Use of highly sensitive sublethal stress responses in the social amoeba Dictyostelium discoideum for an assessment of freshwater quality.
In this work, the sensitivity of a battery of tests on the social amoeba Dictyostelium discoideum has been assessed within a freshwater toxicity study. The results obtained from the evaluation of survival and replication rate of D. discoideum were compared to those derived with a series of widely used tests for freshwater toxicity assessment, i. e. bioassays using Vibrio fischeri, Daphnia magna and Pseudokirchneriella subcapitata. The effects on sublethal endpoints, i.e. lysosomal membrane stability (LMS) and endocytotic rate, were analysed in conjunction with high-level endpoints to verify the potential to make a typical bioassay more sensitive. The field ecotoxicological investigation employing D. discoideum is part of a monitoring study assessing environmental quality of the Bormida River (Italy), subjected until recently to a chronic industrial pollution. The survey was carried out at several stations (upstream and downstream of a chemical factory outlet) in two different periods. In 2002, the results of chemical analyses performed on river water indicated no contamination. The ecotoxicological data obtained in this period showed that no evidence of biological effects was observed using V. fischeri and D. magna bioassays. In spite of the previous classical acute toxicity tests, significant differences in cell viability of D. discoideum were found. By analysing the effects measured on LMS and endocytotic rate, more relevant changes were observed for these sublethal stress biomarkers compared to survival. The chronic toxicity data showed significant changes in cell growth both of P. subcapitata and D. discoideum. Nevertheless, more sensitive and rapid responses were obtained when assessing the effects of exposure on D. discoideum. The chemical and ecotoxicological data obtained in 2006 indicated a full recovery of the quality of the river water (neither contamination nor toxicity found). Altogether, the results reported in this study underline that the use of a battery of biomarkers in conjunction with high-level endpoints may help follow the pollutant-induced stress syndrome in the organisms from early sublethal effects to starting mortality.


Green fabrication of durable foam composites with asymmetric wettability by an emulsion spray-coating method for photothermally induced crude oil cleanup.
Chemical spills, especially oil spills, are becoming an increasingly serious environmental issue. It remains a challenge to develop green techniques to prepare mechanically robust oil-water separation materials, especially those capable of separating high-viscosity crude oils. Herein, we propose an environmentally friendly emulsion spray-coating method to fabricate durable foam composites with asymmetric wettability for oil-water separation. After the emulsion, composed of acidified carbon nanotubes (ACNTs), polydimethylsiloxane (PDMS) and its curing agent, is sprayed onto melamine foam (MF), water in the emulsion is first evaporated, while PDMS and ACNTs are finally deposited on the foam skeleton. The foam composite exhibits gradient wettability and turns from superhydrophobicity of the top surface (the water contact angle reaches as high as 155.2°) to hydrophilicity of the interior region. The foam composite can be used for the separation of oils with different densities and has a 97% separation efficiency for chloroform. In particular, the photothermal conversion-induced temperature rise can reduce the oil viscosity and complete the high-efficiency cleanup of crude oil. This emulsion spray-coating technique and asymmetric wettability show promise for the green and low-cost fabrication of high-performance oil/water separation materials.


High Prevalence of Cervical High-Risk Human Papillomavirus Harboring Atypical Genotypes in Human Immunodeficiency Virus -Infected and -Uninfected First-Generation Adult Immigrant Women Originating from Sub-Saharan Africa and Living in France.
Human papillomavirus (HPV)-related cervical lesions in first-generation immigrant African women in France should reflect the epidemiology of high-risk (HR)-human papillomavirus (HPV) infection in sub-Saharan Africa. First-generation immigrant African women attending the Centre Hospitalier Régional of Orléans, France, were prospectively subjected to endocervical swabs for HPV DNA PCR and Pap smear. Fifty women (mean age, 41.7 years) living in France (mean stay, 10.7 years) were enrolled, including 26.0% of HIV-negative women from general population and 74.0% of women with known HIV infection. Cervical HPV prevalence was 68.0%, with 56.0% of HR-HPV. HR-HPV -68 and -58 were the predominant genotypes (20.0% and 14.0%, respectively). HR-HPV-16 and HR-HPV-18 were infrequently detected. HIV-infected women showed a trend to be more frequently infected by HPV than HIV-negative women (70.3% versus 61.5%). Most women (84.0%) showed normal cytology, while the remaining (16.0%) exhibited cervical abnormalities and were frequently HIV-infected (87.5%). These observations highlight the unsuspected high burden of cervical HR-HPV infections mostly associated with atypical genotypes, HIV infection and cervical abnormalities in first-generation immigrant African women living in France.


Quantitative morphological evaluation of experimentally induced atheroma.
A computerized operator-interactive system for measurement of atheroma is described. The system utilizes a 64K microcomputer, a high resolution digitizer tablet, dual floppy disc drives, and a video monitor. The method offers significant advantages over earlier systems in speed, accuracy, reproducibility and cost effectiveness.


Rnq1! You are still dangerous, but you can be my wingman anytime.
In this issue of Molecular Cell, Gropp et al. identify how the cellular background affects whether or not the Huntington's disease protein will form toxic pathological aggregates, providing insight into selective neuronal vulnerability in neurodegenerative disease.


Chromosome-level genome assembly of the bar-headed goose (Anser indicus).
Bar-headed geese (Anser indicus) are adaptable to plateau environments. In this study, we sequenced and assembled a high-quality chromosome-level genome of the bar-headed goose using PacBio long reads and Hi-C technique, and generated 115.73 Gb of Illumina short-reads and 95.89 Gb of PacBio long-reads. The assembled bar-headed goose genome, with a contig N50 of 5.734 Mb and a scaffold N50 of 65.77 Mb, is 1.129 Gb in length and includes 33 chromosomes and 451 fragments. BUSCO assessment yielded a completeness score of 94.4%. In total, 15,376 protein-coding genes were predicted, of which 94.95% had homologs in protein databases. We identified 78 positively selected genes (PSGs) in the bar-headed goose genome, which were mainly enriched in calcium ion and ATP-binding. This bar-headed goose genome will be an important resource for increasing our understanding regarding the genetic basis of adaptation to life at a high altitude.


An approach to analyzing the intensity of the daytime surface urban heat island effect at a local scale.
A landscape index LI is proposed to evaluate the intensity of the daytime surface urban heat island (SUHI) effect at a local scale. Three aspects of this landscape index are crucial: the source landscape, the sink landscape, and the contribution of source and sink landscapes to the intensity of the SUHI. Source and sink landscape types are identified using the thermo-band of Landsat 7 with a spatial resolution of 60 m, along with appropriate threshold values for the Normalized Difference Vegetation Index, Modified Normalized Difference Water Index, and Normalized Difference Built-up Index. The landscape index was defined as the ratio of the contributions of the source and sink landscapes to the intensity of the SUHI. The intensity of the daytime SUHI is assessed with the help of the landscape index. Our analysis indicates the landscape index can be used to evaluate and compare the intensity of the daytime SUHI for different areas.


Myocardial Involvement in Rheumatic Disorders.
Autoimmune rheumatic diseases (ARDs) affect 8% of the population and approximately 78% of patients are women. Myocardial disease in ARDs is the endpoint of various pathophysiologic mechanisms including atherosclerosis, valvular disease, systemic, myocardial, and/or vascular inflammation, as well as myocardial ischemia and replacement/diffuse fibrosis. The increased risk of CVD in ARDs leads to excess comorbidity not fully explained by traditional cardiovascular risk factors. It seems that the chronic inflammatory status typically seen in ARDs, promotes both the development of myocardial inflammation/fibrosis and the acceleration of atherosclerosis. CMR (cardio-vascular magnetic resonance) is the ideal imaging modality for the evaluation of cardiac involvement in patients with ARDs, as it can simultaneously assess cardiac function and characterize myocardial tissues with regard to oedema and fibrosis. Due to its high spatial resolution, CMR is capable of identifying various disease entities such as myocardial oedema /inflammation, subendocardial vasculitis and myocardial fibrosis, that are often missed by other imaging modalities, notably at an early stage of development. Although generally accepted guidelines about the application of CMR in ARDs have not yet been formulated, according to our experience and the available published literature, we recommend CMR in ARD patientS with new-onset heart failure (HF), arrhythmia, for treatment evaluation/change or if there is any mismatch between patient symptoms and routine non-invasive evaluation.


Randomised controlled trial of spinal anaesthesia with bupivacaine or 2-chloroprocaine during caesarean section.
Neuraxial anaesthesia is the desired method for Caesarean section. Bupivacaine is a well-known local anaesthetic. It has a long duration of action and can cause unpredictable levels of anaesthesia with subsequent prolonged discharge time. 2-Chloroprocaine has a rapid onset of action, producing an excellent sensory and motor block and has a rapid hydrolysis in the bloodstream by pseudocholinesterase. We compared bupivacaine and 2-chloroprocaine for spinal anaesthesia during Caesarean section. The primary endpoint was the earliest reversal sign of the motor block. Sixty ASAI/II patients, planned for elective singleton Caesarean section, were equally randomised to three groups. All patients received a combined spinal-epidural anaesthesia. The first group received 2-chloroprocaine (40 mg) without sufentanil, the second group received 2-chloroprocaine (40 mg) with sufentanil (1 μg) and the third group received hyperbaric bupivacaine (7.5 mg) with sufentanil (1 μg) as a spinal anaesthetic. Motor and sensory blockade were assessed at specific time points. There was no difference between the three groups regarding the time to regression of the motor block. However, at 5 min post spinal injection, the level of sensory block was higher for both groups with 2-chloroprocaine, in comparison with the bupivacaine group. 2-Chloroprocaine can be used for low risk Caesarean section in healthy parturients. There is no difference in time to motor block resolution compared to bupivacaine. Motor recovery seems more predictable for 2-chloroprocaine and may be beneficial for the breastfeeding initiation.


A hybrid approach to measuring electrical activity in genetically specified neurons.
The development of genetically encoded fluorescent voltage probes is essential to image electrical activity from neuronal populations. Previous green fluorescent protein (GFP)-based probes have had limited success in recording electrical activity of neurons because of their low sensitivity and poor temporal resolution. Here we describe a hybrid approach that combines a genetically encoded fluorescent probe (membrane-anchored enhanced GFP) with dipicrylamine, a synthetic voltage-sensing molecule that partitions into the plasma membrane. The movement of the synthetic voltage sensor is translated via fluorescence resonance energy transfer (FRET) into a large fluorescence signal (up to 34% change per 100 mV) with a fast response and recovery time (0.5 ms). Using this two-component approach, we were able to optically record action potentials from neuronal cell lines and trains of action potentials from primary cultured neurons. This hybrid approach may form the basis for a new generation of protein-based voltage probes.


