[Studies on cytogeography of Pinellia ternata poliploid complex].
In order to clarify the genetic background of Pinellia ternata germplasm resources in China, the chromosomal constitution and cytogeographical distribution of P. ternata were investigated in 27 different populations among 16 provinces and regions in China systematically. Cytological and cytogeographical methods were used in the study. P. ternata in China is a polyploid complex, which contains septuploid (2n = 7x = 91) , octoploid (2n = 8x = 104) , nonuploid (2n = 9x = 117) and decaploid (2n = 10x = 130). Meanwhile the aneuploid series (2n = 92, 103, 105, 115) of a minority of P. ternata were also found. The genetic differentiation and the phenomenon of ploidy miscellany commonly exist in the species of P. ternata in China, both for natural populations and cultivated populations. Toxicity and chemical components of different ploidy P. ternata should be clarified before the superior multiploid is selected for normalized plantation of the plant.


Relapse prevention program for treatment of obsessive-compulsive disorder.
Eighteen participants with obsessive-compulsive disorder received 3 weeks of intensive treatment by exposure and response prevention, which were followed by either a relapse prevention (RP) program or associative therapy (AT; an attention-control program). Independent evaluators conducted assessments of obsessive-compulsive symptoms, anxiety, and depression, before and after intensive behavior therapy, after the week of intensive RP or AT and at a 6-month follow-up. Results indicated that the RP program was effective in preventing relapse: Both treatment groups improved immediately after the intensive treatment, but the RP group remained improved at follow-up, whereas the AT group showed some return of symptoms.


3D Printing Processability of a Thermally Conductive Compound Based on Carbon Nanofiller-Modified Thermoplastic Polyamide 12.
A polyamide (PA) 12-based thermoplastic composite was modified with carbon nanotubes (CNTs), CNTs grafted onto chopped carbon fibers (CFs), and graphene nanoplatelets (GNPs) with CNTs to improve its thermal conductivity for application as a heat sink in electronic components. The carbon-based nanofillers were examined by SEM and Raman. The laser flash method was used to measure the thermal diffusivity in order to calculate the thermal conductivity. Electrical conductivity measurements were made using a Keithley 6517B electrometer in the 2-point mode. The composite structure was examined by SEM and micro-CT. PA12 with 15 wt% of GNPs and 1 wt% CNTs demonstrated the highest thermal conductivity, and its processability was investigated, utilizing sequential interdependence tests to evaluate the composite material behavior during fused filament fabrication (FFF) 3D printing processing. Through this assessment, selected printing parameters were investigated to determine the optimum parametric combination and processability window for the composite material, revealing that the selected composition meets the necessary criteria to be processable with FFF.


Rotavirus Spike Protein VP4 Mediates Viroplasm Assembly by Association to Actin Filaments.
Rotavirus (RV) viroplasms are cytosolic inclusions where both virus genome replication and primary steps of virus progeny assembly take place. A stabilized microtubule cytoskeleton and lipid droplets are required for the viroplasm formation, which involves several virus proteins. The viral spike protein VP4 has not previously been shown to have a direct role in viroplasm formation. However, it is involved with virus-cell attachment, endocytic internalization, and virion morphogenesis. Moreover, VP4 interacts with actin cytoskeleton components, mainly in processes involving virus entrance and egress, and thereby may have an indirect role in viroplasm formation. In this study, we used reverse genetics to construct a recombinant RV, rRV/VP4-BAP, that contains a biotin acceptor peptide (BAP) in the K145-G150 loop of the VP4 lectin domain, permitting live monitoring. The recombinant virus was replication competent but showed a reduced fitness. We demonstrate that rRV/VP4-BAP infection, as opposed to rRV/wt infection, did not lead to a reorganized actin cytoskeleton as viroplasms formed were insensitive to drugs that depolymerize actin and inhibit myosin. Moreover, wild-type (wt) VP4, but not VP4-BAP, appeared to associate with actin filaments. Similarly, VP4 in coexpression with NSP5 and NSP2 induced a significant increase in the number of viroplasm-like structures. Interestingly, a small peptide mimicking loop K145-G150 rescued the phenotype of rRV/VP4-BAP by increasing its ability to form viroplasms and hence improve virus progeny formation. Collectively, these results provide a direct link between VP4 and the actin cytoskeleton to catalyze viroplasm assembly. IMPORTANCE The spike protein VP4 participates in diverse steps of the rotavirus (RV) life cycle, including virus-cell attachment, internalization, modulation of endocytosis, virion morphogenesis, and virus egress. Using reverse genetics, we constructed for the first time a recombinant RV, rRV/VP4-BAP, harboring a heterologous peptide in the lectin domain (loop K145-G150) of VP4. The rRV/VP4-BAP was replication competent but with reduced fitness due to a defect in the ability to reorganize the actin cytoskeleton, which affected the efficiency of viroplasm assembly. This defect was rescued by adding a permeable small-peptide mimicking the wild-type VP4 loop K145-G150. In addition to revealing a new role of VP4, our findings suggest that rRV harboring an engineered VP4 could be used as a new dual vaccination platform providing immunity against RV and additional heterologous antigens.


