Determination of diffusion coefficient of hydrogen in metals and their elastic modulus by generalised impedance

Transport of hydrogen in elastic metals has been analysed in terms of an impedance-like non-linear transfer function (TF). The equilibrium in a membrane specimen is perturbed by a sinusoidal signal of the concentration of hydrogen, of large amplitude, applied to one of its surfaces. The fundamental harmonics of periodically reproducible flux at the same surface is considered as a response. The TF is defined as the ratio of the signal to the response. The power of the said TF in determining the diffusion coefficient of hydrogen in a metal–hydrogen system and its bulk elastic modulus was analysed for the example of α-phase Pd–H and Pd₈₁Pt₁₉–H systems. It has been found that such a TF is suitable for determination of the above parameters. Also, the sensitivity of these estimates to the uncertainty of concentration of hydrogen in the metal, its partial molar volume and the thickness of the specimen has been explored.     

Effects of omalizumab and budesonide on markers of inflammation in human bronchial epithelial cells.

BACKGROUND: Many patients with asthma have an IgE-mediated allergic component to the disease. Omalizumab, a monoclonal anti-IgE antibody, has demonstrated clinical efficacy in patients with allergic asthma. The effects of omalizumab on inflammation in asthma are not completely understood. OBJECTIVES: To evaluate the effects of omalizumab on allergen- and growth factor-stimulated proinflammatory cytokine and nitric oxide (NO) production in human bronchial epithelial cells (BECs) and to compare them to the effects of budesonide, a corticosteroid with known anti-inflammatory properties. METHODS: Human BECs were stimulated in duplicate with interleukin 1beta (IL-1beta), 100 U/mL; ragweed, 10 microg/mL; dust mite, 1000 AU; and epithelial growth factor, 40 ng/mL; and either 10(-7) M budesonide or 0.1 microg/mL of omalizumab in a 4% dust mite atopic serum medium for 6 and 24 hours in 5% carbon dioxide at 37 degrees C. Tumor necrosis factor alpha and transforming growth factor betaexpression and production and IL-4, IL-13, and NO production were assayed using gene-specific messenger RNA or sensitive enzyme-linked immunosorbent assays. RESULTS: Omalizumab inhibited the expression and of production proinflammatory cytokines and growth factor in antigen-stimulated BECs at 6 and 24 hours. Production of NO was inhibited at 6 hours and increased at 24 hours by omalizumab and budesonide. CONCLUSIONS: The effects of omalizumab were similar to those of budesonide. These results, consistent with previously reported evidence of anti-inflammatory effects of omalizumab, demonstrate that omalizumab may reduce airway inflammation and probably contributes to decreased airway remodeling in patients with asthma.     

The toxicology of heparin reversal with protamine: past,present and future

Introduction: Unfractionated heparin is a strongly anionic anticoagulant used extensively in medicine to prevent blood clotting. In the case of an emergency bleeding in response to heparin, the protamine sulfate is administered. Despite its extensive clinical use, protamine may produce life-threatening side effects such as systemic hypotension, catastrophic pulmonary vasoconstriction or allergic reactions. Recent studies have demonstrated new organ-specific complications of the heparin reversal with protamine.

Areas covered: Past and present knowledge of the mechanisms responsible for the toxicity of protamine and the most promising potential replacements of protamine in the different phases of development.

Expert opinion: Despite of the low therapeutic index, protamine is the only registered antidote of heparins. The toxicology of protamine depends on a complex interaction of the high molecular weight, a cationic peptide with the surfaces of the vasculature and blood cells. The mechanisms involve membrane receptors and ion channels targeted by different vasoactive compounds, such as nitric oxide, bradykinin or histamine. Unacceptable side effects of protamine have led to a search for new alternatives: UHRA, LMWP, and Dex40-GTMAC3 are in the preclinical stage; the two other agents (andexanet alfa and PER977) are already in the advanced clinical phases.     

Single-Step Transepithelial PRK vs Alcohol-Assisted PRK in Myopia and Compound Myopic Astigmatism Correction

Transepithelial photorefractive keratectomy (tPRK), where both the epithelium and stroma are removed in a single-step, is a relatively new procedure of laser refractive error correction. This study compares the 3-month results of myopia and compound myopic astigmatism correction by tPRK or conventional alcohol-assisted PRK (aaPRK).This prospective, nonrandomized, case–control study recruited 148 consecutive patients; 93 underwent tPRK (173 eyes) and 55 aaPRK (103 eyes). Refractive results, predictability, safety, and efficacy were evaluated during the 3-month follow-up. The main outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and mean refractive spherical equivalent (MRSE).Mean preoperative MRSE was −4.30 ± 1.72 D and −4.33 ± 1.96 D, respectively (P = 0.87). The 3-month follow-up rate was 82.1% in the tPRK group (n = 145) and 86.4% in aaPRK group (n = 90), P = 0.81. Postoperative UDVA was 20/20 or better in 97% and 94% of eyes, respectively (P = 0.45). In the tPRK and aaPRK groups, respectively, 13% and 21% of eyes lost 1 line of CDVA, and 30% and 31% gained 1 or 2 lines (P = 0.48). Mean postoperative MRSE was −0.14 ± 0.26 D in the tPRK group and −0.12 ± 0.20 D in the aaPRK group (P = 0.9). The correlation between attempted versus achieved MRSE was equally high in both groups.Single-step transepithelial PRK and conventional PRK provide very similar results 3 months postoperatively. These procedures are predictable, effective, and safe for correction of myopia and compound myopic astigmatism.     

