Appendicular mucinous cystadenoma: a case report.
Mucinous cystadenoma of the appendix is a rare condition characterized by abnormal mucus accumulation in the appendiceal. Laparoscopic appendectomy is a common approach worldwide and can be used in the management of mucinous cystadenoma with lower postoperative complication rates. A 30-year-old female had sharp pain localized to the right abdomen for 2 days. It was aggravated by movement and associated with nausea and vomiting. Laboratory findings were normal, but the abdominal computerized tomography scan demonstrated a cystic tumor in the right abdomen dorsal to the cecum and the ascending colon. Diagnostic laparoscopy showed a large cystic mass well-circumscribed encapsulated involving the appendix in the lower right abdomen. After demonstrating pathologic examination, the final diagnosis was mucinous cystadenoma of the appendix. Management of the appendicular mucinous cystadenoma can be successfully achieved through atraumatic laparoscopic excision of the tumor, it is safe, feasible and has a short postoperative recovery period.


Two-Dimensional Organic-Inorganic Hybrid Perovskite Photonic Films.
Organic-inorganic hybrid perovskites have created enormous expectations for low-cost and high-performance optoelectronic devices. In prospect, future advancements may derive from reaping novel electrical and optical properties beyond pristine perovskites through microscopic structure design and engineering. Herein, we report the successful preparation of two-dimensional inverse-opal perovskite (IOP) photonic films, featuring unique nanostructures and vivid colors. Further compositional and structural managements promise optical property and energy level tunability of the IOP films. They are further functionalized in solar cells, resulting in colorful devices with respectable power conversion efficiency. Such concept has not been previously applied for perovskite-based solar cells, which could open a route for more versatile optoelectronic devices.


Pressure-volume relationships of the respiratory system in normal cats.
We studied the pressure-volume (PV) relationships of the total respiratory system, lung and chest wall in 8 anesthetized and paralyzed normal adult cats. The PV relationships of the total respiratory system had a sigmoid shape with a relatively linear portion with an alveolar pressure between 0 to +15 cmH2O. The relative impact of the lung and chest wall to the total elastic recoil forces of the respiratory system was approximately equal within a physiological pressure range. The results suggest that measurements of PV relationships of the respiratory system may offer a physiologic basis for accurate interpretation of pulmonary functions, leading to a better therapeutic strategy in animals with lung diseases.


Haematopoietic stem cell transplantation for sickle cell disease - current practice and new approaches.
Sickle cell disease is an inherited disorder that affects over 5 million people worldwide. Current maintenance therapy has been successful in reducing complications and enhancing life expectancy; yet subclinical complications persist. To date, allogeneic haematopoietic stem cell transplant (HSCT) remains the only available curative therapy for sickle cell disease. With declining incidences of rejection and transplant- related mortality, disease-free survival after human leucocyte antigen-identical sibling transplant exceeds 90%. However, the majority of individuals with sickle cell disease do not have an human leucocyte antigen (HLA)-identical sibling; therefore, research is expanding to focus on new approaches to alternative donor transplant. Advances in supportive care and conditioning regimens have led to expansion of the pool of donors to unrelated donors and haploidentical donors. Challenges remain in improving the safety and efficacy of HSCT from alternate donors. Early results from gene therapy may provide another curative option in patients with sickle cell disease. These approaches show early promise, but larger, longitudinal studies are needed to better determine the optimal clinical circumstances for transplant in sickle cell disease.


Change in end-tidal position in children after suxamethonium.
The change in end-tidal position (ETP) after suxamethonium-induced paralysis was measured in 15 children during routine general anaesthesia. In all patients the onset of muscle paralysis was associated with an increase in lung volume from ETP. This increase may be the result of paralysis of the expiratory muscles which are active during anaesthesia.


Evaluation and validation of an enzyme-linked immunosorbent assay and an immunochromatographic test for serological diagnosis of severe acute respiratory syndrome.
A newly developed severe acute respiratory syndrome (SARS)-specific enzyme-linked immunosorbent assay (ELISA) was further validated to confirm cutoff values and evaluate its diagnostic performance with clinical samples. In parallel, an immunochromatographic test was also evaluated. A total of 227 clinical serum specimens collected from SARS patients were used in the study, together with 385 samples from healthy donors. By use of an immunofluorescent (IF) test as the "gold standard", both the ELISA and the immunochromatographic test were able to detect immunoglobulin G antibodies to SARS not only from late-convalescent-stage samples (>21 days from the onset of clinical symptoms), as previously established, but also from early-acute-phase samples (1 to 10 days from onset). The ELISA, using an optical density (OD) of 0.25 as its cutoff value, produced the best sensitivity while maintaining high specificity. It detected SARS-specific antibodies in 58, 70, 75, and 95%, respectively, of the four groups of samples collected from patients 1 to 10 days, 11 to 20 days, 21 to 30 days, and more than 30 days after the onset of clinical symptoms. Similarly, the immunochromatographic test detected SARS-specific antibodies in 55, 68, 81, and 79% of the four groups, respectively. The overall specificities for the ELISA and the rapid test were 99.5 and 97.7%, respectively. Although the positive correlation observed between the ELISA OD values and the IF titers was moderate (r = 0.6915; P < 0.001), the detection rates of both the ELISA and the rapid test were found well in agreement with the IF titers.


ATR-Chk1 activation mitigates replication stress caused by mismatch repair-dependent processing of DNA damage.
The mismatch repair pathway (MMR) is essential for removing DNA polymerase errors, thereby maintaining genomic stability. Loss of MMR function increases mutation frequency and is associated with tumorigenesis. However, how MMR is executed at active DNA replication forks is unclear. This has important implications for understanding how MMR repairs O6-methylguanine/thymidine (MeG/T) mismatches created upon exposure to DNA alkylating agents. If MeG/T lesion recognition by MMR initiates mismatch excision, the reinsertion of a mismatched thymidine during resynthesis could initiate futile repair cycles. One consequence of futile repair cycles might be a disruption of overall DNA replication in the affected cell. Herein, we show that in MMR-proficient HeLa cancer cells, treatment with a DNA alkylating agent slows S phase progression, yet cells still progress into the next cell cycle. In the first S phase following treatment, they activate ataxia telangiectasia and Rad3-related (ATR)-Checkpoint Kinase 1 (Chk1) signaling, which limits DNA damage, while inhibition of ATR kinase activity accelerates DNA damage accumulation and sensitivity to the DNA alkylating agent. We also observed that exposure of human embryonic stem cells to alkylation damage severely compromised DNA replication in a MMR-dependent manner. These cells fail to activate the ATR-Chk1 signaling axis, which may limit their ability to handle replication stress. Accordingly, they accumulate double-strand breaks and undergo immediate apoptosis. Our findings implicate the MMR-directed response to alkylation damage as a replication stress inducer, suggesting that repeated MMR processing of mismatches may occur that can disrupt S phase progression.


N400 amplitude reduction correlates with an increase in pupil size.
Pupil dilation is classically associated with increase in cognitive load in humans. Here, we studied the potential link between human pupil dilation and meaning integration effort as indexed by event-related brain potentials (ERPs). We recorded pupil size variation and ERPs simultaneously while participants were presented with matching or unrelated picture-word pairs. Whilst relatedness in meaning between spoken words and pictures typically modulated ERPs, pupil size was also affected quickly after picture onset. Moreover, during the time-window associated with meaning integration, greater pupil dilation correlated with less negative N400 amplitudes elicited by unrelated pictures. Since pupil dilation has been linked to activity of the locus coeruleus-norepinephrine (LC-NE) system, these findings may provide new insights into the suggested link between human high-level cognitive function and activity of the LC-NE system.


Influence of a nursing intervention on regimen adherence and societal adjustments postmyocardial infarction.
One hundred three first-time myocardial infarction (MI) patients were randomly assigned to either an experimental or a control condition. Patients completed a cardiac rehabilitation program during hospitalization and were interviewed to assess intentions to follow regimen prescriptions, attitudes toward the prescriptions, coping methods, and the perceived beliefs of others concerning their intentions. Patients were visited at home 30 days after discharge and reassessed on each of the above variables except that their behavior was substituted for intentions and societal adjustment was assessed. The experimental group was given an intervention program which included a discussion of assessment data, identification of problems, and establishment of goals. The assessment was repeated 60 days after discharge. No differences were found between experimental and control groups for either medical regimen adherence or societal adjustment. There was a significant decrease in mean scores for all variables from hospital to 30 days for both groups, but no change from 30 to 60 days. Attitudes and perceived beliefs of others were predictive of adherence, and it was concluded that these variables need to be included in any rehabilitation program.


Radioimmunoassay for Bacteroides fragilis infections.
Radioimmunoassay methods were evaluated for immunoglobulin G and immunoglobulin M antibodies against Bacteroides fragilis antigen. Of 12 serum samples from patients with B fragilis infections, 9 had higher concentrations of immunoglobulin G antibodies than any from 11 control subjects. Of 9 serum samples from infected patients, 6 had higher concentrations of immunoglobulin M than any from control subjects. Six serum samples from patients with Escherichia coli bacteremia did not contain elevated concentrations of immunoglobulin G or immunoglobulin M antibodies against B. fragilis antigen.


Preferential modification of nuclear proteins by a novel ubiquitin-like molecule.
Sentrin is a novel ubiquitin-like protein that protects cells against both anti-Fas and tumor necrosis factor-induced cell death. Antiserum recognizing the N terminus of sentrin revealed the presence of a 18-kDa sentrin monomer, a 90-kDa band (p90), and multiple high molecular mass bands. Because sentrin possesses the conserved Gly-Gly residues near the C terminus, it is likely that these additional bands represent conjugation of sentrin to other proteins in a manner that is similar to the ubiquitination pathway. Transient expression of hemagglutinin epitope-tagged sentrin mutants in COS cells demonstrated that the sentrin C terminus is cleaved, which allows it to be conjugated to other proteins via the conserved C-terminal Gly residue. Immunocytochemical staining and cell fractionation analysis demonstrated that sentrin monomer is localized predominantly to the cytosol. However, p90 and the majority of sentrinized proteins appeared to be localized to the nucleus. When the conserved Gly-Gly residues of sentrin were changed to Gly-Ala, only sentrin monomer and p90 but not the high molecular mass bands were observed. Thus, p90 generation appears to be required for the formation of high molecular mass bands in the nucleus. Taken together, sentrinization represents a novel pathway for nuclear protein modification, which is distinct from ubiquitination.