Identification and Characterization of Lipopolysaccharide Induced TNFα Factor from Blunt Snout Bream, Megalobrama amblycephala.
Lipopolysaccharide induced TNFα factor (LITAF) is an important transcription factor responsible for regulation of tumor necrosis factor α. In this study, a novel litaf gene (designated as Malitaf) was identified and characterized from blunt snout bream, Megalobrama amblycephala. The full-length cDNA of Malitaf was of 956 bp, encoding a polypeptide of 161 amino acids with high similarity to other known LITAFs. A phylogenetic tree also showed that Malitaf significantly clustered with those of other teleost, indicating that Malitaf was a new member of fish LITAF family. The putative maLITAF protein possessed a highly conserved LITAF domain with two CXXC motifs. The mRNA transcripts of Malitaf were detected in all examined tissues of healthy M. amblycephala, including kidney, head kidney, muscle, liver, spleen, gill, and heart, and with the highest expression in immune organs: spleen and head kidney. The expression level of Malitaf in spleen was rapidly up-regulated and peaked (1.29-fold, p < 0.05) at 2 h after lipopolysaccharide (LPS) stimulation. Followed the stimulation of Malitaf, Matnfα transcriptional level was also transiently induced to a high level (51.74-fold, p < 0.001) at 4 h after LPS stimulation. Taken together, we have identified a putative fish LITAF ortholog, which was a constitutive and inducible immune response gene involved in M. amblycephala innate immunity during the course of a pathogenic infection.


Isolation and structural identification of complex feruloylated heteroxylan side-chains from maize bran.
Three complex heteroxylan side-chains acylated with ferulate and one arabinosyl ester of p-coumaric acid have been isolated from maize bran insoluble fibre after acidic hydrolysis and fractionation by gel permeation chromatography and semi-preparative RP-HPLC. The complete structural elucidation of all isolated compounds was achieved by 1D/2D NMR spectroscopy and HPLC-MS in combination with methylation analysis. The absolute configuration of the carbohydrate constituents was determined by chiral GC after acidic hydrolysis and trifluoroacetylation. The identified feruloylated tetrasaccharides alpha-d-xylopyranosyl-(1-->3)-alpha-l-galactopyranosyl-(1-->2)-beta-d-xylopyranosyl-(1-->2)-5-O-trans-feruloyl-l-arabinofuranose (FAXGX) and alpha-d-galactopyranosyl-(1-->3)-alpha-l-galactopyranosyl-(1-->2)-beta-d-xylopyranosyl-(1-->2)-5-O-trans-feruloyl-l-arabinofuranose (FAXGG) are the most complex heteroxylan side-chains from maize bran that have been isolated to date. The isolated trisaccharide alpha-l-galactopyranosyl-(1-->2)-beta-d-xylopyranosyl-(1-->2)-5-O-trans-feruloyl-l-arabinofuranose (FAXG) contributes to the complexity of heteroxylan side-chains from maize bran and 5-O-trans-p-coumaroyl-l-arabinofuranose represents the first p-coumaroylated heteroxylan side-chain isolated from cereal grains. Complex feruloylated heteroxylan side-chains are possibly, like ferulate cross-linking of the heteroxylans and binding of heteroxylans to lignin, a factor contributing to limited enzymatic degradation of fibre.


Complete replacement of the ascending aorta and the aortic valve with coronary reimplantation.
In 6 patients with cystic medial necrosis of the ascending aorta and the aortic root complete elective replacement of these structures with coronary reimplantation was performed. Two patients died from postoperative left ventricular failure, 4 patients survived and were hemodynamically unaffected at follow-up. Also the heart size in these patients decreased postoperatively. Survival seemed mainly related to the degree of preoperative cardiac failure and cardiomegaly.


Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival.
To describe the incidence and outcomes associated with venous thromboembolism (VTE) among patients with colorectal cancer. This was a retrospective analysis of all colorectal cancer patients diagnosed in California between 1993 and 1995 and 1997 to 1999. Principal outcomes were incident symptomatic VTE events and death. Associations between specific risk factors and principal outcomes were analyzed using Cox proportional hazards models. Among 68,142 colorectal cancer patients, 50% were women, mean age was 70 +/- 15 years, and approximately 70% underwent a major operation. The 2-year cumulative incidence of VTE was 2,100 patients (3.1%), with an incidence rate that decreased significantly over time from 5.0% (events/100 patient-years) in months 0 to 6 to 1.4% during months 7 to 12 to 0.6% during the second year. Significant predictors of VTE included metastatic stage (hazard ratio [HR] = 3.2; 95% CI, 2.8 to 3.8) and three or more comorbid conditions (HR = 2.0; 95% CI, 1.7 to 2.3). The risk of VTE was significantly reduced among Asians/Pacific Islanders (HR = 0.4; 95% CI, 0.3 to 0.5.) and patients who underwent an abdominal operation (HR = 0.4; 95% CI, 0.3 to 0.4). In risk-adjusted models, VTE was a significant predictor of death within 1 year of cancer diagnosis among patients with local- (HR = 1.8; 95% CI, 1.4 to 2.3) or regional-stage disease (HR = 1.5; 95% CI, 1.3 to 1.8) but not among patients with metastatic disease (HR = 1.1; 95% CI, 1.0 to 1.2). The incidence of VTE among colorectal cancer patients was highest in the first 6 months after diagnosis and decreased rapidly thereafter. Metastatic disease and the number of medical comorbidities were the strongest predictors of VTE. Incident VTE reduced survival among patients with local or regional disease, suggesting that, in these patients, VTE may reflect the presence of a biologically more aggressive cancer.


Protective Effect of Gochujang on Inflammation in a DSS-Induced Colitis Rat Model.
Gochujang is a traditional Korean fermented soy-based spicy paste made of meju (fermented soybean), red pepper powder, glutinous rice, and salt. This study investigated the anti-inflammatory effects of Gochujang containing salt in DSS-induced colitis. Sprague-Dawley (SD) rats were partitioned into five groups: normal control, DSS control, DSS + salt, DSS + mesalamine, and DSS + Gochujang groups. They were tested for 14 days. Gochujang improved the disease activity index (DAI), colon weight/length ratio, and colon histomorphology, with outcomes similar to results of mesalamine administration. Moreover, Gochujang decreased the serum levels of IL-1β and IL-6 and inhibited TNF-α, IL-6, and IL-1β mRNA expression in the colon. Gochujang downregulated the expression of iNOS and COX-2 and decreased the activation of NF-κB in the colon. Gochujang induced significant modulation in gut microbiota by significantly increasing the number of Akkermansia muciniphila while decreasing the numbers of Enterococcus faecalis and Staphylococcus sciuri. However, compared with the DSS group, the salt group did not significantly change the symptoms of colitis or cytokine levels in serum and colon. Moreover, the salt group significantly decreased the gut microflora diversity. Gochujang mitigated DSS-induced colitis in rats by modulating inflammatory factors and the composition of gut microflora, unlike the intake of salt alone.


