[Percutaneous sclerotherapy with polidocanol : Successful relapse therapy of infantile aneurysmal bone cyst].
The aneurysmal bone cyst (ABC) is well-known for its local expansile growth form and for the high risk of recurrence after treatment. We present the case of a 6‑year-old patient with a large ABC in the metaphysis of the proximal tibia, which showed recurrence only five months after treatment with curettage and autologous bone graft. By using six percutaneous intralesional injections of polidocanol the patient was successfully treated with no recurrence. After 18 months, a mild genu valgum was clinically noted.


Does the high biodiversity of lactococcal bacteriophages allow predictions about their different UV-C susceptibilities?
Fermentation processes can only succeed if intact and active starter cultures are present. Bacteriophages, which can lyse bacteria and thus bring entire fermentation processes to a standstill, therefore pose a major threat. Cheese production, for example, is often affected. The by-product whey can be highly contaminated with bacteriophages (≤109 plaque-forming units/mL) and in this state, further utilization is a quality and processing risk. Therefore, an orthogonal process consisting of membrane filtration followed by UV-C irradiation could be applied to eliminate bacteriophages and to generate "phage-free" whey. In order to define suitable process parameters, 11 lactococcal bacteriophages belonging to different families and genera and differing in their morphology, genome size, heat resistance, and other attributes, were screened for their UV-C resistance in whey. P369 was found to be the most resistant and could thus be well-suited as a biomarker. Starting from a 4 log unit bacteriophage reduction by membrane filtration, another 5 log unit decrease should be realized when applying a UV-C dose of 5 J/cm2. A clear correlation of UV-C sensitivity to the chosen attributes studied such as bacteriophage morphology and genome size was difficult and ambiguous, presumably because other yet unidentified parameters are important. Mutation experiments were performed with the representative bacteriophage P008 by multiple cycles of UV-C irradiation and propagation. A few mutational events were found, but could not be linked to an artificially generated UV-C resistance, indicating that the process used would probably not lose its effectiveness over time.


Examining demographic and psychosocial factors related to self-weighing behavior during pregnancy and postpartum periods.
Black childbearing individuals in the US experience a higher risk of postpartum weight retention (PPWR) compared to their White counterparts. Given that PPWR is related to adverse health outcomes, it is important to investigate predictors of weight-related health behaviors, such as self-weighing (i.e., using a scale at home). Regular self-weighing is an evidence-based weight management strategy, but there is minimal insight into sociodemographic factors related to frequency. The Postpartum Mothers Mobile Study (PMOMS) facilitated longitudinal ambulatory weight assessments to investigate racial inequities in PPWR. Our objective for the present study was to describe self-weighing behavior during and after pregnancy in the PMOMS cohort, as well as related demographic and psychosocial factors. Applying tree modeling and multiple regression, we examined self-weighing during and after pregnancy. Participants (N = 236) were 30.2 years old on average (SD = 4.7), with the majority being college-educated (53.8%, n = 127), earning at least $30,000 annually (61.4%, n = 145), and self-identifying as non-Hispanic White (NHW; 68.2%, n = 161). Adherence to regular self-weighing (at least once weekly) was highest among participants during pregnancy, with a considerable decline after giving birth. Low-income Black participants (earning < $30,000) were significantly less likely to reach a completion rate of ≥ 80% during pregnancy (AOR = 0.10) or the postpartum period (AOR = 0.16), compared to NHW participants earning at least $30,000 annually. Increases in perceived stress were associated with decreased odds of sustained self-weighing after delivery (AOR = 0.79). Future research should consider behavioral differences across demographic intersections, such as race and socioeconomic status, and the impact on efficacy of self-weighing.


Urinary protein patterns and EPH-gestosis.
In pregnancy a glomerular or mixed glomerular/tubular proteinuria in excess of 0.5 g/day was found in EPH-gestosis or preceding glomerular disease. A pure tubular proteinuria was not found in EPH-gestosis. The severity of the clinical picture was positively correlated with the daily protein loss.


[Changes in bladder compliance and detrusor contraction/relaxation of diabetic rats].
To provide experimental basis for further study on the mechanism of diabetic cystopathy (DCP). The bladder compliance and contraction/relaxation of whole bladder/detrusor strips were evaluated in vitro on diabetic rats. Significant decrease of detrusor contraction/relaxation and increase of bladder compliance were observed (P < 0.01). The contractile force of diabetes, diuresis and control were (20.80 +/- 6.38), (31.66 +/- 6.17) and (40.10 +/- 7.21) g/100 mg T respectively. The results suggest that both the injury of detrusor contraction/relaxation and bladder compliance are important factors for diabetic cystopathy, however, diuresis does not play a major role in the development of DCP.


Risk factors for delayed bleeding after endoscopic submucosal dissection of colorectal tumors.
To investigate the risk factors for delayed bleeding following endoscopic submucosal dissection (ESD) for colorectal neoplasms. We retrospectively reviewed the medical records of 991 consecutive patients who underwent ESD for colorectal neoplasms at our hospital from January 2007 to November 2016. Delayed post-ESD bleeding was defined as bleeding within 6 h to 30 days after ESD that resulted in either of the three situations: overt hematochezia, bleeding spots confirmed by repeat colonoscopy, or the requirement of a blood transfusion. Delayed bleeding was furtherly separated into early and late delayed bleeding by the end of post-ESD day 2. We analyzed the relationship between delayed bleeding and candidate factors including patient-, lesion-, and treatment-related details. Delayed post-ESD bleeding was found in 47 patients (4.7%), of which 18 cases were late delayed bleeding. Among all patients, 14 patients required a second colonoscopy, and 2 other patients were transferred to surgery. Univariate analysis revealed that patients with hypertension (p = 0.017) and using hot biopsy forceps for wound management (p = 0.028) were significantly associated with late delayed bleeding. Both risk factors remained significant after multivariate analysis: hypertension (OR 2.829, 95% CI 1.101-7.265, p = 0.031), hot biopsy forceps (OR 2.873, 95% CI 1.013-8.147, p = 0.047). Using hot biopsy forceps was also the significant risk factor for late delayed bleeding compared with early delayed bleeding. Patient with hypertension and using hot biopsy forceps for wound management during procedure call for attention on high risk of delayed post-ESD bleeding. Therefore, additional perioperative treatment is recommended in patients with these risk factors.


Micronized purified flavonoid fraction may prevent formation of intraperitoneal adhesions in rats.
To evaluate the efficacy of an anti-inflammatory and capillary regulator drug, micronized purified flavonoid fraction (MPFF), in the prevention of postoperative formation of adhesions. A double-blind, controlled study evaluated the efficacy of MPFF in reducing postoperative adhesion formation in a rat model. Animal care facility of an academic research setting. Thirty Sprague-Dawley female rats randomly divided into three groups. Starting on day of surgery, group 2 rats received oral MPFF (100 mg/kg per day for 7 days). Group 3 rats were intraperitoneally injected with 5 mL of saline (containing 200 mg/kg per day of MPFF for 3 days). Control rats received no medication. A standardized surgical trauma was applied in all animals. Three weeks after surgery, the rats were killed, and the adhesions were scored according to macroscopic and microscopic scales. Postoperative adhesions. Both oral and intraperitoneal administration of MPFF reduced the scores of adhesions according to macroscopic and microscopic scales. There was no difference between the routes of administration. A statistically significant reduction in postoperative formation of adhesions was observed after oral and intraperitoneal administration of MPFF in our experimental animal model. However, further studies are required to reveal its mechanism of action.


Wound-healing improvement by resurfacing split-thickness skin donor sites with thin split-thickness grafting.
Split-thickness skin graft (STSG) donor site dressing has been controversial until now. Our study aimed to assess the patient comfort and wound-healing efficacy with the application of thin split-thickness skin grafts regrafting on STSG donor sites. One hundred ninety-two consecutive patients undergoing split-thickness skin grafting were included in the study, and the participants were randomly divided into the following three groups: group A was regrafted with thin STSGs and groups B and C were covered with occlusive hydrocellular dressing and paraffin gauze, respectively. The participants were compared according to the epithelialization time, pain and scar formation. The average time of epithelialization was 6.2 ± 1.1 days in group A, 11.1 ± 2.1 days in group B and 13.5 ± 2.5 days in group C. The pain scores on days 2 and 5 after operation were 2.3 ± 0.8 and 1.9 ± 0.8 in group A, 2.5 ± 1.1 and 3.9 ± 1.3 in group B, and 3.8 ± 1.4 and 5.9 ± 2.1 in group C. The scar scores at half a year and one year after operation were 4.3 ± 0.6 and 2.50 ± 0.6 in group A, 7.4 ± 0.6 and 6.2 ± 0.6 in group B, and 11.8 ± 0.4 and 10.9 ± 1.0 in group C, separately. The difference in the three groups was significant. Utilizing thin STSGs regrafting on donor sites could significantly shorten the epithelialization time, reduce pain and prevent hyperplastic scar formulation.


Escherichia coli cells bearing a ribosomal ambiguity mutation in rpsD have a mutator phenotype that correlates with increased mistranslation.
Escherichia coli cells bearing certain mutations in rpsD (coding for the 30S ribosomal protein S4) show a ribosomal ambiguity (Ram) phenotype characterized by increased translational error rates. Here we show that spontaneous mutagenesis increases in Ram cells bearing the rpsD14 allele, suggesting that the recently described translational stress-induced mutagenesis pathway is activated in Ram cells.


Role of parainfluenza virus-specific IgE in pathogenesis of croup and wheezing subsequent to infection.
In order to determine the role of parainfluenza virus-specific IgE antibody production and release of histamine in the pathogenesis of lower respiratory disease caused by parainfluenza virus infection, we studied 84 infants and children at the time of parainfluenza virus infection. Parainfluenza virus-IgE antibody was detected in samples of nasopharyngeal secretions by means of an enzyme-linked immunosorbent assay, and histamine content of nasopharyngeal secretions was determined by a fluorometric technique. Virus-specific IgE responses appeared earlier and were of greater magnitude in patients with croup, wheezing, and croup with wheezing caused by parainfluenza virus infection than in patients with parainfluenza virus-induced upper respiratory illness. Histamine was detectable in nasopharyngeal secretions of patients with parainfluenza virus-related croup significantly more often than in patients with upper respiratory illness caused by parainfluenza virus. These observations suggest a role for immunologic mechanisms in the pathogenesis of severe forms of respiratory illness caused by parainfluenza virus infection.


