acetonitrile and ethanol (1:1) or pure ethanol), and the molar ratio between the functional monomer and the cross-linker (2.3:1 and 1:1). Two out of three of the prepared polymers showed a very good template rebinding capacity both in phosphate buffer solution (pH 6.9) and in ethanol. In particular the nanoparticles rebound 115.4 mg cholesterol/g polymer in buffer solution, and 57 mg cholesterol/g polymer in ethanol. The deposition of the nanoparticles on the surface of the phase inversion membranes produced devices with interesting rebinding performances towards cholesterol in buffer solution: a specific recognition of 14.09 mg cholesterol/g system (membrane and nanoparticles) was detected, indicating maintained binding capacity of supported particles as well.


Design of charge-balanced time-optimal stimuli for spiking neuron oscillators.
In this letter, we investigate the fundamental limits on how the interspike time of a neuron oscillator can be perturbed by the application of a bounded external control input (a current stimulus) with zero net electric charge accumulation. We use phase models to study the dynamics of neurons and derive charge-balanced controls that achieve the minimum and maximum interspike times for a given bound on the control amplitude. Our derivation is valid for any arbitrary shape of the phase response curve and for any value of the given control amplitude bound. In addition, we characterize the change in the structures of the charge-balanced time-optimal controls with the allowable control amplitude. We demonstrate the applicability of the derived optimal control laws by applying them to mathematically ideal and experimentally observed neuron phase models, including the widely studied Hodgkin-Huxley phase model, and by verifying them with the corresponding original full state-space models. This work addresses a fundamental problem in the field of neural control and provides a theoretical investigation to the optimal control of oscillatory systems.


Collaborative Depression Care in a Safety Net Medical Home: Facilitators and Barriers to Quality Improvement.
Little is known about how to integrate primary care with mental/behavioral services outside of clinical trials. The authors implemented a collaborative care model (CCM) for depression in a safety net patient-centered medical home. The model focused on universal screening for symptoms, risk stratification based on symptom severity, care management for intensive follow-up, and psychiatry consultation. CCM increased rates of primary care physician encounters, timely follow-up for monitoring symptoms of depression, and documentation of treatment response. Contextual factors that facilitated or hindered practice redesign included clinic leadership, quality improvement culture, staffing, technology infrastructure, and external incentives/disincentives for organizational change.


The postfire discomycete Geopyxis carbonaria (Ascomycota) is a biotrophic root associate with Norway spruce (Picea abies) in nature.
The hypothesis that the postfire discomycete Geopyxis carbonaria (Ascomycota, Pezizales, Pyronemataceae) has a biotrophic association with roots of Norway spruce (Picea abies) in nature was tested by isolation of fungal strains from fresh, brown, smooth mycorrhiza-like root tips of Norway spruce collected from below the depth of detrimental heat penetration in a postfire site. The morphology of seven culture isolates originating from the smooth mycorrhiza-like root tips of two different spruce trees was congruent with the morphology of axenic culture isolates obtained from ascospores of G. carbonaria. DNA sequences of the nuclear ribosomal internal transcribed spacers ITS1 and ITS2 from these root-derived cultures and the ascosporic G. carbonaria culture isolates were found to be identical, further supporting the conclusion that the isolates were conspecific. The extensive ascocarp and ascospore formation of G. carbonaria which succeeds a forest fire may be explained in terms of a fungal escape from a moribund tree associate. Possible ecological adaptations of G. carbonaria to the pre- and postfire community are discussed.


Research to practice in occupational health nursing.
Occupational health nursing research has gained a significant place in national and international nursing programs and has advanced occupational health nurses' understanding of the most effective ways to prevent occupational illness and injury, provide access to quality care for workers, and manage occupational injuries and return to work. This article describes the history of nursing research in general and highlights the current national shortages that must be addressed to ensure that nurses continue to impact the field. Occupational health nursing priorities are described and examples are given of nurse scientists who have established the foundation of occupational health nursing research and who illustrate varied expertise and the interdisciplinary context in which the work is conducted.


