Management of acute pulmonary exacerbations in cystic fibrosis: a critical appraisal.
Optimal management of acute exacerbations of pulmonary symptoms in patients with cystic fibrosis remains questionable. The underlying cause of such exacerbations has not been identified, and the microbiology of the sputum does not differ substantially during these exacerbations. Despite the absence of conclusive evidence that antibiotic therapy enhances treatment of cystic fibrosis, the consensus favors its use. Various combination and single-agent therapies with aminoglycosides, cephalosporins, and beta-lactam antibiotics are reviewed critically. The importance of high activity against Pseudomonas strains is addressed, as is the potential value of antibiotic prophylaxis. The drawbacks of aminoglycoside treatment are reported. No evidence proves the superiority of combination therapy over monotherapy. Recent results suggesting the effectiveness of monotherapy with piperacillin or ceftazidime are encouraging and deserve follow-up to test continued efficacy and the absence of development of resistant antibiotic strains. Further investigation into the prevention of acute pulmonary exacerbations in cystic fibrosis is essential.


Genetic heterogeneity of primary open-angle glaucoma in Pakistan.
Glaucoma is a neurodegenerative ophthalmic disorder and is considered among the leading causes of irreversible blindness. Primary open-angle glaucoma (POAG) is the most common type of glaucoma that affects after 30 years of life, progressing slowly, and manifests as decreased visual acuity leading to blindness if not treated. POAG is genetically heterogeneous, inherited most commonly in autosomal dominant mode. Several genes have been reported for POAG with myocilin (Myoc) being most common. The present study has been conducted to screen 25 POAG families with 2 or more affected members for their association with Myoc and CYP1B1 (the most common gene in primary congenital glaucoma). After approval from Institutional Ethical Review Committee (ERC), 25 POAG families were enrolled from the southern province (Sindh) of Pakistan. Written informed consent was obtained from all participating individuals and diagnosis was confirmed by consultant ophthalmologists using various instruments and means. Venous blood was obtained from affected individuals and their normal family members for DNA extraction and subsequent analysis. All samples were initially screened for the Myoc gene followed by CYP1B1. Screening for Myoc revealed one previously reported variant c.144G>T in POAG-06 whereas screening for CYP1B1 in all 25 families showed a novel variant c.649G>A in POAG-02. The pathogenicity of the novel variant was confirmed using various bioinformatics tools. This is the first report of any POAG family found associated with a novel variant in CYP1B1 from the southern province of Pakistan whereas one family found associated with a reported variant in Myoc. The remaining 23 POAG families did not found to be associated with either Myoc or CYP1B1 indicating genetic heterogeneity of the population in this part of the world.


Soluble epoxide hydrolase inhibition enhances anti-inflammatory and antioxidative processes, modulates microglia polarization, and promotes recovery after ischemic stroke.
Ischemic stroke triggers inflammatory responses and oxidative stress in the brain, and microglia polarization affects the degree of neuroinflammation. It has been reported that the inhibition of soluble epoxide hydrolase (sEH) activity protects brain tissue. However, the anti-inflammatory and antioxidative effects of sEH inhibition in the ischemic brain are not fully understood. This study aimed to investigate the effects of a selective sEH inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), after ischemic stroke. Adult male rats with middle cerebral artery occlusion (MCAO) were administered with AUDA or a vehicle. Behavioral outcome, infarct volume, microglia polarization, and gene expression were assessed. Rats treated with AUDA showed better behavioral outcomes and smaller infarct volumes after MCAO. After AUDA treatment, a reduction of M1 microglia and an increase of M2 microglia occurred at the ischemic cortex of rats. Additionally, there was an increase in the mRNA expressions of antioxidant enzymes and anti-inflammatory interleukin-10, and pro-inflammatory mediators were decreased after AUDA administration. Heme oxygenase-1 was mainly expressed by neurons, and AUDA was found to improve the survival of neurons. The results of this study provided novel and significant insights into how AUDA can improve outcomes and modulate inflammation and oxidative stress after ischemic stroke.


Postablation Atrial Flutters.
Mapping and ablation of post-atrial fibrillation (AF) atrial tachycardia (AT) are challenging electrophysiologic procedures. These tachycardias may be caused by multiple mechanisms and may arise from the left or right atrium, or the coronary sinus. The precise mechanism must be defined before ablation because the procedural end point depends on the correct diagnosis. Postablation ATs can be successfully ablated in approximately 90% of patients. Many patients experience recurrence despite rigorous procedural end points. Efforts should focus on decreasing the incidence of AT after AF ablation and identifying patients who require linear ablation during a procedure for persistent AF.


Pregnancy History, Hypertension, and Cognitive Impairment in Postmenopausal Women.
Risks for developing cardiovascular disease and cognitive decline increase with age. In women, these risks may be influenced by pregnancy history. This review provides an integrated evaluation of associations of pregnancy history with hypertension, brain atrophy, and cognitive decline in postmenopausal women. Atrophy in the occipital lobes of the brain was evident in women who had current hypertension and a history of preeclampsia. Deficits in visual memory in women with a history of preeclampsia are consistent with these brain structural changes. The blood velocity response to chemical and sympathoexcitatory stimuli were altered in women with a history of preeclampsia linking impairments in cerebrovascular regulation to the structural and functional changes in the brain. Having a history of preeclampsia should require close monitoring of blood pressure and initiation of anti-hypertensive treatment in perimenopausal women. Mechanisms by which preeclampsia affects cerebrovascular structure and function require additional study.


Assessing Platelet Mitochondrial Dysfunction in a Murine Model of Acute Acetaminophen Toxicity.
Acetaminophen (APAP) toxicity remains a significant cause of adult and pediatric liver failure in North America and Europe. Previous research has evaluated the impaired mitochondrial function associated with APAP toxicity. The primary aim of this study was to evaluate the effects of APAP toxicity on platelet mitochondrial function using platelet oxygen consumption in a murine model in vivo. Our secondary objectives were to determine the effect of 4-MP on platelet mitochondrial function and hepatic toxicity in the setting of APAP overdose, and to correlate platelet mitochondrial function with other markers of APAP toxicity. Male C57Bl/6 mice were randomized to receive APAP (300 or 500 mg/kg) or vehicle followed 90 minutes later by either 4-MP (50 mg/kg) or vehicle via intraperitoneal injection. Mice were euthanized 0, 12, or 24 hours later and platelets isolated from cardiac blood and counted. Platelet oxygen consumption (POC) was determined using a closed-system respirometer. Liver injury was assessed by measuring alanine transferase (ALT) and histological evaluation. Injection of 500 mg/kg APAP led to increased POC versus pair-matched control (vehicle) (p < 0.001). Administration of 4-MP did not affect POC in control or 300 mg/kg APAP mice. In mice receiving 500 mg/kg APAP and 4-MP, POC decreased significantly compared to mice receiving 500 mg/kg APAP alone (p < 0.01). Serum and histological analysis confirmed APAP-induced hepatic damage in mice receiving 500 mg/kg APAP and these effects blunted by treatment with 4-MP. Platelet oxygen consumption as a measure of mitochondrial function may be useful as a biomarker of hepatic APAP toxicity in the setting of moderate to severe overdose. Treatment with 4-MP decreases hepatic necrosis and may mitigate the harmful effects of APAP on platelet mitochondrial function detected via POC.


Quantitative analysis of phosphoproteins using microspot immunoassays.
Protein microarrays are an ideal technology platform which allow for a robust and standardized profiling of the cellular proteome. Many cellular functions are not simply controlled by the presence of certain proteins, especially the propagation of external stimuli, which depend on transient post-translational modifications that determine whether a protein is in its active or inactive state. Thus, complex biological processes require the availability of a sound set of quantitative and time-resolved measurements to be understood. For this reason, new assay platforms which allow for the investigation of several proteins in parallel are necessary. The current best understood mode of cellular regulation occurs via phosphorylation and dephosphorylation processes, which are mediated via a large panel of kinases and phosphatases. The microspot immunoassay technique described here allows for an exact determination of several different phosphorylated proteins in parallel, as well as from small sample amounts, and is therefore an appropriate system to deepen the understanding of the complex regulatory networks implicated in health and disease.


Experimental techniques for study of chromatin mechanics in intact nuclei and living cells.
While the structure of chromatin and its physical properties have been well studied on isolated chromatin fibres and DNA strands in vitro, its organization and function in the intact interphase nucleus is less clear. Chromatin organization is critical for transcriptional regulation and DNA replication, and mounting evidence suggests that cells respond to changes in the mechanical environment with alterations in nuclear architecture that are accompanied by modifications in gene expression. Since the nucleus forms part of a continuous physical network spanning the extracellular matrix, the cytoskeleton and the nuclear envelope, environmentally mediated forces can be transmitted to the nucleus and induce deformations of the chromatin.Here, we describe a subset of techniques that can be applied to probe nuclear mechanics, ranging from micropipette aspiration to strain experiments on living cells. These experiments probe the physical properties of the nuclear envelope, the nucleoplasm, and the chromatin. We discuss the advantages and disadvantages of each technique and elaborate on their use to examine specific aspects of chromatin. In the end, a combination of these technologies can provide important insights into the delicate relationship between form and function of chromatin organization in the living cell.


Unsuspected nonmedullary carcinoma of the thyroid in patients with hyperparathyroidism.
All patients with hyperparathyroidism seen in a large referral military hospital within a twenty month period underwent neck exploration by one of us (HN). Three patients were found to have an unsuspected solid thyroid nodule measuring 0.5 to 1.5 cm. All were widely excised by thyroid lobectomy and isthmectomy and found to be follicular or papillary carcinoma of the thyroid. These three patients join thirty-one previously reported clinical cases documenting an association between parathyroid adenoma and nonmedullary carcinoma of the thyroid. Because of the high potential for malignancy in this clinical setting, we urge careful examination and palpation of the thyroid gland during neck exploration for hypercalcemia in order to detect and cure "early" malignancies of the thyroid.


