Locomotion patterns in cerebral palsy syndromes.
Locomotion patterns were studied in 160 children with cerebral palsy. Ten patterns were distinguished, which were typical of the type of impairment: (1) crawling--mildly impaired children who will achieve independent walking; (2) creeping and crawling--diplegic children with moderate motor impairment; (3) creeping, never leading to independent walking--children with severe diplegia or tetraplegia; (4) bottom shuffling--children with hemiplegia and ataxia and minimal or mild motor impairment; (5) bunny-hopping--dyskinetic children with marked motor impairment but generally not mentally retarded; (6) rolling--severely diplegic and dyskinetic children; (7) other forms of locomotion, such as bridging or grub-type creeping, rare and typical of children with ataxic elements; (8) just walk--children with hemiplegia, diplegia, ataxic diplegia or ataxia, generally in cases of mild motor impairment but mental retardation; (9) just walk with aids--children with severe diplegia; and (10) no mobility. The locomotion pattern, age at onset and even manner of execution all influenced prognosis for walking. Severe deformity affected the choice of locomotion pattern. Though physiotherapy probably would not greatly influence the adoption of a particular locomotion pattern, early intervention might help prevent deformities.


The effect of hypoxemic reperfusion on cerebral protection after a severe global ischemic brain insult.
Reactive oxygen species contribute to membrane lipid peroxidation and neuronal death and have been implicated in anoxic encephalopathy. We tested whether hypoxemic reperfusion (HR) after global cerebral ischemia would improve neurological recovery. Two groups of pigs (n = 11 in each group) were subjected to a model of a 10-min global cerebral and systemic ischemia to compare the effect of hypoxemic reperfusion (group HR) with the classical hyperoxemic control (group C). A third group not subjected to ischemia served as control to the control group (n = 6, group CC), but received hyperoxygenation at the respective period of reperfusion. The outcome was evaluated by means of neurological assessment and the extent of lipid peroxidation measuring the plasma malonaldehyde (MDA) together with hydroxyalkenals (HALK). Animals of group HR exhibited a significantly superior neurological outcome compared with those of group C at all three consecutive assessments after reperfusion (post-resuscitation P = 0.006, at 8 h P = 0.003, and at 24 h P = 0.007). The levels of MDA and HALK are lower in the HR group than in group C (P = 0.029). Additionally, in the CC group these molecules increased significantly early at hyperoxygenation (P = 0.02). A faster lactate metabolism in the HR group was observed during reperfusion, though non-significant. Hypoxemic reperfusion during resuscitation from a severe global ischemic cerebral insult improves the neurological outcome compared with classic hyperoxemic reperfusion. This is additionally confirmed by the decreased production of the molecules of lipid peroxidation. In the absence of preceding ischemia, these molecules may increase by simple over-oxygenation.


A Mexican population-based study on exposure to paracetamol and the risk of wheezing, rhinitis, and eeczema in childhood.
There is some evidence suggesting a link between paracetamol exposure and atopy in both adults and children. We aimed to investigate whether further epidemiological support for a link between paracetamol intake and allergy could be found in a population of Mexican children. In a cross-sectional study design, we applied the ISAAC questionnaire to 3493 children aged 6 to 7 years old. Two analyses were performed: (1) children were classified as cases if they had wheezing, rhinitis, or eczema at any time from their neonatal period up until they reached the age of 6 to 7 years, or as controls if they had never experienced these conditions, and (2) children were classified as cases if they had wheezing, rhinitis, or eczema in the 12 months prior to the study. Paracetamol intake was considered positive if it frequently occurred during the first year of life (first analysis) or in the last 12 months (second analysis). Paracetamol intake in the first year of life was significantly associated with an increased risk of ev having wheezing (adjusted odds ratio [OR], 1.69; 95% confidence interval [CI], 1.23 to 2.34) and rhinitis (adjusted OR, 1.37; 95% CI, 1.20 to 1.59) but not eczema (adjusted OR, 1.45; 95% CI, 0.91 to 2.32). Frequent paracetamol intake in the last year increased the risk of wheezing (OR, 3.3; 95% CI, 1.54 to 7.18), rhinitis (OR, 1.61; 95% CI, 1.33 to 1.95), or eczema (OR, 1.82; 95% CI, 1.24 to 2.66). Frequent paracetamol exposure was associated with a significantly increased risk of wheezing and rhinitis and probably eczema in a Mexican population of children.


An ensemble approach to predict binding hotspots in protein-RNA interactions based on SMOTE data balancing and Random Grouping feature selection strategies.
The identification of binding hotspots in protein-RNA interactions is crucial for understanding their potential recognition mechanisms and drug design. The experimental methods have many limitations, since they are usually time-consuming and labor-intensive. Thus, developing an effective and efficient theoretical method is urgently needed. Here, we present SREPRHot, a method to predict hotspots, defined as the residues whose mutation to alanine generate a binding free energy change ≥2.0 kcal/mol, while others use a cutoff of 1.0 kcal/mol to obtain balanced datasets. To deal with the dataset imbalance, Synthetic Minority Over-sampling Technique (SMOTE) is utilized to generate minority samples to achieve a dataset balance. Additionally, besides conventional features, we use two types of new features, residue interface propensity previously developed by us, and topological features obtained using node-weighted networks, and propose an effective Random Grouping feature selection strategy combined with a two-step method to determine an optimal feature set. Finally, a stacking ensemble classifier is adopted to build our model. The results show SREPRHot achieves a good performance with SEN, MCC and AUC of 0.900, 0.557 and 0.829 on the independent testing dataset. The comparison study indicates SREPRHot shows a promising performance. The source code is available at https://github.com/ChunhuaLiLab/SREPRHot. Supplementary data are available at Bioinformatics online.


lncRNA-MALAT1 expression in patients with coronary atherosclerosis and its predictive value for in-stent restenosis.
This study was designed to investigate the long non-coding RNA (lncRNA)-metastasis associated lung adenocarcinoma transcript 1 (MALAT1) expression in patients with coronary atherosclerosis and its predictive value for in-stent restenosis. Ninety-five patients with coronary heart disease who came to our hospital for treatment and underwent stent implantation were selected as a research group (RG), and 95 volunteers undergoing physical examination who did not suffer from coronary heart disease during the same period were selected as a control group (CG). MALAT1 of subjects in both groups before and after treatment were detected by RT-qPCR, and N-terminal pro-brain natriuretic peptide (NT-proBNP), high sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), and creatine kinase isoenzyme (CK-MB) of them in the RG before treatment were detected. The level was evaluated and detected, and its correlation with MALAT1 was analyzed. Then, the predictive value of MALAT1 for in-stent restenosis in patients with coronary heart disease was analyzed. MALAT1 expression in patients with coronary heart disease was higher than that of normal subjects (P<0.05); after treatment, the expression levels of MALAT1, NT-proBNP, hs-CRP, LDH, and CK-MB in the serum of patients were significantly lower than those before treatment (P<0.05); MALAT1 expression was positively correlated with the expression levels of NT-proBNP, hs-CRP, LDH, and CK-MB (P<0.05). Receiver operating characteristic of MALAT1 for predicting in-stent restenosis in patients with coronary heart disease was over 0.8; the number of lesions, MALAT1, diabetes, NT-proBNP and hs-CRP were independent risk factors for in-stent restenosis. MALAT1 is highly expressed in the serum of patients with coronary heart disease, and it has high value in its diagnosis and the prediction of in-stent restenosis. It is also an independent risk factor for in-stent restenosis in patients with coronary heart disease.


Effects of acetylsalicylic acid on experimental atherogenesis induced in rabbits.
Inflammation related processes play a key role in the current etiologic model of atherosclerosis and its acute complications. In addition, platelet-derived growth factors stimulate the neointimal proliferation of restenosis after coronary interventions. Reducing platelet accumulation at treated sites may attenuate restenosis. The purpose of this experimental study was to investigate the effect of acetylsalicylic acid (ASA), a widely used anti-platelet and anti-inflammatory agent on the development and extent of atherosclerosis. Fourty-eight male white New Zealand rabbits were separated in 4 groups (12 animals each group). Group I received a diet of 2% cholesterol and 6% corn oil for 3 months. Group II received a diet of 2% cholesterol and 6% corn oil and in addition received 3 mg of ASA/kg daily intramuscular (i.m.) for 3 months. Group III received the same diet, and in addition received 10 mg of ASA/kg daily i.m. for 3 months. Group IV received the same diet and in addition received 50 mg of ASA/kg daily i.m. for 3 months. Animals were sacrificed after 3 months. ASA reduced the serum levels of total cholesterol, total lipids, triglycerides and LDL cholesterol. There was significant difference in the extent of atherosclerotic lesions between animals which received different doses of ASA and that animals which did not received any ASA. High dose ASA treatment resulted in an increase in fasting plasma glucose, associated with a reduction in total cholesterol and triglycerides. Our results suggest that there is a protective effect on atherosclerosis development of ASA down stream from where it lowers plasma fatty acid concentrations. However, further studies are required to verify that effect.


Evaluation of two different vaccine platforms for immunization against melioidosis and glanders.
Burkholderia pseudomallei and the closely related species, Burkholderia mallei, produce similar multifaceted diseases which range from rapidly fatal to protracted and chronic, and are a major cause of mortality in endemic regions. Besides causing natural infections, both microbes are Tier 1 potential biothreat agents. Antibiotic treatment is prolonged with variable results, hence effective vaccines are urgently needed. The purpose of our studies was to compare candidate vaccines that target both melioidosis and glanders to identify the most efficacious one(s) and define residual requirements for their transition to the non-human primate aerosol model. Studies were conducted in the C57BL/6 mouse model to evaluate the humoral and cell-mediated immune response and protective efficacy of three Burkholderia vaccine candidates against lethal aerosol challenges with B. pseudomallei K96243, B. pseudomallei MSHR5855, and B. mallei FMH. The recombinant vaccines generated significant immune responses to the vaccine antigens, and the live attenuated vaccine generated a greater immune response to OPS and the whole bacterial cells. Regardless of the candidate vaccine evaluated, the protection of mice was associated with a dampened cytokine response within the lungs after exposure to aerosolized bacteria. Despite being delivered by two different platforms and generating distinct immune responses, two experimental vaccines, a capsule conjugate + Hcp1 subunit vaccine and the live B. pseudomallei 668 ΔilvI strain, provided significant protection and were down-selected for further investigation and advanced development.


