An association between Type 2 diabetes and alpha-antitrypsin deficiency.
Alpha(1)-Antitrypsin (AAT) is a serine protease inhibitor which recently has been shown to prevent Type 1 diabetes development, to prolong islet allograft survival and to inhibit pancreatic B-cell apoptosis in vivo. It has also been reported that Type 1 diabetic patients have significantly lower plasma concentrations of AAT, suggesting the potential role of AAT in the pathogenesis of Type 1 diabetes. We have investigated whether plasma AAT levels are altered in Type 2 diabetes. The study included patients with Type 2 diabetes (n = 163) and non-diabetic control subjects matched for age, sex and smoking habits (n = 158) derived from the population-based Malmö Diet and Cancer study. Plasma samples were analysed for AAT concentration and phenotype and serum glucose, insulin, C-reactive protein and lipid levels were measured. Glycated haemoglobin was also measured. In the diabetic group, the women had higher mean plasma AAT levels than men (P < 0.05). The mean plasma AAT levels did not differ between diabetic and control subjects. However, the number of individuals with low AAT levels (< 1.0 mg/ml) was 50% higher in the diabetic group (P < 0.05) and the frequency of AAT deficiency genotypes was 50% higher (NS) in diabetic compared with control subjects. In the group of diabetic patients with AAT < 1 mg/ml, AAT directly correlated with systolic blood pressure (P = 0.048) and inversely correlated with waist-hip ratio (P = 0.031). Our results provide evidence that deficiency of AAT may be associated with an increased risk of developing Type 2 diabetes.


Clinical characteristics and response to therapy in Egyptian children infected with Schistosoma haematobium.
Forty-one Egyptian students with infections due to Schistosoma haematobium, who were selected by results of a urine screening examination, were evaluated for morbidity and response to chemotherapy. Symptoms associated with infection were hematuria, dysuria, and swimmer's itch. A positive correlation existed between the intensity of infection and frequency of exposure to water. Laboratory abnormalities included eosinophilia (41), anemia (9), hematuria (38), pyuria (33), and proteinuria (8). Three of 26 subjects had abnormalities intravenous pyelograms: hydroureter, bladder polyp , and bladder calcification. The bladder polyp was noted also by sonography. Cure rates were 66.7% in 18 subjects treated with two 10-mg/kg doses of trichlorfon and were 89.5% in 19 subjects given three doses. Those not cured had an average reduction in ova excretion of 96%. Follow-up at 12 months of 33 subjects showed that nine had S. haematobium ova in urine, although 75% admitted to exposure to canal or irrigation water in the interim.


New species and records of Dissomphalus Ashmead (Hymenoptera, Bethylidae) from Cerrado, Caatinga and relicts of the Atlantic Forest from northeastern Brazil.
The main goal of this paper is to study the Dissomphalus material deposited at the Coleção Zoológica do Maranhão (Maranhão, Brazil). The material was collected in six parks: Parque Nacional Chapada das Mesas, Parque Estadual do Mirador and Reserva Ecológica do Inhamum in the state of Maranhão; Parque Nacional Serra das Confusões and Parque Nacional de Sete Cidades in the state of Piauí, and Parque Nacional de Ubajara in the state of Ceará. Forty species are recognized from these six parks. Twenty-two of them are previously described species, namely: D. bifurcatus Azevedo, D. cervoides Azevedo, D. conicus Azevedo, D. curvilongus Azevedo, D. geniculatus Azevedo, D. gilvipes Evans, D. infissus Evans, D. krombeini Azevedo, D. laminaris Redighieri Azevedo, D. latimerus Azevedo, D. linearis Azevedo, D. lobisserratus Azevedo, D. magnus Redighieri Azevedo, D. megomphalus Evans, D. microstictus Evans, D. napo Evans, D. plaumanni Evans, D. scamatus Azevedo, D. subpilosus Azevedo, D. tubulatus Redighieri Azevedo, D. ubracus Brito Azevedo and D. verrucosus Redighieri Azevedo. Eighteen species are newly described and illustrated: Dissomphalus acutipupu Colombo Azevedo sp. nov., D. boibumba Colombo Azevedo sp. nov., D. boitata Colombo Azevedo sp. nov., D. boiuna Colombo Azevedo sp. nov., D. boto Colombo Azevedo sp. nov., D. caipora Colombo Azevedo sp. nov., D. capelobo Colombo Azevedo sp. nov., D. cuca Colombo Azevedo sp. nov., D. curupira Colombo Azevedo sp. nov., D. iara Colombo Azevedo sp. nov., D. iracema Colombo Azevedo sp. nov., D. irupe Colombo Azevedo sp. nov., D. joaquinae Colombo Azevedo sp. nov., D. jurupari Colombo Azevedo sp. nov., D. mapinguari Colombo Azevedo sp. nov., D. matintaperera Colombo Azevedo sp. nov., D. saci Colombo Azevedo sp. nov. and D. torem Colombo Azevedo sp. nov.. A key for these species is provided. The genus is newly recorded from the state of Piauí, Brazil.


Usage patterns and attitudes towards emergency contraception: the International Emergency Contraception Research Initiative.
The aim of the survey was to gain understanding of women's usage patterns and attitudes towards emergency contraception (i.e., the 'morning after pill') and to gain insight into the role and attitudes of pharmacists as providers of emergency contraception. As part of the International Emergency Contraception Research Initiative, approximately 6500 women (15-49 years) and nearly 500 pharmacists from 14 countries in Western, Central and Eastern Europe, and Central Asia completed questionnaires via web-based interrogation or computer-assisted/paper-assisted personal interviews. Common to almost all countries and cultures was that, while awareness of emergency contraception was high (≥84% of respondents, except in Kazakhstan), usage was generally low (4-18%). In Austria, the Czech Republic, Spain, and the UK, better underlying protection with hormonal contraceptives or male condoms would have meant less need for emergency contraception. In Bulgaria, Lithuania, Romania, and Russia, greater dependence on less reliable contraceptive methods such as calendar + withdrawal was associated with higher use of the emergency contraceptive pill (11-18%) but also with higher abortion rates (19-21%). Overt rejection of emergency contraception in the event of an accident was low, except in countries (e.g., Austria, Poland) where the misperception that it acts as an abortifacient was common. Except for Bulgaria, pharmacists elsewhere tended to have limited knowledge and moralistic attitudes towards emergency contraception. Improved educational efforts, probably country-specific, are required to increase the use of highly effective methods of regular contraception and overcome barriers to acceptance of emergency contraception as a suitable postcoital solution to avoid unwanted pregnancy or abortion.


Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab and tofacitinib monotherapies in rheumatoid arthritis patients who are naïve to treatment with biologic or conventional synthetic disease-modifying antirheumatic drugs: a matching-adjusted indirect comparison.
To compare improvement in pain and physical function for patients treated with baricitinib, adalimumab, tocilizumab and tofacitinib monotherapy from randomised, methotrexate (MTX)-controlled trials in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)/biologic (bDMARD)-naïve RA patients using matching-adjusted indirect comparisons (MAICs). Data were from Phase III trials on patients receiving monotherapy baricitinib, tocilizumab, adalimumab, tofacitinib or MTX. Pain was assessed using a visual analogue scale (0-100 mm) and physical function using the Health Assessment Questionnaire-Disability Index (HAQ-DI). An MAIC based on treatment-arm matching, an MAIC with study-level matching and Bucher's method without matching compared change in outcomes between therapies. Matching variables included age, gender, baseline disease activity and baseline value of outcome measure. With all methods, greater improvements were observed in pain and HAQ-DI at 6 months for baricitinib compared with adalimumab and tocilizumab (p<0.05). Differences in treatment effects (TEs) favouring baricitinib for pain VAS for treatment-arm matching, study-level matching and Bucher's method, respectively, were -12, -12 and -12 for baricitinib versus adalimumab and -7, -7 and -9 for baricitinib versus tocilizumab; the difference in TEs for HAQ-DI was -0.28, -0.28 and -0.30 for adalimumab and -0.23, -0.23 and -0.26 for tocilizumab. For baricitinib versus tofacitinib, no statistically significant differences for pain improvement were observed except with one of the three methods (Bucher method) and none for HAQ-DI. Results suggest greater pain reduction and improved physical function for baricitinib monotherapy compared with tocilizumab and adalimumab monotherapy. No statistically significant differences in pain reduction and improved physical function were observed between baricitinib and tofacitinib with the MAIC analyses.


PainVision® Apparatus for Assessment of Efficacy of Pulsed Radiofrequency Combined with Pharmacological Therapy in the Treatment of Postherpetic Neuralgia and Correlations with Measurements.
Objective. PainVision device was a developed application for the evaluation of pain intensity. The objective was to assess the efficacy and safety of pulsed radiofrequency (PRF) combined with pharmacological therapy in the treatment of postherpetic neuralgia (PHN). We also discussed the correlation of the measurements. Method. Forty patients with PHN were randomized for treatment with PRF combined with pharmacological therapy (PRF group, n = 20) or pharmacological therapy (control group, n = 20) at postoperative 48 hours. The efficacy measure was pain degree (PD) that was assessed by PainVision and visual analog scale (VAS), short form Mcgill pain questionnaire (SF-Mcgill), and numeric rate scale sleep interference score (NRSSIS). Correlations between PD, VAS, SF-Mcgill, and NRSSIS were determined. Results. The PD for persistent pain (PP) and breakthrough pain (BTP) at postoperative 48 hours assessed by PainVision were significantly lower in PRF group than in control group (PD-PP, P < 0.01; PD-BTP, P < 0.01). PD and VAS were highly correlated for both persistent pain (r = 0.453, ρ = 0.008) and breakthrough pain (r = 0.64, ρ = 0.001). Conclusion. PRF was well tolerated and superior to isolated pharmacological therapy in the treatment of PHN. PainVision device showed great value in the evaluation of pain intensity and PD had an excellent correlation with VAS and SF-Mcgill.


[Serum proteomic study on hypertension patients with Gan-Dan damp-heat syndrome].
To study the serum proteomics in hypertension patients with Gan-Dan damp-heat syndrome (GDDH) for tentatively find special proteins associated with the syndrome. Study was performed in 60 hypertensive patients and 39 healthy persons as control. In the patients enrolled, 40 were differentiated as GDDH syndrome and the other 20 as non-GDDH syndrome. Their serum proteins were captured by weak cation nano-magnetic beads, and proteomic fingerprint was made by matrix assistant laser demodulation ionizing time-of-flight mass spectrometry (MALDI-TOF-MS) through mapping with protein chip reader type PBS II-C. After all the proteomic fingerprints being analyzed by Biomarker Wizard 3.1, the special expressed proteins for GDDH syndrome were identified by Biomarker Patterns Software 5.0 to create the syndrome decision model. Totally, 182 difference protein peaks between patients of GDDH and healthy persons (P<0.05); and 132 difference protein peaks between patients of GDDH and non-GDDH were detected (P<0.05). A decision model consisted 5 screened out protein peaks with mass-to-charge ratio of 2761.555, 6624.362, 2487.192, 2461.610 and 2744.318 was created, which could well differentiate the GDDH syndrome, with the sensitivity of 96.55%, specificity of 90%, false positive rate of 10% and false negative rate of 3.45%. Further blind test for prospective check showed its sensitivity being 81.82%, specificity 89.66%, false positive rate 10.34% and false negative rate 18.18%. The differently expressed protein is the material foundation of GDDH syndrome; molecular biological decision model established on the basis of this foundation can offer a tool for making Chinese medicine syndrome differentiation more objectively and accurately.


