Characterization and comparison of lipids in different squid nervous tissues.
We have studied the lipid composition of brain (optic and cerebral lobes), stellate ganglia and fin nerves of the squid. Cholesterol, phosphatidylethanolamine and phosphatidylcholine were the major lipids in these nervous tissues. Phosphatidylethanolamine contained about 3% of its amount in [corrected] plasmalogen form. Phosphatidylserine and -inositol, sphingomyelin and ceramide 2-aminoethylphosphonate were also present in significant amounts. In addition, cardiolipin and free fatty acids were detected in brain (each 2-3% of total lipids) and stellate ganglia (about 1% each), but not in fin nerves. Phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol from brain contained large amounts of polyunsaturated fatty acids, namely 20:4, 20:5 and 22:6 in the n-3 family. On the other hand, phosphatidylcholine, cardiolipin, and sphingomyelin, and ceramide 2-aminoethylphosphonate contained only saturated or monounsaturated C16-C18 fatty acids. The aldehyde moieties of ethanolamine plasmalogen were also C16-C18 saturated or monounsaturated. These lipid compositions are compared with those in other invertebrate nervous systems.


Implications of maternal nutrient restriction in transgenerational programming of hypertension and endothelial dysfunction across F1-F3 offspring.
An extensive variety of prenatal insults are associated with an increased incidence of metabolic and cardiovascular disorders in adult life. We previously demonstrated that maternal global nutrient restriction during pregnancy leads to increased blood pressure and endothelial dysfunction in the adult offspring. This study aimed to assess whether prenatal exposure to nutritional insult has transgenerational effects in F2 and F3 offspring. For this, female Wistar rats were randomly divided into two groups on day 1 of pregnancy: a control group fed standard chow ad libitum and a restricted group fed 50% of the ad libitum intake throughout gestation. At delivery, all animals were fed a standard laboratory chow diet. At 11 weeks of age, one female and one male from each restricted litter were randomly selected and mated with rats from another restricted litters in order to generate the F2 offspring. The same procedure produced F3 generation. Similarly, the rats in the control group were bred for each generation. Our findings show that the deleterious effects of maternal nutrient restriction to which the F0 mothers were exposed may not be limited to the male first generation. In fact, we found that elevated blood pressure, an impaired vasodilatory response to acetylcholine and alterations in NO production were all transferred to the subsequent males from F2 and F3 generations. Our data show that global nutrient restriction during pregnancy results in a specific phenotype that can be passed transgenerationally to a second and third generation.


Characterization of waiting times in a simulation of kidney paired donation.
A national kidney paired donation (KPD) program will substantially increase transplant opportunities for recipients with blood type incompatible or cross-match positive donors. It seems likely that donor-recipient pairs with certain blood types, races or restrictions will wait longer than others for a match, although no data exist to confirm this assumption. We simulated patients and characterized the predicted waiting times for different blood type sub-groups, as well as the effects of patient-imposed restrictions on waiting time. We also compared waiting times of different racial sub-groups. Almost all patients with panel-reactive antibody (PRA) less than 80% match within a few months in a national KPD program, with the longest waiting time seen by O recipients with AB donors. Highly sensitized patients wait considerably longer, especially those unwilling to travel or accept older donors, and those with AB or B donors may not match in a timely manner. Although patients are better served by matching in a combined pool than within their own race, racial inequalities exist and bonus points can offset some of these differences. These data provide the first waiting time predictions that can aid patients with incompatible donors in choosing between KPD and desensitization, and can also facilitate planning for a national KPD program.


Validation of assessment methods for the apparent diffusion coefficient in a clinical trial of axial spondyloarthritis patients treated with golimumab.
To compare three region-of-interest (ROI) settings in the assessment of ADC in a clinical trial, and to evaluate the effectiveness of ADC in assessing therapy-induced changes and predicting clinical outcomes. In a 52-week clinical trial involving patients with axial spondyloarthritis, mean sacroiliac joint (SIJ) ADC measurements using structured, lesion-based, and index-lesion ROI-settings were assessed at baseline and weeks 4, 16, and 52. Variation among the three ROI-settings, correlations with Spondyloarthritis Research Consortium of Canada (SPARCC)-bone marrow edema (BME) SIJ inflammation indices, standardized response means (SRMs), and effectiveness in predicting clinical outcomes were analyzed. Forty of the 53 patients had at least one assessable SIJ lesion on ADC at baseline. The mean of the structured ROI ADC (ADCstruc) was 230 μmm2/s (standard deviation [SD] = 120). This was significantly lower (p < 0.01) than the means of the lesion-based ROI ADC (ADClesion = 420 μmm2/s, SD = 210) and index-lesion ROI ADC (ADCindex = 471 μmm2/s, SD = 278), which did not differ. ADC correlated with SPARCC-BME scores at baseline (p < 0.01) as did changes over time in ADC- and SPARCC-BME (p<0.05). At all follow-up time points, responsiveness was high for ADClesion (SRM > 0.92) and ADCindex (SRM > 0.87) while moderate for ADCstruc (SRM:0.54-0.67). Baseline ADC and changes in ADC did not predict clinical outcomes. Lesion-based and index-lesion ROI ADC could both be used to evaluate the effectiveness of tumor necrosis factor inhibitor therapy. None of the methods could predict clinical outcomes.


Infrared thermography as a tool for the measurement of negative emotions in dairy cows.
In commercial dairy cows, the conditions in which they are kept may lead to negative emotional states associated with the development of chronic physiological and behavioural abnormalities that may compromise their health, welfare and productivity. Such states include fear, stress or anxiety. Behavioural rather than physiological tests are more likely to be used to indicate these states but can be limited by their subjectivity, need for specialised infrastructure and training (of the operator and sometimes the animal) and the time-consuming nature of data collection. Popularly used physiological measures such as blood cortisol may be more appropriate for acute rather than chronic assessments but are easily confounded, for example by a response to the act of measurement per se. More sophisticated physiological measures such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) may be impractical due to cost and time and, like blood cortisol, have the confounding associated with the act of measurement. By contrast, infrared thermography of external body surfaces is remote, non-invasive, easily repeated and follows an objective methodology, allowing longitudinal data acquisition for the inference of changes in chronic emotional state over time. The objective of this review was to investigate the potential of infrared thermography to measure cow emotions. In lactating dairy cows, maximum IRT of the eyes and coronary band of the limbs seem to be most representative of thermoregulatory changes, which are repeatable and correlate with behavioural and physiological indicators of emotional state. IRT methodologies have the potential to become a fundamental tool for the objective assessment of welfare state in dairy cows.


Unusual causes for meralgia paresthetica: systematic review of the literature and single center experience.
Meralgia paresthetica is often idiopathic, but sometimes symptoms may be caused by traumatic injury to the lateral femoral cutaneous nerve (LFCN) or compression of this nerve by a mass lesion. In this article the literature is reviewed on unusual causes for meralgia paresthetica, including different types of traumatic injury and compression of the LFCN by mass lesions. In addition, the experience from our center with the surgical treatment of unusual causes of meralgia paresthetica is presented. A PubMed search was performed on unusual causes for meralgia paresthetica. Specific attention was paid to factors that may have predisposed to LFCN injury and clues that may have pointed at a mass lesion. Moreover, our own database on all surgically treated cases of meralgia paresthetica between April 2014 and September 2022 was reviewed to identify unusual causes for meralgia paresthetica. A total of 66 articles was identified that reported results on unusual causes for meralgia paresthetica: 37 on traumatic injuries of the LFCN and 29 on compression of the LFCN by mass lesions. Most frequent cause of traumatic injury in the literature was iatrogenic, including different procedures around the anterior superior iliac spine, intra-abdominal procedures and positioning for surgery. In our own surgical database of 187 cases, there were 14 cases of traumatic LFCN injury and 4 cases in which symptoms were related to a mass lesion. It is important to consider traumatic causes or compression by a mass lesion in patients that present with meralgia paresthetica.


Genetic heterogeneity of X-linked mental retardation with fragile X. Association of tight linkage to factor IX and incomplete penetrance in males.
X-linked mental retardation with fragile X or Martin-Bell Syndrome (MBS) is a frequent cause of mental retardation. So far segregation analysis of MBS in pedigrees ascertained by different, incomplete criteria has produced results, difficult to interpret, which suggest genetic complexity (Sherman et al. 1985). Biochemical and cell biological studies have failed to provide an assay for genetic heterogeneity in MBS and linkage analysis is the only available method. Such analysis, however, is complicated by the incomplete penetrance of the disease in males and the variable penetrance and expression of the defect in heterozygous females. We have used a new approach to test the heterogeneity of recombination between MBS and the coagulation factor IX gene or the anonymous probe 52A in a group of nine families who have sought genetic counselling at Guy's Hospital. We find that both our families alone and our families plus apparently complete samples of pedigrees reported in the literature, separate into two groups: one tightly and one loosely linked to factor IX. In the combined family sample these represent respectively 0.3 and 0.7 of the total and show recombination fractions of 0.0-0.15 and 0.25-0.5. Furthermore, the families with non-penetrant carrier males show tighter linkage to factor IX than the others, thus confirming the suggestion of a systematic difference among MBS families in the recombination between the disease and the factor IX locus. By contrast, no significant differences were found in the recombination between 52A and factor IX in the two groups of MBS families or in these families versus those with Hunter syndrome examined in our laboratory. The causes of the linkage heterogeneity we describe are not known. At least two alternatives can be considered: The existence of two MBS loci or differences in the recombination between a single MBS locus and the factor IX gene. The association between incomplete penetrance and tight linkage to factor IX as well as the discontinuous variation in recombination fraction we have observed seem to favour the former alternative.