Prevalence, frequency, onset, desistance and criminal career duration in self-reports compared with official records.
The main aim of this article is to compare prevalence and frequency, ages of onset and desistance, and criminal career duration, according to self-reports and convictions. In the Cambridge Study in Delinquent Development, 411 London males have been followed up from age 8 to age 48, in interviews and criminal records. Virtually all males admitted at least one of eight offences, compared with about one third who were convicted. In self-reports, the number of offences was over 30 times greater, the age of onset was earlier and the career duration was longer, compared with convictions. However, the age of desistance was generally later according to convictions. Self-reported ages of desistance may be affected by increasing concealment with age. The gap between the first self-reported offence and the first conviction provides an opportunity for early intervention.


Mechanisms of action and potential therapeutic uses of thalidomide.
Thalidomide was first introduced to the market in Germany under the brand name of Contergan in 1956, as a non-barbiturate hypnotic, advocated to ensure a good nights sleep and to prevent morning sickness in pregnancy. It was advertised for its prompt action, lack of hangover, and apparent safety. It has been banned from the market since 1963 after it caused the worldwide teratogenic disaster: babies exposed to thalidomide in utero during the first 34-50 days of pregnancy were born with severe life-threatening birth defects. Despite its unfortunate history, thalidomide has attracted scientific interest again because of its recently discovered action against inflammatory diseases and cancer. Its broad range of biological activities stems from its ability to moderate cytokine action in cancer and inflammatory diseases. Early studies examined its anxiolytic, mild hypnotic, antiemetic, and adjuvant analgesic properties. Subsequently, thalidomide was found to be highly effective in managing the cutaneous manifestations of leprosy, being superior to Aspirin in controlling leprosy-associated fever. Recent research has shown promising results with thalidomide in patients with myeloma, myelodysplastic syndrome, a variety of infectious diseases, autoimmune diseases, cancer, and progressive body weight loss related to advanced cancer and AIDS. Here we review the history of its development, pharmacokinetics, metabolism, biologic effects, and the results of clinical trials conducted thus far. Further research in this field should be directed towards better understanding of thalidomide metabolism, its mechanism of action, and the development of less toxic and more active analogs.


Therapeutic and Histopathological Effect of Aloe vera and Salvia officinalis Hydroethanolic Extracts against Streptococcus iniae in Rainbow Trout.
Some of the medicinal plants have antibacterial contents and appear to be proper alternatives for antibiotics in the treatment of streptococcal disease, which causes plenty of mortalities in fish farms annually. Therefore, this study investigated the therapeutic effect of Aloe vera and Salvia officinalis hydroethanolic extracts against Streptococcus iniae in rainbow trout. Plant extracts components were analyzed by Gas chromatography-mass spectrometry method and tested in vitro against S. iniae by disk diffusion assay. In in vivo, 480 rainbow trout (10±0.1 g) were distributed in 9 groups (with 3 replication), and all groups (except for the first group as the negative control that was injected with 100 µl of physiologic serum) were injected by 100 µl of LD50 (3.66×108.5CFU/ml) of S. iniae suspension, intraperitoneally. The fish of groups were treated by A. vera and S. officinalis extracts in doses 0 (positive control group was fed by commercial diet without plant extract), 0.5, 1, and 1.5% (supplemented diet) and 80 mg/kg body weight erythromycin for the next 10 days. At the end of the study period, tissue samples of the gills and livers of all groups were taken for the histopathological lesion assay. The results showed that A. vera and S. officinalis had antibacterial components as Cineol, and S. iniae was sensitive to both A. vera (MBC=4.067 mg/ml) and S. officinalis (MBC=5.185 mg/ml) extracts. At the end of the treatment period, there were no significant differences among erythromycin, A. vera (1.5%), and A. vera (1%) in terms of the mortality of the infected fish (P˂0.05). Moreover, A. vera (1.5%) showed a significantly lower mortality rate, compared to the positive control (P˂0.05). A. vera (1.5%) was the best group to moderate all histopathological lesions, compared to other groups. Accordingly, A. vera (1.5 %) is useful to treat streptococcosis (caused by S. iniae) and alter gill and liver histopathological lesions in rainbow trout.


Effects of isoflurane anesthesia on equine liver function.
The acute 2-hour effects of isoflurane anesthesia on liver function and biliary excretion were examined in 2 ponies prepared surgically with chronic external biliary fistulas (T-tubes). Studies were conducted 2 to 8 months postoperatively with the enterohepatic circulation held intact between studies. Bile acid infusion IV (8.1 to 8.8 mumol/min) helped maintain bile flow and bile acid and bilirubin excretion during complete biliary diversion throughout each study. Following 3-hour control periods, anesthesia was induced and maintained at 1.3 to 1.5 minimal alveolar concentration plus O2 (spontaneous breathing) for 2 hours. Compared with the immediate 2-hour preanesthesia values, isoflurane caused significant increases in PCV (27%) and biliary bilirubin excretion (24%). However, no significant differences were detected in plasma or biliary bilirubin concentrations, biliary bile acid concentration or excretion, bile flow, or plasma aspartate aminotransferase concentrations between preanesthesia control and anesthesia periods. The results indicate that although isoflurane anesthesia enhanced hepatic bilirubin excretion, its effects on hepatic bilirubin formation and/or clearance are modest, compared with effects of halothane anesthesia which have previously been shown to enhance equine bilirubin excretion by 138% and reduce bile acid excretion by 27%. Isoflurane anesthesia in ponies does not appear to affect hepatic bile acid transport or bile formation significantly.


Synthesis and Characterization of Water-soluble Conjugates of Cabazitaxel Hemiesters-Dextran.
Cabazitaxel (CTX) is a second- generation taxane derivative, a class of potent anticancer drugs with very low water solubility. CTX is used in patients with resistant prostate cancer unresponsive to the first generation taxane, docetaxel. Currently marketed formulations of CTX contain high concentrations of surfactant and ethanol, which cause severe hypersensitivity reactions in patients. In order to increase its solubility, two hemiester analogs; CTX-succinate and CTX-glutarate were synthesized and characterized. To improve the solubility of hemiesters even more, dextran as a biocompatible polymer was also conjugated to hemiester analogs. MTT assay was performed on MCF-7 cell line to evaluate the cytotoxicity effect of hemiesters and conjugates. Based on the results, hemiester analogs increased water solubility of the drug up to about 3 and 8 fold. Conjugation to dextran enhanced the CTX solubility to more than 1500 fold. These conjugates released the conjugated CTX in less than 24 hours in a pH dependent manner and showed proper hemocompatibility characteristics. The hemiesters had approximately similar cytotoxicity in comparison with CTX and the dextran conjugates showed higher cytotoxicity effect on MCF-7 cell line.


Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy.
Introduction: Despite the availability of new vaccines for SARS-CoV-2, there has been slow uptake and problems with supply in some parts of the world. Hence, there is still a necessity for drugs that can prevent hospitalization of patients and reduce the strain on health care systems. Drugs with sigma affinity potentially provide protection against the most severe symptoms of SARS-COV-2 and could prevent mortality via interactions with the sigma-1 receptor.Areas covered: This review examines the role of the sigma-1 receptor and autophagy in SARS-CoV-2 infections and how they may be linked. The authors reveal how sigma ligands may reduce the symptoms, complications, and deaths resulting from SARS-CoV-2 and offer insights on those patient cohorts that may benefit most from these drugs.Expert opinion: Drugs with sigma affinity potentially offer protection against the most severe symptoms of SARS-CoV-2 via interactions with the sigma-1 receptor. Agonists of the sigma-1 receptor may provide protection of the mitochondria, activate mitophagy to remove damaged and leaking mitochondria, prevent ER stress, manage calcium ion transport, and induce autophagy to prevent cell death in response to infection.


Novel HLA-B27-restricted epitopes from Chlamydia trachomatis generated upon endogenous processing of bacterial proteins suggest a role of molecular mimicry in reactive arthritis.
Reactive arthritis (ReA) is an HLA-B27-associated spondyloarthropathy that is triggered by diverse bacteria, including Chlamydia trachomatis, a frequent intracellular parasite. HLA-B27-restricted T-cell responses are elicited against this bacterium in ReA patients, but their pathogenetic significance, autoimmune potential, and relevant epitopes are unknown. High resolution and sensitivity mass spectrometry was used to identify HLA-B27 ligands endogenously processed and presented by HLA-B27 from three chlamydial proteins for which T-cell epitopes were predicted. Fusion protein constructs of ClpC, Na(+)-translocating NADH-quinone reductase subunit A, and DNA primase were expressed in HLA-B27(+) cells, and their HLA-B27-bound peptidomes were searched for endogenous bacterial ligands. A non-predicted peptide, distinct from the predicted T-cell epitope, was identified from ClpC. A peptide recognized by T-cells in vitro, NQRA(330-338), was detected from the reductase subunit. This is the second HLA-B27-restricted T-cell epitope from C. trachomatis with relevance in ReA demonstrated to be processed and presented in live cells. A novel peptide from the DNA primase, DNAP(211-223), was also found. This was a larger variant of a known epitope and was highly homologous to a self-derived natural ligand of HLA-B27. All three bacterial peptides showed high homology with human sequences containing the binding motif of HLA-B27. Molecular dynamics simulations further showed a striking conformational similarity between DNAP(211-223) and its homologous and much more flexible human-derived HLA-B27 ligand. The results suggest that molecular mimicry between HLA-B27-restricted bacterial and self-derived epitopes is frequent and may play a role in ReA.


Terminal Syme Amputation of the Great Toe in the Pediatric Population.
In the pediatric population, chronic ingrown toenails (onychocryptosis) can cause infection (paronychia), debilitating pain, and may be unresponsive to conservative treatments. Following multiple failed interventions, a terminal Syme amputation is one option for definitive treatment of chronic onychocryptosis. This procedure involves amputation of the distal aspect of the distal phalanx of the great toe with complete removal of the nail bed and germinal center, preventing further nail growth and recurrence. A retrospective review was performed to determine outcomes of a terminal Syme amputation in the pediatric population. Inclusion criteria included treatment of onychocryptosis involving terminal Syme amputation with a minimum follow-up of 1 year. The medical record was reviewed to assess previous failed treatment efforts, perioperative complications, radiographic outcomes, and the need for additional procedures. From 1984 to 2017, 11 patients (13 halluces) with onychocryptosis were treated with a terminal Syme amputation. There were no intraoperative complications. One hallux had a postoperative infection requiring antibiotics as well as partial nail regrowth following the terminal Syme procedure that required subsequent removal of the residual nail. Following partial nail ablation, the patient had no further nail growth. An additional patient also developed a postoperative infection requiring oral antibiotic treatment. All patients returned to full weight-bearing physical activities within 6 weeks of surgery. Terminal Syme amputation was successful in treating pediatric patients who have recalcitrant onychocryptosis and paronychia. There was little functional consequence following terminal Syme amputation of the great toe in this patient population, making it an effective salvage procedure. Level IV-retrospective comparative study.


