Mesh Inguinal Hernia Repair and Appendectomy in the Treatment of Amyand's Hernia with Non-Inflamed Appendices.
Amyand's hernia is defined as protrusion of the vermiform appendix in an inguinal hernia sac. It is a rare entity with variable clinical presentation from normal vermiform appendix to abscess formation due to perforation of acute appendicitis. Although surgical treatment includes appendectomy and hernia repair, appendectomy in the absence of an inflamed appendix and use of a mesh in cases of appendectomy remain to be controversial. The aim of this study was to review the experience of mesh inguinal hernia repair plus appendectomy performed for Amyand's hernia with noninflamed appendices. There were five male patients with a mean age of 42.4 ± 16.1 years in this retrospective study in which Amyand's hernia was treated with mesh inguinal hernia repair plus appendectomy for noninflamed appendices. Patients with acute appendicitis and perforated vermiform appendix were excluded. There were four right sided and one bilateral inguinal hernia. Postoperative courses were uneventful. During the follow-up period (14.0 ± 7.7 months), there was no inguinal hernia recurrence. Mesh inguinal hernia repair with appendectomy can be performed for Amyand's hernia in the absence of acute appendicitis. However, presence of fibrous connections between the vermiform appendix and the surrounding hernia sac may be regarded as a parameter to perform appendectomy.


Vulval and perianal inflammatory linear verrucous epidermal naevus.
Inflammatory linear verrucous epidermal naevus (ILVEN) is a rare form of epidermal naevus. It occurs as a linear dermatitic or psoriasiform plaque, with onset usually in the first 5 years of life. Lesions are characteristically intensely itchy. We present a case of ILVEN occurring on the vulva and perianal region of a 6-year-old girl. The lesion was initially thought to be an area of lichenified dermatitis; however, treatment with even super-potent topical corticosteroids did not significantly improve the inflammation. A biopsy was performed and histopathological examination showed characteristic features. ILVEN is frequently refractory to topical treatment and surgical excision of lesions may be an option for relief of symptoms. ILVEN occasionally presents in the inguinogenital region and in this area may, like many vulval naevi, be misdiagnosed as vulvitis, psoriasis, genital warts or sexual abuse.


Dynamic O-GlcNAcylation of the small heat shock protein alpha B-crystallin.
alphaB-Crystallin, originally described as a structural lens protein, is now known to be a member of the small heat shock protein family and is expressed in a number of nonlens tissues. This highly conserved 20 kDa protein aggregates with homologous proteins, including alphaA-crystallin and the small heat shock protein HSP28, to form large heteromeric complexes. Recently, Roquemore et al. (1992) have established that both phosphorylated and unphosphorylated forms of lens alphaB-crystallin are modified with O-linked N-acetylglucosamine, a dynamic posttranslational modification abundant on nuclear and cytoplasmic proteins. In this paper, we have identified the major site of O-GlcNAcylation on lens alphaB as Thr 170. We have further shown that this modification is not restricted to lens alphaB-crystallin but occurs on alphaB isolated from rat heart tissue and human astroglioma cells. Two-dimensional electrophoresis of rat heart alphaB-crystallin revealed two O-GlcNAcylated forms with mobilities corresponding to the unphosphorylated form (alphaB2) and an unidentified, slightly more acidic form. Phosphorylated alphaB-crystallin (alphaB1) was not detected in the rat heart preparation. The major O-GlcNAcylation site on alphaB-crystallins from rat heart also appears to be at Thr 170. Metabolic pulse-chase labeling studies of U373-MG astroglioma cells indicated that turnover of the carbohydrate on alphaB-crystallin is not static but proceeds many-fold more rapidly than turnover of the protein backbone itself, consistent with a regulatory role for O-GlcNAc on this small heat shock protein.


Thermal and acidic denaturation of phycocyanin from Arthrospira platensis: Effects of complexation with λ-carrageenan on blue color stability.
The pH and temperature sensitivity of the natural blue pigment phycocyanin from Arthrospira platensis limits its application as food colorant. This study examines the effect of protein stabilization by the anionic polysaccharide λ-carrageenan on phycocyanins color appearance at pH 2.5-6.0, unheated and after heat treatments (70/90 °C). Electrostatic interactions, hydrophobic interactions, hydrogen bonds and disulfide-bridges were assessed by adding NaCl, urea and dithiothreitol (DTT) to the samples. Measurements of the zeta potential, transmittance and two-dimensional gel electrophoresis coupled to mass spectrometry confirmed electrostatic interactions around the zero surface charge of phycocyanin over a broad pH range (∼4.1-6.4). Despite a color shift towards turquoise, the color remained stable during heating, especially below of pH 3.5. Precipitation was inhibited over the entire pH range. Overall, electrostatic complexation of phycocyanin and λ-carrageenan is a promising technique to stabilize proteinaceous colorants, helping to reduce food waste and foster a shift to renewable materials.


Ultrastructure of Fusarium-induced tibial dyschondroplasia in chickens: a sequential study.
Female broiler chicks were randomly placed into two groups; one was treated twice daily with TDP-1 (a mycotoxin produced by Fusarium roseum), the other was controls. Chicks were sacrificed after 2, 4, 6, 8, 10, and 14 days of treatment and were evaluated for tibial dyschondroplasia. TDP-1-treated chicks examined after 2, 4, or 6 days of treatment had either no gross lesions (2 days) or mild gross lesions (4 and 6 days); growth plates from these groups did not have ultrastructural changes. TDP-1-treated chicks examined after 8, 10, or 12 days of treatment had moderate to severe gross lesions of tibial dyschondroplasia. These groups also had intracellular lipid accumulation and necrosis of chondrocytes within the retained cartilage. It was concluded that the cellular changes in tibial dyschondroplasia develop only after the cartilage accumulates; the changes are sequelae, possibly due to nutrient depletion from an increased distance between chondrocytes and perforating epiphyseal vessels, their nutrient source.


Stable Tunable Luminescence of Hetero-valent Eu Ion Activated Ba2InTaO6 Phosphors Synthesized by Defect-Induced Self-Reduction in the Molten-Salt Method.
Functional materials with stable and adjustable luminescence have recently become a research hotspot for their broad application prospects. Tunable luminescence can be realized by the doping of hetero-valent europium ions. High-temperature hydrogen atmosphere reduction is required in the traditional preparation of Eu2+-doped phosphors. Herein, an anoxic molten-salt medium environment was established to form oxygen vacancy defects in the reaction system and induce the self-reduction of Eu3+ ions to obtain Eu2+ ions. X-ray photoelectron spectroscopy (XPS) results confirm the existence of Eu2+ and Eu3+ ions in the samples, and the fluorescence spectrum shows that hetero-valent Eu ions can synergistically emit light effectively. Under 266 nm ultraviolet light excitation, the white light emission was successfully realized for a Ba2InTaO6:Eu phosphor by different emission combinations of Eu3+ and Eu2+ ions. In addition, the Ba2InTaO6:Eu phosphor exhibits adjustable luminescence from greenish-yellow to red exciting at 390-490 nm, which has superior stability in a high-temperature and high-humidity environment. Therefore, it is very promising that Ba2InTaO6:Eu will be used as multi-color functional materials in many fields such as communication encryption and colorful decoration.


Protein-resistant polymer coatings based on surface-adsorbed poly(aminoethyl methacrylate)/poly(ethylene glycol) copolymers.
We report on the protein-resistant properties of glass substrates coated with novel copolymers of 2-aminoethyl methacrylate hydrochloride and poly(ethylene glycol) methyl ether methacrylate (AEM-PEG). In comparison to currently available protein-blocking polymer systems, such as poly-l-lysine-poly(ethylene glycol), silane-based poly(ethylene glycol), and poly(ethylene glycol) brushes prepared by surface-initiated polymerization, the proposed AEM-PEG offers the combined advantages of low cost, simplicity of use, and applicability in aqueous solutions. We demonstrate the capability of AEM-PEG to block the surface binding of globular proteins (tubulin), their assemblies (microtubules), and functional motor proteins (kinesin-1). Moreover, we demonstrate the applicability of AEM-PEG for surface patterning of proteins in microfluidic devices.


[Rosette forming B- and T-lymphocytes in allergic contact eczema (author's transl)].
The number of rosette forming lymphocytes with mouse and sheep red blood cells was examined in the time course of more localized (n = 16) and generalized (n = 12) allergic contact eczema. 1. In 25 healthy probands the mean number of B and T lymphocytes were 10 +/- 2.1% and 51 +/- 4.9%, respectively. 2. In generalized eczema a short significant increase of the number of both lymphocyte populations was observed. At the first day of examination 12 +/- 1.6% (p less than or equal to 1%) B and 59.1 +/- 5% (p less than or equal to 0.1%) T lymphocytes were counted. At the second day only the number of T lymphocytes (55 +/- 4.8%; p less than or equal to 5%) was increased, at the third day the number of T lymphocytes had normalized, too. 3. In the more localized eczema no changes in the number of lymphocytes could be found.


[Neuroendocrine differentiation in adenocarcinoma of the prostate during hormonal treatment : a case report].
A case of neuroendocrine (NE) differentiated prostate cancer is reported herein, which was progressed with NE differentiation during hormonal treatment in adenocarcinoma of the prostate. A 65-year-old man was admitted to our department with increased serum prostate specific antigen (PSA) (150 ng/ml). A prostate biopsy was performed and histological examinations indicated poorly differentiated adenocarcinoma with a Gleason score of 5 + 4 = 9. Further examinations showed metastases to systemic bones. The clinical stage was T3bN0M1b and hormonal therapy using leuprorelin was started. Eighteen months after hormonal therapy, the serum PSA level declined to 1.702 ng/ml. He subsequently experienced edema in his legs. Computed tomography (CT) demonstrated enlargement of the prostate and swelling of multiple pelvic lymph nodes. Immunohistochemical examination of a re-biopsy specimen revealed a neuroendocrine carcinoma. The neuron-specific enolase (NSE) level was 50.9 ng/ml. The treatment measure was changed from hormonal therapy to combination chemotherapy comprising cisplatin (CDDP) and irinotecan (CPT-11). Pelvic radiotherapy (50 Gy) was then performed. Two courses of the chemotherapy resulted in a great reduction of the tumor volume. However, he had liver metastases 3 months later. His condition worsened rapidly and he died at 8 months after definite diagnosis.