Entropic interactions on a colloidal sphere near the edge of a terrace.
We calculated the entropic interactions between a colloidal sphere and the hard edge of a terrace by means of Monte Carlo simulation with the acceptance ratio method. Comparison with the Asakura-Oosawa approximation indicates that the AO approximation is more accurate in this model than other known models. Our simulation results are also in qualitative agreement with the experimental results obtained by A.D. Dinsmore et al.


CT invertograms.
Direct sagittal CT can provide an accurate assessment of anorectal anomalies in selected patients. Images are easily obtained and enable direct imaging of the soft tissues of the rectum and anus.


Assessing weaning stress - Relations between enamel hypoplasia, δ18O and δ13C values in human teeth obtained from early modern cemeteries in Wroclaw, Poland.
The aim of this paper is to assess linear enamel hypoplasia (LEH) on canines of adults from early modern Wroclaw cemeteries to compare δ13C and δ18O values in enamel formed before, during and after LEH formation, and to attempt to find a link between the selected indicators of the weaning process. 15 permanent canines with visible LEH were selected for analysis. Age at LEH formation was estimated using the Reid and Dean method. The perikymata count was used to estimate the duration of LEH formation. Incremental stable oxygen and carbon isotopes analysis was performed on tooth enamel to infer stress related to weaning and dietary patterns. Kruskal-Wallis ANOVA, Mann-Whitney U test and Spearman correlation were used in statistical inference. The average age of LEH formation was 3.14 years, with an average duration of 111 days. Stable carbon isotope values consistently increase in 73% of the individuals sampled. The values of δ18O do not show a dominant pattern. The average value of δ13C increases over the time of enamel formation. The δ13C values collected below LEH were negatively correlated with δ18O values and the duration of LEH termination. Marking of carbon and oxygen isotopes indicates different stages of weaning. Advancements in diet change (determined by higher δ13C) corresponds with faster recovery after physiological stress episode. There is no evidence for different breastfeeding models between distinct parishes in early modern Wroclaw.


LDL-cholesterol lowering effect of a generic product of simvastatin compared to simvastatin (Zocor) in Thai hypercholesterolemic subjects -- a randomized crossover study, the first report from Thailand.
It is commonly agreed that people with a high blood LDL-cholesterol will have a higher risk of coronary artery disease (CAD) than people with low blood LDL-cholesterol. Due to the increasingly high costs of medication in Thailand, the government has set up several measures to combat the problem. One of such strategies is to promote the utilization of locally manufactured drug products, especially those contained in the National Drug List. Simvastatin, an HMG-CoA reductase inhibitor, is listed as an essential drug for the treatment of hypercholesterolemia. Here, we reported the study on the LDL-cholesterol-lowering effect of a generic simvastatin product in comparison with the Zocor, in 43 healthy thai volunteers. The generic product tested was Eucor, locally manufactured by Greater Pharma Ltd., Part, Thailand, and the reference product was Zocor (Merck Sharp & Dohme, USA). The two products were administered as 10-mg single oral doses in a two-period crossover design. After drug administration, serial blood samples were collected every 4 weeks for 16 weeks. The major parameter monitored in this study was blood LDL-cholesterol. After taking the drugs for the first 8 weeks, no statistically significant difference was detected in blood LDL-cholesterol between the first (Zocor-treated) and the second (Eucor-treated) groups. After crossover and taking drugs for further 8 weeks, a similar result was obtained, i.e., no significant difference in blood LDL-cholesterol between the first (Eucor-treated) and the second (Zocor-treated) groups was observed. Upon completion of the 16-week study, there was also no statistically significant difference in the changes of all tested blood parameters between the two products (randomized block ANOVA, N = 37). Only minor side effects, mainly dizziness and nausea, were observed in both products. Our study demonstrated no significant differences in the therapeutic effect and safety between the generic and original simvastatin products.


A kinetic study on the influence of the parameters in the determination of inorganic phosphate by the molybdenum blue reaction.
Parameters which influence the initial rate of formation of phosphomolybdenum blue from phosphate, molybdate, polyvinylpyrrolidone and o-phenylenediamine were investigated. From kinetic data it is concluded that polyvinylpyrrolidone not only acts as a protective colloid, but that it takes part in the reaction and a reaction mechanism is proposed dealing with the stoichiometry of polyvinylpyrrolidone. A rate procedure for the determination of inorganic phosphate in serum and urine, based on this study, is given. Deproteinization of samples is not necessary. The method is rapid requiring one minute for quantitative readings. Because of this short period there is hardly any hydrolysis of organic phosphate esters. As the rate of color development is determined blanks can be omitted. Turbid samples may be analysed with little error.


CD38 expression is an important prognostic marker in chronic lymphocytic leukaemia.
Employing a multicolour flow cytometry assay, 133 B-chronic lymphocytic leukaemia (B-CLL) cases were analysed for surface expression of CD38. Based on a cut-off value of 20%, CLL patients were categorised into a CD38-positive (> or = 20%, n = 56) and a CD38-negative subgroup (< 20%, n = 77) and separately analysed for clinical and laboratory parameters. Patients in the CD38-positive cohort were characterised by an unfavourable clinical course with a more advanced disease stage, poor responsiveness to chemotherapy, short time to initiation of first treatment and shorter survival. In contrast, the CD38- negative group required minimal or no treatment, remained treatment-free for a longer time period and had prolonged survival (P < 0.05). CD38 expression was a robust marker in the majority of patients in that it was stable over time and not significantly influenced by chemotherapy. In conclusion, our data confirm recent studies suggesting a role of CD38 as a predictor of clinical outcome in patients with B-CLL.


Effect on quality of life of continuous positive airway pressure in patients with obstructive sleep apnea syndrome: a meta-analysis.
Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnea syndrome (OSAS). However, the impact of CPAP on quality of life (QOL) is controversial. The aim of this study was to systematically review and determine whether CPAP improves QOL in patients with OSAS. We performed a comprehensive literature search to identify studies published between 1966 and 2007 comparing values of CPAP with control. Weighted mean difference (WMD) was used to analyze the data. The pooled WMD was calculated by using a fixed or random-effect model. The outcomes for 1,256 patients from 16 studies, of whom 656 patients underwent CPAP and 600 were controls, were included. CPAP led to significant improvements in the Nottingham health profile part 2 (WMD=1.657; 95% CI=3.005, -0.308; p=0.016), but there was no difference in other general QOL scores. Patients undergoing CPAP scored better in physical function (WMD=3.457; 95% CI=0.144, 6.771; p=0.041), body pain (WMD=4.017; 95% CI= -0.008, 8.042; p=0.05), energy vitality (WMD=6.984; 95% CI = 0.557, 13.411; p=0.033) and physical component summary (PCS) (WMD=2.040; 95% CI=0.045, 4.035; p=0.045) using the SF-36 tool. This meta-analysis shows that CPAP does not improve general QOL scores but does improve physical domains and vitality. Study design and QOL questionnaire tools are important to capture and evaluate information efficiently. However, generic QOL instruments may not be adequate in detecting important changes in quality of life in patients with OSAS.


Expression in bacteria of small and specific protein domains of two transcription factor isoforms, purification and monospecific polyclonal antibodies generation, by a two-step affinity chromatography procedure.
The detection and analysis of protein isoforms is a complicated task especially if they differ only in small specific domains. Obtaining specific polyclonal antibodies against these domains is a challenge, but if successful it can have a wide range of applications, such as in proteomics and immunochemical analysis. We show herein a method of overexpression and purification of two small specific domains corresponding to the isoforms b and c of the murine transcription factor Pitx2, and the generation and purification of monospecific polyclonal antibodies against them, by using a two-step affinity purification procedure, based on the use of CNBr-Sepharose matrix. Such a method also allows recovering monospecific polyclonal antibodies against the tag fusion peptide (C-LYTAG tag). The specificity of the isolated polyclonal antibodies was demonstrated by Western blot and immunohistochemical analysis. In addition, our protocol is easily scalable and allows the generation of monospecific polyclonal antibodies for large-scale analysis.


Atypical clinical presentation and management of urinary stone disease in non-verbal non-ambulatory children.
Management of kidney stones primarily depends on various factors such as the presence of urinary tract obstruction, pain, stone size, location, impact on renal function, and the existence of infection. Renal colic is the classic presentation of an obstructive kidney stone. However, in this study, we present a cohort of non-verbal non-ambulatory (NVNA) patients who exhibit a distinct and uncommon presentation of kidney stones due to their medical conditions. Information about kidney stone disease in this gropup of complex pediatric patients is, scarce and their associated risk factors are not well understood. Therefore, we aim to summarize the clinical presentation, and management challenges in this unique group of NVNA patients to identify potential variables for prospective studies. A retrospective chart review was completed for all NVNA patients seen at the pediatric multidisciplinary kidney stone clinic between July 2020 to August 2022. Demographic variables, clinical presentation data, metabolic evaluation, radiological imaging, and surgical management was included for analysis. A total of 224 pediatric patients were referred to the multidisciplinary stone clinic. Of those, 27 were identified to be NVNA. The most common primary diagnosis was Cerebral Palsy followed by Lennox-Gastaut syndrome. Average age at first kidney stone presentation was 11.5 years ± 5.7 years. An obstructing stone was diagnosed in 18 (66%) patients, 4 (22.2%) of these presented with sepsis. Average stone burden was 9.2 mm ( ± 5.8 mm). Of the obstructing stones, 13 (72%) were in the kidney. All patients with an obstructing stone underwent surgical management with retrograde endoscopic approach. Metabolic 24-h-urine analysis was completed in 24 (89%) patients. 17 (62%) had an elevated urine density, 15 (55%) demonstrated calcium oxalate supersaturation, 12 (44%) met criteria for acidosis, and 7 (26%) had significant hypocitraturia. NVNA patients represent a unique cohort whose clinical presentation is atypical. Limited ability to express symptoms makes early detection difficult to recognize. Twenty two percent of patients present with sepsis as their first manifestation of an acutely obstructing kidney stone. Pain is subjectively interpreted by caregivers and is an uncommon symptom. Our cohort demonstrates common risk factors for stones including propensity for chronic dehydration, slow urinary tract transit, ineffective bladder emptying, G-tube feeding, and lithogenic medications. NVNA pediatric patients have atypical kidney stone clinical presentation. Awareness of this unique group of patients should support future collaborative studies to focus on understanding these atypical presentations and reflect on improving management.