The molecular mechanisms in prenatal drug exposure-induced fetal programmed adult cardiovascular disease.
The "developmental origins of health and disease" (DOHaD) hypothesis posits that early-life environmental exposures have a lasting impact on individual's health and permanently shape growth, structure, and metabolism. This reprogramming, which results from fetal stress, is believed to contribute to the development of adulthood cardiovascular diseases such as hypertension, coronary artery disease, heart failure, and increased susceptibility to ischemic injuries. Recent studies have shown that prenatal exposure to drugs, such as glucocorticoids, antibiotics, antidepressants, antiepileptics, and other toxins, increases the risk of adult-onset cardiovascular diseases. In addition, observational and animal experimental studies have demonstrated the association between prenatal drug exposure and the programming of cardiovascular disease in the offspring. The molecular mechanisms underlying these effects are still being explored but are thought to involve metabolism dysregulation. This review summarizes the current evidence on the relationship between prenatal drug exposure and the risk of adult cardiovascular disorders. Additionally, we present the latest insights into the molecular mechanisms that lead to programmed cardiovascular phenotypes after prenatal drug exposure.


Axillary lymph node and early breast cancer diagnostics. A case report.
Understanding of the anatomy of the axillary lymph nodes is important in diagnostic and treatment procedures for breast cancer. An interesting case is presented here of breast cancer without a breast tumour. The first symptom of the disease was lymphadenopathy of the axillary region. This kind of case is extremely rare in clinical practise (one case per 1-5 years) and constitutes a great problem for specialists, since in many cases the primary neoplasm source is unknown. The anatomical and clinical implications of such a situation are discussed.


Resistance to deformation of axial structures in living guinea-pig spermatozoa.
Rotation of living guinea-pig spermatozoa can be effected by drawing the shaft of a long microneedle of diameter 0.5 to 1.0 micro across the tail; the special characteristics of this rotation demonstrated in the tail a polygonal structure and high resistance of the peripheral fibrils to deformation by pressure of the microneedle.


The Effect of Recombinant Human Erythropoietin on Bacterial Growth: A Dual-Edged Sword.
Hypererythropoietinemia is associated with common diseases like non-uremic anaemia where infection burden is high. Erythropoietin (EPO) is also given as therapy for anaemia associated with chronic kidney disease and cancer and in those who are at a higher risk of infections. EPO is known to have an effect on macrophages by which it helps in the growth of some intracellular pathogens. However, its direct role on bacterial growth is currently unknown. Here, we investigated the direct effect of recombinant human erythropoietin (rhuEPO) on the growth of pathogenic Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. In silico experiments were designed to gain insight into the mechanisms. We found that 30 IU/L rhuEPO promoted the growth of E. coli and S. aureus and inhibited the growth of P. aeruginosa. In silico observations suggest that bacterial cell surface proteins may interact with the EPO and may cause the observed effects. It appears that some pathogens can explore EPO to proliferate and growth of others are inhibited by the same. The consequence of such observation is a matter of widespread concern for future research.


A review of ureteral injuries after external trauma.
Ureteral trauma is rare, accounting for less than 1% of all urologic traumas. However, a missed ureteral injury can result in significant morbidity and mortality. The purpose of this article is to review the literature since 1961 with the primary objective to present the largest medical literature review, to date, regarding ureteral trauma. Several anatomic and physiologic considerations are paramount regarding ureteral injuries management. Eighty-one articles pertaining to traumatic ureteral injuries were reviewed. Data from these studies were compiled and analyzed. The majority of the study population was young males. The proximal ureter was the most frequently injured portion. Associated injuries were present in 90.4% of patients. Admission urinalysis demonstrated hematuria in only 44.4% patients. Intravenous ureterogram (IVU) failed to diagnose ureteral injuries either upon admission or in the operating room in 42.8% of cases. Ureteroureterostomy, with or without indwelling stent, was the surgical procedure of choice for both trauma surgeons and urologists (59%). Complications occurred in 36.2% of cases. The mortality rate was 17%. The mechanism for ureteral injuries in adults is more commonly penetrating than blunt. The upper third of the ureter is more often injured than the middle and lower thirds. Associated injuries are frequently present. CT scan and retrograde pyelography accurately identify ureteral injuries when performed together. Ureteroureterostomy, with or without indwelling stent, is the surgical procedure of choice of both trauma surgeons and urologists alike. Delay in diagnosis is correlated with a poor prognosis.


GSTP1 I105V polymorphism and susceptibility to colorectal cancer in Kashmiri population.
The glutathione S-transferase (GST) enzyme encoded by the GSTP1 gene is one of the critical enzymes involved in detoxification of carcinogens. The substitution of isoleucine to valine residue at position 105 of the GSTP1 protein results in decreased enzyme activity and hence less capability of effective detoxification. Hence, we investigated the role of GSTP1 I105V polymorphism in modulating the risk of colorectal cancer (CRC) associated in a Kashmiri population. We designed a case-control study in which 86 CRC cases were studied for GSTP1 I105V polymorphism against 160 controls taken from the general population employing the polymerase chain reaction-restriction length fragment polymorphism technique. There was no significant association between GSTP1 I105V genotypes and the disease, but the Val/Val genotype was associated with an increased risk with some clinicopathological parameters (odds ratio=1.5; 95% confidence interval=0.55-4.57). This study suggests that the GSTP1 I105V polymorphism may modulate CRC risk in the Kashmiri population.