Identification of a novel gene hbrB required for polarised growth in Aspergillus nidulans.
We have cloned a novel gene, hbrB, by complementation of a temperature sensitive hyperbranching (hbr) mutant of Aspergillus nidulans. The mutant, hbrB3, exhibits hyperseptation and shows a marked increase in hyphal branching at the restrictive temperature. A genomic library incorporating the AMA1 sequence, which confers autonomous replication on the plasmid, was used to clone the gene. Co-ordinate loss of the complementing plasmid and wild type phenotype was shown. The 847 amino acid predicted product of the hbrB gene shows significant identities with Neurospora crassa and Aspergillus fumigatus hypothetical proteins but no other obvious relative outside the filamentous fungi. The gene was placed under control of the alcA promoter and downregulation resulted in a loss of polarity phenotype. These results suggest that A. nidulans hbrB is specific to filamentous fungi and is essential for hyphal growth and polarity. Index descriptors: Aspergillus nidulans; branching; hbrB; hyphal growth and polarity


Distribution of plasma alpha 1-antichymotrypsin levels in Alzheimer disease patients and controls and their genetic controls.
Alzheimer's disease (AD) is a complex multifactorial disease in which many genetic and environmental factors are involved. Recent studies have shown that alpha(1)-antichymotrypsin (ACT) is one of the candidate genes for AD. Elevated levels of ACT have been widely, but not universally reported in the cerebrospinal fluid and plasma of AD patients. The genetic association between the ACT/codon -17*A allele of the signal peptide polymorphism and AD has been shown in some studies. One hypothesis is that the ACT/codon -17*A allele is in linkage disequilibrium with unknown functional mutation(s) in the ACT gene. Alternatively, the more hydrophobic character of the alanine (codon -17*A) may enhance ACT translocation into the endoplasmic reticulum and the Golgi apparatus, thus being secreted at higher levels. Therefore, this study was undertaken to determine the distribution of ACT plasma levels in cases (n = 397) and controls (n = 118) and the impact of ACT polymorphisms, including codon -17, on plasma ACT levels. In our cohort, plasma ACT levels were significantly higher in AD patients than controls (542.13 +/- 7.11 mg/liter vs. 496.62 +/- 12.79 mg/liter; P = 0.002). The ACT/codon -17 polymorphism showed significant association with ACT levels in male AD patients, while the effect of the intron 4 polymorphism was significant in both male and female patients. Codon 227 polymorphism was associated with lower ACT levels in AD patients. In conclusion, ACT may play an important role in the AD pathogenesis and genetic variation in the ACT gene appears to have some effect on plasma ACT concentrations.


The use of the Hellige Oxymonitor to study skin blood flow changes.
Transcutaneous oxygen tension is a flow related parameter. Detailed analysis of the physiology and physical chemistry of oxygen consumption and diffusion indicates that tcPO2 is not proportional to skin blood flow. Measurement of tcPO2 at 37 degrees C allows changes in skin blood flow to be clearly demonstrated and is of use in many areas of clinical medicine. Transcutaneous oxygen tension recorded using a polarographic oxygen electrode depends on skin blood flow, skin respiration, arterial oxygen concentration, temperature, skin and electrode permeability and the oxygen consumption of the electrode. Applying clearance principles, the relationship between blood flow, respiration and the difference between arterial and venous oxygen concentrations is well established. This has long been used to measure cardiac output, since the other three parameters are readily determined. Arterial saturation is normally greater than 95% of maximum in subjects without lung disease and it may thus be considered to be constant. Tissue respiration is independent of oxygen concentration when PO2 exceeds 2 mm Hg. If skin respiration is invariant at constant temperature, when the tissue oxygen tension exceeds 2 mm Hg, then blood flow is inversely proportional to the difference in concentration between arterial and venous blood. It has recently been directly shown that the inference that tissue respiration is independent of tissue blood flow is accurate. Correcting for the oxyhaemoglobin dissociation curve and for the deviation from zero order respiration kinetics when tissue PO2 less than 2 mm Hg, the relationship between venous oxygen tension and blood flow at 37 degrees C is shown when arterial oxygen concentration is constant (Figure 1).(ABSTRACT TRUNCATED AT 250 WORDS)


Pretreatment serum hemoglobin level as a predictive factor of response to neoadjuvant chemotherapy in patients with locally advanced squamous cervical carcinoma: a preliminary report.
The aim of this study was to evaluate the predictive value of pretreatment serum hemoglobin level (Hb) together with a series of clinical and pathological variables available before neoadjuvant chemotherapy in locally advanced squamous cervical cancer. The influence on response to neoadjuvant chemotherapy of a series of pretreatment clinico-pathological features: hemoglobin level at diagnosis, age, parity, menopausal status, body mass index, clinical stage, tumor diameter, and nuclear grading were analyzed on 73 patients with locally advanced cervical cancer treated with platinum-based neoadjuvant chemotherapy followed by radical surgery. The relationships between pretreatment variables and response to chemotherapy were assessed in univariate and multivariate settings. A univariate and multivariate logistic regression model was adapted to predict an "optimal" response (pathological complete response or more than 50% reduction in tumoral diameter) or "sub-optimal" response (<50% reduction in tumoral diameter). Seventy-three patients-clinical stage: Ib2: 29 (39.7%) IIa: 22 (30.1%) IIb: 22 (30.1%)-received 3 cycles of platinum-based neoadjuvant chemotherapy followed by type III radical hysterectomy. A complete response to neoadjuvant chemotherapy was significantly associated with higher level of pretreatment hemoglobin (mean 14.0 mg/dl) compared to patients with > or =50% response (12.7 mg/dl) or <50% (11.9 mg/dl) (P = 0.002). At multivariate analysis, Hb level was found to be the most powerful and significantly related factor to response to neoadjuvant chemotherapy. A hemoglobin threshold of 12 mg/dl was able to distinguish between patients-with > or =12 mg/dl-at higher probability to respond to neoadjuvant chemotherapy from the ones at lower probability (hemoglobin level under 12 mg/dl). Patients with a complete response to chemotherapy had a 100% survival compared to 93.1% and 53.8% for patients with responses > or =50% and <50% respectively (P = 0.0001). Patients with a pretreatment hemoglobin level of > or =12 mg/dl showed a survival of 87% compared to 63% for patients with a lower hemoglobin level (P = 0.008). Pretreatment Hb level showed a prognostic and independent predictive value for response to neoadjuvant chemotherapy in locally advanced cervical cancer. In our preliminary report, performed on a limited sample, a threshold of 12 mg/dl seems to be helpful to distinguish between "optimal" and "non-optimal" response.


Measurement of sample temperatures under magic-angle spinning from the chemical shift and spin-lattice relaxation rate of 79Br in KBr powder.
Accurate determination of sample temperatures in solid state nuclear magnetic resonance (NMR) with magic-angle spinning (MAS) can be problematic, particularly because frictional heating and heating by radio-frequency irradiation can make the internal sample temperature significantly different from the temperature outside the MAS rotor. This paper demonstrates the use of (79)Br chemical shifts and spin-lattice relaxation rates in KBr powder as temperature-dependent parameters for the determination of internal sample temperatures. Advantages of this method include high signal-to-noise, proximity of the (79)Br NMR frequency to that of (13)C, applicability from 20 K to 320 K or higher, and simultaneity with adjustment of the MAS axis direction. We show that spin-lattice relaxation in KBr is driven by a quadrupolar mechanism. We demonstrate a simple approach to including KBr powder in hydrated samples, such as biological membrane samples, hydrated amyloid fibrils, and hydrated microcrystalline proteins, that allows direct assessment of the effects of frictional and radio-frequency heating under experimentally relevant conditions.


Bilitranslocase is the protein responsible for the electrogenic movement of sulfobromophthalein in plasma membrane vesicles from rat liver: immunochemical evidence using mono- and poly-clonal antibodies.
Monoclonal antibodies raised against bilitranslocase, may display either inhibitory or enhancing activity on the electrogenic transport of sulfobromophthalein, evoked in rat liver plasma-membrane vesicles by the addition of valinomycin in the presence of K+. In both cases, the target protein is identified with a 37 kDa band in SDS-mercaptoethanol gel electrophoresis of solubilized membranes. The electrophoretically homogeneous protein isolated by ion-exchange chromatography, corresponds in all respects to the 37 kDa protein band of bilitranslocase, obtained in the past by different techniques. Using this protein as antigen, a polyclonal monospecific antibody preparation has been obtained. As expected, the antibody preparation inhibits the electrogenic movement of sulfobromophthalein in plasma membrane vesicles from rat liver. It is concluded that the 37 kDa protein of bilitranslocase is at least a necessary component of the transport system involved in the sulfobromophthalein movement in plasma membrane.


Participation in two phase II prophylactic HIV vaccine trials in the UK.
There will be a continued imperative to recruit large numbers of healthy volunteers to early phase prophylactic HIV vaccine (PHV) trials. We studied mechanisms associated with participation in two related phase II PHV trials. The most cited reasons for volunteering were altruism and a personal connection to HIV. The most successful recruiting strategies targeted organisations dealing with HIV, health or social issues, or were directed to large audiences through the mass media. However, circulated emails and word of mouth were the most resource-effective approaches. Group discussions and the collection of a pool of potential volunteers were much less effective than one-to-one discussions and immediate screening after recruitment. We utilised our findings to devise key recommendations to assist PHV trial teams who are planning future studies.


Gold Nanoparticles Adsorb DNA and Aptamer Probes Too Strongly and a Comparison with Graphene Oxide for Biosensing.
Using fluorescently labeled DNA oligonucleotides and nanomaterials for developing biosensors has been extensively reported for gold nanoparticles (AuNPs) and graphene oxide (GO) among others. These materials have vastly different affinities and mechanisms for interacting with DNA, and their analytical performance is likely to be different. In this work, we used several DNA sequences and, respectively, adsorbed them on AuNPs and GO to quench fluorescence. Different from previous work, we used KCN to fully dissolve the AuNPs to calculate the percentage of the desorbed DNA due to the complementary DNA (cDNA) and aptamer target. The desorbed probe DNA from the AuNPs was less than 5% for all of the targets including DNA, adenosine, Hg2+, and lysozyme, indicating a very strong DNA adsorption affinity. Desorption of DNA was achieved by adding HEPES buffer, NaCl, and As(III), but such desorption was attributed to the adsorption of these molecules or ions by the AuNPs instead of their interaction with the adsorbed DNA. For GO, more probes desorbed with addition of target analytes but so did nonspecific desorption by random DNA and proteins. In summary, AuNPs are unlikely to be a good surface for developing biosensors relying solely on the desorption of probe DNA, while for GO the main problem is nonspecific desorption.


Effects of thermal sterilization on soy protein isolate/polyphenol complexes: Aspects of structure, in vitro digestibility and antioxidant activity.
The main purpose of this work was to investigate the influence of typical thermal sterilization approaches (pasteurization, high-temperature sterilization) on the structure, in vitro digestibility, and antioxidant activity of soy protein isolate (SPI)/black soybean seed coat extract (BE) complexes at pH 7.0. The results of zeta potential and particle size demonstrated that the addition of BE was contributed to inhibit protein thermal aggregation. Heat sterilization resulted in protein unfolding revealed by UV-Vis, circular dichroism, and fluorescence spectroscopy analysis. The increase of BE led to the reduction of fluorescence intensity and surface hydrophobicity of SPI. Moreover, the formation of SPI/BE complexes inhibited protein digestion in vitro, while thermal sterilization promoted protein digestion. The SPI/BE complexes showed a strong radical scavenging ability both before and after thermal treatment.