Politics matters for individual attitudes toward vaccine donation: cross-national evidence from the United States and Taiwan.
Vaccine equity has been a major concern during the COVID-19 pandemic. According to the principle of vaccine equity, donor countries should apply the criterion of needs to make decisions about vaccine donation instead of considering recipient countries' economic status. We examine whether people follow the same criterion or consider other factors to decide which country to donate vaccines and how many vaccines should be delivered. We conducted online surveys with the design of conjoint experiment in the United States and Taiwan in 2021. 1,532 American citizens and 1,587 Taiwanese citizens were interviewed. The respondents were broadly quota-matched to their respective demographic proportions on the dimensions of age, gender, and education. We estimated the average marginal component effects (AMCEs) of the conjoint attributes by using the OLS regression models with standard errors clustered at the respondent level. 15,320 and 15,870 decisions on vaccine donation generated by conjoint experiment respectively in the United States and Taiwan were included in the analysis. Both American and Taiwanese people tend to donate vaccines to countries that suffer severe consequences of COVID-19 and democracies compared to authoritarian countries. However, they are less willing to donate vaccines to those with higher levels of capability in response to COVID-19. Taiwanese people tend to donate vaccines to countries having formal diplomatic relations with Taiwan (AMCE 13.4%, 95% CI 11.8%-15.1%). Nonetheless, American people would rather donate vaccines to countries without formal diplomatic relations with the United States (AMCE - 4.0%, 95% CI -5.6%--2.4%). The findings reveal that politics plays a significant role in people's decisions about vaccine donation. Under electoral pressure, political leaders must think about how to respond to the public's preferences over vaccine donation to achieve vaccine equity and address the global health crisis.


Motor resonance to non-visible postural adaptation: A novel aspect of the mirror mechanism.
The activation of the Mirror Neuron System (MNS) has been described to reflect visible movements, but not postural, non-visible, adaptations that accompany the observed movements. Since any motor act is the result of a well-tailored dialogue between these two components, we decided to investigate whether a motor resonance to nonvisible postural adaptations could be detected. Possible changes in soleus corticospinal excitability were investigated by eliciting the H-reflex during the observation of three videos, corresponding to three distinct experimental conditions: 'Chest pass', 'Standing' and 'Sitting', and comparing its size with that measured during observation of a control videoclip (a landscape). In the observed experimental conditions, the Soleus muscle has different postural roles: a dynamic role in postural adaptations during the Chest pass; a static role while Standing still; no role while Sitting. The H-reflex amplitude was significantly enhanced in the 'Chest pass' condition compared to the 'Sitting' and 'Standing' conditions. No significant difference was found between 'Sitting' and 'Standing' conditions. The increased corticospinal excitability of the Soleus during the 'Chest pass' condition suggests that the mirror mechanisms produce a resonance to postural components of an observed action, although they may not be visible. This observation highlights the fact that mirror mechanisms echo non intentional movements as well and points to a novel possible role of mirror neurons in motor recovery.


[Ability of qSOFA1-lactate to predict 30-day mortality in patients seen for infection in the Emergency Department].
To evaluate lactate and the Quick Sepsis-Related Organ Failure Assessment (qSOFA) and compare their ability to predict 30-day mortality in patients treated for infection in emergency departments (ED). Prospective multicenter observational cohort study. We enrolled a convenience sample of patients aged 18 years or older attended in 71 Spanish ED from October 1, 2019, to March 31, 2020. Each model's predictive power was analyzed with the area under the receiver operating characteristic curve (AUC), and its values of sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative (NPV). A total of 4439 patients with a mean (SD) age of 18 years were studied; 2648 (59.7%) were men and 459 (10.3%) died within 30 days. For 30-day mortality, the AUC-COR obtained with the qSOFA = 1 model plus 2 mmol/l lactate was 0.66 (95% CI, 0.63-0.69) with Se: 68%, Es: 70% and NPV:92%, while qSOFA = 1 obtained AUC-COR of 0.52 (95% CI, 0.49-0.55) with a Se:42%, Es:64% and NPV:90%. To predict 30-day mortality in patients presenting to the ED due to an episode of infection, the qSOFA =1 + lactate≥2 mmol/L model significantly improves the predictive power achieved individually by qSOFA1 and becomes very similar to qSOFA≥2.


Reduced upper obstructions in N3 and increased lower obstructions in REM sleep stage detected with manometry.
In obstructive sleep apnea (OSA), airway obstruction occurs at different anatomic levels. The frequency and location of obstructions play a crucial role in the planning of surgical treatment. The aim of this study was to evaluate the pharyngeal obstruction levels in different sleep stages with manometry in OSA patients. In addition, the manometry results were compared with drug-induced sleep endoscopy (DISE). Forty-one patients with OSA received manometry measurements during one night of sleep. All patients were simultaneously evaluated with polysomnography. The frequency of obstructions in different sleep stages was assessed. Twenty patients were additionally studied with DISE. Obstruction levels detected with manometry were compared with DISE. The frequency of upper and to a lesser extent lower obstructions decreased in sleep stage N3. In rapid eye movement (REM) sleep, lower obstructions increased. The overall proportion of upper and lower obstructions detected with manometry corresponded with DISE in 13 of 20 cases. A significant change in the obstruction levels was detected with manometry in N3 and REM sleep. The reduction of both upper and to a lesser extent lower obstructions in N3 suggests more stable airways in slow-wave sleep. Relevant lower obstructions were not detected in DISE compared to manometry in 5 out of 20 examinations. This could be a potential reason for treatment failure of site-specific surgical OSA treatment when only performing DISE preoperatively. Therefore, manometry could be a useful complementary tool in the preoperative evaluation for OSA.


Preparation and application of zeolite-zinc oxide nano composite for nitrate removal from groundwater.
Nanomaterial assisted removal of pollutants from water has got great attention. This study aimed to remove nitrate from groundwater using zeolite and zeolite-ZnO nanocomposite as synergetic effect. Zeolite-ZnO nanocomposite was prepared using the co-precipitation method. The Physico-chemical characteristics of the nanomaterials were determined using XRD, SEM, and FTIR. The results revealed that; Zeolite-ZnO nanocomposites with 13.12 nm particle size have successfully been loaded into the zeolite. In addition, its chemical composition was determined using AAS. The removal efficiency of nitrate from groundwater was studied using a batch experiment. The removal of nitrate was investigated as a function of adsorbent dose, pH, initial concentration of nitrate, contact time, and agitation speed. Moreover, the adsorption isotherm and kinetics were also determined. The results showed that the removal of nitrate was 92% at an optimum dose of 0.5 g, pH 5, initial nitrate concentration of 50 mg/L, the contact time of 1 h, and agitation speed of 160 rpm. The removal nitrate has been fitted well by the Langmuir isotherm model with correlation coefficients of R2 = 0.988. Thus, indicating the applicability of monolayer coverage of the nitrate ion on the surface of the nanocomposite. The adsorption process follows the pseudo-second-order model with a correlation coefficient of R2 = 0.997. The results of this work might find application in remediation of water by removing nitrate to meet the standards of water quality.


Cost estimate of chronic hemodialysis in Kinshasa, the Democratic Republic of the Congo: A prospective study in two centers.
The number of patients on dialysis has significantly increased worldwide. However, prospective studies estimating the cost of hemodialysis (HD) in sub-Saharan Africa remain scarce. The present study aimed to evaluate the direct cost of treating end stage renal disease. Determinants of additional direct cost were also assessed. This study is an analytical, prospective study of cost performed at two HD centers in Kinshasa for a period of 3 months among HD patients enrolled consecutively. The cost analyzed includes only expenditures: consultation, HD session, drugs, comorbidities, laboratory tests, and imaging. Transportation, patient hospitalization, and indirect costs are not taken into account. The determinants of the additional direct cost of HD are identified by multivariate logistic regression analysis. P < 0.05 is the level of statistical significance. The average quarterly direct cost of chronic HD in United States Dollars (US$) is $7070 (~US$28,280 annual cost) at a rate of US$287 per patient per HD session. This cost includes the HD session (US$237) and medicine (US$33) costs, which account for 82.5% and 11.3% of the direct costs, respectively. The presence of at least 4 comorbidities (OR adjusted 4.3, 95% CI [1.23-14.95], P = 0.022) and infection (adjusted OR 4.56, 95% CI [1.05-19.85], P = 0.043) emerged as independent determinants of additional direct cost. The direct cost of HD is very high in Kinshasa, where more than 80% of Congolese people live on less than US$1.25 a day.


Cryptogenic new-onset refractory status epilepticus responded to anti-interleukin-6 treatment.
The aim of this case report was to describe a potential anti-interleukin (IL)-6 treatment for cryptogenic new-onset refractory status epilepticus (C-NORSE). Although an underlying immune-mediated pathogenesis is considered present in some C-NORSE cases, many cases do not respond to classical immunotherapies. We describe the case of a 46-year-old woman with C-NORSE who achieved cessation of long-lasting status epilepticus following administration of tocilizumab, an IL-6 receptor-blocking antibody, although the final outcome was poor. Anti-IL-6 treatment may prove effective in stopping status epilepticus in some C-NORSE cases.


Erratum for Huber et al., "The Microtubule-Stabilizing Protein CLASP1 Associates with the Theileria annulata Schizont Surface via Its Kinetochore-Binding Domain".
[This corrects the article DOI: 10.1128/mSphere.00215-17.].


Structural characterization of cevimeline and its trans-impurity by single crystal XRD.
Cevimeline is muscarinic receptor agonist which increases secretion of exocrine glands. Cevimeline base is a liquid (m.p. 20-25 °C) at ambient conditions, therefore its pharmaceutical formulation as a solid hydrochloride hemihydrate has been developed. The synthesis of cevimeline yields its cis- and trans-isomers and only the cis-isomer is recognized as the API and used in the finished formulation. In this study structural and physicochemical investigations of hydrochloride hemihydrates of cis- and trans-cevimelines have been performed. Single crystal X-ray analyses of both cis- and trans-isomers of cevimeline are reported here for the first time. It was found that the cis-isomer, the API, has less dense crystal packing, lower melting point and higher solubility in comparison to the trans-isomer.


Gene switching by metabolic enzymes--how did you get on the invitation list?
Histone gene expression in mammalian cells is codependent upon the Oct-1 transcription factor and its cognate, OCA-S coactivator complex. Surprisingly, GADPH plays an essential role in the OCA-S complex and confers redox dependence upon the in vitro transcription of histone genes.


Sensory Neurotransmitter Calcitonin Gene-Related Peptide Modulates Tumor Growth and Lymphocyte Infiltration in Oral Squamous Cell Carcinoma.
Head and neck squamous cell carcinoma are highly innervated by peripheral sensory neurons. Local neurotransmitter release (e.g., calcitonin gene-related peptide (CGRP)) from sensory neurons innervating cancer is linked to tumorigenesis. CGRP-immunoreactive nerve presence comprised 9.53±1.9% of total nerve area across 11 HNSCC patients. A syngeneic tongue tumor transplant mouse model of oral cancer and a global Calca knockout mouse (CGRPKO ) are used to investigate the impact of CGRP signaling on tumor growth and the associated immune response in vivo. In tumor-bearing CGRPKO mice, there is a significant reduction in tumor size over time compared to wildtype mice using two different mouse oral cancer cell lines. Furthermore, tumor tissue from CGRPKO mice had a significant increase in tumor-infiltrating CD4+ T cells, cytotoxic CD8+ T cells, and NK1.1+ NK cells compared to wildtype. Fluorescent-activated cell sorting and real-time qPCR are used to confirm that CD4+ T cells are isolated from tumor-bearing wildtype mice containing a high expression of Ramp1 compared to sham mice. These data suggest that sensory neurotransmitter CGRP may modulate oral cancer progression via tumor immunosurveillance. Understanding the relationship between sensory neurons and cancer will aid in repurposing clinically available nervous system drugs for the treatment of cancer.