Halogen- and hydrogen-bonded self-assembled fibrillar networks of substituted 1,3:2,4-dibenzylidene-D-sorbitols (DBS).
Substituting the sole primary hydroxyl group of the low molecular weight organogelator (LMOG), 1,3:2,4-dibenzylidene-D-sorbitol (DBS), with a halogen atom (Cl, Br, or I; i.e., 6-Cl-DBS, 6-Br-DBS, or 6-I-DBS) drastically alters the supramolecular self-assembled fibrillar network (SAFiN) that forms when the molecules aggregate. The SAFiN varies depending on the solvent properties, impacting the role of non-covalent hydrogen- and halogen-bonding interactions along and between fibers. The halogenated DBS derivatives have more coherent crystalline fibers than DBS, with larger length-to-width aspect ratios. High-resolution synchrotron powder X-ray diffraction of each wet-state gel in toluene and DFT optimization obtained complete structures for the three halogenated DBS derivatives in their SAFiNs. The presence of a halogen atom reduces the reliance on hydrogen bonding by enabling new halogen bonding interactions that impact the self-assembly behavior, especially in solvents of higher polarity. For 6-I-DBS and 6-Br-DBS, the primary forces driving molecular self-assembly are C-H⋯π and intermolecular halogen-to-halogen interactions, and there is one unique molecule in each unit cell. However, the Cl atoms of 6-Cl-DBS are not close, and its SAFiN structures rely more on hydrogen bonding. As a result, the enhanced hydrogen bonding, electronic differences among the halogens, and spatial factors allow its unit cell to include two independent molecules of 6-Cl-DBS.


Induction of an auto-anti-IgE response in rats. III. Inhibition of a specific IgE response.
An auto-anti-IgE response was induced in conventional (PVG-RT1U and high IgE-producing (BN) rat strains by immunization with a highly purified rat IgE myeloma IR2. Earlier work established that total serum IgE levels were decreased by this procedure (Marshall & Bell, 1985) but only in the PVG-RT1U strain. IR2-immunized rats were tested for their ability to produce a specific IgE response to ovalbumin (OVA). The primary anti-OVA IgE response was inhibited by 60-75% in both rat strains, regardless of whether the total serum levels of IgE were reduced. The secondary IgE response to OVA was also inhibited in anti-IgE-producing animals but not in rats primed with OVA before anti-IgE induction. The inhibition of the anti-OVA response was isotype specific; the IgG response to OVA was unaffected. These studies may help elucidate the regulatory role played by naturally occurring anti-IgE antibodies found particularly in atopic individuals.


Rat lung carbonic anhydrase: activity, localization, and isozymes.
Carbonic anhydrase activity in rat lungs perfused free of blood was localized by homogenization of the tissue followed by differential centrifugation. Four fractions were obtained from the homogenate, a cell debris pellet with a mitochondrial pellet and a microsomal pellet with a clear cytosol supernatant. The last named fraction contained 67% of the total enzyme activity; the cell debris contained 18%, and the mitochondrial and microsomal contained 8 and 7%, respectively. Of the 33% of enzyme activity associated with the pellet fraction, 25% could be experimentally defined as membrane associated by its solubilization with 0.3 M tris-(hydroxymethyl) aminoethane sulfate buffer. The remainder was defined as membrane bound. Purification of the soluble carbonic anhydrase from the lung yielded two isozymes with electrophoretic and inhibitor sensitivities apparently identical with the blood isozymes. Hemoglobin analysis showed that the lung isozymes could not have included more than 0.03% enzyme from blood contamination. The carbonic anhydrase activity present in the whole rat lung would give an average acceleration of the CO2 hydration reaction under physiological conditions over the uncatalyzed rate of 122, sufficient to maintain equilibration between CO2 and plasma HCO3- during blood transit of the lung. If the membrane-associated activity is mostly on the plasma membrane of the endothelial cells and available to the capillary blood, it would be sufficient to give this acceleration. We suggest that the possible source of this membrane-associated activity might be adsorption from the blood of carbonic anhydrase liberated by erythrocyte lysis.


Serum ceruloplasmin levels in acute decompensated heart failure.
Ceruloplasmin (Cp) is a serum protein that belongs to the family of α2-globulins and it is increased in patients with after acute myocardial infarction complicated with heart failure. Aim of the study was to investigate levels of serum Cp in patients with acute decompensated heart failure. The present cross-sectional observational study consists of three groups: Fifty patients with decompensated heart failure (Group 1) and same 50 patients after compensation (Group 2); 50 control patients group with comparable age and sex without heart failure (Group 3). Demographic, echocardiographic and biochemical data of patients were collected. Serum Cp level was determined spectrophotometrically. Serum ceruloplasmin was significantly increased in Groups 1 (820.8 ± 78.5 IU/dL) and 2 (873.5 ± 121.0 IU/dL) compared, to Group 3 (640.6 ± 132.4 IU/dL) (p<0.001). In the sub-group analysis, this difference was due to the difference between Groups 3, Group 1 and 2 (both p=0.0001) whereas no significant difference was present between Group I and Group 2 (p>0.063). A positive correlation was found between Cp and female sex, heart rate, systolic and diastolic blood pressure, acetylsalisilic acid and diuretic use, left ventricular systolic and diastolic diameter, mitral regurgitation, and negative correlation was found between Cp and ejection fraction (p<0.05 for all) whereas none of the parameters were independently associated with serum Cp level (p>0.05). Findings of the present study suggest that serum Cp level is increased in both decompensated and compensated HF compared to controls. Further large scale studies are needed to elucidate the pathophysiological mechanisms of increased Cp in HF.


Gain dependence of the linewidth of Brillouin amplification in optical fibers.
We report a novel, pump-power dependent, linewidth broadening effect in stimulated Brillouin amplification of a continuous-wave probe by a pulsed pump. This behavior is different from the case of two interacting continuous-wave pump and probe fields, where the shape of the logarithmic Brillouin gain spectrum is independent of the pump power. Studying this effect numerically and experimentally and also analytically, we find that for a given width of the pump pulse the Brillouin linewidth grows linearly with the Brillouin logarithmic gain with a slope, which inversely depends on the pulse width. Thus, for example, in a standard single-mode fiber, a 15ns pump pulse, strong enough to generate a gain of 0.5dB, broadens the logarithmic lineshape by ~1.5MHz, while a 45ns pulse, providing the same gain, increases the linewidth by only ~0.5MHz. Since the rising and falling slopes of the shape of the Brillouin gain spectrum are also gain dependent, this effect might challenge the calibration of Brillouin distributed slope-assisted sensing techniques.


Study the effect of s-methyl L-cysteine on lipid metabolism in an experimental model of diet induced obesity.
S-methyl L-cysteine (SMC) is a hydrophilic cysteine-containing compound naturally found in Alium plants such as, garlic and onion. The present study was aimed to evaluate the hypoglycemic and antihyperlipidemic properties of SMC in high fructose induced diabetic rats. The present study was designed to evaluate the hypoglycemic and antihyperlipidemic properties of SMC in high fructose induced diabetic rats. Blood samples were collected and the fasting plasma glucose, lipid profile, total antioxidant status (TAS) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were estimated using standard procedures. Differences between the groups were assessed by using One way Analysis of Variance with (ANOVA) Tukey post hoc test. Oral administration of SMC at a dose of 100 mg/kg bodyweight/day to HFD-treated rats for a period of 60 days showed significant reduction in the animal weight, fasting plasma glucose, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), VLDL-C and elevation in the level of high-density lipoprotein cholesterol (HDL-C) and TAS compared with fructose fed group. The effects of SMC was compared with metformin; a well-known antihyperglycemic drug. In conclusion, SMC found to be effective in improving the high fructose induced hyperglycemia and dyslipidemia. It may possibly provide a potential adjuvant for the treatment and management of diabetes.


Numerical investigation of particle formation mechanisms in silane discharges.
The formation of particles in low-pressure silane discharges has been studied extensively over the last decade. In this paper we try to identify, by numerical simulations, the precursors of the dust formation and we examine the gas-phase reactions leading to larger clusters, and finally to nanometer or micrometer sized particles. A one-dimensional fluid model is used, which incorporates silicon hydrides (Si(n)H(m)) containing up to 12 silicon atoms. A set of 68 species, including neutrals, radicals, ions, and electrons, is taken into account. The importance of various cluster reaction sequences is discussed. Besides the discussion of ion-molecule and ion-ion reactions, the role of the vibrationally excited silane molecules and of SiH3 radicals on the particle growth process is studied. Finally, the effect of temperature variation on the density of the dust particles is investigated.


Problem-based learning in clinical bioinformatics education: Does it help to create communities of practice?
We have now reached the genomics era within medicine; genomics is being used to personalise treatment, make diagnoses, prognoses, and predict adverse outcomes resulting from treatment with certain drugs. Genomic data is now abundant in healthcare, and the newly created profession of clinical bioinformaticians are responsible for its analysis. In the United Kingdom, clinical bioinformaticians are trained within a 3-year programme, integrating a work-based placement with a part-time Master's degree. As this profession is still developing, trainees can feel isolated from their peers whom are located in other hospitals and can find it difficult to gain the mentorship that they require to complete their training. Building strong networks or communities of practice (CoPs) and allowing sharing of knowledge and experiences is one solution to addressing this isolation. Within the Master's delivered at the University of Manchester, we have integrated group-centred problem-based learning (PBL) using real clinical case studies worked on during each course unit. This approach is combined with a flipped style of teaching providing access to online content in our Virtual Learning Environment before the course. The face-to-face teaching is used to focus on the application of the students' knowledge to clinical case studies. In this study, we conducted semistructured interviews with 8 students, spanning 3 cohorts of students. We evaluated the effectiveness of this style of teaching and whether it had contributed to the formation of CoPs between our students. Our findings demonstrated that this style of teaching was preferred by our students to a more traditional lecture-based format and that the problem-based learning approach enabled the formation of CoPs within these cohorts. These CoPs are valuable in the development of this new profession and assist with the production of new guidelines and policies that are helping to professionalise this new group of healthcare scientists.