Massage therapy for cancer pain.
Therapeutic massage as a cancer pain intervention appears to be safe and effective. Patients who receive massage have less procedural pain, nausea, and anxiety and report improved quality of life. The use of massage in cancer care centers and hospitals is on the rise. Massage has a positive effect on biochemistry, increasing levels of dopamine, lymphocytes, and natural killer cells. Specialized training of massage therapists in caring for people with cancer is recommended. Most studies to date are small but promising. Exact methodology and best practices warrant further investigation by the industry. More randomized clinical trials and case studies must be conducted.


In vitro differentiation of macrophages from peripheral blood cells of celiac patients.
Macrophages have both a protective and pathological role in many autoimmune and inflammatory diseases. Macrophages phenotype is regulated by the environment that affects their polarization toward a pro- or anti-inflammatory phenotype. We describe a protocol for in vitro differentiation of macrophages from blood peripheral monocytes, that may be adopted to study different pathologies. Here, we are interested to study the phenotype of macrophages differentiated from patients affected by acute celiac disease (CD) or subjects following a gluten free diet (GFD), after in vitro gliadin challenge. We assess the pro-inflammatory phenotype of these macrophages by cytokines quantization on the cell supernatant. Moreover, our proposed protocol allows the preparation of total RNA to analyze the expression profile of many genes.


FASL -844C polymorphism is associated with increased activation-induced T cell death and risk of cervical cancer.
The FAS receptor-ligand system plays a key role in regulating apoptotic cell death, and corruption of this signaling pathway has been shown to participate in tumor-immune escape and carcinogenesis. We have recently demonstrated (Sun, T., X. Miao, X. Zhang, W. Tan, P. Xiong, and D. Lin. 2004. J. Natl. Cancer Inst. 96:1030-1036; Zhang, X., X. Miao, T. Sun, W. Tan, S. Qu, P. Xiong, Y. Zhou, and D. Lin. 2005. J. Med. Genet. 42:479-484) that functional polymorphisms in FAS and FAS ligand (FASL) are associated with susceptibility to lung cancer and esophageal cancer; however, the mechanisms underlying this association have not been elucidated. We show that the FAS -1377G, FAS -670A, and FASL -844T variants are expressed more highly on ex vivo-stimulated T cells than the FAS -1377A, FAS -670G, and FASL -844C variants. Moreover, activation-induced cell death (AICD) of T cells carrying the FASL -844C allele was increased. We also found a threefold increased risk of cervical cancer among subjects with the FASL -844CC genotype compared with those with the -844TT genotype in a case-control study in Chinese women. Together, these observations suggest that genetic polymorphisms in the FAS-FASL pathway confer host susceptibility to cervical cancers, which might be caused by immune escape of tumor cells because of enhanced AICD of tumor-specific T cells.


Effectiveness of herbal medicine (Rokumigan and Hachimijiogan) for fatigue or loss of energy in patients with partial remitted major depressive disorder.
Some patients with major depressive disorder (MDD) do not show remission of their depressive symptomatology. We investigated the efficacy of Rokumigan (TJ-87) and Hachimijiogan (TJ-7) in 20 patients with prolonged partial remitted MDD associated with fatigue or loss of energy. In these 20 patients, TJ-7 or TJ-87 was added to the previous regimen for 4 weeks. Six patients were 'much improved', six were 'minimally improved' (responders), and eight showed 'no change' (non-responders), on the Clinical Global Impression Global Improvement scale. All responders had Shofuku-fujin (tenderness or weakness of the lower abdomen). In conclusion, we experienced 12 outpatients with prolonged partial remitted MDD with fatigue or loss of energy, which was successfully treated with TJ-87 or TJ-7.


Environmental reprogramming of the expression of protein kinase CK2beta subunit in fish.
The dramatic segregation of the nucleolar components in winter-acclimatized carp is the most striking cellular-phenotypical feature observed during the seasonal adaptation of this fish toward the circannual changes in its habitat. Our studies also show that the carp habitat temperature and photoperiod winter conditions provoke a remarkable reduction of both rRNA transcription and the processing of their precursors. To gain knowledge on the mechanisms involved in the regulation of nucleolar activity during the seasonal adaptation process, we studied the behavior of some genes, specifically snoRNA U3 and protein kinase CK2. Consistent with the reduction in the synthesis and processing of pre-rRNA observed during the cold season, the level of CK2beta expression decreases in winter when compared to that attained in summer. Similarly, in winter, liver and kidney cells contain lower levels of CK2beta subunit protein compared to summer. CK2 is associated with or modifies different factors and enzymes involved in the nucleolar activity; therefore, its higher or lower content could be part of the molecular mechanisms underlying the nucleolar seasonal changes that occur during the compensatory acclimatization process.


The History of ERAS (Enhanced Recovery After Surgery) Society and its development in Latin America.
The shortage of hospital beds and changes in the payment model have promoted an increased attention and financing of programs that focus on perioperative care efficiency in. Latin America. In this paper, Enhanced Recovery After Surgery (ERAS) programs developed by the ERAS® Society will be discussed. The implementation and use of ERAS®Society Guidelines consistently demonstrated a reduction in postoperative complications, hospital stay and costs. In the current paper, the definition of ERAS programs, their core elements, and the results of their implementation and regional developments are presented with special focus on Latin America.


Lipidomic markers of sperm cryotolerance in cattle.
The objective of the current study was to determine the fatty acid composition of sperm from Holstein bulls with different freezability (Good and Poor; n = 12). Fatty acids were extracted from frozen sperm in 1:2 (v/v) chloroform-methanol solvent, fractionated into neutral and polar fractions, and composition determined by gas chromatography-mass spectrometry. Thirty-four fatty acids were quantified and their concentrations and percentages within each lipid fraction were calculated. Overall, saturated fatty acids (SFA) were predominant, accounting for 71 to 80% of fatty acids in neutral and polar lipid factions. There were marked differences in fatty acid composition between the lipid fractions (P < 0.001). The branched chain fatty acid (BCFA) concentration (15 to 18 µg) was almost twice as much as polyunsaturated fatty acids (PUFA) concentration found in the polar lipid fraction (8 to 9 µg; P < 0.001). Sperm with different freezability phenotypes only had a few differences in 22:0, 18:1 cis 9, and 14:0 13-methyl fatty acids (P ≤ 0.011). These results are significant because they reveal key understandings of fatty acid composition of sperm membrane and lay a foundation for the manipulation of membrane integrity, fluidity, and stability to advance the assisted reproductive technologies.


Natural killer cell-based immunotherapeutic strategies.
Not until recently have Natural killer (NK) cells stepped out of the shadow of T-cells to be considered for cellular therapy of malignant diseases. This evolution has been facilitated by the discovery of specific receptors on NK cells that interact with HLA molecules on target cells but also the discovery of specific activating receptors. Since NK cells represent only about 10% of the lymphocyte population in blood, separation and enrichment are important steps if NK cells are to be used clinically. This is of particular consideration in the setting of allogeneic NK cell infusion where contaminating T-cells could potentially induce graft versus host disease. This review will describe the requirements for NK cells to recognize target cells, their ex vivo expansion and potential therapeutic applications.


Hurried driver dispositions: their relationship to risky traffic behaviors.
To examine the relationship of driver dispositions with traffic safety behaviors and beliefs. A random digit-dial telephone survey was conducted of 796 licensed drivers. Binary and multivariate logistic regression analyses compared hurried and nonhurried drivers and found that hurried drivers were more likely to admit to a variety of risky behaviors. They were also less likely to believe they would be ticketed for speeding and to report wearing their seat belt than were nonhurried drivers. More research is needed into identifying the underlying motivational factors of hurried drivers and what countermeasures will be most effective for them.


Rubella virus infection and associated factors among pregnant women attending the antenatal care clinics of public hospitals in Hawassa City, Southern Ethiopia: a cross-sectional study.
To assess the seroprevalence of recent/acute and past exposure to rubella virus infection and associated risk factors among pregnant women. A hospital-based cross-sectional study. The study was conducted in two public hospitals in Hawassa City, Southern Ethiopia. A total of 422 pregnant women attending antenatal care clinics were selected using a systematic random sampling technique from March to June 2016. Data on sociodemography and related factors were collected using a structured questionnaire. Blood samples were also collected from each study participant and tested for antirubella IgM and IgG antibodies using ELISA. IgG seropositivity indicates past exposure to rubella (protective immunity). IgM seropositivity indicates recent exposure to rubella (or reinfection). The seroprevalence of antirubella IgM and IgG antibodies was 2.1% and 86.3%, respectively. Thus, the rate of susceptibility to rubella virus infection among pregnant women was found to be 13.7%. A significant association between residence site and IgG seropositivity was observed, where urban dwellers had higher past rubella exposure compared with rural residents (crude OR 6.3; 95% CI 3.29 to 12.14, p<0.001). The high rate of rubella exposure and its similar distribution by sociodemography (except residence site) suggests the continuous transmission and endemicity of the infection in the study area. These findings emphasise the importance of introducing rubella-containing vaccine into routine childhood immunisation programme and vaccinating susceptible women of childbearing age.


Early detection of glaucomatous visual field loss: why, what, where, and how.
This article provides a basis for understanding modern visual field analysis techniques. It describes some of these tests, including their advantages and disadvantages, and the settings in which different tests might be used most successfully. It also includes an examination of the value of visual field assessment from a public health standpoint with particular attention paid to morbidity, cost/benefit ratios, and quality of life correlations.


Sequence analysis of two mutants of Sindbis virus defective in the intracellular transport of their glycoproteins.
We have sequenced the complementary DNA corresponding to the genes encoding the viral glycoproteins of ts10 and ts23, mutants of Sindbis virus defective in the intracellular transport of their glycoproteins, and of revertants of these mutants. These studies have been augmented by direct amino acid sequencing of the amino-terminal regions of the glycoproteins of several virus strains. By comparing the deduced amino acid sequence with that of Sindbis HR virus, the parental strain of these mutants, and with the sequence of the revertants, we found ts23 to have a double mutation in glycoprotein E1, while ts10 was a single mutant in the same glycoprotein. In each case reversion to temperature insensitivity occurred by changes at the same site as the mutation, in two cases restoring the original amino acid and in the third case substituting an homologous amino acid (arginine in place of lysine). The three mutations were far apart from each other in the protein, suggesting that the three-dimensional conformation is very important for the correct migration of the glycoproteins from the rough endoplasmic reticulum to the plasma membrane. The sequence data also reveal that a number of other changes have occurred in the various virus strains during mutagenesis or passage.