Analysis of pVU3695, a plasmid encoding glutathione-dependent formaldehyde dehydrogenase activity and formaldehyde resistance in the Escherichia coli VU3695 clinical strain.
The formaldehyde resistance of Escherichia coli VU3695 is due to the expression of glutathione-dependent formaldehyde dehydrogenase (GSH-FDH) activity, which is encoded by the adhC gene located on the plasmid pVU3695. Conjugation of this plasmid to an unrelated PolA deficient strain of E. coli indicated that it encodes its own replication initiation protein and does not confer resistance to several other antimicrobial agents tested in this work. In addition, pVU3695 has homology with replicons that belong to the IncL/M plasmid incompatibility group, which are widely distributed among the Enterobacteriaceae. Curing of pVU3695 abolished the expression of formaldehyde resistance and the presence of a 46-kDa periplasmic protein immunologically related to GSH-FDH. However, the curing of pVU3695 reduced drastically but did not abolish the expression of a protein with similar electrophoretic motility, which was associated with the expression of GSH-FDH activity still present in the cytoplasm of the plasmidless derivative. The data demonstrate that E. coli VU3695 contains a chromosomal and a plasmid copy of adhC actively expressed, with the latter being involved in resistance to exogenous formaldehyde.


Surgical versus Medical Castration for Metastatic Prostate Cancer: Use and Overall Survival in a National Cohort.
Surgical castration for metastatic prostate cancer is used less frequently than medical castration yet costs less, requires less followup and may be associated with fewer adverse effects. We evaluated temporal trends and factors associated with the use of surgical castration. This retrospective cohort study sampled 24,805 men with newly diagnosed (de novo) metastatic prostate cancer from a national cancer registry in the United States (2004 to 2016). Multivariable logistic regression assessed the association between sociodemographic factors and surgery. Multivariable Cox regression evaluated the association between castration type and overall survival. Overall 5.4% of men underwent surgical castration. This figure decreased from 8.5% in 2004 to 3.5% in 2016 (per year later OR 0.89, 95% CI 0.87-0.91, p <0.001). Compared to Medicare, private insurance was associated with less surgery (OR 0.73, 95% CI 0.61-0.87, p <0.001) while Medicaid or no insurance was associated with more surgery (OR 1.68, 95% CI 1.34-2.11, p <0.001 and OR 2.12, 95% CI 1.58-2.85, p <0.001, respectively). Regional median income greater than $63,000 was associated with less surgery (vs income less than $38,000 OR 0.61, 95% CI 0.43-0.85, p=0.004). After a median followup of 30 months castration type was not associated with differences in survival (surgical vs medical HR 1.02, 95% CI 0.95-1.09, p=0.6). In a contemporary, real-world cohort surgical castration use is low and decreasing despite its potential advantages and similar survival rate compared to medical castration. Men with potentially limited health care access undergo more surgery, perhaps reflecting a provider bias toward the perceived benefit of permanent castration.


Rehabilitation of sensorimotor integration deficits in balance impairment of patients with stroke hemiparesis: a before/after pilot study.
Balance impairment in patients with stroke hemiparesis is frequently related to deficits of central integration of afferent inputs (somatosensory, visual, vestibular). Our aim was to evaluate whether balance exercises performed under various sensory input manipulations can improve postural stability and/or walking ability in patients with stroke. Seven chronic hemiparetic subjects were recruited. Patient performance was assessed before, immediately after and one week after treatment (consisting of 20 one-hour daily sessions of several balance exercises) by means of the Sensory Organization Balance Test and the Ten Metre Walking Test. Before treatment, all patients showed balance impairment with difficulty integrating somatosensory information from the lower extremities and excessive reliance upon visual input in standing balance control. After treatment, balance and walking speed significantly increased and this improvement was maintained for one week. These findings indicate that rehabilitation of sensorimotor integration deficits can improve balance in patients with stroke hemiparesis.


[Apoptosis increased by bcl-2 antisense ODN in MCF-7 cell line].
To study the effects of bcl-2 antisense oligonucleotides (ODN) on the expression of bcl-2 and apoptosis in MCF-7 cell line. Artificially synthesized bcl-2 specific antisense OND was introduced into MCF-7 cells by gene pulser electroprotocol. Fluorescence microscope, electron microscope, immunocytochemical staining assay, and FCM were used to detect the effects on cell apoptosis, expressional level of bcl-2 protein and cell cycle after transfecting bcl-2 antisense ODN. The number of apoptotic cells was increased and expression of bcl-2 protein was declined (P < 0.05). FCM showed that the number of G(0)-G(1) phase cells was decreased and the number of G(2)-M, S phase cells were increased. The effective transient expression of bcl-2 antisense ODN can be obtained by gene pulser electroprotocol in MCF-7 cell, the function of bcl-2 gene was declined and the number of apoptotic cells was increased after transfecting bcl-2 antisense ODN. bcl-2 may be used as an useful target in tumor research.


Loss-of-function mutations in melanocortin-1 receptor modulate immune response in teleost fishes.
The melanocortin system is an ancient neuroendocrine system conserved from teleosts to mammals. The melanocortin system is a set of complex neuroendocrine signaling pathways involved in numerous physiological processes, and particularly associated with the hypothalamic-pituitary-interrenal (HPI) axis response. The melanocortin 1 receptor (MC1R) is the central melanocortin receptor involved in pigmentation in vertebrates, including fish. In order to assess the immune role of MC1R, this study used a homozygous Mc1r knockout zebrafish. Hence, skin cortisol levels, variations in the blood leucocyte population, as well as the expression levels of immune genes in various tissues of wild-type TU strain (Tübingen, Nüsslein-Volhard Lab) (WT) and homozygous mc1r knockout zebrafish (mc1rK.O.) stimulated with LPS was carried out. Results show that the mc1rK.O. mutant fish produce lower levels of cortisol in mucus and fewer macrophages in blood after exposure to LPS compared to control fish. Regarding the expression of immune genes, mutant fish show a significant increase in the expression of the anti-inflammatory interleukin il10. These results suggest that the mc1rK.O. mutant fish may follow an alternative mechanism among the immune responses, where macrophages seem to have an anti-inflammatory function, attenuating nitric oxide (NO) production and providing an advantage through the mitigation of excessive or strong inflammatory reactions. Nonetheless, a lower number of this cell type could imply a reduced phagocytic potential in the face of an infection. At the same time, lower cortisol levels in the mc1rK.O. mutant fish could be an advantage as for the lower susceptibility to stress and the physiological and metabolic consequences of high cortisol levels.


Computed tomography in the evaluation of pediatric neck infections.
In children, infections involving both the superficial and deep neck spaces are common. Children so affected typically present with fever, neck mass, neck stiffness, and, occasionally, airway compromise. Radiologic modalities used in the evaluation of neck infections include plain lateral neck radiography, ultrasound, computed tomography, and magnetic resonance imaging. All these modalities have proved useful in the treatment of such infections, specifically the decision to perform incision and drainage. The charts of 66 patients-33 with superficial and 33 with deep neck infections-were analyzed with respect to symptoms, signs, computed tomography findings, and need for surgical intervention. Computed tomography was not particularly helpful in superficial neck infections with regard to the decision to perform surgical drainage; however, it did localize and demonstrate the extent of infection. In deep neck infections we found a 92% correlation between computed tomographic evidence of an abscess and surgical confirmation of one. Contrast-enhanced computed tomography remains an excellent tool in the treatment of neck infections in children.


Self-microemulsifying drug delivery system (SMEDDS) of curcumin attenuates depression in olfactory bulbectomized rats.
Current therapies for depression remain limited and plagued by various side effects. Problems associated with curcumin administration include poor aqueous solubility and bioavailability issues. Hence to overcome these, curcumin self micro emulsifying drug delivery system (SMEDDS) which will result in a nanosize emulsion droplets when administered in vivo were formulated in the present study. Depression was induced by bilateral olfactory bulbectomy and the animals were randomized into 8 groups as normal, control [(vehicle 10 ml/kg, p.o., (per oral)], pure curcumin (10, 20, 40 mg/kg, p.o.), and curcumin SMEDDS (10, 20, 40 mg/kg, p.o). After 14 days of respective treatment, behavioral parameters such as open field test (OFT), ambulation counts and passive avoidance response (PAR) were evaluated. At the end of experiments, blood was withdrawn from r.o.p (retro orbital plexus) for serum cortisol estimation. In OFT, increased central area frequency, peripheral area frequency, central area duration and decreased rearing and grooming were recorded with an increased ambulation counts. In PAR, significant reduction in number of trials and step down from platform was observed in the animals treated with test drug. Serum cortisol level was also found to be decreased in the test groups. Behavioral and biochemical estimations in the present study revealed the improved brain permeability and further increase in biological activity of curcumin SMEDDS.


Preoperative colonoscopic diagnosis of villous adenoma of the appendix. Report of a case and review of the literature.
This case of villous adenoma of the appendix reported is unique by virtue of its having been diagnosed preoperatively using colonoscopy. Only 45 such lesions have been described previously, and a review of those cases reveals that 93 percent were discovered at appendectomy performed either incidentally or for acute appendicitis. The malignant potential of this entity is unknown and its treatment is controversial. Because of a report association between adenomas of the appendix and other gastrointestinal neoplasms, long-term surveillance is recommended.


Exact quasi-relativistic wavefunctions of Hydrogen-like atoms.
Exact solutions of a novel quasi-relativistic quantum mechanical wave equation are found for Hydrogen-like atoms. This includes both, an exact analytical expression for the energies of the bound states, and exact analytical expressions for the wavefunctions, which successfully describe quantum particles with mass and spin-0 up to energies comparable to the energy associated to the mass of the particle. These quasi-relativistic atomic orbitals may be used for improving ab-initio software packages dedicated to numerical simulations in physical-chemistry and atomic and solid-state physics.