In vitro and ex vivo effects of the phosphodiesterase 4 inhibitor, rolipram, on thromboxane production in equine blood.
Phosphodiesterase 4 (PDE4) inhibitors have been shown to inhibit equine neutrophil function in vitro and may be of benefit in recurrent airway obstruction (RAO), an allergy-based respiratory disease characterized by inflammatory cell recruitment and activation within the lungs following exposure of susceptible horses to allergens in mouldy hay. The aim of this study was to evaluate the inhibitory effects of the PDE4 inhibitor, rolipram, in an in vitro assay of thromboxane (Tx) production. The assay was then used to monitor the activity of this compound in vivo in normal and RAO-affected horses. Rolipram and the structurally distinct PDE4 inhibitor, denbufylline, attenuated both lipopolysaccharide (LPS)-induced and unstimulated Tx production in blood from normal horses. Thromboxane production appeared to involve a calcium-dependent interaction between leucocytes and platelets (LPS-induced Tx production = 2.3 +/- 0.4, 4.5 +/- 1.1 and 20.8 +/- 3.6 ng/mL for platelets, leucocytes and blood, respectively) and rolipram-inhibited Tx production via an effect on leucocytes. Inhibition of ex vivo LPS induced Tx production was detected after intravenous administration of rolipram (5 microg/kg) to normal ponies. This dose did not significantly affect either lung function or neutrophil accumulation when administered to three horses with clinical signs of RAO. This study suggests that inhibition of Tx production in equine blood can be used to measure PDE4 activity. However, PDE4 inhibitors with improved therapeutic profiles are required for evaluation in RAO.


Emergency department overcrowding and inpatient boarding: a statewide glimpse in time.
This was a point-prevalence study designed to quantify the magnitude of emergency department (ED) overcrowding and inpatient boarding. Every ED in Michigan was surveyed at a single point in time on a Monday evening. Given the high patient volumes on Monday evenings, the effect on inpatient boarding the next morning was also reviewed. All 134 EDs within the state of Michigan were contacted and surveyed on Monday evening, March 16, 2009, over a single hour and again the following morning. Questions included data on annual census, bed number, number of admitted patients within the ED, ambulance diversion, and ED length of stay. Data were obtained from 109 of the 134 (81%) hospitals on Monday evening and 99 (74%) on Tuesday morning. There was no difference in annual visits or ED size between participating and nonparticipating EDs. Forty-seven percent of EDs were boarding inpatients on Monday evening, compared with 30% on Tuesday morning. The mean estimated boarding times were 3.7 hours (Monday evening) and 7.2 hours (Tuesday morning). Twenty-four percent of respondents met the definition of overcrowded during sampling times. There was a significant relationship between inpatient boarding and ED overcrowding (p < 0.001). Only three EDs were actively diverting ambulances. In this study on a single Monday evening, 47% of EDs in Michigan were actively boarding inpatients, while 24% were operating beyond capacity. On the following morning (Tuesday), EDs had fewer boarded inpatients than on Monday evening. However, these boarded inpatients remained in the ED for a significantly longer duration.


CCR6 Deficiency Impairs IgA Production and Dysregulates Antimicrobial Peptide Production, Altering the Intestinal Flora.
Intestinal immunity exists as a complex relationship among immune cells, epithelial cells, and microbiota. CCR6 and its ligand-CCL20 are highly expressed in intestinal mucosal tissues, such as Peyer's patches (PPs) and isolated lymphoid follicles (ILFs). In this study, we investigated the role of the CCR6-CCL20 axis in intestinal immunity under homeostatic conditions. CCR6 deficiency intrinsically affects germinal center reactions in PPs, leading to impairments in IgA class switching, IgA affinity, and IgA memory B cell production and positioning in PPs, suggesting an important role for CCR6 in T-cell-dependent IgA generation. CCR6 deficiency impairs the maturation of ILFs. In these follicles, group 3 innate lymphoid cells are important components and a major source of IL-22, which stimulates intestinal epithelial cells (IECs) to produce antimicrobial peptides (AMPs). We found that CCR6 deficiency reduces IL-22 production, likely due to diminished numbers of group 3 innate lymphoid cells within small-sized ILFs. The reduced IL-22 levels subsequently decrease the production of AMPs, suggesting a critical role for CCR6 in innate intestinal immunity. Finally, we found that CCR6 deficiency impairs the production of IgA and AMPs, leading to increased levels of Alcaligenes in PPs, and segmented filamentous bacteria in IECs. Thus, the CCR6-CCL20 axis plays a crucial role in maintaining intestinal symbiosis by limiting the overgrowth of mucosa-associated commensal bacteria.