Inter-relationships between the secretory dynamics of thyrotrophin-releasing hormone, thyrotrophin and prolactin in periovulatory mares: effect of hypothyroidism.
We used our nonsurgical technique for collecting pituitary venous blood to relate the dynamics of thyrotrophin-releasing hormone (TRH) secretion to the secretion patterns of both prolactin and thyrotrophin in periovulatory mares, either euthyroid (n = 5) or made hypothyroid by treatment with propyl-thiouracil (n = 5). Pituitary venous blood was collected continuously and divided into 1-min aliquots for 4 h. To test the effect of dopamine on the relationship between secretion patterns, sulpiride, a selective D2 receptor antagonist, was given i.m. after 2 h of sampling. Thorough testing of the model and blood collection procedure revealed no sites of TRH loss. Hypothyroidism increased the mean secretion rates of TRH (P = 0.04) and thyrotrophin (P < 0.0001) but not prolactin. Sulpiride increased prolactin secretion rates in hypothyroid (P < 0.0001) and control (P = 0.007) mares, but did not alter TRH or thyrotrophin secretion rates. In both groups of mares, all three hormones were secreted episodically but not rhythmically. In both groups, the secretion pattern of TRH was almost always significantly related to that of thyrotrophin, as assessed by cross correlation and cross approximate entropy (ApEn) analysis. However, the degree of linear correlation was weak, with only 14% (hypothyroid) or 8% (controls) of the variation in thyrotrophin secretion rates attributable to TRH. Prolactin and TRH secretion patterns before sulpiride were coupled on cross ApEn analysis in both groups, and the minute-to-minute secretion rates of the two hormones were correlated in four hypothyroid and three euthyroid mares. Overall, the small, but significant, degree of association between TRH and prolactin was similar to that between TRH and thyrotrophin. In hypothyroid mares, sulpiride increased (P = 0.02) the synchrony between TRH and prolactin patterns. We conclude that in horses: (i) little TRH degradation occurs during passage through the pituitary or in blood after 1 h at 37 degrees C; (ii) TRH is not the major factor controlling minute-to-minute fluctuations in either thyrotrophin or prolactin; and (iii) reducing two strongly inhibitory inputs (i.e. dopamine and thyroid hormones) may magnify the stimulatory effect of TRH on prolactin secretion.


Hyperbolicity of exact hydrodynamics for three-dimensional linearized Grad's equations.
We extend to the three-dimensional situation a recent proof of hyperbolicity of the exact (to all orders in Knudsen number) linear hydrodynamics obtained from Grad's moment system [M. Colangeli, I. Karlin, M. Kröger, Phys. Rev. E 75, 051204 (2007)]. Proof of an H theorem is also presented.


A new class of 2-(4-cyanophenyl amino)-4-(6-bromo-4-quinolinyloxy)-6-piperazinyl (piperidinyl)-1,3,5-triazine analogues with antimicrobial/antimycobacterial activity.
This study presents the synthesis and in vitro pharmacological evaluations of novel 2-(4-cyanophenyl amino)-4-(6-bromo-4-quinolinyloxy)-6-piperazinyl (piperidinyl)-1,3,5-triazines. The title compounds were assayed for their in vitro antimicrobial activity against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Shigella flexneria) and four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus clavatus, Candida albicans) using paper disc diffusion and agar streak dilution method as well as against Mycobacterium tuberculosis H37Rv strain using BACTEC MGIT and Lowenstein-Jensen MIC method. The bioassay results indicate that nine compounds namely 5d, 5h, 5n, 5p, 5q, 5r, 5s, 5t and 5u could be considered as possible potential agents with dual antimicrobial and antimycobacterial activities. The structures of the compounds were elucidated with the aid of IR, (1)H NMR, (13)C NMR, (19)F NMR spectroscopy and CHN analysis.


Glycemic and urinary volume responses in diabetic mellitus rats treated with Solanum lycocarpum.
Dietary fiber performs important functions in diabetes mellitus control and treatment. In this study, we evaluate the reduction in plasma glucose after the treatment of diabetic rats with high-fiber Solanum lycocarpum flour. We found that serum glucose, water and food intake, urine excretion, and urine sodium concentration were reduced in S. lycocarpum flour-treated diabetic rats (TDRs), compared with diabetic control rats (DCRs). In addition, TDRs did not show signs of kidney hypertrophy, unlike those in the DCR group. These results suggest that the use of S. lycocarpum flour can be an effective support in diabetes mellitus treatment.


Ginkgo biloba Extract Stimulates Adipogenesis in 3T3-L1 Preadipocytes.
Smaller adipocytes are related to the reversal of metabolic disorders, suggesting that molecules that can act in the adipogenesis pathway are of great interest. The objective of this study was to investigate the effect of Ginkgo biloba extract (GbE) in modulating the differentiation in preadipocytes. 3T3-L1 preadipocytes were differentiated for 7 days into adipocytes without (control group) and with GbE at 1.0 mg/mL. Lipid content and gene expression were analyzed on day 7 (D7) by Oil Red O staining and PCR Array Gene Expression. Western blotting analysis of the key adipogenesis markers was evaluated during the differentiation process at days 3 (D3), 5 (D5), and 7 (D7). GbE increased lipid content and raised the gene expression of the main adipogenesis markers. Key proteins of the differentiation process were modulated by GbE, since C/EBPβ levels were decreased, while C/EBPα levels were increased at D7. Regarding the mature adipocytes' markers, GbE enhanced the levels of both FABP4 at D5, and perilipin at D3 and D5. In summary, the present findings showed that GbE modulated the adipogenesis pathway suggesting that the treatment could accelerate the preadipocyte maturation, stimulating the expression of mature adipocyte proteins earlier than expected.