An examination of the impact of the Maudsley Collaborative Care skills training workshops on patients with anorexia nervosa: a qualitative study.
The objective of this study was to examine the experience of adult inpatients with Anorexia Nervosa (AN) whose carers had taken part in the Collaborative Care skills training workshops. Workshops were offered to carers of someone with an eating disorder (ED) to address carer distress and proposed interpersonal maintaining factors. Semi-structured interviews were conducted probing the sufferer's perception of the workshops, their experience of their carers attending the workshops and any associated behaviour change. Qualitative data were analysed using Interpretative Phenomenological Analysis (IPA). Key findings suggest that patients hold positive attitudes towards involving carers in their care and that the skills training approach can have positive effects for AN adult inpatients. Positive effects are congruent with workshop aims supporting fidelity of the skills based training. Negative effects and ideas for improvements were examined. Involving carers in skills based Collaborative Care workshops based on an interpersonal maintenance model of EDs may be beneficial for adult inpatients with AN and future research is warranted to extend these findings.


Microcosm evaluation of the fate, toxicity, and risk to aquatic macrophytes from perfluorooctanoic acid (PFOA).
Perfluorooctanoic acid (PFOA) is an anthropogenic contaminant detected in various environmental and biological matrices. This compound is a fluorinated surfactant, belonging to a class of molecules known for persistence and their global distribution, but for which little ecotoxicological data are currently available, especially under field conditions. The environmental fate and toxicity of PFOA to the aquatic macrophytes Myriophyllum sibiricum and M. spicatum were investigated using 12,000 L outdoor microcosms. Replicate microcosms (n = 3) were treated with 0.3, 1, 30, and 100 mg/L PFOA as the sodium salt, plus controls, and assessed at regular intervals over 35 days. PFOA showed no significant dissipation from the water column, except at the greatest concentration, where partitioning from the water column into other compartments is suspected. The two species of Myriophyllum were similar in their sensitivity to PFOA under these simulated field conditions. Toxicity after 14 to 35 days of exposure in the evaluated endpoints for M. spicatum was > or = 5.7 mg/L PFOA for EC10s and > or = 31.8 mg/L PFOA for EC50s and in M. sibiricum was > or = 8.4 mg/L PFOA for EC10s and > or = 35.8 mg/L PFOA for EC50s. The no observed effects concentrations (NOECs) for Myriophyllum spp. were consistently > or = 23.9 mg/L PFOA. A risk assessment for these plant species estimated a negligible probability of toxicity being observed from PFOA exposure at current environmental concentrations.


A combination of cranial and peripheral nerve palsies in infectious mononucleosis.
A 44 year old woman presented with bilateral brachial neuritis and an isolated Bell's palsy. Subsequently she was found to have infectious mononucleosis. The association of cranial and brachial neuropathy has not previously been reported. Without any specific drug therapy she recovered completely within 5 months.


Intranasal administration of sodium nitroprusside augments antigen-specific mucosal and systemic antibody production in mice.
The coronavirus disease 2019, i.e., the COVID-19 pandemic, caused by a highly virulent and transmissible pathogen, has profoundly impacted global society. One approach to combat infectious diseases caused by pathogenic microbes is using mucosal vaccines, which can induce antigen-specific immune responses at both the mucosal and systemic sites. Despite its potential, the clinical implementation of mucosal vaccination is hampered by the lack of safe and effective mucosal adjuvants. Therefore, developing safe and effective mucosal adjuvants is essential for the fight against infectious diseases and the widespread clinical use of mucosal vaccines. In this study, we demonstrated the potent mucosal adjuvant effects of intranasal administration of sodium nitroprusside (SNP), a known nitric oxide (NO) donor, in mice. The results showed that intranasal administration of ovalbumin (OVA) in combination with SNP induced the production of OVA-specific immunoglobulin A in the mucosa and increased serum immunoglobulin G1 levels, indicating a T helper-2 (Th2)-type immune response. However, an analog of SNP, sodium ferrocyanide, which does not generate NO, failed to show any adjuvant effects, suggesting the critical role of NO generation in activating an immune response. In addition, SNPs facilitated the delivery of antigens to the lamina propria, where antigen-presenting cells are located, when co-administered with antigens, and also transiently elicited the expression of interleukin-6, interleukin-1β, granulocyte colony-stimulating factor, C-X-C motif chemokine ligand 1, and C-X-C motif chemokine ligand 2 in nasal tissue. These result suggest that SNP is a dual-functional formulation with antigen delivery capabilities to the lamina propria and the capacity to activate innate immunity. In summary, these results demonstrate the ability of SNP to induce immune responses via an antigen-specific Th2-type response, making it a promising candidate for further development as a mucosal vaccine formulation against infectious diseases.


Interleukin 7 and thymic stromal lymphopoietin: from immunity to leukemia.
Cancer is often caused by deregulation of normal developmental processes. Here, we review recent research on the aberrant activation of two hematopoietic cytokine receptors in acute lymphoid leukemias. Somatic events in the genes for thymic stromal lymphopoietin and Interleukin 7 receptors as well as in their downstream JAK kinases result in constitutive ligand-independent activation of survival and proliferation in B and T lymphoid precursors. Drugs targeting these receptors or the signaling pathways might provide effective therapies of these leukemias.


Minimally invasive esophageal surgery.
Laparoscopic procedures have achieved results equivalent to their open counterparts, with shorter hospital stays and less incisional morbidity. These procedures should be performed by surgeons trained in minimally invasive techniques. Overall, patient satisfaction with regard to symptom response is excellent.


Youth Mobile Response and Stabilization Services: Factors Associated with Multiple Episodes of Care.
Mobile response and stabilization services (MRSS) provide short-term, community-based, care to individuals in crisis. Minimal studies have explored which factors are associated with multiple episodes of MRSS care. We used a retrospective cohort design of MRSS electronic health records to explore demographic and clinical characteristics associated with multiple episodes of care among 2,641 youth ages 5-21 years old in New York, USA. Youth with multiple episodes of care (n = 585; 22.2%) were more likely to be non-Hispanic, have treatment histories including presenting problems related to adjustment, conduct, mood, or suicidal thoughts and behaviors, have high-level mental health visits, and more follow-up visits. Future research should examine the unmet needs of non-Hispanic populations and whether characteristics associated with multiple MRSS episodes are consistent across populations to inform procedures targeting unmet needs that prevent or minimize repeated use during crises.


Early and late histopathological changes in renal allografts procured by laparoscopic donor nephrectomy.
Subcapsular cortical damage (SCCD) is a characteristic pathological change, which is seen in renal allograft biopsy specimen obtained immediately after laparoscopic donor nephrectomy (LDN). In this study we evaluated the early and late histopathological effect of SCCD examining renal allograft biopsy specimens obtained after kidney transplantation. Laparoscopic donor nephrectomy was performed on 250 donors between July 2000 and September 2004 in our institution. Allograft biopsy of all 250 kidneys was performed immediately after LDN (zero hour biopsy). Of 250 biopsy specimens, 105 were diagnosed as SCCD and the allograft biopsy specimens obtained from 105 recipients after transplantation were enrolled in this study. All specimens were routinely examined by using light microscopy and immunofluorescence. In 87 patients 256 allograft biopsy specimens did not show post-pathological changes of SCCD. Twenty biopsy specimens obtained from 18 recipients showed tubular necrosis and a partly tubular regeneration and patchy interstitial hemorrhage, which seemed to be caused by SCCD. Ten allograft biopsy specimens from nine recipients demonstrated residual pathologic changes in SCCD early after transplantation. The other 10 specimens from nine recipients had abnormal histopathologic changes including interstitial edema and fibrosis, tubular atrophy and glomerular sclerosis in the subcapsular cortex late after transplantation. The early change of SCCD after transplantation remained intact and partial regeneration and the late showed subcapsular fibrosis with glomerular sclerosis. The incidence of the subcapsular lesions due to SCCD after transplantation was 17% in 105 allografts.


The atrophic dermatofibroma: a delled dermatofibroma.
Atrophic dermatofibroma has been proposed as a term to designate a new and specific type of dermatofibroma. We report the clinical and histopathological findings in two cases of atrophic dermatofibroma. The peculiar morphology of these lesions simply represents a conspicuous example of the frequently seen central depression in dermatofibroma. On histopathology, no authentic atrophy is present, because the thinning of the dermis compared with that of the adjacent non-lesional skin results from this depression rather than from loss of tissue of the dermis. Delled dermatofibroma is a more appropriate appellation than atrophic dermatofibroma, because of the striking shape of these lesions.


Effects of the daily heat load duration exceeding determined heat load thresholds on activity traits of lactating dairy cows.
In recent years, the problem of the welfare and heat load of dairy cows has become increasingly important in moderate climate zones. The objective of the present study was to determine heat load thresholds of average daily temperature-humidity index (THI) that lead to changes in different activity traits of lactating high-yielding dairy cows. Furthermore, we studied how the activity of the cows to heat load was influenced by the daily heat load duration which exceeded the heat load we had determined as threshold in our experiments. The study was conducted from June 2015 to May 2017 in a naturally ventilated dairy barn in Groß Kreutz, Germany. The climate was measured at several positions inside the barn, and the average THI was calculated every 10 min. The THI was used to define the dairy cows' heat load exposure. In addition, the activity of the cows was measured by pedometers, and different activity traits were recorded in the functional groups "resting behavior" and "locomotion behavior". The heat load thresholds determined by broken-stick models were 47 THI (standing bout duration, number of steps) as well as 67 THI (total lying/standing time, number of lying/standing bouts, lying bout duration). During the experimental period, the most reliable heat load threshold of 67 THI was exceeded from May to September for up to 480 h per month. The analysis model of each activity trait included the effect of the average daily THI values below and above the determined heat load threshold and the effect of the daily heat load duration exceeding the determined heat load threshold. The total lying/standing time and the number of steps showed significant changes related to increasing daily heat load duration. The effect of the daily heat load duration additionally intensified the effect of the average daily THI.