Transjugular mitral valve repair with the MitraClip: A step-by-step guide.
The MitraClip procedure is carried out almost exclusively via the transfemoral approach. However, in some patients transfemoral delivery of MitraClip is not technically feasible (e.g., occluded inferior vena cava or tortuous/obstructive iliofemoral venous anatomy). The technical considerations and challenges of the MitraClip procedure are amplified when an alternate route is considered. We describe a successful case of MitraClip performed via the right internal jugular (IJ) approach in a patient with a flail A3 scallop and previous mitral valve repair. We reviewed prior cases in the literature and discuss step-by-step the pertinent clinical and technical considerations for performing this procedure via the transjugular route. In summary, the right IJ access site provides a reasonable alternative to perform the MitraClip procedure in cases where femoral access is contraindicated or prohibitive. A thorough understanding of the technical considerations is crucial in improving procedural success rates.


Accumulation of herpes simplex virus type 1 glycoprotein D in adhesion areas of infected cells.
By indirect immunofluorescence microscopy (IIF) we have localized glycoprotein D (gD) of herpes simplex virus-infected cells to the vinculin-containing junctional areas and to the focal adhesion sites on the ventral surface of the cells. Double-staining IIF showed that gD and vinculin co-distributed in the infected cells and treatment of the infected cells 4 h post-infection with rabbit antibodies to gD prevented attachment of the cells to the growth substratum. Our results therefore support the hypothesis that gD plays a central role in the social behaviour of infected cells.


Dosage-dependent impacts of a floral volatile compound on pollinators, larcenists, and the potential for floral evolution in the alpine skypilot Polemonium viscosum.
All volatile organic compounds (VOCs) vary quantitatively, yet how such variation affects their ecological roles is unknown. Because floral VOCs are cues for both pollinators and floral antagonists, variation in emission may have major consequences for costs and benefits in plant-pollinator interactions. In Polemonium viscosum, the emission rate for the floral VOC 2-phenylethanol (2PE) spans more than two orders of magnitude. We investigated the ecological and evolutionary impacts of this immense phenotypic variation. The emission rate of 2PE varies independently of nectar rewards and thus is uninformative of profitability. Emission is elevated in flowers that are morphologically vulnerable to ant larcenists, suggesting that chemical deterrence may compensate for weak physical barriers. In nature, plants emitting more 2PE than their neighbors escape ant damage. Flower-damaging ants die when exposed to 2PE in the laboratory, and they avoid high 2PE emitters in the field. High 2PE also reduces bumblebee visitation and pollination, suggesting an ecological cost of defense in pollinator service. However, at more moderate emission rates, 2PE enhances the amount of nectar left in flowers, at no pollination cost. In conclusion, repellency of 2PE is highly sensitive to dosage, giving it a key role in shaping ecological interactions between skypilot plants and their floral visitors.


Noncoplanar ferrimagnetism and local crystalline-electric-field anisotropy in the quasicrystal approximant Au70Si17Tb13.
Neutron scattering experiments have been performed to elucidate magnetic properties of the quasicrystal approximant Au70Si17Tb13, consisting of icosahedral spin clusters in a body-centered-cubic lattice. Bulk magnetic measurements performed on the single crystalline sample unambiguously confirm long-range ordering at T C = 11.6 ± 1 K. In contrast to the simple ferromagnetic response in the bulk measurements, single crystal neutron diffraction confirms a formation of intriguing non-collinear and non-coplanar magnetic order. The magnetic moment direction was found to be nearly tangential to the icosahedral cluster surface in the local mirror plane, which is quite similar to that recently found in the antiferromagnetic quasicrystal approximant Au72Al14Tb14. Inelastic neutron scattering on the powdered sample exhibits a very broad peak centered at ℏω ≃ 4 meV. The observed inelastic spectrum was explained by the crystalline-electric-field model taking account of the chemical disorder at the fractional Au/Si sites. The resulting averaged anisotropy axis for the crystalline-electric-field ground state is consistent with the ordered moment direction determined in the magnetic structure analysis, confirming that the non-coplanar magnetic order is stabilized by the local uniaxial anisotropy.