Dental complications in homocystinurias.
Cystathionine beta synthase deficiency (causing classical homocystinuria) has been associated with high-arched palates and crowded teeth, but little has been said about other oral health complications. Other homocystinurias (e.g., the remethylation defects) also have had little reported in terms of oral health. Individuals with the homocystinurias have been described as having bone density issues which can correlate with oral health. Moreover, elevations in homocysteine have a theoretical impact on tooth health and the paucity of clinical reports of oral health issues in homocystinuria may be the consequence of lack of attention by the medical community. Oral health is essential to overall health. If inadequate attention is paid to the oral health complications which can be seen in homocystinurias, then appropriate referrals and attention in therapeutic guidelines will not reflect the importance of oral health. What oral health complications are reported by individuals with homocystinurias? Do these differ according to diagnosis? Data were collected from patients with homocystinurias by a series of questionnaires using the RARE-X platform. All subjects were consented prior to the collection of their data. All research was performed in accordance with the Declaration of Helsinki. Demographic data were collected as the initial questionnaire and other data were collected via the oral health questionnaire. Questionnaires were opened to the community in mid-2022 and collection of data for this study ended with data submitted up to November 2022. Descriptive statistics were done. Due to the small size of the cohort, additional statistical analyses were not attempted. Patients with homocystinuria, not related to cystathionine beta synthase deficiency, are reporting some tooth structure differences. The cohort taken as a whole does not have increased risk for gingivitis, but there appears to be a risk for long-term gum disease possibly due to the rate of osteoporosis/osteopenia in this population. A large number of individuals have malalignment and malocclusion of the teeth. These data highlight oral health as an important component of care in individuals with the homocystinurias as is true of the general population at large.


Awareness and distress after traumatic brain injury: a relative's perspective.
To examine the relationship between relatives' distress level and their ratings of impaired awareness for persons with traumatic brain injury (TBI). Participants were 25 patients with TBI, 16 with probably dementia, and 15 with memory complaints but no dementia. Participants completed the Barrow Neurological Institute Screen for Higher Cerebral Functions. Relatives of all patients completed the Patient Competency Rating Scale (Relative Form). Relatives also rated their distress level on a scale from 0 (no distress) to 10 (severe distress) and then rated the patient's level of awareness of their difficulties, also on a scale from 0 (not aware) to 10 (completely aware). Clinical neuropsychology outpatient service of a neurological institute and medical center. For relatives of patients with TBI, a significant correlation of -0.52 (P = .006) was found. Correlations for the dementia and memory complaint groups were -0.62 (P = .03) and -0.39 (P = .20), respectively. The presence of brain dysfunction associated with neuropsychological disturbances appears to influence the magnitude of the relationship between the distress level of family members and their ratings of impaired awareness in persons with TBI.


Xanthine oxidase inhibitor in Duchenne muscular dystrophy.
The treatment with xanthine oxidase inhibitor, allopurinol, was evaluated in 17 patients with Duchenne muscular dystrophy (aged 2 years 9 months to 13 years 9 months) using the double blind technique. The total observed period was 27 months. The results of 100-point scale of graded functional abilities revealed that an improvement, unchange and progression of dysfunction were found in 2, 2 and 6 patients, respectively, in allopurinol group and in 0, 2 and 5 patients, respectively in placebo group. The patients' age and stage of the disease seemed to be related to the effectiveness or allopurinol treatment.


Differences in Warfarin Pharmacodynamics and Predictors of Response Among Three Racial Populations.
Population differences in warfarin dosing requirement have been reported; however, unlike the pharmacokinetics (PK) of warfarin, the quantitative influences of pharmacodynamic (PD) factors on the anticoagulation response to warfarin in different ethnic populations are totally unknown. Using population PK/PD analysis, we attempted to identify predictors of S-warfarin clearance [CL(S)] and half maximal effective concentration (EC50) to quantify racial differences in both PK and PD parameters, and to assess the contribution of these parameters to the international normalized ratio (INR) and over-anticoagulation response (INR ≥ 4) in a cohort of 309 White, Asian and African American patients. Similar to our previous findings, the median CL(S) was 30% lower in African American patients than Asian and White patients (169 vs. 243 and 234 mL/h, p < 0.01). EC50 showed a greater racial difference than CL(S) [1.03, 1.70 and 2.76 μg/mL for Asian, White and African American patients, respectively, p < 0.01). Significant predictors of INR included demographic/clinical (age, body weight, creatinine clearance and sex) and genotypic (CYP2C9*3,*8 and VKORC1 -1639G>A) factors, as well as African American ethnicity. In all three racial groups, genetic predictors of INR appeared to have greater influence than demographic/clinical predictors. Both CL(S) and EC50 contributed to the over-anticoagulation response to warfarin. Patients having VKORC1 -1639 G>A and/or factors associated with reduced CYP2C9 activity were more likely to have an INR ≥ 4. Although there were contrasting racial differences in CL(S) and EC50 that impacted on the INR, the racial difference in EC50 was greater than that for CL(S), thus explaining the higher warfarin requirement for African American patients.


Effects of ants on the foraging of birds in spruce trees.
I experimentally excluded ants from randomly selected spruce trees Picea abies near colonies of the wood ant Formica aquilonia. Foraging activity of birds in these trees was then compared to the foraging activity of birds in neighboring spruce trees, where ants were allowed to continue foraging. Birds which foraged in the foliage showed the effects of competition with ants: they visited the trees without ants more frequently, and for longer periods. In addition, the insects and spiders that they utilized as food were more abundant in the foliage of trees without ants. Cone-foraging birds, however, which fed on seeds in cones at the tops of the trees, did not show a preference for trees without ants. The differences of tree usage between foliage-gleaning and coneforaging birds can be explained by alteration of the birds' food supply by wood ants: ants did not feed on seeds in cones, and so did not compete with cone-foraging birds. However, foraging wood ants did feed on arthropods living in the foliage, thus reducing the amount of food available to birds there.


Recent pollution records in Sidi Moussa coastal lagoon (western Morocco) inferred from sediment radiometric dating.
The Sidi Moussa lagoon, located in western coastal Morocco and ranked as a wetland of biological and ecological importance (Ramsar site), is contaminated due to its proximity to the industrial phosphate plants and other anthropogenic activities around it. This study was carried out to assess the current environmental state of the lagoon as well as historical inputs of pollutants over several decades. Three sediment cores were collected and analyzed for the determination radionuclide activities (210Pb, 226Ra, 238U and 137Cs) by gamma spectrometry and element concentrations by Inductively Coupled Plasma - Mass Spectrometry. Age-depth relationships were established in two cores using 210Pb and 137Cs as chronometer and time-marker, respectively, and Constant Rate of Supply as radiometric dating model. 210Pb and 238U were present in sediment in activities much higher than those reported for non-contaminated coastal systems. Sediment accumulation rates showed a slight increase over time with a depth-averaged value of 0.16 g cm-2 y-1. Enrichment Factors and practically derived sediment quality guidelines were used to assess sediment contamination/pollution and toxicological effects linked with the measured concentrations of sediment-bound elements. The profiles of Cr, Co, Cu, As and Ni displayed maximums at depths matching the start of the phosphate industrial plants, and decreasing concentrations in the sections above the maximums, revealing the positive effects of the environmental management system adopted by the phosphate company since early 2000s.


Relevance of selenoprotein transcripts for selenium status in humans.
The most commonly used methods for assessing the selenium (Se) status in humans involve analysis of Se concentration, selenoprotein activity, and concentration in the blood and its compartments. Recently, it has been suggested that the expression of selenoprotein mRNA in circulating blood leukocytes could differently reflect Se status, due to prioritization of specific selenoprotein synthesis in response to dietary Se supply. Whereas the Se levels required for optimization of selenoprotein P level and plasma glutathione peroxidise activity are well known, estimation of Se level that is required for maximal mRNA expression of selenoprotein in humans is the subject of current investigations. Studies on rats suggest that whole blood selenoprotein mRNA level can be used as the relevant molecular biomarker for assessing Se status, and suboptimal Se intake may be sufficient to achieve effective expression. Human studies, however, did not confirm this hypothesis. According to studies on rodents and humans discussed in this review, it appears that suboptimal Se intake may be sufficient to satisfy molecular requirements of Se and it is lower than current recommended dietary intake in humans. The use of selenoprotein transcripts as a molecular biomarker of Se status requires further studies on a large group of healthy individuals with different baseline Se, including data regarding genetic polymorphism of selenoproteins and data regarding potential modifiers of Se metabolism.


Nutrition and the surgical patient: triumphs and challenges.
The understanding of the role of nutrition in the surgical patient has lead to major developments in the nutritional support of patients undergoing surgery. Reductions in morbidity by ensuring that patients receive optimal nutritional support can be achieved. Furthermore, the use of nutrients to modify immune, inflammatory and metabolic processes also offers new possibilities for reducing morbidity following major surgery. However, we are only at an embryonic stage in our understanding of how nutrients and nutrition affect the genome and this knowledge offers exciting possibilities in the future for modulating many key intracellular processes, particularly in the patient with cancer.


Functional properties of granulocytes after thermal injury.
Thermal injury, as well as other forms of severe trauma, induces simultaneous hyper- and anti-inflammatory response. While data about decreased number and responsiveness of T lymphocytes are largely consistent, reports concerning granulocytes following trauma are contradictory. Contrary to the evidence on the increased accumulation of granulocytes in the lungs or liver, the results from our laboratory demonstrated reduced granulocyte influx in the wound that heals in conditions of thermal injury. We also demonstrated evidence that indicates impaired signal transduction in granulocytes following thermal injury, as well as their divergent response regarding the adhesiveness, oxidative burst and nitric oxide production at the wound site.


Best of both (BOB) maneuver for rapid reduction of anterior shoulder dislocation.
This article describes a combination maneuver for the reduction of anterior glenohumeral dislocations. It maximizes the force counter to the patient's musculature by using downward motion, with the physician's body mass and gravity doing the work, and the base of the ED gurney providing countertraction. It couples this force with the benefit of a scapulothoracic manipulation maneuver, which rotates the glenoid fossa into a position more amenable to "reaccepting" the humeral head. Some might regard this as a variation of the scapulothoracic manipulation maneuver. Because minimal sedation and analgesia is necessary, this technique may be useful for shoulder reductions at sporting events, wilderness areas, or accident scenes. It may also expedite the care of patients in busy emergency department settings.