Mid-term assessment of subtalar arthroereisis with Talar-Fit implant in pediatric patients with flexible flatfoot and comparing the difference between different sizes and exploring the position of the inserted implant.
Subtalar arthroereisis (STA) has gained growing acceptance as a viable approach solution for the management of pediatric flexible flatfoot. However, STA still remains controversial. The purpose of this study is to assess the effect of STA using the Talar-Fit implant for treating pediatric flexible flatfoot. Specifically, the aims of the study are as follows: first, to present the mid-term outcomes of STA using the Talar-Fit implant; second, to compare the radiographic and clinical outcomes associated with varying sizes of Talar-Fit implant; and third, to analyze the optimal position of the inserted implants. A retrospective analysis was conducted on a cohort of 57 pediatric patients diagnosed with flexible flatfoot (77 feet) who underwent STA utilizing Talar-Fit between January 2014 and December 2021. The participants were categorized into five groups according to the size of the implant: Group 8, Group 9, Group 10, Group 11, and Group 12. The evaluation included the assessment of clinical function using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind foot score, as well as the assessment of radiographic data such as the calcaneal pitch angle (CPA), lateral Meary angle (LMA), talar declination angle (TDA), and medial longitudinal arch angle (MLAA) were evaluated. Furthermore, the position of the inserted implants was also recorded, including angle, depth, and distance. The comparison of pre- and postoperation was conducted using the paired Student's t-test, whereas the analysis of differences among subgroups was performed using the Wilcoxon rank-sum test. A P-value < 0.05 is considered statistically significant. In total, 57 pediatric patients (77 feet) were successfully followed-up for an average period of 26.8 months. The overall AOFAS score significantly improved from 58.6 ± 10.9 to 85.2 ± 8.6 (P < 0.001). Furthermore, the LMA decreased from 20.3° ± 3.6° to 4.5° ± 1.3°, the CPA increased from 14.8° ± 1.6° to 23.6° ± 2.7°(P < 0.05), the TDA decreased from 40.2° ± 2.3° to 25.5° ± 3.2°(P < 0.05), and the MLAA decreased from 140.1° ± 2.8° to 121.4° ± 3.9°(P < 0.05). No statistically significant differences were observed among subgroups regarding the final outcomes. The improvements of CPA, TDA, and MLAA among different groups were significantly different; however, the adjusted P-values were all greater than 0.05. The implant were inserted at a mean angle of 89.5° ± 2.4°, a mean depth of 0.9 mm ± 2.1 mm, and a mean distance of 9.9 mm ± 0.9 mm. Eight patients experienced complications, including six cases of pain occurrence and two cases of implant dislocation. STA with Talar-Fit has demonstrated satisfactory mid-term outcomes. A Talar-Fit with a larger size may demonstrate a superior effect when compared with that of a smaller size. The implants were inserted in a similar position, indicating that the medial edge of the implant may be possible to transcend the midline of the talus neck.


Functional networks in parallel with cortical development associate with executive functions in children.
Children begin performing similarly to adults on tasks requiring executive functions in late childhood, a transition that is probably due to neuroanatomical fine-tuning processes, including myelination and synaptic pruning. In parallel to such structural changes in neuroanatomical organization, development of functional organization may also be associated with cognitive behaviors in children. We examined 6- to 10-year-old children's cortical thickness, functional organization, and cognitive performance. We used structural magnetic resonance imaging (MRI) to identify areas with cortical thinning, resting-state fMRI to identify functional organization in parallel to cortical development, and working memory/response inhibition tasks to assess executive functioning. We found that neuroanatomical changes in the form of cortical thinning spread over bilateral frontal, parietal, and occipital regions. These regions were engaged in 3 functional networks: sensorimotor and auditory, executive control, and default mode network. Furthermore, we found that working memory and response inhibition only associated with regional functional connectivity, but not topological organization (i.e., local and global efficiency of information transfer) of these functional networks. Interestingly, functional connections associated with "bottom-up" as opposed to "top-down" processing were more clearly related to children's performance on working memory and response inhibition, implying an important role for brain systems involved in late childhood.


Predictive Value of an Alternative Strategy for Measuring Depth and Size of Stage 1 Vulvar Squamous Cell Carcinoma.
Despite poor reproducibility for measuring vulvar cancer depth, 1-mm or greater invasion triggers lymphadenectomy for small tumors. Previous literature suggests that measuring depth from the nearest dysplastic rete peg (alternative method) rather than highest dermal papilla (conventional method) may be acceptable. Pathologic staging and follow-up information were recorded for 100 pT1 vulvar squamous cell carcinoma (SCC) resected from 1990 to 2019. Conventional depth, alternative depth, gross/clinical size, and size of the invasive component were measured for each tumor. In this retrospective study, we evaluated which clinicopathologic factors were most predictive of lymph node involvement and recurrence. Depending on the measurements used (conventional vs alternative depth, clinical lesion size vs cumulative extent of invasive component), between 1 and 18 cases were downstaged to pT1a. All such cases were pN0, without lymphovascular or perineural invasion. Infiltrative cords (hazard ratio [HR] = 5.15; 95% CI = 1.63-16.2; p = .005) and perineural invasion (HR = 3.16; 1.18-8.45; p = .022) were most strongly associated with groin recurrence. Of staging criteria evaluated, only cumulative extent of the invasive component 2 cm or greater was significantly associated with groin recurrence (HR = 2.87; 1.01-8.17; p = .048). The Kaplan-Meier curves for local recurrence-free survival by stage did not show significant separation regardless of method. Patients downstaged using alternative measurement techniques lacked nodal disease/recurrence; one-third of those with nodal sampling experienced postoperative morbidity. Our data suggest that the use of alternative depth and cumulative extent of invasion could safely allow some conventional stage IB vulvar SCC patients to avoid groin surgery, thereby reducing treatment-related morbidity.


[Fermentation and colicinogeny for differentiation of Salmonella enteritidis (Gaertner's bacterium)].
Study material of 435 strains of Salmonella enteritidis which were predominantly cultivated from human specimens in Schleswig-Holstein in the years from 1968 to 1978, was used for investigating the biochemical differentiation by the fermentation of arabinose, dulcitol, rhamnose and glycerol (method after Kauffmann); moreover, the decarboxylation of lysine and the gas formation from glucose as well as the colicinogenicity (indicator Escherichia coli K 12 ROW) were tested. The 4 classical biotypes showed the following rates of incidence (in %): Jena 77.2; Danysz 2.3; Chaco 1.6; Essen 9.0; 9.9 per cent of all isolates did not permit classification, among them there were 19 (4.4%) strains of unknown rhamnose-negative biotypes some of which formed no gas from glucose. Four cultures (1 Jena strain, 3 Danysz strains) were LDC-negative. The colicinogenicity was identified in 20 isolates, among them 18 strains alone in a single outbreak. The analyses revealed that the fermentation properties were constant within outbreaks while the colicinogenicity may get lost in some strains within an outbreak.


Elimination of plasmids from Enterobacteriaceae by 4-quinolone derivatives.
Twelve 4-quinolones (cinoxacin, ciprofloxacin, enoxacin, flumequin, nalidixic acid, norfloxacin, oxolinic acid, pefloxacin, pipemidic acid, rosoxacin, and piromidic and beta-hydroxypiromidic acids) and novobiocin, were used at subinhibitory concentrations to eliminate from Escherichia coli 11 antibiotic resistance plasmids belonging to different incompatibility groups. The 12 4-quinolones were also tested for their ability to cure virulence plasmids from five species of Enterobacteriaceae. All quinolones eliminated three antibiotic resistance plasmids (R446b, R386, S-a) and one virulence plasmid (pWR105), but at a low rate. Optimal curing of antibiotic resistance plasmids was obtained in human urine. Two virulence plasmids (pWR24 and pWR110) were eliminated only by flumequin and pefloxacin. Novobiocin eliminated three antibiotic resistance plasmids (R446b, R386, pIP24). The variable and low level of plasmid loss may be explained by the induction of the recA system. In addition, the inability to eliminate certain plasmids could be due to their presence in high numbers per cell.


RGD surface functionalization of the hydrophilic acrylic intraocular lens material to control posterior capsular opacification.
Posterior Capsular Opacification (PCO) is the capsule fibrosis developed on implanted IntraOcular Lens (IOL) by the de-differentiation of Lens Epithelial Cells (LECs) undergoing Epithelial Mesenchymal Transition (EMT). Literature has shown that the incidence of PCO is multifactorial including the patient's age or disease, surgical technique, and IOL design and material. Reports comparing hydrophilic and hydrophobic acrylic IOLs have shown that the former has more severe PCO. On the other hand, we have previously demonstrated that the adhesion of LECs is favored on hydrophobic compared to hydrophilic materials. By combining these two facts and contemporary knowledge in PCO development via the EMT pathway, we propose a biomimetically inspired strategy to promote LEC adhesion without de-differentiation to reduce the risk of PCO development. By surface grafting of a cell adhesion molecule (RGD peptide) onto the conventional hydrophilic acrylic IOL material, the surface-functionalized IOL can be used to reconstitute a capsule-LEC-IOL sandwich structure, which has been considered to prevent PCO formation in literature. Our results show that the innovative biomaterial improves LEC adhesion, while also exhibiting similar optical (light transmittance, optical bench) and mechanical (haptic compression force, IOL injection force) properties compared to the starting material. In addition, compared to the hydrophobic IOL material, our bioactive biomaterial exhibits similar abilities in LEC adhesion, morphology maintenance, and EMT biomarker expression, which is the crucial pathway to induce PCO. The in vitro assays suggest that this biomaterial has the potential to reduce the risk factor of PCO development.


Studying the non-thermal effects of terahertz radiation on E. coli/pKatG-GFP biosensor cells.
Studies of the impact of terahertz radiation on living objects present a significant interest since its use for security systems is currently considered promising. We studied the non-thermal impact of terahertz radiation on E. coli/pKatG-gfp biosensor cells. The Novosibirsk free electron laser (NovoFEL), which currently has the world's highest average and peak power, was used as the source of terahertz radiation. We demonstrated that exposure to terahertz radiation at the wavelengths of 130, 150, and 200 µm and a power of 1.4 W/cm(2) induces changes in green fluorescent protein (GFP) fluorescence values and thus induces the expression of GFP in E. coli/pKatG-gfp biosensor cells. Possible mechanisms of the E. coli response to non-thermal exposure to terahertz radiation are discussed.