RECENT ADVANCES IN PHARMACEUTICAL RHEOLOGY.
Significant advances in rheology of pharmaceutical and allied materials since 1965 are covered in a review of 292 references. The subject matter is divided into considerations of powders, suspensions and suspending agents, semi-solids (creams and ointments), emulsions, suppositories and pessaries, foam aerosols and a general section. Material related to tablets, biorheology, and surface and interfacial films is not considered.


The rem mutations in the ATP-binding groove of the Rad3/XPD helicase lead to Xeroderma pigmentosum-Cockayne syndrome-like phenotypes.
The eukaryotic TFIIH complex is involved in Nucleotide Excision Repair and transcription initiation. We analyzed three yeast mutations of the Rad3/XPD helicase of TFIIH known as rem (recombination and mutation phenotypes). We found that, in these mutants, incomplete NER reactions lead to replication fork breaking and the subsequent engagement of the homologous recombination machinery to restore them. Nevertheless, the penetrance varies among mutants, giving rise to a phenotype gradient. Interestingly, the mutations analyzed reside at the ATP-binding groove of Rad3 and in vivo experiments reveal a gain of DNA affinity upon damage of the mutant Rad3 proteins. Since mutations at the ATP-binding groove of XPD in humans are present in the Xeroderma pigmentosum-Cockayne Syndrome (XP-CS), we recreated rem mutations in human cells, and found that these are XP-CS-like. We propose that the balance between the loss of helicase activity and the gain of DNA affinity controls the capacity of TFIIH to open DNA during NER, and its persistence at both DNA lesions and promoters. This conditions NER efficiency and transcription resumption after damage, which in human cells would explain the XP-CS phenotype, opening new perspectives to understand the molecular basis of the role of XPD in human disease.


Should nasogastric tube insertion during the COVID-19 pandemic be considered as an aerosol-generating procedure?
Nasogastric tubes are used frequently in surgical patients for bowel decompression, provision of enteral nutritional support and preventing aspiration of gastric contents. There is no conclusive research into the risk of COVID-19 transmission associated with nasogastric tube insertion, although evidence from the severe acute respiratory syndrome outbreak appears to suggest that there is no increased risk of transmission. However, close contact with a COVID-19 patient, especially those displaying respiratory symptoms, is likely to increase the risk of transmission. Nasogastric tube insertion requires increased time spent at a patient's bedside and can also cause pharyngeal irritation, resulting in coughing. In addition, the nasogastric tube can expose the healthcare worker to potentially infectious saliva. Therefore, there is a clear need for increased evidence regarding the risk of transmission associated with nasogastric tube insertion, to ensure that such risks can be mitigated.


Understanding the role of gold nanoparticles in enhancing the catalytic activity of manganese oxides in water oxidation reactions.
The Earth-abundant and inexpensive manganese oxides (MnOx) have emerged as an intriguing type of catalysts for the water oxidation reaction. However, the overall turnover frequencies of MnOx catalysts are still much lower than that of nanostructured IrO2 and RuO2 catalysts. Herein, we demonstrate that doping MnOx polymorphs with gold nanoparticles (AuNPs) can result in a strong enhancement of catalytic activity for the water oxidation reaction. It is observed that, for the first time, the catalytic activity of MnOx/AuNPs catalysts correlates strongly with the initial valence of the Mn centers. By promoting the formation of Mn(3+) species, a small amount of AuNPs (<5%) in α-MnO2/AuNP catalysts significantly improved the catalytic activity up to 8.2 times in the photochemical and 6 times in the electrochemical system, compared with the activity of pure α-MnO2.


Multiple losses of neutral C14H14 in the tandem mass spectrometry of several perbenzyl ether intermediates in the synthesis of green tea constituents.
Electrospray and matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry (MS/MS) experiments were used to investigate an unusual fragmentation in collision-induced dissociation (CID) of sodiated and potassiated perbenzyl ether intermediates obtained in the total synthesis of gallate ester constituents of green tea. Prominent fragments correspond to multiple sequential losses of neutral C14H14 that were not observed in the protonated and ammoniated species, that instead present fragment ion series in which members are separated by C7H6. High-resolution MALDI quadrupole time-of-flight (Q-TOF) and electrospray-Fourier transform mass spectrometry (FTMS) were used to confirm elemental compositions of these and related ions.


Cosmic radiation exposure of biological test systems during the EXPOSE-E mission.
In the frame of the EXPOSE-E mission on the Columbus external payload facility EuTEF on board the International Space Station, passive thermoluminescence dosimeters were applied to measure the radiation exposure of biological samples. The detectors were located either as stacks next to biological specimens to determine the depth dose distribution or beneath the sample carriers to determine the dose levels for maximum shielding. The maximum mission dose measured in the upper layer of the depth dose part of the experiment amounted to 238±10 mGy, which relates to an average dose rate of 408±16 μGy/d. In these stacks of about 8 mm height, the dose decreased by 5-12% with depth. The maximum dose measured beneath the sample carriers was 215±16 mGy, which amounts to an average dose rate of 368±27 μGy/d. These values are close to those assessed for the interior of the Columbus module and demonstrate the high shielding of the biological experiments within the EXPOSE-E facility. Besides the shielding by the EXPOSE-E hardware itself, additional shielding was experienced by the external structures adjacent to EXPOSE-E, such as EuTEF and Columbus. This led to a dose gradient over the entire exposure area, from 215±16 mGy for the lowest to 121±6 mGy for maximum shielding. Hence, the doses perceived by the biological samples inside EXPOSE-E varied by 70% (from lowest to highest dose). As a consequence of the high shielding, the biological samples were predominantly exposed to galactic cosmic heavy ions, while electrons and a significant fraction of protons of the radiation belts and solar wind did not reach the samples.


Further evidence for the involvement of cyclic AMP in Ca2+-dependent, but not Ca2+-independent, noradrenaline release in the rabbit pulmonary artery.
Strips of the rabbit pulmonary artery were incubated with 3H-noradrenaline and subsequently superfused. In strips superfused with Ca2+-free solution containing K+ 64.7 mmol/l, tritium overflow was stimulated by introduction of Ca2+ 1.6 mmol/l; in strips superfused with physiological salt solution, stimulation was carried out with veratridine 30 mumol/l, acetylcholine 1 mmol/l (in the presence of atropine 1 mumol/l) or tyramine 100 mumol/l. The Ca2+-, veratridine- or acetylcholine-induced tritium overflow was facilitated by forskolin, AH 21-132 (a cAMP phosphodiesterase inhibitor) and/or 8-Br-cAMP, i.e. compounds which increase intraneuronal cAMP content. In contrast, the Ca2+-independent tyramine-evoked tritium overflow was not affected by these drugs. It is concluded that cAMP is involved in the regulation of stimulation-evoked Ca2+-dependent noradrenaline release, and that the sympathetic nerve terminals are endowed with an adenylate cyclase system. Facilitation of release may be caused by an alteration of Ca2+ influx or utilization.


A less-than-perfect experience.
Plastic surgical nurses frequently work with pediatric patients who have physical or cognitive differences. In a society that puts such high value on physical appearance and perfection, these children are vulnerable to discrimination. Parents and children look to the plastic surgical nurse for support and acceptance.


Role of peak current in conversion of patients with ventricular fibrillation.
Peak currents are the final arbiter of defibrillation in patients with ventricular fibrillation (VF). However, biphasic defibrillators continue to use energy in joules for electrical conversion in hopes that their impedance compensation properties will address transthoracic impedance (TTI), which must be overcome when a fixed amount of energy is delivered. However, optimal peak currents for conversion of VF remain unclear. We aimed to determine the role of peak current and optimal peak levels for conversion in collapsed VF patients. Adult, non-pregnant patients presenting with non-traumatic VF were included in the study. All defibrillations that occurred were included. Impedance values during defibrillation were used to calculate peak current values. The endpoint was return of spontaneous circulation (ROSC). Of the 197 patients analysed, 105 had ROSC. Characteristics of patients with and without ROSC were comparable. Short duration of collapse < 10 minutes correlated positively with ROSC. Generally, patients with average or high TTI converted at lower peak currents. 25% of patients with high TTI converted at 13.3 ± 2.3 A, 22.7% with average TTI at 18.2 ± 2.5 A and 18.6% with low TTI at 27.0 ± 4.7 A (p = 0.729). Highest peak current conversions were at < 15 A and 15-20 A. Of the 44 patients who achieved first-shock ROSC, 33 (75.0%) received < 20 A peak current vs. > 20 A for the remaining 11 (25%) patients (p = 0.002). For best effect, priming biphasic defibrillators to deliver specific peak currents should be considered.


A ligand-receptor interactome platform for discovery of pain mechanisms and therapeutic targets.
In the peripheral nervous system, ligand-receptor interactions between cells and neurons shape sensory experience, including pain. We set out to identify the potential interactions between sensory neurons and peripheral cell types implicated in disease-associated pain. Using mouse and human RNA sequencing datasets and computational analysis, we created interactome maps between dorsal root ganglion (DRG) sensory neurons and an array of normal cell types, as well as colitis-associated glial cells, rheumatoid arthritis-associated synovial macrophages, and pancreatic tumor tissue. These maps revealed a common correlation between the abundance of heparin-binding EGF-like growth factor (HBEGF) in peripheral cells with that of its receptor EGFR (a member of the ErbB family of receptors) in DRG neurons. Subsequently, we confirmed that increased abundance of HBEGF enhanced nociception in mice, likely acting on DRG neurons through ErbB family receptors. Collectively, these interactomes highlight ligand-receptor interactions that may lead to treatments for disease-associated pain and, furthermore, reflect the complexity of cell-to-neuron signaling in chronic pain states.