Providing personal information to the benefit of others.
Personal information is a precious resource, not only for commercial interests but also for the public benefit. Reporting personal location data, for example, may aid efficient traffic flows and sharing one's health status may be a crucial instrument of disease management. We experimentally study individuals' willingness to contribute personal information to information-based public goods. Our data provide evidence that-compared to monetary contributions to public goods-information may be substantially under-provided. We show that the degree of information provision is strongly correlated to the information's implicit (emotional and cognitive) costs. Individual's reluctance to share personal information with high implicit, in particular emotional costs, may seriously limit the effectiveness of information-based public goods.


Studies of idiopathic intestinal pseudoobstruction. I. Hereditary hollow visceral myopathy: clinical and pathological studies.
A 15-year-old girl with idiopathic intestinal pseudoobstruction is reported. She presented with a long term history of low grade obstructive symptoms, diarrhea, and poor nutrition culminating in an acute obstructive attack leading to exploratory laparotomy. At surgery, the small bowel and colon were dilated, with no mechanical obstruction found. Further evaluation revealed her to have a diffuse disorder of gastrointestinal smooth muscle function involving esophagus, small bowel, and colon. Because medical management failed to control symptom, a gastrojejunostomy was done to bypass a megaduodenum. A third laparotomy was necessary 2 months later because of intractable obstructive symptoms. At this last laparotomy, the afferent loop was taken down and a duodenoplasty and duodenojejunostomy were performed, resulting in clinical improvement. Light and electron microscopic study of the excised small intestine showed marked thinning and degeneraton of the smooth muscle, with replacement by fibrous tissue. The myenteric plexus was normal. This case demonstrates that a degenerative disease of smooth muscle may be one cause of idiopathic intestinal pseudoobstruction.


Characterization and Separation of Cancer Cells with a Wicking Fiber Device.
Current cancer diagnostic methods lack the ability to quickly, simply, efficiently, and inexpensively screen cancer cells from a mixed population of cancer and normal cells. Methods based on biomarkers are unreliable due to complexity of cancer cells, plasticity of markers, and lack of common tumorigenic markers. Diagnostics are time intensive, require multiple tests, and provide limited information. In this study, we developed a novel wicking fiber device that separates cancer and normal cell types. To the best of our knowledge, no previous work has used vertical wicking of cells through fibers to identify and isolate cancer cells. The device separated mouse mammary tumor cells from a cellular mixture containing normal mouse mammary cells. Further investigation showed the device separated and isolated human cancer cells from a heterogeneous mixture of normal and cancerous human cells. We report a simple, inexpensive, and rapid technique that has potential to identify and isolate cancer cells from large volumes of liquid samples that can be translated to on-site clinic diagnosis.


Thyroid hormone exerts site-specific effects on SRC-1 and NCoR expression selectively in the neonatal rat brain.
Thyroid hormone receptors (TRs) are ligand-gated transcription factors. Recently, many coregulator proteins have been identified that interact with steroid/TRs and are required for the activation or repression of hormone sensitive genes. We tested whether steroid receptor coactivator-1 (SRC-1) and nuclear corepressor (N-CoR) expression is altered by hypothyroidism in rat brains on gestational day 16 and postnatal day 15. We found that both SRC-1 and N-CoR mRNA levels were decreased in the cortex and dentate gyrus of 6-n-propyl-2 thiouracil treated rats only on P15, while mRNA levels for both genes were increased in the same CA3 region of the brains. These findings do not support the idea that cofactors are involved in the compensatory mechanisms for conserving TH action, but they do suggest that hypothyroidism affects the responsiveness of tissues to steroid hormones by altering the expression of necessary cofactors.


[Prognostic significance of EBMT score system for hematological malignancies with allogeneic hematopoietic stem cell transplantation].
To evaluate the impact of EBMT score system in patients with hematological malignancies received allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 144 consecutive patients were analyzed retrospectively. According to the EBMT score system, including age, disease status before transplantation, interval between diagnoses to transplantation, donor/recipient sex match and donor type, patients were divided into 3 risk groups: low risk (score 0-1), intermediate risk (score 2-3) and high risk (score 4-7). The median follow-up duration were 413 (10-1827) days for all patients and 837 (166-1827) days for alive patients. The estimated 4-year overall survival (OS), transplant-related mortality (TRM) and relapse rate (RR) were (57.5±4.6)%, (21.6±3.7)% and (42.7±6.1)%, respectively. The 4-year OS, TRM and RR were (72.2±9.0)%, (8.1±4.5)% and (27.3±8.7)% in the low-risk group, significantly superior to both intermediate-risk group [(57.7±6.0)%, (23.1±5.1)% and (44.9±8.3)%] and high-risk group [(36.9±10.2)%, (33.5±9.2)% and (51.5±11.8)%] (P<0.01, 0.02 and 0.009 for OS, TRM and RR respectively). The EBMT score system provides prognostic significance for OS, TRM and RR in patients with hematological malignancies received allo-HSCT.


Zero-valent iron doped carbons readily developed from sewage sludge for lead removal from aqueous solution.
Low-cost but high-efficiency composites of iron-containing porous carbons were prepared using sewage sludge and ferric salts as raw materials. Unlike previous time- and energy-consuming manufacturing procedures, this study shows that pyrolyzing a mixture of sludge and ferric salt can produce suitable composites for lead adsorption. The specific surface area, the total pore volume and the average pore width of the optimal composite were 321m(2)/g, 0.25cm(3)/g, and 3.17nm, respectively. X-ray diffraction analysis indicated that ferric salt favored the formation of metallic iron, while Fourier transform infrared spectroscopy revealed the formation of hydroxyl and carboxylic groups. The result of batch tests indicated that the adsorption capacity of carbons activated with ferric salt could be as high as 128.9mg/g, while that of carbons without activation was 79.1mg/g. The new manufacturing procedure used in this study could save at least 19.5kJ of energy per gram of activated carbon.


Advanced Imaging in Female Infertility.
This review highlights the role of imaging in the diagnosis and management of reproductive disorders. The additional information that imaging studies can contribute to reproductive medicine is emphasized, including the role of pelvic ultrasonography (US, including sonohysterography and contrast-enhanced hysterosalpingosonography), hysterosalpingography (HSG), and magnetic resonance imaging (MRI) of the female reproductive tract. In addition, the implications of congenital causes of infertility on the urinary tract in females are reviewed. While the evaluation of infertility in women is initially focused on the assessment of ovulation via serum hormone levels, imaging plays a role in evaluating other causes of infertility. Recent research in this field focuses on the establishment of a comprehensive single imaging study for the assessment of female reproductive disorders. Two proposed methods are MR hysterosalpingography and Fertiliscan, a combination of high-quality 3D ultrasound and assessment of tubal patency with hysterosalpingo-foam-sonography, though more research is needed to determine the risks and benefits of each method, as well as their reliability.


Similar as well as distinct MHC class I-binding peptides are generated by exogenous and endogenous processing of hepatitis B virus surface antigen.
Murine MHC class I-restricted cytotoxic T lymphocyte (CTL) responses can be primed by exogenous as well as endogenous hepatitis B surface antigen (HBsAg). Immunodominant CTL-defined epitopes of this viral envelope protein are the Ld-binding 12-mer S28-39 peptide IPQSLDSWWTSL in H-2d mice, and the Kb-binding 8-mer S208-215 peptide ILSPFLPL in H-2b mice. We tested if CTL recognizing these epitopes can be primed in vivo by HBsAg delivered as either an exogenous antigen (native HBsAg lipoprotein particles), or an endogenous antigen (plasmid DNA encoding HBsAg). Primed T cells were restimulated in vitro prior to the cytotoxicity assay with cells presenting the H-2 class I-binding epitopes generated by either exogenous or endogenous processing of HBsAg. The data indicate that the Ld-binding peptide S28-39 is generated during exogenous as well as endogenous processing of HBsAg. In contrast, the Kb-binding peptide S208-215 is generated during exogenous but not endogenous processing of HBsAg. Hence, some but not all MHC class I-binding, immunogenic peptides are generated during endogenous and exogenous processing of HBsAg but there also exists a repertoire of immunogenic peptides of viral origin that is only revealed after exogenous processing of viral proteins.


Analysing the quality of routine malaria data in Mozambique.
In Mozambique, malaria is the principal cause of morbidity and mortality. Efforts are being made to increase control activities within communities. These activities require management decisions based on evidence of malaria incidence. Although some data generated are of poor quality, there is little research towards improving the reporting systems. An analysis of the quality of routine malaria data was performed in selected districts in Southern Mozambique from August to September 2003. The aim was to assess the quality of the source data in terms of completeness, correctness and consistency across management levels. Analysis revealed primary data to be of poor quality. The diversity of reporting systems with limited coordination give rise to redundancies and wastage of resources. There was evidence of "invention" of data in health facilities contributing to an incorrect representation of malaria incidence. Large, "non-clinical", time-based variations of malaria cases due to reporting delays were also noted, contributing to false alerts of outbreaks.Furthermore, targets established in the national strategic plan for malaria cannot be calculated through the existing systems; this is the case, for example, for data related to pregnant women and children under-five years. The existing reporting system for malaria is currently not satisfying the information needs of managers. It is suggested that one standardized system, including the creation of one form to include the essential variables required for the calculation of key indicators by age, gender and pregnancy status, and to establish a national database that maps malaria by location.