Genome-wide mutant profiling predicts the mechanism of a Lipid II binding antibiotic.
Identifying targets of antibacterial compounds remains a challenging step in the development of antibiotics. We have developed a two-pronged functional genomics approach to predict mechanism of action that uses mutant fitness data from antibiotic-treated transposon libraries containing both upregulation and inactivation mutants. We treated a Staphylococcus aureus transposon library containing 690,000 unique insertions with 32 antibiotics. Upregulation signatures identified from directional biases in insertions revealed known molecular targets and resistance mechanisms for the majority of these. Because single-gene upregulation does not always confer resistance, we used a complementary machine-learning approach to predict the mechanism from inactivation mutant fitness profiles. This approach suggested the cell wall precursor Lipid II as the molecular target of the lysocins, a mechanism we have confirmed. We conclude that docking to membrane-anchored Lipid II precedes the selective bacteriolysis that distinguishes these lytic natural products, showing the utility of our approach for nominating the antibiotic mechanism of action.


Patient personality and outcome in short-term psychodynamic psychotherapy.
The current study examines pretherapy patient personality characteristics that may be related to outcome in Short-Term Psychodynamic Psychotherapy. The prognostic ability of the Capacity for Dynamic Process Scale (CDPS; Thackrey et al., A Collection of Psychological Scales. 1993:57-63) was examined in a sample of 71 outpatient adults seeking treatment at a university-based community clinic. The relationship of CDPS to various outcome variables, including both patient and clinician perspectives, were investigated. A Principal Components Factor Analysis of the items comprising the CDPS was used to identify salient item clusters representing the insight, affective, or relational capacities of patients. Results indicated that the CDPS Total score was positively correlated to several of the outcome measures, but not at a level of significance. Certain CDPS items, and to a greater extent items composing the Insight subscale, demonstrated significant positive relationships to a number of patient and clinician rated outcome measures. Results from the study will be discussed in regard to their applied clinical implications.


Clinical-practice recommendations for the management of bowel obstruction in patients with end-stage cancer.
The paper highlights a series of questions that doctors need to consider when faced with end-stage cancer patients with bowel obstruction: Is the patient fit for surgery? Is there a place for stenting? Is it necessary to use a venting nasogastric tube (NGT) in inoperable patients? What drugs are indicated for symptom control, what is the proper route for their administration and which can be administered in association? When should a venting gastrostomy be considered? What is the role of total parenteral nutrition (TPN) and parenteral hydration (PH)? A working group was established to review issues relating to bowel obstruction in end-stage cancer and to make recommendations for management. A steering group was established by the (multidisciplinary) Board of Directors of the European Association for Palliative Care (EAPC) to select members of the expert panel, who were required to have specific clinical and research interests relating to the topic and to have published significant papers on advanced cancer patients in the last 5 years, or to have particular clinical expertise that is recognised internationally. The final constitution of this group was approved by the Board of the EAPC. This Working Group was made up of English, French and Italian physicians involved in the field of palliative care for advanced and terminal cancer patients; and of English, American and Italian surgeons who also specialized in artificial nutrition (Dr. Bozzetti) and a professor of health economics. We applied a systematic review methodology that showed the relative lack of RCTs in this area and the importance of retrospective and clinical reports from different authors in different countries. The brief was to review published data but also to provide clinical opinion where data were lacking. The recommendations reflect specialist clinical practice in the countries represented. Each member of the group was allocated a specific question and briefed to review the literature and produce a position paper on the indications, advantages and disadvantages of each symptomatic treatment. The position papers were circulated and then debated at a meeting held in Athens and attended by all panel members. The group reviewed all the available data, discussed the evidence and discussed what practical recommendations could be derived from it. An initial outline of the results of the review and recommendations was produced. Where there were gaps in the evidence, consensus was achieved by debate. Only unanimous conclusions have been incorporated. Subsequently the recommendations were drawn together by Carla Ripamonti (Chairperson) and Robert Twycross (Co-Chair) and refined with input from all panel members. The recommendations have been endorsed by the Board of Directors of the EAPC. It was concluded that surgery should not be undertaken routinely in patients with poor prognostic criteria, such as intra-abdominal carcinomatosis, poor performance status and massive ascites. A nasogastric tube should be used only as a temporary measure. Medical measures such as analgesics, anti-secretory drugs and anti-emetics should be used alone or in combination to relieve symptoms. A venting gastrostomy should be considered if drugs fail to reduce vomiting to an acceptable level. TPN should be considered only for patients who may die of starvation rather than from tumour spread. PH is sometimes indicated to correct nausea, whereas regular mouth care is the treatment of choice for dry mouth. A collaborative approach involving both surgeons and physicians can offer patients an individualized and appropriate symptom management plan.


Thermoelectric clathrates of type I.
Thermoelectric clathrates hold significant promise for high temperature applications with zT values exceeding 1.3. The inorganic clathrates have been shown to be both chemically and thermally stable at high temperatures, and high performance can be obtained from both single crystals and processed powders. The clathrates also show excellent compatibility factors in segmented module applications. For a materials chemist it is furthermore of great importance that the clathrates exhibit a very rich chemistry with the ability for substitution of many different elements. This allows delicate tuning of both the crystal structure as well as the physical properties. With all these assets, it is not surprising that clathrates have been intensely investigated in the thermoelectric community during the past decade. The present perspective provides a review of the many studies concerned with the synthesis, crystal structure and thermoelectric properties of clathrates with emphasis on the type I clathrate.