Bcl-2 as a predictor of chemosensitivity and prognosis in primary epithelial ovarian cancer.
This retrospective study of ovarian cancer aimed to elucidate whether expression of apoptosis-related proteins, bcl-2, p53 or MDM-2, is associated with resistance to chemotherapy, especially cisplatin (CDDP) based chemotherapy. Expression of bcl-2, p53 and MDM-2 was assessed by immunohistochemical staining of tumour tissues collected at initial surgery prior to treatment with CDDP-based chemotherapy. Among 66 patients with advanced ovarian cancer with measurable tumour following surgery and evaluable for response to chemotherapy, 42, 45 and 56% were positive for bcl-2, p53 and MDM-2, respectively. Significantly fewer tumours of patients who had a complete response to chemotherapy (CR) showed positivity for bcl-2 (2/20) than for p53 (6/20) and MDM-2 (8/20, P < 0.001). There was an inverse correlation between bcl-2 staining and initial response to chemotherapy, especially in serous and endometrial adenocarcinomas. In patients with stage III-IV, serous or endometrioid adenocarcinomas, significantly poorer survival was seen for those with bcl-2 positive tumours than those with negative bcl-2 staining (P = 0.0064). p53 and MDM-2 were not correlated with initial response to chemotherapy. Multivariate analysis revealed that bcl-2, residual tumour size and histology were significant independent prognostic factors. These results suggest that bcl-2 can be a possible predictor of response to chemotherapy and prognosis in patients with advanced ovarian carcinoma.


Access to an Electronic Health Record: A Polish National Survey.
In Poland, as in many countries around the world, e-health services are becoming more and more popular. Obligatory e-sick leave was implemented, followed by e-prescriptions and e-referrals. Therefore, it is worth considering the introduction of a complete electronic health record (EHR) that can be accessed by doctors and patients. The main aim of the study is to find out whether patients want to have access to their EHRs and if they would agree to pay for such a service. The research was based on three surveys conducted among 1000 Polish adults in 2007, 2012, and 2018. The sample collection was carried out by the national opinion poll agency, with the use of computer-assisted telephone interviews. Over 60% of respondents were interested in the possibility of accessing EHRs in general, and almost 50% of them were ready to pay for it. Nevertheless, when analyzing all the year-on-year trends, they were subject to a gradual decrease. The youngest age group was the one most interested in EHRs, while the group comprising respondents in middle age was the one mostwilling to pay for it. There is still great potential in implementing EHRs on a bigger scale.


Reduced mRNA and protein expression of the genomic caretaker RAD9A in primary fibroblasts of individuals with childhood and independent second cancer.
The etiology of secondary cancer in childhood cancer survivors is largely unclear. Exposure of normal somatic cells to radiation and/or chemotherapy can damage DNA and if not all DNA lesions are properly fixed, the mis-repair may lead to pathological consequences. It is plausible to assume that genetic differences, i.e. in the pathways responsible for cell cycle control and DNA repair, play a critical role in the development of secondary cancer. To identify factors that may influence the susceptibility for second cancer formation, we recruited 20 individuals who survived a childhood malignancy and then developed a second cancer as well as 20 carefully matched control individuals with childhood malignancy but without a second cancer. By antibody microarrays, we screened primary fibroblasts of matched patients for differences in the amount of representative DNA repair-associated proteins. We found constitutively decreased levels of RAD9A and several other DNA repair proteins in two-cancer patients, compared to one-cancer patients. The RAD9A protein level increased in response to DNA damage, however to a lesser extent in the two-cancer patients. Quantification of mRNA expression by real-time RT PCR revealed lower RAD9A mRNA levels in both untreated and 1 Gy γ-irradiated cells of two-cancer patients. Collectively, our results support the idea that modulation of RAD9A and other cell cycle arrest and DNA repair proteins contribute to the risk of developing a second malignancy in childhood cancer patients.


A Commentary on the Limits of Alcoholic Beverage Policies.
Providing one set of policy measures for all countries as if they were a single, homogeneous entity does not appear to be evidence-based, according to recent research on the effectiveness of alcoholic beverage control policies. Contextual and cultural determinants-social, economic, demographic, cultural and political-appear to be major factors of influencing change in drinking trends, drinking patterns and drinking-related harms. The variable interplay between contextual determinants and alcohol control policy measures implies diverse impacts on consumption and harm according to time, and to the different countries and groups of countries. In addition, epidemiology research manifests some limitations when applied to alcohol drinking and results are transferred from one culture to another. The conditions of individual cultures and countries should be considered when planning and evaluating alcohol control policies.


Venous compression syndromes: clinical features, imaging findings and management.
Extrinsic venous compression is caused by compression of the veins in tight anatomic spaces by adjacent structures, and is seen in a number of locations. Venous compression syndromes, including Paget-Schroetter syndrome, Nutcracker syndrome, May-Thurner syndrome and popliteal venous compression will be discussed. These syndromes are usually seen in young, otherwise healthy individuals, and can lead to significant overall morbidity. Aside from clinical findings and physical examination, diagnosis can be made with ultrasound, CT, or MR conventional venography. Symptoms and haemodynamic significance of the compression determine the ideal treatment method.


Ethnic variations in chest pain and angina in men and women: Scottish Ethnicity and Health Linkage Study of 4.65 million people.
European research on ethnic variations in cardiovascular disease has mostly examined mortality endpoints using country of birth as a proxy for ethnicity. We report on chest pain and angina by ethnic group. Retrospective cohort linking the Census 2001 for Scotland (providing 14 ethnic group categories) and hospital discharge/community and hospital deaths data. Directly age-standardized rates and rate ratios were calculated. Risk ratios were adjusted for age and then highest educational qualification of the individual using Poisson regression. Ratios were multiplied by 100 and 95% confidence intervals (CI) were calculated. The reference was the White Scottish population (100). In the results below, the 95% CI excludes 100. There was raised chest pain mortality/hospital discharge risk in Indian men (rate ratio 141.2), Other South Asian women (rate ratio 140.9), and Pakistanis (rate ratio 216.2 in men, 243.0 in women). Rate ratios were lowest in other White British (rate ratio 76.1 in men, 73.7 in women) and Chinese (rate ratio 67.6 in men, 76.7 in women). Adjustment for age and education attenuated, but did not abolish, differences in other White British (risk ratio from 73.5 to 83.5) and Pakistani (risk ratio from 209.0 to 198.2) male populations and increased them in most others, e.g. other South Asian men (from risk ratio of 128.9 to 140.1). Pakistani populations had the highest risk of angina (rate ratio 189.3 in men, 159.7 in women). Other White British (rate ratio 81.4 for men, 78.0 for women), Other White (rate ratio 89.6 men, 85.2 women), and Chinese (rate ratio 60.5 men, 67.4 women) had the lowest risk. Adjustment for education did not greatly alter these patterns. There were important ethnic variations. The results call for replication elsewhere in Europe and targeted prevention programmes and vigilant diagnosis and management by clinicians.


Safety and availability of dapivirine (TMC120) delivered from an intravaginal ring.
Vaginal delivery of 200 mg or 25 mg dapivirine from intravaginal rings (IVRs) was evaluated over a 7-day period in two phase 1 safety trials (IPM001 and IPM008, respectively) in a total of 25 healthy women 19 to 46 years of age. The IVR was generally safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Across both studies, dapivirine concentrations in vaginal fluids measured at the introitus, cervix, and ring area were within the mean range of 0.7-7.1 microg/ml. Mean dapivirine concentrations in vaginal and cervical tissues on day 7 were 0.3-0.7 microg/g in IPM001 and 1.5-3.5 microg/g in IPM008. Mean plasma concentrations of dapivirine were <50 pg/ml. Dapivirine from both IVRs was successfully distributed throughout the lower genital tract at concentrations >1000x the EC(50) against wild-type HIV-1 (LAI) in MT4 cells suggesting that IVR delivery of microbicides is a viable option meriting further study.


Protection against cyclophosphamide-induced renal oxidative stress by amifostine: the role of antioxidative mechanisms.
Cyclophosphamide, an alkylating compound used in chemotheraphy, is metabolized into active metabolites that form reactive oxygen species. Reactive oxygen species can modify the components of both healthy and neoplastic cells in circumstances of decreased antioxidative abilities. That leads to the dysfunction of organs, including the kidneys. Therefore, drugs like amifostine, which protect healthy cells against reactive oxygen species, may be applied during cyclophosphamide therapy. The aim of this study was to evaluate the influence of amifostine on the antioxidative system of the kidneys of rats that were exposed to cyclophosphamide. Intraperitoneal administration of cyclophosphamide was found to decrease the activity of the kidney's antioxidative enzymes, such as superoxide dismutase, glutathione peroxidase, gluthatione reductase, and catalase. Amifostine, however, caused an increase in the activity of these enzymes. The administration of amifostine with cyclophosphamide partially prevented changes in the activities of the examined enzymes observed after cyclophosphamide injection. Cyclophosphamide also evoked a decrease in the levels of nonenzymatic antioxidants, such as reduced gluthatione, vitamin C, and vitamin E as well as the total antioxidant status. The administration of amifostine together with cyclophosphamide prevented changes in the concentration of evaluated nonenzymatic antioxidative parameters, increasing values of their concentration to the values in the control group. Changes in the kidneys' antioxidative abilities during detoxification from cyclophosphamide were accompanied by intensified lipid peroxidation, which was manifested by an increase in the concentration of malondialdehyde and 4-hydroxynonenal. Amifostine caused the inhibition of lipid peroxidation in the kidneys of control and cyclophosphamide-treated rats. In conclusion, our results suggest that amifostine significantly protects kidney antioxidant parameters from changes caused by cyclophosphamide treatment and, in consequence, prevents oxidative stress and phospholipid peroxidative damage. Thus, amifostine prevents renal injury and dysfunction.


Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications.
The poor oral bioavailability arising from poor aqueous solubility should make drug research and development more difficult. Various approaches have been developed with a focus on enhancement of the solubility, dissolution rate, and oral bioavailability of poorly water-soluble drugs. To complete development works within a limited amount of time, the establishment of a suitable formulation strategy should be a key consideration for the pharmaceutical development of poorly water-soluble drugs. In this article, viable formulation options are reviewed on the basis of the biopharmaceutics classification system of drug substances. The article describes the basic approaches for poorly water-soluble drugs, such as crystal modification, micronization, amorphization, self-emulsification, cyclodextrin complexation, and pH modification. Literature-based examples of the formulation options for poorly water-soluble compounds and their practical application to marketed products are also provided. Classification of drug candidates based on their biopharmaceutical properties can provide an indication of the difficulty of drug development works. A better understanding of the physicochemical and biopharmaceutical properties of drug substances and the limitations of each delivery option should lead to efficient formulation development for poorly water-soluble drugs.


Genetic heterozygosity in polecat Mustela putorius populations from western France.
Allozymic variations were investigated in 49 European polecats Mustela putorius from Western France by starch gel electrophoresis. Out of 31 surveyed loci, eight (25.8%) were shown polymorphic and observed heterozygosity averaged 0.057. Deviations from Hardy-Weinberg equilibrium and heterozygote deficiency suggest that populations were not in panmixia. Heterozygotes for two loci or more totalled 42.9% of individuals. Thus, although carnivores were previously considered as less variable, polecat populations from Western France showed a high genetic variability.