Endotypes in T1D: B lymphocytes and early onset.
Although type 1 diabetes (T1D) is characterized by destruction of the pancreatic beta cells by self-reactive T cells, it has become increasingly evident that B cells also play a major role in disease development, likely functioning as antigen-presenting cells. Here we review the biology of islet antigen-reactive B cells and their participation in autoimmune diabetes. Relative to late onset, individuals who develop T1D at an early age display increased accumulation of insulin-reactive B cells in islets. This B-cell signature is also associated with rapid progression of disease and responsiveness to B-cell depletion therapy. Also suggestive of B-cell participation in disease is loss of anergy in high-affinity insulin-reactive B cells. Importantly, loss of anergy is seen in patient's healthy first-degree relatives carrying certain T1D risk alleles, suggesting a role early in disease development. Recent studies indicate that islet-reactive B cells may play a pathogenic role very early in T1D development in young patients, and suggest utility of therapies that target these cells.


Dynamically controlling the emission of single excitons in photonic crystal cavities.
Single excitons in semiconductor microcavities represent a solid state and scalable platform for cavity quantum electrodynamics, potentially enabling an interface between flying (photon) and static (exciton) quantum bits in future quantum networks. While both single-photon emission and the strong coupling regime have been demonstrated, further progress has been hampered by the inability to control the coherent evolution of the cavity quantum electrodynamics system in real time, as needed to produce and harness charge-photon entanglement. Here using the ultrafast electrical tuning of the exciton energy in a photonic crystal diode, we demonstrate the dynamic control of the coupling of a single exciton to a photonic crystal cavity mode on a sub-nanosecond timescale, faster than the natural lifetime of the exciton. This opens the way to the control of single-photon waveforms, as needed for quantum interfaces, and to the real-time control of solid-state cavity quantum electrodynamics systems.


Association between Survival Time and Changes in NT-proBNP in Cats Treated for Congestive Heart Failure.
Reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations after treatment have been associated with improved survival in people with congestive heart failure (CHF), but have not been reported in cats with CHF. To evaluate changes in NT-proBNP concentrations in cats with CHF after treatment and determine whether serial NT-proBNP measurements provide prognostic information. Thirty-one client-owned cats. Prospective, observational study in cats with new onset CHF secondary to cardiomyopathy. Concentrations of NT-proBNP were measured within 4 hours of admission to the hospital, on the day of discharge, and at re-evaluation 7-10 days later. Median NT-proBNP concentrations decreased significantly from admission (1,713 pmol/L [range, 160-3,784 pmol/L]) to discharge (902 pmol/L [range, 147-3,223 pmol/L]); P = .005) and from admission to re-evaluation (1,124 pmol/L [range, 111-2,727 pmol/L]; P = .024). Median survival time was 109 days (range, 1-709 days), with 5 cats still alive at the time of analysis. Cats with a larger percent decrease in NT-proBNP from admission to discharge had a longer survival time (P = .048). Cats with evidence of active CHF at the time of re-evaluation (P = .010) and cats whose owners had difficulty administering medications (P = .045) had shorter survival times. Cats with a larger percent decrease in NT-proBNP during hospitalization and no evidence of CHF at the time of re-evaluation had longer survival times. Additional studies are needed to determine whether NT-proBNP can help guide treatment in cats with CHF.


Effects of normovolemic hemodilution on blood flow in the rabbit ear.
The effect of isovolemic hemodilution using dextran-60 on arterial blood flow in the rabbit ear was investigated. The animals were anesthetized and an electromagnetic flow probe was applied around the central artery of the ear. Isovolemic hemodilution was performed during a 15 min exchange period. Two degrees of hemodilution were investigated [8.5 and 17 ml dextran-60/kg body weight (b.w.)] and compared with a nontreated control group. The two levels of hemodilution induced reductions in hematocrit to 29 and 21%, respectively, from the control level of about 40%. In all groups, blood pressure maintained constant levels throughout each experiment, which lasted 240 min. In the controls, ear artery blood flow was unchanged or decreased slightly during the experiment. The lower level of hemodilution caused a slight increase of blood flow after 4 h. In the group treated with 17 ml/kg b.w. dextran, blood flow gradually increased after 90 min following hemodilution. After 240 min, flow rates had increased to two- or threefold the initial rate in this group. Although other possibilities exist, the increased blood flow following hemodilution may be interpreted as reflecting a decreased resistance to flow in the tissue due to the decreased viscosity of the blood.


Efficacy and safety of low dose desmopressin orally disintegrating tablet in women with nocturia: results of a multicenter, randomized, double-blind, placebo controlled, parallel group study.
Previous studies suggest a lower dose of desmopressin orally disintegrating tablet may be effective in females compared to males with nocturia. We confirm the efficacy and safety of 25 μg desmopressin orally disintegrating tablet compared to placebo in female patients. In this 3-month, randomized, double-blind, parallel group study 25 μg desmopressin once daily was compared to placebo in women with nocturia (2 or more nocturnal voids). The co-primary efficacy end points were change from baseline in mean number of nocturnal voids and proportion of patients achieving at least a 33% reduction from baseline in the mean number of nocturnal voids (33% responders). The full analysis set comprised 261 patients (age range 19 to 87 years). Desmopressin significantly reduced the mean number of nocturnal voids and increased the odds of a 33% or greater response compared to placebo during 3 months, assessed by longitudinal analysis (-0.22, p = 0.028 and OR 1.85, p = 0.006, respectively). Desmopressin increased the mean time to first nocturnal void by 49 minutes compared to placebo at 3 months (p = 0.003). The response to desmopressin was seen by week 1 of treatment and was sustained throughout the trial. Significant increases in health related quality of life and sleep quality were observed compared to placebo. Desmopressin was well tolerated. Serum sodium levels remained greater than 125 mmol/L throughout the trial and 3 transient decreases to less than 130 mmol/L were recorded. At a dose of 25 μg, desmopressin orally disintegrating tablet is an effective and well tolerated treatment for women with nocturia. Treatment provides rapid and sustained improvement in nocturia and quality of life.


Differential expression and cytoplasm/membrane distribution of endoglin (CD105) in human tumour cell lines: Implications in the modulation of cell proliferation.
Endoglin (CD105, an accessory component of the TGF-beta receptor complex) expression and distribution on different human tumour cells and its role in cellular proliferation were evaluated. We examined: 1) sixteen human carcinoma cell lines, 2) eight human sarcoma cell lines, 3) five miscellaneous tumour cell lines. HECV (endothelial cells) were employed as a positive control for endoglin expression. Normal Human Dermal Fibroblasts (NHDF) and 293 cells (epithelial kidney cells) were used as normal controls for connective and epithelial tissues, respectively. The results showed that CD105 was poorly expressed in the majority of human carcinoma cells (10/16), whereas it was highly expressed in most human sarcoma cells (7/8), and differently expressed by miscellaneous tumour cell lines. These data reflect endoglin expression by the normal counterparts of tumour cell lines, i.e. NHDF and 293 cells. However, CD105 levels in sarcoma cell lines, even though consistently lower than in NHDF, were significantly higher than those observed in carcinoma cells. Interestingly, CD105 presented a strong expression in the cytoplasm of MDA-MB-453 (breast carcinoma), NPA (papillary thyroid carcinoma), COLO-853 (melanoma) and SaOS-2 (osteosarcoma), but was weakly expressed on their cell membrane. This differential expression in the cytoplasm and on the membrane of some tumour cells, suggests a complex mechanism of translocation for this protein. The analysis of clonal growth in soft agar of some cell lines, characterized by high CD105 expression, showed an increased colony formation potential that was antagonized by the addition of anti-CD105 blocking mAb. The results indicated that endoglin is differentially expressed in human carcinoma and sarcoma cells and its overexpression modulates the proliferative rate of human solid tumour cells. Moreover, these data suggest that CD105 is involved in the regulation of TGF-beta effects in human solid malignancies, and therefore it could play an important role in tumour diagnosis and treatment.


GABAergic modulation is involved in the ventrolateral orbital cortex 5-HT 1A receptor activation-induced antinociception in the rat.
The ventrolateral orbital cortex (VLO) is a component of an endogenous analgesic system consisting of an ascending pathway from the spinal cord to VLO via the thalamic nucleus submedius (Sm) and a descending pathway relaying in the periaqueductal gray matter (PAG). This study examines whether the activation of 5-HT 1A receptors in VLO produces antinociception and whether GABAergic modulation is involved in the VLO 5-HT 1A receptor activation-evoked antinociception. The radiant heat-evoked tail flick (TF) reflex was used as an index of nociceptive response in lightly anesthetized rats. Microinjection of the 5-HT 1A receptor agonist 8-OH-DPAT (1.0, 2.0, 5.0 microg) into VLO produced dose-dependent antinociception, which was reversed by the 5-HT 1A receptor antagonist (NAN-190, 20 mug). We also found that VLO application of the GABA A receptor antagonist bicuculline or picrotoxin (100 ng) enhanced the 8-OH-DPAT-induced inhibition of the TF reflex, whereas the GABA A receptor agonist muscimol (250 ng) or THIP (1.0 microg) significantly attenuated the 8-OH-DPAT-induced inhibition. These results suggest that 5-HT 1A receptors are involved in VLO-induced antinociception and that GABAergic disinhibitory mechanisms participate in the 5-HT 1A receptor-mediated effect. These findings provide support for the hypothesis that 5-HT 1A receptor activation may inhibit the inhibitory action of the GABAergic interneurons on the output neurons projecting to PAG leading to activation of the brainstem descending inhibitory system and depression of nociceptive inputs at the spinal cord level.


Dental management service organizations. Lessons from medicine.
While management service organizations are new to dentistry, they have existed in medicine for many years. The author examined why they developed and what happened to three of them during 1998 to provide dentistry with insights into the future of dental management service organizations, or DMSOs. The author identified and examined the three largest physician practice management firms, or PPMs, as of early 1998. He monitored their stock prices and fiscal changes through 1998. He also tracked all publicly traded DMSOs for growth and evaluated their stock price changes. Economic pressures to control the cost of health care led to the development of organizational structures designed to increase the cost effectiveness of, and to control more variables associated with, health care delivery. The lure of vertical integration of health care delivery with the resultant control of multiple variables-including primary and specialty care, pharmaceuticals and hospitals-promoted the development of many PPMs and DMSOs, although many variables differ for dentistry. The realities associated with the loss of control in the corporate model, the lack of sufficient operating margins to support investor expectations and plummeting stock prices call into question the wisdom of universally embracing similar models for dentistry.