Comparison of linoleic acid-containing water-in-oil emulsion with urea-containing water-in-oil emulsion in the treatment of atopic dermatitis: a randomized clinical trial.
Application of topical moisturizers is an essential part of the management of atopic dermatitis (AD). Linoleic acid (LA), the most abundant fatty acid in the epidermis, and its derivatives have an essential role in the structure and function of the epidermal barrier, and their defects are prominent in AD. The aim of this study was to compare the efficacy and safety of two cosmetic products containing either LA or urea in patients with AD. A total of 20 patients with AD who met the eligibility criteria and provided written informed consents were enrolled in this randomized, intra-individual split-body, single-center trial. Symmetrical lesions of patients were randomized for treatment with LA- or urea-containing water-in-oil (w/o) emulsions applied two to three times daily for 4 weeks. The efficacy of the two products was evaluated by local Scoring Atopic Dermatitis (SCORAD) of both lesions and also patient (or guardian) satisfaction. In addition, trans-epidermal water loss (TEWL), stratum corneum (SC) hydration, pH, sebum, temperature, erythema, melanin content, and ultrasonographic thickness and echo density of epidermis and dermis were measured before, and 2 and 4 weeks after, treatment. Four weeks of treatment with the LA-containing product resulted in a significant decrease in local SCORAD, TEWL, erythema, and echo density of dermis, as well as an increase in SC hydration compared to baseline. The urea-containing product also reduced the local SCO-RAD and echo density of dermis and increased SC hydration. In contrast to the LA-containing product, changes in TEWL and erythema were not significant. Moreover, the reduction of erythema was significantly higher in the LA-containing product-treated side compared to the urea-containing product-treated side (p = 0.006). Both LA- or urea-containing w/o emulsions can significantly improve barrier dysfunction and clinical severity of AD. In agreement with literature, it was confirmed that an LA-containing w/o emulsion exhibited erythema-reducing effects. Since emollients should be used on a regular basis, patients should choose a product by individual preference following recommendation by their dermatologists.


Progesterone-induced miR-152 interferes with embryonic implantation by downregulating GLUT3 in endometrial epithelium.
To investigate the role of progesterone-induced micro-RNA (miR)-152 in early embryonic development and implantation by regulating GLUT3 in endometrial epithelium, qRT-PCR was used to detect the expression of miR-152, GLUT1, and GLUT3 in the endometrial epithelial cells of female mice. GLUT1 and GLUT3 proteins were detected by immunohistochemical staining in the mouse endometrial epithelium. Bioinformatics prediction associated with a luciferase assay was performed to determine whether GLUT1 and GLUT3 are target genes of miR-152. Specific miR-152 mimics or inhibitors were transfected into the endometrial epithelial cells to, respectively, overexpress or downregulate miR-152. Next, the glucose concentration of uterine fluid was measured by conducting high-performance liquid chromatography in vivo, and the glucose uptake of the endometrial epithelial cells was observed using a fluorometric assay in vitro. Early embryonic development and implantation were also observed after the miR-152 mimics or inhibitors had been transfected. Embryo transfer was observed after the miR-152 mimic transfection. miR-152 was found to directly target and thereby downregulate GLUT3 expression. The expressions of both miR-152 and GLUT3 in the mouse endometrial epithelium had spatiotemporal characteristics on days 1-4 of pregnancy. miR-152 affected the glucose concentration of uterine fluid and the glucose uptake of endometrial epithelial cells. The transfection of specific miR-152 mimics led to impaired embryonic development and implantation. To conclude, in endometrial epithelial cells, progesterone-induced miR-152 downregulates GLUT3 at the posttranscriptional level to maintain a proper glucose concentration in the uterine fluid, which is necessary for early embryonic development and implantation.


The small-bat-in-summer paradigm: Energetics and adaptive behavioural routines of bats investigated through a stochastic dynamic model.
Strong seasonality at high latitudes represents a major challenge for many endotherms as they must balance survival and reproduction in an environment that varies widely in food availability and temperature. To avoid energetic mismatches caused by limited foraging time and stochastic weather conditions, bats employ the energy-saving state of torpor during summer to save accumulated energy reserves. However, at high-latitude small-bats-in-summer face a particular challenge: as nocturnal foragers, they rely on the darkness at night to avoid predators and/or interspecific competition, but live in an environment with short, light summer nights, and even a lack of true night at the northernmost distributions of some bat species. To predict optimal behaviour in relation to latitudinal variation in diurnal cycles, we constructed a stochastic dynamic programming model of bats living at high latitudes. Using a stochastic dynamic programming framework with values that are representative for our study system, we show that individual energetic reserves are a strong driver of daytime use of torpor and night-time foraging behaviour alike, with these linked effects being both temperature- and photoperiod-dependent. We further used the model to predict survival probabilities at five locations across a latitudinal gradient (60.1° N to 70.9° N), finding that combinations of photoperiod and temperature conditions limited population distributions in the model. To verify our model results, we compared predictions for optimal decisions with our own empirical data collected on northern bats (Eptesicus nilssonii) from two latitudes in Norway. The similarities between our predictions and observations provide strong evidence that this model framework incorporates the most important drivers of diurnal decision-making in bat physiology and behaviour. Comparing empirical data and model predictions also revealed that bats facing lighter night conditions further north restrict their mass gain, which strengthens the hypothesis that predation threat is a main driver of bat nocturnality. Our model findings regarding state-dependent decisions in bats should contribute to the understanding of how bats cope with the summer challenges at high latitudes.


Comparison of ultrasound guided surgery and radio-guided occult lesions localization (ROLL) for nonpalpable breast cancer excision.
There is little literature comparing intraoperative ultrasound (IOUS) with radio-guided occult lesions localization (ROLL) in nonpalpable invasive tumors in breast conserving surgery (BCS). There is a need to compare these two methods in terms of safety and efficacy. This is an observational cohort study. All patients treated with BCS for nonpalpable invasive breast cancer using IOUS from March 2016 to March 2020 were included and compared with a historical reference control group operated on using ROLL from March 2013 to March 2017. For each detection method, the ability to locate tumors intraoperatively, tumor and surgical specimen sizes, total resection volume (TRV), optimal resection volume, excess of healthy tissue resected (ETR), margin status, re-excision rate, surgical time, complications and costs were studied. One hundred and fifty-eight were included, 83 with IOUS and 75 with ROLL. The mean tumor size is equivalent in both groups (11.88 mm IOUS vs. 12.29 mm ROLL, P=0.668). TRV is significantly lower with IOUS (24.92 vs. 60.32 cm3, P<0.001), and the ETR is also significantly lower in the IOUS group (21.74 vs. 58.37 cm3, P<0.001). The rate of positive margins did not differ (10.98% vs. 12.16%, P=1), nor did re-excision rate (10.98% vs. 8.11%, P=0.597). Complication rate did not differ (12.2% IOUS vs. 10.81% ROLL, P=0.808). Surgical time was shorter in IOUS (45.5 vs. 57 min, P>0.05). IOUS in BCS for nonpalpable invasive breast cancer is more accurate than ROLL because it decreases excision volumes with the same rate of free margins and re-excision. Also, IOUS is a more efficient and comfortable technique, and just as safe as ROLL.


Supervised learning to quantify amyloidosis in whole brains of an Alzheimer's disease mouse model acquired with optical projection tomography.
Alzheimer's disease (AD) is characterized by amyloidosis of brain tissues. This phenomenon is studied with genetically-modified mouse models. We propose a method to quantify amyloidosis in whole 5xFAD mouse brains, a model of AD. We use optical projection tomography (OPT) and a random forest voxel classifier to segment and measure amyloid plaques. We validate our method in a preliminary cross-sectional study, where we measure 6136 ± 1637, 8477 ± 3438, and 17267 ± 4241 plaques (AVG ± SD) at 11, 17, and 31 weeks. Overall, this method can be used in the evaluation of new treatments against AD.


Role of Ceramides in the Molecular Pathogenesis and Potential Therapeutic Strategies of Cardiometabolic Diseases: What we Know so Far.
Ceramides represent a class of biologically active lipids that are involved in orchestrating vital signal transduction pathways responsible for regulating cellular differentiation and proliferation. However, accumulating clinical evidence have shown that ceramides are playing a detrimental role in the pathogenesis of several diseases including cardiovascular disease, type II diabetes and obesity, collectively referred to as cardiometabolic disease. Therefore, it has become necessary to study in depth the role of ceramides in the pathophysiology of such diseases, aiming to tailor more efficient treatment regimens. Furthermore, understanding the contribution of ceramides to the pathological molecular mechanisms of those interrelated conditions may improve not only the therapeutic but also the diagnostic and preventive approaches of the preceding hazardous events. Hence, the purpose of this article is to review currently available evidence on the role of ceramides as a common factor in the pathological mechanisms of cardiometabolic diseases as well as the mechanism of action of the latest ceramides-targeted therapies.


The cytotoxicity of the parvovirus minute virus of mice nonstructural protein NS1 is related to changes in the synthesis and phosphorylation of cell proteins.
Autonomous parvoviruses exert lytic and cytostatic effects believed to contribute to their antineoplastic activity. Studies with inducible clones have demonstrated a direct involvement of parvovirus nonstructural proteins (NS) in oncolysis. Human and rat fibroblasts have been stably transfected with MVM(p) (minute virus of mice prototype strain) NS genes cloned under the control of a hormone-inducible promoter. Dexamethasone-induced synthesis of the NS proteins in sensitive transformed cells results in cell killing within a few days. From these sensitive cell lines have been isolated some NS-resistant clones that also prove resistant to MVM(p) infection, suggesting that cell factors modulate NS cytotoxicity. We have previously reported that factors involved in cell cycle regulation may contribute to this modulation, since NS toxicity requires cell proliferation and correlates with a cell cycle perturbation leading to an arrest in phase S/G2. In addition to its role in cytotoxicity, NS1 can regulate transcription driven by parvovirus and nonparvovirus promoters. Since phosphorylation is a critical event in controlling the activity of many proteins, notably transcription factors and cell cycle-regulated proteins, we have examined the effect of NS1 on the synthesis and phosphorylation of cell proteins. Our results indicate that NS1 interferes, within 7 h of induction, with phosphorylation of a protein of about 14 kDa (p14). Cell synchronization has enabled us to show that phosphorylation of this protein occurs in early S phase and is prevented when NS1 is induced. This early effect of NS1 on p14 phosphorylation may be directly linked to cytotoxicity and is probably related to the previously reported inhibition of cell DNA synthesis. Late in the induction period (24 h), NS1 also alters the synthesis of a 50-kDa protein and a 35-kDa protein (p50 and p35, respectively). Microsequencing of p35 reveals sequence homology with beta-tubulin. These effects of NS1, observed only in NS1-sensitive cell lines, may be related to the protein's cytotoxicity.