Physiological effects of a novel immune stimulator drug, (1,4)-α-D-glucan, in rats.
The (1,4)-α-D-glucan (α-D-glucan), derived from medicinal plant, Tinospora cordifolia, activates human lymphocytes with downstream synthesis of the pro- and anti-inflammatory cytokines, in vitro. We investigated physiological and immunological effects of a low and a high dose of α-D-glucan (0.5 and 10 mg/kg), in vivo, testing the hypothesis that intravenous administration of α-D-glucan does not affect haemodynamic, respiratory, haematological, and immune responses in normal rats. Male rats (300-400 g) were anaesthetized, tracheostomized, and catheterized in one femoral artery and vein. The mean arterial blood pressure and heart rate were continuously recorded. The baselines for gas exchange, differential blood cell count, and plasma concentration of TNF-α, IL-1β, IL-4, IL-6, and IFN-γ were determined. Rats were then randomly assigned to controls (n = 7), a low dose (0.5 mg/kg; n = 10), and a high dose (10 mg/kg; n = 7) of α-D-glucan for a six 6 hr study period. Gas exchange, differential cell count, plasma concentration of TNF-α, IL-1β, IL-4, IL-6, and IFN-γ, and mean arterial blood pressure values remained within physiological range. Intravenous administration of 10 mg/kg α-D-glucan created tachycardia, associated with hyperventilation, and significant reductions in the blood haemoglobin and haematocrit concentrations. We suggest that these in vivo effects of α-D-glucan should be considered for future clinical and/or experimental trials.


Cloning of the guanylate kinase homologues AGK-1 and AGK-2 from Arabidopsis thaliana and characterization of AGK-1.
Guanylate kinase is an essential enzyme for nucleotide metabolism, phosphorylating GMP to GDP or dGMP to dGDP. The low molecular mass cytosolic forms of guanylate kinase are implicated primarily in the regulation of the supply of guanine nucleotides to cell signalling pathways. The high molecular mass and membrane-associated forms of guanylate kinase homologues, notably found in neuronal tissues, are assigned roles in cell junction organization and transmembrane regulation. Here, we describe the first plant guanylate kinase-encoding genes, AGK1 and AGK2, from Arabidopsis thaliana. The nucleotide sequences of their genomic and cDNA clones predict proteins that carry N-terminal and C-terminal extensions of the guanylate kinase-like domain. The amino acid sequences of this domain share 46-52% identity with guanylate kinases from yeast, Escherichia coli, human, mouse and Caenorhabditis elegans. Arabidopsis guanylate kinases (AGKs) exhibit a high degree of conservation of active site residues and sequence motifs in common with other nucleoside monophosphate kinases, which suggests overall structural similarity of the plant proteins. Although bacterially expressed AGK-1 is enzymatically much less active than yeast guanylate kinase, its kinase domain is shown to complement yeast GUK1 recessive lethal mutations. AGKs are expressed ubiquitously in plant tissues with highest transcriptional activity detected in roots. The identification of AGKs provides new perspectives for understanding the role of guanylate kinases in plant cell signalling pathways.


1H-Observe/13C-decouple spectroscopic measurements of lactate and glutamate in the rat brain in vivo.
We have used (13C)-1H NMR spectroscopy at 360.13 MHz to resolve the 13C coupled proton resonance of glutamate and lactate in the rat brain in vivo. The time required for the 13C fractional enrichment of the 4-CH2 position of brain glutamate to reach isotopic steady state was determined during a continuous infusion of D-[1-13C]glucose. Under conditions of ischemia, measurements made of the 3-CH3 of lactate in (13C)-1H NMR spectra revealed the relative contribution of brain glucose and glycogen to lactate formation. (13C)-1H NMR was 11 times more sensitive than 13C NMR for the detection of 13C in the 3-CH3 position of lactate and 6 times more sensitive for the detection of 13C in the 4-CH2 of glutamate under similar in vivo conditions.


Purification and assay of insulin-like growth factor-binding protein-1: measurement of circulating levels throughout pregnancy.
Insulin-like growth factor-binding protein-1 (IGFBP-1) has been purified from amniotic fluid by anion exchange, hydrophobic interaction and gel filtration chromatography. The overall recovery of the purification process was 12.2%. The purified IGFBP-1 yielded a single band on SDS-PAGE gel but showed two bands (34 kDa and 68 kDa) on Western blot under non-reducing conditions. Polyclonal antisera were raised by immunization of sheep using the purified IGFBP-1. The best antiserum bound 50% of 125I-labelled IGFBP-1 at a final dilution of 1:500,000. A radioimmunoassay for IGFBP-1 was developed. This assay had a minimum detection limit of 5 micrograms/l, and was used to determine serum levels in non-pregnant and pregnant women. There was no cross-reaction with a wide variety of materials tested. Serum IGFBP-1 levels in non-pregnant individuals (33 +/- 16 (S.D.) micrograms/l) were found to be significantly lower than those in the second (96 +/- 64 micrograms/l) and third trimesters (95 +/- 60 micrograms/l) of pregnant women. During pregnancy, circulating IGFBP-1 levels increased rapidly in the first trimester and reached a peak at 12-13 weeks of gestation (107 +/- 75 micrograms/l). The level then remained at 80 +/- 53 to 103 +/- 70 micrograms/l until term.


The Role of PKC and HIF-1 and the Effect of Traditional Chinese Medicinal Compounds on Cerebral Ischemia-Reperfusion Injury.
Neuronal death occurs during cerebral ischemia. However, when hemoperfusion and oxygen supply are resumed to the ischemic focus of the brain tissue, the brain tissue damage is further aggravated, resulting in cerebral ischemia-reperfusion injury (CIRI) to the patients. Protein kinase C (PKC) plays an important role in CIRI. Through the IP3/DAG/Ca2+ signaling pathway, it promotes the influx of calcium ions in neurons and causes calcium overload, which aggravates the damage. At the same time, when brain cells are hypoxic, hypoxia-inducible factor-1 (HIF-1) is expressed, which regulates the expression of Bcl-2 and Bax through the PI3K/Akt signaling pathway and reduces nerve cell injury. It also fights hypoxic-ischemic injury by increasing the production of vascular endothelial growth factor (VEGF) to promote blood vessel formation. The PKC and HIF-1 signaling pathways are also linked to CIRI. HIF-1 activates the PKC and ERK pathways via the upregulation of VEGF, leading to increased Cx43 phosphorylation and dysfunction and aggravating CIRI. Existing studies have shown that certain traditional Chinese medicine (TCM) compounds regulate the PKC and HIF-1 signaling pathways and alleviate CIRI. These compounds downregulate the PKC and the activity of the PKC-related signaling pathways to alleviate CIRI. They can also promote the expression of HIF-1, increase the content of VEGF in ischemic tissues to promote the generation of blood vessels, and improve microcirculation. TCM compounds can inhibit the cascade of reactions underlying disease occurrence and development by targeting multiple components using different herbal formulations to improve the structural and material changes in the brain cells, which alleviate CIRI and protect the brain tissue. This study briefly describes the role of PKC and HIF-1, their relationship in CIRI, and the effect of TCM on them.


IL-32 expression indicates unfavorable prognosis in patients with colon cancer.
Recently, interleukin (IL)-32 has been demonstrated to represent a novel biomarker for evaluating the prognosis of patients with gastric and lung cancer; however, its clinical significance in colon cancer remains unknown. In the present study, the IL-32 expression in 60 patients with colon cancer was examined with an immunohistochemistry assay. IL-32 expression was determined in 37 (61.67%) patients with colon cancer. Additionally, IL-32 was associated with tumor size and Dukes' stage. By using the Kaplan-Meier method, patients with positive IL-32 expression had shorter overall survival time, compared with those with negative IL-32 expression. Multivariate analysis indicated that IL-32 could be an independent prognostic factor in patients with colon cancer; therefore, IL-32 may be a novel prognostic biomarker and therapeutic target for colon cancer.


Subcutaneous epinephrine administration decreases lower oesophageal sphincter pressure and gastro-oesophageal pressure gradient in children under general anaesthesia.
Children are vulnerable to regurgitation with a relatively high incidence of aspiration during general anaesthesia which is attributed to the high intragastric pressure, a short oesophagus, an immature laryngeal reflex and incomplete lower oesophageal sphincter muscle function. Subcutaneous administration of epinephrine is generally used in surgery to decrease bleeding due to local vasoconstriction. The effect of epinephrine on the sphincter muscle tone was investigated during general anaesthesia in children. Ten children scheduled for skin graft or plastic surgery of the ear were studied. A gastrointestinal pressure sensor was inserted nasally, and the intraluminal pressures of the lower oesophagus, lower oesophageal sphincter and stomach were monitored under sevoflurane, nitrous oxide anaesthesia. The effect of epinephrine on the lower oesophageal sphincter muscle tone was measured. The resting pressure of the lower oesophageal sphincter muscle tone significantly decreased from 4.56 +/- 1.85 to 3.79 +/- 1.11 kPa after 3 microg kg(-1) epinephrine for 4 min. The barrier pressure is the difference between the lower oesophageal sphincter and intragastric pressure, and that decreased to 1.23 +/- 1.17 kPa from the 2.07 +/- 1.77 kPa resting level. The observations implied that epinephrine had a long-lasting relaxing effect on lower oesophageal sphincter muscle in children. The observations may give some explanation about the mechanism of gastro-oesophageal reflux during general anaesthesia, especially in the participation of the adrenergic receptors.


Utility of gaussian-type orbitals in molecular collisions: electronic excitation of the first positive system of the nitrogen molecule.
The use of gaussian-type orbitals (GTO) as basis sets of electronic wave functions of molecules for calculating electron-collision excitation cross sections is discussed. A test calculation of the electron excitation cross section of the 2p state of atomic hydrogen at 60-1000 eV in which the hydrogenic wave functions were expressed as linear combinations of GTO indicates that an expansion of the is wave function by six GTO's and the 2p by four GTO's gives quite accurate results. Methods for evaluating the multicenter integrals which appear in the expressions of electron-excitation cross section (by the Born-type approximation) of diatomic molecules are described. Cross sections of direct electron excitation of the B(3)II(g) state (the first positive bands) of the N(2) molecule are calculated by this scheme, and the results are in good agreement with experiments.


The safety and effectiveness of the Le Fort I approach to removing central skull base lesions.
The difficulty of gaining access to the central skull base has led to the development of many surgical approaches to this area during the past decade. Yet we believe that the Le Fort I technique, which has been used for almost 140 years in orthognathic surgery, is still an excellent approach to treating anterior skull base lesions. This procedure, which entails the horizontal sectioning of the dentoalveolar maxillary segment, seemed to fall out of favor with otolaryngologists after a few reports of complications surfaced during the past 10 to 15 years. In this article, we report a series of seven patients whom we treated with a Le Fort I approach during a 3-year period for a variety of benign and malignant anterior skull base lesions. We have encountered no significant complications of surgery or recurrence of disease at a maximum postoperative followup of 3 years.