Utility of Rectus Abdominis Ultrasound as a Respiratory Function Test for Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) causes deterioration of respiratory function. Muscle weakness of the orbicularis oris interferes with the accurate assessment of respiratory function using spirometry. Reduced forced vital capacity (FVC) is an indicator that helps determine the appropriate timing to provide noninvasive ventilation (NIV) for the survival of ALS patients. We employed ultrasonography to evaluate changes in respiratory function by measuring the thickness of the rectus abdominis (RA) muscle as a possible alternative to spirometry. Sixteen subjects with ALS were included in this study. The thickness of RA muscles was measured using ultrasonography, and respiratory fluctuations, such as vital capacity (VC), FVC, FEV1, percentage of predicted VC (%VC), percentage of predicted FVC (%FVC), percentage of predicted FEV1 (%FEV1), and FEV1/FVC, were evaluated using spirometry. Sixteen subjects underwent assessment by ultrasonography. A positive correlation was observed between the percent change in RA muscle thickness evaluated from maximal expiration to maximal inspiration and %VC (P = .001), %FVC (P = .001), FEV1 (P = .009), and %FEV1 (P = .02). RA ultrasonography was useful for predicting a reduction in VC in subjects with ALS and may help determine the best timing for introducing NIV.


A validation of estimated total peripheral resistance using twin data.
Chronically elevated total peripheral resistance (TPR) is a suspected contributor to the greater rates of hypertension in African Americans. Previous research suggests that over 50% of the variability in measures of vascular resistance may be attributable to genetic effects and genetic effects may play an even greater role in variability of TPR in African Americans. We have previously demonstrated the coherence of a simple equation-based estimate of total peripheral resistance (TPRest) with TPR obtained via a validated method (Hill et al, 2013). We sought further validation by estimating heritability for this measure. Using quantitative genetic analysis, heritabilites were calculated for TPRest during both a resting baseline and orthostasis in a population-based sample of African American mono- and dizygotic twins (mean age = 49.82 ± 14.62). Estimated heritability was greater for males (h2 = .40) both at rest and during orthostasis, compared to all other groups. This value is consistent with previously published point estimates of heritability. Collectively, these findings provide additional support for the validity of TPRest as a practical alternative for deriving additional hemodynamic data from archival sources.


Statistical approach for the enhanced production of cold-active β-galactosidase from Thalassospira frigidphilosprofundus: a novel marine psychrophile from deep waters of Bay of Bengal.
In the present investigation Thalassospira frigidphilosprofundus, a novel species from the deep waters of the Bay of Bengal, was explored for the production of cold-active β-galactosidase by submerged fermentation using marine broth medium as the basal medium. Effects of various medium constituents, namely, carbon, nitrogen source, pH, and temperature, were investigated using a conventional one-factor-at-a-time method. It was found that lactose, yeast extract, and bactopeptones are the most influential components for β-galactosidase production. Under optimal conditions, the production of β-galactosidase was found to be 3,864 U/mL at 20 ± 2°C, pH 6.5 ± 0.2, after 48 hr of incubation. β-Galactosidase production was further optimized by the Taguchi orthogonal array design of experiments and the central composite rotatable design (CCRD) of response surface methodology. Under optimal experimental conditions the cold-active β-galactosidase enzyme production from Thalassospira frigidphilosprofundus was enhanced from 3,864 U/mL to 10,657 U/mL, which is almost three times higher than the cold-active β-galactosidase production from the well-reported psychrophile Pseudoalteromonas haloplanktis.


CT Image Conversion among Different Reconstruction Kernels without a Sinogram by Using a Convolutional Neural Network.
The aim of our study was to develop and validate a convolutional neural network (CNN) architecture to convert CT images reconstructed with one kernel to images with different reconstruction kernels without using a sinogram. This retrospective study was approved by the Institutional Review Board. Ten chest CT scans were performed and reconstructed with the B10f, B30f, B50f, and B70f kernels. The dataset was divided into six, two, and two examinations for training, validation, and testing, respectively. We constructed a CNN architecture consisting of six convolutional layers, each with a 3 × 3 kernel with 64 filter banks. Quantitative performance was evaluated using root mean square error (RMSE) values. To validate clinical use, image conversion was conducted on 30 additional chest CT scans reconstructed with the B30f and B50f kernels. The influence of image conversion on emphysema quantification was assessed with Bland-Altman plots. Our scheme rapidly generated conversion results at the rate of 0.065 s/slice. Substantial reduction in RMSE was observed in the converted images in comparison with the original images with different kernels (mean reduction, 65.7%; range, 29.5-82.2%). The mean emphysema indices for B30f, B50f, converted B30f, and converted B50f were 5.4 ± 7.2%, 15.3 ± 7.2%, 5.9 ± 7.3%, and 16.8 ± 7.5%, respectively. The 95% limits of agreement between B30f and other kernels (B50f and converted B30f) ranged from -14.1% to -2.6% (mean, -8.3%) and -2.3% to 0.7% (mean, -0.8%), respectively. CNN-based CT kernel conversion shows adequate performance with high accuracy and speed, indicating its potential clinical use.


Comments on an obstructed death -- a case conference revisited: commentary 1.
The paper comments on Scott Dunbar's "An obstructed death and medical ethics," arguing contra Dunbar that we should not view truth-telling to the terminally ill as primarily governed by principles of veracity and respect for autonomy. All such rules are of limited value in medical ethics. We should instead turn to an ethics deriving from the centrality of moral relationships and virtues. A brief analysis of the connections between moral relationships and moral rules is offered. Such an ethics would lower the value that philosophical fashion places on truth-telling and autonomy and leave decisions about truth-telling and the terminally ill more dependent on the circumstances of particular cases.


Physical Activity and Bone Health in Men: A Systematic Review and Meta-Analysis.
Research on osteoporosis and physical activity often focuses on women. We aimed to conduct a systematic review to assess the benefits and harms of physical activity interventions for men's bone health. We used standard methods and searched for randomized controlled trials (RCTs) (duration, ≥6 months) published in all languages across multiple databases and trial registries. The last search was conducted on July 22, 2020. We included 11 studies (14 publications), resulting in a sample of N=723 men (range, 17-132 participants). We found low-certainty evidence that physical activity has little influence on the areal bone mineral density (aBMD) at the total hip (5 RCTs, N=324; mean difference [MD], 0.03 [95 confidence interval (CI), 0.01 to 0.05]) and little or no influence on the aBMD at the femoral neck (3 RCTs, N=186; MD, 0.00 [95% CI, -0.04 to 0.04]), lumbar spine (3 RCTs; N=213; MD, 0.05 [95% CI, -0.01 to 0.11]), and whole body (4 RCTs, N=203; MD, -0.00 [95% CI, -0.03 to 0.02]). We found low-certainty evidence that physical activity (≥6 months) has some effect on the total hip in men, but new evidence may change this finding. This review highlights the gap in the evidence on specific intervention prescriptions that can benefit the bone geometry, structure, microarchitecture, and, ultimately, bone strength in men. Future research should engage in comprehensive reporting of harms, quality of life outcomes, advanced imaging findings, and long-term interventions.


Prenatal diagnosis of endocardial fibroelastosis.
In a case of fetal heart failure caused by endocardial fibroelastosis, prenatal echocardiography clearly demonstrated a thickened endocardium. We therefore suggest that an abnormal endocardium may be detected in utero by ultrasound, thus representing an important clue in the differential diagnosis of fetal nonimmune hydrops and in the evaluation of pregnancies at risk for endocardial fibroelastosis.


Awareness of albuminuria in an Italian population-based cohort of patients treated with hypoglycemic drugs.
Albuminuria is a powerful predictor of renal and cardiovascular outcomes in type 2 diabetes and a good indicator of the evolution of renal disease. Our aim was to obtain information concerning the identification of albuminuria as well as the utilization of antihypertensive, lipid-lowering and antiplatelet drugs in patients with diabetes. Subjects were enrolled from individuals registered with 3 Italian local health units by querying the drugs reimbursable, hospital laboratory investigation and hospital discharge databases. The determination of albumin to creatinine ratio (ACR) throughout 2007 and 2008 was defined as the index date. Patients who received at least 2 prescriptions of hypoglycemic drugs in the 12 months before the index date were classified as diabetics. We looked also for prescriptions of antihypertensive, lipid-lowering and antiplatelet drugs. Among a population of 701,133 subjects, we identified 29,350 patients with diabetes (4.2% of the cohort). ACR had been determined in 5,644 diabetic subjects (19.2% of that cohort). The prevalence of determination of ACR in nontreated subjects was 16.0%, while in treated subjects, it ranged from 13.6% to 34.9% according to different schedules of treatment. Drugs acting on the renin-angiotensin system were prescribed in more then 80% of diabetics. The ratio of angiotensin receptor blockers to angiotensin-converting enzyme inhibitors regimen was 0.64 in subjects without determination of ACR, 0.88 in subjects with normal albuminuria, 1.02 in subjects with microalbuminuria and 1.43 in subjects with macroalbuminuria. Our methodology can easily be applied to obtain an epidemiological view of albuminuria and pharmacological treatments of diabetics in a general population.


The mitochondrial phylogeny of land plants shows support for Setaphyta under composition-heterogeneous substitution models.
Congruence among analyses of plant genomic data partitions (nuclear, chloroplast and mitochondrial) is a strong indicator of accuracy in plant molecular phylogenetics. Recent analyses of both nuclear and chloroplast genome data of land plants (embryophytes) have, controversially, been shown to support monophyly of both bryophytes (mosses, liverworts, and hornworts) and tracheophytes (lycopods, ferns, and seed plants), with mosses and liverworts forming the clade Setaphyta. However, relationships inferred from mitochondria are incongruent with these results, and typically indicate paraphyly of bryophytes with liverworts alone resolved as the earliest-branching land plant group. Here, we reconstruct the mitochondrial land plant phylogeny from a newly compiled data set. When among-lineage composition heterogeneity is accounted for in analyses of codon-degenerate nucleotide and amino acid data, the clade Setaphyta is recovered with high support, and hornworts are supported as the earliest-branching lineage of land plants. These new mitochondrial analyses demonstrate partial congruence with current hypotheses based on nuclear and chloroplast genome data, and provide further incentive for revision of how plants arose on land.


Impact of Choroidal Melanoma Characteristics on Progression-Free Survival in Patients Undergoing Hypofractionated Stereotactic Photon Radiotherapy.
In an effort to replace ultrasonography-based thickness measurements, we investigated whether choroidal melanoma characteristics are related to progression-free survival (PFS) in patients monitored after linear accelerator (LINAC)-based hypofractionated stereotactic photon radiotherapy. In a retrospective dataset, we used a linear mixed model to assess the associations between PFS and tumor characteristics; in particular, thickness, largest basal diameter (LBD), base area and volume. Thickness and LBD are statistically significantly associated with PFS. In a subgroup of 16 patients undergoing enucleation due to melanoma recurrence or progression, there were statistically significant changes in mean thickness and LBD before surgery. Mean PFS was 42 ± 30 months. Ultrasonography-based thickness measurements may not be necessary for treated choroidal melanoma monitoring; instead, we propose sequential LBD assessments, which should preferably be performed using fundus photography in future.