The Potential Impact of Internet and Mobile Use on Headache and Other Somatic Symptoms in Adolescence. A Population-Based Cross-Sectional Study.
The purpose of this cross-sectional study was to determine whether migraine or tension-type headaches are associated with abuse of the internet and/or mobile phones and to explore whether headache and the abuse of the two technologies are associated with sleep disturbances and other self-reported somatic symptoms. In the last several years, estimates indicate the increasing pervasiveness of the internet and other technologies in the lives of young people, highlighting the impact on well-being. A population-based cross-sectional study was conducted between February 2013 and June 2014. The initial sample was composed of 1004 Italian students (aged 10-16 years) recruited within public middle schools not randomly selected in central Italy. The final convenience sample consisted of 841 students (Males = 51.1%; Females = 48.9%) who were included in the analysis. Data were collected using self-reported measures. Headache was reported by 28.0% of the total sample. A significant relationship was determined with gender (χ(2) (1) = 7.78, P < .01), with female students being overrepresented in the headache group. Approximately 39.6% of subjects were non-abusers of both technologies, internet and mobile. Mobile only abusers were approximately 26.0% of the study population; internet only abusers were approximately 14.9%; and abusers of both media were 19.5%. No significant relationship was found between students with and without headache with respect to the abuse of internet and mobile phone categories (headache was, respectively, the 26% in no abusers, the 30% in internet abusers, the 29% in mobile abusers, and the 29% in internet and mobile abusers, P = .86). Additionally, also by excluding the no headache group, the relationship between the two groups of headache (migraine and tension type headache) and the abuse of media (tension type headache was the 31% in no abusers, the 43% in internet abusers, the 49% in mobile abusers, and the 29% in internet and mobile abusers) is not statistically significant (P = .06). No significant relationship emerged between headache and the internet and mobile phone addiction groups (headache was the 28% in no addiction group, the 35% in mobile addiction group, the 25% of internet addiction group, and the 28% in mobile and internet addiction group, P = .57) as well as no significant relationship was found when only the different headache types were considered (tension type headache was the 39% in no addiction group, the 40% in mobile addiction group, the 32% in internet addiction group, and the 31% in mobile and internet addiction group, P = .71). Daily internet users reported higher median scores for somatic symptoms than the occasional internet users in the no-headache group (Kruskal-Wallis χ(2) (1) = 5.44, P = .02) and in the migraine group (Kruskal-Wallis χ(2) (1) = 6.54, P = .01). Results highlighted the potential impact of excessive internet and mobile use, which ranges from different types of headache to other somatic symptoms. Further studies are needed to confirm these findings and to determine if there is a need for promoting preventive health interventions, especially in school setting.


Herpes simplex virus type 2 UL24 gene is a virulence determinant in murine and guinea pig disease models.
A herpes simplex virus type 2 (HSV-2) UL24 beta-glucuronidase (UL24-betagluc) insertion mutant was derived from HSV-2 strain 186 via standard marker transfer techniques. Cell monolayers infected with UL24-betagluc yielded cytopathic effect with syncytium formation. UL24-betagluc replicated to wild-type viral titers in three different cell lines. UL24-betagluc was not virulent after intravaginal inoculation of BALB/c mice in that all inoculated animals survived doses up to 400 times the 50% lethal dose (LD50) of the parental virus. Furthermore, few UL24-betagluc-inoculated mice developed any vaginal lesions. Intravaginal inoculation of guinea pigs with UL24-betagluc at a dose equivalent to the LD50 of parental virus (approximately 5 x 10(3) PFU) was not lethal (10/10 animals survived). Although genital lesions developed in some UL24-betagluc-inoculated guinea pigs, both the overall number of lesions and the severity of disease were far less than that observed for animals infected with parental strain 186.


Spin-mediated shear oscillators in a van der Waals antiferromagnet.
Understanding how microscopic spin configuration gives rise to exotic properties at the macroscopic length scale has long been pursued in magnetic materials1-5. One seminal example is the Einstein-de Haas effect in ferromagnets1,6,7, in which angular momentum of spins can be converted into mechanical rotation of an entire object. However, for antiferromagnets without net magnetic moment, how spin ordering couples to macroscopic movement remains elusive. Here we observed a seesaw-like rotation of reciprocal lattice peaks of an antiferromagnetic nanolayer film, whose gigahertz structural resonance exhibits more than an order-of-magnitude amplification after cooling below the Néel temperature. Using a suite of ultrafast diffraction and microscopy techniques, we directly visualize this spin-driven rotation in reciprocal space at the nanoscale. This motion corresponds to interlayer shear in real space, in which individual micro-patches of the film behave as coherent oscillators that are phase-locked and shear along the same in-plane axis. Using time-resolved optical polarimetry, we further show that the enhanced mechanical response strongly correlates with ultrafast demagnetization, which releases elastic energy stored in local strain gradients to drive the oscillators. Our work not only offers the first microscopic view of spin-mediated mechanical motion of an antiferromagnet but it also identifies a new route towards realizing high-frequency resonators8,9 up to the millimetre band, so the capability of controlling magnetic states on the ultrafast timescale10-13 can be readily transferred to engineering the mechanical properties of nanodevices.


Characterization of rat liver microsomal and hepatocytal metabolites of brevetoxins by liquid chromatography-electrospray tandem mass spectrometry.
Brevetoxins are natural neurotoxins that are produced by "red tide" algae. This class of compounds can cause neurotoxic shellfish poisoning and other health problems. Brevetoxin-2 is the most abundant among the nine brevetoxins that have been characterized, whereas brevetoxin-1 is the most toxic. In this study, brevetoxin-1 and brevetoxin-2 were incubated with rat liver hepatocytes and rat liver microsomes, respectively. After clean-up steps were taken to remove the proteins, samples were analyzed by liquid chromatography (LC) coupled with electrospray mass spectrometry (LC-MS). After incubation of brevetoxin-1, two metabolites were found: brevetoxin-1-M1 (molecular weight = 900 Da), and brevetoxin-1-M2 (molecular weight = 884 Da). The increase in molecular weight combined with evidence from tandem mass spectrometry showing an increased tendency for loss of water molecules, along with considerations of established precedents for chemical transformations led to the conclusion that brevetoxin-1-M1 was formed by converting one double bond in the E or F ring of brevetoxin-1 into a diol. The second metabolite (brevetoxin-1-M2) is proposed to be a hydrolysis product of brevetoxin-1 involving opening of the lactone ring with the addition of a water molecule. The incubation study of the other starting compound, brevetoxin-2, found two metabolites in the LC-ES-MS selected ion chromatogram. Brevetoxin-2-M1 (molecular weight = 912 Da) gave a large [M-H]- peak at m/z 911, and its product ion mass spectrum allowed the deduction that this metabolite was the hydrolysis product of brevetoxin-2 involving conversion of the lactone to a carboxylic acid and an alcohol. The second metabolite (brevetoxin-2-M2, molecular weight = 896 Da) was deduced to have the same structure as that of brevetoxin-3 based on identical chromatographic retention times and similar mass spectra as those obtained for a brevetoxin-3 standard.


Assessment of acute bronchodilator effects from specific airway resistance changes in stable COPD patients.
In COPD patients, reversibility is currently evaluated from the changes of forced expiratory volume at 1s (ΔFEV1) and forced vital capacity (ΔFVC). By lowering peripheral airway smooth muscle tone, bronchodilators should decrease dynamic hyperinflation, gas trapping, and possibly dyspnea at rest. Hence, we hypothesize that specific airway resistance changes (ΔsRAW) should better characterize the acute response to bronchodilators. On two days, 60 COPD patients underwent dyspnea evaluation (VAS score) and pulmonary function testing at baseline and one hour after placebo or 300μg indacaterol administration. Spirographic and ΔsRAW-based criteria identified as responders 24 and 45 patients, respectively. ΔsRAW correlated with changes of intrathoracic gas volume (ΔITGV) (r=0.61; p<0.001), residual volume (ΔRV) (r=0.60; p<0.001), ΔFVC (r=0.44; p=0.001), and ΔVAS (r=0.73; p<0.001), while ΔFEV1 correlated only with ΔFVC (r=0.34; p=0.008). Significant differences in terms of ΔITGV (p=0.002), ΔRV (p=0.023), and ΔVAS (p<0.001) occurred only if patients were stratified according to ΔsRAW. In assessing the acute functional effect of bronchodilators, ΔsRAW-based criterion is preferable to FEV1-FVC-based criteria, being more closely related to bronchodilator-induced improvements of lung mechanics and dyspnea at rest.


Amniotomy and early oxytocin infusion vs amniotomy and delayed oxytocin infusion for labour augmentation amongst nulliparous women at term: A randomised controlled trial.
to compare the effect of amniotomy with early vs delayed oxytocin infusion on successful vaginal delivery. randomised controlled trial of nulliparous women with spontaneous labour at term. labour suite of a university teaching hospital in Kuala Lumpur, Malaysia. 240 women were included (120 randomised into two arms). the randomisation sequence was generated using a computer randomisation program in two blocks: oxytocin infused early following amniotomy; and oxytocin infused 2 h after amniotomy. labour duration, mode of delivery, oxytocin dosage used, uterine hyperstimulation, postpartum haemorrhage, Apgar score and admission to the neonatal intensive care unit were recorded. No differences in vaginal delivery rate (62.9% vs 70.9%; p = 0.248) and second-stage labour were found between the early and delayed oxytocin infusion groups (21.2 ± 18.3 min vs 25.5 ± 19.9 min; p = 0.220). The mean interval from amniotomy to vaginal delivery was significantly shorter for the early group (5.8 ± 1.7 h vs 7.0 ± 1.9 h; p = 0.001), and more women in the early group delivered during/before the planned review at 4 h after amniotomy (53.6% vs 10.6%; p<0.001). Maximum oxytocin usage was lower in the early group (5.6 ± 4.4 mL/hour vs 6.8 ± 5.3 mL/hour; p = 0.104). early oxytocin augmentation following amniotomy could be employed in low-risk primigravida, given that it is associated with a shorter labour duration without jeopardising maternal or neonatal outcomes. low-risk primigravida benefit from early oxytocin infusion following amniotomy, and this can be offered as an additional practice in labour room care.


Sclerostin Antibody Treatment Increases Bone Mass and Normalizes Circulating Phosphate Levels in Growing Hyp Mice.
X-linked hypophosphatemia (XLH), caused by a loss-of-function mutation in the phosphate regulating gene with homology to endopeptidase located on the X chromosome (PHEX), is the most common form of vitamin D-resistant rickets. Loss of functional PHEX results in elevated fibroblast growth factor 23 (FGF23) levels, impaired phosphate reabsorption, and inhibited skeletal mineralization. Sclerostin, a protein produced primarily in osteocytes, suppresses bone formation by antagonizing Wnt signaling and is reported to be elevated in XLH patients. This study used the Hyp mouse model to investigate sclerostin's role in the pathophysiology of XLH by evaluating the use of a monoclonal antibody to sclerostin in a mouse model of XLH, the Hyp mouse. Male and female wild-type and Hyp littermates were injected with 25 mg/kg of vehicle or sclerostin antibody (Scl-Ab) twice weekly, beginning at 4 weeks of age and euthanized at 8 weeks of age. Scl-Ab treatment increased serum phosphate levels and suppressed circulating levels of intact FGF23 in treated wild-type and Hyp mice of both sexes. Cortical area, trabecular bone volume fraction (BV/TV), metaphyseal apparent density, and the peak load increased with Scl-Ab treatment in both sexes. This short-term treatment study suggests that Scl-Ab treatment can effectively improve some of the pathologies associated with XLH, including normalization of phosphate, and that sclerostin may play a role in regulating FGF23 and phosphate metabolism in XLH. © 2019 American Society for Bone and Mineral Research.