Treatment of invasive candidal infections: systematic review and meta-analysis.
To compare available antifungal treatments for invasive candidiasis, a leading cause of nosocomial bloodstream infections. We performed a systematic review and meta-analysis of randomized controlled trials that compared different antifungal agents for the treatment of candidemia and other forms of invasive candidiasis. Two reviewers independently appraised the quality of trials and extracted data. The primary outcome was all-cause mortality, and secondary outcomes were microbiological failure, treatment failure, and adverse events. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled. Of the 15 included trials, 9 compared fluconazole with other drugs (amphotericin B, itraconazole, or a combination of fluconazole and amphotericin B), 4 compared echinocandins with other drugs (fluconazole, amphotericin B, liposomal amphotericin B), 1 compared micafungin and caspofungin, and 1 compared amphotericin B plus fluconazole and voriconazole. No difference in mortality was observed with fluconazole vs amphotericin B (RR, 0.92; 95% CI, 0.72-1.17); however, the rate of microbiological failure increased in the fluconazole arm (RR, 1.52; 95% CI, 1.12-2.07). Anidulafungin decreased the rate of microbiological failure compared with fluconazole (RR, 0.50; 95% CI, 0.29-0.86) with fewer adverse events. Caspofungin was comparable to amphotericin B in mortality and efficacy, with fewer adverse events requiring discontinuation (RR, 0.11; 95% CI, 0.04-0.36). Micafungin was comparable to liposomal amphotericin B in mortality. All assessed antifungal agents showed similar efficacy, but the rate of microbiological failure increased with fluconazole vs amphotericin B or anidulafungin. Amphotericin B is associated with a higher rate of adverse events than fluconazole and echinocandins.


Hypercalcemia of Malignancy: An Update on Pathogenesis and Management.
Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy including parathyroid hormone-related peptide-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25 Vitamin D-mediated hypercalcemia, and parathyroid hormone-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers. Diagnosis should include the history and physical examination as well as measurement of the above mediators of hypercalcemia. Management includes hydration, calcitonin, bisphosphonates, denosumab, and in certain patients, prednisone and cinacalcet. Patients with advanced underlying kidney disease and refractory severe hypercalcemia should be considered for hemodialysis. Hematology or oncology and palliative care specialists should be involved early to guide the options of cancer targeted therapies and help the patients and their closed ones with the discussion of comfort-oriented care.


Neutralization of the lethal activity from Bothrops atrox venom by hyperimune llama serum (Lama glama).
To evaluate the capacity of the hyperimmune llama serum (Lama glama) to neutralize the lethal activity of Bothrops atrox venom in laboratory mice. Mean lethal dose (LD50) was calculated from a Bothrops atrox venom sample pool from Peru. The antibody titers were measured by ELISA assay; and the immune serum neutralization potency was measured by calculating the mean effective dose (ED50) during the immunization period. The venom's LD50 was 3.96 μg/g; similar to what was found in other studies about Bothrops atrox carried out in Peru. The titers of antibodies against the venom increased rapidly in the llama, demonstrating a fast immune response; however, the neutralization capacity increased slowly and required several doses and immunization reinforcements, obtaining a ED50 of 3.30 μL/g mouse and a neutralization potency of 3.6 mg/mL after 15 immunizations. The hyperimmune llama serum is able to neutralize the lethality of the Bothrops atrox venom from Peru in laboratory mice.


Surgical Management of Distal Tibia Fracture: Towards An Outcome-based Treatment Algorithm.
Distal tibia fractures are frequently associated with an extensive soft tissue injury which then leads to a higher risk of complications such as infection, non-union and eventually poor overall outcome. The purpose of this study is to measure the outcome of distal tibia fractures treated with internal fixation, external fixator or Ilizarov external fixator(IEF). We aim to propose an algorithm for management of distal tibia fractures by evaluating the treatment options, outcomes and risk factors present. This study is a cross-sectional study of all distal tibia fractures treated surgically in Tengku Ampuan Rahimah Hospital, Klang from 1st January 2016 till 30th June 2018. Patient records were reviewed to analyse the outcomes of surgical treatment and risk factors associated with it. Ninety-one patients were included with a mean age of 41.5 years (SD = 16.4). Thirty-nine cases (42.9%) were open fractures. Thirty-eight patients (41.8%) were treated with internal fixation, 27 patients (29.7%) were treated with IEF and 26 patients (28.6%) were treated with an external fixator. Among open fractures cases, no significant finding can be concluded when comparing each surgical option and its outcome, although one option was seen better than the other in a particular outcome. Initial skeletal traction or temporary spanning external fixator in close fractures reduced the risk of mal-alignment (p value=0.001). Internal fixation is seen superior to IEF and external fixator in close fractures in term of articular surface reduction (p value = 0.043) and risk of mal-alignment (p value = 0.007). There is no single method of fixation that is ideal for all pilon fractures and suitable for all patients. This proposed algorithm can help surgeons in deciding treatment strategies in the challenging management of distal tibia fractures to reduce associated complications.