Clinical significance of e-antigen/anti-e, with special reference to HBc-antigen in the liver.
e-antigen and anti-e were assayed in sera of asymptomatic HBs-Ag carriers and of patients with liver diseases. Thirteen out of 34 (38.2%) asymptomatic carriers were positive for e-antigen, which was in sharp contrast to the reports from USA and Europe. e-antigen was detected to a greater extent in patients with chronic active hepatitis, reversely anti-e in patients with chronic persistent hepatitis. However, e-antigen was found rarely in patients with cirrhosis and never in 23 cases with hepatoma positive for HBs-Ag. HBc-Ag in the liver was detected in 4 out of 8 e-antigen positive asymptomatic carriers and in 4 out of 5 patients with chronic liver diseases with e-antigen respectively, and moreover in 3 out of 14 anti-e positive cases, so that the presence of anti-e did not necessarily mean the negativity of HBc-Ag in the liver. Anti-HBc titer, however, was lower in anti-e positive sera than in e-antigen positive ones. This may implicate the decreased replication of HBV in cases with anti-e. These results emphasize that the investigation of e-antigen/anti-e is mandatory for the evaluation of the prognosis of asymptomatic carriers and of patients with chronic hepatitis.


Orally delivered solid lipid nanoparticles of irinotecan coupled with chitosan surface modification to treat colon cancer: Preparation, in-vitro and in-vivo evaluations.
Irinotecan-loaded solid lipid nanoparticles (IRI-SLNs) was formulated and tested for its potential activity against colon cancer. IRI-SLNs were prepared by applying the principles of DoE. Nanoparticles were further surface modified using chitosan. Characterizations such as size, poly-dispersity, surface charge, morphology, entrapment, drug release pattern, cytotoxicity were conducted. In-vivo studies in male Wistar rats were carried to ascertain distribution pattern of SLNs and their acute toxicity on various vital organs. Lastly, stability of the SLNs were evaluated. Particles had a size, polydispersity and zeta potential of 430.77 ± 8.69 nm, 0.36 ± 0.02 and -40.06 ± 0.61 mV, respectively. Entrapment of IRI was 62.24 ± 2.90% in IRI-SLNs. Sustained drug release was achieved at a colonic pH and long-term stability of NPs was seen. Cytotoxicity assay results showed that SLNs exhibited toxicity on HCT-116 cells. Biodistribution studies confirmed higher concentration of drug in the colon after surface modification. An acute toxicity study conducted for 7 days showed no severe toxic effects on major organs. Thus, we picture that the developed SLNs may benefit in delivering IRI to the tumour cells, therefore decreasing the dose and dose-associated toxicities.


Suicidal nucleotide sequences for DNA polymerization.
Studying the activity of T7 DNA polymerase (Sequenase) on open circular DNAs, we observed virtually complete termination within potential triplex-forming sequences. Mutations destroying the triplex potential of the sequences prevented termination, while compensatory mutations restoring triplex potential restored it. We hypothesize that strand displacement during DNA polymerization of double-helical templates brings three DNA strands (duplex DNA downstream of the polymerase plus a displaced overhang) into close proximity, provoking triplex formation, which in turn prevents further DNA synthesis. Supporting this idea, we found that Sequenase is unable to propagate through short triple-helical stretches within single-stranded DNA templates. Thus, DNA polymerase, by inducing triplex formation at specific sequences in front of the replication fork, causes self-termination. Possible biological implications of such 'conformational suicide' are discussed. Our data also provide a novel way to target DNA polymerases at specific sequences using triplex-forming oligonucleotides.


A study on the mixture repairing effect of biochar and nano iron oxide on toxicity of Cd toward muskmelon.
Soil contamination with cadmium (Cd) has become a serious problem, adversely affecting food safety and human health. Effective methods are urgently needed to alleviate toxicity of Cd in plants. In this study, a nine-week continuous pot experiments was conducted to explore the effectiveness of the different nano iron oxide (α-Fe2O3, γ-Fe2O3, Fe3O4) alone and combined with biochar in muskmelon grown on a Cd-contaminated soil. The antioxidant system, chlorophyll, soluble protein, other physiological indexes of muskmelon leaves and the distribution of Cd in matrix soil, leaves and fruit were detected. The results showed that Cd was readily absorbed by plants and caused oxidative stress on plants, while biochar, α-Fe2O3 nanoparticles (NPs) and their mixture group (BFe1 group) could significantly improve it. Specifically, the three treatments reduced the Cd content of the fruit by 19.51-78.86%, reduced the Cd content of leaves by 15.44-36.23% and 22.36-31.77% in weeks 3 and 5, respectively. For the activity of enzymes, three treatments decreased superoxide dismutase (SOD) activity and catalase (CAT) activity by 3.41-38.57% and 24.27-30.33% in week 7, respectively. So BFe1 group application immobilized Cd in soil and reduced Cd partitioning in the aboveground tissues. Overall the combination of biochar and α-Fe2O3 NPs can alleviate Cd toxicity in muskmelon and can protect human beings from Cd exposure.


PLA/modified-starch blends and their application for the fabrication of non-woven fabrics by melt-blowing.
Blends of polylactic acid (PLA) and thermoplastic starch (TS) with and without chemical modification were obtained by melt extrusion and used to obtain non-woven fabrics by melt-blowing for the first time. Different TS were obtained by reactive extrusion from native cassava, oxidized, maleated, and dual modified (oxidized and maleated) starch. The chemical modification of starch decreases the difference in viscosity and favors blending, resulting in more homogeneous morphologies, unlike the blends with unmodified TS, which displayed a visible phase separation with large TS droplets. The dual modified starch showed a synergistic effect to process TS by melt-blowing. Regarding non-woven fabrics, values in diameter (2.5-82.1 μm), thickness (0.4-0.6 mm), and grammage (49.9-103.8 g/m2) were explained due to differences in viscosity of the components, and to the fact that during melt the hot air preferentially stretches and thins the areas without large droplets of TS. Moreover, plasticized starch acts as a flow modifier. The porosity of the fibers increased with the addition of TS. Further studies and optimization of blends with low contents of TS and type starch modification will be necessary to completely understand these systems with very complex behavior to obtain non-woven fabrics with improved properties and application.


Dried Blood-Based Protein Profiling Using Antibody Arrays.
Dried blood samples have been increasingly considered for clinical applications in recent years. The main disadvantages that limit DBS utility in clinical applications are the small sample volume collected, area bias and homogeneity issues, and sample preparation requirements for the necessary sensitivity and reproducibility required for clinical assessment. The recent advances in antibody array technology overcome the common disadvantages of immunoassay approaches by increasing the multiplex capabilities and decreasing the sample volume requirements as well as minimizing the expense and technical expertise required with many alternative high-density approaches like mass spectrometry.


Persistence Pays Off: Milvexian Emerges from the Industry's Longstanding Search for Orally Bioavailable Factor XIa Inhibitors.
Over the past two decades, Factor XIa inhibitors have emerged as an exciting new class of antithrombic agents. Identification of orally bioavailable small molecule inhibitors has presented a formidable challenge for medicinal chemists. Herein, those challenges and the problem-solving that resulted in the discovery of milvexian will be presented.


Correction: A randomized controlled trial of nitrate supplementation in well-trained middle and older-aged adults.
[This corrects the article DOI: 10.1371/journal.pone.0235047.].


Synthesis, structure and in vitro cytotoxic studies of novel paramagnetic palladium(III) complexes with hematoporphyrin IX.
Two coordination compounds of Pd(III) with hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp), dinuclear [Pd(III)2(Hp-3H)Cl3(H2O)5]·2PdCl2, 1 and mononuclear [Pd(III)(Hp-2H)Cl(H2O)]·H2O, 2 were obtained and structurally characterized in solid state and solution using spectroscopic, thermal and magnetic methods. In the dinuclear complex, 1 one of the Pd(III) ions is coordinated to the deprotanated COO(-) groups from the side chains of the porphyrin ligand and the second Pd(III) ion - to two adjacent pyrrole N-atoms on the top of the porphyrin ring and a Pd(III)-Hp-Pd(III) system was formed. The Pd(III) ion in the mononuclear complex, 2 is incorporated in the porphyrin core. The Pd(III) centers in both complexes have a distorted octahedral coordination filled with additional donor species such as Cl(-) and H2O. The studied compounds showed in vitro cell growth inhibitory effects at micromolar concentration against a panel of human tumor cell lines. A DNA fragmentation assay indicated that the growth inhibitory effects are at least partly mediated by induction of apoptosis.


Phosphocreatine and adenine nucleotides in postasphyxial hearts with normal basal function and normal oxygen demand.
We investigated whether there is a relationship between the prolonged dysfunction after myocardial ischaemia and the postischaemic phosphocreatine overshoot phenomenon. In 16 open-chest rats 3 periods of 4 minutes of oxygen deficiency were performed and basal haemodynamic variables and the myocardial oxygen demand were determined during the recovery period. At the end of the 20 minutes recovery period, left ventricular pressure, dp/dtmax, ejection fraction, and myocardial oxygen demand were completely recovered. High energy phosphate levels, however, were still altered. The sum of adeninenucleotides was decreased to 78 +/- 4% of control (mean +/- SEM, p less than 0.05). The level of phosphocreatine was markedly elevated to 162 +/- 14 (mean +/- SEM). The persistence of the phosphocreatine overshoot phenomenon, while basal function was already normalized, indicates that a reduced function and thus a reduced energy demand of the contractile apparatus are not the cause of the phosphocreatine overshoot. We found no close relationship between high energy levels and basal function or oxygen demand in myocardium after mild oxygen deficiency.


Dose proportionality of amrinone.
Amrinone was given to 18 healthy subjects in doses of 75, 150, and 225 mg in a randomized crossover design. Plasma levels were shown to rise in proportion to dose. The mean plasma AUC, extrapolated to infinite time, was determined for each dose level; the values obtained were 4, 8.18, and 12.35 micrograms . hr/ml for the 75-, 150-, and 225-mg doses. Mean maximum observed plasma concentrations were 1.03, 1.74, and 2.58 micrograms/ml. At higher doses the extrapolated AUC is more variable, but it is linear over the range of 0.73 to 3.81 mg/kg. The apparent first-order terminal elimination rate is not dose dependent and corresponds to a t1/2 of 3.85 hr.