Relationship between short latency stretch reflex and fascicle behavior in the soleus muscle in vivo.
Stretch reflex responses were considered to be affected by the velocity of muscle fiber lengthening and angular velocity. However, the results of previous studies in vivo and in vitro are inconsistent in this regard. The purpose of the present study was to investigate the effects of the velocity of fascicle lengthening on the amplitude of the stretch reflex for each trial with a high angular velocity and wide range of motion. Thirteen healthy men volunteered for this study. While the ankle was passively moved from 100 to 80 deg at five different angular velocities (100, 200, 300, 500, and 600 deg⋅s-1), the velocity of fascicle lengthening in the soleus muscle was measured using ultrasonography. In addition, the amplitude of the short latency stretch reflex in the soleus muscle was also measured. As angular velocity increased, the amplitude of the stretch reflex and velocity of fascicle lengthening significantly increased (both p<0.001). For each trial in all subjects, the amplitude of the stretch reflex was not correlated with the velocity of fascicle lengthening at any of the angular velocities. In conclusion, the stretch reflex size is not related to the fascicle behavior in each trial.


Nucleotide composition of deoxyribonucleic acid of some species of Cryptococcus, Rhodotorula, and Sporobolomyces.
The buoyant density of deoxyribonucleic acid (DNA) from nine species and two varieties of Cryptococcus, three species and two varieties of Rhodotorula, and six species of Sporobolomyces was determined by CsCl density gradient equilibrium centrifugation. Several species were represented by two to four different strains. Expressed in moles per cent of guanine plus cytosine (GC content) the ranges were 49 to 65%, 52 to 70%, and 51 to 65% for Cryptococcus, Rhodotorula, and Sporobolomyces, respectively. For each genus, the GC content was distributed into two discrete groups with averages ranging from 52 to 54 and 60 to 66, respectively. An analysis of these results suggested that the determination of GC content of DNA had a taxonomic value for these yeast genera.


Side-on end-on bound dinitrogen: an activated bonding mode that facilitates functionalizing molecular nitrogen.
Molecular nitrogen is the source of all of the nitrogen necessary to sustain life on this planet. How it is incorporated into the biosphere is complicated by its intrinsic inertness. For example, biological nitrogen fixation takes N(2) and converts it into ammonia using various nitrogenase enzymes, whereas industrial nitrogen fixation converts N(2) and H(2) to NH(3) using heterogeneous iron or ruthenium surfaces. In both cases, the processes are energy-intensive. Is it possible to discover a homogeneous catalyst that can convert molecular nitrogen into higher-value organonitrogen compounds using a less energy-intensive pathway? If this could be achieved, it would be considered a major breakthrough in this area. In contrast to carbon monoxide, which is reactive and an important feedstock in many homogeneous catalytic reactions, the isoelectronic but inert N(2) molecule is a very poor ligand and not a common industrial feedstock, except for the above-mentioned industrial production of NH(3). Because N(2) is readily available from the atmosphere and because nitrogen is an essential element for the biosphere, attempts to discover new processes involving this simple small molecule have occupied chemists for over a century. Since the first discovery of a dinitrogen complex in 1965, inorganic chemists have been key players in this area and have contributed much fundamental knowledge on structures, binding modes, and reactivity patterns. For the most part, the synthesis of dinitrogen complexes relies on the use of reducing agents to generate an electron-rich intermediate that can interact with this rather inert molecule. In this Account, a facile reaction of dinitrogen with a ditantalum tetrahydride species to generate the unusual side-on end-on bound N(2) moiety is described. This particular process is one of a growing number of new, milder ways to generate dinitrogen complexes. Furthermore, the resulting dinitrogen complex undergoes a number of reactions that expand the known patterns of reactivity for coordinated N(2). This Account reviews the reactions of ([NPN]Ta)(2)(mu-H)(2)(mu-eta(1):eta(2)-N(2)), 2 (where NPN = PhP(CH(2)SiMe(2)NPh)(2)), with a variety of simple hydride reagents, E-H (where E-H = R(2)BH, R(2)AlH, RSiH(3), and Cp(2)ZrCl(H)), each of which results in the cleavage of the N-N bond to form various functionalized imide and nitride moieties. This work is described in the context of a possible catalytic cycle that in principle could generate higher-value nitrogen-containing materials and regenerate the starting ditantalum tetrahydride. How this fails for each particular reagent is discussed and evaluated.


The hypolipidemic effect of Hibiscus sabdariffa polyphenols via inhibiting lipogenesis and promoting hepatic lipid clearance.
Hibiscus sabdariffa extract (HSE) was shown to lower the plasma lipid level and reduce the liver damage. In the present study, we investigated if Hibiscus sabdariffa polyphenols (HPE) exerted a hypolipidemic effect and its putative mechanism on liver. HPE exhibited more potency to decrease plasma cholesterol and LDL cholesterol than the crude extract HSE, and increased HDL cholesterol dose-dependently. It decreased the lipid content of hepatocyte through the activation of AMPK and reduction of SREBP-1, thus inhibiting the expression of fatty acid synthase and HMG-CoA reductase. LDLR and LDL binding of HepG2 cells were enhanced when treated with HPE. In conclusion, HPE is worthy of being further investigated and could be developed as an adjunctive for hepatic lipid control and hypolipidemic therapy.


Risk Factors for Acute Kidney Injury after Congenital Cardiac Surgery in Infants and Children: A Retrospective Observational Study.
Acute kidney injury (AKI) after pediatric cardiac surgery is associated with high morbidity and mortality. Modifiable risk factors for postoperative AKI including perioperative anesthesia-related parameters were assessed. The authors conducted a single-center, retrospective cohort study of 220 patients (aged 10 days to 19 years) who underwent congenital cardiac surgery between January and December 2012. The incidence of AKI within 7 days postoperatively was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Ninety-two patients (41.8%) developed AKI and 18 (8.2%) required renal replacement therapy within the first postoperative week. Among patients who developed AKI, 57 patients (25.9%) were KDIGO stage 1, 27 patients (12.3%) were KDIGO stage 2, and eight patients (3.6%) were KDIGO stage 3. RACHS-1 (Risk-Adjusted classification for Congenital Heart Surgery) category, perioperative transfusion and fluid administration as well as fluid overload were compared between patients with and without AKI. Multivariable logistic regression analyses determined the risk factors for AKI. AKI was associated with longer hospital stay or ICU stay, and frequent sternal wound infections. Younger age (<12 months) [odds ratio (OR), 4.01; 95% confidence interval (CI), 1.77-9.06], longer cardiopulmonary bypass (CPB) time (OR, 2.45; 95% CI, 1.24-4.84), and low preoperative hemoglobin (OR, 2.40; 95% CI, 1.07-5.40) were independent risk factors for AKI. Fluid overload was not a significant predictor for AKI. When a variable of hemoglobin concentration increase (>3 g/dl) from preoperative level on POD1 was entered into the multivariable analysis, it was independently associated with postoperative AKI (OR, 6.51; 95% CI, 2.23-19.03 compared with no increase). This association was significant after adjustment with patient demographics, medication history and RACHS-1 category (hemoglobin increase >3g/dl vs. no increase: adjusted OR, 6.94; 95% CI, 2.33-20.69), regardless of different age groups and cyanotic or non-cyanotic heart disease. Prospective trials are required to evaluate whether correction of preoperative anemia and prevention of hemoconcentration may ameliorate postoperative AKI in patients who underwent congenital cardiac surgery.


Lateral pterygoid muscle dystonia. A new technique for treatment with botulinum toxin guided by electromyography and arthroscopy.
Lateral pterygoid muscle dystonia is characterized by mandibular displacement towards the opposite side of the affected muscle. It may be associated with functional disorders affecting speech, swallowing, chewing and facial symmetry. Injection with botulinum toxin is recognized as the most effective treatment. Locating the lower head of the lateral pterygoid muscle for the injection is not difficult using electromyographic guidance; however, location of the upper head is more complicated, even with electromyography. We report a case of lateral pterygoid muscle dystonia in which precise injection of the upper head was achieved with the aid of arthroscopy.


Membrane estrogen receptor alpha is an important modulator of bone marrow C-Kit+ cells mediated cardiac repair after myocardial infarction.
It has been validated that c-kit positive (c-kit+) cells in infarcted myocardium are from bone marrow (BM). Given the recent study that in the heart, estrogen receptor alpha (ERα) is involved in adaptive mechanisms by supporting cardiomyocytes survival via post-infarct cardiac c-kit+ cells, we tested a novel hypothesis that membrane ERα (mERа) supports survival of BM c-kit+ cells and enhance protective paracrine function for cardiac repair. Our data showed that myocardial infarction (MI) leads to an increase in c-kit+ first in bone marrow and then specifically within the infarcted myocardium. Also up-regulated mERа in post-infarct BM c-kit+ cells was found in day 3 post MI. In vitro co-culture system, mERа+ enhances the beneficial effects of BM c-kit+ cells by increasing their viability and reducing apoptosis. Post-infarct c-kit+ mERа+ cells population expresses predominant ERα and holds self-renewal as well as cardiac differentiation potentials after MI. In vivo, BM c-kit+ cells reduced infarct size, fibrosis and improved cardiac function. In conclusion, BM c-kit+ mERа+ exerted significantly cardiac protection after MI. A potential important implication of this study is that the manipulation of BM c-kit+ stem cells with ERа-dependent fashion may be helpful in recovering functional performance after cardiac tissue injury.


Interrater reliability of the outcomes and assessment information set: results from the field.
The Outcomes and Assessment Information Set (OASIS) is now used extensively for regulatory, reimbursement, research, and clinical purposes in home health care. However, little is known about the interrater reliability of OASIS items based on assessments from home-health-agency clinicians. Therefore, we evaluated OASIS item interrater reliability among 88 patients from 21 agencies. Of 25 items studied, all except 2 had weighted kappa values of kappa > or = 0.60. We conclude that OASIS item interrater reliability was highly adequate in this study, but we recommend routine interrater-reliability evaluation by agencies to maximize the quality of OASIS data nationally.