Metabolic Profiling of Resistant and Susceptible Tobaccos Response Incited by Ralstonia pseudosolanacearum Causing Bacterial Wilt.
The causal agent of bacterial wilt, Ralstonia pseudosolanacearum, can cause significant economic losses during tobacco production. Metabolic analyses are a useful tool for the comprehensive identification of plant defense response metabolites. In this study, a gas chromatography-mass spectrometry (GC-MS) approach was used to identify metabolites differences in tobacco xylem sap in response to R. pseudosolanacearum CQPS-1 in two tobacco cultivars: Yunyan87 (susceptible to R. pseudosolanacearum) and K326 (quantitatively resistant). Metabolite profiling 7 days post inoculation with R. pseudosolanacearum identified 88 known compounds, 42 of them enriched and 6 depleted in the susceptible cultivar Yunyan87, while almost no changes occurred in quantitatively resistant cultivar K326. Putrescine was the most enriched compound (12-fold) in infected susceptible tobacco xylem, followed by methyl-alpha-d-glucopyranoside (9-fold) and arabinitol (6-fold). Other sugars, amino acids, and organic acids were also enriched upon infection. Collectively, these metabolites can promote R. pseudosolanacearum growth, as shown by the increased growth of bacterial cultures supplemented with xylem sap from infected tobacco plants. Comparison with previous metabolic data showed that beta-alanine, phenylalanine, and leucine were enriched during bacterial wilt in both tobacco and tomato xylem.


Double red blood cell donors with increased ferritin levels: a descriptive study.
One of the measures proposed to mitigate iron loss in blood donors is monitoring of their ferritin levels. Occasionally, high ferritin levels are found in monitored donors. We report the results of the clinical and laboratory investigation of 80 double red blood cell (DRBC) donors with high ferritin levels. All DRBC donors' ferritin levels were measured during each visit for a donation. Donors with high ferritin levels who agreed to participate underwent a clinical and laboratory evaluation. A total of 165 of 2757 DRBC donors had at least one high ferritin level. Five were already known to suffer from hemochromatosis. A full investigation was available for 80 other donors. A total of 61 of 80 donors had normalized their ferritin level at the time of their laboratory evaluation. Only 16 donors had high serum iron levels, of whom four had increased saturation index. Genetic analysis gave the following results: C282Y homozygous, two; H63D homozygous, six; C282Y/HC3D double heterozygote, six; C282Y heterozygote, six; H63D heterozygote, 19; and no mutations, 39. None of the other laboratory investigations contributed data explaining the high ferritin levels observed. In most donors with high ferritin levels, the phenomenon was transient, with normal ferritin levels found in follow-up. Less than 10% of these donors had evidence of iron overload. Only eight were homozygous for mutations associated with hemochromatosis. An extensive laboratory investigation by the treating physician should only be recommended in donors with persistently high ferritin levels.


Effects of low-frequency underwater sound on hair cells of the inner ear and lateral line of the teleost fish Astronotus ocellatus.
Fish (Astronotus ocellatus, the oscar) were subject to pure tones in order to determine the effects of sound at levels typical of man-made sources on the sensory epithelia of the ear and the lateral line. Sounds varied in frequency (60 or 300 Hz), duty cycle (20% or continuous), and intensity (100, 140, or 180 dB re: 1 muPa). Fish were allowed to survive for 1 or 4 days posttreatment. Tissue was then evaluated using scanning electron microscopy to assess the presence or absence of ciliary bundles on the sensory hair cells on each of the otic endorgans and the lateral line. The only damage that was observed was in four of five fish stimulated with 300-Hz continuous tones at 180 dB re: 1 muPa and allowed to survive for 4 days. Damage was limited to small regions of the striola of the utricle and lagena. There was no damage in any other endorgan, and the size and location of the damage varied between specimens. No damage was observed in fish that had been allowed to survive for 1 day poststimulation, suggesting that damage may develop slowly after exposure.


Distribution and persistence of topical clotrimazole after sinus infusion in normal canine cadavers.
To determine the in vitro persistence of clotrimazole 1% cream in the canine frontal sinus and to evaluate the distribution of clotrimazole solution over the sino-nasal mucosa using a previously described surgical treatment protocol for canine nasal aspergillosis. Two canine skulls were used to monitor the persistence of clotrimazole cream in the lateral frontal sinus at 37°C. The distribution of irrigation solution around the frontal sinus compartments and nasal cavity was determined using six canine cadaver heads by trephining either the lateral or both the lateral and rostral compartments of the frontal sinus. Stain was added to the sinus irrigation solution before visually inspecting the sagittally sectioned heads. Clotrimazole cream persisted in the frontal sinus for at least 96 hours. The nasal cavity mucosa was completely stained in 8 of 12 sides and almost completely stained in the remaining 4 of 12 sides. Flushing irrigation solution through the lateral compartment of the frontal sinus resulted in inadequate staining of the rostral compartment but medicating both the lateral and rostral compartments resulted in complete coating of all frontal sinus mucosa in eight of eight sides. Clotrimazole cream has the potential to be retained in the frontal sinus for several days and is distributed effectively in normal canine cadavers. Medicating both the rostral and lateral compartments of the frontal sinus may be indicated in some clinical cases.


Preventive Approaches for Post-Stroke Depression: Where Do We Stand? A Systematic Review.
Post-stroke depression (PSD) occurs in one-third of stroke survivors, leading to a substantial decrease in quality of life as well as delayed functional and neurological recovery. Early detection of patients at risk and initiation of tailored preventive measures may reduce the medical and socioeconomic burden associated with PSD. We sought to review the current evidence on pharmacological and non-pharmacological prevention of PSD. We conducted a systematic review using PubMed/MEDLINE and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including randomized controlled studies. Eligible studies were included when performed within 1 year after the index cerebrovascular event. Animal and basic research studies, studies lacking a control group, review papers, and case reports were excluded. Out of 150 studies screened, 37 met our criteria. Among the strategies identified, administration of antidepressants displayed the most robust evidence for preventing PSD, whereas non-pharmacological interventions such as psychotherapy appear to be the most frequently used approaches to prevent depression after stroke. Research suggests that the efficacy of PSD prevention increases with the duration of preventive treatment. Seven out of 11 studies (63%) that used pharmacological and eight out of 16 (50%) that used non-pharmacological interventions reported a positive preventive effect on PSD. Overall, the current literature on PSD prevention shows heterogeneity, substantiating a need for well-designed randomized controlled trials to test the safety and efficacy of pharmacological as well as non-pharmacological and composite prevention regimens to minimize the risk of PSD in stroke survivors. Integrative strategies combining personalized non-pharmacological interventions such as educational, mental, and physical health support, and pharmacological strategies such as SSRIs may be the most promising approach to prevent PSD.


Coenzyme Q cytoprotective mechanisms for mitochondrial complex I cytopathies involves NAD(P)H: quinone oxidoreductase 1(NQO1).
The commonest mitochondrial diseases are probably those impairing the function of complex I of the respiratory electron transport chain. Such complex I impairment may contribute to various neurodegenerative disorders e.g. Parkinson's disease. In the following, using hepatocytes as a model cell, we have shown for the first time that the cytotoxicity caused by complex I inhibition by rotenone but not that caused by complex III inhibition by antimycin can be prevented by coenzyme Q (CoQ1) or menadione. Furthermore, complex I inhibitor cytotoxicity was associated with the collapse of the mitochondrial membrane potential and reactive oxygen species (ROS) formation. ROS scavengers or inhibitors of the mitochondrial permeability transition prevented cytotoxicity. The CoQ1 cytoprotective mechanism required CoQ1 reduction by DT-diaphorase (NQO1). Furthermore, the mitochondrial membrane potential and ATP levels were restored at low CoQ1 concentrations (5 microM). This suggests that the CoQ1H2 formed by NQO1 reduced complex III and acted as an electron bypass of the rotenone block. However cytoprotection still occurred at higher CoQ1 concentrations (>10 microM), which were less effective at restoring ATP levels but readily restored the cellular cytosolic redox potential (i.e. lactate: pyruvate ratio) and prevented ROS formation. This suggests that CoQ1 or menadione cytoprotection also involves the NQO1 catalysed reoxidation of NADH that accumulates as a result of complex I inhibition. The CoQ1H2 formed would then also act as a ROS scavenger.


The Polycomb group protein EED is dispensable for the initiation of random X-chromosome inactivation.
The Polycomb group (PcG) proteins are thought to silence gene expression by modifying chromatin. The Polycomb repressive complex 2 (PRC2) plays an essential role in mammalian X-chromosome inactivation (XCI), a model system to investigate heritable gene silencing. In the mouse, two different forms of XCI occur. In the preimplantation embryo, all cells undergo imprinted inactivation of the paternal X-chromosome (Xp). During the peri-implantation period, cells destined to give rise to the embryo proper erase the imprint and randomly inactivate either the maternal X-chromosome or the Xp; extraembryonic cells, on the other hand, maintain imprinted XCI of the Xp. PRC2 proteins are enriched on the inactive-X during early stages of both imprinted and random XCI. It is therefore thought that PRC2 contributes to the initiation of XCI. Mouse embryos lacking the essential PRC2 component EED harbor defects in the maintenance of imprinted XCI in differentiating trophoblast cells. Assessment of PRC2 requirement in the initiation of XCI, however, has been hindered by the presence of maternally derived proteins in the early embryo. Here we show that Eed-/- embryos initiate and maintain random XCI despite lacking any functional EED protein prior to the initiation of random XCI. Thus, despite being enriched on the inactive X-chromosome, PcGs appear to be dispensable for the initiation and maintenance of random XCI. These results highlight the lineage- and differentiation state-specific requirements for PcGs in XCI and argue against PcG function in the formation of the facultative heterochromatin of the inactive X-chromosome.