[Bullous emphysema of the lung (our experience)].
Ten patients (9 males and 1 female; mean age: 44.8 yrs) with bullous lung disease were treated. Frequent patient-history findings were smoking and spontaneous pneumothorax. Nine cases were treated surgically either by bullectomy or atypical resection. In one case, an attempt at endobullous aspiration failed owing to the patient's very poor general condition. Among the postoperative complications in three cases we observed difficult pulmonary re-expansion and infection of the surgical wound with consequent pleural empyema in another.


Overall versus socioeconomic health inequality: a measurement framework and two empirical illustrations.
This paper outlines a framework for comparing empirically overall health inequality and socioeconomic health inequality. The framework, which is developed for both individual-level data and grouped data, is illustrated using data on malnutrition amongst Vietnamese children and on health utility amongst Canadian adults. In both cases, the degree of socioeconomic inequality is estimated at around 25% of overall inequality.


Late-onset autosomal recessive limb-girdle muscular dystrophy with rimmed vacuoles.
We report on two siblings with late-onset, limb-girdle muscular dystrophy (LGMD) inherited in an autosomal recessive manner. The LGMD was characterized by many rimmed vacuoles and reduced expression of the laminin beta1 chain in skeletal muscle. Both patients developed a progressive wasting and weakness of limb-girdle muscles in the late forties or early fifties; their facial, ocular, bulbar, and cardiac muscles were not involved. Histopathology of skeletal muscles biopsies showed typical dystrophic changes with many rimmed vacuoles. The immunoreactivity of the laminin beta1 chain was reduced in the muscle fibers, while dystrophin, sarcoglycans, beta-dystroglycan, dysferlin, and other laminin components were normally expressed. A mutation search revealed that no mutation existed in the coding region of the calpain 3, telethonin and UDP-N-acetylglucosamine 2-epimerase/N-acetylmanosamine kinase (GNE) genes. We conclude that this autosomal recessive LGMD is unknown and characterized by its late onset, rimmed vacuoles and reduction of the laminin beta1 chain in muscle fibers.


First-order UV-derivative spectrophotometry in the analysis of omeprazole and pantoprazole sodium salt and corresponding impurities.
The first-order UV-derivative spectrophotometry, applying zero-crossing method was developed for the determination of omeprazole (OM), omeprazole sulphone (OMS), pantoprazole sodium salt (PANa), and N-methylpantoprazole (NPA) in methanol-ammonia 4.0% v/v, where the sufficient spectra resolutions of drug and corresponding impurity were obtained, using the amplitudes 1D(304), 1D(307), 1D(291.5) and 1D(296.5), respectively. Method showed good linearity in the ranges (microg ml(-1)): 1.61-17.2 for OM; 2.15-21.50 for OMS; 2.13-21.30 for PANa and 2.0-20.0 for NPA, accuracy and precision (repeatability and reproducibility). The experimentally determined values of LOD (microg ml(-1)) were 1.126; 0.76; 0.691 and 0.716 for OM, OMS, PANa and NPA, respectively. The obtained values of 2.91% w/w for OMS and 3.58% w/w for NPA in the presence of their parent drug, by applying the method of standard additions, point out the usage of the proposed method in stability studies. Zero-crossing method in the first-order derivative spectrophotometry showed the impurity-drug intermolecular interactions, due to the possible intermolecular hydrogen bonds, confirmed by divergences of experimentally obtained amplitudes for impurities OMS and NPA in comparison to expected values according to regression equations of calibration graphs.


[Thumb replacement by microsurgery].
Our experiences with 11 heterotopic finger replantations and 18 cases of free second toe transfer for thumb reconstruction are reported. The wrap-around flap technique (Morrison) is also described.


Incidence and bacterial aetiology of neonatal conjunctivitis.
Two hundred and twenty-nine infants born consecutively at the maternity ward of the Middelheim Hospital in Antwerp, over a period of 5 months, and an additional 55 randomly selected infants born at the same hospital were clinically and microbiologically investigated before leaving the maternity ward. All infants born at this maternity ward received argyrol eye drops immediately after birth. Twenty-six (11%) of the infants consecutively investigated had neonatal conjunctivitis diagnosed before leaving the maternity ward, where they stayed from 7-10 days. Another 29 infants were reported to have developed sticky eyes and/or red eyes after leaving the maternity hospital and before 1 month of age. The instantaneous risk of developing, a conjunctivitis was equal for each day of the first month of life. Chlamydia trachomatis was isolated from the eyes of 11 of the 229 (4.8%) consecutively born infants but only one had conjunctivitis symptoms before leaving the maternity ward. Overall one or more bacterial species could be isolated from the eyes of 143 (48%) of the infants, but only viridans streptococci and Staphylococcus aureus were cultured significantly more often from the eyes of cases with conjunctivitis than from the eyes of the infants without conjunctivitis (P less than 0.001).


Assessing the impact of drinking water iodine concentrations on the iodine intake of Chinese pregnant women living in areas with restricted iodized salt supply.
The supply of non-iodized salt and the water improvement project have been conducted to reduce the iodine concentration in drinking water in areas with elevated water iodine. We aimed to assess the impact of water iodine concentration (WIC) on the iodine intake of pregnant women in areas with restricted iodized salt supply, and determine the cutoff values of WIC in areas with non-iodized salt supply. Overall, 534 pregnant women who attended routine antenatal outpatient visits in Zibo Maternal and Child Health Hospital in Gaoqing County were recruited. The 24-h urine iodine excretion (UIE) in 534 samples and the iodine concentration in 534 drinking water samples were estimated. Urinary iodine excretion, daily iodine intake, and daily iodine intake from drinking water (WII) were calculated. The relationship between WIC and daily iodine take was analyzed. The median WIC, spot urine iodine concentration (UIC), and 24-h UIE were 17 (6, 226) μg/L, 145 (88, 267) μg/L, and 190 (110, 390) μg/day, respectively. A significant positive correlation was found between WIC and UIE (R2 = 0.265, p < 0.001) and UIC (R2 = 0.261, p < 0.001). The contribution rate of WII to total iodine intake increased from 3.0% in the group with WIC of < 10 μg/L to 45.7% in the group with WIC of 50-99 μg/L. The iodine content in drinking water is the major iodine source in pregnant women living in high-water iodine areas where iodized salt supply is restricted. The contribution rate of daily iodine intake from drinking water increases with the increase in water iodine concentration.


Tissue expression of TGF-β1 in uterine cervical samples from HIV/AIDS patients.
Case-control study based on the immunohistochemistry for TGF-β1 evaluation of cervical samples obtained from two groups of women: CIN/HIV- and CIN/HIV+. Eleven women infected with HIV and with a histopathological diagnosis of CIN were included. The control group consisted of 12 patients with CIN. Cervical tissue samples obtained from all patients were submitted to histopathology and semiquantitative analysis of immunostaining for TGF-β1 protein. In addition, the peripheral CD4+ cell count and viral load were evaluated in HIV + patients. Tissue expression of the cytokine was higher in the CIN/HIV+ group compared to control (p = 0.0023). In addition, higher TGF-β1 expression was observed in higher grade cervical lesions in the two groups. There was a trend toward a direct correlation between peripheral CD4+ T cell count and tissue TGF-β1, and toward an inverse correlation between viral load and cytokine expression. Thus, TGF-β1 was more marked in situations in which cervical lesions are known to present a more aggressive behavior, suggesting that this cytokine is involved in the pathogenesis of tumor growth in these lesions. Tissue expression of TGF-β1 is increased in cervical samples from HIV-infected women with CIN.


Characterization on nicotine degradation and research on heavy metal resistance of a strain Pseudomonas sp. NBB.
The remediation of polluted sites containing multiple contaminants like nicotine and heavy metals poses significant challenges, due to detrimental effects like cell death. In this study, we isolated a new strain Pseudomonas sp. NBB capable of efficiently degrading nicotine even in high level of heavy metals. It degraded nicotine through pyrrolidine pathway and displayed minimum inhibitory concentrations of 2 mM for barium, copper, and lead, and 5 mM for manganese. In the presence of 2 mM Ba2+ or Pb2+, 3 g L-1 nicotine could be completely degraded within 24 h. Moreover, under 0.5 mM Cu2+ or 5 mM Mn2+ stress, 24.13% and 72.56% of nicotine degradation were achieved in 60 h, respectively. Strain NBB tolerances metal stress by various strategies, including morphological changes, up-regulation of macromolecule transporters, cellular response to DNA damage, and down-regulation of ABC transporters. Notably, among the 153 up-regulated genes, cds_821 was identified as manganese exporter (MneA) after gene disruption and recovery experiments. This study presents a novel strain capable of efficiently degrading nicotine and displaying remarkable resistance to heavy metals. The findings of this research provide valuable insights into the potential application of nicotine bioremediation in heavy metal-contaminated areas.


Comparative evaluation of a novel measurement tool to assess lumbar spine posture and range of motion.
The diagnosis of low back pain pathology is generally based upon invasive image-based assessment of structural pathology, but is limited in methods to evaluate function. The accurate and robust measurement of dynamic function may assist in the diagnosis and monitoring of therapy success. Epionics SPINE is an advanced strain-gauge measurement technology, based on the two sensor strips SpineDMS system, which allows the non-invasive assessment of lumbar and thoraco-lumbar motion for periods of up to 24 h. The aim of this study was to examine the reliability of Epionics SPINE and to collect and compare normative data for the characterisation of spinal motion in healthy subjects. Furthermore, the identification of parameters that influence lumbar range of motion (RoM) was targeted. Spinal shape was measured using Epionics SPINE in 30 asymptomatic volunteers during upright standing, as well as maximum flexion and extension, to check intra-rater reliability. Furthermore, back shape was assessed throughout repeated maximum flexion and extension movements in 429 asymptomatic volunteers in order to collect normative data of the lordosis angle and RoM in different gender and age classes. The lordosis angle during standing in the healthy collective measured with Epionics SPINE was 32.4° ± 9.7°. Relative to this standing position, the average maximum flexion angle was 50.8° ± 10.9° and the average extension angle 25.0° ± 11.5°. Comparisons with X-ray and Spinal Mouse data demonstrated good agreement in static positions. Age played a larger role than gender in influencing lumbar posture and RoM. The Epionics SPINE system allows the practical and reliable dynamic assessment of lumbar spine shape and RoM, and may therefore provide a clinical solution for the evaluation of lower back pain as well as therapy monitoring.