Association of Vaccination with the Persistence of Post-COVID Symptoms.
Patients who have had COVID-19 often report persistent symptoms after resolution of their acute illness. Recent reports suggest that vaccination may be associated with improvement in post-acute symptoms. We used data from a prospective cohort to assess differences in post-acute sequelae of COVID (PASC) among vaccinated vs. unvaccinated patients. We used data from a cohort of COVID-19 patients enrolled into a prospective registry established at a tertiary care health system in New York City. Participants underwent a baseline evaluation before COVID-19 vaccines were available and were followed 6 months later. We compared unadjusted and propensity score-adjusted baseline to 6-month change for several PASC-related symptoms and measures: anosmia, respiratory (cough, dyspnea, phlegm, wheezing), depression, anxiety, post-traumatic stress disorder (PTSD; COVID-19-related and other trauma), and quality-of-life domains among participants who received vs. those who did not receive COVID-19 vaccination. The study included 453 COVID-19 patients with PASC, of which 324 (72%) were vaccinated between the baseline and 6-month visit. Unadjusted analyses did not show significant differences in the baseline to 6-month change in anosmia, respiratory symptoms, depression, anxiety, PTSD, or quality of life (p > 0.05 for all comparisons) among vaccinated vs. unvaccinated patients. Similar results were found in propensity-adjusted comparisons and in secondary analyses based on the number of vaccine doses received. Our findings suggest that COVID vaccination is not associated with improvement in PASC. Additional studies are needed to better understand the mechanisms underlying PASC and to develop effective treatments.


Acid-induced unfolding of flounder hemoglobin: evidence for a molten globular state with enhanced pro-oxidative activity.
The acid-induced unfolding of flounder oxyhemoglobin was investigated and the effect on pro-oxidative activity assessed. Hemoglobin exhibited multistep unfolding transitions as pH was lowered, with the major transition between pH 3.5 and 4 5. The protein was maximally acid-unfolded (but not fully unfolded) at approximately pH 2.5, and further titration with HCl led to a partially refolded protein due to a stabilizing effect of Cl(-) anions. At low pH, the protein retained a sizable amount of secondary structure and had increased ANS binding, suggesting a molten globular form at low pH. Dramatic changes in the heme environment occurred concurrently with the changes in protein conformation. These changes resulted in an enhancement in the pro-oxidative activity of the protein. The results show that an increase in flounder hemoglobin pro-oxidation was correlated with the extent of its unfolding, and they provide useful insight into what may occur with hemoglobin in processes where highly acidic conditions are employed.


Electronic Connectivity Among US Hospitals Treating Shared Patients.
Increasing electronic health information exchange (HIE) between provider organizations is a top policy priority that has been pursued by establishing varied types of networks. To measure electronic connectivity enabled by these networks, including community, electronic health record vendor, and national HIE networks, across US hospitals weighted by the volume of shared patients and identify characteristics that predict connectivity. Cross-sectional analysis of 1721 hospitals comprising 16,344 hospital pairs and 6,492,232 shared patients from 2018 CareSet Labs HOP data and national hospital surveys. Pairs of US acute care hospitals that delivered care to 11 or more of the same fee-for-service Medicare beneficiaries in 2018. Whether a patient was treated by a pair of hospitals connected through participation in the same HIE network ("connected hospitals") or not connected because the hospitals participated in different networks, only 1 participated, or both did not participate. Sixty-four percent of shared patients were treated by connected hospitals. Of the remaining shared patients, 14% were treated by hospital pairs that participated in different HIE networks, 21% by pairs in which only 1 hospital participated in an HIE network, and 2% by pairs in which neither participated. Patients treated by pairs with at least 1 for-profit hospital, and by pairs located in competitive markets, were less likely to be treated by connected hospitals. While the majority of shared patients received care from connected hospitals, remaining gaps could be filled by connecting HIE networks to each other and by incentivizing certain types of hospitals that may not participate because of competitive concerns.


Using Portable Voice Accumulators to Study Transfer of Speech Outcomes Following Intervention - A Feasibility Study.
To evaluate the process and scientific feasibility of using a portable voice accumulator (PVA) to study carry-over of treatment effects on speech and voice in people with mild-moderate Parkinson's disease. The study was guided by the checklist in Consolidated Standards of Reporting Trials (CONSORT) 2010 statement: extension to randomized pilot and feasibility trials. Participants with Parkinson's disease were recruited within the context of a randomized controlled trial with random allocation to intervention with either HiCommunication, a program targeting speech and communication, or HiBalance, a program targeting balance and strength. Before and after intervention data was collected from standardized studio recordings of speech and registrations of voice use in daily life with the PVA VoxLog. Fifteen participants were included in the study and sufficient data was yielded from six of them. Reasons for insufficient data included technical issues and difficulties handling the PVA. Changes in voice sound level from pre to post intervention differed at an individual level when assessed in daily life compared to studio recordings. Registrations in daily life provided information on phonation ratio and ability to adapt voice sound level to environmental noise. This study highlights the challenges of studying intervention effects on voice use in daily life using a PVA. Improvements of test protocols in future studies are suggested. We exemplify how PVA data may generate a more detailed and ecologically valid picture of voice use complementing studio recordings of speech. Finally, we encourage technical development of more user-friendly PVAs.


Analysis of phosphate kinetics in hemofiltration and hemodiafiltration: formulation of an efficiency index.
The kinetics of phosphate (P) during a treatment of hemofiltration or hemodiafiltration follows a simple exponential law, and P in 90 min reaches a stationary level that remains constant until the end of the treatment. The theoretical compartmental model cannot be estimated by a dialytic treatment, but a simpler diffusive model may be considered. Once the stationary level is reached, the net flux of P from the inaccessible compartments to the accessible compartment may be estimated via the parameters obtained in the exponential model. Hemodiafiltration seems more efficient than hemofiltration in determining P clearance. Thus an efficiency index that accounts for the period in which P is eliminated from the accessible compartment has been formulated.


Looking for Thom's biomarkers with proteomics.
In recent years, large numbers of putative disease biomarkers have been identified. Combinations of protein biomarkers have been proposed to overcome the lack of single, magic-bullet identifiers of disease conditions. The number of biomarkers in a panel must be kept small to avoid the combinatorial explosion that requires very large, uneconomical sample cohorts for validation. Recent results on high sensitivity blood-based diagnostic proteomics (Godovac-Zimmermann, J et al., J. Proteome Res. 2006) suggest that the keys to identifying useful panels include judicious application of physiological knowledge to choose appropriate combinations of local, tissue/disease markers and global, systemic markers and to use very high sensitivity protein detection. Biomarkers that show non-Gaussian landscapes reminiscent of Rene Thom's multiple, stable-state landscapes seem to have the greatest predictive value for breast cancer (Godovac-Zimmermann, J. et al., J. Proteome Res. 2006).


Effective streptozocin therapy for metastatic pancreatic polypeptide apudoma.
An apparently complete remission of metastases in the liver from a resected pure pancreatic polypeptide apudoma occurred following intra-arterial and intravenous administration of streptozocin to a patient in a family with multiple endocrine adenopathy, type 1. Plasma concentrations of human pancreatic polypeptide constitute an excellent marker system for the detection and assessment of tumor status before and after surgical and streptozocin therapy.


Features of the overexpressed V1-69 genes in the unmutated subset of chronic lymphocytic leukemia are distinct from those in the healthy elderly repertoire.
Chronic lymphocytic leukemia (CLL) comprises 2 subsets, distinguished by expression of unmutated or mutated V(H) genes, with the former having a worse prognosis. Biased usage of the V1-69 gene is found in unmutated cases and is combined with selected D gene segments and J(H)6. It is controversial whether this is a CLL-associated feature or mirrors the normal B-cell pattern. Since CLL is a disease of the elderly, where changes in the B-cell repertoire may occur, we have analyzed V1-69 usage in the elderly (older than 75 years) population. Using monoclonal antibody (MoAb) G6, specific for 51p1-related V1-69 alleles, we found no increased expression with age. In 51p1-encoded immunoglobulin M (IgM), complementarity-determining region 3 (CDR3) length and frequency of D and J(H) genes were similar to those in the healthy young and distinct from those in CLL. These findings support the concept that CLL arises from B cells driven by antigen/superantigen and is not a stochastic event in the elderly B-cell population.


Synergistic promotion of blood vessel regeneration by astragaloside IV and ferulic acid from electrospun fibrous mats.
The promotion of blood vessel initiation and growth plays an important role in the realization of therapeutic vascularization and regeneration of functional tissues. Astragalus membranaceus and angelica sinensis are commonly used traditional Chinese medicines for enriching the blood. In the current study astragaloside IV (AT, the main active ingredient of astragalus) and ferulic acid (FA, the main ingredient of angelica) were loaded into electrospun fibrous scaffolds to provide abundant and sustained biological factors required to initiate vascularization and bring it to maturity. The cell viability after AT and FA treatment was dose-dependent with an optimal concentration of around 50 μg/mL, and the most significant synergistic effect was demonstrated for the combined treatment with AT and FA with the ratio of 7/3 on both primary endothelial and smooth muscle cells. The in vitro release study showed that the amount of AT and FA release could be regulated by their loading amount and ratios in electrospun fibers. The localized and sustained codelivery of AT and FA indicated significantly high cell viability and secretion of extracellular matrices for both endothelial and smooth muscle cells, and induced significantly high densities of vascular structures after subcutaneous implantation. The most significant angiogenesis promotion with few inflammatory reactions was demonstrated for electrospun fibers containing AT and FA with the ratio of 7/3. It was suggested that the integration of the synergistic effect of Chinese medicine into electrospun fibrous scaffolds should provide clinical relevance for therapeutic vascularization, full vascularization in engineered tissues, and regeneration of blood vessel substitutes.


PYK10 myrosinase reveals a functional coordination between endoplasmic reticulum bodies and glucosinolates in Arabidopsis thaliana.
The endoplasmic reticulum body (ER body) is an organelle derived from the ER that occurs in only three families of the order Brassicales and is suggested to be involved in plant defense. ER bodies in Arabidopsis thaliana contain large amounts of β-glucosidases, but the physiological functions of ER bodies and these enzymes remain largely unclear. Here we show that PYK10, the most abundant β-glucosidase in A. thaliana root ER bodies, hydrolyzes indole glucosinolates (IGs) in addition to the previously reported in vitro substrate scopolin. We found a striking co-expression between ER body-related genes (including PYK10), glucosinolate biosynthetic genes and the genes for so-called specifier proteins affecting the terminal products of myrosinase-mediated glucosinolate metabolism, indicating that these systems have been integrated into a common transcriptional network. Consistent with this, comparative metabolite profiling utilizing a number of A. thaliana relatives within Brassicaceae identified a clear phylogenetic co-occurrence between ER bodies and IGs, but not between ER bodies and scopolin. Collectively, our findings suggest a functional link between ER bodies and glucosinolate metabolism in planta. In addition, in silico three-dimensional modeling, combined with phylogenomic analysis, suggests that PYK10 represents a clade of 16 myrosinases that arose independently from the other well-documented class of six thioglucoside glucohydrolases. These findings provide deeper insights into how glucosinolates are metabolized in cruciferous plants and reveal variation of the myrosinase-glucosinolate system within individual plants.