"Prevention" and Human Gene Editing Governance.
The Holocaust and the racial hygiene doctrine that helped rationalize it still overshadow contemporary debates about using gene editing for disease prevention. In part, this is because prevention can mean 3 different things, which are often conflated. Phenotypic prevention involves modifying the expression of pathogenic DNA variants to forestall their clinical effects in at-risk patients. Genotypic prevention involves controlling transmission of pathogenic variants between generations to avoid the birth of affected offspring. Preventive strengthening seeks to improve normal human traits to resist disease. These distinctions have been neglected in human gene editing governance discussions and are clarified in this article.


Adverse reactions of aspirin and related drugs.
The term "aspirin intolerance" is defined as acute urticaria-angioedema, bronchospasm, severe rhinitis, or shock occurring within three hours of aspirin ingestion. Aspirin intolerance occurs most commonly in patients with chronic urticaria (23%), in whom it is mostly manifested by the urticaria type of aspirin tolerance, and in asthmatic individuals (4%), in whom it is mostly manifested by the bronchospastic type. There is no definite evidence that aspirin intolerance is mediated by an immunologic reaction. In the bronchospastic type, an association between prostaglandins and the slow-reacting substance of anaphylaxis (SRS-A) seems likely. It is possible that aspirin causes a preponderance of prostaglandin F2 alpha (PGF2 alpha), resulting in bronchospasm. The effect of aspirin on blood histamine is controversial. The two major types of aspirin intolerance seem to be mediated by different mechanisms.


Novel roles for saccharomyces cerevisiae mitotic spindle motors.
The single cytoplasmic dynein and five of the six kinesin-related proteins encoded by Saccharomyces cerevisiae participate in mitotic spindle function. Some of the motors operate within the nucleus to assemble and elongate the bipolar spindle. Others operate on the cytoplasmic microtubules to effect spindle and nuclear positioning within the cell. This study reveals that kinesin-related Kar3p and Kip3p are unique in that they perform roles both inside and outside the nucleus. Kar3p, like Kip3p, was found to be required for spindle positioning in the absence of dynein. The spindle positioning role of Kar3p is performed in concert with the Cik1p accessory factor, but not the homologous Vik1p. Kar3p and Kip3p were also found to overlap for a function essential for the structural integrity of the bipolar spindle. The cytoplasmic and nuclear roles of both these motors could be partially substituted for by the microtubule-destabilizing agent benomyl, suggesting that these motors perform an essential microtubule-destabilizing function. In addition, we found that yeast cell viability could be supported by as few as two microtubule-based motors: the BimC-type kinesin Cin8p, required for spindle structure, paired with either Kar3p or Kip3p, required for both spindle structure and positioning.