Identifying and prioritizing do-not-do recommendations in Dutch primary care.
Low-value care provides minimal or no benefit for the patient, wastes resources, and can cause harm. Explicit do-not-do recommendations in clinical guidelines are a first step in reducing low-value care. The aim of this study was to identify and prioritize do-not-do recommendations in general practice guidelines with priority for implementation. We used a mixed method design in Dutch primary care. First, we identified do-not-do recommendations through a systematic assessment of 92 Dutch guidelines for general practitioners (GPs), resulting in 385 do-not-do recommendations. Second, we selected 146 recommendations addressing high prevalent conditions. Third, a random sample of 5000 Dutch GPs was invited for an online survey to prioritize recommendations based on the prevalence of the condition and low-value care practice, potential harm, and potential cost reduction on a scale from 1 to 5/6. Total scores could range from 4 to 22. Recommendations with a median score > 12 were included. In total, 440 GPs completed the survey. The selection process led to 30 prioritised recommendations. These covered drug treatments (n = 12), diagnostics (n = 10), referral to other healthcare professions (n = 5), and non-drug treatment (n = 3). Dutch clinical guidelines include many do-not-do recommendations that are perceived as highly relevant by the GPs. The list of 30 high-priority do-not-do recommendations can be used to raise awareness of low-value care among GPs. As the recommendations are supported with the latest evidence from international studies, primary healthcare professionals and policy makers worldwide can use the list for further validating the list in their local context and designing strategies to reduce low-value care.


Bifidobacterium animalis subsp. lactis HN019 has antimicrobial activity against endodontic pathogens in vitro.
The aim of the present study was to evaluate, in vitro, the antimicrobial activity of the probiotic Bifidobacterium animalis subsp. lactis HN019, through the well technique, against 10 microorganisms can be found involved in endodontic infections. The antimicrobial activity of the probiotic was performed on Streptococcus mutans, Streptococcus sobrinus, Lacticaseibacillus casei, Enterococcus faecalis, Staphylococcus aureus, Candida albicans, Porphyromonas gingivalis, Porphyromonas endodontalis, Fusobacterium nucleatum and Prevotella intermedia. For the control group, it was used non-pathogenic bacteria Escherichia coli, Saccharomyces cerevisiae, and Kocuria rizhopilla. After 48 to 72 h of incubation of the petri dishes containing the culture medium, the microorganism strains, and the probiotic, the plates were examined to assess the uniformity of microbial growth, presence of contaminants, and the halo of inhibition. After visual inspection, the reading of the halo of inhibition was performed with the aid of a digital caliper using a reflected light source to illuminate the inverted plate on a black, opaque background after removing the cap. Thus, 3 values were obtained from each bacterial inoculum, which were added and divided by three to obtain the average of the values. The results of the in vitro study demonstrated that the probiotic B. animalis subsp. lactis HN019 promoted the inhibition of all strains of the pathogens evaluated, with the exception of Candida albicans, demonstrating antimicrobial activity on these microorganisms.


Modifications of The Human Liver Cancer Cells through microRNA-145-Mediated Targeting of CDCA3.
Owing to the lethality of liver cancer, it is considered as one of the devastating types of cancers across the globe. Consistently, the study was designed to elucidate the role and to explore the therapeutic implications of miR-145 in human liver cancer. In the current experimental study, gene expression was determined by RT-PCR analysis. Transfection of cancer cells was carried out using Lipofectamine 2000. The cell proliferation of liver cancer cells was estimated by MTT assay. Clonogenic assay was performed for analysis of colony forming potential of cancer cells. Flow cytometry was done to analyze the cell cycle phase distribution of cancer cells. Transwell chamber assay was performed to assess the motility of cancer cells. Western blotting was done to estimate the expression levels of proteins. Dual luciferase assay was performed for interaction analysis of miR-145 with CDCA3. The miR-145 expression was found to be downregulated in liver cancer cells. The transfection mediated overexpression of miR-145 inhibited the cancer cell proliferation and when miR-145 inhibitor was transfected, cancer cells showed higher proliferation rates. Enrichment of miR-145 levels led to cell cycle arrest at G2/M phase by inhibiting cyclin B1. miR-145 also restricted the migration and invasion of cancer cells. CDCA3 was shown to be the intracellular target of miR-145 and it was found that the inhibitory effects of miR-145 were modulated through CDCA3, intracellularly. The current study clearly revealed that there is a need to investigate the regulatory role of different molecular entities like microRNAs in cancer development to better understand mechanics behind this pathogenesis and design more effective combating strategies against cancer.


Highly Conductive Carbon Fiber Reinforced Concrete for Icing Prevention and Curing.
This paper aims to study the feasibility of highly conductive carbon fiber reinforced concrete (CFRC) as a self-heating material for ice formation prevention and curing in pavements. Tests were carried out in lab ambient conditions at different fixed voltages and then introduced in a freezer at -15 °C. The specimens inside the freezer were exposed to different fixed voltages when reaching +5 °C for prevention of icing and when reaching the temperature inside the freezer, i.e., -15 °C, for curing of icing. Results show that this concrete could act as a heating element in pavements with risk of ice formation, consuming a reasonable amount of energy for both anti-icing (prevention) and deicing (curing), which could turn into an environmentally friendly and cost-effective deicing method.


Saccadic eye movements in myasthenia gravis.
The peak velocities of horizontal saccades were measured in patients with myasthenia gravis (MG) to determine whether they can differentiate MG from other causes of ophthalmoplegia. Eye movements were recorded with electrooculography (EOG) or infrared scleral reflection (IR) in 42 patients with MG, 26 patients with sixth cranial nerve palsy (CNP), 19 patients with chronic progressive external ophthalmoplegia (PEO) and 28 normal subjects. Despite limitation of ductions in MG, the group means of velocities of 10 deg saccades recorded with IR were similar in MG and normal subjects. With EOG, small but statistically significant decreases in mean velocities of 10, 20 and 30 deg saccades were found in MG, compared to those in normal subjects. Twenty-one to 28% of MG patients had velocities outside of the normal range (outliers). In contrast, the group means in CNP and PEO were markedly lower than those in MG and normal subjects. The frequencies of outliers were 89 to 100% in CNP and 88 to 100% in PEO. Measurement of saccadic velocities can be helpful in differentiating MG from other causes of ophthalmoplegia.


Analysis of trace contamination of phthalate esters in ultrapure water using a modified solid-phase extraction procedure and automated thermal desorption-gas chromatography/mass spectrometry.
The present study was aimed to develop a procedure modified from the conventional solid-phase extraction (SPE) method for the analysis of trace concentration of phthalate esters in industrial ultrapure water (UPW). The proposed procedure allows UPW sample to be drawn through a sampling tube containing hydrophobic sorbent (Tenax TA) to concentrate the aqueous phthalate esters. The solid trap was then demoisturized by two-stage gas drying before subjecting to thermal desorption and analysis by gas chromatography-mass spectrometry. This process removes the solvent extraction procedure necessary for the conventional SPE method, and permits automation of the analytical procedure for high-volume analyses. Several important parameters, including desorption temperature and duration, packing quantity and demoisturizing procedure, were optimized in this study based on the analytical sensitivity for a standard mixture containing five different phthalate esters. The method detection limits for the five phthalate esters were between 36 ng l(-1) and 95 ng l(-1) and recovery rates between 15% and 101%. Dioctyl phthalate (DOP) was not recovered adequately because the compound was both poorly adsorbed and desorbed on and off Tenax TA sorbents. Furthermore, analyses of material leaching from poly(vinyl chloride) (PVC) tubes as well as the actual water samples showed that di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) were the common contaminants detected from PVC contaminated UPW and the actual UPW, as well as in tap water. The reduction of DEHP in the production processes of actual UPW was clearly observed, however a DEHP concentration of 0.20 microg l(-1) at the point of use was still being quantified, suggesting that the contamination of phthalate esters could present a barrier to the future cleanliness requirement of UPW. The work demonstrated that the proposed modified SPE procedure provided an effective method for rapid analysis and contamination identification in UPW production lines.


Strategies to therapeutically modulate cytokine action.
Cytokines are secreted or membrane-presented molecules that mediate broad cellular functions, including development, differentiation, growth and survival. Accordingly, the regulation of cytokine activity is extraordinarily important both physiologically and pathologically. Cytokine and/or cytokine receptor engineering is being widely investigated to safely and effectively modulate cytokine activity for therapeutic benefit. IL-2 in particular has been extensively engineered, to create IL-2 variants that differentially exhibit activities on regulatory T cells to potentially treat autoimmune disease versus effector T cells to augment antitumour effects. Additionally, engineering approaches are being applied to many other cytokines such as IL-10, interferons and IL-1 family cytokines, given their immunosuppressive and/or antiviral and anticancer effects. In modulating the actions of cytokines, the strategies used have been broad, including altering affinities of cytokines for their receptors, prolonging cytokine half-lives in vivo and fine-tuning cytokine actions. The field is rapidly expanding, with extensive efforts to create improved therapeutics for a range of diseases.


Formative assessment based on an audit and feedback improves nuchal translucency ultrasound image quality.
The purpose of this work was to study the impact of an audit and feedback on the quality of routine first-trimester nuchal transparency ultrasound images. Eighty-eight sonographers were each sent 2 different series of 30 consecutive nuchal translucency images at a mean interval of 3 months to a dedicated, protected server for remote double-blind independent analysis based on the new Collège Français d'Echographie Foetale/Centre National de la Recherche Scientifique image-scoring method (https://www.cfef.org/evaluation/ISMCFEFCNRS.pdf). The sonographers were classified as low (score below the median) or high (score above the median) scorers for each series. Before their second evaluation, 73 of the 88 sonographers received a feedback report on their first series of images, whereas the other 15 participants received no feedback. The baseline characteristics of the participants who did and did not receive feedback were comparable. Participants who received feedback increased their average score significantly, from a mean ± SD of 11.1 ± 1.3 to 13.4 ± 1.4 among low scorers (P < .00001) and from 15.1 ± 1.2 to 16.0 ± 1.4 among high scorers (P < .001), whereas no significant change was seen among participants who received no feedback (low scorers, 10.9 ± 1.5 to 12.1 ± 2.0; P = .11; high scorers, 14.7 ± 1.3 to 14.6 ± 1.3; P = .99). The proportion of satisfactory images increased by 48% among low scorers who received feedback. Formative assessment based on a moderately intensive audit and feedback is feasible and effective for improving the quality of routine first-trimester nuchal transparency ultrasound images.