POMzites: A Family of Zeolitic Polyoxometalate Frameworks from a Minimal Building Block Library.
We describe why the cyclic heteropolyanion [P8W48O184]40- (abbreviated as {P8W48}) is an ideal building block for the construction of intrinsically porous framework materials by classifying and analyzing >30 coordination polymers incorporating this polyoxometalate (POM) ligand. This analysis shows that the exocyclic coordination of first-row transition metals (TMs) to {P8W48} typically yields frameworks which extend through {W-O-TM-O-W} bridges in one, two, or three dimensions. However, despite the rich structural diversity of such compounds, the coordination of TMs to the {P8W48} ring is poorly understood, and therefore largely unpredictable, and had not until now been present with any structural classification that could allow rational design. Herein, not only do we present a new approach to understand and classify this new class of materials, we also present three {P8W48}-based frameworks which complement those frameworks which have previously been described. These new compounds help us postulate a new taxonomy of these materials. This is possible because the TM coordination sites of the {P8W48} ring are found, once fully mapped, to lead to well-defined classes of connectivity. Together, analysis provides insight into the nature of the building block connectivity within each framework, to facilitate comparisons between related structures, and to fundamentally unite this family of compounds. Hence we have tentatively named these compounds as "POMzites" to reflect the POM-based composition and zeolitic nature of each family member, although crucially, POMzites differ from zeolites in the modular manner of their preparation. As the synthesis of further POMzites is anticipated, the classification system and terminology introduced here will allow new compounds to be categorized and understood in the context of the established materials. A better understanding of TM coordination to the {P8W48} ring may allow the targeted synthesis of new frameworks rather than the reliance on serendipity apparent in current methods.


Adjuvant therapy of resected non-small-cell lung cancer.
Surgical resection of early-stage non-small-cell lung cancer (NSCLC) remains the standard of care in patients fit for surgery. Careful preoperative staging is imperative, as is pathologic documentation of the mediastinal nodal contents. Adjuvant postoperative thoracic radiation therapy (RT) clearly has an impact in reducing locoregional recurrence but has no clear impact on survival. The Postoperative RT (PORT) metaanalysis raised concerns about PORT, particularly in stage I/II NSCLC, suggesting it may negatively impact survival. This was not a concern in stage III NSCLC, in which the risk of locoregional recurrence is higher. However, distant recurrence remains the dominant pattern in resected NSCLC, suggesting that the majority of patients with early-stage resected NSCLC harbor occult micrometastatic disease. Historically, the role of adjuvant chemotherapy has been controversial, and its routine use was not supported by the published data, which consisted of a small number of underpowered trials using inadequately delivered, antiquated chemotherapy. More recently, larger trials have been reported with conflicting results. Like adjuvant PORT, chemotherapy combined with RT has not improved survival over PORT alone. The use of adjuvant cisplatin-based therapy did not show a survival advantage in the Adjuvant Lung Project Italy study but did in the International Adjuvant Lung Trial, creating controversy in the routine implementation of adjuvant therapy in all patients. Recently completed randomized trials by the Cancer and Leukemia Group B and the National Cancer Institute of Canada provide convincing evidence of a substantial benefit from adjuvant therapy in well-staged and completely resected stage I/II NSCLC. Currently, the totality of the data supports a discussion with patients with resected NSCLC regarding the potential benefits of adjuvant therapy.


Cell surface expression of the bovine leukemia virus-binding receptor on B and T lymphocytes is induced by receptor engagement.
Bovine leukemia virus (BLV), one of the most common infectious viruses of cattle, is endemic in many herds. Approximately 30-40% of adult cows in the United States are infected by this oncogenic C-type retrovirus and 1-5% of animals will eventually develop a malignant lymphoma. BLV, like the human and simian T cell leukemia viruses, is a deltaretrovirus but, in contrast with the latter, the BLV receptor remains unidentified. In this study, we demonstrate that the amino-terminal 182 residues of the BLV envelope glycoprotein surface unit encompasses the receptor-binding domain. A bona fide interaction of this receptor-binding domain with the BLV receptor was demonstrated by specific interference with BLV, but not human T cell leukemia virus, envelope glycoprotein-mediated binding. We generated a rabbit Ig Fc-tagged BLV receptor-binding domain construct and ascertained that the ligand binds the BLV receptor on target cells from multiple species. Using this tool, we determined that the BLV-binding receptor is expressed on differentiating pro/pre-B cells in mouse bone marrow. However, the receptor was not detected on mature/quiescent B cells but was induced upon B cell activation. Activation of human B and T lymphocytes also induced surface BLV-binding receptor expression and required de novo protein synthesis. Receptor levels were down-regulated as activated lymphocytes returned to quiescence. In the human thymus, BLV-binding receptor expression was specifically detected on thymocytes responding to the IL-7 cytokine. Thus, expression of the BLV-binding receptor is a marker of enhanced metabolic activity in B cells, T cells, and thymocytes.


Recurrent DMD Deletions Highlight Specific Role of Dp71 Isoform in Soft-Tissue Sarcomas.
Soft-tissue sarcomas (STS) are rare tumors whose oncogenesis remains unknown and for which no common therapeutic target has yet been identified. Analysis of 318 STS by CGH array evidenced a frequent deletion affecting the DMD gene (encoding dystrophin isoforms) in 16.5% of STS, including sarcomas with complex genomics, gastrointestinal tumors (GIST), and synovial sarcomas (SS). These deletions are significantly associated with metastatic progression, thus suggesting the role of DMD downregulation in the acquisition of aggressive phenotypes. We observed that targeted deletions of DMD were restricted to the 5' region of the gene, which is responsible for the transcription of Dp427. Analysis of STS tumors and cell lines by RNA sequencing revealed that only the Dp71 isoform was widely expressed. Dp427 depletion had no effect on cell growth or migration. However, Dp71 inhibition by shRNA dramatically reduced the cell proliferation and clonogenicity of three STS cell lines, likely by altering the cell cycle progression through the G2/M-phase. Our work demonstrates that DMD deletions are not restricted to myogenic tumors and could be used as a biomarker for metastatic evolution in STS. Dp71 seems to play an essential role in tumor growth, thus providing a potential target for future STS treatments.


Lesions of Marek's disease in some modified cutaneous appendages of chicken.
Studies were undertaken to determine the presence of lesions and immuno-fluorescent (IF) antigen of Marek's disease (MD) in the comb, wattles and skin overlaying the shank of MD affected birds. Lesions were more common in the comb than in the wattles and shanks, and were characterized by degeneration of epithelial lining cells and accumulation of lympho-reticular cells around the blood vessels of the dermis. Diffuse infiltration of these cells replacing varialbe areas of dermis were also seen in some cases. Immunofluorescent antigen was mostly confined to epidermal epithelium and was detected in comb from majority of cases, and the frequency of detection of IF antigen was similar to the presence of MD lesions in these tissues. This study indicates that the presence of lesions and viral antigen (If) of MD in these cutaneous appendages might play a significant role in epidemiology and diagnosis of this disease.


Thyroid Hormone Profile in Patients With Acute Coronary Syndrome.
Thyroid hormone has the a major role in the cardiovascular system function and cardiac a As well as to maintain the cardiovascular homeostasis A slightly change ind thyroid status actually affects cardiovascular mortality hemodynamic. The background of this study was to define the prevalence of thyroid dysfunction in acute coronary syndrome (ACS). The primary objective was to define the prevalence of thyroid dysfunction in acute coronary syndrome, including Non-ST Segment Elevation Myocardial Infarction (NSTEMI), ST-segment Elevation Myocardial Infarction (STEMI), and unstable angina groups. The secondary objective was to determine any associations of thyroids function tests with cardiac catheterization and mortality. In a prospective, observational, and cross section study, we enrolled 400 patients admitted at the coronary care unit of King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Venous blood samples were collected from patients for the evaluation of thyroid function (thyroids stimulating hormones, free triiodothyronine, and free thyroxin). Excluding those taking thyroid hormone preparations, 76.7% of patients admitted with acute coronary heart disease (ST-segment elevation myocardial infarction and Non-ST segment elevation myocardial infarction), and unstable angina had euthyroidism. Thyroid dysfunction was reported in 23.3% of patients with coronary heart disease. Overall hypothyroidism prevalence was 7.8%, while subclinical hyperthyroidism in our study was 2.7%. Overt hyperthyroidism and subclinical hyperthyroidism was reported 2.0% and 0.5%, respectively. Euthyroid sick syndrome was noticed in 41 (10.2%) of critically ill patients. The mortality rate was 9.8%; all death patients had low triiodothyronine (T3) syndrome and were associated with statistically significant low free triiodothyronine (FT3) (P > 0.001). No significant variance was observed among patients underwent for cardiac catheterization, STEMI, NSTEMI, unstable angina, and atrial fibrillation with respect to FT4, FT3, and TSH levels during coronary care unit hospitalization based on their profile data.


Two Cross-Protective Antigen Sites on Foot-and-Mouth Disease Virus Serotype O Structurally Revealed by Broadly Neutralizing Antibodies from Cattle.
Foot-and-mouth disease virus (FMDV) is a highly contagious virus that infects cloven-hoofed animals. Neutralizing antibodies play critical roles in antiviral infection. Although five known antigen sites that induce neutralizing antibodies have been defined, studies on cross-protective antigen sites are still scarce. We mapped two cross-protective antigen sites using 13 bovine-derived broadly neutralizing monoclonal antibodies (bnAbs) capable of neutralizing 4 lineages within 3 topotypes of FMDV serotype O. One antigen site was formed by a novel cluster of VP3-focused epitopes recognized by bnAb C4 and C4-like antibodies. The cryo-electron microscopy (cryo-EM) structure of the FMDV-OTi (O/Tibet/99)-C4 complex showed close contact with VP3 and a novel interprotomer antigen epitope around the icosahedral 3-fold axis of the FMDV particle, which is far beyond the known antigen site 4. The key determinants of the neutralizing function of C4 and C4-like antibodies on the capsid were βB (T65), the B-C loop (T68), the E-F loop (E131 and K134), and the H-I loop (G196), revealing a novel antigen site on VP3. The other antigen site comprised two group epitopes on VP2 recognized by 9 bnAbs (B57, B73, B77, B82, F28, F145, F150, E46, and E54), which belong to the known antigen site 2 of FMDV serotype O. Notably, bnAb C4 potently promoted FMDV RNA release in response to damage to viral particles, suggesting that the targeted epitope contains a trigger mechanism for particle disassembly. This study revealed two cross-protective antigen sites that can elicit cross-reactive neutralizing antibodies in cattle and provided new structural information for the design of a broad-spectrum molecular vaccine against FMDV serotype O. IMPORTANCE FMDV is the causative agent of foot-and-mouth disease (FMD), which is one of the most contagious and economically devastating diseases of domestic animals. The antigenic structure of FMDV serotype O is rather complicated, especially for those sites that can elicit a cross-protective neutralizing antibody response. Monoclonal neutralization antibodies provide both crucial defense components against FMDV infection and valuable tools for fine analysis of the antigenic structure. In this study, we found a cluster of novel VP3-focused epitopes using 13 bnAbs against FMDV serotype O from natural host cattle, which revealed two cross-protective antigen sites on VP2 and VP3. Antibody C4 targeting this novel epitope potently promoted viral particle disassembly and RNA release before infection, which may indicate a vulnerable region of FMDV. This study reveals new structural information about cross-protective antigen sites of FMDV serotype O, providing valuable and strong support for future research on broad-spectrum vaccines against FMD.