Effect of Chrysin on Mechanical Hyperalgesia in Chronic Constriction Injury-Induced Neuropathic Pain in Rat Model.
The present study aimed to assess the effect of Chrysin on mechanical hyperalgesia in chronic constriction injury (CCI)-induced neuropathic pain in Wistar rats. Neuropathic pain was induced by CCI to the sciatic nerve in rats. Oral treatment of chrysin was given at doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg in neuropathic rats. Mechanical hyperalgesia (in terms of paw withdrawal threshold [PWT]) was measured using Randall-Selitto analgesy-meter, and percent PWT was determined. Statistical analysis was carried out using GraphPad Prism 5 tool. In mechanical hyperalgesia test, treatment with chrysin 200 mg/kg, naive PWT, predose PWT, 0.5 h, 1 h, 2 h, and 4 h postdose PWT were found to be 141 ± 8.94 g, 60 ± 7.91 g, 107 ± 9.08 g, 113 ± 5.70 g, 106.0 ± 7.42 g, and 97 ± 9.08 g, respectively. The peak effect was observed at 2 h posttreatment for 50 mg and 100 mg while the peak effect for 200 mg was reached at 1 h, and the same was maintained till 2 h posttreatment. Chrysin 200 mg dose has shown maximal percent reversal (74%) at 2 h posttreatment. The percent reversal PWT of 50 mg/kg, 100 mg/kg, and 200 mg/kg at 2 h were 68%, 67%, and 74%, respectively. Chrysin has exhibited dose-dependent efficacy in CCI-induced neuropathic pain. In mechanical allodynia test, In chrysin (200 mg/kg) treatment group, naive PWT, predose PWT, 0.5 h, 1 h, 2 h, and 4 h postdose PWT were found to be 60.0 ± 0.0 g, 5.0 ± 1.10 g, 22.45 ± 6.62 g, 52.64 ± 18.29 g, 37.33 ± 17.56 g, and 29.83 ± 9.22 g, respectively. The percent reversal PWT of 50 mg/kg, 100 mg/kg, and 200 mg/kg at 2 h were 43%, 68%, and 87%, respectively. Chrysin attenuates neuropathic pain by ameliorating mechanical hyperalgesia and allodynia. Further studies are warranted to establish the mechanism.


Nephrology Nursing Scope and Standards of Practice: Take Pride in Practice.
The Nephrology Nursing Scope and Standards of Practice, 9th Edition, published by the American Nephrology Nurses Association, defines the scope of nephrology nursing and provides standards of practice, standards of professional performance, and competencies for registered nurses and graduate-level prepared registered nurses (e.g., advanced practice registered nurses, clinical nurse specialists) in an approach consistent with the American Nurses Association's Nursing Scope and Standards of Practice, published in 2021. Discussions addressing respect, equity, inclusion, and social justice have been included in the 9th edition. A new section related to altered/crisis standards has been added to assist nephrology nurses in developing strategies for implementing those standards. The section on how to use the standards has been updated with forms that organizations can download and individualize. This article provides an overview of the scope, standards, competencies, and strategies for implementing them in clinical practice.


Recovery of Renal Function following Kidney-Specific VEGF Therapy in Experimental Renovascular Disease.
Chronic renovascular disease (RVD) can lead to a progressive loss of renal function, and current treatments are inefficient. We designed a fusion of vascular endothelial growth factor (VEGF) conjugated to an elastin-like polypeptide (ELP) carrier protein with an N-terminal kidney-targeting peptide (KTP). We tested the hypothesis that KTP-ELP-VEGF therapy will effectively recover renal function with an improved targeting profile. Further, we aimed to elucidate potential mechanisms driving renal recovery. Unilateral RVD was induced in 14 pigs. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified by multidetector CT imaging. Pigs then received a single intrarenal injection of KTP-ELP-VEGF or vehicle. CT quantification of renal hemodynamics was repeated 4 weeks later, and then pigs were euthanized. Ex vivo renal microvascular (MV) density and media-to-lumen ratio, macrophage infiltration, and fibrosis were quantified. In parallel, THP-1 human monocytes were differentiated into naïve macrophages (M0) or inflammatory macrophages (M1) and incubated with VEGF, KTP-ELP, KTP-ELP-VEGF, or control media. The mRNA expression of macrophage polarization and angiogenic markers was quantified (qPCR). Intrarenal KTP-ELP-VEGF improved RBF, GFR, and MV density and attenuated MV media-to-lumen ratio and renal fibrosis compared to placebo, accompanied by augmented renal M2 macrophages. In vitro, exposure to VEGF/KTP-ELP-VEGF shifted M0 macrophages to a proangiogenic M2 phenotype while M1s were nonresponsive to VEGF treatment. Our results support the efficacy of a new renal-specific biologic construct in recovering renal function and suggest that VEGF may directly influence macrophage phenotype as a possible mechanism to improve MV integrity and function in the stenotic kidney.


The immunolocalization and divergent roles of phosducin and phosducin-like protein in the retina.
These investigations were undertaken to compare and contrast the roles of phosducin and phosducin-like protein in the retina. Phosducin and phosducin-like protein were compared in an in vitro assay measuring their inhibition of transducin binding to light-activated rhodopsin. The two proteins were localized within the retina by immunoblot analyses and immunocytochemistry using affinity-purified antibodies with high specificity for each of the two homologs. The sensitivity of phosducin-like protein to phosphorylation was probed using in vitro protein kinase reactions. Phosducin and phosducin-like protein were found to have similar, though not identical, transducin inhibiting activity in vitro. These two proteins were found to be localized dissimilarly within the retina, with spatial overlap limited to the inner segments of the photoreceptors. Phosducin is found exclusively in photoreceptor cells, including the synaptic and nuclear layers, while phosducin-like protein is found throughout the inner retinal layers, most abundantly in the bipolar cells of the inner nuclear layer. Phosducin-like protein is not efficiently phosphorylated by the protein kinases tested, indicating that its regulation differs from that of phosducin. It appears that phosducin and phosducin-like protein play distinct roles in the retina. While phosducin is likely to be important in feedback regulation of the visual signal, such as in light adaptation, phosducin-like protein probably has little if any function in the phototransduction cascade. Phosducin-like protein may have a role in regulating the processing of visual signals by the neural cells of the inner retina.


Implementing a Patient-Reported Outcome Measure for Hemodialysis Patients in Routine Clinical Care: Perspectives of Patients and Providers on ESAS-r:Renal.
The Edmonton Symptom Assessment System Revised: Renal is a patient-reported outcome measure used to assess physical and psychosocial symptom burden in patients treated with maintenance dialysis. Studies of patient-reported outcome measures suggest the need for deeper understanding of how to optimize their implementation and use. This study examines patient and provider perspectives of the implementation process and the influence of the Edmonton Symptom Assessment System Revised: Renal on symptom management, patient-provider communication, and interdisciplinary communication. Eight in-facility hemodialysis programs in Ontario, Canada, assessed patients using the Edmonton Symptom Assessment System Revised: Renal every 4-6 weeks for 1 year. Screening and completion rates were tracked, and pre- and postimplementation surveys and midimplementation interviews were conducted with patients and providers. A chart audit was conducted 12 months postimplementation. In total, 1459 patients completed the Edmonton Symptom Assessment System Revised: Renal; 58% of eligible patients completed the preimplementation survey (n=718), and 56% of patients who completed the Edmonton Symptom Assessment System Revised: Renal at least once completed the postimplementation survey (n=569). Provider survey response rates were 71% (n=514) and 54% (n=319), respectively. Nine patients/caregivers from three sites and 48 providers from all sites participated in interviews. A total of 1207 charts were audited. Seven of eight sites had mean screening rates over 80%, suggesting that routine use of the Edmonton Symptom Assessment System Revised: Renal in clinical practice is feasible. However, the multiple data sources painted an inconsistent picture of the value and effect of the Edmonton Symptom Assessment System Revised: Renal. The Edmonton Symptom Assessment System Revised: Renal standardized symptom screening processes across providers and sites; improved patient and provider symptom awareness, particularly for psychosocial symptoms; and empowered patients to raise issues with providers. Yet, there was little, if any, statistically significant improvement in the metrics used to assess symptom management, patient-provider communication, and interdisciplinary communication. The Edmonton Symptom Assessment System Revised: Renal patient-reported outcome measure may be useful to standardize symptom screening, enhance awareness of psychosocial symptoms among patients and providers, and empower patients rather than to reduce symptom burden.


The effects of intermittent exercise on physiological outcomes in an obese population: continuous versus interval walking.
This study compared the effects of 12 weeks of caloric restriction and interval exercise (INT) and caloric restriction and continuous aerobic exercise (CON) on physiological outcomes in an obese population. Forty-four individuals (BMI ≥ 30 kg·m(-2)) were randomised into the INT or CON group. Participant withdrawal resulted in 12 and 14 participants in the INT and CON groups, respectively. All participants were on a strict monitored diet. Exercise involved two 15-min bouts of walking performed on five days per week. Interval exercise consisted of a 2:1 min ratio of low-intensity (40-45% VO2peak) and high- intensity (70-75% VO2peak) exercise, while the CON group exercised between 50-55% VO2peak. Exercise duration and average intensity (%VO2peak) were similar between groups. There were no significant differences (p > 0.05) between the two groups for any variable assessed apart from very low density lipoprotein (VLDL-C), which significantly decreased over time in the INT group only (p < 0.05, d = 1.03). Caloric restriction and interval exercise compared to caloric restriction and continuous aerobic exercise resulted in similar outcome measures apart from VLDL-C levels, which significantly improved in the INT group only. Key pointsTwelve weeks of interval exercise and caloric restriction resulted in significant improvement in very low density lipoprotein cholesterol in an obese population, as compared to continuous aerobic exercise and caloric restriction.Twelve weeks of either interval exercise or continuous exercise resulted in similar improvements in aerobic fitness in an obese population.


Kif7 is required for the patterning and differentiation of the diaphragm in a model of syndromic congenital diaphragmatic hernia.
Congenital diaphragmatic hernia (CDH) is a common birth defect that results in a high degree of neonatal morbidity and mortality, but its pathological mechanisms are largely unknown. Therefore, we performed a forward genetic screen in mice to identify unique genes, models, and mechanisms of abnormal diaphragm development. We identified a mutant allele of kinesin family member 7 (Kif7), the disorganized diaphragm (dd). Embryos homozygous for the dd allele possess communicating diaphragmatic hernias, central tendon patterning defects, and increased cell proliferation with diaphragmatic tissue hyperplasia. Because the patterning of the central tendon is undescribed, we analyzed the expression of genes regulating tendonogenesis in dd/dd mutant embryos, and we determined that retinoic acid (RA) signaling was misregulautted. To further investigate the role of Kif7 and RA signaling in the development of the embryonic diaphragm, we established primary mesenchymal cultures of WT embryonic day 13.5 diaphragmatic cells. We determined that RA signaling is necessary for the expression of tendon markers as well as the expression of other CDH-associated genes. Knockdown of Kif7, and retinoic acid receptors alpha (Rara), beta (Rarb), and gamma (Rarg) indicated that RA signaling is dependent on these genes to promote tendonogenesis within the embryonic diaphragm. Taken together, our results provide evidence for a model in which inhibition of RA receptor signaling promotes CDH pathogenesis through a complex gene network.