Effects of acupuncture combined with medication on patients with COVID-19 complicated with bipolar disorder: A protocol of systematic review and meta-analysis.
There is growing evidence that coronavirus disease 2019 (COVID-19) can trigger acute episodes of mood disorders or psychotic symptoms. Reports on the treatment of COVID-19-related bipolar disorder (BD) are limited. Our study aimed to investigate the potential for new or recurrent BD due to COVID-19. We qualitatively evaluate clinical treatments (acupuncture combined with medication) and any potential pathophysiological links between infection and BD. We searched Embase, PubMed, Cochrane Library, Web of Science and MEDLINE (via Web of Science), Scopus, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database, and the Wanfang Database from December 1, 2019, to September 15, 2022, to identify all articles on acupuncture combined with drugs used to treat COVID-19 complicated with bipolar disorders. Two researchers will screen the articles and extract the relevant information. The results will provide a systematic overview of the current evidence on the use of acupuncture combined with drug therapy to treat COVID-19 complicated with bipolar disorder. The conclusions of this study will help clarify the effects of acupuncture combined with drug therapy on patients with COVID-19-related BD.


18F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study.
Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions. Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation. Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2). In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance.


Detection of HLA-C*08:178, a novel HLA-C*08 variant, in a Taiwanese hematopoietic stem cell donor.
Nucleotide replacement at residue 12 of HLA-C*08:22 results in a novel allele, HLA-C*08:178.


Non-pharmacological Options in Postoperative Hospital-Based and Rehabilitation Pain Management (NOHARM): Protocol for a Stepped-Wedge Cluster-Randomized Pragmatic Clinical Trial.
Opioids may be necessary for guideline-concordant acute perioperative pain management, but their use carries risks for unintended prolonged use and addiction. Guidelines recommend use of validated non-pharmacological pain care (NPPC) approaches in conjunction with prescribed opioids and other analgesics. Our protocol outlines a population-level, pragmatic trial that will test a bundled intervention comprised of an electronic health record (EHR) portal-based conversation guide, EHR clinical decision support (CDS), and a suite of self-management educational and support materials to encourage and advance NPPC use. We are conducting a stepped-wedge, cluster-randomized pragmatic trial spanning seven surgical specialties across six geographically diverse locations within the Mayo Clinic Enterprise. Thirty two surgical practices across six locations (Rochester, Minnesota; Mankato, Minnesota; La Crosse, Wisconsin; Eau Claire, Wisconsin; Phoenix, Arizona; Jacksonville, Florida) comprise 22 distinct practice clusters that are randomly assigned to one of five steps using constrained randomization. Steps "go live" by initiating the intervention at 7-month intervals between March 2021 and July 2023. Patients over 18 years of age who are scheduled for qualifying procedures within "live" consenting practices are sent a Healing After Surgery guide via their patient portals pre-operatively, directing them to identify their preferred NPPC modalities among 13 approaches. These selections create CDS options for care teams to support patients with self-management materials that reinforce safe NPPC use. Patients' clinical, demographic, and outcome data will be abstracted from the Epic EHR. Primary outcomes will be the Patient Reported Outcomes Measurement Information System (PROMIS) pain interference and physical functioning computer adaptive tests (CAT) collected at 1, 2, and 3 months postoperatively via the patient portal. We will mail printed versions of the 6-item PROMIS short forms to portal non-responders to minimize bias. Secondary outcomes will include the PROMIS anxiety CAT, opioid consumption, and self-reported NPPC use. ClinicalTrials.gov identifier, NCT04570371.


Sex Hormone Signaling Suppresses Ferroptosis via Phospholipid Remodeling.
ER+ breast and AR+ prostate cancers suppress ferroptosis through MBOAT1 and MBOAT2, respectively.


Roquin paralogs add a new dimension to ICOS regulation.
Two studies in the current issue of Immunity (Pratama et al., 2013; Vogel et al., 2013) demonstrate that the RNA-binding proteins Roquin-1 and Roquin-2 have redundant function in the posttranscriptional repression of Icos messenger RNA by CD4(+) T cells.


Nervous lesions in a case of local gigantism.
A case of local gigantism of the thumb was studied by light and electron microscopy. In the lesion, proliferation of fibroadipose tissue and typical alterations of the nerves were found. The alterations in the nerve were isolated hypertrophy of the perineural cells. The relation of the changes to other peripheral nerve tumours especially in neurofibromatosis, is discussed.


Microbial production of docosahexaenoic acid (DHA): biosynthetic pathways, physical parameter optimization, and health benefits.
Omega-3 fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and α-linolenic acid (ALA), are essential polyunsaturated fatty acids with diverse health benefits. The limited conversion of dietary DHA necessitates its consumption as food supplements. Omega-3 fatty acids possess anti-arrhythmic and anti-inflammatory capabilities, contributing to cardiovascular health. Additionally, DHA consumption is linked to improved vision, brain, and memory development. Furthermore, omega-3 fatty acids offer protection against various health conditions, such as celiac disease, Alzheimer's, hypertension, thrombosis, heart diseases, depression, diabetes, and certain cancers. Fish oil from pelagic cold-water fish remains the primary source of omega-3 fatty acids, but the global population burden creates a demand-supply gap. Thus, researchers have explored alternative sources, including microbial systems, for omega-3 production. Microbial sources, particularly oleaginous actinomycetes, microalgae like Nannochloropsis and among microbial systems, Thraustochytrids stand out as they can store up to 50% of their dry weight in lipids. The microbial production of omega-3 fatty acids is a potential solution to meet the global demand, as these microorganisms can utilize various carbon sources, including organic waste. The biosynthesis of omega-3 fatty acids involves both aerobic and anaerobic pathways, with bacterial polyketide and PKS-like PUFA synthase as essential enzymatic complexes. Optimization of physicochemical parameters, such as carbon and nitrogen sources, pH, temperature, and salinity, plays a crucial role in maximizing DHA production in microbial systems. Overall, microbial sources hold significant promise in meeting the global demand for omega-3 fatty acids, offering an efficient and sustainable solution for enhancing human health.


Evaluation of debris and smear layer formation using three different NI-TI rotary instrument systems: An in vitro scanning electron microscope study.
The aim of the study is to evaluate of debris and smear layer formation after using rotary ProTaper Universal, Twisted File, and XP Endo file systems under scanning electron microscope. Forty freshly extracted mandibular second premolar teeth were taken to decoronate at the cementoenamel junction to make the remaining root length 15 mm. Specimens were divided into four groups of 10 teeth each, Group I (control) - no instrumentation. Group II - ProTaper Universal rotary file (F2), Group III - twisted file (ISO size 0.25 and 6% taper), Group IV - XP Endo file (ISO size 0.25). During instrumentation, 5 ml normal saline was used as irrigating agent. Grooves parallel to the longitudinal axis of the root were made on the mesial and distal surface of each specimen to split it into two halves and examined under scanning electron microscope at ×1500 and ×5000 magnification. Photomicrographs were taken to evaluate debris and smear layer. Evaluation of photomicrographs was done using a score index. One-way analysis of variance (ANOVA) was used to compare more than one means at a time. Tukey's critical difference followed by ANOVA was used to compare the mean values pair wise. P <0.05 was considered to be statistically significant. Among all the file systems, Group II showed maximum amount of debris (3.50 ± 1.109) followed by Group III (2.83 ± 1.238) and least amount was showed by Group IV (2.65 ± 1.122) at all levels (cervical, middle, and apical third). Among all the experimental groups, Group II showed maximum amount of smear layer (2.75 ± 1.149) followed by Group III (2.40 ± 0.982) and least amount of smear layer shown by Group IV (2.10 ± 0.841) at all levels (cervical, middle and apical third), the result was statistically significant (P < 0.05). At all the levels (cervical third, middle third, and apical third), among all the experimental groups, highest amount of debris and smear layer was formed by ProTaper Universal rotary file followed by Twisted file and least amount showed by XP Endo file system. In all the levels, control group showed highest amount of debris but least amount of smear layer.


Linkage of speech sound disorder to reading disability loci.
Speech sound disorder (SSD) is a common childhood disorder characterized by developmentally inappropriate errors in speech production that greatly reduce intelligibility. SSD has been found to be associated with later reading disability (RD), and there is also evidence for both a cognitive and etiological overlap between the two disorders. The present study tested whether SSD is linked to replicated risk loci for RD. One hundred and eleven probands with SSD and their 76 siblings were tested with measures of speech, phonological memory (Nonword Repetition-NWR), and phonological awareness and genotyped for linkage markers on chromosomes 1p36, 6p22, and 15q21. Both single point and multipoint linkage were tested with multiple methods. The speech and NWR phenotypes were linked to the RD loci on chromosomes 6 and 15, with suggestive results for the RD locus on chromosome 1. It now appears that several RD loci are pleiotropic for SSD, extending the findings of Stein et al. (2004) for the RD locus on Chromosome 3.


SAR of biphenyl carboxamide ligands of the human melanin-concentrating hormone receptor 1 (MCH R1): discovery of antagonist SB-568849.
We report here the discovery of a class of MCH R1 ligands based on a biphenyl carboxamide template. A docked-in model is presented indicating key interactions in the putative binding site of the receptor. Parallel high throughput synthetic techniques were utilised to allow rapid exploration of the structure-activity relationship around this template, leading to compound SB-568849 which possessed good receptor affinity and selectivity. This compound proved to be an antagonist with stability in vivo, an acceptable brain-blood ratio and oral bioavailability.


Reversible zinc-induced injuries to erythrocyte membrane nanostructure.
Zinc-induced injuries to red blood cell membrane nanostructures at different zinc concentrations were studied by atomic force microscopy. In order to distinguish the intrinsic characteristics of membrane nanostructures, the membrane surfaces were represented by three orders using 3D Fourier transform. Increasing the concentrations of zinc ions modified the pattern of induced injuries: their depths and diameters and their number on the membrane surface test area increased. The injuries and their distribution for each order of membrane surface were analyzed. Albumin restored membrane nanosurface.