Refractory hypoxemia during liver cirrhosis. Hepatopulmonary syndrome or "primary" pulmonary hypertension?
We report an uncommon mechanism of severe hypoxemia in two cirrhotic patients under long-term beta-blocker therapy. Our patients presented with profound hypoxemia refractory to oxygen therapy, normal lung radiography and pulmonary function tests, and evidence of right-to-left anatomic shunt. Although these features are highly suggestive of hepatopulmonary syndrome, pulmonary hypertension was present, and a right-to-left shunt through a patent foramen ovale was demonstrated by contrast-enhanced echocardiography. No cause of pulmonary hypertension other than portal hypertension was identified. Pulmonary hypertension and intracardiac right-to-left shunt eventually regressed after discontinuation of beta-blocker therapy. We conclude that "primary" pulmonary hypertension associated with portal hypertension may because of severe hypoxemia during liver cirrhosis. Differential diagnosis of hepatopulmonary syndrome relies upon contrast-enhanced echocardiography and may be of critical importance because of possible therapeutic implications.


T cell and dendritic cell interactions in lymphoid organs: More than just being in the right place at the right time.
The initiation of T lymphocyte responses within secondary lymphoid organs involves interactions with different subsets of dendritic cells (DCs). Recent studies have revealed the complexity of microanatomical organization within lymphoid organs. Exactly how T cells and DCs locate each other and the type of cellular interactions required for optimal priming of effector and memory T cell responses are beginning to be unraveled. Here we review advances in our understanding of how T cell priming is choreographed during infections, highlight the importance of cell positioning in this process and discuss how a spectrum of cellular interactions shapes T cell activation and differentiation.


[Natural inducing factors of grape bud dormancy and their regulation on respiratory metabolism during dormancy induction].
High chilling requirement grape (Vitis vinifera-V. labrusca cv. Summer Black) was used to evaluate its dormancy under short sunlight day (SD), long sunlight day (LD) and natural condition (CK). The results indicated that grape bud dormancy could be induced by natural low temperature and short sunlight alone or together. Short sunlight was the main contributor to the dormancy of grape bud, followed by natural low temperature. SD had more effect on dormancy induction under the same temperature when compared with LD. The grape dormancy induction stopped when the total respiratory rate reached the highest level. During the dormancy induction period, the proportion of pentose phosphate pathway (PPP) operation activity or capacity to total respiratory rate increased from 16.0% to 20.1% or 22.3% to 26.0%, respectively; similarly, the proportion of operation activity or capacity of alternate pathway to total respiratory rate rapidly increased, i.e., from 19.4% to 27.3% or 38.2% to 46.8%. Both low temperature and short sunlight could induce change of respiratory pathway on electron transport chain level.


Productive interactions between B and natural killer cells.
In this report, we have established that natural killer (NK) cells can increase IgG2a secretion by B lymphocytes as well as alter the distribution of the remaining immunoglobulin isotypes. The effect of NK cells on B cell differentiation is similar to that obtained by the direct addition of recombinant interferon-gamma (IFN-gamma) and, therefore, most likely results from the elaboration of IFN-gamma by NK cells, this is a clear demonstration that NK cells can regulate cell function(s) via a mechanism other than cytotoxicity. In addition, we have shown that the induction of NK cells by B lymphocytes requires close interactions between the two cell types. Further, while only low-density B lymphocytes activated in vivo are effective inducers of NK cells, high-density, resting B cells can be rendered effective by preactivation with either interleukin-4 or anti-mu.


Sex and attributions on reactions toward alleged spousal abuse victims.
This study examined the emotional and behavioral reactions of 118 predominantly Euro-American, middle-class university students toward an alleged spousal abuse victim. In the context of a decision-making task, participants encountered another male or female student (a confederate) who was supposedly injured in an accident or a spousal abuse incident. Participants completed the Trait Questionnaire, Emotional Reaction Measure, and Social Distancing Measure. Generally, participants felt less sympathy and more anger and ascribed less positive traits to the abuse victim than to the accident victim. In addition, they distanced themselves socially from the abuse victim. Further analyses showed that female participants displayed more negative trait ascriptions and behavioral reactions to the abuse victims than did male participants.


Genome-wide analysis of therapeutic response uncovers molecular pathways governing tamoxifen resistance in ER+ breast cancer.
Prioritization of breast cancer patients based on the risk of resistance to tamoxifen plays a significant role in personalized therapeutic planning and improving disease course and outcomes. In this work, we demonstrate that a genome-wide pathway-centric computational framework elucidates molecular pathways as markers of tamoxifen resistance in ER+ breast cancer patients. In particular, we associated activity levels of molecular pathways with a wide spectrum of response to tamoxifen, which defined markers of tamoxifen resistance in patients with ER+ breast cancer. We identified five biological pathways as markers of tamoxifen failure and demonstrated their ability to predict the risk of tamoxifen resistance in two independent patient cohorts (Test cohort1: log-rank p-value = 0.02, adjusted HR = 3.11; Test cohort2: log-rank p-value = 0.01, adjusted HR = 4.24). We have shown that these pathways are not markers of aggressiveness and outperform known markers of tamoxifen response. Furthermore, for adoption into clinic, we derived a list of pathway read-out genes and their associated scoring system, which assigns a risk of tamoxifen resistance for new incoming patients. We propose that the identified pathways and their read-out genes can be utilized to prioritize patients who would benefit from tamoxifen treatment and patients at risk of tamoxifen resistance that should be offered alternative regimens. This work was supported by the Rutgers SHP Dean's research grant, Rutgers start-up funds, Libyan Ministry of Higher Education and Scientific Research, and Katrina Kehlet Graduate Award from The NJ Chapter of the Healthcare Information Management Systems Society.


Post cholecystectomy common bile duct dilatation and associated symptomatology.
Relationship between postcholecystectomy bile duct dilatation and associated symptomatology is a potential dilemma for treating surgeon for which various studies with variable results have been documented. This study is a 1 year prospective study conducted at IGMC, Shimla after taking proper consent and ethical approval from institutional ethical committee. Total 50 cases of symptomatic cholelithiasis belonging to either sex admitted in surgical wards of IGMC, Shimla for elective surgery were selected for present study. Cholecystectomy was done in all cases after doing all investigations. Postoperatively within 48 h symptoms were observed in 29 patients. Out of these, flatulence was present in 1, nausea and vomiting in 7 and 8, respectively. Combined flatulence vomiting in 5 and flatulence-reflux-nausea in 1 patient. After 1 month of interval, all patients were symptom free. Symptoms which were present in the postoperative patients were unrelated to dilatation of common bile duct. Either these symptoms were the persistent symptoms present before the operation or related to anaesthetic drugs.


Clinical Considerations on the Root Coverage of Gingival Recessions in Thin or Thick Biotype.
Gingival biotype is a clinical term used to describe the thickness of the gingiva. It has been classified as being thick or thin and may be related to the clinical outcome of root coverage procedures. This study evaluated the impact of gingival biotype on the clinical outcome of root coverage procedures following subepithelial connective tissue graft plus coronally positioned flap. A total of 19 patients, 10 with thin and 9 with thick gingival biotype, were treated for localized Miller Class I or II gingival recessions. After 6 months, 14 patients achieved complete root coverage, 7 from each group. The overall mean pooled root coverage rate was 90.93%. The thin biotype cases yielded a reduced mean root coverage of 88.51% compared with 93.63% for patients who had the thick biotype classification. Although the thin gingival biotype may impair the clinical outcome of root coverage procedures, this limitation does not appear to have a strong influence on the success of the root coverage therapy when subepithelial connective tissue graft was associated with the coronal positioning of the flap.


Cost-effectiveness of telerehabilitation versus traditional care after total hip replacement: A trial-based economic evaluation.
Physical rehabilitation for total hip replacement patients following hospital discharge is beneficial; however, accessing rehabilitation is often challenging. Telerehabilitation helps negate access issues and is efficacious in total knee and hip replacement patients. This study aims to compare the cost-effectiveness of a telerehabilitation programme delivered remotely into patients' homes versus traditional care for total hip replacement patients following hospital discharge. A cost-effectiveness (cost-utility) analysis was conducted from the perspective of a health service alongside a two-arm randomised controlled trial comparing telerehabilitation (n=35) with in-person care (n=35) following hospital discharge after total hip replacement. The primary analysis used an Incremental Cost-Effectiveness Ratio to compare the cost per Quality Adjusted Life Year (QALY) accrued in the telerehabilitation group versus in-person control using costs and effects data from the randomised trial. A secondary analysis was conducted whereby the time accrued by patients attending rehabilitation sessions (including travel time) was considered the "cost" (i.e. a time burden), rather than cost from the health service perspective. Estimated mean differences in healthcare costs and QALYs gained were detected but were not significant. The estimated mean (95%CI) difference in cost of telerehabilitation versus in-person was -$28.90 (-$96.37 to $40.45), favouring the telerehabilitation group. The estimated mean (95%CI) difference in QALYs gained from telerehabilitation versus in-person was -0.0025 (-0.0227 to 0.0217). The estimated mean (95%CI) difference in time burden favoured less time burden for the telerehabilitation group (-4.21 (-4.69 to -3.74) hours). Telerehabilitation in the total hip replacement population incurred similar costs and yielded similar effects to traditional in-person care. Telerehabilitation significantly reduced the time burden for patients and carers. These findings are valuable for healthcare providers seeking to implement accessible patient-centred rehabilitation services.


Hepatic alpha 1 and beta adrenergic receptors in various animal species.
Plasma membranes were isolated from the livers of various animal species representing the four vertebrate classes: Amphibia, Reptilia, Aves and Mammalia. These liver plasma membranes displayed comparable levels of purity as judged by marker enzyme analysis. The activities of the two marker enzymes, 5'-nucleotidase and gamma-glutamyltranspeptidase displayed striking, and quite different, species-dependent differences, with no apparent relationship to phylogeny. alpha 1 and beta-adrenergic receptors were characterized in isolated liver plasma membranes by radioligand binding techniques. The hepatic beta-adrenergic receptor was found to be expressed in all animals studied; the hepatic alpha 1-adrenergic receptor was absent in Amphibia and Reptilia, co-expressed with the beta receptor in Aves, and dominant over the beta receptor in Mammalia. These results suggest that, in liver, the beta-adrenergic receptor is more primitive while the alpha 1-adrenergic receptor is of a more recent phylogenetic origin. It is proposed that the latter may have evolved in conjunction with hepatic sympathetic innervation.