Molecular analysis of pleckstrin: the major protein kinase C substrate of platelets.
Activation of protein kinase C (PKC) in platelets causes the immediate phosphorylation of pleckstrin, an apparent Mr 40-47,000 protein previously called 40K or P47. Pleckstrin presumably plays an important but as yet unknown role in mediating cellular responses evoked by agonist-induced phosphoinositide turnover. We have cloned the cDNA for pleckstrin from the HL-60 human promyelocytic leukemia cell line by immunological screening of a lambda gt11 expression library (Tyers et al.: Nature 333:470-473, 1988) and now report further analysis of the pleckstrin sequence. Pleckstrin has a deduced Mr of 40,087 and is encoded by a 1,050-bp open reading frame which is preceded by a short open reading frame that terminates before the correct initiator methionine. A single polymorphic site was found in the coding region. An unusual pattern of sequence heterogeneity occurred about a poly(A) tract in the 3' untranslated region. The 3.0-kb pleckstrin mRNA induced upon differentiation of HL-60 cells apparently has heterogeneous 5' ends which undergo differential regulation during HL-60 cell maturation. Analysis by multiple sequence alignment with known PKC substrates identified a strong candidate site for phosphorylation by PKC and a potential Ca2+-binding EF-hand motif. No other similarities to proteins in current databases were found.


Efficacy of doramectin against naturally acquired adult and inhibited larval infections by some nematode parasites in cattle in New Zealand.
A study was conducted to determine the therapeutic efficacy of 1% doramectin injected subcutaneously at 200 microg/kg into cattle harbouring naturally acquired infections of inhibited Ostertagia ostertagi larvae. Sixteen yearling Friesian bulls, grazed without anthelmintic treatment throughout the autumn-winter, were selected on the basis of similar body weights and serum pepsinogen activities. After removal from pasture on day -23 they were weighed and randomly assigned to two treatment groups on the basis of this weight. On day 0, one group was given saline (1 ml/50 kg) while the second was treated with doramectin (200 microg/kg). Both treatments were given by subcutaneous injection. All stock were slaughtered 14-15 days after treatment. Moderate to high levels of adult O. ostertagi and Trichostrongylus axei and early and late 4th larval stages of O. ostertagi were recovered from saline-treated calves at necropsy. Doramectin was highly effective in eliminating all stages of O. ostertagi (99.9%; p<0.0001) and T. axei (100%; p<0.0001). No evidence of lesions were detected at the injection sites at necropsy. These results confirm that doramectin is an extremely effective broad-spectrum avermectin anthelmintic with efficacy against inhibited as well as maturing larval and adult forms of O. ostertagi.


Effects of Maternal Dietary Cottonseed on the Profile of Minerals in the Testes of the Lamb.
The use of cotton co-products in animal feed is restricted by the presence of gossypol, which is a toxic and highly reactive molecule of complex minerals. In mammals, part of the offspring phenotype is influenced by dam nutrition. The aim of this study was to investigate the effect of ewe diet, with and without cottonseed (gossypol), on the testicular development of lambs from birth to weaning through the assessment of lamb live weight (LW), macro and histological morphology of testes, and mass fraction of chemical elements by neutron activation analysis (NAA) and microprobe X-ray fluorescence spectroscopy, as well as the multielement distribution map in the testes. Eighteen lambs were used with an average LW at birth of 4 ± 1.0 kg. All lambs were offspring of Santa Inês ewes, fed on ration either with or without cottonseed during mating, gestation, and lactation, thus forming two treatments: control group (C) without cottonseed and treatment group with cottonseed (G). The animals were weighed from birth to 60 days of age, at fortnightly intervals. At 60 days of age, the lambs were orchidectomized to collect their testes for macroscopy, histological, neutron activation, and X-ray fluorescence analysis. Besides dry matter (DM), protein, ether extract (EE), calcium (Ca), and potassium (K) were higher in the ewe milk from the C group compared with the G group (P < 0.05). Lambs from the C group showed higher LW from 45 days onwards, as well as higher average daily gain when compared with the G group (P < 0.05). They also presented higher testicular weight, volume, length, width, as well as tubule and lumen diameters compared with lambs from the G treatment (P < 0.05). Multielementary NAA revealed higher mass fractions of rubidium (Rb), selenium (Se), and cesium (Cs) in the testes of lambs from the C group when compared with the G group, while G showed higher zinc (Zn) content (P < 0.05). No differences between treatments were found for element levels and distribution using X-ray fluorescence microanalysis (P > 0.05). In conclusion, the maternal cottonseed diet compromised performance and testes development of the lambs and reduce the content of Se in the testes.


A metagenomic-based method to study hospital air dust resistome.
As a symbol of the defense mechanisms that bacteria have evolved over time, the genes that make bacteria resist antibiotics are overwhelmingly present in the environment. Currently, bacterial antibiotic resistance genes (ARGs) in the air are a serious concern. Previous studies have identified bacterial communities and summarized putative routes of transmissions for some dominant hospital-associated pathogens from hospital indoor samples. However, little is known about the possible indoor air ARG transportation. In this study, we mainly surveyed air-conditioner air dust samples under different airflow conditions and analyzed these samples using a metagenomic-based method. The results show air dust samples exhibited a complex resistome, and the average concentration is 0.00042 copies/16S rRNA gene, which is comparable to some other environments. The hospital air-conditioners can form resistome over time and accumulate pathogens. In addition, our results indicate that the Outpatient hall is one of the main ARG transmission sources, which can distribute ARGs to other departments (explains >80% resistome). We believe that the management should focus on ARG carrier genera such as Staphylococcus, Micrococcus, Streptococcus, and Enterococcus in this hospital and our novel evidence-based network strategy proves that plasmid-mediated ARG transfer can occur frequently. Overall, these results provide insights into the characteristics of air dust resistome and possible route for how ARGs are spread in air.


Partial rotator cuff repair and biceps tenotomy for the treatment of patients with massive cuff tears and retained overhead elevation: midterm outcomes with a minimum 5 years of follow-up.
A subset of patients with massive irreparable rotator cuff tears present with retained overhead elevation and pain as their primary complaint. Our aim was to evaluate the outcomes of partial arthroscopic rotator cuff repair with biceps tenotomy and to report the failure rate of this procedure for patients with >5 years of follow-up. Thirty-four patients underwent partial rotator cuff repair and biceps tenotomy for treatment of a massive rotator cuff tear. Patients had preoperative active forward elevation >120° and no radiographic evidence of glenohumeral arthritis. Patients were followed up clinically and radiographically, and 28 patients had a minimum of 5 years of follow-up. Failure was defined as an American Shoulder and Elbow Surgeons score of <70, loss of active elevation >90°, or revision to reverse shoulder arthroplasty during the study period. Patients demonstrated improvements in average preoperative to postoperative American Shoulder and Elbow Surgeons scores (46.6 to 79.3 [P < .001]) and Simple Shoulder Test scores (5.7 to 9.1 [P < .001]) along with decrease in visual analog scale for pain scores (6.9 to 1.9 [P < .001]). No significant change in forward elevation (168° to 154° [P = .07]), external rotation (38° to 39° [P = 1.0]), or internal rotation (84% to 80% [P = 1.0]) was identified; 36% of patients had progression of the Hamada stage. The failure rate was 29%; 75% of patients were satisfied with their index procedure. Partial rotator cuff repair and biceps tenotomy for patients with massive irreparable rotator cuff tears with retained overhead elevation and pain as the primary complaint produced reasonable outcomes at midterm follow-up of at least 5 years.


Establishment and validation of a model for brain injury state evaluation and prognosis prediction.
Traumatic brain injury (TBI) is one of the leading causes of disability and death in modern times, whose evaluation and prognosis prediction have been one of the most critical issues in TBI management. However, the existed models for the abovementioned purposes were defective to varying degrees. This study aims to establish an ideal brain injury state clinical prediction model (BISCPM). This study was a retrospective design. The six-month outcomes of patients were selected as the end point event. BISCPM was established by using the split-sample technology, and externally validated via different tests of comparison between the observed and predicted six-month mortality in validating group. TBI patients admitted from July 2006 to June 2012 were recruited and randomly divided into establishing model group and validating model group. Twenty-one scoring indicators were included in BISCPM and divided into three parts, A, B, and C. Part A included movement, pupillary reflex and diameter, CT parameters, and secondary brain insult factors, etc. Part B was age and part C was medical history of the patients. The total score of part A, B and C was final score of BISCPM. Altogether 1156 TBI patients were included with 578 cases in each group. The score of BISCPM from validating group ranged from 2.75 to 31.94, averaging 13.64 ± 5.59. There was not statistical difference between observed and predicted mortality for validating group. The discrimination validation showed that the BISCPM is superior to international mission for prognosis and analysis of clinical trials (IMPACT) lab model. BISCPM is an effective model for state evaluation and prognosis prediction of TBI patients. The use of BISCPM could be of great significance for decision-making in management of TBI.


Sex differences in the association between muscle quality, inflammatory markers, and cognitive decline.
Aspects of frailty such as sarcopenia and dementia are associated with a proinflammatory state; however, little research has examined the concurrence of these pathologies. This study examined sex-specific differences in the relationship between low muscle quality and impaired cognitive functioning, while considering the role of inflammatory markers. The nationally representative sample was drawn from a cross-sectional study. Four hundred forty-five females and four hundred twenty-two males over age 60 from the National Health and Nutrition Examination Survey for 2001-2002 were included. Muscle quality was calculated as isokinetic strength per unit muscle mass. Skeletal muscle mass of the legs was measured using dual energy x-ray absorptiometry and isokinetic strength of the knee extensors was estimated using a Kin-Com dynamometer. Participants were assessed for cognitive functioning using the Wechsler Adult Intelligence Scale, Third Edition (WAIS-III) Digit Symbol - Coding module. High sensitivity C-reactive protein (CRP) assays were performed on blood samples using a Behring Nephelometer to estimate levels of inflammation. Sex stratified ordinary least squares regression models were utilized to estimate the relationship between muscle quality and cognitive functioning, while examining CRP as a possible mechanism and controlling for potential confounds. In the first model a statistically significant positive relationship was found between cognitive functioning and muscle quality for both sex groups. In the second model, CRP was found to have a statistically significant negative association with cognitive functioning for females but not males. Furthermore, the inclusion of CRP in the second model significantly reduced the predictive power of muscle quality for females, as compared to model 1. Measures of sarcopenia are associated with lower cognitive functioning in older adults, and for females, this association may be partly due to systemic inflammation. Further research is need to examine the relationship between these frailty-related pathologies, which have substantial health and economic implications.