High-throughput fingerprinting of bacterial artificial chromosomes using the snapshot labeling kit and sizing of restriction fragments by capillary electrophoresis.
We have developed an automated, high-throughput fingerprinting technique for large genomic DNA fragments suitable for the construction of physical maps of large genomes. In the technique described here, BAC DNA is isolated in a 96-well plate format and simultaneously digested with four 6-bp-recognizing restriction endonucleases that generate 3' recessed ends and one 4-bp-recognizing restriction endonuclease that generates a blunt end. Each of the four recessed 3' ends is labeled with a different fluorescent dye, and restriction fragments are sized on a capillary DNA analyzer. The resulting fingerprints are edited with a fingerprint-editing computer program and contigs are assembled with the FPC computer program. The technique was evaluated by repeated fingerprinting of several BACs included as controls in plates during routine fingerprinting of a BAC library and by reconstruction of contigs of rice BAC clones with known positions on rice chromosome 10.


Memory performance in tree shrews: effects of stressful experiences.
Male tree shrews were exposed to alternating non-stressful and stressful conditions, and their memory performance was tested during three different stress periods and after rest periods of various lengths using a modified holeboard. This paradigm circumvents confounding factors, e.g. food or water deprivation, transport to a special testing arena, and excludes the development of automatic cognitive processes by complex memory tasks. In experimental tree shrews, psychosocial conflict caused elevated cortisol levels during the stress phases. While this resulted in an impairment of the stress-sensitive declarative memory during the second stress phase, no memory deficit was found during the first and third stress phase. Despite normalized cortisol levels, significant memory deficits in experimental animals were observed even 10 weeks after the last stressful experience. The alternating order of stressful events revealed that the negative correlation between the level of adrenal steroid hormones and memory performance does not account for the long-lasting effects of psychosocial stress in tree shrews.


[Establishment of a sandwich ELISA for testing serum sB7-H3 and detection of sB7-H3 levels in liver disease].
To establish quantitative ELISA for soluble sB7-H3 and evaluate its clinical application. Two mAbs of mouse anti-human sB7-H3(4H7 and 2E6)established by our lab were used. The mAb 4H7 was used as coating antibody and the 2E6 as a sandwich antibody, which recognized a different epitope and was labeled by biotin. The serum sB7-H3 levels of healthy volunteers and patients were measured by this method. Sandwich ELISA was established with the linear range covering from 8.192 ng/L to 2 000 ng/L. The outcomes of repeatability test, recovery test, stability test and specificity test were quite good. The increased levels of sB7-H3 were found in schistosomiasis cirrhosis, the reduced levels in severe hepatitis and the difference in both situations showed significance. A specific and sensitive sandwich ELISA is developed, the detection in liver disease indicates that the ELISA kit provides a potential tool in the clinical application.


Reducing needle-to-balloon time by using a single guiding catheter during transradial primary coronary intervention.
It is unknown whether using a single guiding catheter for both nonculprit and culprit vessel angiography and intervention during transradial primary percutaneous coronary intervention (PCI) is feasible. This single-center study enrolled 242 consecutive patients with ST segment elevation myocardial infarction (STEMI) who received primary PCI. Among them, 102 patients received primary PCI via transfemoral approach (TFI), 109 patients received primary PCI via transradial approach using conventional technique (Conventional TRI), and 31 underwent primary TRI using a single guiding catheter (Single Guiding TRI). The catheter used for this purpose was 6 Fr RM® 3.5 guiding catheter. Using a single guiding catheter, both coronary artery angiograms and intervention were successful in 30 of 31 patients (96.7%). Needle-to-balloon time (from puncture to first balloon) and door-to-balloon (D2B) time were similar between TFI and Conventional TRI groups and significantly lower in the Single Guiding TRI group (13.8 [TFI] and 14.1 [Conventional TRI] vs. 7.6 minutes, P < 0.001; 89.5 [TFI] and 91.0 [Conventional TRI] vs. 68.5 minutes, P = 0.008, respectively), whereas proportion of patients achieving D2B time within 90 minutes increased significantly in the Single Guiding TRI group from 51.0% for TFI and 49.5% for Conventional TRI to 74.2% (P = 0.023). Primary transradial PCI using a single guiding catheter is feasible and highly successful and might allow timely restoration of blood flow in infarct-related artery.


The impact of caring for dying patients in intensive care units on a physician's personhood: a systematic scoping review.
Supporting physicians in Intensive Care Units (ICU)s as they face dying patients at unprecedented levels due to the COVID-19 pandemic is critical. Amidst a dearth of such data and guided by evidence that nurses in ICUs experience personal, professional and existential issues in similar conditions, a systematic scoping review (SSR) is proposed to evaluate prevailing accounts of physicians facing dying patients in ICUs through the lens of Personhood. Such data would enhance understanding and guide the provision of better support for ICU physicians. An SSR adopts the Systematic Evidenced Based Approach (SEBA) to map prevailing accounts of caring for dying patients in ICUs. To enhance the transparency and reproducibility of this process, concurrent and independent use of tabulated summaries, thematic analysis and directed content analysis (Split Approach) is adopted. Eight thousand three hundred fifty-eight abstracts were reviewed from four databases, 474 full-text articles were evaluated, 58 articles were included, and the Split Approach revealed six categories/themes centered around the Innate, Individual, Relational and Societal Rings of Personhood, conflicts in providing end of life care and coping mechanisms employed. This SSR suggests that caring for dying patients in ICU impacts how physicians view their personhood. To resolve conflicts within individual concepts of personhood, physicians use prioritization, reframing and rely on accessible, personalized support from colleagues to steer coping strategies. An adapted form of the Ring Theory of Personhood is proposed to direct timely personalized, appropriate and holistic support.


H-scan, Shear Wave and Bioluminescent Assessment of the Progression of Pancreatic Cancer Metastases in the Liver.
The non-invasive quantification of tumor burden and the response to therapies remain an important objective for imaging modalities. To characterize the performance of two newly optimized ultrasound-based analyses, we applied shear wave and H-scan scattering analyses to repeated trans-abdominal ultrasound scans of a murine model of metastatic pancreatic cancer. In addition, bioluminescence measurements were obtained as an alternative reference. The tumor metastases grow aggressively and result in death at approximately 4 wk if untreated, but longer for those treated with chemotherapy. We found that our three imaging methods (shear wave speed, H-scan, bioluminescence) trended toward increasing output measures with time during tumor growth, and these measures were delayed for the group receiving chemotherapy. The relative sensitivity of H-scan tracked closely with bioluminescence measurements, particularly in the early to mid-stages of tumor growth. The correlation between H-scan and bioluminescence was found to be strong, with a Spearman's rank correlation coefficient greater than 0.7 across the entire series. These preliminary results suggest that non-invasive ultrasound imaging analyses are capable of tracking the response of tumor models to therapeutic agents.


Self-facilitation of ganglion cells in the retina of the turtle.
1. Ganglion cells responses to illumination and to optic nerve stimulation were recorded intracellularly from the retina of the turtle. All ganglion cells were identified by their antidromic responses to optic nerve stimulation.2. When solitary spikes are produced following antidromic, orthodromic or intracellular stimulation, about 20% of the recorded ganglion cells show an additional depolarization along the falling phase of the action potential (post-spike depolarization, PSD).3. The PSD following the antidromic action potential disappears upon collision with a direct spike or when the antidromic spike is prevented from invading the cell soma.4. By pairing two optic nerve stimuli the PSD is depressed with brief interstimulus intervals, but gradually recovers to the control amplitude 600-800 msec after the conditioning shock.5. The PSD is tentatively interpreted as an e.p.s.p. transmitted by ganglion cell collaterals originating at the level of the soma dendritic complex of the recorded cell.6. The interspike interval histogram of ganglion cells showing PSD is characterized by a peak at about 10 msec, as opposed to a peak between 12 and 100 msec observed in cells without PSD. It is suggested that the occurrence of PSD facilitate the onset of additional action potentials at brief interspikes intervals, thus potentiating ganglion cell discharges.


The global landscape of cross-border reproductive care: twenty key findings for the new millennium.
Cross-border reproductive care (CBRC), also known as procreative tourism, fertility tourism, or reproductive tourism, is an increasing global phenomenon. This article reviews the expanding scholarly literature on CBRC, with 2010-2011 representing watershed years for CBRC scholarship and activism. Terminological debates, missing data, and lack of international monitoring plague the study of CBRC. Nonetheless, it is widely acknowledged that CBRC is a growing industry, with new global hubs, new intermediaries, new media, and new spaces of interaction. Religious bans and legal restrictions have created a patchwork of 'restrictive' and 'permissive' countries, with law evasion being a primary driver of CBRC. Yet, patient motivations for CBRC are diverse and patients' levels of satisfaction with CBRC and its outcomes are generally high. Thus, scholarly concern with CBRC as law evasion must be tempered with qualitative studies of positive patient experiences. CBRC can be considered a form of 'global gynecology' in which reproductive medicine, tourism, and commerce are converging in the second decade of the new millennium.