Immunogenicity of protein aggregates--concerns and realities.
Protein aggregation is one of the key challenges in the development of protein biotherapeutics. It is a critical product quality issue as well as a potential safety concern due to the increased immunogenicity potential of these aggregates. The overwhelming safety concern has led to an increased development effort and regulatory scrutiny in recent years. The main purposes of this review are to examine the literature data on the relationship between protein aggregates and immunogenicity, to highlight the linkage and existing inconsistencies/uncertainties, and to propose directions for future investigations/development.


3-Deoxy-3,4-dehydro analogs of XM462. Preparation and activity on sphingolipid metabolism and cell fate.
Three analogs of the dihydroceramide desaturase inhibitor XM462 are reported. The compounds inhibit both dihydroceramide desaturase and acid ceramidase, but with different potencies depending on the N-acyl moiety. Other enzymes of sphingolipid metabolism, such as neutral ceramidase, acid sphingomyelinase, acid glucosylceramide hydrolase, sphingomyelin synthase and glucosylceramide synthase, are not affected. The effect on the sphingolipidome of the two best inhibitors, namely (R,E)-N-(1-hydroxy-4-(tridecylthio)but-3-en-2-yl)octanamide (RBM2-1B) and (R,E)-N-(1-hydroxy-4-(tridecylthio)but-3-en-2-yl)pivalamide (RBM2-1D), is in accordance with the results obtained in the enzyme assays. These two compounds reduce cell viability in A549 and HCT116 cell lines with similar potencies and both induced apoptotic cell death to similar levels than C8-Cer in HCT116 cells. The possible therapeutic implications of the activities of these compounds are discussed.


Weight loss and health-related quality of life: results at 1-year follow-up.
To evaluate the 1-year results of treatment-induced weight loss on health-related quality of life (HRQL), 32 mildly to moderately overweight persons who participated in a 13-week weight loss program completed the Medical Outcomes Study Short Form-36 Health Survey (SF-36) at baseline, immediately after the program, and at 1-year follow-up. At 1 year, 65.6% of participants maintained at least some weight loss. The improvements on HRQL observed immediately after treatment on the physical functioning, role-physical, general health, vitality, and mental health scales of the SF-36 were maintained only on the general health and vitality scales at 1 year. There were no significant differences between weight maintainers and weight regainers on change from baseline to 1-year follow-up on HRQL. Our findings suggest that treatment-induced weight loss among mildly to moderately overweight persons improves HRQL and that at least some of these benefits are maintained at 1-year follow-up regardless of whether the weight loss is maintained.


The role of ultrasound in the diagnosis and management of psoriatic arthritis.
Psoriatic arthritis (PsA) presents many diagnostic, management and research challenges for rheumatologists who wish to obtain early diagnosis, differentiate synovitis and enthesitis, monitor disease activity accurately and objectively, prevent the development of structural damage, deliver local therapy accurately, and obtain PsA tissue for research purposes. Musculoskeletal ultrasound (MSUS) is widely used by European rheumatologists in their clinical practice to meet these challenges and has the potential to become the rheumatologist's stethoscope in Europe and North America. This paper examines the evidence that MSUS can improve clinical evaluation of patients with PsA for synovitis and enthesitis, that MSUS is more sensitive than plain radiography in detecting structural damage in joints, that MSUS can improve the success of joint aspiration and guide biopsy of PsA tissues. Recent exciting developments in the management of PsA are detailed including the role of power Doppler in the diagnosis of enthesitis in PsA, the role of MSUS in objective monitoring of disease activity, the evaluation of MSUS in the diagnosis of sacroiliitis, and the use of MSUS to guide therapeutic injection of the sacroiliac joints.


Electrophysiology Practice During COVID-19 Pandemic: A New York Tertiary Hospital Experience.
As hospitals became overwhelmed during the Covid-19 pandemic in March-May in New York, Cardiology and Electrophysiology (EP) departments rapidly developed protocols for case selection as well modifying the practice of managing the cases. Recommendations by the AHA/HRS as well as American Society of Anesthesiology (ASA) were considered in the multidisciplinary collaborative approach to patient care and personnel safety and the anesthesiology team had an integral role in developing protocols for workflow, care, recovery and transport during these challenging times.


Discovery of novel 1,2,3,4-tetrahydrobenzo[4, 5]thieno[2, 3-c]pyridine derivatives as potent and selective CYP17 inhibitors.
The inhibition of CYP17 to block androgen biosynthesis is a well validated strategy for the treatment of prostate cancer. Herein we reported the design, synthesis and structure-activity relationship (SAR) study for a series of novel 1,2,3,4- tetrahydrobenzo[4,5]thieno[2,3-c]pyridine derivatives. Some analogs demonstrated a potent inhibition to both rat and human CYP17 protein and reduced testosterone production in human H295R cell line. Some analogs also showed high selectivity against other CYP enzymes such as 3A4, 1A2, 2C9, 2C19 and 2D6, which may limit side effects due to drug-drug interactions. Among these analogs, the most potent compound 9c showed 1.5 fold more potent against rat and human CYP17 protein than that of abiraterone (IC50 = 16 nM and 20 nM vs. 25 nM and 36 nM respectively). In NCI-H295R cells, the inhibitory effect of compound 9c on testosterone production (52± 2%) was also more potent than that of abiraterone (74± 15%) at the concentration of 1 μM. Further, it was shown that 9c reduced plasma testosterone level in a dose-dependent manner in Sprague-Dawley rats. Thus, analog 9c maybe a potential agent used for the treatment of prostate cancer.


HLA-G 3' untranslated region gene variants are promising prognostic factors for BK polyomavirus replication and acute rejection after living-donor kidney transplant.
The immunosuppressive non-classical human leukocyte antigen-G (HLA-G) promotes transplant tolerance as well as viral immune escape. HLA-G expression is associated with regulatory elements targeting certain single nucleotide polymorphisms (SNPs) in the HLA-G 3' untranslated region (UTR). Thus, we evaluated the impact of HLA-G 3'UTR polymorphisms as surrogate markers for BK polyomavirus (BKPyV) replication or nephropathy (PyVAN) and acute cellular and antibody mediated rejection (ACR/AMR) in 251 living-donor kidney-transplant recipient pairs. After sequencing of the HLA-G 3'UTR, fourteen SNPs between +2960 and +3227 and the 14 bp insertion/deletion polymorphism, which arrange as UTR haplotypes, were identified. The UTR-4 haplotype in donors and recipients was associated with occurrence of BKPyV/PyVAN compared to the other UTR haplotypes. While the UTR-4 recipient haplotype provided protection against AMR, the UTR-2 donor haplotype was deleteriously associated with ACR/AMR. Deduction of the UTR-2/4 haplotypes to specific SNPs revealed that the +3003C variant (unique for UTR-4) in donors as well as in recipients is responsible for BKPyV/PyVAN and also provides protection against AMR; whereas the +3196G variant (unique for UTR-2) promotes allograft rejection. Thus, HLA-G 3'UTR variants are promising genetic predisposition markers both in donors and recipients that may help to predict susceptibility to either viral infectious complication of BKPyV or allograft rejection.


Single cell transcriptomic analysis of Graves' disease thyroid glands reveals the broad immunoregulatory potential of thyroid follicular and stromal cells and implies a major re-interpretation of the role of aberrant HLA class II expression in autoimmunity.
The study of the immune response in thyroid autoimmunity has been mostly focused on the autoantibodies and lymphocytes, but there are indications that intrinsic features of thyroid tissue cells may play a role in disrupting tolerance that needs further investigation. The overexpression of HLA and adhesion molecules by thyroid follicular cells (TFC) and our recent demonstration that PD-L1 is also moderately expressed by TFCs in autoimmune thyroid indicates that TFCs they may activate but also inhibit the autoimmune response. Intriguingly, we have recently found that in vitro cultured TFCs are able to suppress the proliferation of autologous lymphocyte T in a contact-dependent manner which is independent of the PD-1/PD-L1 signaling pathway. To get a more comprehensive picture of TFC activating and inhibitory molecules/pathways driving the autoimmune response in the thyroid glands, preparations of TFCs and stromal cells from five Graves' disease (GD) and four control thyroid glands were compared by scRNA-seq. The results confirmed the previously described interferon type I and type II signatures in GD TFCs and showed unequivocally that they express the full array of genes that intervene in the processing and presentation of endogenous and exogeneous antigens. GD TFCs lack however expression of costimulatory molecules CD80 and CD86 required for priming T cells. A moderate overexpression of CD40 by TFCs was confirmed. GD Fibroblasts showed widespread upregulation of cytokine genes. The results from this first single transcriptomic profiling of TFC and thyroid stromal cells provides a more granular view of the events occurring in GD. The new data point at an important contribution of stromal cells and prompt a major re-interpretation of the role of MHC over-expression by TFC, from deleterious to protective. Most importantly this re-interpretation could also apply to other tissues, like pancreatic beta cells, where MHC over-expression has been detected in diabetic pancreas.


An in vitro cataract model for practice of cataract surgery.
We have developed an in vitro cataract model using enucleated animal eyes. A cataract is produced by immersing the enucleated eyes in hypertonic sodium chloride solution for one hour and re-incubating them for another hour in normal saline solution. The model is useful for practicing various techniques of cataract extraction.


Processing of microcrystalline cellulose in dimethyl sulfoxide, urea and supercritical carbon dioxide.
Efficient utilization of cellulose in polymer blends is limited because of its high crystallinity. In this work, an attempt to change the inherent crystallinity of cellulose was performed by exposing it to two systems viz. dimethyl sulfoxide (DMSO)-supercritical CO2 and DMSO-urea-supercritical CO2. The cellulose samples processed in DMSO-supercritical CO2 system at 2500psi, 3500psi, and 4500psi showed a reducing trend of the relative crystallinity with increasing pressure. The reduction in the relative crystallinity occurred due to weakening of inter-chain hydrogen bonds in cellulose. The cellulose samples were processed in DMSO-urea-supercritical system at 2500psi and 4500psi. A maximum 55% reduction in relative crystallinity was found in the sample that contained 1.80mol fractions of urea and processed at 2500psi. This reduction in crystallinity was due to the presence of a DMSO-urea complex, which caused weakening of intermolecular hydrogen bond and an intramolecular hydrogen bond.