An in-situ real-time optical fiber sensor based on surface plasmon resonance for monitoring the growth of TiO2 thin films.
An optical fiber sensor based on surface plasmon resonance (SPR) is proposed for monitoring the thickness of deposited nano-thin films. A side-polished multimode SPR optical fiber sensor with an 850 nm-LD is used as the transducing element for real-time monitoring of the deposited TiO2 thin films. The SPR optical fiber sensor was installed in the TiO2 sputtering system in order to measure the thickness of the deposited sample during TiO2 deposition. The SPR response declined in real-time in relation to the growth of the thickness of the TiO2 thin film. Our results show the same trend of the SPR response in real-time and in spectra taken before and after deposition. The SPR transmitted intensity changes by approximately 18.76% corresponding to 50 nm of deposited TiO2 thin film. We have shown that optical fiber sensors utilizing SPR have the potential for real-time monitoring of the SPR technology of nanometer film thickness. The compact size of the SPR fiber sensor enables it to be positioned inside the deposition chamber, and it could thus measure the film thickness directly in real-time. This technology also has potential application for monitoring the deposition of other materials. Moreover, in-situ real-time SPR optical fiber sensor technology is in inexpensive, disposable technique that has anti-interference properties, and the potential to enable on-line monitoring and monitoring of organic coatings.


Chemotherapy inhibits skeletal muscle ubiquitin-proteasome-dependent proteolysis.
Chemotherapy has cachectic effects, but it is unknown whether cytostatic agents alter skeletal muscle proteolysis. We hypothesized that chemotherapy-induced alterations in protein synthesis should result in the increased incidence of abnormal proteins, which in turn should stimulate ubiquitin-proteasome-dependent proteolysis. The effects of the nitrosourea cystemustine were investigated in skeletal muscles from both healthy and colon 26 adenocarcinoma-bearing mice, an appropriate model for testing the impact of cytostatic agents. Muscle wasting was seen in both groups of mice 4 days after a single cystemustine injection, and the drug further increased the loss of muscle proteins already apparent in tumor-bearing animals. Cystemustine cured the tumor-bearing mice with 100% efficacy. Surprisingly, within 11 days of treatment, rates of muscle proteolysis progressively decreased below basal levels observed in healthy control mice and contributed to the cessation of muscle wasting. Proteasome-dependent proteolysis was inhibited by mechanisms that include reduced mRNA levels for 20S and 26S proteasome subunits, decreased protein levels of 20S proteasome subunits and the S14 non-ATPase subunit of the 26S proteasome, and impaired chymotrypsin- and trypsin-like activities of the enzyme. A combination of cisplatin and ifosfamide, two drugs that are widely used in the treatment of cancer patients, also depressed the expression of proteasomal subunits in muscles from rats bearing the MatB adenocarcinoma below basal levels. Thus, a down-regulation of ubiquitin-proteasome-dependent proteolysis is observed with various cytostatic agents and contributes to reverse the chemotherapy-induced muscle wasting.


Wide State-Level Variation In Commercial Health Care Prices Suggests Uneven Impact Of Price Regulation.
Prices charged for health care services in the commercial insurance market are high and vary widely within and between market areas. As a result, prices have been the focus of much policy debate. We extended the literature on commercial prices by examining state-level price variation in the commercial market, relative to Medicare, for a broader set of states and a wider set of services than had been examined. We assessed the potential impact on provider revenue of setting commercial prices at Medicare rates. Consistent with the existing literature, we found that average commercial prices for inpatient and outpatient facility services were about double Medicare fees, while commercial prices for professional services were about 60 percent higher. Finally, average hospital revenue would fall about 35 percent if commercial prices were limited to Medicare rates, but this would vary widely by state. If Medicaid rates were also increased to match Medicare rates, hospital revenue would likely fall by about 30 percent. Given the potentially large impact, policies to address the market failures that lead to high and variable prices in the commercial insurance sector are needed, but they should be structured to avoid the large disruptions that could occur if there were a very rapid transition to Medicare rates in the commercial market.


Benchmarking of Human Dose Prediction for Inhaled Medicines from Preclinical In Vivo Data.
A scientifically robust prediction of human dose is important in determining whether to progress a candidate drug into clinical development. A particular challenge for inhaled medicines is that unbound drug concentrations at the pharmacological target site cannot be easily measured or predicted. In the absence of such data, alternative empirical methods can be useful. This work is a post hoc analysis based on preclinical in vivo pharmacokinetic/pharmacodynamic (PK/PD) data with the aim to evaluate such approaches and provide guidance on clinically effective dose prediction for inhaled medicines. Five empirically based methodologies were applied on a diverse set of marketed inhaled therapeutics (inhaled corticosteroids and bronchodilators). The approaches include scaling of dose based on body weight or body surface area and variants of PK/PD approaches aiming to predict the therapeutic dose based on having efficacious concentrations of drug in the lung over the dosing interval. The most robust predictions of dose were made by body weight adjustment (90% within 3-fold) and by a specific PK/PD approach aiming for an average predicted 75% effect level during the dosing interval (80% within 3-fold). Scaling of dose based on body surface area consistently under predicted the therapeutic dose. Preclinical in vivo data and empirical scaling to man can be used as a baseline method for clinical dose predictions of inhaled medicines. The development of more sophisticated translational models utilizing free drug concentration and target engagement data is a desirable build.


Quantitative analysis of Wenckebach behavior in DDD pacemakers.
Wenckebach-type behavior in P-synchronous pacing modes allows a gradual transition into 2:1 block. As this behavior is dependent on precise timing intervals, it can be quantitated with mathematical equations. In this report, equations for quantitating the Wenckebach escape rate and the (N + 1)/N block points have been derived. These equations were then used to produce plots of Wenckebach escape rates for given AV intervals, atrial refractory periods, and atrial rates. These equations were validated utilizing a DDD pulse generator interfaced with a patient simulation device. The predicted values for the Wenckebach escape rate and ratio (n = 33) correlated highly with the observed values (r = 0.99, P less than 0.0001, and r = 0.97, P less than 0.0001, respectively) thereby validating the derived equations. This quantitative analysis has allowed a close look at the pacing behavior between the maximum tracking rate and the 2:1 block point. These equations may be clinically useful for assessing whether a nontriggering P wave resulted from Wenckebach type block or atrial undersensing and for the more complicated interval analysis in DDDR pacing with rate responsive AV delays and postventricular atrial refractory periods.


Muscle diseases in elders: a 10-year retrospective study.
Muscle complaints are frequent among older adults, but histological data in this setting are scarce. Our objective was to detect the major categories of muscle diseases in the elderly population based on histological study. We reviewed all muscle biopsies performed in our hospital on patients older than the age of 65 during a 10-year period (1988-1997). As a control group, we included the next patient younger than 65 who underwent muscle biopsy after each elderly patient. We recorded demographic, clinical, and histological data of the patients, as well as the final diagnosis. Concordance between pre- and postbiopsy diagnosis was also analyzed. We included 239 muscle biopsies corresponding to elderly patients and 239 to controls. Compared with the control group, elderly patients more frequently exhibited type II fiber atrophy and were diagnosed with a specific myopathy. The latter was achieved in 86 cases (36%), idiopathic inflammatory myopathies and vasculitis being the most frequent diagnoses. Interestingly, in about one quarter of the elderly patients in whom a definite diagnosis of muscle disease was achieved, this diagnosis had not been clinically suspected prior to muscle biopsy. Overall, in 60 out of 239 elderly patients (25%), a specific therapeutic regimen could be instituted on the basis of the muscle biopsy results. Muscle diseases are not rare in elderly patients. Therefore, muscle biopsy constitutes a safe and useful tool for diagnosis because, if not performed, some potentially treatable diseases may be undiagnosed or misdiagnosed.


Exploring the activated adipogenic niche: interactions of macrophages and adipocyte progenitors.
Adult adipose tissue contains a large supply of progenitors that can renew fat cells for homeostatic tissue maintenance and adaptive growth or regeneration in response to external challenges. However, the in vivo mechanisms that control adipocyte progenitor behavior are poorly characterized. We recently demonstrated that recruitment of adipocyte progenitors by macrophages is a central feature of adipose tissue remodeling under various adipogenic conditions. Catabolic remodeling of white adipose tissue by β3-adrenergic receptor stimulation requires anti-inflammatory M2-polarized macrophages to clear dying adipocytes and to recruit new brown adipocytes from progenitors. In this Extra Views article, we discuss in greater detail the cellular elements of adipogenic niches and report a strategy to isolate and characterize the subpopulations of macrophages and adipocyte progenitors that actively participate in adrenergic tissue remodeling. Further characterization of these subpopulations may facilitate identification of new cellular targets to improve metabolic and immune function of adipose tissue.


Animal model of sensitization by inhalation.
Groups of rats exposed to daily inhalation challenge with aerosolized pigeon serum developed precipitating antibody within 2 weeks and definitive granulomatous inflammatory changes in the lung after 7 weeks of exposure. The dissociation of the two responses to an inhalation challenge indicate that the rat model may serve for screening of the various inhalant antigens for their sensitizing potential, and for investigation of the contributory role of some of the factors involved in the pathogenesis of hypersensitivity pneumonitis.


Coronoid impingement syndrome: literature review and clinical management.
This case report discusses the unusual presentation of limited mouth opening as a result of bilateral coronoid process hyperplasia. A 14.5-year-old male patient of white Caucasian ethnicity presented with limited mouth opening, mandibular asymmetry, and dental crowding. Investigations confirmed bilateral coronoid process hyperplasia and management involved bilateral intraoral coronoidectomy surgery under general anaesthesia, followed by muscular rehabilitation. Mouth opening was restored to average maximum opening within 4 months of surgery. Limited mouth opening is a common presentation to medical and dental professionals. The rare but feasible diagnosis of coronoid impingement syndrome should not be overlooked.


Iodocyclization of chiral CF3-allylmorpholinones: a versatile strategy for the synthesis of enantiopure alpha-Tfm-prolines and alpha-Tfm-dihydroxyprolines.
An efficient iodocyclization reaction of a chiral Tfm-allylmorpholinone provides a straightforward route to alpha-Tfm-prolines and alpha-Tfm-dihydroxyprolines. The methodologies developed are particularly well adapted for gram-scale synthesis of enantiopure compounds.