Effects of ketone supplements on blood β-hydroxybutyrate, glucose and insulin: A systematic review and three-level meta-analysis.
Effects of ketone supplements as well as relevant dose-response relationships and time effects on blood β-hydroxybutyrate (BHB), glucose and insulin are controversial. This study aimed to summarize the existing evidence and synthesize the results, and demonstrate underlying dose-response relationships as well as sustained time effects. Medline, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were searched for relevant randomized crossover/parallel studies published until 25th November 2022. Three-level meta-analysis compared the acute effects of exogenous ketone supplementation and placebo in regulating blood parameters, with Hedge's g used as measure of effect size. Effects of potential moderators were explored through multilevel regression models. Dose-response and time-effect models were established via fractional polynomial regression. The meta-analysis with 327 data points from 30 studies (408 participants) indicated that exogenous ketones led to a significant increase in blood BHB (Hedge's g = 1.4994, 95% CI [1.2648, 1.7340]), reduction in glucose (Hedge's g = -0.3796, 95% CI [-0.4550, -0.3041]), and elevation in insulin of non-athlete healthy population (Hedge's g = 0.1214, 95%CI [0.0582, 0.3011]), as well as insignificant change in insulin of obesity and prediabetes. Nonlinear dose-response relationship between ketone dosage and blood parameter change was observed in some time intervals for BHB (30-60 min; >120 min) and insulin (30-60 min; 90-120 min), with linear relationship observed for glucose (>120 min). Nonlinear associations between time and blood parameter change were found in BHB (>550 mg/kg) and glucose (450-550 mg/kg), with linear relationship observed in BHB (≤250 mg/kg) and insulin (350-550 mg/kg). Dose-response relationships and sustained time effects were observed in BHB, glucose and insulin following ketone supplementation. Glucose-lowering effect without increasing insulin load among population of obesity and prediabetes was of remarkable clinical implication. PROSPERO (CRD42022360620).


siRNA injection induces sequence-independent protection in Penaeus monodon against white spot syndrome virus.
White spot syndrome virus (WSSV) is a major disease in crustaceans, particularly shrimp, due to the current intensity of aquaculture practices. Novel strategies including vaccination to control this virus would be highly desirable. However, invertebrates lack a true adaptive immune response system and seem to rely on various innate immune responses. An alternative and more specific approach to counteract WSSV infections in shrimp could be by the exploitation of RNA interference. As long dsRNA molecules induce a general, sequence-independent anti-viral immunity in shrimp [Robalino, J., Browdy, C.L., Prior, S., Metz, A., Parnell, P., Gross, P., Warr, G., 2004. J. Virol. 78, 10442-10448], it was investigated whether shorter 21 nt siRNAs with homology to the WSSV vp15 and vp28 genes would give a sequence-specific interference response in the shrimp Penaeus monodon. Vp28 siRNAs as well as nonspecific control gfp siRNAs were able to specifically and efficiently silence their homologous genes in a heterologous baculovirus insect cell expression system. However, in shrimps no such a specific effect was observed. Shrimp injected with vp15 or vp28 siRNAs before WSSV challenge gave a significantly lower mortality rate, but not significantly different when shrimps were injected with gfp siRNA. Thus, large dsRNA molecules as well as siRNAs induce a sequence-independent anti-viral immunity when injected in shrimp.


Genomic retargeting of p53 and CTCF is associated with transcriptional changes during oncogenic HRas-induced transformation.
Gene transcription is regulated by distant regulatory elements via combinatorial binding of transcription factors. It is increasingly recognized that alterations in chromatin state and transcription factor binding in these distant regulatory elements may have key roles in cancer development. Here we focused on the first stages of oncogene-induced carcinogenic transformation, and characterized the regulatory network underlying transcriptional changes associated with this process. Using Hi-C data, we observe spatial coupling between differentially expressed genes and their differentially accessible regulatory elements and reveal two candidate transcription factors, p53 and CTCF, as determinants of transcriptional alterations at the early stages of oncogenic HRas-induced transformation in human mammary epithelial cells. Strikingly, the malignant transcriptional reprograming is promoted by redistribution of chromatin binding of these factors without major variation in their expression level. Our results demonstrate that alterations in the regulatory landscape have a major role in driving oncogene-induced transcriptional reprogramming.


Palladium-Catalyzed [3+2] Annulation of Naphthalimide Acceptors and Thiophene Donors.
Donor-acceptor (D-A) dyes constitute one of the fundamental structural motifs of functional organic materials. In most cases, the donor and acceptor moieties are connected by a single bond, which could potentially be replaced by a fused aromatic ring to enhance the rigidity and conjugation of the dye moieties. However, there is still a lack of synthetic methodologies for such fused D-A systems. Here we report the synthesis of D-A and A-D-A dyes that possess fully annulated donor and acceptor moieties based on palladium (Pd)-catalyzed [3+2] annulation reaction between bromo-chloro-naphthalene dicarboximide and thiophene- and indole-based boronic esters. Thus, a series of fused D-A and A-D-A conjugated dyes were synthesized in good to high yields by a cascade of Pd-catalyzed Suzuki-Miyaura cross-coupling and direct arylation reactions. The newly synthesized fused D-A and A-D-A dyes with one or two naphthalimide units fused to five-membered electron-rich heterocyles were systematically investigated by ultraviolet-visible spectroscopy, cyclic and square wave voltammetry, and density functional theory calculations. These dyes possess desirable optical and electrochemical properties for application as organic electronic materials as they show absorption up to the near-infrared region, undergo up to 4-fold reduction processes, and have low-lying LUMO energy levels down to -3.62 eV.


Palliative treatment for advanced non-small cell lung cancer.
It should go without saying that all patients with advanced NSCLC are entitled to the treatment and care described in this article. It is probably also true that in many countries where these patients are often elderly and socially disadvantaged, they may have very variable access to this treatment and care. There is reasonable research evidence that both chemotherapy and palliative radiotherapy are modestly effective in controlling symptoms and prolonging life for some patients, but with significant risks of unpleasant and sometimes life-threatening toxicity. For this large and important group of patients, however, there are a large number of unanswered questions about the best regimens to use, how best to select patients so that they get the greatest benefit, how to mitigate side effects, and how best to integrate all the available treatment options. There have been significantly more trials in chemotherapy, but we must not overlook the need for research into palliative radiotherapy and other supportive care measures. There is still plenty of scope for intelligent and coordinated research.


[The value of angiography of the popliteal artery and its branches in the successful reconstruction of the thigh].
The difficulties occuring in angiography of popliteal artery and its branches are here presented. The presentation of these arteries on angiogram is very important due to establishing operative andications on arteries of thigh and upper parts of leg. Successfully performed peripheral angiographies on 1000 patients are here presented.


Effect of early vasopressin combined with norepinephrine on short-term mortality in septic shock: A retrospective study based on the MIMIC-IV database.
Septic shock is a leading cause of death in intensive care units (ICUs), with short-term mortality rates of 35-40%. Vasopressin (AVP) is a second-line vasoactive agent for septic shock, and recent studies suggest that early AVP use can be beneficial. However, differences between early initiation of AVP combined with norepinephrine (NE) and nonearly AVP with NE are unclear. A retrospective cohort research was designed to explore the effects of early AVP initiation versus nonearly AVP initiation. This retrospective single-center cohort study included adult patients with septic shock from the MIMIC (Medical Information Mart for Intensive Care)-IV database. According to whether AVP was used early in the ICU (intensive care unit), patients were assigned to the early- (within 6 h of septic shock onset) and non-early-AVP (at least 6 h after septic shock onset) groups. The primary outcome was 28-day mortality. The secondary outcomes were ICU and hospital mortality, the numbers of vasopressor-free and ventilation-free days at 28 days, ICU length of stay (LOS), hospital LOS, sequential organ failure assessment (SOFA) score on days 2 and 3, and renal replacement therapy (RRT) use on days 2 and 3. Univariate and multivariate cox proportional-hazards regression, propensity-score matching were used to analyze the differences between the groups. The study included 531 patients with septic shock: 331 (62.5%) in the early-AVP group and 200 (37.5%) in the non-early-AVP group. For 1:1 matching, 158 patients in the early-AVP group were matched with the same number of patients with nonearly AVP. Regarding the primary outcome, there was no significant difference between the early- and non-early-AVP groups in 28-day mortality (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.68-1.24). For the secondary outcomes, there were no differences between the early- and non-early-AVP groups in ICU mortality (HR = 0.95, 95% CI = 0.67-1.35), hospital mortality (HR = 0.95, 95% CI = 0.69-1.31), the numbers of vasopressor-free and ventilation-free days at 28 days, ICU LOS, hospital LOS, SOFA score on days 2 and 3, and RRT use on days 2 and 3. There was no difference in short-term mortality between early AVP combined with NE and nonearly AVP with NE in septic shock.


Use of machine learning to assess the prognostic utility of radiomic features for in-hospital COVID-19 mortality.
As portable chest X-rays are an efficient means of triaging emergent cases, their use has raised the question as to whether imaging carries additional prognostic utility for survival among patients with COVID-19. This study assessed the importance of known risk factors on in-hospital mortality and investigated the predictive utility of radiomic texture features using various machine learning approaches. We detected incremental improvements in survival prognostication utilizing texture features derived from emergent chest X-rays, particularly among older patients or those with a higher comorbidity burden. Important features included age, oxygen saturation, blood pressure, and certain comorbid conditions, as well as image features related to the intensity and variability of pixel distribution. Thus, widely available chest X-rays, in conjunction with clinical information, may be predictive of survival outcomes of patients with COVID-19, especially older, sicker patients, and can aid in disease management by providing additional information.


Development of a capillary zone electrophoresis method for the separation of a furan combinatorial library.
Nine component mixtures of a furan library were simultaneously separated by capillary zone electrophoresis (CZE) using a phosphate buffer as a background electrolyte at low pH. The effects of buffer concentration, buffer pH, type and concentration of organic solvents on the electrophoretic mobility, resolution, and analysis time were systematically investigated. Resolution and efficiency of furan library components were further improved using cyclodextrin (CD)-modified CZE. Under optimum conditions, eight of the nine furans were baseline-resolved in less than 10 min at 30 kV using 50 mM phosphate buffer, 10% v/v acetonitrile (ACN), pH 2.0, with 5 mM gamma-CD.


Lenalidomide in combination with dexamethasone: effective regimen in patients with relapsed or refractory multiple myeloma complicated by renal impairment.
Over the past decade, treatment options for patients with multiple myeloma (MM) have improved substantially, resulting in better response rates and prolonged overall survival (OS). Nevertheless, MM remains a challenging disease, especially if renal insufficiency (RI) or extensive pre-treatment aggravates the assignment of the optimal treatment schedule. In this retrospective study, we analyzed the outcome of lenalidomide plus dexamethasone in 167 patients with relapsed or refractory MM with focus on RI. The baseline creatinine clearance (CLCr) was normal in 94 patients (CLCr≥80 ml/min), while RI was observed in 73 patients, including 40 patients with mild RI (50≤CLCr<80 ml/min) and 33 patients with moderate or severe RI (CLCr<50 ml/min). Response rates declined depending on the severity of RI, being 67% among patients with normal kidney function, 60% among patients with mild RI and 49% among patients with moderate or severe RI. Time to progression (TTP) was significantly reduced in patients with severe RI and in case of >2 previous treatment lines. OS was not significantly different between patients with normal and impaired renal function. In contrast, the number of previous treatment lines (2 vs. <2) and the use of novel agents like bortezomib or thalidomide prior to lenalidomide plus dexamethasone therapy had a more adverse effect on OS. In conclusion, lenalidomide plus dexamethasone is an effective regimen for relapsed or refractory patients with MM complicated by RI with manageable toxicity.