Estimating apparent age using artificial intelligence: Quantifying the effect of blepharoplasty.
Quantify the rejuvenation effect of blepharoplasty. A dataset of facial photographs was assembled and randomly split into 90% training and 10% validation sets. An artificial intelligence model was trained to input a facial photograph and output the apparent age of the depicted face. A retrospective chart review of patients who underwent blepharoplasty was used to assemble a test set-preoperative and postoperative photographs were culled and subsequently analyzed by the model. A total of 47394 images of patients aged 26-89 years old were used for model training and validation. On the validation set, the model achieved 75% accuracy with a mean absolute error of 1.38 years and Pearson's r of 0.92. A total of 103 patients (29 males and 74 females) met the test set inclusion criteria (upper blepharoplasty n = 28, lower blepharoplasty n = 33, and quadrilateral blepharoplasty n = 42). The test set age ranged from 30.3 to 83.8 years old (mean 60.8, standard deviation 11.4). Overall, the model-predicted test set patients to be 0.74 years younger preoperatively versus 2.52 years younger postoperatively (p < 0.01). Significant underestimation of age was observed in women who underwent lower blepharoplasty (n = 23, 1.28 years older preoperatively vs. 2.32 years younger postoperatively, p = 3.8 × 10-4) and men who underwent quadrilateral blepharoplasty (n = 10, 0.71 years younger preoperatively vs. 5.34 years younger postoperatively, p = 0.02). The deep learning algorithm developed in this study demonstrates that, on average, blepharoplasty provides a rejuvenating effect of approximately 2 years.


Cost-effectiveness assessment of interferon alfa-2b as adjuvant therapy of high-risk resected cutaneous melanoma.
The use of interferon alfa-2b (IFN-alpha 2b) as adjuvant therapy of high-risk resected cutaneous melanoma was recently found to significantly improve relapse-free and overall survival in the Eastern Cooperative Oncology Group trial 1684 (E1684). However, treatment toxicities and costs may limit its widespread use. A cost-effectiveness and cost-utility analysis of this therapy was conducted using a hypothetical cohort of patients as if they had entered E1684. Survival and recurrence rates were calculated at 7 and 35 years for typical 50-year-old melanoma patients based on the clinical results of E1684 and natural history databases. Costs included all treatment-related costs (i.e. drug acquisition and administration, monitoring and treatment-related toxicity) and the costs of treating recurrences. Estimated utility values were assigned based on data from other oncology trials. The model predicted that IFN-alpha 2b provided an extra 0.52 years of life compared with observation at 7 years; however, at 35 years, the survival benefit of IFN-alpha 2b increased almost 4-fold to nearly 2 years. At 7 years, the cost per year of life gained was U.S. $32,600 and the cost per quality-adjusted life-year (QALY) gained was U.S. $43,200. At 35 years, these costs decreased to U.S. $13,700 and $15,200, respectively. These costs are comparable with those of other well-established medical interventions. Although these results require confirmation in a prospective study, it appears that the use of high-dose IFN-alpha 2b for patients with high-risk melanoma is cost-effective.


The cyclin-dependent kinase 11 interacts with NOT2.
The caspase-processed cyclin-dependent kinase 11 (formerly known as PITSLRE) is implicated in apoptotic signaling. However, the mechanism of apoptotic signal transduction through CDK11(p46) is still unclear. We used a yeast two-hybrid screening strategy and identified NOT2 as an interacting partner of caspase-processed C-terminal kinase domain of CDK11 (CDK11(p46)). We demonstrate that CDK11(p46) directly interacts with NOT2 in vitro and in human cells. The NOT domain in the C-terminal part of NOT2 is responsible for the association between CDK11(p46) and NOT2. Both NOT2 and CDK11(p46) predominantly co-localized in the nucleus. Furthermore, we show that overexpression of NOT2 reduces luciferase mRNA and induces apoptosis. However, NOT2 is not phosphorylated by CDK11(p46). These findings suggest that CDK11 may contribute to apoptosis by regulating the activity of NOT2 independent of its kinase activity.


Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin.
The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infection by ferristatin II, an inducer of transferrin receptor 1 (TfR1) degradation, prompted the study of competition between Spike protein and TfR1 ligands, especially lactoferrin (Lf) and transferrin (Tf). We hypothesized molecular mimicry of Spike protein as cross-reactivity of Spike-specific antibodies with Tf and Lf. Thus, strong positive correlations (R2 > 0.95) were found between the level of Spike-specific IgG antibodies present in serum samples of COVID-19-recovered and Sputnik V-vaccinated individuals and their Tf-binding activity assayed with peroxidase-labeled anti-Tf. In addition, we observed cross-reactivity of Lf-specific murine monoclonal antibody (mAb) towards the SARS-CoV-2 Spike protein. On the other hand, the interaction of mAbs produced to the receptor-binding domain (RBD) of the Spike protein with recombinant RBD protein was disrupted by Tf, Lf, soluble TfR1, anti-TfR1 aptamer, as well as by peptides RGD and GHAIYPRH. Furthermore, direct interaction of RBD protein with Lf, but not Tf, was observed, with affinity of binding estimated by KD to be 23 nM and 16 nM for apo-Lf and holo-Lf, respectively. Treatment of Vero E6 cells with apo-Lf and holo-Lf (1-4 mg/mL) significantly inhibited SARS-CoV-2 replication of both Wuhan and Delta lineages. Protective effects of Lf on different arms of SARS-CoV-2-induced pathogenesis and possible consequences of cross-reactivity of Spike-specific antibodies are discussed.


Has the COVID-19 pandemic affected nursing students' career self-efficacy and professional calling? The mediating impact of professional identity.
Professional calling (PC) is crucial for ascertaining their professional goals and fulfilling career choices in nursing students. Thus, understanding its antecedents and helping schools improve PC among nursing students is critical. This study aims to explore whether professional identity (PI), as a crucial antecedent of PC, acts as an intermediary between career self-efficacy (CSE) and professional calling during the COVID-19 pandemic. A sample of 565 nursing students were selected by a web-based survey through convenience sampling. The study was conducted from October to November 2020. Measures of CSE, PI, and PC were assessed during the COVID-19 pandemic. We analyzed demographic data and the correlation of the research variables. The significance of the mediation effect was assessed using a bootstrap method with SPSS. CSE during the COVID-19 pandemic outbreak (r = 0. 359, p < 0. 01) and PI (r = 0. 670, p < 0. 01) were both relevant to PC among nursing students. In addition, CSE had a positive indirect effect on PC through PI (β = 0. 288, p < 0. 05). Higher scores in CSE and a better PI were associated with PC in nursing students. Furthermore, a better CSE had an indirect effect on the PC of students through PI. The favorable evidence in our study confirms that nursing educators can adopt PI interventions to improve the sense of PC among nursing students.


New techniques in electron energy-loss spectroscopy and energy-filtered imaging.
This article is a survey of hardware and software advances that promise to increase the power and sensitivity of electron energy-loss spectroscopy (EELS) and energy-filtered imaging (EFTEM) in a transmission electron microscope. Recent developments include electron-gun monochromators, lens-aberration correctors, and software for spectral sharpening, spectral processing and interpretation of fine structure. Future improvements could include the deployment of new electron sources. The expected enhancements in energy and spatial resolution are compared with fundamental limitations that arise from the natural widths of spectral peaks, the delocalization of inelastic scattering and the problem of electron-irradiation damage.


'Scarless reverse umbilicoplasty': A new technique of umbilical transposition in abdominoplasty.
The navel plays a major role in the aesthetics of the abdomen. A navel that is abnormally shaped, malpositioned or has evident scarring may compromise the outcome of an otherwise well-executed full abdominoplasty. The aim of the technique in question is to recreate a navel that looks natural, with no visible scar, and that is properly positioned. The technique was performed in 147 abdominoplasties of patients of both sexes (123 females and 24 males), with an average age of 35 years and a mean BMI of 24 kg/m2. The procedure involves the creation of a navel of reduced size, 10 × 5 mm, and its inset in the abdominal wall. Subsequently, the as-yet-not sutured abdominal flap is extended caudally to determine the point of projection of the navel. The abdominal skin is marked, the flap is reversed and an internal suture is carried out. The appearance of the navel is aesthetically pleasant and natural looking and with no visible scarring. In addition, the position of the umbilicus is always correct. At the two-year follow-up, the results remain stable. No major complication occurred. The technique allows for the attainment of an extremely natural looking navel that satisfies the aesthetic criteria of attractiveness without visible scarring. The navel is always correctly positioned, without requiring measurements during surgery. The procedure is rapid, and although it does require a short learning curve, the results are extremely aesthetically pleasing and reproducible. The patient satisfaction rate is extremely high.


A model for the firing pattern of a paced nerve cell.
When a nerve cell is paced by another cell or by external stimuli, its firing pattern is generally not regular. In a given stimulus and frequency interval the cell responds only on a fraction of the stimuli, and this fraction is not necessarily a nice simple fraction as 1/2, 1/3, etc. but may be any fraction less than one, why the firing pattern becomes accordingly irregular. The paper demonstrates the rules for these irregularities and supplies a mathematical tool to analyse the firing pattern. In the analysis only a cell with the so-called impulse dependent type of adaptation is considered, but similar analyses may be done with other cell types. The analysis is restricted to a case where a resting cell is stimulated by repetitively applied stimuli of constant strength and repetition frequency. Cases with more than one input, spontaneously firing cells, and transient phenomena are not included in the analysis.


Epidemiology of genital Chlamydia trachomatis infection among young women in Costa Rica.
To investigate Chlamydia trachomatis (Ct) epidemiology among 5829 women 18 to 25 years old, in Costa Rica. Data are from a community-based human papillomavirus 16/18 vaccine trial. Before randomization, eligible women who reported previous sexual activity were interviewed and tested for Ct DNA by Hybrid Capture 2 and polymerase chain reaction-based genotyping. Multivariate models were developed. Overall prevalence was 14.2% (95% confidence interval, 13.3-15.1). Among Ct genotypes, serovar E was the most common (4.3%), followed by serovar F (3.0%), serovar D/Da (2.9%), and serovar I/Ia (2.1%).Ct increased with lifetime sexual partners of the women, and among women with 1 lifetime partner, with sexual partners of the partner. Current intrauterine device users had an increase in Ct detection [odds ratio (OR) 1.6, 1.1-2.5] but hormonal contraceptives or condom users did not. Miscarriages were associated with a reduction in Ct detection (OR 0.7, 0.5-1.0) while current regular smoking increased it (OR 1.7, 1.2-2.5). Vaginal discharge, reactive changes, ASCUS or LSIL and moderate to severe inflammation in the cytology were significantly more common among Ct positive women (P <0.001). Gonorrhea prevalence was 0.8%, and it was, as other STIs, highly correlated with Ct detection. This is a high-prevalence population where we confirmed the strong link between Ct and sexual behavior of women and their partners. The establishment of a screening program in the age group included in this study should be considered. More studies are needed in developing countries to further investigate the role of intrauterine devices and the lack of protection by condoms, in addition to the interplay between Ct and other STIs, ectopy, inflammation, and epithelial abnormalities.