Liquid-Based Endometrial Cytology Using SurePath™ Is Not Inferior to Suction Endometrial Tissue Biopsy in Clinical Performance for Detecting Endometrial Cancer Including Atypical Endometrial Hyperplasia.
We evaluated the clinical performance of liquid-based endometrial cytology (SurePath™) for detecting endometrial malignancies by comparison with the performance of suction endometrial tissue biopsy. From November 2011 to May 2013, we consecutively collected 1,118 liquid-based endometrial cytology specimens and 674 suction endometrial tissue biopsy specimens. The rate of nonpositive final histology in nonpositive liquid-based endometrial cytology (98.2%) was higher than the rate of nonpositive final histology in nonpositive suction endometrial tissue biopsy (97.0%). None of the clinical performance values of liquid-based endometrial cytology for detecting the endometrial malignancies were statistically inferior to those of the suction endometrial tissue biopsy. When the positivity threshold was more than "atypical endometrial cells of undetermined significance," the rate of positive liquid-based endometrial cytology from cases with a positive final histology (84.5%) was higher than the rate of positive suction endometrial tissue biopsy from cases with a positive final histology (69.8%). However, there were still no significant differences among all the performance values. Our liquid-based endometrial cytology would be more appropriate in various clinical situations as the initial detection tool for endometrial malignancies, rather than suction endometrial tissue biopsy. In addition, it could be used in screening for endometrial malignancies on a broader scale.


Effect of acute heat exposure on the determination of critical power and W' in women and men.
The goal of this study was to investigate to what extent acute heat exposure would affect the parameters of the power-duration relationship, i.e. CP and W', using multiple constant workload tests to task failure, in women and men. Twenty four young physically active participants (12 men, 12 women) performed 3-5 constant load tests to determine CP and W', both in temperate (TEMP; 18°C) and hot (HOT; 36°C) environmental conditions. A repeated-measures ANOVA was executed to find differences between TEMP and HOT, and between women and men. In HOT, CP was reduced by 6.5% (227 ± 50 vs. 212 ± 47 W), while W' increased 12.4% (16.4 ± 4.4 vs. 18.5 ± 5.6 kJ). No significant two-way sex × temperature interactions were observed, indicating that the environmental conditions did not have a different effect in men compared with women. The intersection of the average curvatures in TEMP and HOT occurred at 137 s and 280 W in women, and 153 s and 397 W in men. Acute heat exposure had an impact on the parameters CP and W', i.e. CP decreased whereas W' increased. The increase in W' might be a consequence of the mathematical modelling for the used test methodology, rather than a physiological accurate value of W' in HOT. No differences induced by heat exposure were observed between women and men.


Predictive ability of the sequential organ failure assessment score for in-hospital mortality in patients with cardiac critical illnesses: a nationwide observational study.
Several studies have reported a high predictive ability of the Sequential Organ Failure Assessment (SOFA) score for in-hospital mortality specifically for patients with cardiac critical illnesses, however, differences according to the admission classification (surgical or non-surgical) are unknown. The present study aimed to evaluate the predictive ability of the SOFA score in surgical and non-surgical patients with cardiac critical illnesses. Using the Japanese nationwide Diagnosis Procedure Combination database, we identified patients with cardiac critical illnesses, defined as patients admitted to the intensive care unit (ICU) and treated by cardiologists or cardiovascular surgeons as their physicians in charge from April 2018 to March 2020. The discriminatory ability of the SOFA score for in-hospital mortality was assessed by calculating the area under the receiver operating characteristic curve (AUROC). Among 52 819 eligible patients with available data on their SOFA scores, 33 526 (64%) were postoperative cardiac surgeries. The median SOFA score on ICU admission was 5.0 (interquartile range, 2.0-8.0) and overall in-hospital mortality 6.8%. The AUROC of the SOFA score was 0.75 [95% confidence interval (CI), 0.75-0.76]. In the subgroup analyses, the AUROCs were 0.76 (95% CI, 0.74-0.77) in the surgical patients, 0.83 (95% CI, 0.83-0.84) in the non-surgical patients, and 0.88 (95% CI, 0.87-0.89) in the non-surgical acute coronary syndrome patients. The predictive ability of the SOFA score on the day of ICU admission for in-hospital mortality was confirmed to be acceptable in the patients with cardiac critical illnesses and varied according to the admission classification and primary diagnoses.


Resection plus whole-brain irradiation versus resection plus whole-brain irradiation plus boost for the treatment of single brain metastasis.
The optimal treatment for patients with a single brain metastasis is controversial. This study investigated the value of a radiation boost given in addition to neurosurgerical resection and whole-brain irradiation (WBI). In this retrospective study, outcome data of 105 patients with a single brain metastasis receiving metastatic surgery plus WBI (S + WBI) were compared to 90 patients receiving the same treatment plus a boost to the metastatic site (S + WBI + B). The outcomes that were compared included local control of the resected metastasis (LC) and overall survival (OS). In addition to the treatment regimen, eight potential prognostic factors were evaluated including age, gender, performance status, extent of metastatic resection, primary tumor type, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from first diagnosis of cancer to metastatic surgery. The LC rates at 1 year, 2 years, and 3 years were 38%, 20%, and 9%, respectively, after S + WBI, and 67%, 51%, and 33%, respectively, after S + WBI + B (p = 0.002). The OS rates at 1 year, 2 years, and 3 years were 52%, 25%, and 19%, respectively, after S + WBI, and 60%, 40%, and 26%, respectively, after S + WBI + B (p = 0.11). On multivariate analyses, improved LC was significantly associated with OP + WBI + B (p = 0.006) and total resection of the metastasis (p = 0.014). Improved OS was significantly associated with age ≤ 60 years (p = 0.028), Karnofsky Performance Score > 70 (p = 0.015), breast cancer (p = 0.041), RPA class 1 (p = 0.012), and almost with the absence of extracerebral metastases (p = 0.05). A boost in addition to WBI significantly improved LC but not OS following resection of a single brain metastasis.


Comprehensive DNA methylation profiling of human repetitive DNA elements using an MeDIP-on-RepArray assay.
Hypomethylation of repetitive DNA elements is a common epigenetics event in cancer. Although it is believed that this hypomethylation impacts chromosomal and transcriptional stability of the genome, the extent of repetitive sequences contribution to the development and progression of human cancers remains to be clarified. Repetitive sequences have largely been ignored by genome-wide studies, and thus little is known about the DNA methylation profiles of different repetitive DNA elements types. As a step toward investigating epigenetic landscape of repetitive DNA, we have developed a repeat-specific DNA microarray called RepArray. The RepArray comprises 236 prototypic oligonucleotides that span the main repetitive elements families found in the human genome. Combined to a methylated DNA immunoprecipitation (MeDIP) approach, RepArray allows depicting simultaneously the global trends that affect multiple repeat classes through the analysis of a restricted number of targets. Here, we present the MeDIP-on-RepArray protocol as it was established in our laboratory to delineate DNA methylation changes after chemical or genetic disruption of DNA methyltransferase activity in cells. It might serve as a workflow guideline for screening DNA methylation changes on repetitive elements during development and aging, among tissues and in various types of stress or pathological situations.


[Total hepatic ischemia and reperfusion under normal conditions and submitted to controlled hemorrhagic shock state: effects of neutrophil sequestration in kidney of rats].
The evaluate the effects of total hepatic ischemia and reperfusion under normal conditions and submitted to controlled hemorrhagic shock state on the accumulation of neutrophils in the cortex renal of rats. In this experiment 32 male adult Wistar mice, were divided into four groups: Control Group (CG), submitted to the catheterizations and laparotomy, followed by a period 60 minutes of observation; Shock Group (SG): controlled of hemorrhagic shock (CHS) for 20 minutes (20'), mean arterial pressure (MAP) 40 mmHg, followed by reanimation and reperfusion for 60 minutes (RP60); Pringle Group (PG): Pringle's Maneuver (PM) for 15 minutes (15'), followed for RP60'; Shock-Pringle Group (SPG): CHS (MAP = 40 mmHg) for 20' followed by laparotomy and PM for 15', followed for RP60'. To characterize the poor tissular perfusion blood lactate and the base reserve were measured. The means values neutrophils were: CG = 0.24 (+/-0.28); SG = 1.06 (+/-0.61); PG = 0.18 (+/-0.16); SPG = 0.24 (+/-0.19). The CG demonstrated significant neutrophils accumulation in the renal córtex, when compared between others groups. In this experimental study showed that CHS for 20' followed for RP60 was principal factor by major sequestration of neutrophils in the renal cortex of rats.


A novel variant in the tropomyosin 3 gene presenting as an adult-onset distal myopathy - a case report.
We report a patient with a novel c.737 C > T variant (p.Ser246Leu) of the TPM3 gene presenting with adult-onset distal myopathy. A 35-year-old Chinese male patient presented with a history of progressive finger weakness. Physical examination revealed differential finger extension weakness, together with predominant finger abduction, elbow flexion, ankle dorsiflexion and toe extension weakness. Muscle MRI showed disproportionate fatty infiltration of the glutei, sartorius and extensor digitorum longus muscles without significant wasting. Muscle biopsy and ultrastructural examination showed a non-specific myopathic pattern without nemaline or cap inclusions. Genetic sequencing revealed a novel heterozygous p.Ser246Leu variant (c.737C>T) of the TPM3 gene which is predicted to be pathogenic. This variant is located in the area of the TPM3 gene where the protein product interacts with actin at position Asp25 of actin. Mutations of TPM3 in these loci have been shown to alter the sensitivity of thin filaments to the influx of calcium ions. This report further expands the phenotypic spectrum of myopathies associated with TPM3 mutations, as mutations in TPM3 had not previously been reported with adult-onset distal myopathy. We also discuss the interpretation of variants of unknown significance in patients with TPM3 mutations and summarise the typical muscle MRI findings of patients with TPM3 mutations.


Exploring the use of a Comic for Education about Expanded Carrier Screening among a Diverse Group of Mothers.
Expanded carrier screening (ECS) during prenatal care is an important test for identifying prospective parents' risk of inherited genetic diseases. However, barriers remain for effectively educating patients about ECS. Graphic medicine (i.e. comics) has grown as a mechanism for patient education. The purpose of this study was to explore attitudes and opinions of a comic to educate about ECS during prental care. Focus groups were conducted with pregnant women or women who recently gave birth (6 groups, n=54). The participants were all female, 44.4% Latino/Hispanic, 16.7% Bi-Racial/Other, and 43.3% reporting some college education or high school degree. Most participants reported high enjoyment with the comic due to their relatability to the characters, simplicity of the story, description of medical outcomes in everyday terms and the exploration of multiple outcomes possible with ECS. In addition, participants reported that during pregnancy their reading habits increase as well as emotional reactions to the content and some participants stated they avoided reading information that may cause stress or anxiety. More research is needed to assess what features of the comic promote understanding and how that influences decisions and pre-test patient education for ECS. The use of graphic narratives may enable individuals to better understand medical information in general.