Ultrasensitive detection of explosives and chemical warfare agents by low-pressure photoionization mass spectrometry.
On-spot monitoring of threat agents needs high sensitive instrument. In this study, a low-pressure photoionization mass spectrometer (LPPI-MS) was employed to detect trace amounts of vapor-phase explosives and chemical warfare agent mimetics under ambient conditions. Under 10-s detection time, the limits of detection of 2,4-dinitrotoluene, nitrotoluene, nitrobenzene, and dimethyl methyl phosphonate were 30, 0.5, 4, and 1 parts per trillion by volume, respectively. As compared to those obtained previously with PI mass spectrometric techniques, an improvement of 3-4 orders of magnitude was achieved. This study indicates that LPPI-MS will open new opportunities for the sensitive detection of explosives and chemical warfare agents.


Application of statistically-based experimental designs for the optimization of nisin production from whey.
Statistically-based experimental designs were applied for the optimization of nisin production by Lactococcus lactis in a whey-based medium. Yeast extract, KH2PO4, and MgSO4 were identified to have significant effects on nisin biosynthesis by a Plackett-Burman design. These three significant factors were subsequently optimized using central composite design, and the optimal conditions were determined to be 12.067 g l(-1) for yeast extract, 0.569 g l(-1) for KH2PO4, and 0.572 g l(-1) for MgSO4. The validity of the optimal conditions was verified by a separate experiment.


[Investigation of monoamine oxidase gene restriction polymorphism in male populations of the Volga-Ural region].
Restriction polymorphism at the monoamine oxidase A (MAO A) gene was typed in eight male populations of the Volga-Ural region (Bashkirs, Chuvashes, Tatars, Udmurts, Maris, Mordovians, Komis, and Russians inhabiting the Republic of Bashkortostan). Analysis of the MAO A alleles frequency distribution patterns did not reveal statistically significant differences between the Volga-Ural populations examined. The results obtained suggest genetic homogeneity of the populations described in respect of the polymorphic locus examined.


[Management of secretion in patients with neuromuscular diseases].
Many patients with neuromuscular diseases suffer from a weak cough. Due to infection or aspiration a life-threatening situation may occur. There are different options for the therapists to improve secretion clearance from the airways in the patient with a weak cough. Furthermore, there are indications that consequent practice of techniques to ameliorate bronchial clearance may also improve the prognosis of patients with neuromuscular diseases. The management of secretions in neuromuscular disorders does not consist of single actions but is rather a complex programme. Diagnostics and several therapeutic measures have to be performed intensely and regularly. The diagnosis of a weak cough flow is based on anamnestic data, e. g., increase in secretions or dysphagia, physical examination, e. g., paradoxical breathing, and easily measured lung function parameters like vital capacity and peak cough flow (PCF). The diagnosis of an accumulation of secretions in the airways can be made easily by means of a pulse oximetry: while breathing room air the oxygen saturation in the case of a healthy lung and clean airways will be better than 95 %. A decline can, among others, be induced by amounts of secretions in the airways. The consequence should be measures to improve secretion expectoration (so-called oximetry-feedback protocol). To assist in secretion elimination from the airways several means are available like air stacking, manually assisted cough and mechanical assisted coughing--e. g., mechanical insufflator-exsufflator. Which of these techniques should be used depends on the extent of the disease: with preserved facial and bulbar muscles, air stacking alone or in combination with manually assisted coughing may be adequate and effective in the home care of the patient. In case of failure of these means, e. g., in bulbar paralysis, there is the possibility to apply mechanically assisted coughing by means of the mechanical insufflator-exsufflator. In case of tracheostomy, air stacking or mechanical assisted coughing has to be combined with tracheal suctioning. Acute infections of the lower airways are a special challenge: personnel intensive application of a combination of different secretion eliminating techniques, e. g., bronchoscopy in the hospital, manually assisted coughing and mechanically assisted coughing have to be performed in high intensity to avoid intubation. The early diagnosis of a weak cough in NMD patients is important for the timely start of existing and effective measures for improving the capacity of elimination of secretions--air stacking, manually assisted cough and mechanically assisted cough. Although there is no high degree of evidence, we believe that morbidity and possibly mortality can be affected in a positive manner.


Efficacy of an Algorithm-Based Nursing Intervention to Promote a Balance Between Cancer Patients' Social Roles and Outpatient Treatment: A Quasi-Experimental Study.
Cancer patients undergoing treatment are often unable to balance treatment and work because of the time required for care at the hospital and a desire to avoid problems at work. The aim of this study was to elucidate the efficacy of an algorithm-based nursing intervention (ANI) to promote balance between social roles and outpatient treatment in cancer patients. Participants were outpatients receiving cancer therapy and randomly assigned to a control or an intervention group, the latter to receive ANI for 2 months. The outcomes were assessed using the Distress and Impact Thermometer and changes in employment status. Data from 54 evaluable participants in each group were analyzed. Distress and Impact Thermometer scores in the intervention group were significantly lower than those in the control group ( P < .001). In addition, 2 months later, 20 participants had resigned from their employment or were on leave in the control group (37.0%); this was twice the number in the intervention group, a significant difference ( χ2 = 4.573, P < .05). Logistic regression analysis showed that the odds ratio in the control group was 3.6 times that of the intervention group of having resigned. The ANI appears to have reduced distress and impact scores associated with the course of treatment and to have reduced the likelihood of resignations at 2 months after implementation. The intervention appears to be effective and may be a new tool for use by outpatient oncology nurses.


Metabolism of 2,4-dinitrotoluene (2,4-DNT) by Alcaligenes sp. JS867 under oxygen limited conditions.
Transformation of 2,4-dinitrotoluene (2,4-DNT) by Alcaligenes JS867 under varying degrees of oxygen limitation was examined. Complete 2,4-DNT removal was observed under oxygen excess with near stoichiometric release (83%) of nitrite. Average kinetic parameters were estimated based on a dual-Monod biokinetic model with 2,4-DNT and O2 as growth limiting substrates. The negative impact of nitrite accumulation on the reaction rate was adequately described by inclusion of a noncompetitive inhibition term for NO2-. Under aerobic conditions, mumax, KsDNT, and KiNO were 0.058 (0.004)hr(-1), 3.3(+/-1.3) mg 2,4-DNT/L, and 1.2(+/-0.2)hr(-1), respectively. At increasing oxygen limitation, rates of 2,4-DNT disappearance and nitrite production decreased and incomplete removal of 2,4-DNT commenced. JS867 was able to use NO2- as a terminal electron acceptor when grown on glucose or succinate under anaerobic conditions. However, during growth on 2,4-DNT and under O2-limited conditions, JS867 did not use released nitrite as electron acceptor. The nearly constant molar ratios of DNT removed over NO2- released under various degrees of oxygen limitation suggested that oxygenolytic denitration pathways continued. No evidence of nitroreduction was obtained under the examined oligotrophic conditions. JS867 displayed a high affinity for oxygen consumption with K(SO2) value of 0.285(+/-0.198) mg O2/L. Our results indicate that under oligotrophic conditions with 2,4-DNT as dominant carbon source, oxygen availability and nitrite accumulation may limit 2,4-DNT biomineralization, but the accumulation of reduced 2,4-DNT transformation products will be small.


Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6.
Herbs as alternative cancer therapies have attracted a great deal of recent attention due to their low toxicity and costs. In this study, the antitumor activity and anticachectic effect of Coptidis rhizoma, an anti-inflammatory herb, were investigated in nude mice carrying a human esophageal cancer cell line YES-2, which constitutively secretes interleukin-6 (IL-6) and induces cachexia when injected into these mice. In this study, in vivo growth of YES-2 cells was not affected by an oral supplement containing the extract powder of C. rhizoma at a final concentration of 1% (CR supplement). However, in comparison with normal diet, CR supplement significantly attenuated weight loss of tumor-bearing mice without a change in food or water intake. Tumor IL-6 levels were significantly lower in mice treated with CR supplement than in control mice (P<0.001). Serum IL-6 was detectable in four (50%) of eight control mice; IL-6 was not detected in mice treated with CR supplement. We also confirmed that berberine (8-32 microM), a major component of C. rhizoma, dose-dependently inhibited secretion of IL-6 by YES-2 cells in vitro. Moreover, reverse transcription-PCR assay showed that treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA expression. Our results suggest that C. rhizoma may have an anticachectic effect on esophageal cancer and an effect is associated with the ability of berberine to down-regulate tumor IL-6 production.


Synthetic Plant Glycan Microarrays as Tools for Plant Biology.
Chemically synthesized plant oligosaccharides have recently evolved as powerful molecular tools for plant cell wall biology. Synthetic plant glycan microarrays equipped with these oligosaccharides enable high-throughput analyses of glycan-binding proteins and carbohydrate-active enzymes. To produce these glycan microarrays, small amounts of glycan solution are printed on suitable surfaces for covalent or non-covalent immobilization. Synthetic plant glycan microarrays have been used for example to map the epitopes of plant cell wall-directed antibodies, to characterize glycosyl hydrolases and glycosyl transferases, and to analyze lectin binding. In this chapter, detailed experimental procedures for the production of synthetic glycan microarrays and their use for the characterization of cell wall glycan-directed antibodies are described.