Gamma delta T cell receptor variable region usage during the development of experimental allergic encephalomyelitis.
The molecular diversity of gamma delta T cells has not previously been investigated in experimental allergic encephalomyelitis (EAE). This study characterised the gamma delta T cell receptor (TCR) variable (V) region repertoires of T cells infiltrating the brains of EAE mice during development of the disease. TCR gamma- and delta-specific cDNAs were synthesised from total RNA prepared from brain samples and transcription of rearranged V genes was assessed by polymerase chain reaction amplification of TCR V-C transcripts and Southern blot analysis. In the early stages of EAE, the TCR gamma-chain repertoire consisted of V gamma 1-3 and V gamma 6 transcripts and, similarly, a few V delta transcripts that used primarily V delta 1, V delta 4 and V delta 5 gene segments were detected. During the progression of EAE, however, most V gamma and V delta TCR transcripts were observed in the brain. These results indicate that in the course of murine EAE there is an initial infiltration into the brain of a restricted population of gamma delta T cells followed by a heterogeneous gamma delta TCR repertoire as the disease develops. Moreover, the data suggest that gamma delta T cells may play a role in the pathogenesis of demyelinating autoimmune disease.


Hydrophilic Species Are the Most Biodegradable Components of Freshwater Dissolved Organic Matter.
Aquatic dissolved organic matter (DOM) is a crucial component of the global carbon cycle, and the extent to which DOM escapes mineralization is important for the transport of organic carbon from the continents to the ocean. DOM persistence strongly depends on its molecular properties, but little is known about which specific properties cause the continuum in reactivity among different dissolved molecules. We investigated how DOM fractions, separated according to their hydrophobicity, differ in biodegradability across three different inland water systems. We found a strong negative relationship between hydrophobicity and biodegradability, consistent for the three systems. The most hydrophilic fraction was poorly recovered by solid-phase extraction (SPE) (3-28% DOC recovery) and was thus selectively missed by mass spectrometry analysis during SPE. The change in DOM composition after incubation was very low according to SPE-ESI (electrospray ionization)-mass spectrometry (14% change, while replicates had 11% change), revealing that this method is sub-optimal to assess DOM biodegradability, regardless of fraction hydrophobicity. Our results demonstrate that SPE-ESI mass spectrometry does not detect the most hydrophilic and most biodegradable species. Hence, they question our current understanding of the relationships between DOM biodegradability and its molecular composition, which is built on the use of this method.


Teriparatide in the Treatment of Severe Postmenopausal Osteoporosis: A Cost-Utility Analysis.
Teriparatide is a new agent serves as a treatment of choice for severe post-menopausal osteoporotic patients who are at high risk of fracture or have failed or been intolerant of previous osteoporosis therapy. The objective of this study is to estimate the cost-utility of teriparatide compared with no treatment from health system perspective in Iran. A micro-simulation model was developed for a cohort of hypothetical Iranian patient population (women aged 70 years, T-score -2.5 with previous fracture or T-score -3.0 without prior fracture) over a lifetime horizon. The model consisted of the seven health states. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Background fracture risks, mortality rates, persistence rates, utilities, medical and drug costs were derived using published sources. Total accumulated life-time costs and quality-adjusted life years (QALYs) were estimated. Teriparatide was associated with 4.786 QALYs and total direct costs of IRR 143,168,259 over a lifetime horizon. Compared to no treatment, teriparatide provided an additional 0.145 QALY at an incremental cost of IRR 33,511,013. The resulting incremental cost-effectiveness ratio was IRR 230,333,030/QALYs gained. The probabilistic analysis showed that accepting a willingness-to-pay 2 and 3 GDP/capita in Iran, the probability of teriparatide being cost-effective were 51% and 83%, respectively. Compared to no treatment, teriparatide was indicated to be more costly and associated with fewer fractures, more life-years, and more QALYs. The result showed that teriparatide may be considered a cost-effective intervention when targeted to the appropriate patients.


Career opportunities for graduates with professional master's vs. PhD degrees.
Professional science master's degree programs are an appealing option to those who want to pursue a professional career and/or seek advancement in their career that does not necessarily require the more advanced PhD degree. These programs are designed to meet a workforce need for professionals and can be completed within 2 years. The student learns the professional skills to be successful in their chosen field, and data indicate a great deal of satisfaction by graduates from these programs. In contrast, those who wish to have a career goal in academia or research usually will pursue a PhD degree. Table 1 shows the important similarities and differences a student should consider when deciding whether to pursue a PSM or Ph.D. degree.


[Imaging of the parathyroid gland].
Diseases of the parathyroid gland are rare and are especially in case of hyperparathyroidism associated with hyperacalcaemia. Enlarged glands are, therefore, generally not detected with imaging modalities. The aim of imaging studies is to locialize abnormal glands. Ultrasound is the modality of choice for the primary investigation followed by nuclear medicine studies. Computed tomography or angiography with vein sampling should only be performed if the results of other investigations are equivocal. Magnetic resonance imaging is performed rarely in Austria with its high prevalence of endemic goiter.


Divergent migration within lake sturgeon (Acipenser fulvescens) populations: Multiple distinct patterns exist across an unrestricted migration corridor.
Population structure, distribution, abundance and dispersal arguably underpin the entire field of animal ecology, with consequences for regional species persistence, and provision of ecosystem services. Divergent migration behaviours among individuals or among populations are an important aspect of the ecology of highly mobile animals, allowing populations to exploit spatially or temporally distributed food and space resources. This study investigated the spatial ecology of lake sturgeon (Acipenser fulvescens) within the barrier free Huron-Erie Corridor (HEC), which connects Lake Huron and Lake Erie of the North American Laurentian Great Lakes. Over 6 years (2011-2016), movements of 268 lake sturgeon in the HEC were continuously monitored across the Great Lakes using acoustic telemetry (10 years battery life acoustic transmitters). Five distinct migration behaviours were identified with hierarchical cluster analysis, based on the phenology and duration of river and lake use. Lake sturgeon in the HEC were found to contain a high level of intraspecific divergent migration, including partial migration with the existence of residents. Specific behaviours included year-round river residency and multiple lake-migrant behaviours that involved movements between lakes and rivers. Over 85% of individuals were assigned to migration behaviours as movements were consistently repeated over the study, which suggested migration behaviours were consistent and persistent in lake sturgeon. Differential use of specific rivers or lakes by acoustic-tagged lake sturgeon further subdivided individuals into 14 "contingents" (spatiotemporally segregated subgroups). Contingents associated with one river (Detroit or St. Clair) were rarely detected in the other river, which confirmed that lake sturgeon in the Detroit and St. Clair represent two semi-independent populations that could require separate management consideration for their conservation. The distribution of migration behaviours did not vary between populations, sexes, body size or among release locations, which indicated that intrapopulation variability in migratory behaviour is a general feature of the spatial ecology of lake sturgeon in unfragmented landscapes.


Search method for inhibitors of Staphyloxanthin production by methicillin-resistant Staphylococcus aureus.
Staphyloxanthin, a yellow pigment produced by methicillin-resistant Staphylococcus aureus (MRSA), is a virulent factor escaping from the host immune system. A new screening method for inhibitors of staphyloxanthin production by MRSA was established using paper disks. By this screening method, inhibitors of staphyloxanthin production were selected from the natural product library (ca. 300) and from actinomycete culture broths (ca. 1000). From the natural product library, four known inhibitors of lipid metabolism, cerulenin, dihydrobisvertinol, xanthohumol and zaragozic acid, were found to inhibit staphyloxanthin production; however, typical antibiotics used clinically, including vancomycin, had no effect on staphyloxanthin production. From actinomycete culture broths, two known anthraquinones, 6-deoxy-8-O-methylrabelomycin and tetrangomycin, were found to inhibit staphyloxanthin production by MRSA in the paper disk assay. These results suggested that this screening method is useful and effective to find compounds targeting staphyloxanthin production, leading to a new type of chemotherapeutics against MRSA infection.


Intracranial hemorrhage in coronavirus disease 2019 (COVID-19) patients.
Emerging evidence suggests that a subset of coronavirus disease 2019 (COVID-19) patients may present with or develop cerebrovascular disease during the course of hospitalization. Whereas ischemic stroke in COVID-19 patients has been well described, data on intracranial hemorrhage (ICH) in these patients is still limited. We, therefore, conducted a rapid systematic review of current scientific literature to identify and consolidate evidence of ICH in COVID-19 patients. A systematic search of literature was conducted between November 1, 2019, and August 14, 2020, on PubMed and China National Knowledge Infrastructure (CNKI) to identify eligible studies. A total of 23 studies describing ICH in 148 COVID-19 patients were included. The pooled incidence of ICH in COVID-19 patients was 0.7% (95% CI 0.5-0.9), with low levels of inter-study heterogeneity observed (I2 = 33.6%, Cochran's Q = 12.05, p = 0.149). Most of the patients were elderly male patients (65.8%) with comorbidities, the most common being systemic hypertension (54%). Hemorrhage involving multiple cranial compartments was reported in 9.5% of cases. Single compartments were involved in the rest, with intraparenchymal hemorrhage (IPH) being the most common variety (62.6%) and intraventricular hemorrhage (IVH) the least common (1.4%). Half of these patients were on some form of anticoagulation. Overall, the mortality rate in the COVID-19 patients with ICH was about 48.6%. Although relatively uncommon among COVID-19 patients, ICH is associated with a high mortality rate. Early identification of patients at risk of developing ICH, particularly with comorbid conditions and on anticoagulant therapy, may be important to improve outcomes.


Does Botulinum Toxin A Treatment Enhance the Walking Pattern in Idiopathic Toe-Walking?
Objective We conducted a randomized controlled trial to evaluate whether a combination of repeated botulinum toxin A (BTX-A) and conservative treatment is more effective in decreasing toe-walking than conservative treatment alone at 24 months follow-up. Patients and Methods Children between 2 and 9 years of age were randomized either into the conservative (CO) or botulinum treatment (BTX) group. The treatment in the CO group consisted of firm shoes, night splints, a home stretching program and physiotherapy. The BTX arm had all the same conservative treatments added with calf muscle BTX-A injections repeated in 6 months intervals if needed. Change in toe-walking pattern, ankle range of movement (ROM), and overall function were assessed at baseline and 6, 12, 18, and 24 months posttreatment. Results A total of 30 toe-walkers participated: 14 in CO and 16 in BTX group. At 24 months, all children in the BTX group and 85% in the CO group evaluated by the blinded physiotherapist (p = 0.065), 75% in the BTX group and 70% in the CO group graded by the research physiotherapist (p = 0.730), and 50% in the BTX group and 54% in the CO group reported by the parents ceased toe-walking (p = 0.837). The most prominent change was noted during the 1st year. The BTX group seemed to reach the goal earlier. No significant differences between the treatment groups in function or in ankle ROM ensued. Conclusion Adding BTX injections did not significantly enhance the goal to walk either flat foot or with heel strike at 24 months posttreatment.