Oxidative stress mediates the inhibitory effects of Manzamine A on uterine leiomyoma cell proliferation and extracellular matrix deposition via SOAT inhibition.
Uterine fibroids, the most common benign tumors of the myometrium in women, are characterized by abnormal extracellular matrix deposition and uterine smooth muscle cell neoplasia, with high recurrence rates. Here, we investigated the potential of the marine natural product manzamine A (Manz A), which has potent anti-cancer effects, as a treatment for uterine fibroids. Manz A inhibited leiomyoma cell proliferation in vitro and in vivo by arresting cell cycle progression and inducing caspase-mediated apoptosis. We performed target prediction analysis and identified sterol o-acyltransferases (SOATs) as potential targets of Manz A. Cholesterol esterification and lipid droplet formation were reduced by Manz A, in line with reduced SOAT expression. As a downstream target of SOAT, Manz A also prevented extracellular matrix deposition by inhibiting the β-catenin/fibronectin/metalloproteinases axis and enhanced autophagy turnover. Excessive free fatty acid accumulation by SOAT inhibition led to reactive oxygen species to impair mitochondrial oxidative phosphorylation and trigger endoplasmic reticulum stress via PERK/eIF2α/CHOP signaling. The inhibitory effect of ManzA on cell proliferation was partially restored by PERK knockdown and eliminated by tauroursodeoxycholic acid, suggesting oxidative stress plays a critical role in the mechanism of action of Manz A. These findings suggest that targeting SOATs by Manz A may be a promising therapeutic approach for uterine fibroids.


Pharmacokinetics of modified-release prednisone tablets in healthy subjects and patients with rheumatoid arthritis.
In rheumatoid arthritis (RA), nocturnal release of proinflammatory cytokines is not adequately counteracted by endogenous glucocorticoid and is associated with symptoms of morning stiffness and pain. Taking exogenous glucocorticoid during the night reduces morning stiffness significantly more than treatment at the conventional time in the morning, although waking to take tablets is unacceptable for patients. Modified-release prednisone tablets were developed to allow administration at bedtime for programmed delivery of glucocorticoid during the night. Single-center crossover studies were conducted, each in ≤24 healthy subjects, to compare the pharmacokinetics of a single 5-mg oral dose of modified-release prednisone and conventional prednisone, as well as the effect of food on bioavailability. There was no substantial difference in pharmacokinetic parameters of the formulations apart from the programmed delay in release of glucocorticoid from the modified-release tablets (C(max) 97%, AUC(0-∞) 101%, 90% confidence intervals within the requisite range for bioequivalence). Administration after a full or light meal did not affect pharmacokinetic characteristics, but bioavailability was reduced under fasted conditions. Pharmacokinetic evaluation in 9 patients with RA confirmed that modified-release prednisone tablets taken at bedtime (around 22:00 h) with or after an evening meal result in programmed release of glucocorticoid 4 to 6 hours after intake.


'Complete 5p' trisomy: 1 case and 19 translocation carriers in 6 generations.
A description is given of a female infant with multiple malformations and mental retardation who died at 31 months. Cytogenetic studies indicate trisomy of the complete short arm of chromosome 5, resulting from the unbalanced segregation of a balanced translocation in the mother whose karyotype was interpreted as 46,XX,t(5; 15)(p11; p12). The karyotype of the proband was designated 46,XX, der(5)t(5; 15)(p11; p12)mat. Family studies indicate that the translocation has been present in the family for at least 6 generations.


Relationship between SCR, heart rate and information processing.
This study was designed to investigate the relationship between the amount of information processing in concept learning (CL) and autonomic physiological activity as measured by skin conductance response (SCR). Heart rate (HR) was also measured. Two conceptual rules were used: a conjunctive and an inclusive disjunctive concept. The results indicated that the SCR rose with increasing amount of information processing at the feedback during CL. Furthermore, it was shown that SCR increased with increasing difficulty of the conceptual rule. HR appeared not to vary with amount of information processing, nor with type of concept. In the conjunctive series, however, there was a significant difference between HR at stimulus presentation and HR at feedback.


Weakly coupled traveling waves for a model of growth and competition in a flow reactor.
For a reaction-diffusion model of microbial flow reactor with two competing populations, we show the coexistence of weakly coupled traveling wave solutions in the sense that one organism undergoes a population growth while another organism remains in a very low population density in the first half interval of the space line; the population densities then exchange the position in the next half interval. This type of traveling wave can occur only if the input nutrient slightly exceeds the maximum carrying capacity for these two populations. This means, lacking an adequate nutrient, two competing organisms will manage to survive in a more economical way.


Evaluating coronary artery disease noninvasively--which test for whom?
The generally accepted indications for stress testing in patients with coronary artery disease include confirming the diagnosis of angina, determining the limitation of activity caused by angina, assessing prognosis in patients with known coronary artery disease, assessing perioperative risk, and evaluating responses to therapy. In patients with a clinical scenario strongly suggestive of angina, testing is not necessary to diagnose coronary artery disease. The exercise treadmill-electrocardiogram test is the oldest and most extensively used stress test and can be reliably performed in patients who are clinically stable and who have an interpretable resting electrocardiogram. The addition of myocardial imaging agents such as thallium 201, technetium Tc 99m sestamibi, and technetium Tc 99m teboroxime increases the sensitivity and specificity for detecting coronary disease. Pharmacologic agents such as dipyridamole, adenosine, and dobutamine may be used in patients who cannot exercise adequately. Myocardial ischemia can also be evaluated by echocardiography, computed tomography, or magnetic resonance imaging, especially when additional information such as left ventricular and valvular function is desired. We review the indications for the noninvasive evaluation of coronary artery disease and the rationale for selecting a diagnostic test.


Phosphorylated proteomics analysis of human coronary artery endothelial cells stimulated by Kawasaki disease patients serum.
Kawasaki disease (KD) is an acute febrile childhood systemic vasculitis that disturbs coronary arteries. The pathogenesis remains unknown. The study of phosphorylated proteins helps to elucidate the relevant pathophysiological mechanisms of cardiovascular disease. However, few researches explored phosphorylated proteins in KD patients. We compared phosphoprotein profiles of HCAECs stimulated by the serum of KD patients and normal children using iTRAQ technology, TiO2 enrichment phosphorylated peptide and MS analysis. Then we conducted the functional analysis by ClueGO and the biological interaction networking analysis by ReactomeFIViz. Western blotting was performed to identify the hub proteins. Our results revealed that phosphorylation of 148 proteins showed different intensities between the two HCAECs groups, which are enriched in MAPK, VEGFR, EGFR, Angiopoietin receptor, mTOR, FAK signaling pathway and so on. Through the Network Analyzer analysis, the hub proteins are CDKN1A, MAPK1 and POLR2A, which were experimentally validated. In summary, we provided evidence addressing the valuable phosphorylation signaling that could be useful resource to understand the molecular mechanism and the potential targets for novel therapy of KD.


Erythropoietin and its antagonist regulate hypoxic fictive breathing in newborn mice.
Clinical use of erythropoietin in adult and newborn patients has revealed its involvement in neuroprotection, neurogenesis, and angiogenesis. More recently, we showed in adult mouse, that brain erythropoietin interacts with the major brainstem centers associated with respiration to enhance the ventilatory response to acute and chronic conditions of physiological hypoxia (e.g., as occurring at high altitude). However, whether brain erythropoietin is involved in breathing regulation in newborns remains unknown. In this study, en bloc brainstem-spinal cord preparations were obtained from mice at postnatal day 4. After various periods (30, 60, or 90 min) of incubation with 0, 25, or 250 U of erythropoietin, preparations were superfused with artificial cerebrospinal fluid bubbled with normoxic or hypoxic gas mixtures. The electrophysiological fictive breathing produced by axons at the C4 ventral root was next recorded. Our results show that erythropoietin attenuates the hypoxia-mediated decrease of the central respiratory activity and improves post-hypoxic recovery. Additional analysis revealed that the soluble erythropoietin receptor (the endogenous erythropoietin antagonist) dramatically decreases neural hypoxic respiratory activity, confirming the specific erythropoietin effect on respiratory drive. These results imply that erythropoietin exerts main modulation and maintenance of respiratory motor output during hypoxic and post-hypoxic challenges in 4-days old mice.


Multireference Fock-space coupled-cluster and equation-of-motion coupled-cluster theories: the detailed interconnections.
The multireference Fock-space coupled-cluster (FS-CC) equations constructed via the effective Hamiltonian approach are reduced to those obtained through a partitioning technique for the matrix diagonalization. This allows finding a better route to solve the FS-CC equations for the (1,1) sector by the direct diagonalization of the properly constructed matrix, which is identical to that obtained with the intermediate Hamiltonian approach. The detailed connections with the equation-of-motion CC (EOM-CC) approach also provides alternative routes for studying the higher-sectors of Fock space, and for the treatment of properties other than the energy. The approach studied in this work is formulated at the CC singles, doubles (CCSD) and CC singles, doubles, triples (CCSDT) level. The performance of the method is illustrated by numerical examples for the C(2), C(2)H(4), and H(2)CO molecules in comparison with the EOM-CC method and available experimental data.


Pediatric expert consensus on the application of glucocorticoids in Kawasaki disease.
Kawasaki disease (KD) is one of the common acquired heart diseases in under-5-year-old children and is an acute self-limiting vasculitis. After nearly 60 years of research, intravenous immunoglobulin combined with oral aspirin has become the first-line treatment for preventing coronary artery aneurysm in the acute stage of KD. However, glucocorticoid (GC), infliximab, and other immunosuppressants are options for the treatment of KD patients with a high risk of coronary artery aneurysm, no response to intravenous immunoglobulin and a confirmed diagnosis of coronary artery aneurysm. At present, there are still controversies over the use of GC in the treatment of KD. With reference to the latest research findings of KD treatment in China and overseas, this consensus invited domestic pediatric experts to fully discuss and put forward recommendations on the indications, dosage, and usage of GC in the first-line and second-line treatment of KD.