Biochemistry of anxiety.
The identification of a biochemical (cellular, molecular) basis of anxiety has not only a heuristic value but also considerable consequences for any kind of prophylaxis and therapy of anxiety. An abnormally high activity of noradrenergic and/or serotoninergic neuronal pathways, all originating in the lower brainstem has been proposed by various authors to be critical for the activation of neuronal networks generating anxiety. Recent progress in the understanding of the mechanism of action of anxiolytic drugs and of a variety of anxiogenic agents suggests the possibility that an abnormal neuronal activity of the nonconvulsive type in the limbic system generates the emotion of anxiety and the accompanying behavioral, autonomic and motor symptoms. A central role is suggested for gamma-aminobutyric acid (GABA), which normally prevents those types of neurones possessing the inherent properties for paroxysmal activity to respond with epileptiform activity to normal or excessive stimuli. The GABA receptor/chloride channel complex with its regulatory sites may be the site of a primary biochemical functional lesion.


[Gastric stromal tumor. Case report].
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastro intestinal tract and express the c-kit proto-oncogene protein (CD-117). We report herein a case of a 58 years old male with upper abdominal pain and anaemia. Preoperative endoscopic and barium meal exams showed a submucosal tumor in the gastric fornix. Endoscopic biopsy revealed spindle-shaped cells with elongated nuclei specific of GIST. We performed a stapled resection of the gastric fornix associated with Hiss angle reconstruction. Postoperative histologic exam revealed the same spindle-shape cells characteristic of GIST with 2-5 mitosis/50HPF. Almost all of the cells showed immunoreactivity for c-kit, CD-34 and a Ki-67 labeling index of 30%. Postoperative course was non eventful and after 3 month the patient has no recurrence. GIST are rare gastric tumors and are usually associated with bleeding and abdominal pain. The preoperative diagnosis is usually established by endoscopy with biopsy or endoscopic ultrasonography fine needle aspiration and barium meal exam. Only immunoreactivity is able to differentiate GIST from other mesenchymal tumors. Surgical resection is a safe and effective treatment. The chemotherapy with tyrosine kinases competitive inhibitors (e.g. imatinib mesylate) is also recommended.


Fatty acid-releasing activities in Sinorhizobium meliloti include unusual diacylglycerol lipase.
Phospholipids are well known for their membrane-forming properties and thereby delimit any cell from the exterior world. In addition, membrane phospholipids can act as precursors for signals and other biomolecules during their turnover. Little is known about phospholipid signalling, turnover and remodelling in bacteria. Recently, we showed that a FadD-deficient mutant of Sinorhizobium meliloti, unable to convert free fatty acids to their coenzyme A derivatives, accumulates free fatty acids during the stationary phase of growth. Enzymatic activities responsible for the generation of these free fatty acids were unknown in rhizobia. Searching the genome of S. meliloti, we identified a potential lysophospholipase (SMc04041) and two predicted patatin-like phospholipases A (SMc00930, SMc01003). Although SMc00930 as well as SMc01003 contribute to the release of free fatty acids in S. meliloti, neither one can use phospholipids as substrates. Here we show that SMc01003 converts diacylglycerol to monoacylglycerol and a fatty acid, and that monoacylglycerol can be further degraded by SMc01003 to another fatty acid and glycerol. A SMc01003-deficient mutant of S. meliloti transiently accumulates diacylglycerol, suggesting that SMc01003 also acts as diacylglycerol lipase (DglA) in its native background. Expression of the DglA lipase in Escherichia coli causes lysis of cells in stationary phase of growth.


Effectiveness of different emulsifiers for neem oil against the western flower thrips (Thysanoptera, Thripidae) and the warehouse moth (Lepidoptera, Pyralidae).
The neem tree produces highly specified acting insecticides mainly in its seeds. By pressurizing or extracting the seeds an insecticide oil can be manufactured. For successful application emulsifiers are needed to render the oil soluble in water. The heavy oil has to be stable in emulsion, but on the other hand the surfactant should not reduce the ecological property of the neem oil. The emulsifiers Lutensol TO10, Emulan ELP, Rimulgan and Tween 80 and for comparison the formulation NeemAzal-T/S were tested in their emulsion stability, as well as in their insecticidal effects towards two different insect pests: The western flower thrips Frankliniella occidentalis and the ware house moth Ephestia elutella. The emulsifiers were applied purely, and in different contents mixed in neem oil. Data showed significant differences of mortality and development on the tested pests. Lutensol TO10 and Emulan ELP caused spontaneous mortality on the western flower thrips and an additive efficacy when mixed with neem oil. Rimulgan led to mortality of the larvae of the warehouse moth. NeemAzal showed in both bioassays the highest efficacy of 95% mortality.


Mechanical, Microstructural and Drying Shrinkage Properties of NaOH-Pretreated Crumb Rubber Concrete: RSM-Based Modeling and Optimization.
One of the primary causes of the low mechanical properties of rubberized concrete is the weak bond between crumb rubber (CR) and hardened cement paste. Many CR pretreatment techniques have been researched in an attempt to mitigate this problem. The NaOH pretreatment method is one of the most widely used, although the reported results are inconsistent due to the absence of standardized NaOH pretreatment concentrations and CR replacement levels. This study aims to develop models for predicting the mechanical and shrinkage properties of NaOH-pretreated CR concrete (NaOH-CRC) and conduct multi-objective optimization using response surface methodology (RSM). The RSM generated experimental runs using three levels (0, 5, and 10%) of both NaOH pretreatment concentration and the CR replacement level of fine aggregate by volume as the input factors. At 28 days, the concrete's compressive, flexural, and tensile strengths (CS, FS, and TS), as well as its drying shrinkage (S), were evaluated as the responses. The results revealed that higher CR replacements led to lower mechanical strengths and higher shrinkage. However, the strength loss and the shrinkage significantly reduced by 22%, 44%, 43%, and 60% for CS, FS, TS, and S, respectively, after the pretreatment. Using field-emission scanning electron microscopy (FESEM), the microstructural investigation indicated a significantly reduced interfacial transition zone (ITZ) with increasing NaOH pretreatment. The developed RSM models were evaluated using ANOVA and found to have high R2 values ranging from 78.7% to 98%. The optimization produced NaOH and CR levels of 10% and 2%, respectively, with high desirability of 71.4%.