Physiotherapeutic assessment and management of chronic pelvic pain syndrome: A case report

Introduction:Chronic pelvic pain syndrome is difficult for the diagnosis and therapy and that means the patient attending the physician or physiotherapist may present various symptoms. There are no guidelines concern physiotherapy diagnosis and treatment of chronic pelvic pain syndrome. This study presents the physiotherapeutic assessment and management in men with pelvic pain symptoms.Patient concerns:Forty-six-year-old man attended the physiotherapy consulting room due to symptoms of pain in the perineum, lower abdomen, urethra, and scrotum for a year. Earlier, the patient had consulted a urologist who made a diagnosis of cystitis and prescribed medications that did not get results.Diagnosis:Ultrasound imaging and manual inspection (per rectum) of the pelvic floor was conducted by physiotherapist. Also, the abdominal and lower extremities muscles were assessed. Patient reported pain symptoms during examination of the musculus ischiocavernosus, puboanalis, pubococcygeus, iliococcygeus, coccygeus, and canalis pudentalis seu Alcocki.Interventions:The patient was given physiotherapeutic interventions consisting in the manual therapy of the lumbopelvic hip complex and the manual therapy per rectum.Outcomes:During 10th session of the physiotherapeutic treatment, patient reported improvement in pain symptoms. A month later, patient reported total alleviation of the pain symptoms during control visit.Conclusion:Therapy of chronic pelvic pain syndrome is a process that involves application of different therapies and different approaches. Functional and structural assessment and also therapy conducted by physiotherapist is becoming an integral part of urology and represents 1 possible conservative treatment form.     

Characterization of the Global Stabilizing Substitution A77V and Its Role in the Evolution of CTX-M β-Lactamases

The widespread use of oxyimino-cephalosporin antibiotics drives the evolution of the CTX-M family of β-lactamases that hydrolyze these drugs and confer antibiotic resistance. Clinically isolated CTX-M enzymes carrying the P167S or D240G active site-associated adaptive mutation have a broadened substrate profile that includes the oxyimino-cephalosporin antibiotic ceftazidime. The D240G substitution is known to reduce the stability of CTX-M-14 β-lactamase, and the P167S substitution is shown here to also destabilize the enzyme. Proteins are marginally stable entities, and second-site mutations that stabilize the enzyme can offset a loss in stability caused by mutations that enhance enzyme activity. Therefore, the evolution of antibiotic resistance enzymes can be dependent on the acquisition of stabilizing mutations. The A77V substitution is present in CTX-M extended-spectrum β-lactamases (ESBLs) from a number of clinical isolates, suggesting that it may be important in the evolution of antibiotic resistance in this family of β-lactamases. In this study, the effects of the A77V substitution in the CTX-M-14 model enzyme were characterized with regard to the kinetic parameters for antibiotic hydrolysis as well as enzyme expression levels in vivo and protein stability in vitro. The A77V substitution has little effect on the kinetics of oxyimino-cephalosporin hydrolysis, but it stabilizes the CTX-M enzyme and compensates for the loss of stability resulting from the P167S and D240G mutations. The acquisition of global stabilizing mutations, such as A77V, is an important feature in β-lactamase evolution and a common mechanism in protein evolution.     

Loss of heterozygosity in 7q myeloid disorders: clinical associations and genomic pathogenesis

Loss of heterozygosity affecting chromosome 7q is common in acute myeloid leukemia and myelodysplastic syndromes, pointing toward the essential role of this region in disease phenotype and clonal evolution. The higher resolution offered by recently developed genomic platforms may be used to establish more precise clinical correlations and identify specific target genes. We analyzed a series of patients with myeloid disorders using recent genomic technologies (1458 by single-nucleotide polymorphism arrays [SNP-A], 226 by next-generation sequencing, and 183 by expression microarrays). Using SNP-A, we identified chromosome 7q loss of heterozygosity segments in 161 of 1458 patients (11%); 26% of chronic myelomonocytic leukemia patients harbored 7q uniparental disomy, of which 41% had a homozygous EZH2 mutation. In addition, we describe an SNP-A-isolated deletion 7 hypocellular myelodysplastic syndrome subset, with a high rate of progression. Using direct and parallel sequencing, we found no recurrent mutations in typically large deletion 7q and monosomy 7 patients. In contrast, we detected a markedly decreased expression of genes included in our SNP-A defined minimally deleted regions. Although a 2-hit model is present in most patients with 7q uniparental disomy and a myeloproliferative phenotype, haplodeficient expression of defined regions of 7q may underlie pathogenesis in patients with deletions and predominant dysplastic features.     

Refractory Heart Failure Dependent on Short‐Term Mechanical Circulatory Support: What Next? Heart Transplant or Long‐Term Ventricular Assist Device

Chronic heart failure is a progressive and eventually fatal illness. Although the disease cannot be cured and treatment is symptom oriented, most of the patients benefit from optimum medical treatment. Patients with rapid deterioration in chronic advanced heart failure refractory to medical treatment need inotropic support and may need intra‐aortic balloon pump to maintain circulatory support, which of course cannot be prolonged beyond a certain limit. The outcome of heart transplant and long‐term ventricular assist device (VAD) in such patients is poor. The short‐term mechanical circulatory support (MCS) offered to such patients not only provides effective circulatory support and stabilizes them hemodynamically, but also halts the ensuing or reverts the established end‐organ failure. As the name suggests, the short‐term MCS offers support for the short term, usually less than a month. Although some patients with acute heart failure experience recovery of myocardial function with short‐term MCS support, others become dependent. These patients, stabilized and “stuck” with short‐term MCS, can be “rescued” with long‐term VAD or heart transplantation. Both the procedures, when done in this special situation, have their inherent advantages, disadvantages, and complications and hence need the careful consideration about the choice of the procedure. We have tried to elucidate this situation by considering the advantages and disadvantages of both options.