Bacterial peptidoglycan induces CD14-dependent activation of transcription factors CREB/ATF and AP-1.
Peptidoglycan (PGN), the major cell wall component of Gram-positive bacteria, induces secretion of cytokines in macrophages through CD14, the pattern recognition receptor that binds lipopolysaccharide and other microbial products. To begin to elucidate the mechanisms that regulate the transcription of cytokine genes, we wanted to determine which transcription factors are activated by PGN in mouse RAW264.7 and human THP-1 macrophage cells. Our results demonstrated that: (i) PGN induced phosphorylation of the transcription factors ATF-1 and CREB; (ii) ATF-1 and CREB bound DNA as a dimer and induced transcriptional activation of a CRE reporter plasmid, which was inhibited by dominant negative CREB and ATF-1; (iii) PGN induced phosphorylation of c-Jun, protein synthesis of JunB and c-Fos, and transcriptional activation of the AP-1 reporter plasmid, which was inhibited by dominant negative c-Fos; and (iv) PGN-induced activation of CREB/ATF and AP-1 was mediated through CD14. This is the first study to demonstrate activation of CREB/ATF and AP-1 transcription factors by PGN or by any other component of Gram-positive bacteria.


[Effects of early supplement of exogenous L-carnitine on renal function in severely scalded rats].
Objective: To explore the effects of early exogenous L-carnitine supplementation on renal function in severely scalded rats. Methods: According to the random number table, sixty-six adult female Sprague-Dawly rats were divided into healthy control group (n=6), scald alone group (n=30), and scald+ carnitine group (n=30). In the latter two groups, the rats were inflicted with full-thickness scald of 30% total body surface area on the back, and the lactated Ringer's solution was injected through the tail vein for resuscitation immediately after scald. At post injury hour (PIH) 1, rats in scald+ carnitine group were intraperitoneally injected with 100 mg/mL L-carnitine solution 400 mg/kg, while rats in scald alone group were intraperitoneally injected with the same volume of normal saline. Rats in these two groups were injected once every 24 hours thereafter. Six rats were taken from each of scald alone group and scald+ carnitine group to collect the renal tissue and abdominal aorta blood at PIH 6, 12, 24, 48, and 72, respectively. The serum content of total protein, albumin, urea nitrogen, creatinine, and cystatin C were determined by the automatic biochemical analyzer. Renal tissue was stained with hematoxylin-eosin to observe histopathological changes. Rats in healthy control group did not undergo any treatment, and their renal tissue and blood sample were extracted and analyzed in the same way as those of severely scalded rats. Data were statistically analyzed with one-way analysis of variance and Bonferroni method. Results: (1) The serum content of total protein and albumin of rats in scald alone group at each time point after injury was significantly lower than that in healthy control group (P<0.05). The serum content of total protein of rats in scald+ carnitine group was significantly higher than that in scald alone group at PIH 12 and 24 (P<0.05), and the serum content of albumin of rats in scald+ carnitine group was significantly higher than that in scald alone group at PIH 12 (P<0.05). The serum content of total protein and albumin of rats in scald alone group and scald+ carnitine group showed a trend of decrease followed by an increase, with the lowest value at PIH 24. (2) The serum content of urea nitrogen and creatinine of rats in scald alone group at each time point after injury was significantly higher than that of healthy control group (P<0.05). The serum content of urea nitrogen of rats in scald+ carnitine group was significantly lower than that in scald alone group at PIH 6, 48, and 72 (P<0.05). The serum content of creatinine of rats in scald+ carnitine group was significantly lower than that in scald alone group at PIH 12, 24, 48, and 72 (P<0.05). The serum content of urea nitrogen and creatinine of rats in scald alone group and scald+ carnitine group showed a trend of increase followed by a decrease, with the peak value at PIH 12. (3) The serum content of cystatin C of rats in scald alone group at PIH 6, 12, 24, 48, and 72 was (0.250±0.030), (0.330±0.070), (0.300±0.060), (0.240±0.060), and (0.190±0.030) mg/L, and the content at the first 4 time points were significantly higher than (0.170±0.020) mg/L of healthy control group (P<0.05). At PIH 24, the serum content of cystatin C of rats in scald+ carnitine group was (0.210±0.040) mg/L, which was significantly lower than that of scald alone group (P<0.05). The serum content of cystatin C of rats in scald alone group and scald+ carnitine group showed a trend of increase followed by a decrease, with the peak value at PIH 12. (4) The renal tissue of rats in healthy control group was almost normal, and the degree of renal tissue injury of rats in scald+ carnitine group was lighter than that in scald alone group at each time point after injury. At PIH 24, the renal tissue of rats in scald alone group showed extensive swelling of the renal tubular epithelial cells, vacuolar degeneration and necrosis, loss of brush borders, and nuclear shrinkage; more than 2/3 of the renal tubular cell nuclei disappeared, the tubular lumen was narrowed, necrotic exfoliated cells could be seen in the lumen, and edema and inflammatory cell infiltration could be seen in the renal interstitial. Compared with those of scald alone group, significantly reduced severity of edema and necrosis of renal tubular epithelial cells, as well as less inflammatory cell infiltration were observed in the renal tissue of rats in scald+ carnitine group. Conclusions: Early supplement of L-carnitine in severely scalded rats can reduce the damage of renal cells, accelerate the restoration of the content of total protein, albumin, urea nitrogen, creatinine, and cystatin C, thereby maintaining the stability of renal function metabolism level.


Case Report: Neuropsychological Findings in IgLON5 Antibody Disorder.
IgLON5 antibody encephalopathy is a rare but increasingly recognized disorder with a variety of clinical signs. Typical symptoms are sleep disorder, gait disturbances, signs of bulbar dysfunction and a variety of neurological symptoms like oculomotor abnormalities and movement disorders. In addition, cognitive decline can be a prominent symptom. So far, there are only a few studies that have dealt with the course and possible treatment options of IgLON5 antibody encephalopathy. In this study the clinical case of a female patient with IgLON5 antibody disease and the response to treatment is described. Here we report on the case of a 67-year-old female patient who showed cognitive deterioration, gait difficulties, and chronic obstructive sleep disorder. The diagnostic course showed a positive anti-IgLON5 serum and anti-IgLON5 IgG antibodies in cerebrospinal fluid. The patient was subsequently treated with high dosage i.v. methylprednisolone, i.v. immunoglobulins and plasmapheresis. Neuropsychological tests showed cognitive deficits in different domains, including verbal and visual memory. Both, neuropsychological deficits and antibody titer, showed an improvement after plasmapheresis. The presented case shows that IgLON5 disease can present with rapidly progressing cognitive deterioration as the prominent symptom, adding to the variety of clinical signs in this disorder. Testing for IgLON5-antibodies should be considered in patients with progressing cognitive decline, especially if accompanied by sleep disorders or neurological symptoms like oculomotor abnormalities, dysautonomia or bulbar signs.


Efficient removal of ibuprofen and ofloxacin pharmaceuticals using biofilm reactors for hospital wastewater treatment.
Hospital wastewater is harmful to the environment and human health due to its complex chemical composition and high potency towards becoming a source of disease outbreaks. Due to these complexities, its treatment is neither efficient nor cost-effective. It is a challenging issue that requires immediate attention. This effort focuses on the treatment of hospital wastewater (HWW) by removing two selected drugs, namely ibuprofen (IBU) and ofloxacin (OFX) using individual biological treatment methods, such as moving bed biofilm reactors (MBBR) and physicochemical treatment, such as ozonation and peroxane process. The both methods are compared to find the best method overall based on effectiveness and removal efficiency. The optimal removal for ozone dosing range was nitrate (9.00% and 62.00%), biological oxygen demand (BOD) (92.00% and 64.00%), and chemical oxygen demand (COD) (96.00% and 92.00%) that required at least 10 min to reach considerable degradation. The MBBR process assured a better performance for ibuprofen removal, overall. The IBU and OFX removal was found to be 14.32-96.00% at a higher COD value and 11.33-94.00% at a lower COD value due to its biodegradation. This work strives to pave the way forward to build an HWW treatment technology using integrated MBBR processes for better efficiency and cost-effectiveness.


Modification of glucose import capacity in Escherichia coli: physiologic consequences and utility for improving DNA vaccine production.
The bacterium Escherichia coli can be grown employing various carbohydrates as sole carbon and energy source. Among them, glucose affords the highest growth rate. This sugar is nowadays widely employed as raw material in industrial fermentations. When E. coli grows in a medium containing non-limiting concentrations of glucose, a metabolic imbalance occurs whose main consequence is acetate secretion. The production of this toxic organic acid reduces strain productivity and viability. Solutions to this problem include reducing glucose concentration by substrate feeding strategies or the generation of mutant strains with impaired glucose import capacity. In this work, a collection of E. coli strains with inactive genes encoding proteins involved in glucose transport where generated to determine the effects of reduced glucose import capacity on growth rate, biomass yield, acetate and production of an experimental plasmid DNA vaccine (pHN). A group of 15 isogenic derivatives of E. coli W3110 were generated with single and multiple deletions of genes encoding glucose, mannose, beta-glucoside, maltose and N-acetylglucosamine components of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), as well as the galactose symporter and the Mgl galactose/glucose ABC transporter. These strains were characterized by growing them in mineral salts medium supplemented with 2.5 g/L glucose. Maximum specific rates of glucose consumption (qs) spanning from 1.33 to 0.32 g/g h were displayed by the group of mutants and W3110, which resulted in specific growth rates ranging from 0.65-0.18 h(-1). Acetate accumulation was reduced or abolished in cultures with all mutant strains. W3110 and five selected mutant derivatives were transformed with pHN. A 3.2-fold increase in pHN yield on biomass was observed in cultures of a mutant strain with deletion of genes encoding the glucose and mannose PTS components, as well as Mgl. The group of E. coli mutants generated in this study displayed a reduction or elimination of overflow metabolism and a linear correlation between qs and the maximum specific growth rate as well as the acetate production rate. By comparing DNA vaccine production parameters among some of these mutants, it was possible to identify a near-optimal glucose import rate value for this particular application. The strains employed in this study should be a useful resource for studying the effects of different predefined qs values on production capacity for various biotechnological products.


Suppression of autoimmune disease by dietary n-3 fatty acids.
Previous studies have demonstrated that dietary fish oil preparations have anti-inflammatory effects in humans and in experimental animals, but the individual components of fish oils that are responsible for their anti-inflammatory effects have not been documented. We therefore investigated in (NZB x NZW)F1 mice, a model for human systemic lupus erythematosus, the effects of diets containing ethyl esters of two purified n-3 fatty acids, eicosapentaenoic acid (EPA-E) and docosahexaenoic acid (DHA-E), a refined fish oil triglyceride (FO) which contained 55% n-3 fatty acids, and beef tallow (BT) which contains no n-3 fatty acids. The diets were initiated prior to the development of overt renal disease at age 22 weeks, and continued for 14 weeks. The extent of the renal disease was quantified by light microscopy and by proteinuria. Diets containing either 10 wt% FO, 10% EPA-E, or 6% or 10% DHA-E alleviated the severity of the renal disease, compared to the BT diet, whereas diets containing either 3% or 6% EPA-E or 3% DHA-E were less effective. Two diets containing approximately 3:1 mixtures of EPA-E and DHA-E alleviated the renal disease to a greater extent than expected for either of these fatty acids given singly. We believe that these experiments provide the first demonstration of anti-inflammatory effects of individual dietary n-3 fatty acids. The results also indicate that the anti-inflammatory effects of fish oils depend on synergistic effects of at least two n-3 fatty acids.