[Implementation of BIRADSTM together with an organization of percutaneous breast biopsies: experiences, reactions].
To record the acceptance and reactions of radiologists and physicians who recommend patients for mammography after simultaneous establishment of BIRADS TM and a registration of the results of percutaneous breast biopsies. To improve clarity of mammographic reports and to provide guidance concerning any necessary percutaneous breast biopsies the Breast Imaging Data And Reporting System (BIRADS TM) has been introduced regionally together with a registration of percutaneous breast biopsies. Using a questionnaire, 25 radiologists and 230 referring physicians were asked on acceptance and reactions concerning the established system. Of the 15 answering radiologists, 93 % considered BIRADS TM a worthwhile effort and 87 % found the biopsy guidelines to be useful. They regarded the acceptance of the referring physicians and patients as high (80 %). Up to 69 % of the 52 participating physicians stated a better understanding of the mammographic reports, an easier comprehension of the dignity classification of a mammographic lesion and the feeling of an improvement in their work. Preoperative assessment of histology was found to be valuable by 94 % of the referring physicians. They believe that more than half of the patients benefit from the biopsy guidelines and that the majority of patients accept this approach. BIRADS TM is useful to standardize and improve mammographic reports. It is advantageous to link BIRADS TM with guidelines for percutaneous breast biopsies.


Cherimolin-1, new selective inhibitor of the first energy-coupling site of the NADH: ubiquinone oxidoreductase (complex I).
The mechanism linking electron transport to proton translocation in the NADH:ubiquinone oxidoreductase (complex I of the mitochondrial respiratory chain) is still unclear. Inhibitors acting at different sites of the enzyme are powerful tools to clarify this mechanism. Up to now, a unique inhibitor, the Annonaceous acetogenin rolliniastatin-2, selectively blocks the most internal proton-translocation site. This study introduces cherimolin-1, a new acetogenin that inhibits the complex I with this special mode of action, which is more easily available from the plant material. Moreover, the mode of action of this scarce type of complex I inhibitor is further characterized.


Electrophysiological studies on rat dorsal root ganglion neurons after peripheral axotomy: changes in responses to neuropeptides.
The effect of three peptides, galanin, sulfated cholecystokinin octapeptide, and neurotensin (NT), was studied on acutely extirpated rat dorsal root ganglia (DRGs) in vitro with intracellular recording techniques. Both normal and peripherally axotomized DRGs were analyzed, and recordings were made from C-type (small) and A-type (large) neurons. Galanin and sulfated cholecystokinin octapeptide, with one exception, had no effect on normal C- and A-type neurons but caused an inward current in both types of neurons after sciatic nerve cut. In normal rats, NT caused an outward current in C-type neurons and an inward current in A-type neurons. After sciatic nerve cut, NT only caused an inward current in both C- and A-type neurons. These results suggest that (i) normal DRG neurons express receptors on their soma for some but not all peptides studied, (ii) C- and A-type neurons can have different types of receptors, and (iii) peripheral nerve injury can change the receptor phenotype of both C- and A-type neurons and may have differential effects on these neuron types.


[Operative treatment of proximal humeral fractures with helix wire].
Between 1 January 2000 and 31 December 2002, a total of 50 patients with a dislocated or unstable fracture of the proximal humerus were treated surgically with a titanium helix wire introduced retrogradely into the medullary cavity. Fracture classification showed 8 cases of a two-fragment fracture, 32 cases of a three-fragment fracture, and 10 cases of a so-called four-fragment fracture. A retrospective radiographic and medical review of all 50 patients showed postoperative complications in 24% of the cases; in 8 cases (16%) secondary loss of retention occurred with consecutive projection of the helix wires into the subacromial joint space. There were two cases each (4%) of perforation of the helix wire into the joint space without loss of retention and fracture dehiscence because of a blocking mechanism by the helix wire in the subcapital fracture gap. The postoperative revision rate was 18% (9/50) as a result. Of 50 patients with a titanium helix wire, 38 (76%) were reviewed after an average of 23 months (12-31). Radiologically partial necrosis of the head of the humerus was seen in two patients and there was necrosis of the head of the humerus with pseudarthrosis in one patient, which had a negative effect on the Constant score. Because of a change of procedure (n=5) and intercurrent deaths (n=5) only 2 of 12 patients, in whom complications had occurred postoperatively, could be followed up clinically; the results of the follow-up are sure to be distorted by this selection effect. Of 38 patients, 32 (84%) showed very good to good results functionally; the average Constant score was 74 points and the average age- and sex-specific corrected score was 92%. Thus, the procedure does not achieve better functional results compared to other rigid and semirigid internal fixation methods while it has a high complication and revision rate compared to other rigid and semirigid internal fixation methods. Moreover, early functional treatment is not possible so that the titanium helix wire represents a retention aid rather than stable internal fixation. Overall we cannot recommend the procedure for the operative management of proximal humerus fractures further and have abandoned it ourselves.


Oxcarbazepine in the treatment of epilepsy in children and adolescents with intellectual disability.
Oxcarbazepine is similar to carbamazepine in its mechanisms of action and antiepileptic efficacy, but has better tolerability and fewer interactions with other drugs. Very few data are available on the usefulness of oxcarbazepine in patients with intellectual disability and epilepsy. From January 1991 until October 1994, the present authors treated 40 patients with intellectual disability and epilepsy under the age of 18 years with oxcarbazepine. The mean age at onset of epilepsy was 12 months (range = 0-132 months). All patients had previously been intractable to antiepileptic drugs (including carbamazepine in 29 patients). The age at onset of oxcarbazepine therapy ranged from 0.8 to 17.1 years (mean = 6.2 years). Thirty-one patients (78%) received other antiepileptic drugs simultaneously with oxcarbazepine. The mean follow-up with oxcarbazepine treatment was 18.8 months. The mean maximum oxcarbazepine dose was 49 mg kg(-1) day(-1) (range = 21-86 mg kg(-1) day(-1). A reduction in seizures of at least 50% during oxcarbazepine treatment was observed in 14 out of 28 (50%) patients with localization-related epilepsy and in 5 out of 12 (42%) patients with generalized epilepsy. Efficacy was transient in three patients. An increase of atypical absences was observed in one child and an emergence of drop attacks in another. Side-effects were observed in 16 (40%) patients; in eight (20%), these lead to dose reduction or discontinuation. Oxcarbazepine appears to be an effective and well-tolerated drug for children and adolescents with intellectual disability and epilepsy.


FH535 inhibited metastasis and growth of pancreatic cancer cells.
FH535 is a small-molecule inhibitor of the Wnt/β-catenin signaling pathway, which a substantial body of evidence has proven is activated in various cancers, including pancreatic cancer. Activation of the Wnt/β-catenin pathway plays an important role in tumor progression and metastasis. We investigated the inhibitory effect of FH535 on the metastasis and growth of pancreatic cancer cells. Western blotting and luciferase reporter gene assay indicated that FH535 markedly inhibited Wnt/β-catenin pathway viability in pancreatic cancer cells. In vitro wound healing, invasion, and adhesion assays revealed that FH535 significantly inhibited pancreatic cancer cell metastasis. We also observed the inhibitory effect of FH535 on pancreatic cancer cell growth via the tetrazolium and plate clone formation assays. Microarray analyses suggested that changes in the expression of multiple genes could be involved in the anti-cancer effect of FH535 on pancreatic cancer cells. Our results indicate for the first time that FH535 inhibits pancreatic cancer cell metastasis and growth, providing new insight into therapy of pancreatic cancer.


Mechanisms of distribution and targeting of neuronal ion channels.
The discovery and development of pharmaceutical drugs targeting ion channels is important for treating a variety of medical conditions and diseases. Ion channels are expressed ubiquitously throughout the body, and are involved in many basic physiological processes. Neuronal ion channels are particularly appealing drug targets, and recent advances in screening ion channel function using optical-based and electrophysiological technologies have improved drug development in this field. Moreover, methods for the discovery of peptide-based neurotoxins and other natural products have proven useful in the pharmacological assessment of ion channel structure and function, while also contributing to the identification of lead molecules for drug development.


Enantioselective Topological Frequency Conversion.
Two molecules are enantiomers if they are nonsuperimposable mirror images of each other. Electric dipole-allowed cyclic transitions |1⟩ → |2⟩ → |3⟩ → |1⟩ obey the symmetry relation OR=-OS, where OR,S = (μ21R,SE21)(μ13R,SE13)(μ32R,SE32) and R and S label the two enantiomers. Herein, we generalize the concept of topological frequency conversion to an ensemble of enantiomers. We show that, within a rotating-frame, the pumping power between fields of frequency ω1 and ω2 is sensitive to enantiomeric excess, P2→1 = ℏ[ω1ω2CLR/(2π)](NR - NS), where Ni is the number of enantiomers i and CLR is an enantiomer-dependent Chern number. Connections with chiroptical microwave spectroscopy are made. Our work provides an underexplored and fertile connection between topological physics and molecular chirality.


Contactless conductivity detection of sodium monofluoroacetate in fruit juices on a CE microchip.
Rapid and quantitative determination of sodium monofluoroacetate in diluted fruit juices (dilution 1:9 v/v in deionized water) and tap water was performed by microchip CE, using contactless conductivity detection. A separation buffer consisting of 20 mM citric acid and histidine at pH 3.5 enabled the detection of the monofluoroacetate (MFA) anion in diluted apple juice, cranberry juice, and orange juice without lengthy sample pretreatments. The analyte was very well separated from interfering anionic species present in juices and tap water. LODs in diluted juices and tap water were determined to be 125, 167, 138, and 173 microg/L for tap water, apple juice, cranberry juice, and orange juice, respectively, based upon an S/N of 3:1. Taking into account the dilution factor, the LODs for juice samples range from 1 to 2 mg/L, which is adequate for monitoring the toxicity of MFA in these juice beverages and tap water. The calibration curves for MFA in diluted fruit juices were linear over the range of 500 microg/L to 80 mg/L. The total analysis time for detecting the MFA anion in fruit juices was less than 5 min, which represents a considerable reduction in analysis time compared to other analytical methods currently used in food analysis.