Self-limiting paratransgenesis.
Presently, the principal tools to combat malaria are restricted to killing the parasite in infected people and killing the mosquito vector to thwart transmission. While successful, these approaches are losing effectiveness in view of parasite resistance to drugs and mosquito resistance to insecticides. Clearly, new approaches to fight this deadly disease need to be developed. Recently, one such approach-engineering mosquito resident bacteria to secrete anti-parasite compounds-has proven in the laboratory to be highly effective. However, implementation of this strategy requires approval from regulators as it involves introduction of recombinant bacteria into the field. A frequent argument by regulators is that if something unexpectedly goes wrong after release, there must be a recall mechanism. This report addresses this concern. Previously we have shown that a Serratia bacterium isolated from a mosquito ovary is able to spread through mosquito populations and is amenable to be engineered to secrete anti-plasmodial compounds. We have introduced a plasmid into this bacterium that carries a fluorescent protein gene and show that when cultured in the laboratory, the plasmid is completely lost in about 130 bacterial generations. Importantly, when these bacteria were introduced into mosquitoes, the bacteria were transmitted from one generation to the next, but the plasmid was lost after three mosquito generations, rendering the bacteria non-recombinant (wild type). Furthermore, no evidence was obtained for horizontal transfer of the plasmid to other bacteria either in culture or in the mosquito. Prior to release, it is imperative to demonstrate that the genes that thwart parasite development in the mosquito are safe to the environment. This report describes a methodology to safely achieve this goal, utilizing transient expression from a plasmid that is gradually lost, returning the bacterium to wild type status.


Strain on Scarce Intensive Care Beds Drives Reduced Patient Volumes, Patient Selection, and Worse Outcome: A National Cohort Study.
Strain on ICUs during the COVID-19 pandemic required stringent triage at the ICU to distribute resources appropriately. This could have resulted in reduced patient volumes, patient selection, and worse outcome of non-COVID-19 patients, especially during the pandemic peaks when the strain on ICUs was extreme. We analyzed this potential impact on the non-COVID-19 patients. A national cohort study. Data of 71 Dutch ICUs. A total of 120,393 patients in the pandemic non-COVID-19 cohort (from March 1, 2020 to February 28, 2022) and 164,737 patients in the prepandemic cohort (from January 1, 2018 to December 31, 2019). None. Volume, patient characteristics, and mortality were compared between the pandemic non-COVID-19 cohort and the prepandemic cohort, focusing on the pandemic period and its peaks, with attention to strata of specific admission types, diagnoses, and severity. The number of admitted non-COVID-19 patients during the pandemic period and its peaks were, respectively, 26.9% and 34.2% lower compared with the prepandemic cohort. The pandemic non-COVID-19 cohort consisted of fewer medical patients (48.1% vs. 50.7%), fewer patients with comorbidities (36.5% vs. 40.6%), and more patients on mechanical ventilation (45.3% vs. 42.4%) and vasoactive medication (44.7% vs. 38.4%) compared with the prepandemic cohort. Case-mix adjusted mortality during the pandemic period and its peaks was higher compared with the prepandemic period, odds ratios were, respectively, 1.08 (95% CI, 1.05-1.11) and 1.10 (95% CI, 1.07-1.13). In non-COVID-19 patients the strain on healthcare has driven lower patient volume, selection of fewer comorbid patients who required more intensive support, and a modest increase in the case-mix adjusted mortality.


Changes in knowledge, perceptions, preventive behaviours and psychological responses in the pre-community outbreak phase of the H1N1 epidemic.
To investigate the changes in community responsiveness during the pre-community-outbreak phase of the H1N1 epidemic in Hong Kong, a pooled sample of 999 adults was interviewed in three surveys (S1, S2, S3) from 7 May to 6 June 2009. Over time, fewer people felt confident in staying free from H1N1 infection in the following year (S1, 63·3%; S3, 46%; P<0·001). The level of distress due to H1N1 remained modest throughout the study period. People's confidence in the government's ability to control a large-scale H1N1 outbreak declined slightly at the third survey (S1, 80·5%; S3, 73·8%; P=0·025). Across the three surveys, respondents remained vigilant with frequent adoption of preventive measures (e.g. wearing face masks in public areas when suffering from influenza-like symptoms and frequent hand-washing). The public was generally supportive of the Hong Kong government although misconceptions regarding the disease were common. Provision of evidence-based public-health education is still warranted as the disease outbreak unfolds.


Development of an Antigen Detection ELISA for Bancroftian Filariasis Using BmSXP-Specific Recombinant Monoclonal Antibody.
Lymphatic filariasis is a mosquito-borne parasitic disease responsible for morbidity and disability that affects 1.2 billion people worldwide, mainly the poor communities. Currently, filarial antigen testing is the method of choice for the detection of bancroftian filariasis, and to date, there are two commonly used tests. In the present study, a recently reported recombinant monoclonal antibody (5B) specific to BmSXP filarial antigen was used in developing an ELISA for the detection of circulating filarial antigen in sera of patients with bancroftian filariasis. The performance of the ELISA was evaluated using 124 serum samples. The ELISA was positive with all sera from microfilaremic bancroftian filariasis patients (n = 34). It also showed 100% diagnostic specificity when tested with sera from 50 healthy individuals and 40 patients with other parasitic diseases. The developed assay using the novel 5B recombinant monoclonal antibody could potentially be a promising alternative antigen detection test for bancroftian filariasis.