Impact of cerebral aneurysm size on distal intracranial hemodynamics and changes following flow diversion.
The impact of cerebral aneurysm size on distal intracranial hemodynamics such as arterial pressure and Pulsatility Index is not completely understood, either before or after flow diversion. The aim of the study is to assess the impact of aneurysm size on distal Pulsatility Index and pressure before and after flow diversion. From December 2015, prospective measurement of middle cerebral artery pressure and Pulsatility Index was performed in consecutive patients with unruptured cerebral aneurysms in the cavernous to communicating segments of the internal carotid artery, which were treated with single flow diversion. Pressure and Pulsatility Index were recorded at the M1-segment ipsilateral to the cerebral aneurysm. Ratio of middle cerebral artery to radial arterial pressure (pressure ratio) was calculated to control for variations in systemic blood pressure. Correlations between aneurysm size and pressure ratio and Pulsatility Index were assessed before and after treatment. A total of 28 aneurysms were treated. The mean aneurysm size was 7.2 mm. Aneurysm size correlated linearly with systolic pressure ratio (1% pressure ratio increase per mm aneurysm size increase, P = 0.002, r2 = 0.33), mean pressure ratio (0.6% per mm, P = 0.03, r2 = 0.17) and Pulsatility Index (5% Pulsatility Index increase per mm, P = 0.003, r2 = 0.43). After flow diversion, aneurysm size preserved a linear correlation with the systolic pressure ratio (1% per mm, P = 0.004, r2 = 0.28), but not with the mean pressure ratio (0.4% per mm, P = 0.15, r2 < 0.1) or Pulsatility Index (0.3% per mm, P = 0.78, r2 < 0.1). Aneurysm size affects distal hemodynamics: patients with larger aneurysms have increased systolic and mean pressure ratio, and increased Pulsatility Index. After flow diversion, mean pressure ratio and Pulsatility Index no longer associate with the aneurysm size, suggesting an effect of the flow diversion also on distal intracranial hemodynamics.


Complete nucleotide sequence of the nucleoprotein gene from the human influenza strain A/PR/8/34 (HON1).
The complete nucleotide sequence of the influenza A/PR/8/34 nucleoprotein gene was determined after cloning for dsDNA copy in pBR322. The nucleoprotein gene is 1517 nucleotides long of which 1446 nucleotides code for 482 amino acids. The calculated amino acid composition is in good agreement with those published for influenza A nucleoprotein genes. The amino acid sequence of the nucleoprotein contains clusters of basic amino acids and proline, a property shared with other nucleic-acid-associated proteins like Semliki forest virus nucleocapsid protein, VP1 protein of polyoma virus and Simian virus 40, and the core antigen of hepatitis B virus. The described nucleoprotein structure brings the number of sequenced genes of influenza A/PR/8/34 to five out of eight genes.


Retroviral env glycoprotein trafficking and incorporation into virions.
Together with the Gag protein, the Env glycoprotein is a major retroviral structural protein and is essential for forming infectious virus particles. Env is synthesized, processed, and transported to certain microdomains at the plasma membrane and takes advantage of the same host machinery for its trafficking as that used by cellular glycoproteins. Incorporation of Env into progeny virions is probably mediated by the interaction between Env and Gag, in some cases with the additional involvement of certain host factors. Although several general models have been proposed to explain the incorporation of retroviral Env glycoproteins into virions, the actual mechanism for this process is still unclear, partly because structural data on the Env protein cytoplasmic tail is lacking. This paper presents the current understanding of the synthesis, trafficking, and virion incorporation of retroviral Env proteins.


Old Is (Not) Gold: Midazolam Monotherapy versus Midazolam Plus Fentanyl for Sedation during Cardiac Catheterization.
We aimed to study the differences in perception of pain during cardiac catheterization with midazolam monotherapy compared to the current standard of midazolam plus fentanyl. Procedural sedation is important to ensure comfort and safety in patients undergoing left heart catheterization. Despite the widespread use of midazolam and fentanyl for procedural sedation, the effectiveness of this dual agent approach to sedation has never been studied in comparison to midazolam monotherapy. A total of 129 patients undergoing sedation for outpatient elective cardiac catheterization were randomly assigned to either midazolam monotherapy (n = 69) or combination of midazolam and fentanyl (n = 60). The primary outcome was assessment of pain perception prior to discharge by patient completion of a pain questionnaire. Participants were asked if they experienced any pain during their procedure (yes/no) and, if yes, asked to rate their overall pain level using a 10-point Likert scale that ranged from 1 (minimal pain) to 10 (worst pain imaginable). Most patients (n = 94, 73%) reported no pain during their procedure. Patients sedated with midazolam monotherapy reported similar average pain scores compared to patients sedated with the combination of midazolam and fentanyl (1.1 vs. 1.1, p=0.95). Among patients undergoing elective cardiac catheterization, no significant differences in pain scores were noted between sedation with midazolam alone compared to midazolam and fentanyl. Due to fentanyl's unfavorable interaction with P2Y12 agents, increased costs, and addiction potential, it is imperative that cardiologists revisit the role of effective procedural sedation with a single agent and avoid the use of fentanyl.


Surface plasmon resonance studies of the interaction between factor VII and tissue factor. Demonstration of defective tissue factor binding in a variant FVII molecule (FVII-R79Q).
The blood coagulation cascade is initiated when vessel injury allows factor VII (FVII) to form a complex with tissue factor (TF). Complete deficiency of FVII causes a lethal bleeding diathesis, but individuals with moderately reduced FVII levels are often asymptomatic. Some of these individuals have circulating partially functional FVII, as a result of point missense mutations in critical parts of the molecule. One such mutation has been reported at position 79 in the first epidermal growth factor-like (EGF) domain of FVII, where an arginine residue has been replaced by glutamine. There is controversy as to whether or not this mutation reduces the affinity of the FVII/TF interaction compared to wild-type FVII. To address this problem, we have expressed recombinant FVII-R79Q and subjected it to detailed biochemical analysis. One-stage FVII:C assays show the variant FVII to have reduced activity with respect to the wild type. Rates of autoactivation and activation by FXa to the two-chain molecule were identical for wild-type and variant FVII. The Vmax for FX activation was lower for the mutant as measured using an amidolytic assay for FX activity. In contrast, the Km for FX was lower for the variant than the wild-type molecule. Peptidyl substrate hydrolysis was virtually identical for both variant and normal FVIIa in the presence and absence of TF. The variant has reduced affinity for TF as measured by surface plasmon resonance. FVII-R79Q has an association rate constant (kassoc) one-fifth of that of normal FVII, but a similar kdiss, resulting in a decrease in the affinity of the enzyme for its cofactor.(ABSTRACT TRUNCATED AT 250 WORDS)


Gelling Your Dermatology Nursing Practice: A Practical Guide for Managing the Treatment of Mycosis Fungoides Cutaneous T-Cell Lymphoma With Mechlorethamine Gel.
Mycosis fungoides is the most common form of cutaneous T-cell lymphoma. Stage IA and IB mycosis fungoides cutaneous T-cell lymphoma can be effectively controlled by skin-directed therapies such as the mechlorethamine gel approved by the Food and Drug Administration. Dermatology nurses play a key role in promoting good patient compliance through patient education about mycosis fungoides cutaneous T-cell lymphoma disease, proper administration of mechlorethamine gel, and connecting patients with patient assistance programs or other supportive services. This article provides the dermatology nurse with a background about early-stage mycosis fungoides cutaneous T-cell lymphoma, skin-directed treatment options, questions that a patient may ask about mycosis fungoides cutaneous T-cell lymphoma and mechlorethamine gel, and patient education tools such as questions dermatology nurses may ask of their patients and a patient handout outlining mechlorethamine gel administration.


Vasomotor symptoms are associated with a lower bone mineral density.
The severity of vasomotor symptoms has been hypothesized to be linked to a lower bone mineral density (BMD). We examined whether women with vasomotor symptoms are different from women without symptoms with regard to BMD. We used data from a population-based sample of 5,600 women, aged 46 to 57 years and free from bone diseases, who participated in the first cross-sectional part of the Eindhoven Perimenopausal Osteoporosis Study between 1994 and 1995. Questionnaires at baseline were used to collect data on vasomotor symptoms and potential confounders. At baseline, BMD of the lumbar spine was measured using dual energy x-ray absorptiometry. Linear regression analysis was used to analyze the data. Flushing was reported by 39% of all women, and night sweats, by 38% of all women. The average BMD was 1.01 +/- 0.14 g/cm and decreased with increasing frequency of flushing (P for trend < 0.0001) and night sweats (P for trend = 0.03). After multivariate adjustments for age, body mass index, menopause status, smoking, education, exercise, and hormone use, women with the highest frequency of symptoms had a 0.022 g/cm (95% CI, -0.03 to -0.01) lower BMD compared with asymptomatic women. Women who reported having the highest frequency of night sweats had a 0.011 g/cm (95% CI, -0.02 to -0.001) lower BMD compared with women with no symptoms of night sweats. Our findings show that vasomotor symptoms are associated with reduced bone density. It could be hypothesized that women with vasomotor symptoms might be more susceptible to the beneficial effects of estrogens, possibly by neutralizing the effect of estrogen fluctuations. Further research is needed to extend these findings to other estrogen-sensitive end organs.


Biological response to a new composite polymer augmentation device used for cruciate ligament reconstruction.
A resorbable composite augmentation cord braided of poly(L-lactide) and poly(L-lactide-co-glycolide) fibers was designed for the temporary protection of repaired cruciate ligaments. This study examined the biocompatibility of the new device and the influence of augmentation duration on ligament healing in a sheep model. The anterior cruciate ligament (ACL) was cut close to the femoral insertion and reinserted with sutures. The repaired ACLs were augmented with the slowly degrading new composite cord and alternatively with a faster degrading polydioxanone cord (PDS). A tendon graft group (gold standard) served as control. Histological evaluation and biomechanical testing were performed after 6 months. The composite cord showed no signs of degradation, whereas the PDS was intra-articularly resorbed. Both devices showed only minor foreign body reactions, proving their good biocompatibility. However, 9 of 11 composite cords had ruptured too early because of fatigue at the bone tunnel entrances. All operated knees were less stable than the nonoperated collateral joints. Knees equipped with the composite cord showed the largest anterior instabilities, whereas the PDS-augmented group exhibited in some cases knee instabilities comparable with that of the tendon group. A positive effect of a longer mechanical protection by a slowly degrading augmentation could not yet be shown. The fatigue strength of the device still needs improvement.