Orbital leiomyoma: report of a case and review of the literature.
A 10-year-old female presented with slowly progressive proptosis of 1 year's duration. Orbital MRI revealed an extraconal oval mass occupying the lateral half of the mid and posterior orbit. The tumor was isointense to the extraocular muscle and cerebral gray matter on T1-weighted images and hyperintense on T2-weighted images. The patient underwent superolateral orbitotomy, and it was felt that the tumor was totally excised in a piecemeal fashion. Histopathologic examination showed that the tumor was composed of spindle cells arranged in a fibrous stroma rich in dilated sinusoidal capillaries. The nuclei of tumor cells were oval with blunted ends. There were no mitotic figures. Immunohistochemically, the tumor stained positive with smooth muscle actin, desmin, and vimentin. Based on the histopathologic and immunohistochemical staining results, a diagnosis of orbital leiomyoma was made. At 34 months follow-up, the patient continues to have 20/20 vision and is free of tumor recurrence clinically. Orbital leiomyoma is an uncommon tumor. Search of the English literature showed only 15 previous cases of orbital leiomyoma that have been published since 1963.


Behavioral Economic Consequences of Disasters: A Basis for Inclusion in Benefit-Cost Analysis.
The purpose of this paper is to develop an analytical framework for estimating the behavioral effects of disasters and their economic consequences. The reduction of these losses represents the benefits of pre-disaster mitigation and post-disaster recovery. We provide conceptualizations, definitions, classifications, and a formal welfare analysis of this category of economic consequences. We also examine methods used to measure behavioral reactions to fear for insight into improving their delineation. Because we are interested in a comprehensive assessment of behavioral effects, we also include resilience adjustments and extend our initial partial equilibrium analysis to the general equilibrium level. The analysis is intended to serve as the basis for the legitimate inclusion of behavioral consequences of disasters in benefit-cost analysis.


Serum lipoprotein(a) level in relation to severity of coronary artery disease and coronary artery patency in acute myocardial infarction.
Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle that may accelerate atherogenesis and promote thrombosis. In the present study, relationships between serum Lp(a) levels and the severity of coronary artery disease and infarct artery patency were studied in 14 patients with acute myocardial infarction. Lp(a) was measured by enzyme-linked immunosorbent assay and the timing of reperfusion was evaluated using the creatine kinase myosin-brain fraction and myoglobin release curves. Thrombolysis in Myocardial Infarction (TIMI) flow grade and severity of coronary artery disease were assessed using a scoring system based on coronary angiography performed during hospitalization and 6 months thereafter. The median Lp(a) level on admission was 127 (range 11-2,513) mg/l. The overall coronary score was higher in patients with Lp(a) levels greater than 127mg/l than in those with Lp(a) less than 127mg/l (P < 0.01). Lp(a) level correlated with the coronary score measured during hospitalization (r = 0.80, P < 0.01) and 6 months later (r = 0.79, P < 0.01). The timing of reperfusion and infarct artery patency were not depen dent on the serum Lp(a) level. The results show that the serum Lp(a) level is associated with the angiographic severity of coronary artery disease postmyocardial infarction bu does not determine the patency of the infarct-related artery.


Blocking the insulin-like growth factor-I receptor as a strategy for targeting cancer.
Clear links between cancer and cellular signaling triggered by the insulin-like growth factor-I (IGF-I) receptor (IGF-IR) and its cognate ligands (IGF-I and IGF-II) have been reported throughout the past two decades. Experimental results suggest that the pharmaceutical targeting of this signaling pathway could be beneficial for the treatment of cancer. Here, more recent advances towards potentially clinically viable strategies to interfere with the function of IGF-IR will be discussed.


Extracorporeal membrane oxygenation for Kawasaki disease: two case reports and the Extracorporeal Life Support Organization experience 1999-2015.
Kawasaki disease is usually a limited illness of early childhood. However, life-threatening cardiac manifestations can occur, either at acute presentation or as a consequence of coronary arterial involvement. We report the successful use of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) for cardiac support in two children with Kawasaki disease: one with acute Kawasaki disease shock syndrome, the other with complications of coronary arteritis and subsequent surgery. We also reviewed the reported experience in the ELSO database and available literature.


Endothelial function in women using levonorgestrel-releasing intrauterine system (LNG-IUS).
Oral levonorgestrel has been linked to increased cardiovascular risk, but currently, no information is available on the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) on endothelial dysfunction. The objective of this study was to assess endothelial function in LNG-IUS users. Sixty women underwent insertion of either an LNG-IUS (n=30) as study group or Copper-T intrauterine contraceptive device (TCu 380A intrauterine device) as control group (n=30). In the midluteal phase of menstrual cycle, endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation of brachial artery were studied before and after 3, 6 and 12 months of device insertion. We also assessed the correlation of FMD and serum concentrations of estradiol (E2), progesterone (P) and LNG. With LNG-IUS, there was a nonsignificant decrease in mean FMD of brachial artery (p>.05) compared with the control group at different time points of the study. Before LNG-IUS, reactive hyperemia caused an 8.3%±1.3% increase in brachial artery diameter compared with 7.1%±1.1%, 7.4%±0.9% and 7.5%±0.9% after 3, 6 and 12 months of LNG-IUS (p>.05). The mean±SD LNG plasma levels at 3, 6 and 12 months of LNG-IUS application were 228±87, 204±94 and 191±79 pg/mL, respectively. E2 levels were comparable in women of both studied groups. Mean P levels were significantly lower after LNG-IUS insertion compared with before device insertion and with the control group (p<.05) at all study visits. No correlation was found between LNG levels and FMD. A nonsignificant change detected in endothelial function in LNG-IUS indicates that it has no increased cardiovascular risk.


Oncology nurses' attitudes towards alternative medicine.
Little is known about nurses' attitudes towards alternative medicine. The purpose of this study was to describe attitudes towards alternative medicine among nurses working on oncology wards in three university and one central hospital in Finland. The data were collected with a questionnaire specifically developed for this project. The response rate was 68.1% (n = 92). The nurses did not regard alternative medicine as a safe and natural method in the treatment of cancer. On the contrary, many nurses believed that alternative therapies are offered by quack doctors for financial gain. However, the nurses considered it important that cancer patients have the opportunity to talk about their use of alternative medicine both with nurses and physicians. Overall the results indicated that nurses' attitudes are for the most part negative. An interesting question that deserves further attention is whether this attitude is reflected in nursing practice.


Diagnosis and management of mitochondrial diseases.
Mitochondrial dysfunction should be considered in the differential diagnosis of any progressive multisystem disorder. The diagnosis is most challenging when only one symptom is present. In contrast, the diagnosis is easier to consider when two or more seemingly unrelated symptoms are present, involving more than one organ system. It is important to consider the diagnosis of a mitochondrial disorder when dealing with an unexplained association of symptoms, with an early onset and progressive course involving seemingly unrelated organs. The investigation can be relatively straightforward if a person has a recognizable phenotype and if it is possible to identify a known pathogenic mtDNA mutation. The difficulty arises when no known mtDNA defect can be found or when the clinical abnormalities are complex and not easily matched to those of more common mitochondrial disorders. In summary: A full mitochondrial evaluation often is warranted in children with a complex neurologic picture or a single neurologic symptom and other system involvement. When the presentation is classic for a maternally inherited mitochondrial syndrome, such as MELAS, MERRF, or Leber's hereditary optic neuropathy, appropriate mtDNA studies should be obtained first. When the clinical picture is classic for a nuclear DNA inherited syndrome and the gene or linkage is known, such as MNGIE, the clinician should proceed with genetic studies. When the clinical picture is nonspecific but highly suggestive of a mitochondrial disorder, the clinician should start with plasma or CSF lactic acid, ketone bodies, plasma acylcarnitines, and urinary organic acids. If these studies are abnormal, the clinician should proceed with muscle biopsy and assessment of the respiratory chain enzymes. Normal plasma or CSF lactic acid does not rule out a mitochondrial disorder.


Sodium hyaluronate in treatment of diffuse nephrogenic adenoma of the bladder in a child.
Nephrogenic adenoma is a rare, benign lesion of the bladder, occurring as an epithelial response to chronic infection or trauma, probably arising from nephrogenic metaplasia. In contrast to nephrogenic adenomas in adults, who present with this tumor in the entire ureteral tract, it has been observed exclusively in the bladder of children thus far. We report and discuss here the case of a 12-year-old boy with diffuse calculus-producing nephrogenic adenoma successfully treated with sodium hyaluronate.


Laparoscopy in a case of pediatric blunt abdominal trauma.
The use of laparoscopy in the assessment and treatment of blunt abdominal trauma has been reported for both adults and children. With increasing surgical experience and improvements in equipment, an expanding range of therapeutic interventions is available. The management of a 7-year-old boy who sustained blunt abdominal trauma during a fall from a bicycle is described. He was hemodynamically stable, but his abdomen remained tender, with guarding in the right upper quadrant. Serial ultrasound scans showed a thick-walled gallbladder and increasing intraabdominal fluid. Laparoscopy was used both as a diagnostic tool, and then as a therapeutic method. Diagnostic laparoscopy showed a ruptured gallbladder treated by laparoscopic cholecystectomy. A 3-cm grade 1 liver laceration also was identified, which required no intervention. Free bile was aspirated and the peritoneal cavity thoroughly lavaged. The child made a rapid postoperative recovery. The ultimate aim in the management of blunt trauma is to avoid unnecessary laparotomy while preventing undue delay in the detection of significant intraabdominal pathology. Computed tomography scanning, ultrasound scanning, and diagnostic peritoneal lavage all have strengths for detecting different injury types, but they also have a low specificity in determining the need for laparotomy. The advantages and limitations of laparoscopy in hemodynamically stable children who have sustained injuries from blunt trauma are discussed. The authors recommend laparoscopy in experienced hands as an additional tool for the optimal management of selected trauma cases.