ATP-dependent control of steady-state cytosolic calcium in cultured gastric smooth muscle.
The regulation of intracellular calcium uptake and release in cultured gastric smooth muscle cells was studied in saponin-permeabilized cells derived from the rabbit antrum. Cells were studied in an ATP-regenerating medium in which the value of the ATP-to-ADP ratio was fixed by variation of the relative concentrations of creatine and creatine phosphate in the presence of a constant concentration of adenine nucleotides and creatine kinase. Free calcium in the medium was measured through the use of the fluorescent probe fura-2. As the ratio of ATP/ADP was increased (8.5, 55.0, and 155.0), the rate of calcium sequestration was increased, resulting in a decrease of steady-state free calcium (275.2, 178.4, and 98.1 nM, respectively). The addition of glucose (5 mM) and hexokinase (15 U/ml), which results in an increase of ADP due to the phosphorylation of glucose in the medium, caused an increase of free calcium concentration to a new set point of approximately 400 nM. Mitochondrial blockade with antimycin A before permeabilization had no effect on calcium sequestration or the resultant free calcium concentration, indicating that under physiological conditions calcium is sequestered predominantly into nonmitochondrial storage sites. Specific variation of ATP/ADP had no effect on the concentration dependence of inositol trisphosphate-induced calcium efflux, suggesting the functional independence of intracellular calcium influx and efflux pathways. These results indicate a significant role for cytoplasmic ATP/ADP in the control of intracellular calcium sequestration and the regulation of steady-state calcium concentration in cultured gastrointestinal smooth muscle cells.


Perceived stress and mental health: The mediating roles of social support and resilience among black women exposed to sexual violence.
Black women disproportionately suffer from violence and its subsequent mental health outcomes. Increasing levels of perceived stress are associated with greater symptoms of depression and post-traumatic stress disorder (PTSD). Social support and resilience can potentially mediate the negative consequences of perceived stress on women's mental health. This study assesses the association between perceived stress and mental health outcomes among Black women. In addition, this study examines social support and resilience as mediators of association between perceived stress and mental health. Black women residing in Baltimore, MD (n = 310) were recruited from STD clinics into a retrospective cohort study (2013-2018) on sexual assault and HIV risk. Social support and resilience served as coping variables and were assessed as mediators in the associations between perceived stress and mental health. Analyses were stratified by exposure to sexual violence in adulthood. Almost half of our sample (46%) experienced severe depression and about one-third (27%) experienced severe PTSD. Resilience partially mediated the association between perceived stress and severe depressive symptoms among exposed women. Social support partially mediated the association between perceived stress and severe PTSD symptoms among exposed women. Since this is a cross-sectional analysis, we are unable to determine the temporal relationship between outcome and exposure variables. The CES-D-10 and NSESSS are scales that measure the severity of depressive and PTSD symptoms, respectively, and are not clinical diagnoses. There is a critical need to develop interventions focused on reducing the burden of stress on mental health.


[The mechanism of oxymyoglobin oxidation by copper ions and complexes: myoglobins carboxymethylated and carboxyamidated at histidine residues].
The oxidation of sperm whale oxymyoglobin (MbO2) and its chemically modified derivatives alkylated at solvent-accessible histidines by sodium bromoacetate (CM-MbO2) and iodoacetamide (CA-MbO2) in the presence of ions and glycine complexes of copper, Cu2+, Cu(Gly)+, and Cu(Gly)2, has been studied. The influence of the reagent concentration, pH, and ionic strenth of medium, and also of competitive redox-inactive zinc ions on the reaction was investigated. The localization of Cu(Gly)2 in native sperm whale met-Mb and CM-met-Mb was examined by the high-resolution NMR method. The data obtained confirm that the linkage of copper compounds to surface histidines (all of them are away from the heme, at a distance of 1.8-2.7 nm) has only a minor (no more than 35%) contribution to the overall reaction rate, in particular under conditions of a large, more than 8-10-fold, data, excess of the reagent. The noticeable contribution of His116(113), His48, and His81, which according to NMR are localized on the protein surface and have the greatest affinity to copper, is revealed only at small concentrations of copper, a less than 5-fold excess relative to the protein. This is supported by the sigmoidal pH-dependence curve with the transition pK 6.5 at the equimolar copper concentration. The main contribution to the rate of the reaction studied should involve a linkage of copper to internal histidines, His97(FG4), which is 0.66 nm apart from the heme, and to distal His64(E7). Both are hydrogen bonded, the first with carboxyl group of one of the heme propionates, and the second with liganded O2, have a much lower affinity to copper than surface histidines, and are inaccessible to the modification.