[Morphometric analysis of regression of breast cancer after radiotherapy and thermoradiotherapy].
A study was made of 50 infiltrating breast carcinomas, stages II-III, treated with a combined method with or without local UHF-hyperthermia. The object of investigation were cytological and histological specimens, histotopographic tumor slices. Methods of mathematical analysis of correlations between tumor tissue regression and parameters of parenchymal differentiation in cytological specimens and an area of tumor nodes were employed. Tumor tissue regression and differentiation of cell elements in cytological specimens showed correlation in the course of combined treatment on the basis of radiotherapy. Insignificant correlation was revealed between a volumetric density of the tumor parenchyma, preserved after combined treatment with UHF-hyperthermia, and parameters of cell differentiation in cytological specimens. Significantly positive correlation was found between an area of tumor nodes and an area of necrotic foci, developing in them after thermoradiotherapy.


The P5abc peripheral element facilitates preorganization of the tetrahymena group I ribozyme for catalysis.
Phylogenetic comparisons and site-directed mutagenesis indicate that group I introns are composed of a catalytic core that is universally conserved and peripheral elements that are conserved only within intron subclasses. Despite this low overall conservation, peripheral elements are essential for efficient splicing of their parent introns. We have undertaken an in-depth structure-function analysis to investigate the role of one of these elements, P5abc, using the well-characterized ribozyme derived from the Tetrahymena group I intron. Structural comparisons using solution-based free radical cleavage revealed that a ribozyme lacking P5abc (E(DeltaP5abc)) and E(DeltaP5abc) with P5abc added in trans (E(DeltaP5abc).P5abc) adopt a similar global tertiary structure at Mg(2+) concentrations greater than 20 mM [Doherty, E. A., et al. (1999) Biochemistry 38, 2982-90]. However, free E(DeltaP5abc) is greatly compromised in overall oligonucleotide cleavage activity, even at Mg(2+) concentrations as high as 100 mM. Further characterization of E(DeltaP5abc) via DMS modification revealed local structural differences at several positions in the conserved core that cluster around the substrate binding sites. Kinetic and thermodynamic dissection of individual reaction steps identified defects in binding of both substrates to E(DeltaP5abc), with > or =25-fold weaker binding of a guanosine nucleophile and > or =350-fold weaker docking of the oligonucleotide substrate into its tertiary interactions with the ribozyme core. These defects in binding of the substrates account for essentially all of the 10(4)-fold decrease in overall activity of the deletion mutant. Together, the structural and functional observations suggest that the P5abc peripheral element not only provides stability but also positions active site residues through indirect interactions, thereby preferentially stabilizing the active ribozyme structure relative to alternative less active states. This is consistent with the view that peripheral elements engage in a network of mutually reinforcing interactions that together ensure cooperative folding of the ribozyme to its active structure.


Predicting when precipitation-driven synthesis is feasible: application to biocatalysis.
Precipitation-driven synthesis offers the possibility of obtaining high reaction yields using very low volume reactors and is finding increasing applications in biocatalysis. Here, a model that allows straightforward prediction of when such a precipitation-driven reaction will be thermodynamically feasible is presented. This requires comparison of the equilibrium constant, Keq, with the saturated mass action ratio, Zsat, defined as the ratio of product solubilities to reactant solubilities. A hypothetical thermodynamic cycle that can be used to accurately predict Zsat, in water is described. The cycle involves three main processes: fusion of a solid to a supercooled liquid, ideal mixing of the liquid with octanol, and partitioning from octanol to water. To obtain the saturated mass action ratio using this cycle, only the melting points of the reactants and products, and in certain cases the pKa of ionisable groups, are required as input parameters. The model was tested on a range of enzyme-catalysed peptide syntheses from the literature and found to predict accurately when precipitation-driven reaction was possible. The methodology employed is quite general and the model is therefore expected to be applicable to a wide range of other (bio)-catalysed reactions.


Modulation of the sympathetic nervous system in youngsters by vitamin-D supplementation.
The level of circulating vitamin D is known to be associated with the ejection fraction in heart failure patients and studies in rats have shown that vitamin D depletion leads to increased levels of circulating norepinephrine and decreased atrial contractility. We elucidated the effects of vitamin D supplementation on the autonomous nervous system in healthy youngsters. Thirty healthy subjects aged 18-25 years were recruited based on their serum 25-hydroxyvitamin D (25[OH]D): 15 vitamin D insufficient (25[OH]D < 50 nmol/L) and 15 vitamin D sufficient (25[OH]D > 80 nmol/L) subjects. Both groups had vitamin D supplementation (30 microg/day) and were tested at baseline and after 30, 90, and 180 days. At each visit the serum 25-hydroxyvitamin D was measured and the head-up tilt test performed. Serum 25[OH]D remained stable in the vitamin D sufficient group, while the insufficient group had a significant increase (32.0-64.5 nmol/L), P < 0.0001. Despite the increase, the insufficient group did not reach the level of the vitamin D sufficient group within the 6 months observational period (96.1 vs 64.5 nmol/L), P < 0.01. Serum norepinephrine at baseline was higher in the insufficient group (mean = 1.61 nmol/L) than in the vitamin D sufficient group (mean = 0.94 nmol/L), P < 0.01, whereas the response to tilt was lower in the insufficient group (mean = 0.69 nmol/L) compared to the sufficient group (mean = 1.17 nmol/L), P < 0.01. The heart rate at rest was higher in the insufficient group (mean = 67.7 bpm) than in the vitamin D sufficient group (mean = 56.6 bpm), P < 0.01, for the three first visits. At the last visit no difference was found. The systolic and diastolic blood pressure differed between the groups after a month, with higher pressures in the insufficient group than in the sufficient group. Vitamin D supplementation modulates the sympathetic nervous system in healthy youngsters with low serum vitamin D. The observation might lead to a greater focus on possible prevention of cardiac disease later on in life by vitamin D supplementation early in life.