Lipid emulsion enhances cardiac performance after ischemia-reperfusion in isolated hearts from summer-active arctic ground squirrels.
Hibernating mammals, like the arctic ground squirrel (AGS), exhibit robust resistance to myocardial ischemia/reperfusion (IR) injury. Regulated preference for lipid over glucose to fuel metabolism may play an important role. We tested whether providing lipid in an emulsion protects hearts from summer-active AGS better than hearts from Brown Norway (BN) rats against normothermic IR injury. Langendorff-prepared AGS and BN rat hearts were perfused with Krebs solution containing 7.5 mM glucose with or without 1% Intralipid™. After stabilization and cardioplegia, hearts underwent 45-min global ischemia and 60-min reperfusion. Coronary flow, isovolumetric left ventricular pressure, and mitochondrial redox state were measured continuously; infarct size was measured at the end of the experiment. Glucose-only AGS hearts functioned significantly better on reperfusion than BN rat hearts. Intralipid™ administration resulted in additional functional improvement in AGS compared to glucose-only and BN rat hearts. Infarct size was not different among groups. Even under non-hibernating conditions, AGS hearts performed better after IR than the best-protected rat strain. This, however, appears to strongly depend on metabolic fuel: Intralipid™ led to a significant improvement in return of function in AGS, but not in BN rat hearts, suggesting that year-round endogenous mechanisms are involved in myocardial lipid utilization that contributes to improved cardiac performance, independent of the metabolic rate decrease during hibernation. Comparative lipid analysis revealed four candidates as possible cardioprotective lipid groups. The improved function in Intralipid™-perfused AGS hearts also challenges the current paradigm that increased glucose and decreased lipid metabolism are favorable during myocardial IR.


Protective effect of quercetin against cigarette tar extract-induced impairment of erythrocyte deformability.
Quercetin (3,3',4',5,7-pentahydroxyflavone) is one of the most abundant flavonol-type flavonoids rich in diet and suggested to possess a beneficial role in blood circulation. This study was conducted to know the effect of quercetin aglycone and one of its possible metabolite, quercetin-3-O-beta-D-glucuronide on cigarette tar extract-induced impairment of erythrocyte deformability. Erythrocyte suspension containing quercetin aglycone, quercetin-3-O-beta-D-glucuronide or quercetin-3-O-beta-D-glucoside was forced to flow through microchannels with equivalent diameter of 7 &mgr;m and its transit time was measured as an index of erythrocyte deformability using microchannel array method. Both quercetin aglycone and quercetin-3-O-beta-D-glucuronide, but not quercetin-3-O-beta-D-glucoside, substantially increased erythrocyte deformability indicating that the former two compounds affect the physicochemical state of erythrocyte by interacting with its membranes. Aqueous cigarette tar extract caused marked decrease in erythrocyte deformability with concomitant increase of membranous lipid peroxidation. In that case, quercetin aglycone suppressed the impairment of erythrocyte deformability as well as membranous lipid peroxidation. The same effect was found in quercetin-3-O-beta-D-glucuronide, eventhough its effect was lower than that of quercetin aglycone. Thus, not only quercetin aglycone but also its conjugate metabolite protects erythrocyte membrane from the damage of smoking by scavenging reactive oxygen species generated from cigarette tar. Intake of quercetin-rich food may be helpful to protect membranous damage in erythrocytes from smoking.


Nephrology in South Africa: Not Yet ubuntu.
South Africa (SA) is an upper middle-income country with a human immunodeficiency virus (HIV) epidemic, an accelerated burden of non-communicable diseases, and a concurrent epidemic of tuberculosis. These con-ditions overwhelm a health system struggling under the pressure of restricted resources, including an insufficient workforce. Private practice has become more involved in the care of patients in the country but serves mainly those who are members of a Medical Aid. These Medical Aids will usually cover up to 100% of the costs for management of chronic kidney disease (CKD). There are currently 2.3 nephrologists per million individuals, which is far lower than the global average and grossly inadequate to meet the nephrology care needs in SA. Covert chronic dialysis rationing has occurred in the public sector since the 1960s. However, the lack of formality triggered the formation of explicit rationing guidelines in one province. These guidelines have been ethically endorsed but not embraced nationally. The demand for hemodialysis (HD) has led some provinces to practicing "PD-First" programs. SA remains one of only 12 countries within Africa that perform renal transplantation, and it is the only country in Africa that relies on deceased donation for the majority of its transplants. The first kidney transplant in SA took place at the University of the Witwatersrand, Johannesburg, in 1966 and the first dialysis was performed by a general practitioner working in a town close to Johannesburg in 1957. The University of Cape Town successfully pioneered the transplantation of kidneys from HIV-positive donors to positive recipients. SA was the second country in the world to form a National Kidney Foundation as well as a renal society. Nephrology training is in place and incorporates master's and PhD programs in nephrology. Despite the numerous challenges, SA nephrologists have been among the leading researchers in nephrology from the African continent.


[Blood transfusion : optimizing the use of a scarce and expensive resource].
Haemoglobin transfusion threshold remains debated with a high variability of practice among physicians. Several well-conducted studies revealed that a liberal transfusion policy is not only unnecessary, but can also prove harmful in certain situations. Blood transfusion is a costly act involving risks of infection, allergic and hemodynamic. Optimizing the use of this scarce and expensive resource becomes necessary. This article summarizes the different transfusion thresholds to respect in hospital clinical practice, based on the latest international recommendations, while emphasizing the importance of clinical judgment in each situation.


Evaluating the Impact of Secure Mobile Messaging on Communication and Cancer Care Team Satisfaction in a Large Radiation Oncology Clinic.
Communication is crucial in any clinical environment for efficient delivery of care and ensuring patient safety. A 2016 National Database of Nursing Quality Indicators questionnaire indicated poor physician-nurse satisfaction with communication in our department. We addressed gaps in our communication procedures by implementing a communication policy with a secure mobile messaging platform, and we surveyed care team members to evaluate the effectiveness of the implementation. We designed a policy around best communication practices and implemented a secure mobile messaging platform, Cureatr, which enables closed-loop, two-way communication that is compliant with the Health Insurance Portability and Accountability Act. Pre- and postimplementation surveys evaluated self-reported impression of efficiency, timeliness, effectiveness, and overall quality of communication, which were scored on a 5-point Likert scale. The number of messages sent was evaluated as a measure of uptake in use, and patient navigation data were queried to measure changes in clinic workflow. After implementation of Cureatr and a communication policy, survey responses demonstrated a clear improvement in staff satisfaction with the efficiency, timeliness, effectiveness, and overall quality of communication. The number of messages sent reflected a progressive increase in use of Cureatr; however, a consistent improvement in clinical workflow as measured by a decrease in patient in-room time was not appreciated. Implementing a secure messaging application with a communication policy improved cancer care team satisfaction with communication on all levels. Additional work is needed to evaluate the impact of secure messaging on clinical workflows, patient satisfaction, and staff well-being.


Vascular leiomyoma of the limbs.
After reporting the most significant data in the literature, the authors present 5 cases of vascular leiomyoma of the limbs (1 in the upper limb, 4 in the lower limb) in subjects of both sexes. In all of the patients, diagnosis was only possible thanks to histological examination, confirmed by an immunohistochemical examination. In none of the cases was there recurrence of neoplasm after surgical exeresis.


Response to Comment on "Cultural flies: Conformist social learning in fruitflies predicts long-lasting mate-choice traditions".
Thornquist and Crickmore claim that systematic experimental error may explain the results of Danchin and colleagues. Their claim rests on mistakes in their analyses, for which we provide corrections. We reassert that conformity in fruitflies predicts long-lasting mate-preference traditions.


Promiscuous stimulation of ParF protein polymerization by heterogeneous centromere binding factors.
The segrosome is the nucleoprotein complex that mediates accurate segregation of bacterial plasmids. The segrosome of plasmid TP228 comprises ParF and ParG proteins that assemble on the parH centromere. ParF, which exemplifies one clade of the ubiquitous ParA superfamily of segregation proteins, polymerizes extensively in response to ATP binding. Polymerization is modulated by the ParG centromere binding factor (CBF). The segrosomes of plasmids pTAR, pVT745 and pB171 include ParA homologues of the ParF subgroup, as well as diverse homodimeric CBFs with no primary sequence similarity to ParG, or each other. Centromere binding by these analogues is largely specific. Here, we establish that the ParF homologues of pTAR and pB171 filament modestly with ATP, and that nucleotide hydrolysis is not required for this polymerization, which is more prodigious when the cognate CBF is also present. By contrast, the ParF homologue of plasmid pVT745 did not respond appreciably to ATP alone, but polymerized extensively in the presence of both its cognate CBF and ATP. The co-factors also stimulated nucleotide-independent polymerization of cognate ParF proteins. Moreover, apart from the CBF of pTAR, the disparate ParG analogues promoted polymerization of non-cognate ParF proteins suggesting that filamentation of the ParF proteins is enhanced by a common mechanism. Like ParG, the co-factors may be modular, possessing a centromere-specific interaction domain linked to a flexible region containing determinants that promiscuously stimulate ParF polymerization. The CBFs appear to function as bacterial analogues of formins, microtubule-associated proteins or related ancillary factors that regulate eucaryotic cytoskeletal dynamics.


[Research of different expressions of microRNA in sinus node, atrial myocardium, and ventricular myocardium of mouse].
To study microRNA (miRNA) involved in the regulation of sinus cell differentiation by comparing sinus node, atrial myocardium, and ventricular myocardium specific miRNA expression profile differences in Kunming mice. A total of 180 Kunming mice, aged 60-90 days and weighing 35-45 g, were selected without gender differences after the method of anatomical localization for sinus node had been confirmed by preliminary experiments in another 10 Kunming mice. All the sinus node, atrial myocardium, and ventricular myocardium tissue from 180 mice were dissected and frozen by liquid nitrogen. The structure of tissue was observed by HE staining. Total RNA were extracted and quality-controlled before hybridize with miRNA chip. The chips with miRNA were used to screen specific miRNAs; and correlation analysis of gene function was done. The area of mice sinus node located at juncture of the superior vena cava and the right atrium junction with crista as its longitudinal axis, ranged 2.0 mm x 1.5 mm x 1.0 mm. HE staining showed the sinus cells were less, with no stripes, lightly stained cytoplasm, large and round nucleus, and there were much fibrous connective tissue around cells with a visible sinus node artery. The miRNA microarray results showed that compared with atrial myocardium and ventricular myocardium, there were 39 differentially expressed miRNAs in sinus node, including 12 up-regulated miRNAs and 27 down-regulated miRNAs. Based on the regulatory networks of differential miRNA and target gene, the regulatory miRNA was obtained. The differentially expressed miRNA in mice sinus node possibly may be involved in the regulation of sinus cell differentiation.