The effect of salinity on transovarial transmission of a microsporidian infecting Gammarus duebeni.
This is an investigation of the impact of salinity on transovarial transmission and burden of a microsporidian sex ratio distorter in the inter-tidal crustacean Gammarus duebeni. Exposure of parasitized mothers to increased salinity during the gonotrophic cycle caused an increase in parasite burden in the follicle cells and a decrease in burden in the oocytes. It appears that salinity impedes parasite transmission from the follicle cells to the oocytes during host oogenesis. A lower proportion of the young were infected in broods from elevated salinity and, in infected offspring, parasite burden was lower than in control embryos. Parasite replication occurred during embryogenesis. However, the pattern of parasite growth did not differ between salinities, indicating that differences in parasite burden could be attributed to a reduction in the initial parasite burden transmitted to the gamete, rather than to a reduction in parasite replication during host embryogenesis. We discuss our findings with respect to parasite/host dynamics and the ecology of the host.


Companion Animals Symposium: Obesity in dogs and cats: What is wrong with being fat?
Few diseases in modern pets are diet induced. One possible exception to this is obesity, which is ultimately caused by consuming more calories than needed by the dog or cat. Although fat is the most concentrated and efficiently stored source of calories, and protein least so, an excess of calories from any source will contribute to adiposity. Obesity is an excess of body fat sufficient to result in impairment of health or body function. In people, this is generally recognized as 20 to 25% above ideal BW. This degree of excess is important in dogs as well. A lifelong study in dogs showed that even moderately overweight dogs were at greater risk for earlier morbidity; these dogs required medication for chronic health problems sooner than their lean-fed siblings. The average difference in BW between groups was approximately 25%. Obese cats also face increased health risks, including an increased risk of arthritis, diabetes mellitus, hepatic lipidosis, and early mortality. The risk for development of diabetes increases about 2-fold in overweight cats and about 4-fold [corrected] in obese cats. Altered adipokine secretion appears to be an important mechanism for the link between excess BW and many diseases. Once considered to be physiologically inert, adipose tissue is an active producer of hormones, such as leptin and resistin, and cytokines, including many inflammatory cytokines such as tumor necrosis factor-α, IL-1β and IL-6, and C-reactive protein. The persistent, low-grade inflammation secondary to obesity is thought to play a causal role in chronic diseases such as osteoarthritis, cardiovascular disease, diabetes mellitus, and others. For example, tumor necrosis factor-α alters insulin sensitivity by blocking activation of insulin receptors. In addition, obesity is associated with increased oxidative stress, which also may contribute to obesity-related diseases. Management of obesity involves nutritional modification as well as behavioral modification. Increased protein intake combined with reduced calorie intake facilitates loss of body fat while minimizing loss of lean body mass. Limiting treats to 10% of calorie intake and increasing exercise both aid in successful BW management.


Correlation Nerve Conduction Studies with Findings of the Ultrasound of the Median Nerve in Patients with Carpal Tunnel Syndrome.
Ultrasonography is a diagnostic resource that serves as a complement in the evaluation of patients with carpal tunnel syndrome. The correlation of ultrasonography findings with nerve conduction studies can serve to classify new phenotypes and to evaluate therapeutic responses. To determine the diagnostic sensitivity of ultrasound, the correlation between the diameter of the nerve (CSA) against the motor and sensitive latencies, and the capacity to differentiate the mild, moderate and severe degrees of the electrophysiological classification of carpal tunnel syndrome. A cross-sectional study with prospective data collection was carried out. An ultrasonography system with a 15 MHz transducer was used. Nerve conduction studies of the median nerve were performed with conventional techniques. Data from the most symptomatic hand were used. Determination of the correlations of nerve diameter with motor and sensitive latencies of the median nerve was performed in four age groups: <40(n=11), 40-54 (n=47), 55-70 (n=42) y >70(n=27). A total of 127 patients were evaluated (average age = 58.2 years: minimum = 26; maximum = 85; SD = 13.4); 109 (85.8%) were female patients. According to the electrophysiological classification, 40 (31.5%) were mild ; 60 (47.2%) were moderate ; and 27 (21.3%) were severe . Significant differences in the area of the median nerve were found between the electrophysiological types (mild, moderate and severe; p = 0.000). The diagnostic sensitivity of ultrasonography differed for each age group. In general, the diagnostic sensitivity was high in patients with severe cases and low for mild cases. The capacity for ultrasonography to classify the degrees of electrophysiological severity was different for each age group. For patients above 70 years and in the age group of 40 to 54 years, the CSA did not differentiate the electrophysiologically moderate cases from the severe ones. There is a well-defined and significant correlation between nerve conduction studies and median nerve diameter in patients with Carpal Tunnel Syndrome. However, it shows that the exclusive use of the ultrasonographic measurement of the cross-sectional area through the inlet of the carpal tunnel would not be enough to confirm or rule out an entrapment of the median nerve through the carpal tunnel, nor to predict in every case their electrophysiological severity.


Helicase, a target for novel inhibitors of hepatitis C virus.
Virus-encoded enzymes of hepatitis C virus (HCV) were identified from its genome sequence. This allows application of drug discovery strategies which rely on inhibition of enzymes unique to HCV. Discovery of high-affinity inhibitors is facilitated by knowledge of the target enzyme's three-dimensional structure. For development of inhibitors of the HCV helicase, which belongs to a class of enzymes for which little structural information is available, the impact of structural information on the drug discovery process is greater than for targets belonging to well-characterized classes of enzyme. Here the structure of the HCV helicase is described. Regions required for enzymatic activity, which are also the preferred sites of drug interaction, are highlighted.


Effects of individual vs group penning on the performance of weanling pigs.
Two experiments (five trials) were conducted to determine the effects of individual vs group penning on the performance of 4-wk-old crossbred barrows and gilts. In each experiment, half the pigs were tested in a group pen (four pigs) for two 7-d periods and individually for one 7-d period and the other pigs were fed individually for two periods and as a group for one period. In Exp. 1 (two trials, each with five replicates of eight pigs), individually penned pigs had physical and visual contact with pigs in the adjoining pens; in Exp. 2 (three trials, each with five replicates of eight pigs), such contact was denied. Growth rate, feed intake, and feed efficiency were determined at the end of each period. In addition, during Trial 3 of Exp. 2 blood samples were collected at the end of each period and plasma was assayed for cortisol and triiodothyronine (T3) concentrations. Penning sequences produced inconsistent weight gains and feed intake. Differences in gain favored (P < .04) the individually penned pigs during Trial 3 of Exp. 2 and differences in feed intake favored the individually penned pigs during Trial 2 of Exp. 1 (P < .009) and during Trials 2 and 3 of Exp. 2 (P < .02 and P < .009, respectively). Penning treatment had no effect on feed efficiency, plasma cortisol, or T3 concentrations. These data suggest that pigs perform equally well whether fed and housed individually or in groups, with no indications of stress associated with individual pens and isolation.


Moiré volume Bragg grating filter with tunable bandwidth.
We propose a monolithic large-aperture narrowband optical filter based on a moiré volume Bragg grating formed by two sequentially recorded gratings with slightly different resonant wavelengths. Such recording creates a spatial modulation of refractive index with a slowly varying sinusoidal envelope. By cutting a specimen at a small angle, to a thickness of one-period of this envelope, the longitudinal envelope profile will shift from a sine profile to a cosine profile across the face of the device. The transmission peak of the filter has a tunable bandwidth while remaining at a fixed resonant wavelength by a transversal shift of incidence position. Analytical expressions for the tunable bandwidth of such a filter are calculated and experimental data from a filter operating at 1064 nm with bandwidth range 30-90 pm is demonstrated.


Mothers' views on hyperactivity: a cross-cultural perspective.
To examine cultural variation in mothers' perceptions of hyperactive behaviors in school-age boys, we surveyed 135 mothers in 3 ethnic groups: Puerto Rican, Central and South American, and Anglo. Mothers read or heard 8 taped vignettes of boys with behaviors related to DSM-IV hyperactivity criteria. In 50% of the vignettes, Spanish-responding mothers were less likely to consider the boys' behaviors expected than were the English-responding mothers. In 62.5% of the vignettes, Latina mothers expressed more interest in discussing behaviors with their physicians than did the Anglo mothers, and in 62.5% of the vignettes, Spanish-responding mothers expressed more interest in discussing behaviors with their physicians than did the English-responding mothers. We found no association of the 2 scores by the bicultural scale. Mothers' perception of hyperactivity boys varies both with ethnicity and language of response. Latina mothers, especially Spanish-responding mothers, seem interested in discussing children's behavior with physicians.


Key Mechanistic Features in Palladium-Catalyzed Methylcyclopropanation of Norbornenes With Vinyl Bromides: Insights From DFT Calculations.
DFT calculations were performed to elucidate mechanistic details of an unusual palladium-catalyzed methylcyclopropanation from [2 + 1] cycloadditions of (Z)-2-bromovinylbenzene and endo-N-(p-tolyl)-norbornenesuccinimide. The reaction proceeds via oxidative addition (OA), intermolecular alkene insertion, deprotonation/protonation, intramolecular alkene insertion, β-H elimination and reductive elimination (RE). Protonation is the rate-limiting step and requires an overall barrier of 28.5 kcal/mol. The sources of two protons for protonation and exchange have also been clarified and the calculations agree with experimental observations.


Cytokines in bipolar disorder: paving the way for neuroprogression.
Bipolar disorder (BD) is a severe, chronic, and recurrent psychiatric illness. It has been associated with high prevalence of medical comorbidities and cognitive impairment. Its neurobiology is not completely understood, but recent evidence has shown a wide range of immune changes. Cytokines are proteins involved in the regulation and the orchestration of the immune response. We performed a review on the involvement of cytokines in BD. We also discuss the cytokines involvement in the neuroprogression of BD. It has been demonstrated that increased expression of cytokines in the central nervous system in postmortem studies is in line with the elevated circulating levels of proinflammatory cytokines in BD patients. The proinflammatory profile and the immune imbalance in BD might be regarded as potential targets to the development of new therapeutic strategies.