The current use and attitudes towards tumor genome sequencing in breast cancer.
There is increasing availability of technologies that can interrogate the genomic landscape of an individual tumor; however, their impact on daily practice remains uncertain. We conducted a 28-item survey to investigate the current attitudes towards the integration of tumor genome sequencing in breast cancer management. A link to the survey was communicated via newsletters of several oncological societies, and dedicated mailing by academic research groups. Multivariable logistic regression modeling was carried out to determine the relationship between predictors and outcomes. 215 physicians participated to the survey. The majority were medical oncologists (88%), practicing in Europe (70%) and working in academic institutions (66%). Tumor genome sequencing was requested by 82 participants (38%), of whom 21% reported low confidence in their genomic knowledge, and 56% considered tumor genome sequencing to be poorly accessible. In multivariable analysis, having time allocated to research (OR 3.37, 95% CI 1.84-6.15, p < 0.0001), working in Asia (OR 5.76, 95% CI 1.57 - 21.15, p = 0.01) and having institutional guidelines for molecular sequencing (OR 2.09, 95% 0.99-4.42, p = 0.05) were associated with a higher probability of use. In conclusion, our survey indicates that tumor genome sequencing is sometimes used, albeit not widely, in guiding management of breast cancer patients.


Effect of Mn doping on the electronic and optical properties of Dy2Ti2O7: a combined spectroscopic and theoretical study.
Electronic and optical studies on Dy2Ti2-MnxO7(x= 0.00, 0.05, 0.10, 0.15, & 0.20) have been presented through both, theoretical (density functional theory (DFT) calculations) and experimental (ultraviolet-visible absorption and photoluminescence emission spectroscopy) approaches. DFT calculations were employed considering the local density approximation (LDA) and LDA-1/2 for exchange-correlation interactions. Computed crystallographic parameters and energy band-gap using theoretical formulations are in good agreement with experimental results. The band-gap value obtained through the LDA-1/2 approach indicates insulated ground state of Dy2Ti2-xMnxO7(x= 0.00, 0.05, 0.10, 0.15, 0.20) system. Experimentally obtained band gap value reduces from 3.82 eV to 2.45 eV with increase in positive chemical pressure asxincreases from 0 to 0.20. Reduction in band gap value is attributed to the fact that there exists a lack of hybridization between the O-2p orbital and Ti-3d orbital, which is well correlated with the crystallographic data. Jahn-Teller effect is likely to be responsible for the presence of a mixed state of Mn (explained using x-ray photoelectron spectroscopy results), resulting in the intermediate Mn state between the valence band and the conduction band with immediate inclusion of Mn at Ti site in Dy2Ti2-xMnxO7system.


Estimation of the forces generated by the thigh muscles for transtibial amputee gait.
The forces generated by the muscles with origin on the human femur play a major role in transtibial amputee gait, as they are the most effective of the means that the body can use for propulsion. By estimating the forces generated by the thigh muscles of transtibial amputees, and comparing them to the forces generated by the thigh muscles of normal subjects, it is possible to better estimate the energy output needed from prosthetic devices. The purpose of this paper is to obtain the forces generated by the thigh muscles of transtibial amputees and compare these with forces obtained from the same muscles in the case of normal subjects. Two transtibial amputees and four normal subjects similar in size to the amputees were investigated. Level ground walking was chosen as the movement to be studied, since it is a common activity that most amputees engage in. Inverse dynamics and a muscle recruitment algorithm (developed by AnyBody Technology(®)) were used for generating the muscle activation patterns and for computing the muscle forces. The muscle forces were estimated as two sums: one for all posterior muscles and one for the anterior muscles, based on the position of the muscles of the thigh relative to the frontal plane of the human body. The results showed that a significantly higher force is generated by the posterior muscles of the amputees during walking, leading to a general increase of the metabolic cost necessary for one step.


Phylogenetic analysis of hepatitis E virus isolates from Egypt.
Hepatitis E virus (HEV) genome was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in fecal samples of two sporadic cases of hepatitis E in Cairo Egypt. Sequence of the complete putative structural region [open reading frame (ORF)-2] and complete region of unknown function (ORF-3) was determined for the two HEV isolates. Phylogenetic analysis of the nucleotide sequences was performed using neighbor joining or maximum parsimony methods of tree reconstruction. Direct correspondence between the HEV evolutionary trees and geographic origin of the HEV isolates was observed. Three genotypes of HEV were identified: genotype I (Asia-Africa), genotype II (US), and genotype III (Mexico). Genotype I was further divided into two subgenotypes (Asia and Africa). In the Asian subgenotype, three smaller genetic clusters were observed (China-like sequences, Burma-like sequences, and sequence from a fulminant case of HEV). The segregation of all these genetic clusters was supported by the high level of bootstrap probabilities. Four regions of the HEV genome were used for phylogenetic analysis. In all four regions, Egyptian HEV isolates were grouped in a separate African clade.


Effects of illness representation-focused patient education on illness representations and self-care in patients with heart failure: A randomised clinical trial.
To examine the effect of an illness representation-focused patient education intervention on illness representations and self-care behaviours in patients with heart failure 3 months after discharge from the hospital. Few intervention studies have examined the effect of illness representation-focused interventions on illness representations and self-care in patients with heart failure. A randomised clinical trial based on the Consolidated Standard of Reporting Trials-CONSORT 2010-guidelines was employed. The Clinical Trial Registry number is TCTR20190903002. One hundred and seven participants were randomly assigned to 2 groups, and 62 participants (n = 30 in the intervention group and n = 32 in the usual care group) completed the baseline and one- and three-month postdischarge follow-up assessments. The instruments included the Survey of Illness Beliefs in Heart Failure and the Self-care of Heart Failure Index. The intervention group received illness representation-focused patient education while hospitalised and telephone follow-ups after discharge. Data were analysed with linear mixed-effects model analysis. The 107 participants had a mean age of 62.17 years and a mean left ventricular ejection of 53.03%. At baseline, the two groups tended to have accurate illness beliefs but insufficient self-care confidence and self-care maintenance. The analysis showed no significant differences between groups in the illness representation total scores, dimension scores or self-care maintenance scores but did show a significant difference in the self-care confidence scores (F = 3.42, p < .05) over the three months. The study did not show an effect of the intervention on illness representations or self-care maintenance behaviours. However, the intervention did maintain participants' self-care confidence three months after discharge. It is necessary to conduct long-term follow-ups of patients' illness representations, discuss the implementation of self-care behaviours with patients, enhance patients' self-care confidence, and involve family members or caregivers in self-care practices when needed.


[Detection of sentinel lymph node in patients with early stage breast cancer].
Axillary lymph node dissection (ALND) is routinely performed during surgery for breast cancer, but whether ALND could increase survival rate of early stage breast cancer patients remains controversial. Recently, replacing ALND with sentinel lymph node (SLN) biopsy has became a hotspot in breast cancer research. This study aimed to evaluate the reliability and accuracy of SLN biopsy for early stage breast cancer, and to discover the significance of multiple step section level cytokeratin immunohistochemistry in identifying micrometastatic disease. SLN biopsy was performed on 121 patients with T1 or T2 breast cancer: methylene blue-labeling was used in 38 patients (methylene blue group), double-labeling of (99m)Tc sulfur colloid and methylene blue was used in 83 patients (combination group). Lymphoscintigraphy and hand-hold gamma detector were used to localize SLNs before operation. All SLNs and ALND lymph nodes were pathologically examined. The tumor-negative SLNs were cut at three levels, and detected by immunohistochemistry. Success rates were 81.6% in methylene blue group, and 95.2% in combination group; accurate detection rates of axillary lymph nodes were 93.5% in methylene blue group, and 97.5% in combination group. SLNs were found in 19 patients (23%) by lymphoscintigraphy, and 76 patients (92%) by hand-hold gamma detector, respectively (P=0.04). A total of 194 negative SLNs, detected by routine pathologic examination, were re-examined by multiple step section level cytokeratin immunohistochemistry; micrometastatic diseases were identified in 21 SLNs of 13 patients. The accuracy rate of combined examinations was 98.7%, and the false-negative rate was 3.2%. The axillary node status can be predicted by SLN biopsy; double-staining is better than methylene blue-labeling. The role of lymphoscintigraphy in SLN biopsy needs further explore. Multiple step section level cytokeratin immunohistochemistry can improve detection rate of micrometastatic diseases.


Determination of N-nitrosodiethanolamine in cosmetic products by headspace solid phase microextraction using a novel aluminum hydroxide grafted fused silica fiber followed by gas chromatography-mass spectrometry analysis.
A method based on headspace solid phase microextraction with a new fiber, coupled with gas chromatography-mass spectrometry was developed for the determination of NDELA in cosmetic samples. The fiber provides Lewis acid-base interaction between its surface and analyte functional groups. The fiber was prepared by grafting aluminum tri-tert-butoxide on the surface of a fused silica. The optimization of SPME conditions showed that NDELA can be most effectively extracted at 70°C, in 15 min, with a sample volume of 0.5 (Vs/Vt), stirring rate of 150 rpm, desorption time of 5 min, desorption temperature of 260°C and at 12.5% (w/w) concentration of NaCl. Under the optimized conditions, LOD of 1 μg Kg(-1) and a calibration curve with correlation coefficients greater than 0.9897 and a linearity range from 6 to 10000 μg Kg(-1) were obtained. The intra-day and inter-day precision and accuracy were evaluated at four concentration levels. All of the values for accuracy and precision were lower than the acceptable limit of 15%. The fiber to fiber repeatability was 8.7%. The method was applied for the analysis of real samples including hair shampoo, body shampoo, dishwashing liquid and hand washing liquid. Relative recoveries were achieved in the range of 95-99%.


Interleukin-1 induces conditioned taste aversion in rats: a possible explanation for its pituitary-adrenal stimulating activity.
To investigate the possible aversive stimulus properties of peripherally administered interleukin 1 (IL-1), rats received two pairings of ingestion of a saccharin solution with various doses of recombinant rat interleukin 1 in a conditioned taste aversion paradigm, using 20 mg/kg lipopolysaccharide endotoxin as a positive control. Rats treated with 1 and 10 micrograms IL-1 showed a dose-dependent reduced preference for saccharin together with dose-dependent impairments in weight gain. Since these effects were obtained within the range of doses that has been previously reported to stimulate the release of ACTH, it is proposed that this last action of IL-1 is likely to be secondary to the aversive effects of IL-1.