Systematic stress adaptation of Bacillus subtilis to tetracycline exposure.
To alleviate the harmful effects of antibiotics on the environment and human health, the stress response and molecular network of Bacillus under tetracycline stress were investigated using a proteomics approach. During the exposure process, Bacillus subtilis exhibited a strong adaptation mechanism. Cell membrane and intracellular reactive oxygen species (ROS) level returned to normal after 5 h. A total of 312 upregulated and 65 downregulated proteins were identified, mainly involved in metabolism and the synthesis of ribosomes, DNA, and RNA. After tetracycline exposure, the core metabolism network was accelerated to supply precursors for the synthesis of DNA, RNA, proteins, peptidoglycans, and saturated fatty acids that were involved in ribosome protection, and strengthened the cell wall and cell membrane. The signal transduction pathways involved were analyzed in association with the stress response of B. subtilis at 15 min of exposure to tetracycline. The primary damage to the ribosome by tetracycline activated a series of response proteins. Antitoxin and heat-shock proteins were activated for the global regulation of transcription and metabolism. Trigger factor Tig was upregulated to ensure proper initiation of transcription and aerobic respiration. Temperature-sensor protein VicR from the two-component system was used by the cell to regulate the composition of the cell wall and cell membrane. The over-consumption of metabolites, such as phosphoribosyl diphosphate (PRPP), purine nucleoside triphosphate (GTP), and acetyl-CoA forced the cells to assimilate more sugar for glycolysis. To this end, methyl-accepting chemotaxis proteins (MCPs) and sugar transportation protein PtsG were upregulated, simultaneously. Ultimately, peroxidase was activated to eliminate the redundant ROS, to minimize cell damage. These findings presented a system-level understanding of adaption processes of bacteria to antibiotic stress.


Acute diffusion abnormalities in the hippocampus of children with new-onset seizures: the development of mesial temporal sclerosis.
We studied the role of early diffusion-weighted imaging DWI in the investigation of children with new-onset prolonged seizures which eventually result in unilateral hippocampal sclerosis (HS). We carried out MRI on five children aged 17 months to 7 years including conventional and diffusion-weighted sequences. We calculated apparent diffusion coefficients (ADC) for the affected and the normal opposite hippocampus. Follow-up examinations were performed, including DWI and ADC measurements in four. We studied four children within 3 days of the onset of prolonged psychomotor seizures and showed increased signal on T2-weighted images, and DWI, indicating restricted diffusion, throughout the affected hippocampus. The ADC were reduced by a mean of 14.4% in the head and by 15% in the body of the hippocampus. In one child examined 15 days after the onset of seizures, the ADC were the same on both sides. All five patients showed hippocampal atrophy on follow-up 2-18 months later. In the four patients in whom ADC were obtained on follow-up, they were increased by 19% in the head and 17% in the body. DWI may represent a useful adjunct to conventional MRI for identifying acute injury to the hippocampus which results in sclerosis.


Dinotefuran-induced morphophysiological changes in the ovaries and midgut of semi-engorged females Rhipicephalus sanguineus Latreille, 1806 (Acari: Ixodidae) ticks.
The present study demonstrated the effects of dinotefuran (active compound of the Protetor Pet® acaricide) in germ cells and the digestive processes of semi-engorged females of R. sanguineus exposed to different concentrations of the chemical. For this purpose, 120 semi-engorged females were divided into four treatment groups with 30 individuals each: group I or control (distilled water), group II (5000 ppm), group III (6250 ppm), and group IV (8334 ppm of dinotefuran). All ticks were immersed in different concentrations of dinotefuran or in distilled water for 5 min and then were dried and stored in biological oxygen demand (BOD) incubator for 7 days. The results show the action of this compound, exhibiting morphohistologic and histochemical changes in the oocytes and the midgut cells of individuals of different groups, which were compared with those of group I (control). The alterations occurred mainly in relation to the size of the germ cells and yolk granules; presence, quantity, size, and location of vacuoles found in the cytoplasm of these germ cells; the damage occurred in the generative cells of the midgut; the size of the digestive cells; the quantity of blood elements captured, accumulated digestive wastes and digestive vacuoles found in the cytoplasm of the digestive cells of the midgut, as well as the amount and distribution of proteins, polysaccharides, lipids of all cells in both organs. So, it has demonstrated the effectiveness of dinotefuran in the reduction of fertility and digestive processes of semi-engorged females of R. sanguineus, data that points the possibility of employing this chemical to control these ectoparasites.


A histochemical study of the innervation of cerebral blood vessels in the snake.
Dual innervation of snake cerebral blood vessels by adrenergic and cholinergic fibres was demonstrated with the use of histochemical methods. Although the nerve plexuses are somewhat less dense, the essential features of innervation of the blood vessels are similar to those of mammals with the exception that the adrenergic plexuses are more prominent than the cholinergic plexuses. The major arteries of the cerebral carotid system have a rich nerve supply. However, the innervation is less rich in the basilar and poor in the spinal (vertebral) arteries. Although the arteries supplying the right side of head are poorly developed, three pairs of arteries, cerebral carotids, ophthalmics and spinals, supply the snake brain. The carotids and ophthalmics are densely innervated and are accompanied by thick nerve bundles, suggesting that the nerves preferentially enter the skull along those arteries. Some parenchymal arterioles are also dually innervated. Connection between the brain parenchyma and intracerebral capillaries via both cholinergic and adrenergic fibres was observed. In addition cholinergic nerve fibers, connecting capillaries and the intramedullary nerve fibre bundles, were noticed. Capillary blood flow may be influenced by both adrenergic and cholinergic central neurons. The walls of capillaries also exhibit heavy acetylcholinesterase activity. This may indicate an important role for the capillary in the regulation of intracerebral blood flow.


Tick-borne infections in the United States.
Patients with illnesses caused by ticks may present with flulike symptoms. Physicians should learn how to recognize these illnesses by specific aspects in the patients' histories and physical examinations. Prevention of mortality and morbidity may depend on correct early diagnosis and treatment. Illness prevention may result with early removal of the tick, because infection usually requires 24 to 48 hours of attachment to the host. A bite from one tick may transmit several different pathogens leading to concurrent infections. The prevention of tick-borne illnesses can start with advice on how to prevent tick bites, especially during summer time.


Binding of tissue-type plasminogen activator with human endothelial cell monolayers. Characterization of the high affinity interaction with plasminogen activator inhibitor-1.
The formation and release of covalent complexes between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) limits the application of equilibrium radioligand binding analysis to characterize the interaction between t-PA and human umbilical vein endothelial cell (HUVEC) monolayers. To avoid this difficulty, we used a recombinant mutant of t-PA, S478A rt-PA, in which alanine has been substituted for the active-site serine. Although the mutant is incapable of covalently reacting with PAI-1, 125I-labeled S478A rt-PA binding to HUVEC monolayers is specific and reversible and is characterized by a high affinity (Kd of 1.5 nM) and a large number of sites (1.5 x 10(6)/cell). This binding was shown to occur through noncovalent interaction with PAI-1 in the HUVEC monolayer by the fact that a monoclonal anti-PAI-1 antibody (MA-7D4) completely blocked S478A rt-PA binding. Two solution-phase assays with recombinant PAI-1 (rPAI-1) confirmed this noncovalent interaction: complexes between 125I-S478A rt-PA and rPAI-1 could be isolated by immunoprecipitation with anti-PAI-1 antibodies, and S478A rt-PA competed with rt-PA for inactivation by rPAI-1. In contrast diisopropylphosphate rt-PA (in which the active site serine is chemically modified) showed minimal binding to HUVEC monolayers, as a result of impaired interaction with PAI-1, in the two assays. Thus, both wild-type rt-PA and S478A rt-PA interact with the HUVEC monolayer through PAI-1. With rt-PA this results in the formation of covalent rt-PA.PAI-1 complexes that are released from the monolayer into the supernatant. With S478A rt-PA this results in the formation of noncovalent complexes that remain associated with the HUVEC monolayer, thereby identifying a large pool of reactive PAI-1 molecules in the monolayer.


Risk of natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies.
Previous estimates of risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis receiving natalizumab were stratified by three risk factors: anti-John Cunningham virus (JCV) antibodies in serum, previous immunosuppressant use, and treatment duration, which were estimated using population-based assumptions. We aimed to calculate PML risk estimates from patient-level risk-factor data and to stratify risk by concentrations of anti-JCV antibody in serum (anti-JCV antibody index). Data on natalizumab-treated patients were pooled from four large, observational, open-label studies: STRATIFY-2, STRATA, TOP, and TYGRIS. Data were analysed with and without imputation for missing values of anti-JCV antibody status and previous immunosuppressant use. For anti-JCV antibody-positive patients in this pooled cohort, cumulative PML risk with or without previous immunosuppressant use was estimated using Kaplan-Meier analysis. Annual PML risks (per 12 natalizumab infusions) for patients without PML in the preceding year were estimated using conditional probability based on the life table method. For anti-JCV antibody-positive patients without previous immunosuppressant use, risk estimates were further stratified using a probability distribution for anti-JCV antibody index values, separately for patients with or without PML. Anti-JCV antibody index cutoffs were selected via sensitivity and specificity assessments for identifying PML cases in an index cohort. 156 (<1%) of 37 249 patients in the pooled cohort had PML. We imputed missing values on anti-JCV antibody status (3912 patients) and on previous immunosuppresant use (544 patients) using a multiple imputation method. For anti-JCV antibody-negative patients (n=13 996), estimated PML risk was less than 0·07 per 1000 patients (95% CI 0·00-0·40). In anti-JCV antibody-positive patients (n=21 696), estimated cumulative PML probability over 6 years (72 infusions of natalizumab) was 2·7% (95% CI 1·8-4·0) in patients with previous immunosuppressant use and 1·7% (1·4-2·1) in those without. In patients without previous immunosuppressant use (n=18 616), estimated annual PML risks per 1000 patients, conditional on having no PML before that year, ranged from 0·01 (0·00-0·03) in year 1 (1-12 infusions) to 0·6 (0·0-1·5) in year 6 (61-72 infusions) for people with an index of 0·9 or less; from 0·1 (0·0-0·2) in year 1 to 3·0 (0·2-5·8) in year 6 for those with an index of more than 0·9 up to and including 1·5; and from 0·2 (0·0-0·5) in year 1 to 10·0 (5·6-14·4) in year 6 for those with an index of more than 1·5. Our risk estimates calculated from patient-level clinical data allow individualised annual prediction of risk of PML in patients receiving natalizumab for multiple sclerosis, supporting yearly benefit-risk re-evaluation in clinical practice. Further, our estimates are generally consistent with previously calculated estimates. Incorporating anti-JCV antibody index allows further risk stratification for anti-JCV antibody-positive patients who have not previously taken immunosuppressants. Biogen.