Heterogeneous RNA-binding protein M4 is a receptor for carcinoembryonic antigen in Kupffer cells.
Here we report the isolation of the recombinant cDNA clone from rat macrophages, Kupffer cells (KC) that encodes a protein interacting with carcinoembryonic antigen (CEA). To isolate and identify the CEA receptor gene we used two approaches: screening of a KC cDNA library with a specific antibody and the yeast two-hybrid system for protein interaction using as a bait the N-terminal part of the CEA encoding the binding site. Both techniques resulted in the identification of the rat heterogeneous RNA-binding protein (hnRNP) M4 gene. The rat ortholog cDNA sequence has not been previously described. The open reading frame for this gene contains a 2351-base pair sequence with the polyadenylation signal AATAAA and a termination poly(A) tail. The mRNA shows ubiquitous tissue expression as a 2.4-kilobase transcript. The deduced amino acid sequence comprised a 78-kDa membrane protein with 3 putative RNA-binding domains, arginine/methionine/glutamine-rich C terminus and 3 potential membrane spanning regions. When hnRNP M4 protein is expressed in pGEX4T-3 vector system in Escherichia coli it binds (125)I-labeled CEA in a Ca(2+)-dependent fashion. Transfection of rat hnRNP M4 cDNA into a non-CEA binding mouse macrophage cell line p388D1 resulted in CEA binding. These data provide evidence for a new function of hnRNP M4 protein as a CEA-binding protein in Kupffer cells.


Breast cancer association studies in a Han Chinese population using 10 European-ancestry-associated breast cancer susceptibility SNPs.
Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations. Ten SNPs (rs2075555 in COL1A1, rs12652447 in FBXL17, rs10941679 in 5p12/MRPS30, rs11878583 in ZNF577, rs7166081 in SMAD3, rs16917302 in ZNF365, rs311499 in 20q13.3, rs1045485 in CASP8, rs12964873 in CDH1 and rs8170 in 19p13.1) were here genotyped in 1009 Chinese females (487 patients with breast cancer and 522 control subjects) using the Sequenom MassARRAY iPLEX platform. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each SNP. Stratification analyses were carried out based on the estrogen receptor (ER) and progesterone receptor (PR) status. Among the 10 SNPs, rs10941679 showed significant association with breast cancer when differences between the case and control groups in this Han Chinese population were compared (30.09% GG, 45.4% GA and 23.7% AA; P = 0.012). Four SNPs (rs311499, rs1045485, rs12964873 and rs8170) showed no polymorphisms in our study. The remaining five SNPs showed no association with breast cancer in the present population. Immunohistochemical tests showed that rs2075555 was associated with ER status; the AA genotype showed greater association with ER negative than ER positive (OR = 0.54, 95% CI, 0.29-0.99; P = 0.046). AA of rs7166081 was also associated with ER status, but showed a greater association with ER positive than negative (OR = 1.59, 95% CI = 1.04-2.44; P = 0.031). However, no significant associations were found among the SNPs and PR status. In this study using a Han Chinese population, rs10941679 was the only SNP associated with breast cancer risk, indicating a difference between European and Chinese populations in susceptibility loci. Therefore, confirmation studies are necessary before utilization of these loci in Chinese.


Immunogenicity of Newcastle Disease Vaccine in Southern Ground-hornbill (Bucorvus leadbeateri).
The southern ground-hornbill (Bucorvus leadbeateri; hereafter SGH) is endangered in South Africa, Namibia, and Swaziland. Through a conservation program established in South Africa by the Mabula Ground Hornbill Project, wild populations are being re-established by the reintroduction of captive-reared birds. The SGH is susceptible to infection with avian avulavirus 1, which causes Newcastle disease (ND). Four different vaccines to protect against ND were administered through various vaccination schedules and evaluated by serologic monitoring to assess the efficiency and safety of various combinations of vaccines (live versus inactivated/killed), vaccine strains (Ulster strain, live; Avivac Cellimune, live; VG/GA strain, live; and Avivac Struvac, killed), and administration routes (intraocular versus subcutaneous versus intramuscular injection versus oral). We vaccinated 75 individuals and evaluated antibody titers in 53 individuals (24 juveniles, 13 subadults, and 16 adult SGH; 26 males and 27 females) over a period of 9 years. Antibody titers to avian avulavirus 1 in sera were monitored by a hemagglutination inhibition test. Protective titers were generated with 3/6 vaccine regimes tested in the SGH. The highest vaccine titers were established in birds vaccinated with the Ulster strain in the conjunctiva and followed with an intramuscular Struvac injection (mean log2 titer 8.6 ± 2.6) booster. Our aim was 1) to assess whether optimal vaccination protocols could be developed and 2) to then be able, by oral administration, to remove the need to recapture free-roaming, reintroduced birds to administer the initial vaccine or booster, thus remove the threat or mortality associated with ND to this endangered avian species in both captive birds and birds released back into the wild.


Esophageal Adenocarcinoma: Screening, Surveillance, and Management.
Esophageal adenocarcinoma (EAC) is a growing problem with a rapidly rising incidence. Risk factors include gastroesophageal reflux disease, central obesity, and smoking. The prognosis of EAC remains poor because it is usually diagnosed late, and many efforts have been made to improve prevention, early detection, and treatment. Acid suppression, nonsteroidal antiinflammatory drugs (NSAIDs), and statins may play a role in chemoprevention. Screening for Barrett's esophagus (BE), the only known precursor lesion of EAC, is indicated for individuals with increased risk. Endoscopic surveillance of patients with BE likely improves overall outcomes. Endoscopic ablation and resection is highly effective for treating dysplastic BE and early EAC, whereas esophagectomy is indicated for patients with locally advanced disease. This review covers epidemiology, staging, screening, and prevention of EAC as well as endoscopic and surgical management.


Intra-ocular pressure changes during maximal isometric contraction: does this reflect intra-cranial pressure or retinal venous pressure?
Recent publications have suggested that intra-ocular pressure (IOP) may be an indirect assessment of intra-cranial pressure (ICP). Both IOP and ICP have similar physiologic pressure ranges and similar responses to changes in intra-abdominal, intra-thoracic and aortic pressure. Previous studies have demonstrated the relationships between retinal arterial pressure and aortic pressure, intra-ocular pressure and retinal venous pressure, intra-cranial pressure and retinal venous pressure. Power athletes routinely utilize the Valsalva maneuver during weightlifting. In fact there are reports of stroke, cerebral hemorrhage, subarachnoid hemorrhage, conjunctival, foveal and retinal hemorrhage, retinal detachment, hiatal hernia and pneumothorax associated with weightlifting. These events are thought to occur secondary to the extreme pressure elevations that occur in the intra-abdominal, intra-thoracic, intra-cranial, intra-ocular and vascular compartments. To date no human studies have examined the IOP changes that may occur with heavy resistance exercise. Therefore, we recruited power athletes (n = 11), who had participated in prior studies, from the local metropolitan area. The athletes had blood pressure status, drug screening and medical histories performed during previous investigations. Intra-ocular pressure was measured by noncontact tonometry at rest and during maximal isometric contraction. All subjects resting IOP were within normal ranges (mean 13 +/- 2.8 mmHg). Intra-ocular pressures were significantly (p < 0.0001) elevated in each subject during maximal contraction (mean 28 +/- 9.3 mmHg). One subject's IOP reached 46 mmHg during maximal contraction. Linear regression analysis demonstrated a significant linear relationship (r = 0.62, p < 0.0001) in the net change of IOP from rest to maximal contraction for each subject. This study demonstrates that IOP elevates to pathophysiologic levels during resistance exercise. The findings of conjunctival hemorrhages in two subjects further supports IOP being reflective of retinal venous pressure. The enormous pressures generated by power athletes during weightlifting leads to elevations in ICP which obstruct venous outflow leading to hemorrhage and elevations in IOP. The question remains as to whether these intermittent bursts of elevated IOP can lead to long-term pathological sequelae.


Decreased anti-inflammatory responses to vitamin D in neonatal neutrophils.
Neutrophil activity is prolonged in newborns, suggesting decreased exposure and/or responses to immunosuppressive modulators, such as 1,25-hydroxyvitamin D(3) (1,25-vit D(3)). We hypothesized that 1,25-vit D(3) suppresses neutrophil activation and that this response is impaired in newborns. Consistent with this, 1,25-vit D(3) decreased LPS-induced expression of macrophage inflammatory protein-1β and VEGF in adult, but not neonatal, neutrophils. Expression of vitamin D receptor (VDR) and 25-hydroxyvitamin D(3)-1α-hydroxylase was reduced in neonatal, relative to adult neutrophils. Moreover, 1,25-vit D(3) induced VDR gene expression in activated adult, but not neonatal, neutrophils. 1,25-vit D(3) also suppressed expression of cyclooxygenase-2 and induced expression of 5-lipoxygenase in LPS-exposed adult neutrophils, while neonatal cells were not affected. 1,25-vit D(3) had no effect on respiratory burst in either adult or neonatal cells. Anti-inflammatory activity of vitamin D is impaired in neonatal neutrophils, and this may be due to decreased expression of VDR and 1α-hydroxylase. Insensitivity to 1,25-vit D(3) may contribute to chronic inflammation in neonates.


Alleviation of Androgenetic Alopecia with Aqueous Paeonia lactiflora and Poria cocos Extract Intake through Suppressing the Steroid Hormone and Inflammatory Pathway.
Paeonia lactiflora Pallas (PL) and Poria cocos Wolf (PC) have been traditionally used to treat inflammatory diseases reported in Dongui Bogam and Shen Nong Ben Cao Jing, traditional medical books in Korean and China, respectively. We determined the efficacies and the molecular mechanisms of PL, PC, and PL + PC aqueous extracts on androgenetic alopecia (AGA) induced by testosterone propionate in C57BL/6 mice. The molecular mechanisms of PL and PC in AGA treatment were examined using experimental assays and network pharmacology. The AGA model was generated by topically applying 0.5% testosterone propionate in 70% ethanol solution to the backs of mice daily for 28 days while the normal-control (Normal-Con; no AGA induction) mice applied 70% ethanol. The 0.1% PL (AGA-PL), 0.1% PC (AGA-PC), 0.05% PL + 0.05% PC (AGA-MIX), and 0.1% cellulose (AGA-Con; control) were supplemented in a high-fat diet for 28 days in AGA-induced mice. Positive-control (AGA-Positive) were administered 2% finasteride daily on the backs of the AGA mice. Hair growth rates decreased in the order of AGA-PL, AGA-MIX, AGA-PC, AGA-Positive, and AGA-Con after 21 days of treatment (ED21). On ED28, skins were completely covered with hair in the AGA-PL and AGA-MIX groups. Serum testosterone concentrations were lower in the AGA-PL group than in the AGA-Con group and similar to concentrations in the Normal-Con group, whereas serum 17β-estradiol concentrations showed the opposite pattern with increasing aromatase mRNA expression (p < 0.05). In the dorsal skin, DKK1 and NR3C2 mRNA expressions were significantly lower, but TGF-β2, β-Catenin, and PPARG expressions were higher in the AGA-PL and AGA-PC groups than in the AGA-Con group (p < 0.05), whereas TNF-α and IL-6 mRNA expressions were lower in the AGA-PL, AGA-MIX, and Normal-Con groups than in the AGA-Con group (p < 0.05). The phosphorylation of Akt and GSK-3β in the dorsal skin was lower in AGA-Con than normal-Con, and PL and MIX ingestion suppressed their decrease similar to the Normal-Con. In conclusion, PL or PL + PC intake had beneficial effects on hair growth similar to Normal-Con. The promotion was related to lower serum testosterone concentrations and pro-inflammatory cytokine levels, and inhibition of the steroid hormone pathway, consistent with network pharmacology analysis findings.


Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease.
Background: Recent studies have suggested that IgE sensitization to α-gal is associated with coronary artery disease (CAD). However, the B cell subtype(s) responsible for production of IgE to α-gal and mechanisms mediating this production remain elusive. Methods: Single cell multi-omics sequencing, was utilized to phenotype B cells obtained from 60 subjects that had undergone coronary angiography in whom serum IgE was evaluated by ImmunoCAP. Bioinformatics approaches were used to identify B cell subtype(s) and transcriptomic signatures associated with α-gal sensitization. In vitro characterization of chemokine/chemokine receptor pairs on switched memory B cells associated with IgE to α-gal was performed. Results: Of the 60 patients, 17 (28%) were positive for IgE to α-gal. CITESeq identified CCR6+ class-switched memory (SWM) B cells and CXCR4 expresssion on these CCR6+ SWM B cells as significantly associated with IgE sensitization to α-gal but not to other common allergens (peanut or inhalants). In vitro studies of enriched human B cells revealed significantly greater IgE on SWM B cells with high CCR6 and CXCR4 expression 10 days after cells were treated with IL-4 and CD40 to stimulate class switch recombination. Both CCL20 (CCR6 ligand) and CXCL12 (ligand for CXCR4) increased the expression of IgE on SWM B cells expressing their receptors. However, they appeared to have unique pathways mediating this effect as only CCL20 increased activation-induced cytidine deaminase (AID), while CXCL12 drove proliferation of CXCR4+ SWM B cells. Lastly, correlation analysis indicated an association between CAD severity and the frequency of both CCR6+ SWM and CXCR4+ SWM B cells. Conclusions: CCR6+ SWM B cells were identified as potential producers of IgE to α-gal in CAD patients. Additionally, our findings highlighted non-chemotaxis roles of CCL20/CCR6 and CXCL12/CXCR4 signaling in mediating IgE class switching and cell proliferation of SWM B cells respectively. Results may have important implications for a better understanding and better therapeutic approaches for subjects with IgE sensitization to α-gal.


Fibro-osseous lesions of the jaws: an analysis of 122 cases in Thailand.
There are no previously published reports on fibro-osseous jaw lesions in Thailand. The aims of this study were to determine the relative frequencies and the clinicopathologic features of these lesions in Thailand, and to compare these data with information available in the literature. A total of 122 cases of fibro-osseous lesions of the jaws, out of a total of 4808 biopsy specimens, were collected from the files of the Department of Oral Pathology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand, during a 34-year period from 1973 to 2006. Clinical data and histopathologic diagnoses were reviewed and analyzed. The most common was ossifying fibroma (50.8%), followed by fibrous dysplasia (42.6%). Ossifying fibroma most frequently occurred in the third and fourth decades of life (61.3%) and mostly involved the posterior region of the mandible (41.9%). Fibrous dysplasia was mostly seen in the second decade of life (40.4%). The maxilla was involved far more often than the mandible (53.8% and 6.2%, respectively), most common in the posterior region of the maxilla (28.8%). Both lesions presented as painless swellings (62.9% and 90.4%, respectively). Radiographically, ossifying fibroma mostly was mixed radiolucent-radiopacity (45.2%). Fibrous dysplasia mostly appeared as a radiopaque lesion (34.6%). The relative frequency of osseous dysplasia is underestimated because most lesions are not treated and the patients are kept under long-term follow-up without biopsy. The clinicopathologic features of ossifying fibroma and fibrous dysplasia in Thailand are identical to those in the literature.


Smart skin patterns protect springtails.
Springtails, arthropods who live in soil, in decaying material, and on plants, have adapted to demanding conditions by evolving extremely effective and robust anti-adhesive skin patterns. However, details of these unique properties and their structural basis are still unknown. Here we demonstrate that collembolan skin can resist wetting by many organic liquids and at elevated pressures. We show that the combination of bristles and a comb-like hexagonal or rhombic mesh of interconnected nanoscopic granules distinguish the skin of springtails from anti-adhesive plant surfaces. Furthermore, the negative overhang in the profile of the ridges and granules were revealed to be a highly effective, but as yet neglected, design principle of collembolan skin. We suggest an explanation for the non-wetting characteristics of surfaces consisting of such profiles irrespective of the chemical composition. Many valuable opportunities arise from the translation of the described comb-like patterns and overhanging profiles of collembolan skin into man-made surfaces that combine stability against wear and friction with superior non-wetting and anti-adhesive characteristics.


Defining the roles of advisors and mentors in postgraduate medical education: faculty perceptions, roles, responsibilities, and resource needs.
Residency program directors rely on an informal network of faculty mentors to provide guidance for residents. Faced with increasingly sophisticated competency-based evaluation systems and scrutiny of patient safety and resident well-being in today's environment, residency programs need more structured mechanisms for mentoring. To clarify the role of resident advisors and mentors so that residents receive the right combination of direction and oversight to ensure their successful transition to the next phase of their careers. The Duke Internal Medicine Residency Program undertook a formal assessment of the roles, responsibilities, and resource needs of its key faculty through a focus group made up of key faculty. A follow-up focus group of residents and chief residents was held to validate the results of the faculty group assessment. The distinction between advising and mentoring was our important discovery and is supported by literature that identifies that mentors and advisors differ in multiple ways. A mentor is often selected to match resources and expertise with a resident's needs or professional interests. An advisor is assigned with a role to counsel and guide the resident through the residency processes, procedures, and key learning milestones. The difference between the role of advisor and that of mentor is of critical importance and allowed for the evolution of faculty participants' role as resident advisors, including the formulation of expectations for advisors, and the creation of an advisor toolkit. Our modifiable toolkit can enhance the advising process for residents in many disciplines. We saw an improvement in resident satisfaction from 2006 to 2009.


Growth factor priming in therapy of acute myelogenous leukemia.
Treatment of acute myelogenous leukemia (AML) incorporates the use of growth factors towards several objectives, including abbreviating the time of neutropenia, reducing susceptibility to infections, reducing length of hospitalization, and increasing susceptibility of the blasts to chemotherapy drugs, or priming. Priming is defined as the driving of leukemia cells into cell cycle in order to increase response to S-phase-specific drugs such as cytarabine (Ara-C). Growth factors that have been used in priming include both filgrastim (G-CSF) and sagramostim (GM-CSF). Priming has often been applied in the treatment of older patients, who do not respond as well to standard treatment regimens, and whose disease was transformed from a myelodysplastic syndrome (MDS), or preleukemia. Recent, large randomized trials have demonstrated that although subgroups of patients may benefit, there does not appear to be any improvement in the complete remission rate sustained by inclusion of growth factor priming as part of the initial therapy of acute myelogenous leukemia.


Evaluation of the Antigen-impregnated Discs For Patch Tests.
Antigen-impregnated discs (AlDs) have been developed to standardize the amount of antigen used for each patch test and also to make, the test far easier. in the first experiment, 800 patch tests were applied using, AlDs prepared for parthenium hysterophours, nitrofurazone, nickel sulphate, Potassium dichromate, Mercurochrome, acriflavine, garlic and onion, and the, results were compared with patch tests done with the corresponding standard antigens applied at the same, time in the same patients. In 780 instances, the results were similar with both Mvi of materials,- the:discrepancy being seen in only 20 cases. In a second experiment, AIDs prepared for nitrofurazone, garlic,, nickel sulphate, Calotropis procera, Mercurochrome and acriflavine were each divided into 3 s and stored at room 'soup temperature. 10 C and 420C respectively to study the I stability of AIDS under different climatic conditions. The results of patch tests with each of these'AIDS were compared with the standard antigens prepared at the same time and kept at IOOC. False negative patch tests were more frequent with the standard antigens indicating that AIDS are stable for at least I year at room temperature even when the environmental temperature is as high as 429C.


A Comparative Observational Study of the Use of Saline Uterine Hydrosonography for the Diagnosis and Assessment of Uterine Cavity Lesions in Women.
Aim of this study was to evaluate the performance of saline hydrosonography (HSGM) (also known as saline infusion sonography (SIS)) against transvaginal ultrasound scan (TVS) and hysteroscopy in the diagnosis of uterine cavity lesions. Diagnostic hysteroscopy with biopsy is considered as the "gold standard" to diagnose intrauterine abnormalities. The introduction of HSGM has improved the diagnostic capability of ultrasound. It is important to establish the efficacy and safety of HSGM before it is widely recommended for use. This retrospective observational data was collected from all 223 patients who underwent TVS, HSGM, and hysteroscopy as part of their gynaecological investigations from 1 January 2008 to 31 December 2010 at Central Middlesex Hospital, London. Endometrial Polyps. TVS: sensitivity 60.53%, specificity 97.06%, positive predictive value (PPV) 95.83%, and negative predictive value (NPV) 68.75% and HSGM: sensitivity 95%, specificity 97.14%, PPV 97.44%, and NPV 94.44%. Submucous Leiomyoma. TVS: sensitivity 57.14%, specificity 93.48%, PPV 84.21%, and NPV 78.18% and HSGM: sensitivity 96.55%, specificity 100.00%, PPV 100.00%, and NPV 97.92%. Diagnostic efficacy of HSGM is superior to TVS for the diagnosis of endometrial polyps and submucous fibroids. HSGM should be considered as an intermediate investigation after TVS to assess intracavity pathology and to confirm the diagnosis; hysteroscopy should become a therapeutic intervention.