Involvement of necroptosis, a newly recognized cell death type, in steroid-induced osteonecrosis in a rabbit model.
We investigated the role of programmed necrosis (necroptosis), a newly recognized form of cell necrosis that has been implicated in the development of steroid-induced osteonecrosis. We used an osteonecrosis model in which 30 Japanese white rabbits each weighing 3.5kg were injected once with methylprednisolone at 20 mg/kg body weight into the right gluteal muscle. Ten animals killed 14 days thereafter were designated as S14d groups, while another 10 animals injected with necroptosis, a specific inhibitor of necrostatin-1 i.v. at 1.65mg/kg on the same day as the steroid were also killed on the 14th day and designated as SN14d group. As a control, 10 animals injected only with physiological saline were studied as N group. After the animals were sacrificed the bilateral femoral bone was examined histopathologically and the presence of osteonecrosis determined. Furthermore, animals subjected to the same treatment and killed on the 3rd day after drug administration were set up as S3d group and SN3d group, and Western blotting of Receptor-interacting protein ( RIP ) 1 and RIP3 in femoral bone performed. The osteonecrosis rate was 70% in S14d group, and 0% in both N and SN groups. In 2 of 10 animals in SN group fatty marrow was found. On Western blotting significantly increased expression of both RIP1 and RIP3 was noted in S3d group, confirming that Nec-1 was suppressed. Necroptosis mediated by RIP1 and RIP3 expression was thought to be implicated in the development of steroid-induced osteonecrosis. Also, by suppressing expression of RIP1 and 3 with the administration of Nec-1 the osteonecrosis rate was significantly decreased. These results suggest that necroptosis may have potential as a novel target for both elucidating the mechanisms underlying steroid-induced osteonecrosis and establishing more effective prophylactic countermeasures.


[Respiratory control during sleep and the development of nocturnal hypoxia in patients with obstructive sleep apnea hypopnea syndrome].
It is assumed that the reduced ventilatory control during sleep may be related to the nocturnal hypoxia in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and daytime CO(2) retention. Oxygen desaturation index (ODI(4)), sleep time spent when SaO(2) was below 90% (SIT(90)), the lowest SaO(2) (LSaO(2)) and the mean SaO(2) (MSaO(2)) during sleep were measured in 24 OSAHS patients with daytime PaCO(2) > or = 45 mm Hg and 39 with PaCO(2) < 45 mm Hg. Hypoxic (DeltaP(0.1)/DeltaSaO(2)) and hypercapnic (DeltaP(0.1)/DeltaPaCO(2)) responsiveness were measured in 11 eucapnic and 4 hypercapnic patients during wakefulness, NREM and REM sleep stages. Compared with the eucapnic patients, all the hypercapnic patients had more severe hypoxia during sleep (P < 0.05). Although both groups had similar chemical responsiveness during wakefulness, the hypercapnic patients had lower DeltaP(0.1)/DeltaSaO(2) and DeltaP(0.1)/DeltaPaCO(2) during both REM and NREM sleep (P < 0.05). The depressed chemical responsiveness during sleep plays an important role in the development of nocturnal hypoxia in OSAHS patients with daytime CO(2) retention.


Use of Frame Running for Adolescent Athletes With Movement Challenges: Study of Feasibility to Support Health and Participation.
Children and adolescents with movement challenges have lower instances of physical activity and longer time spent in sedentary behaviors compared to children with typical development. The purpose of this study was to investigate the feasibility of a sport-based youth development running program modified for accessibility using a running frame and to evaluate initial evidence for its efficacy on endurance and functional strength. We completed four 8-week seasons (2-3 times per week) in a combination of 3 different formats by season: online remote (winter and spring), in person in a community park (winter, spring, and summer), and in person in an afterschool setting (autumn). Participants included 13 athletes (average age 14.46 years, range 8-18 years, 4 females), who collectively completed 22 season blocks. Diagnoses included cerebral palsy (n = 10), arthrogryposis (n = 1), Dandy-Walker malformation (n = 1), and transverse myelitis (n = 1). In all settings, participants engaged in activities of social emotional learning, cardiovascular endurance, and muscle strengthening in a progressive manner. We found that each season format was feasible to administer with high attendance rates (76-97%) and positive qualitative feedback from athletes. In addition, promising average improvements in motor performance across a season (6 min frame running test, 170 m; timed up and go test, 8.44 s; five times sit to stand, 14.1 s; and Goal Attainment Scale, t = 65.01) were identified in the pilot data of this non-randomized cohort. Training in any of the proposed settings with an overall goal of completing a community race in a running frame is feasible and warrants further study.


Antibiotics and mucous membrane: pharmacokinetic aspects.
The penetration of chemoantibiotic agents across the mucous membrane is affected by several factors, some of which are related to the drug and others to the membrane. Molecular weight can influence the penetration of chemoantibiotic agents into mucous membranes. Liposolubility is another factor which can enhance the penetration of chemoantibiotic agents. Factors related to the membrane can affect diffusion of the antibiotic. Inflammation of the mucous membrane enhances the volume of blood circulating within tissues and, as a consequence, the rate of drug penetration into them. This condition, however, can be counterbalanced by a high binding rate of the drug to tissues. The pH affects the action of antibacterial agents. Acid pH range enhances the antibacterial activity of beta-lactams, an alkaline range that of macrolides. Besides purely physiochemical factors, there are others able to interfere with the diffusion of a chemoantibiotic agent into and through the mucous membranes. The diffusion into bronchial membrane and the penetration through the hematobronchial barrier seems to occur substantially by means of a passive transfer. There is therefore an establishment of a proportionality relationship between the concentrations in the two blood-bronchial fluid compartments. Exceptions to this rule seem to be some drugs like macrolides, even if a real active transfer mechanism has not yet been demonstrated. A precise knowledge of its pharmacokinetic parameters is an indispensable condition for the characterization of a molecule which penetrates the mucous membranes.


Effects of Surgical and Medical Treatment on Quality of Life for Patients With Chronic Thromboembolic Pulmonary Hypertension.
This study aimed to investigate the predictors of quality of life (QOL) in patients with chronic thromboembolic pulmonary hypertension (CTEPH), changes in QOL after surgical and medical treatments, and the relationship between baseline QOL and survival. QOL was measured in 128 patients with CTEPH (male/female: 42/86, age: 56±12 years, surgical/medical: 65/63) using the Short-Form 36 (SF-36) questionnaire. Multiple regression analysis showed pulmonary vascular resistance (PVR) and 6-min walking distance (6MWD) were associated with physical functioning (PF) (P<0.01) and physical component summary (PCS) (P<0.01). In the surgical group, 7 subscales and 2 summary scores improved significantly, and in the medical group 6 subscales and the mental component summary, although the change in QOL was greater in the surgical group. The patients in the conventional therapy group with higher PF had significantly better survival than those with lower PF (5-years survival: 89.5% vs. 50.8%, P=0.002). This difference in survival was not observed in the group receiving pulmonary arterial hypertension (PAH)-specific therapy (100% vs. 100%, P=0.746). PVR and 6MWD were associated with PF or PCS in CTEPH patients. QOL improved after surgical or medical therapy, with a greater change in the surgical group. PAH-specific therapy improved survival in patients with lower PF at diagnosis.


Dual mechanisms of ABCA1 regulation by geranylgeranyl pyrophosphate.
ATP-binding cassette transporter A1 (ABCA1) mediates an active efflux of cholesterol and phospholipids and is mutated in patients with Tangier disease. Expression of ABCA1 may be increased by certain oxysterols such as 22(R)-hydroxycholesterol via activation of the nuclear hormone receptor liver X receptor (LXR). In searching for potential modulators of ABCA1 expression, we have studied the effects of various mevalonate metabolites on the expression of ABCA1 in two human cell lines, THP-1 and Caco-2 cells. Most of the tested metabolites, including mevalonate, geranyl pyrophosphate, farnesyl pyrophosphate, and ubiquinone, failed to significantly change the expression levels of ABCA1. However, treatment with geranylgeranyl pyrophosphate resulted in a dose- and time-dependent reduction of ABCA1 expression. Geranylgeranyl pyrophosphate appears to reduce ABCA1 expression via two different mechanisms. One of these mechanisms is by acting directly as an antagonist of LXR since it reduces the interaction between LXR alpha or -beta with nuclear coactivator SRC-1. Another mechanism appears to involve activation of the Rho GTP-binding proteins since treatment of Caco-2 cells with inhibitors of geranylgeranyl transferase or the Rho proteins significantly increased the expression and promoter activity of ABCA1. Further studies showed that mutations in the DR4 element of the ABCA1 promoter completely eliminate the inducible activities of these inhibitors. These data indicate that activation of the Rho proteins may change the activation status of LXR.


The humanistic burden of vitiligo: a systematic literature review of quality-of-life outcomes.
Despite historical mischaracterization as a cosmetic condition, patients with the autoimmune disorder vitiligo experience substantial quality-of-life (QoL) burden. This systematic literature review of peer-reviewed observational and interventional studies describes comprehensive evidence for humanistic burden in patients with vitiligo. PubMed, EMBASE, Scopus and the Cochrane databases were searched through February 10, 2021, to qualitatively assess QoL in vitiligo. Two independent reviewers assessed articles for inclusion and extracted data for qualitative synthesis. A total of 130 included studies were published between 1996 and 2021. Geographical regions with the most studies were Europe (32.3%) and the Middle East (26.9%). Dermatology-specific instruments, including the Dermatology Life Quality Index (DLQI; 80 studies) and its variants for children (CDLQI; 10 studies) and families (FDLQI; 4 studies), as well as Skindex instruments (Skindex-29, 15 studies; Skindex-16, 4 studies), were most commonly used to measure humanistic burden. Vitiligo-specific instruments, including the Vitiligo-specific QoL (VitiQoL; 11 studies) instrument and 22-item Vitiligo Impact Scale (VIS-22; 4 studies), were administered in fewer studies. Among studies that reported total scores for the overall population, a majority revealed moderate or worse effects of vitiligo on patient QoL (DLQI, 35/54 studies; Skindex, 8/8 studies; VitiQoL, 6/6 studies; VIS-22, 3/3 studies). Vitiligo also had a significant impact on the QoL of families and caregivers; 4/4 studies reporting FDLQI scores indicated moderate or worse effects on QoL. In general, treatment significantly (P < 0.05) improved QoL, but there were no trends for types or duration of treatment. Among studies that reported factors significantly (P ≤ 0.05) associated with reduced QoL, female sex and visible lesions and/or lesions in sensitive areas were most common. In summary, vitiligo has clinically meaningful effects on the QoL of patients, highlighting that greater attention should be dedicated to QoL decrement awareness and improvement in patients with vitiligo.