Tetanus and botulinum toxins inhibit, and black widow spider venom stimulates the release of methionine-enkephalin-like material in vitro.
The actions of tetanus toxin, botulinum A toxin, and black widow spider venom on the release of methionine-enkephalin-like immunoreactivity have been studied; a particulate fraction prepared from rat striata was used. Depending on the duration of preincubation, tetanus toxin diminished the release evoked by veratridine (50 microM final concentration), and abolished it at final concentrations between 0.1 and 1 micrograms/ml. Botulinum A toxin was about 10 to 20 times less potent. Heating or pretreatment with antitoxin inactivated the clostridial toxins. The particulate fraction pretreated with V. cholerae neuraminidase retained its toxin sensitivity. Tetanus toxin also depressed the release due to sea anemone toxin II and high K+. Spider venom stimulated the release in a concentration-dependent manner and required the presence of Ca2+; its effects were depressed by tetanus toxin. These results support the view that both clostridial toxins and spider venom act as broad-range presynaptic neurotoxins on peptidergic transmitter systems.


Interplay of different synchronization modes and synaptic plasticity in a system of class I neurons.
We analyze the effect of spike-timing-dependent plasticity (STDP) on a system of pulse-coupled class I neurons. Our research begins with a system of two mutually connected quadratic integrate-and-fire (QIF) neurons, which are canonical representatives of class I neurons. Along with various asymptotic modes previously observed in other neuronal models with plastic synapses, we found a stable synchronous mode characterized by unidirectional link from a slower neuron to a faster neuron. In this frequency-locked mode, the faster neuron emits multiple spikes per cycle of the slower neuron. We analytically obtain the Arnold tongues for this mode without STDP and with STDP. We also consider larger plastic networks of QIF neurons and show that the detected mode can manifest itself in such a way that slow neurons become pacemakers. As a result, slow and fast neurons can form large synchronous clusters that generate low-frequency oscillations. We demonstrate the generality of the results obtained with two connected QIF neurons using Wang-Buzsáki and Morris-Lecar biophysically plausible class I neuron models.


Acute toxicity and treatment interruption related to electron and photon craniospinal irradiation in pediatric patients treated at the University of Texas M. D. Anderson Cancer Center.
To determine the incidence of acute toxicity and treatment interruption associated with electron and photon craniospinal irradiation (CSI) in children treated with or without chemotherapy. A retrospective study involving a computerized search of the radiotherapy database at the University of Texas M. D. Anderson Cancer Center identified a total of 79 eligible patients </=18 years old who had received electron (n = 46) or photon (n = 33) CSI from October 1980 to March 2000. Acute toxicity was graded according to the 1998 National Cancer Institute Common Toxicity Criteria. Chemotherapy sequencing was categorized as before or after CSI or no chemotherapy. The incidences of weight loss and skin toxicity were recorded and differences in treatment interruption and hematologic values with respect to modality used (electron vs. photon), age (</=6 or >6 years), and sequencing of chemotherapy were compared using chi-square tests. The median age of the electron group was lower than that of the photon group (6.7 years and 11.7 years, respectively). The two groups were otherwise well matched in terms of median spinal dose (31.1 vs. 33.3 Gy), fraction size (1.57 vs. 1.63 Gy), and total treatment time (32.4 vs. 30.7 days). Only 2 patients in each group (photon and electron) had a treatment break (>3 days). The mean number of days interrupted was 0.94 (photon) and 1.1 (electron) (p = 0.72). The electron and photon groups were well balanced in terms of receiving pre-CSI chemotherapy (37% vs. 41%, p = 0.776). Chemotherapy given before radiotherapy vs. after or not at all was associated with an increased incidence of Grade 3-4 leukopenia (76% vs. 49%, p = 0.02), thrombocytopenia (90% vs. 10%, p = 0), and neutropenia (50% vs. 15%, p = 0.005). A younger age was associated with Grade 3-4 thrombocytopenia (29% vs. 8.7%, p = 0.034), and decreased hemoglobin (29% vs. 6.5%, p = 0.014). The incidence of leukocyte depression of Grade 3-4 toxicity was 62% in the electron group and 32% in the photon group (p = 0.018). The incidence of Grade 3-4 platelet toxicity was higher with electrons (21%) than with photons (4%), but the difference was of borderline significance (p = 0.053). The difference in Grade 1-2 weight loss was not statistically significant (86% electron vs. 55% photon groups, p = 0.53), and Grade 3-4 weight loss did not occur within the entire study group. Most patients experienced Grade 0-1 radiation dermatitis with either electrons or photons. A younger patient age (</=6 years) and the sequence of chemotherapy before radiotherapy were associated with increased acute hematologic toxicity. Grade 3-4 weight loss, a surrogate for gastrointestinal toxicity, was not observed within the entire population. Despite the increased acute hematologic toxicities associated with CSI in very young children, the vast majority of patients were able to complete photon or electron CSI with minimal to no treatment interruptions. CSI with the electron technique can be used as an alternative to photon CSI in young children, and in our experience does not require the routine use of hematopoietic growth factors.


Rapid reversible phosphorylation of rat brain tau proteins in response to cold water stress.
The effect of cold water stress (CWS) on the phosphorylation of tau proteins in rat brain was studied using monoclonal antibodies to phosphorylated (PHF-1) and non-phosphorylated (TAU-1) epitopes. CWS induced an immediate 2-3-fold increase of PHF-1 signal in the soluble fraction of rat brain cortex, hippocampus and cerebellum. A maximal 3-4-fold increase occurred in 30-90 min. The soluble TAU-1 signal decreased following the CWS and at 60 min became significantly lower (P < 0.05) than in the control. Both signals returned to the normal range within 3 h. CWS induced a similar increase in PHF-1 signal in adrenalectomized animals and in animals subchronically treated with cortisone. These data indicate that stress induces rapid phosphorylation of soluble rat brain tau without direct involvement of the hypothalamic-pituitary-adrenal axis.


Nuclear factor erythroid 2-related factor 2 and autophagy regulation in cancer development.
Nuclear factor erythroid 2-related factor 2 (Nrf2) mitigates cell damage due to stress, environmental xenobiotics, and toxic chemicals. Nrf2 is present in the cytoplasm bound to its cysteine-rich Kelch domain-containing partner, Kelch-like ECH-associated protein 1 (Keap1), where is ubiquitinated and degraded. In addition to inducers that disrupt the Keap1-Nrf2 complex, defective autophagy has recently been shown to upregulate endogenous p62, which interacts with Keap1 triggering transcriptional activation of Nrf2 in several cancers. This regulation by Nrf2-dependent transactivation of cytoprotective genes needs to be validated by clinical trials in view of its persistent activation in a p62-dependent manner when there is deregulation of autophagy.


Elevated serum progastrin-releasing peptide (31-98) in metastatic and androgen-independent prostate cancer patients.
Increases in neuroendocrine phenotype and secretory products are closely correlated with tumor progression and androgen independence in prostate cancer. In this study, we explored this correlation using serum progastrin-releasing peptide (ProGRP), a carboxy-terminal region common to three subtypes of precursors for gastrin-releasing peptide (GRP), which is released from the neuroendocrine phenotype to act as a growth factor. In 60 patients with benign prostatic hyperplasia (BPH) and 200 with prostate cancer, serum ProGRP levels were determined with an enzyme-linked immunosorbent assay (ELISA) kit and evaluated in relation to clinical stage, hormonal treatment, and prostate-specific antigen (PSA) values. Fourteen randomly selected patients were entered in the follow-up study. Additionally, expression of ProGRP as determined by immunohistochemical analysis was compared to that of chromogranin-A (CgA) in tissue samples from several subjects. We found a positive correlation between PSA and ProGRP in patients with untreated prostate cancer; no correlation was found in the treated groups. The increases in the ProGRP value and in the percentage of patients with higher than normal values were significant (P < 0.0001), especially in the androgen-independent group (P < 0.0001). A longitudinal study showed that, in a subset of patients, the ProGRP values tended to increase transiently when the cancer became androgen independent, but remained unchanged or decreased at the androgen-dependent stage. Positive staining for ProGRP occurred in a different distribution in neuroendocrine tissues than that of staining for CgA. The clinical results demonstrated the existence of a regulatory mechanism for GRP, which to date had only been observed in cell lines. These findings suggest that GRP is a growth factor potentially upregulated by androgen but that does not rely principally on androgen modulation. The large overlap in levels of ProGRP among the groups limits the use of this value as a monitoring tool. Measurement of ProGRP, however, does have potential as an independent parameter to evaluate androgen-independent progression and to facilitate a new therapeutic strategy that may compensate for current limitations of diagnosis based on PSA alone.


Ethical aspects in the care of a child with infantile spinal muscular atrophy (SMA).
The pediatrician has a privileged relationship with a child with infantile spinal muscular atrophy (SMA). At all times, he/she must be the child's mentor, promoting a comprehensive approach and support in order to ensure the best possible solution for the patient's autonomy. In all circumstances, an ethical stance is essential. After a reminder on the notions of ethics of care, we will address various ethical questions encountered through three critical situations during the care of a child with infantile spinal muscular atrophy: the announcement of the diagnosis, the transmission of information on innovative therapies, and palliative care and end-of-life support. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.


Characteristics of two malignant lymphomas in C57B1/6J mice. Cytogenetic changes and the distribution of i.v. transfused tumor cells with and without enzyme (pronase, neuraminidase) treatment.
Two T-cell lymphomas induced by a combination of antigen stimulation and immunosuppression in inbred C57Bl/6J mice, BWL1 and BWL2 (Ryd et al. 1985), were further characterized. Cytogenetically they have the same trisomy 15 abnormality as chemically, virally and radiation induced T-cell lymphomas. Analyses of early and late tumour generations indicate that both tumours are chromosomally stable. After i.v. transplantation, the two tumors grew in a similar manner and preferentially in spleen and liver. Proteolytic treatment of the tumor cells changed the distribution of both lymphomas from the lungs to other organs. Neuraminidase treatment had no such effect on BWL2, but a similar but weaker effect than pronase on BWL1. Our findings support the notion that the distribution of lymphomas are, at least in part, governed by cell-surface characteristics.