[Effect of pancreatic deoxyribonuclease on growth of Escherichia coli].
Cultivation of Escherichia coli K-12 on a medium containing pancreatic deoxyribonuclease at a concentration of 200 visc. units per 1 ml to 1000 visc. units per 1 ml stimulated growth of the cells but only at the lag phase of synchronous growth of the culture.


[Regulation of foreign plasmid DNA on immune gene after oral administration in mice].
To study the regulation of foreign plasmid DNA on immune gene expression in spleen via the gastrointestinal tract in mice. Mice were orally administered with 200 microg of plasmid pcDNA3 and spleens were isolated at 4 h and 18 h after orally administration. Total RNA was extracted from spleen and spleen gene expression profile of BALB/c mice was analyzed by using Affymetrix oligonucleotide genechip after oral administration of plasmid pcDNA3. Functional cluster analysis was conducted by Genmapp and MAPPFinder software. A lot of immune related genes were up-regulated at 4 h and 18 h after oral plasmid pcDNA3 administration. These genes included transcription factors, cytokines and cytokine receptors, MHC I genes, proteasome genes, complement genes and apoptotic genes. The immunoglobulin genes were down-regulated. MAPPFinder result also showed that plenty of immune response processes were up-regulated. Foreign plasmid DNA can modulate the expression of immune genes via the gastrointestinal tract, and further analysis of related genes and process may help to understand the molecular mechanisms of foreign plasmid DNA in the gastrointestinal tract.


[Strategic management of hospitals in France: balance and perspectives].
The strategic management was introduced in French hospitals in the late 80s, in a context of inefficiency and the need to control healthcare expenditure. This concept has inspired a series of government reforms, the organization and dynamics of hospitals and the mode of regulating the French health system, assuming a real change of professional culture. The changes in the economic context and in the finance of hospitals, the behavior of users, the population aging, the development of chronic diseases and increased competition, are the new challenges to be faced. The involvement of stakeholders is crucial and the strategic management, based on mobilizing these actors, is today, a method of administration particularly well adapted to the health area. This article aims to present the impact of the concept of strategic management in the evolution of French hospitals and the consequences of these developments on the outlook for the dissemination of strategic management in the health sector. To do so, it is examined the evolution of the French context until 2010, the new challenges that French hospitals must face and, finally, the consequences of these challenges on how to design services, manage the relationships between the actors of the health system and organize the operational functioning of hospitals.


Parenting self-efficacy and problem behavior in children at high risk for early conduct problems: the mediating role of maternal depression.
Parenting self-efficacy (PSE) has been positively linked to children's adjustment and negatively associated with maternal depression. However, most PSE research has been cross-sectional, limited to predominantly white, middle-class samples, and has not examined potential mechanisms underlying associations of PSE with children's behavior. The present study investigates: (1) how PSE changes over time, (2) the relationship between age 2 PSE and children's behavior problems 2 years later, and (3) the potential mediating role of maternal depression in relation to the association between PSE and child problem behavior. Participants are 652 ethnically and geographically diverse mothers and their children, at high risk for conduct problems. PSE increased between ages 2 and 4 and higher initial levels predicted lower caregiver-reported age 4 conduct problems after controlling for problem behavior at age 2. The relationship between PSE and later conduct problems was mediated, however, by maternal depression. These findings suggest maternal depression as a potential disruptor of caregiver confidence in early childhood, which has implications for the design and focus of parenting interventions.