SNIP/p140Cap mRNA expression is an unfavourable prognostic factor in breast cancer and is not expressed in normal breast tissue.
The prevalence and clinical relevance of SNIP/p140Cap has not been extensively investigated. Here SNIP/p140Cap mRNA expression was studied in 103 breast tumour biopsies, where it was detected in approximately 37% of tumour specimens, but not in any normal breast specimens. Expression correlated significantly with unfavourable overall survival. This suggests that SNIP/p140Cap may be a useful diagnostic and prognostic marker for breast cancer and its expression in breast cancer, but not in normal breast tissue, suggests that it may have potential as a therapeutic target.


When "lymphoma" is not lymphoma: diagnosing immunoblastic lymphadenopathy.
Immunoblastic lymphadenopathy, a newly described disease, is clinically similar to lymphoma but has a specific histologic picture. It usually does not have malignant potential and is best treated initially by corticosteroid in high doses. Chemotherapy is used when corticosteroid fails or when malignant conversion occurs.


Inflammation-inducing Th1 and Th17 cells differ in their expression patterns of apoptosis-related molecules.
Th1 cells are remarkably more susceptible to activation induced cell death than Th17. Here, we compared cultures of these two cell subpopulations for their expression of apoptosis-related molecules when re-exposed to their specific antigen. We also compared the expression of apoptosis-related molecules in the mouse eye with inflammation induced by Th1 or Th17 cells. Using qPCR we found that the mRNA transcript levels of the majority of tested apoptosis-related molecules were higher in the Th1 cultures, and in eyes with Th1-induced inflammation. Apoptotic intrinsic pathway molecules played minor roles in the processes in vitro or in vivo, whereas extrinsic pathway molecules, as well as PD-1, its ligands and Tim3, were heavily involved.


Posterior ankle pain in dancers.
Treatment of dancers can be as challenging as it is rewarding. Dancers often have unusual difficulties related to the altered kinesiology required by their individual dance form. A thorough understanding of these movements helps guide the physician to the cause of the disability, particularly in the setting of overuse injuries. This knowledge, coupled with a careful physical examination, is essential for the accurate diagnosis and treatment of the dancer, who is both artist and athlete.


General anesthesia with S-ketamine improves the early recovery and cognitive function in patients undergoing modified radical mastectomy: a prospective randomized controlled trial.
Postoperative cognitive dysfunction (POCD) is a common postoperative disorder that is frequently observed after general anesthesia, which seriously threatens the quality of patients' life. Existing studies have demonstrated that S-ketamine plays an important role in improving neuroinflammation. This trial aimed to explore the effects of S-ketamine on quality of recovery and cognitive function in patients following modified radical mastectomy (MRM). Ninety patients aged 45 to 70 years with ASA grades of I or II, who underwent MRM, were selected. Patients were randomly assigned to the S-ketamine or control group. In the S-ketamine group, patients were induced with S-ketamine instead of sufentanil and maintained with S-ketamine and remifentanil. In the control group, patients were induced with sufentanil and maintained with remifentanil. The primary outcome was the Mini-Mental State Examination (MMSE) and Quality of Recovery-15 (QoR-15) score. Secondary outcomes including visual analog scale (VAS) score, cumulative propofol and opioids consumption, post anesthesia care unit (PACU) recovery time, occurrence of remedial analgesia, postoperative nausea and vomiting (PONV), other adverse events, as well as patient satisfaction. The global QoR-15 scores at postoperative day 1 (POD1) were significantly higher in the S-ketamine group than in the control group (124 [119.5-128.0] vs. 119 [114.0-123.5], P = 0.002), with a median difference of 5 points (95% confidence interval [CI] [-8 to -2]). Similarly, the global QoR-15 scores at postoperative day 2 (POD2) in the S-ketamine group were significantly higher than in the control group (140.0 [133.0-145.0] vs. 132.0 [126.5-141.5], P = 0.004). In addition, among the five subcomponents of the 15-item scale, S-ketamine group had a higher score in terms of physical comfort, pain, and emotional state both at POD1 and POD2. In terms of MMSE score, S-ketamine could promote the recovery of postoperative cognitive function at POD1, but not at POD2. Furthermore, the consumption of opioids, VAS score, and remedial analgesia in the S-ketamine group decreased significantly. Collectively, our findings support that general anesthesia with S-ketamine as a potential strategy showed high safety and could not only improve the quality of recovery mainly through improving pain, physical comfort, and emotional state but also promote the recovery of cognitive function on POD1 in patients undergoing MRM. The study was registered in the Chinese Clinical Trial Registry (registration No:ChiCTR2200057226, Date of registration: 04/03/2022).


Modulatory effects of estrogen and progesterone on colorectal hyperalgesia in the rat.
The contribution of estrogen and progesterone to colorectal hyperalgesia was examined in female rats. The electromyogram recorded from the abdominal wall (visceromotor response, vmr) and the discharge of lumbosacral dorsal horn neurons to colorectal distention (CRD) were measured in intact female, ovariectomized (OVx) and estradiol replaced OVx (E2; 50mug, 48h) rats with and without colonic inflammation. Colorectal hyperalgesia was transient in intact rats, but persisted at least 4h in E2 and OVx rats. The magnitude of hyperalgesia in E2 rats was greater than OVx which was greater than intact rats. Dorsal horn neurons that responded to CRD with an Abrupt (on and off with stimulus) excitatory discharge showed similar sensitivity to estradiol as the vmr following colonic inflammation. In contrast, inflammation did not increase the magnitude of response of excitatory neurons with sustained afterdischarges in any of the treatment groups. Intact female rats have a comparable plasma estrogen concentration to E2 rats, suggesting the difference in responses may have been due to antinociceptive effects of progesterone. This was tested by administering E2+/- progesterone (1mg) and measuring the vmr. Progesterone reduced the facilitation of the vmr produced by E2 before and following colonic inflammation. The present study suggests that estrogen replacement enhances visceral signal processing following colonic inflammation. Furthermore, progesterone may counteract the effects of estrogen on colorectal sensitivity.


Successful Management of Heterotopic Cervical Pregnancy with Ultrasonographic-guided Laser Ablation.
Heterotopic pregnancy refers to the simultaneous presence of ectopic pregnancy and intrauterine pregnancy. With the advent of assisted reproductive technology, the overall incidence of heterotopic pregnancies has risen. We report a case of a 36-year-old woman with type 2 diabetes mellitus and 1-year of primary infertility. Following oral ovulation induction cycles and intrauterine insemination, diagnosis of heterotopic cervical pregnancy was made by ultrasonography at 7.4 weeks of gestation. Laser ablation of the cervical pregnancy was performed achieving adequate homeostasis at the implantation site and preserving the intrauterine pregnancy. A healthy infant was delivered at 36 0/7 weeks by cesarean section. Laser ablation is a minimally invasive procedure that appears to lead to successful outcomes in the treatment of heterotopic cervical pregnancy.


Noradrenaline releasing effect of an ouabain-like compound on pulmonary artery.
The effect of ouabain and an endogenous ouabain-like compound (OLC) was studied on (3H)noradrenaline [3H)NA) release from rabbit pulmonary artery. Similarly to ouabain, OLC enhanced the release of (3H)NA in response to electrical stimulation. These findings are the first evidence that OLC is able to act presynaptically and enhance the amount of (3H)NA release per impulse. It is suggested that this mechanism might be involved in the physiological regulation of blood pressure or in the genesis of hypertension.


Visualization of Hidden Epitopes at the Inactive X Chromosome.
Immunodetection of nuclear antigens is often complicated by epitope masking, so that proteins known to function in the nucleus are sometimes not easily detected at their sites of action. Moreover, protein populations that are detected before unmasking can be very different to those seen after removal of nucleic acids. This is particularly true for components of the nuclear matrix, including those known to function at the inactive X chromosome. Here we describe an unmasking protocol that reveals previously undetected proteins at the inactive X chromosome in mouse fibroblasts.


Potential obesogenic effect of a complex contaminant mixture on Cree First Nations adults of Northern Québec, Canada.
Obesity incidence and prevalence is of increasing concern in First Nations communities around Canada. In addition to diet and physical activity, environmental pollutants have been suggested as a potential contributory factor to obesity associated morbidity. Owing to the exposure of Cree First Nations people to various persistent organic pollutants (POPs) and toxic metals, it is important to examine the association between obesity in these communities, and contaminant body burdens. To determine whether selected morphometry measures (body mass index [BMI], waist circumference [WC] and body fat percentage) are associated with body burdens of 10 POPs and toxic metals. Using data from the Nituuchischaayihtitaau Aschii Multi-community Environment-and-Health study in the eastern James Bay (Eeyou Istchee) Cree communities, this cross-sectional study examined morphometric and contaminant measures of 695 eligible participants. Sex stratified principal component analysis was conducted on blood plasma concentrations of 10 POPs and toxic metals. BMI, WC, body fat percent, and resultant contaminant components were used to create generalized linear models, and adjusted for covariates (age, total lipids, smoking, and n-3 fatty acids). Two principal components (PCs; PC-1 and PC-2) were extracted for both males and females. For females, PC-1 explained 73.3% and PC-2 explained 10.5%, and for males, PC-1 explained 71.6% and PC-2 explained 11.2% of the variance in contaminant burden. For both sexes, PC-1 loaded highly for polychlorinated biphenyl (PCB) congeners, organochlorine pesticides and, to a lesser extent, mercury and lead. PC-2 loaded highly for cadmium for females, and cadmium and lead for males. After adjusting for covariates, the generalized linear model showed that PC-2 was significantly and negatively associated with BMI, body fat percent, and WC in males and females. Our cross-sectional analysis indicates a negative association between cadmium with various obesity measures in both males and females. Null associations were found between PCBs and organochlorine pesticides and morphometry.


Molecular genetic studies of familial hypertrophic cardiomyopathy.
Molecular genetic studies of FHC have defined this as disease of the sarcomere. Multiple different mutations in six disease genes, which appear to act through a dominant negative mechanism, have been identified. A relevant murine model of human FHC has been developed. Assessment of the influences that genetics and environment play in disease expression may in the future help direct patient management and assist in the development of novel therapeutics.