Hospital acquired rotaviral gastroenteritis in a general paediatric unit.
Between 1 October 1981 and 30 September 1982, 74 children with acute gastroenteritis were admitted to the paediatric wards at St Thomas' Hospital, and a further 37 patients acquired gastroenteritis while in hospital. Rotaviruses were detected in the stools of 29 of 74 (39 per cent) of patients with community-acquired and 22 of 37 (59 per cent) of patients with hospital-acquired infection. Although patients were also admitted with bacterial stool pathogens, barrier nursing techniques were apparently successful in preventing spread of these. The use of a virucidal agent for handwashing might be effective in preventing hospital-acquired rotaviral infections.


Radiofrequency Ablation in Cooled Monopolar or Conventional Bipolar Modality Yields More Beneficial Short-Term Clinical Outcomes Versus Other Treatments for Knee Osteoarthritis: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
To evaluate various radiofrequency ablation (RFA) treatments for knee osteoarthritis (OA) and determine the best modality, target, number of electrodes, and image guidance for improving knee pain and function. Electronic databases were searched for randomized controlled trials (RCTs) comparing the efficacy of RFA treatments for knee OA from inception up to September 30, 2021. The primary outcome was the visual analog scale (VAS), and the secondary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Bayesian network meta-analysis was performed to synthesize the mean difference (MD) and rank the comparative effectiveness of treatments. A total of 21 eligible RCTs (from 2011 to 2021, involving 1,818 patients) with 8 RFA treatments, 6 intra-articular injections, NSAIDS, exercise, and placebo were assessed. Conventional bipolar genicular nerve RFA (GNRFA) had the greatest net benefit on the VAS at 6 months (MD, -5.5; 95% confidence interval [CI], -4.3 to -6.7; SUCRA, .98). And cooled monopolar GNRFA had the greatest net benefit on the WOMAC at 6 months (MD, -33; 95% CI, -37 to -29; SUCRA, .99). In conventional and pulsed modalities, bipolar RFA was associated with a significant decrease in VAS and WOMAC than monopolar RFA. Combining pulsed intra-articular RFA and platelet-rich plasma injection had no additional positive effects on VAS or WOMAC at 3 months. RFA is effective in improving both knee pain and function in patients with OA, at least in the short term (6 months). Patients respond better to the cooled modality than the conventional and pulsed modalities. Bipolar is more effective than monopolar for improving pain and function in conventional and pulsed modalities. Fluoroscopy and ultrasound guidance showed no differences in improving pain and function. The effectiveness of RFA in cooled modality using bipolar or in combination with various intra-articular injections remains to be compared. II, systematic review and meta-analysis of Level I and II studies.


Limb-girdle muscular dystrophy type 2a with mutation in CAPN3: the first report in Taiwan.
The autosomal recessive limb-girdle muscular dystrophy type 2A (LGMD2A) is caused by mutations in the calpain 3 (CAPN3) gene, and it is characterized by selective atrophy and weakness of proximal limb and girdle muscles. We report a 33-year-old woman with initial presentations of exercise intolerance and running difficulty at age 15 years. At presentation, waddling gait, positive Gowers' sign, and marked muscle atrophy in pelvic and leg muscles were noted. Muscle computed tomography (CT) imaging demonstrated symmetric involvement of the posterior thigh muscles with relative sparing of vastus lateralis, sartorius, and gracilis. Muscle biopsy revealed a dystrophic change and many lobulated fibers on NADH-tetrazolium reductase staining. Genetic analysis of the CAPN3 gene identified a novel homozygous mutation of c2047_2050 del4, p.Lys683fs mutation, confirming the first LGMD2A patient in Taiwan.


Impairment of human CYP1A2-mediated xenobiotic metabolism by Antley-Bixler syndrome variants of cytochrome P450 oxidoreductase.
Y459H and V492E mutations of cytochrome P450 reductase (CYPOR) cause Antley-Bixler syndrome due to diminished binding of the FAD cofactor. To address whether these mutations impaired the interaction with drug-metabolizing CYPs, a bacterial model of human liver expression of CYP1A2 and CYPOR was implemented. Four models were generated: POR(null), POR(wt), POR(YH), and POR(VE), for which equivalent CYP1A2 and CYPOR levels were confirmed, except for POR(null), not containing any CYPOR. The mutant CYPORs were unable to catalyze cytochrome c and MTT reduction, and were unable to support EROD and MROD activities. Activity was restored by the addition of FAD, with V492E having a higher apparent FAD affinity than Y459H. The CYP1A2-activated procarcinogens, 2-aminoanthracene, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and 2-amino-3-methylimidazo(4,5-f)quinoline, were significantly less mutagenic in POR(YH) and POR(VE) models than in POR(wt), indicating that CYP1A2, and likely other drug-metabolizing CYPs, are impaired by ABS-related POR mutations as observed in the steroidogenic CYPs.


Surgical implications of pulmonary actinomycosis.
Four cases of pulmonary actinomycosis are presented. Resection was necessary in three cases before the diagnosis was established. A high index of suspicion for this disease is advised for the thoracic surgeon involved in the treatment of lung masses.


Analysis of AGE modified proteins and RAGE expression in HER2/neu negative invasive ductal carcinoma.
Cancer is associated with increased glycolysis and carbonyl stress. In view of this, AGE modified proteins were identified from clinical breast cancer tissue using 2DE-immunoblot and mass-spectrometry. These proteins were identified to be serotransferrin, fibrinogen gamma chain, glycerol-3-phosphate dehydrogenase, lactate dehydrogenase, annexin II, prohibitin and peroxiredoxin 6, which have established role in cancer. Further, RAGE expression and its downstream signaling proteins NADPH oxidase and NF-kB were studied. Role of these AGE modified proteins and RAGE signaling in breast cancer is discussed.


Echotomographic study in the diagnosis of the nonfunctioning kidney.
The results obtained from the nephrosonographic study of 61 functionally inactive kidneys of 57 patients are presented. Its usefulness as a diagnostic tool in the evaluation of hydronephrosis, renal agenesis and retroperitoneal collections is stressed.


Simple and choice reaction time in Parkinson's disease.
Reaction-times were evaluated in 6 parkinsonian patients and 6 normal control subjects using a simple reaction task and 3 choice reaction tasks of differing complexity. Reaction-times were measured as the time from stimulus onset to the onset of electromyographic activity in the responding muscle. Reaction-time was significantly delayed in patients compared to controls in all tasks, but to a greater extent in the more difficult tasks. The relative magnitude of the change, however, was only 4% in the simple reaction task and 8% in the more difficult choice tasks. These results suggest that the deficit in Parkinson's disease is unlikely to represent a defect in preprogramming as suggested by some investigators. Instead, our results indicate a disturbance in the cerebral processing of the auditory stimuli after their occurrence and prior to the initiation of motor activity.


Treatment of lower limb arterial disease by Dardik graft: It takes one to know one.
To perform a comprehensive literature review on outcomes achieved with the historical Dardik graft, illustrated with a case report of a patient with 13-years primary patency and limb salvage. A comprehensive literature review was performed through MedLine (PubMed.gov, U.S. National Library of Medicine, National Institute of Health) from 1976 to 2018 using search terms (Umbilical Vein Graft), (Dardik graft), (Glutaraldehyde stabilized human umbilical vein [HUV]) and (HUV) to collected data on clinical use of HUV. Only papers in English and reporting adequate information about indication for surgery, short- and long-term patency and complication rate were included. Data about a total of 899 patients (977 limbs) were available. Overall, 45% of patients (438 limbs) underwent HUV implantation for critical limb ischemia (rest pain or tissue loss) or for disabling claudication in 12.2% of cases (120 limbs). Others indication for surgery were acute onset limb ischemia, popliteal aneurysms or aneurysmal degeneration of a previously implanted synthetic graft. At a mean follow-up of 4.3 years (range 3-6 years), primary patency and secondary patency were 61.3% and 61%, respectively. Aneurisms formation was detected in 3% of cases (21 limbs), graft's infection in 24.4% of cases (31 limbs) and graft's thrombosis in 25.5% of cases (193 limbs). This article provide a historical review of the use, outcomes and complications of HUV. Even though it is no longer commercially available, the knowledge of this type of substitute still remains inspirational for the development of innovative vascular conduits and fundamental for the new generations of physician both in diagnostics and in the management of complications.


A prostaglandin E receptor coupled to a pertussis toxin-sensitive guanine nucleotide regulatory protein in rabbit cortical collecting tubule cells.
At different concentrations, prostaglandin E2 (PGE2) can either stimulate or inhibit cAMP formation in freshly isolated rabbit cortical collecting tubule (RCCT) cells, but in cultured RCCT cells PGE2 can only stimulate cAMP synthesis (Sonnenburg, W. K., and Smith W. L. (1989) J. Biol. Chem. 263, 6155-6160). Here, we report characteristics of [3H]PGE2 binding to membrane receptor preparations from both freshly isolated and cultured RCCT cells. [3H]PGE2 binding to membranes from freshly isolated RCCT cells was saturable and partially reversible. Equilibrium binding analyses indicated that in the absence of guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) there is a single class of PGE2 binding sites (KD = 4.2 +/- 0.4 nM; Bmax = 583 +/- 28 fmol/mg); in the presence of 100 microM GTP gamma S, there is also only one class of binding sites but with a somewhat lower KD = 1.2 +/- 0.5 nM (Bmax = 370 +/- 40 fmol/mg). This stimulatory effect of GTP gamma S was blocked by pretreatment of the freshly isolated RCCT cells with pertussis toxin. The relative affinities of prostanoids for the [3H]PGE2-binding site were determined to be 17,18,19,20-tetranor-16-phenoxy-PGE2-methylsulfonylamide (sulprostone) approximately PGE2 approximately PGE1 approximately 16,16-dimethyl-PGE2 greater than carbacyclin approximately PGF2 alpha greater than PGD2. This is the order of potency with which prostaglandins inhibit arginine vasopressin-induced cAMP formation in fresh RCCT cells. Interestingly, [3H]PGE2 binding to membranes from cultured cells, which, unlike fresh cells, fail to show an inhibitory response to PGE2, was only 10-20% of that observed with membranes from fresh cells; moreover, binding of [3H]PGE2 to membranes from cultured cells was neither stimulated by GTP gamma S nor inhibited by sulprostone. The prostanoid binding specificities and the unusual pertussis toxin-sensitive, stimulatory effect of GTP gamma S on binding of [3H]PGE2 to membranes from freshly isolated RCCT cells are characteristics shared by a Gi-linked PGE receptor from renal medulla (Watanabe, T., Umegaki, K., and Smith, W. L. (1986) J. Biol. Chem. 261, 14340-14349). Our results suggest that the [3H]PGE2 binding site of freshly isolated RCCT cells is the PGE receptor which is coupled to a Gi to attenuate arginine vasopressin-induced cAMP synthesis in the renal collecting tubule.