Magnetic resonance angiography: analysis of vascular lesions of the temporal bone and skull base.
Contrast-enhanced, high resolution, computed tomography (CT), along with gadolinium-enhanced magnetic resonance imaging (MRI), provide the skull-base surgeon with essential information for diagnosis and surgical planning. Evaluation of skull-base vasculature has traditionally been performed with angiography. Four-vessel angiography is an invasive procedure that subjects the patient to the potential risks of vascular injury, stroke, renal damage, anaphylaxis, and radiation. The development of gradient-recall echo pulse sequence in MRI provides a means to evaluate the vasculature with a noninvasive, low-risk technique. We review the experience of the House Ear Clinic with magnetic resonance angiography (MRA) in evaluating cranial-base abnormalities including paragangliomas, aberrant vessels, and dural sinus thrombosis. Based on a review of 25 cases, we conclude that MRA is a useful procedure for evaluation of major arteries, veins, and dural sinuses. The technique has been less helpful in defining small vessel detail such as feeding blood supply and tumor staining.


Follow-up recommendations for colon cancer.
Recent evidence suggests that intensive follow-up after curative resection of colorectal cancer is associated with a small but significant improvement in survival. Regimens that employ cross-sectional imaging and carcinoembryonic antigen determination appear to have the greatest benefit. A risk-adapted approach to follow-up, intensively following patients at highest risk of recurrence, increases efficacy and cost-effectiveness. Ongoing improvements in risk stratification, disease detection, and treatment will increase the benefits of postoperative surveillance. Large randomized controlled trials are needed to determine the optimal surveillance regimen and must include an analysis of survival, quality of life, and cost-effectiveness to assess efficacy properly.


Implementing COVID-19 infection prevention and control measures in long-term care settings.
The coronavirus disease 2019 (COVID-19) pandemic has had far-reaching and significant effects worldwide. Many of those identified as most vulnerable to the disease reside in long-term care settings such as nursing and residential homes, so infection prevention and control is an essential area of practice. This article describes how COVID-19 is transmitted and discusses various measures that can be taken to reduce the spread of infection to protect residents, staff and visitors. Such measures include social distancing, routine screening, the use of personal protective equipment and cleaning.


Dual-Modular Aptasensor for Detection of Cardiac Troponin I Based on Mesoporous Silica Films by Electrochemiluminescence/Electrochemical Impedance Spectroscopy.
A simple, dual-modular aptasensor for accurate determination of cardiac troponin I (cTnI), a sensitive biomarker of acute myocardial infarction, is reported. It has the parallel output of electrochemiluminescence (ECL) and electrochemical impedance spectroscopy (EIS) based on target-gated transportation of signal probes (luminol/H2O2 or Fe(CN)63-/4-). The sensing capacity is originated from the amino-functionalized mouth margin of the nanochannels in a vertically oriented mesoporous silica film, which was in situ-grown on indium tin oxide-coated glass. With the linkage of glutaraldehyde to couple the aptamer as a trapper, it brings in the high specific target-gated response toward cTnI as decreased ECL or increased EIS. The concentration of cTnI is measurable by the ECL response within a wide linear range from 0.05 pg mL-1 to 10 ng mL-1, as well as the EIS response for a linear range between 0.05 pg mL-1 and 1 ng mL-1. Significantly, the self-verification of these two data from ECL and EIS validated each other with a satisfactory linear correlation (R2 = 0.999), thereby realizing the more reliable and accurate quantification to avoid false results. The designed strategy is an effective method for detection of cTnI, which is of great potential to apply in clinical detection.


Autophagy: polyQ toxic fragment turnover.
Recent studies have highlighted the importance of the lysosome in degrading proteins that misfold in neurodegenerative diseases. In this study we explore the role for autophagy in the clearance of an N-terminal caspase-7-generated fragment of ataxin-7, a protein with a pathogenic polyglutamine (polyQ) expansion in the neurodegenerative disease spinocerebellar ataxia 7 (SCA7). Using both cellular and transgenic mouse models of SCA7 we show that the stability of wild-type ataxin-7 is modified by macroautophagy, but not by proteasomal, inhibition, whereas both autophagy and proteasomal degradation have little effect on polyQ-expanded ataxin-7. We also create a post-translational modification-deficient ataxin-7 mutant that has increased protein turnover of both wild-type and polyQ-expanded ataxin-7, mediated through the autophagy pathway. Histological analysis reveals that wild-type ataxin-7 colocalizes with markers of chaperone-mediated autophagy (CMA) and macroautophagy, indicating that both of these mechanisms may play a role in the clearance of ataxin-7. Furthermore, there is an increase in LC3, a marker of autophagy initiation, in the cerebellum of SCA7 transgenic mice. Our findings indicate that the ataxin-7 fragment may be cleared via autophagy and that this process is altered in SCA7. Identification of the different types of autophagy involved in ataxin-7 turnover and the influence of post-translational modifications on these processes will be pursued in future studies.


Biliary innate immunity: function and modulation.
Biliary innate immunity is involved in the pathogenesis of cholangiopathies in patients with primary biliary cirrhosis (PBC) and biliary atresia. Biliary epithelial cells possess an innate immune system consisting of the Toll-like receptor (TLR) family and recognize pathogen-associated molecular patterns (PAMPs). Tolerance to bacterial PAMPs such as lipopolysaccharides is also important to maintain homeostasis in the biliary tree, but tolerance to double-stranded RNA (dsRNA) is not found. In PBC, CD4-positive Th17 cells characterized by the secretion of IL-17 are implicated in the chronic inflammation of bile ducts and the presence of Th17 cells around bile ducts is causally associated with the biliary innate immune responses to PAMPs. Moreover, a negative regulator of intracellular TLR signaling, peroxisome proliferator-activated receptor-gamma (PPARgamma), is involved in the pathogenesis of cholangitis. Immunosuppression using PPARgamma ligands may help to attenuate the bile duct damage in PBC patients. In biliary atresia characterized by a progressive, inflammatory, and sclerosing cholangiopathy, dsRNA viruses are speculated to be an etiological agent and to directly induce enhanced biliary apoptosis via the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Moreover, the epithelial-mesenchymal transition (EMT) of biliary epithelial cells is also evoked by the biliary innate immune response to dsRNA.


Analysis of a Hybrid Micro-Electro-Mechanical Sensor Based on Graphene Oxide/Polyvinyl Alcohol for Humidity Measurements.
In this paper, we present a redundant microsensor based on the bulk and etch silicononinsulator (BESOI) process for measuring relative humidity (RH), by using a grapheneoxide/polyvinylalcohol (GO/PVA) composite. The MEMS is a mechanical oscillator, composed of a proof mass with multilayer of nanomaterials (GO/PVA) and suspended by four crab-leg springs. The redundant approach realized concerns the use of different readout strategies in order to estimate the same measurand RH. This is an intriguing solution to realize a robust measurement system with multiple outputs, by using the GO/PVA as functional material. In the presence of RH variation, GO/PVA (1) changes its mass, and as consequence, a variation of the natural frequency of the integrated oscillator can be observed; and (2) varies its conductivity, which can be measured by using two integrated electrodes. The sensor was designed, analyzed and modeled; experimental results are reported here to demonstrate the effectiveness of our implementation.


Prolactin activation of the long form of its cognate receptor causes increased visceral fat and obesity in males as shown in transgenic mice expressing only this receptor subtype.
To date the best defined function of prolactin (PRL) is its action on the ovary and mammary gland, although it has also been shown to have an effect on lipid metabolism. Using mice engineered to express only the long form of the prolactin receptor (PRL-RL), we demonstrate that PRL acting through PRL-RL alone causes severe adipose accumulation in visceral fat of males at 6 months of age. The increase in visceral fat accumulation is attributed to loss of adipose-derived leptin, which results in diminished lipolysis. The reduction in leptin also corresponds to decreased activation of AMP-activated protein kinase (AMPK), which further results in diminished fatty acid oxidation and increased fatty acid synthesis. Interestingly, the blunted AMPK response was only observed in adipose tissue and not in liver suggesting that this PRL mediated effect is tissue specific. A glucose tolerance study inferred that PRL-RL mice may suffer from insulin resistance or a reduction in insulin production that is not due to aberrant expression of glucose transporter 4 (Glut4). Collectively, our findings demonstrate that PRL signaling through the long form receptor causes reduced fatty acid oxidation, increased lipid storage, glucose intolerance, and obesity. These findings are of great importance towards understanding the etiology of obesity associated with hyperprolactinemia in humans as well as the role of PRL as a metabolic regulator in adipose tissue.


Discovery and Optimization of Potent, Selective, and in Vivo Efficacious 2-Aryl Benzimidazole BCATm Inhibitors.
To identify BCATm inhibitors suitable for in vivo study, Encoded Library Technology (ELT) was used to affinity screen a 117 million member benzimidazole based DNA encoded library, which identified an inhibitor series with both biochemical and cellular activities. Subsequent SAR studies led to the discovery of a highly potent and selective compound, 1-(3-(5-bromothiophene-2-carboxamido)cyclohexyl)-N-methyl-2-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamide (8b) with much improved PK properties. X-ray structure revealed that 8b binds to the active site of BACTm in a unique mode via multiple H-bond and van der Waals interactions. After oral administration, 8b raised mouse blood levels of all three branched chain amino acids as a consequence of BCATm inhibition.


Prediction of the globally ecological suitability of Panax quinquefolius by the geographic information system for global medicinal plants (GMPGIS).
American ginseng (Panax quinquefolius L.) is a well-known Asian traditional herbal medicine with a large market demand. The plant is native to eastern North America, and its main producing areas worldwide are decreasing due to continuous cropping obstacles and environmental changes. Therefore, the identification of maximum similarities of new ecological distribution of P. quinquefolius, and prediction of its response to climate change in the future are necessary for plant introduction and cultivation. In this study, the areas with potential ecological suitability for P. quinquefolius were predicted using the geographic information system for global medicinal plants (GMPGIS) based on 476 occurrence points and 19 bioclimatic variables. The results indicate that the new ecologically suitable areas for P. quinquefolius are East Asia and the mid-eastern Europe, which are mainly distributed in China, Russia, Japan, Ukraine, Belarus, North Korean, South Korea, andRomania. Under global climate change scenarios, the suitable planting areas for P. quinquefolius would be increased by 9.16%-30.97%, and expandingnorth and west over the current ecologically suitable areas by 2070. The potential increased areas that are ecologically suitable include northern Canada, Eastern Europe, and the Lesser Khingan Mountains of China, and reduced regions are mainly in central China, the southern U.S., and southern Europe. Jackknife tests indicate that the precipitation of the warmest quarter was the important climatic factor controlling the distribution of P. quinquefolius. Our findings can be used as auseful guide for P. quinquefolius introduction and cultivation in ecologically suitable areas.