Efficacy of Fiberoptic Laryngeal Surgery in Benign VocalCord Lesions in Comparision with Microlaryngeal Surgery.
The use of operating microscope and rigid telescope in laryngeal surgery represents one of the most exciting advances. Both systems provide good illumination, magnification and relative ease of operation. Microlaryngeal surgery (MLS) with suspension laryngoscope is currently considered the gold standard for surgical approach to the larynx for excision of benign lesions of vocal folds. The limitation of this technique is intubation, general anesthesia (GA) related and in difficult exposure of larynx. The development of ideal anesthetic system has not been successful in satisfying both the surgeon and the anesthesiologist. Fiberoptic Laryngeal Surgery (FLS) is convenient as it avoids GA, is an outpatient procedure with less morbidity and reduced costs. FLS is preferable for the patients who have medical contraindications for general GA. To compare the efficacy of MLS and FLS surgical procedures in terms of functional outcome. This is a comparative clinical study done on 42 patients who were diagnosed to have benign vocal fold pathology. Pre and post-operative speech evaluation was done for all the patients by the same examiner, which included GRABS scale, Maximum Phonation Time, voiced consonants, voiceless consonants, s/z ratio along with stroboscopy. In Group A, MLS was the treatment modality, done under GA, while in Group B, FLS was the treatment modality done under Local Anesthesia (LA). After one-month, post-operative evaluation of voice was done. When the Maximum Phonation Time, S/Z ratio and stroboscopic parameters (mucosal wave) were compared between the two study groups there appeared no statistically significant difference between the two groups. Our study shows that when benign vocal cord pathologies were treated by MLS or FLS the voice Quality improvement remains the same. FLS is the procedure of choice when MLS under general anesthesia is contraindicated.


Milky spots (Taches laiteuses) as structures which trap asbestos in mesothelial layers and their significance in the pathogenesis of mesothelial neoplasia.
The UICC standard sample of asbestos, crocidolite, was injected subcutaneously into the flanks of CBA/lac mice. Asbestos fibres were found in milky spots in the serosal cavities more than 442 days after the injection, in the form of either naked fibres or asbestos bodies. Milky spots were the only structure in which asbestos fibres were observed in the mesothelial layer. The fact that asbestos fibres were found in the liver, spleen, kidney, brain, etc., in addition to milky spots, suggested that they were transported by the blood stream throughout the body. This assumption was confirmed by the similar distribution of asbestos after intravenous administration. The vascular and cellular structure of milky spots is such that they are particularly likely to trap blood-borne asbestos fibres. Hyperplastic changes were observed in milky spots after both subcutaneous and intravenous administration of asbestos in mice. The possible involvement of milky spots in the genesis of tumors of the mesothelium following exposure of animals to asbestos is discussed.


Effect of diet on the disruption of operant responding at different ages following exposure to (56)Fe particles.
Rats were exposed to 2.0 Gy of (56)Fe particles to study the relationship between age and diet in the heavy particle-induced disruption of performance on an ascending fixed-ratio task. Irradiation produced a disruption of operant responding in rats tested 5 and 8 months after exposure, which was prevented by maintaining the rats on a diet containing strawberry, but not blueberry, extract. When tested 13 and 18 months after irradiation there were no differences in performance between the radiated rats maintained on control, strawberry or blueberry diets. These observations suggest that the beneficial effects of antioxidant diets may be dependent upon the age of testing.


Performance of random forests and logic regression methods using mini-exome sequence data.
Machine learning approaches are an attractive option for analyzing large-scale data to detect genetic variants that contribute to variation of a quantitative trait, without requiring specific distributional assumptions. We evaluate two machine learning methods, random forests and logic regression, and compare them to standard simple univariate linear regression, using the Genetic Analysis Workshop 17 mini-exome data. We also apply these methods after collapsing multiple rare variants within genes and within gene pathways. Linear regression and the random forest method performed better when rare variants were collapsed based on genes or gene pathways than when each variant was analyzed separately. Logic regression performed better when rare variants were collapsed based on genes rather than on pathways.


Numerical simulation of Electron Energy Loss Spectroscopy using a Generalized Multipole Technique.
We numerically simulate low-loss Electron Energy Loss Spectroscopy (EELS) of isolated spheroidal nanoparticles, using an electromagnetic model based on a Generalized Multipole Technique (GMT). The GMT is fast and accurate, and, in principle, flexible regarding nanoparticle shape and the incident electron beam. The implemented method is validated against reference analytical and numerical methods for plane-wave scattering by spherical and spheroidal nanoparticles. Also, simulated electron energy loss (EEL) spectra of spherical and spheroidal nanoparticles are compared to available analytical and numerical solutions. An EEL spectrum is predicted numerically for a prolate spheroidal aluminum nanoparticle. The presented method is the basis for a powerful tool for the computation, analysis and interpretation of EEL spectra of general geometric configurations.


Biomechanical insult switches PEA-15 activity to uncouple its anti-apoptotic function and promote erk mediated tissue remodeling.
Biomechanical insult contributes to many chronic pathological processes, yet the resulting influences on signal transduction mechanisms are poorly understood. The retina presents an excellent mechanotransduction model, as mechanical strain on sensitive astrocytes of the optic nerve head (ONH) is intimately linked to chronic tissue remodeling and excavation by matrix metalloproteinases (MMPs), and apoptotic cell death. However, the mechanism by which these effects are induced by biomechanical strain is unclear. We previously identified the small adapter protein, PEA-15 (phosphoprotein enriched in astrocytes), through proteomic analyses of human ONH astrocytes subjected to pathologically relevant biomechanical insult. Under resting conditions PEA-15 is regulated through phosphorylation of two key serine residues to inhibit extrinsic apoptosis and ERK1/2 signaling. However, we surprisingly observed that biomechanical insult dramatically switches PEA-15 phosphorylation and function to uncouple its anti-apoptotic activity, and promote ERK1/2-dependent MMP-2 and MMP-9 secretion. These results reveal a novel cell autonomous mechanism by which biomechanical strain rapidly modifies this signaling pathway to generate altered tissue injury responses.


Maternal separation and maternal care act independently on the development of HPA responses in male rats.
Postnatal manipulations such as brief (early handling, EH) and long, daily mother-offspring separations (maternal separation, MS) in rats are used to study the mechanisms underlying developmental plasticity of stress and fear responses, and to model stress-related disorders in humans and in non-human animals. Current evidence suggests that, compared to non-handled rats, EH reduces hypothalamic-pituitary-adrenal (HPA) reactivity in the adult offspring through stimulating increased levels of active maternal care. In contrast, despite a similar increase in active maternal care, MS does not reduce HPA reactivity, thus suggesting that long mother-offspring separations may counteract the effects of increased active maternal care. We therefore attempted to selectively manipulate levels of active maternal care and durations of mother-offspring separations in neonate rats. Rat pups were exposed to different combinations of EH and MS from postnatal day (PND) 2 to 10 using a split-litter design. Maternal behaviour was recorded from PND 2 to 8 and behavioural and endocrine responses to stress were studied in adult male offspring. Low levels of maternal care combined with long mother-offspring separations increased HPA-reactivity compared to both high maternal care combined with long mother-offspring separations and low maternal care combined with brief separations. These findings further support the hypothesis that active maternal care and long mother-offspring separation act independently, and exert opposing effects, on adult offspring's HPA responses, but that increased maternal care may buffer the adverse consequences of long separations.


Focal adhesion kinase and beta1 integrin regulation of Na+, K+, 2Cl- cotransporter in osmosensing ion transporting cells of killifish, Fundulus heteroclitus.
Focal adhesion kinase (FAK), also known as PYK2, is a tyrosine kinase that functions in integrin-mediated signaling in mechanosensitive cells but its role in osmosensing cells is unknown. Antibodies directed against phosphorylated FAK, whose epitopes are conserved among vertebrates, were used to follow phosphorylation patterns in an osmosensing ion secreting epithelium, the killifish (Fundulus heteroclitus) opercular membrane. At the electron microscopic level, a unique combination of integrin beta1, the phosphorylated form of FAK at tyrosine 407 (pY407) and Na(+), K(+), 2Cl(-) cotransporter (NKCC1) were all colocalized only on the basolateral membrane in chloride cells. The three proteins were also coimmunoprecipitated with each other in isotonic conditions, suggesting an osmosensing complex involving the three proteins. Only FAK pY407 was sensitive to hypotonic shock and became dephosphorylated with hypotonic shock, while FAK pY576 in the apical membrane and pY861 in cell-cell adhesions were insensitive to hypotonicity. NKCC1 contributes to NaCl secretion in seawater and previous reports showed that hypotonic shock (-60 mOsm/kg) rapidly inhibits Cl(-) secretion. These results indicate that chloride cells respond to hypotonic shock using integrin beta1 as an osmosensor that is connected to dephosphorylation of FAK pY407 which leads to NKCC1 deactivation in the basolateral membrane and the inhibition of NaCl secretion by these epithelial cells.


Contribution of the one health approach to strengthening health security in Uganda: a case study.
The One Health approach is key in implementing International Health Regulations (IHR, 2005) and the Global Health Security Agenda (GHSA). Uganda is signatory to the IHR 2005 and in 2017, the country conducted a Joint External Evaluation (JEE) that guided development of the National Action Plan for Health Security (NAPHS) 2019-2023. This study assessed the contribution of the One Health approach to strengthening health security in Uganda. A process evaluation between 25th September and 5th October 2020, using a mixed-methods case study. Participants were Subject Matter Experts (SMEs) from government ministries, departments, agencies and implementing partners. Focus group discussions were conducted for five technical areas (workforce development, real-time surveillance, zoonotic diseases, national laboratory systems and emergency response operations), spanning 18 indicators and 96 activities. Funding and implementation status from the NAPHS launch in August 2019 to October 2020 was assessed with a One Health lens. Full funding was available for 36.5% of activities while 40.6% were partially funded and 22.9% were not funded at all. Majority (65%) of the activities were still in progress, whereas 8.6% were fully implemented and14.2% were not yet done. In workforce development, several multisectoral trainings were conducted including the frontline public health fellowship program, the One Health fellowship and residency program, advanced field epidemiology training program, in-service veterinary trainings and 21 district One Health teams' trainings. Real Time Surveillance was achieved through incorporating animal health events reporting in the electronic integrated disease surveillance and response platform. The national and ten regional veterinary laboratories were assessed for capacity to conduct zoonotic disease diagnostics, two of which were integrated into the national specimen referral and transportation network. Multisectoral planning for emergency response and the actual response to prioritized zoonotic disease outbreaks was done jointly. This study demonstrates the contribution of 'One Health' implementation in strengthening Uganda's health security. Investment in the funding gaps will reinforce Uganda's health security to achieve the IHR 2005. Future studies could examine the impacts and cost-effectiveness of One Health in curbing prioritized zoonotic disease outbreaks.