Persistence of ureaplasma urealyticum in the genital tract after antibiotic therapy.
Urine samples from 65 couples attending an infertility clinic were tested for the presence of Ureaplasma urealyticum. Of 36 couples found to harbor the organism, 35 were given antibiotic treatment in an attempt to eradicate these organisms from the genital tract. After the initial antibiotic therapy, tests of 12 of 27 couples (44%) still were Ureaplasma positive; after a second course of treatment, tests for 4 of 9 were positive. Two couples had Ureaplasma organisms that were resistant to all antibiotics tested. One couple remained positive after five courses of treatment, in spite of the demonstrated in vitro sensitivity of the isolate to antibiotics used. Pregnancies in treated patients occurred among those who were Ureaplasma negative after doxycycline therapy.


Trust, medication adherence, and hypertension control in Southern African American men.
We examined the relationship between trust in the medical system, medication adherence, and hypertension control in Southern African American men. The sample included 235 African American men aged 18 years and older with hypertension. African American men with higher general trust in the medical system were more likely to report better medication adherence (odds ratio [OR] = 1.06), and those with higher self-efficacy were more likely to report better medication adherence and hypertension control (OR = 1.08 and OR = 1.06, respectively).


Improving Practice Guideline Adherence Through Peer Feedback: Impact of an Ambulatory Cardiology Curriculum.
Graduate medical trainees must be prepared to practice in a quality-driven system that values adherence to and documentation of evidence-based care. Few validated approaches exist to teach these skills. Our objective was to develop, implement, and evaluate an ambulatory practice improvement curriculum capitalizing on peer feedback aimed at improving cardiology fellow guideline knowledge, adherence, and chart documentation. Four outpatient topics were reviewed in dedicated 1-hour sessions: stable ischemic heart disease, heart failure, atrial fibrillation, and aortic valvular disease. Each session began with peer review, critique, and guideline adherence discussion of deidentified outpatient fellow clinic charts, followed by discussion of clinical guidelines. The open discussion of real clinic notes provided a forum for peer feedback exchange. Before each session and after the final session, participants completed a multiple-choice knowledge assessment and self-assessment of comfort with the guidelines. To evaluate the potential effect on patient care, random clinic chart audits were conducted before and after the curriculum using a chart scoring system. Although the format is broadly applicable, the specific curriculum content was designed for a cardiology fellowship cohort in a large academic medical center. It was organized and implemented by 2 cardiology fellows under the direction and supervision of program directors. The curriculum was implemented during prescheduled noon conference hours. The intention was to carry forward this ambulatory curriculum in subsequent years and to use the first 4 sessions to study its potential successes and opportunities for improvement. All 22 general cardiology fellows attended at least two sessions (M = 3.1). Knowledge test scores rose from 52.6% to 73.0% (20.4% increase, p < .001), 95% confidence interval (CI) [13.6%, 27.2%]. Self-reported guidelines knowledge improved by 15.1% (p = .002), 95% CI [6.2%, 24.0%], and self-reported documentation improved by 12.5% (p = .008), 95% CI [3.8%, 21.7%]. Chart audit scores improved by 17.8% (p < .001), 95% CI [10.6%, 25.0%], driven in part by 16.4% improvement in adherence to Class I therapies (p = .001). A targeted curriculum combining peer chart review, feedback, and guideline discussion was associated with significant improvement in fellows' knowledge and adherence to evidence-based therapies. Peer assessment and group-based education and feedback can be leveraged to improve trainee education and impact patient care.


Synthesis of Trifluoromethylated Naphthoquinones via Copper-Catalyzed Cascade Trifluoromethylation/Cyclization of 2-(3-Arylpropioloyl)benzaldehydes.
A novel copper-catalyzed cascade trifluoromethylation/cyclization of 2-(3-arylpropioloyl)benzaldehydes is described, allowing a direct access to structurally diverse trifluoromethylated naphthoquinones under mild reaction conditions. It represents the first trans-acyltrifluoromethylation of internal alkynes.


Isolated Gastric Tuberculosis Mimicking Malignancy.
Isolated tuberculosis of upper gastrointestinal tract is a rare pathology, often mimicking malignancy in clinical presentation and radiological features. We present a case of middle aged gentleman with isolated tuberculosis of stomach, proven on histopathology and showing remarkable improvement on follow up.


Comprehensive characterization of non-cellulosic recalcitrant cell wall carbohydrates in unhydrolyzed solids from AFEX-pretreated corn stover.
Inefficient carbohydrate conversion has been an unsolved problem for various lignocellulosic biomass pretreatment technologies, including AFEX, dilute acid, and ionic liquid pretreatments. Previous work has shown 22% of total carbohydrates are typically unconverted, remaining as soluble or insoluble oligomers after hydrolysis (72 h) with excess commercial enzyme loading (20 mg enzymes/g biomass). Nearly one third (7 out of 22%) of these total unconverted carbohydrates are present in unhydrolyzed solid (UHS) residues. The presence of these unconverted carbohydrates leads to a considerable sugar yield loss, which negatively impacts the overall economics of the biorefinery. Current commercial enzyme cocktails are not effective to digest specific cross-linkages in plant cell wall glycans, especially some of those present in hemicelluloses and pectins. Thus, obtaining information about the most recalcitrant non-cellulosic glycan cross-linkages becomes a key study to rationally improve commercial enzyme cocktails, by supplementing the required enzyme activities for hydrolyzing those unconverted glycans. In this work, cell wall glycans that could not be enzymatically converted to monomeric sugars from AFEX-pretreated corn stover (CS) were characterized using compositional analysis and glycome profiling tools. The pretreated CS was hydrolyzed using commercial enzyme mixtures comprising cellulase and hemicellulase at 7% glucan loading (~20% solid loading). The carbohydrates present in UHS and liquid hydrolysate were evaluated over a time period of 168 h enzymatic hydrolysis. Cell wall glycan-specific monoclonal antibodies (mAbs) were used to characterize the type and abundance of non-cellulosic polysaccharides present in UHS over the course of enzymatic hydrolysis. 4-O-methyl-d-glucuronic acid-substituted xylan and pectic-arabinogalactan were found to be the most abundant epitopes recognized by mAbs in UHS and liquid hydrolysate, suggesting that the commercial enzyme cocktails used in this work are unable to effectively target those substituted polysaccharide residues. To our knowledge, this is the first report using glycome profiling as a tool to dynamically monitor recalcitrant cell wall carbohydrates during the course of enzymatic hydrolysis. Glycome profiling of UHS and liquid hydrolysates unveiled some of the glycans that are not cleaved and enriched after enzyme hydrolysis. The major polysaccharides include 4-O-methyl-d-glucuronic acid-substituted xylan and pectic-arabinogalactan, suggesting that enzymes with glucuronidase and arabinofuranosidase activities are required to maximize monomeric sugar yields. This methodology provides a rapid tool to assist in developing new enzyme cocktails, by supplementing the existing cocktails with the required enzyme activities for achieving complete deconstruction of pretreated biomass in the future.


Effects of acetate on human immune system.
The immunopharmacologic effects of Ringer's acetate on healthy persons and cancer patients were investigated. Enhancement of in vivo polyclonal antibody production in peripheral blood lymphocytes from healthy subjects and cancer patients was elicited after the intravenous administration of 500 ml Ringer's acetate solution. Allogeneic mixed lymphocyte reaction(MLR) and natural killer(NK) activity were also increased in the majority of healthy individuals and cancer patients when administered Ringer's acetate solution but not Ringer's lactate solution.


Tumefactive demyelinating disease with isolated spinal cord involvement.
Tumefactive multiple sclerosis (TMS) is an unusual variant of demyelinating disease. TMS has a variable and unknown progression and presents with features similar to a neoplasm making the determination a diagnostic challenge to clinicians. This report presents one of the very few reported cases of isolated spinal cord TMS, and the second case to describe TMS of the lower spinal cord, given that the lesions are typically cervical. This case study presents a diagnostic approach based on clinical, laboratory, and imaging characteristics, as well as sheds some light on the response to therapy and disease evolution.


Analysis of symbolic sequences using the Jensen-Shannon divergence.
We study statistical properties of the Jensen-Shannon divergence D, which quantifies the difference between probability distributions, and which has been widely applied to analyses of symbolic sequences. We present three interpretations of D in the framework of statistical physics, information theory, and mathematical statistics, and obtain approximations of the mean, the variance, and the probability distribution of D in random, uncorrelated sequences. We present a segmentation method based on D that is able to segment a nonstationary symbolic sequence into stationary subsequences, and apply this method to DNA sequences, which are known to be nonstationary on a wide range of different length scales.


In Situ-Generated Glycinyl Chloroaminals for a One-Pot Synthesis of Non-proteinogenic α-Amino Esters.
An acetyl chloride-mediated cascade transformation involving a primary carbamate, ethyl glyoxylate, and various types of nucleophiles is reported for the synthesis of orthogonally protected α-amino esters. These reactions proceeded rapidly to afford the pivotal α-chloroglycine intermediate in excellent yields, which can be directly functionalized in situ with various types of nucleophiles. A mild and unique AcOH(cat.)/AcCl system was found to promote an autocatalytic-like condensation and facilitate the multicomponent assembly of non-proteinogenic α-amino esters. To better understand this one-pot transformation and the orchestration of the components' condensations, the investigation of a broader scope of nucleophiles and some kinetic studies are presented. Our findings suggest that the halogenation step toward the formation of α-chloroglycine is the rate-determining step likely proceeding through the formation of N-carbamoyl iminium. Also, the initial kinetic profiling for the nucleophilic substitution supports an SN1-like (SN2C+) mechanism in which nucleophiles add to the iminium-chloride tight ionic pair. These results lead ultimately to the design of a new protocol in which an achiral hydrogen bond donor thiourea catalyst was utilized to enhance the reaction scope and enable silylated nucleophiles to be efficiently exploited to synthesize novel non-proteinogenic α-amino esters.


Lead induced disorders in hematopoietic and drug metabolizing enzyme system and their protection by ascorbic acid supplementation.
Effect of vitamin C supplementation in restoring lead induced alterations in hematopoietic system and drug metabolizing enzymes were investigated in male rats. Intraperitoneal administration of 20 mg/kg lead produced a significant inhibition of heme synthesis in blood and liver and drug metabolism in liver. Toxic insult by lead also resulted into a marked decline in tissue thiols and vitamin C levels. Oral supplementation of vitamin C (100 mg/kg for 3 days) completely restored blood delta aminolevulinic acid dehydratase, uroporphyrinogen I synthetase and a few drug metabolizing enzymes. Level of vitamin C and sulfhydryl contents too recovered to a great extent. A marked reduction in blood and liver lead concentration occurred on vitamin C supplementation although renal lead contents were marginally reduced in lead exposed animals. The results, thus, indicate a significant protective action of vitamin C against toxic effects of lead on heme synthesis and drug metabolism.