Regular control at the general practitioner is positively correlated with patient satisfaction with chronic care management.
The aim of the study is to identify how disease management programmes for patients with a chronic disease work. This issue is explored from the patients' perspective. Specifically, we study how transition and coordination are related to the patient's perception of quality of care, with a particular focus on the general practitioner's (GP) role. The study is based on a survey conducted among patients with Type 2 diabetes, chronic obstructive pulmonary disease (COPD) or acute coronary syndrome (ACS) in the Central Denmark Region in 2011 and 2012. Data are analysed using logistic regression models. A total of 4,174 patients answered the questionnaire. The response rate was 43%. Whether the patient attends regular visits with the GP or not has a significant influence on both the patient's overall perception of the healthcare sector and on the patient's perception of the organisation of care. Variation among patient groups was identified and COPD patients had the least positive overall perception of the care received. Patients who visit their GP for regular control both have a better overall perception of the healthcare sector and are more likely to think that their treatment is well organised. Patients with COPD have a less positive score than patients with ACS and diabetes. none. not relevant.


Elasticity and adhesion force mapping reveals real-time clustering of growth factor receptors and associated changes in local cellular rheological properties.
Cell surface macromolecules such as receptors and ion channels serve as the interface link between the cytoplasm and the extracellular region. Their density, distribution, and clustering are key spatial features influencing effective and proper physical and biochemical cellular responses to many regulatory signals. In this study, the effect of plasma-membrane receptor clustering on local cell mechanics was obtained from maps of interaction forces between antibody-conjugated atomic force microscope tips and a specific receptor, a vascular endothelial growth factor (VEGF) receptor. The technique allows simultaneous measurement of the real-time motion of specific macromolecules and their effect on local rheological properties like elasticity. The clustering was stimulated by online additions of VEGF, or antibody against VEGF receptors. VEGF receptors are found to concentrate toward the cell boundaries and cluster rapidly after the online additions commence. Elasticity of regions under the clusters is found to change remarkably, with order-of-magnitude stiffness reductions and fluidity increases. The local stiffness reductions are nearly proportional to receptor density and, being concentrated near the cell edges, provide a mechanism for cell growth and angiogenesis.


A review of trial and real-world data applying elements of a realist approach to identify behavioural mechanisms supporting practitioners to taper opioids.
This evidence synthesis applying realist concepts and behavioural science aimed to identify behavioural mechanisms and contexts that facilitate prescribers tapering opioids. We identified relevant opioid-tapering interventions and services from a 2018 international systematic review and a 2019 England-wide survey, respectively. Interventions and services were eligible if they provided information about contexts and/or behavioural mechanisms influencing opioid-tapering success. A stakeholder group (n = 23) generated draft programme theories based around the 14 domains of the Theoretical Domains Framework. We refined these using the trial and service data. From 71 articles and 21 survey responses, 56 and 16 respectively were included, representing primary care, hospital, specialist pain facilities and prison services. We identified 6 programme theories comprising 5 behavioural mechanisms: prescribers' knowledge about how to taper; build prescribers' beliefs about capabilities to initiate tapering discussions and manage psychological consequences of tapering; perceived professional role in tapering; the environmental context enabling referral to specialists; and facilitating positive social influence by aligning patient: prescriber expectations of tapering. No interventions are addressing all 6 mechanisms supportive of tapering. Work is required to operationalise programme theories according to organisational structures and resources. An example operationalisation is combining tapering guidelines with information about local excess opioid problems and endorsing these with organisational branding. Prescribers being given the skills and confidence to initiate tapering discussions by training them in cognitive-based interventions and incorporating access to psychological and physical support in the patient pathway. Patients being provided with leaflets about the tapering process and informed about the patient pathway.


Cloning and expression in mammalian cells of porcine tumor necrosis factor alpha: examination of biological properties.
We have cloned a full length complementary DNA (cDNA) of the porcine tumor necrosis factor alpha (pTNF-alpha) gene and expressed it in porcine and murine cells. Total RNA obtained from lipopolysaccharide (LPS) stimulated porcine peripheral blood mononuclear cells was reverse transcribed with a specific antisense pTNF-alpha primer to generate a single stranded cDNA which was subsequently amplified by the polymerase chain reaction utilizing an additional pTNF-alpha specific sense primer. The resulting double stranded cDNA was introduced into the pBMGNeo expression vector and transfected by electroporation in porcine (PK(15)) and murine (L929) cell lines. TNF-alpha bioactivity was detected in the supernatant of the transfected cells using a standard L929 bioassay or a PK(15) bioassay. The activity was zinc inducible as expected for a gene controlled by a metallothionein promoter. The bioactivity was not lowered by an anti-mouse TNF-alpha antiserum neutralizing murine, but not human TNF-alpha and a broad immunoreactive band of 17-19 kD was detected using an anti-mouse TNF-alpha serum suitable for immunoblotting. This newly developed tool will allow us to investigate the role of TNF-alpha in pathogenesis of viral infections and gram-negative sepsis.


Prevalence of Group B Streptococcus Recto-Vaginal Colonization, Vertical Transmission, and Antibiotic Susceptibility Among Pregnant Women in Ethiopia: A Systematic Review and Meta-Analysis.
Maternal Group B Streptococcus (GBS) recto-vaginal colonization is the most common route for early onset neonatal GBS diseases. A good understanding of the rate of maternal GBS colonization, vertical transmission rate, and antibiotic susceptibility profiles is needed to formulate a broad protection mechanism, like vaccine preparation. For that reason, this meta-analysis aimed at determining the pooled prevalence of GBS recto-vaginal colonization, vertical transmission rate, and antibiotic susceptibility profiles in Ethiopia. Both published and unpublished studies were searched from MEDLINE/PubMed, CINAHL (EBSCO), Embase, Cochrane Library, SCOPUS, Web of Sciences databases, and Google Scholar. Independent selection was then carried out by the authors based on the eligibility criteria and data extraction using Microsoft excel. The authors then used STATA version 14.1 software for further cleaning and analysis. The review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses) PRISMA guidelines. Using the random-effect model, the prevalence with a 95% confidence interval (CI) and forest plot were used to present the findings. Besides, the studies' heterogeneity was assessed using Cochrane chi-square (I2) statistics, while Egger intercept was used to assess publication bias. This review included nineteen studies. The pooled prevalence of recto-vaginal colonization was 15% (95% CI: 11, 19), while the prevalence of vertical transmission was 51% (95% CI: 45, 58) and highest-level susceptibility to vancomycin was 99% (95% CI: 98, 100). However, the GBS susceptibility to tetracycline was 23% (95% CI: 9, 36). Nearly one out of seven pregnant women in Ethiopia had recto-vaginal colonization of GBS. As a result, half of the pregnancies end with vertical transmission of GBS. Hence, the review emphasizes that policy and programs should consider planning and implementing prophylactic programs. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021287540.


[The nurse within emergency medical-psychological units].
The growing recognition of post-traumatic stress disorders and the need to intervene early justifies the creation of emergency medical-psychological units. The nurse has a major role to play within these teams.


Rodin has it! The role of hands in improving the selectivity of attention.
We report a new discovery on the role of hands in guiding attention, using the classic Stroop effect as our assay. We show that the Stroop effect diminishes, hence selective attention improves, when observers hold their chin, emulating Rodin's famous sculpture, "The Thinker." In two experiments we show that the Rodin posture improves the selectivity of attention as efficiently as holding the hands nearby the visual stimulus (the near-hands effect). Because spatial proximity to the displayed stimulus is neither present nor intended, the presence of the Rodin effect implies that attentional prioritization by the hands is not limited to the space between the hands.


Synthesis of poly hydroxypropyl methacrylate cryogel incorporated with Zn/Ce substituted hydroxyapatite nanoparticles for rejuvenation of femoral fracture treatment in a rat model.
Designing biomimetic biomaterials influenced by the common complex structure of hard tissues is yet a test these days. The control of bio-mineralization procedure onto biomaterials should be assessed before the use in medical applications. Coming to the bone rejuvenation applications, this work assessed the in vitro antibacterial activity and interacting between osteoblast cells (MG63) on poly (hydroxypropyl methacrylate) (PHPMA) cryogel consolidated with Zn/Ce substituted hydroxyapatite (MHAp) nanocomposite (PHPMA/MHAp). Osteoblast cell multiplication, morphology, and metabolic action were assessed through various conventions. The functional group, texture, mechanical properties, and protein adsorption profiles of the fabricated nanocomposite were analyzed by the FTIR, XRD, SEM, and mechanical examinations, respectively. The bacterial activity of nanocomposites was additionally assessed against E. coli and S. aureus microorganisms, individually. Nanocomposite advanced endo-chondral ossification at the messed up parts of the bone deformity than cryogel did. These results recommend that PHPMA/MHAp nanocomposites joined the good innate properties of each polymer and bioceramic, giving a mechanically powerful, cell-responsive, and permeable stage for hard tissue applications.


Deducing the symmetry of helical assemblies: Applications to membrane proteins.
Helical reconstruction represents a convenient and powerful approach for structure determination of macromolecules that assemble into helical arrays. In the case of membrane proteins, formation of tubular crystals with helical symmetry represents an attractive alternative, especially when their small size precludes the use of single-particle analysis. An essential first step for helical reconstruction is to characterize the helical symmetry. This process is often daunting, due to the complexity of helical diffraction and to the low signal-to-noise ratio in images of individual assemblies. Furthermore, the large diameters of the tubular crystals produced by membrane proteins exacerbates the innate ambiguities that, if not resolved, will produce incorrect structures. In this report, we describe a set of tools that can be used to eliminate ambiguities and to validate the choice of symmetry. The first approach increases the signal-to-noise ratio along layer lines by incoherently summing data from multiple helical assemblies, thus producing several candidate indexing schemes. The second approach compares the layer lines from images with those from synthetic models built with the various candidate schemes. The third approach uses unit cell dimensions measured from collapsed tubes to distinguish between these candidate schemes. These approaches are illustrated with tubular crystals from a boron transporter from yeast, Bor1p, and a β-barrel channel from the outer membrane of E. coli, OmpF.