Thermal challenge alters the transcriptional profile of the breast muscle in turkey poults.
Extremes in temperature represent environmental stressors that impact the well-being and economic value of poultry. As homeotherms, young poultry with immature thermoregulatory systems are especially susceptible to thermal extremes. Genetic variation and differences in gene expression resulting from selection for production traits, likely contribute to thermal stress response. This study was designed to investigate in vivo transcriptional changes in the breast muscle of young turkey poults from an unselected randombred line and one selected for 16 wk body weight under hot and cold thermal challenge. Newly hatched turkey poults were brooded for 3 d at one of 3 temperatures: control (35°C), cold (31°C), or hot (39°C). Samples of the pectoralis major were harvested and subjected to deep RNA sequencing. Significant differential gene expression was observed in both growth-selected and randombred birds at both temperature extremes when compared to control-brooded poults. Growth-selected birds responded to thermal stress through changes in genes predicted to have downstream transcriptional effects and that would result in reduced muscle growth. Slower growing randombred birds responded to thermal stress through modulation of lipid-related genes, suggesting reduction in lipid storage, transport, and synthesis, consistent with changes in energy metabolism required to maintain body temperature.


Calcium in epithelial cell contraction.
Epithelial morphogenesis in many organs involves asymmetric microfilament-mediated cellular contractions. Similar contractions, in terms of ultrastructure and cytochalasin B sensitivity, can be induced in the carcinoma cell line C-4II in culture. This line was used to compare total intracellular calcium levels ([Ca]i) in contracted monolayer fragments and in control cultures, and to determine whether epithelial cell contraction depends on influx of extracellular Ca. [Ca]i, defined as Ca not displaceable by lanthanum, was measured by atomic absorption spectrophotometry. Degrees of contraction were determined from shape changes of monolayer fragments. Detachment from the growth surface initiated cellular contractions and caused an immediate increase in [Ca]i, from 1.0 to 4.0-5.0 micrograms Ca/mg protein in early confluent cultures, and from 0.3 to 1.0-2.0 micrograms Ca/mg protein in crowded cultures. This increase was followed by a gradual decline in [Ca]i, though Ca levels remained higher than in controls and contraction progressed for 30 min. Contraction was inhibited completely by cold (7 degrees C) and by Ca-free medium, and in a dose-dependent manner by papaverine (2.5 x 10(-6) M-2.5 x 10(-4) M), lanthanum (1.0 x 10(-6) M-1.0 x 10(-4) M); and D-600 (1.0-2.0 x 10(-4) M). The Ca ionophore A23187 had no effect at 5.0 x 10(-6) M and was inhibitory at higher concentrations. The results provided direct evidence for increased [Ca]i in contracting epithelial cells, and suggest that Ca influx is required for such contraction to take place.


Comparative Genomic Characterization of Relaxin Peptide Family in Cattle and Buffalo.
Relaxin family peptides significantly regulate reproduction, nutrient metabolism, and immune response in mammals. The present study aimed to identify and characterize the relaxin family peptides in cattle and buffalo at the genome level. The genomic and proteomic sequences of cattle, buffalo, goat, sheep, horse, and camel were accessed through the NCBI database, and BLAST was performed. We identified four relaxin peptides genes (RLN3, INSL3, INSL5, and INSL6) in Bos taurus, whereas three relaxin genes (RLN3, INSL3, and INSL6) in Bubalus bubalis. Evolutionary analysis revealed the conserved nature of relaxin family peptides in buffalo and cattle. Physicochemical properties revealed that relaxin proteins were thermostable, hydrophilic, and basic peptides except for INSL5 which was an acidic peptide. Three nonsynonymous mutations (two in RLN3 at positions A16 > T and P29 > A, and one in INSL6 at position R32 > Q) in Bos taurus, whereas two nonsynonymous mutations (one in RLN3 at positions G105 > w and one in INSL3 at position G22 > R) in Bubalus bubalis, were identified. INSL3 had one indel (insertion) at position 55 in Bos taurus. Gene duplication analysis revealed predominantly segmental duplications (INSL5/RLN3 and INSL6/INSL3 gene pairs) that helped expand this gene family, whereas Bubalus bubalis showed primarily tandem duplication (INSL3/RLN3). Our study concluded that relaxin family peptides remained conserved during the evolution, and gene duplications might help to adapt and enrich specific functions like reproduction, nutrient metabolism, and immune response. Further, the nonsynonymous mutations identified potentially affect these functions in buffalo.


Complications of peripherally inserted central venous catheters in neonates: Lesson learned over 2 years in a tertiary care centre in India.
The objective of this study was to assess the complications of peripherally inserted central venous catheters (PICC) in neonates admitted to neonatal surgical intensive care unit (NSICU). Retrospective analysis of 237 neonates admitted to NSICU from January 2010 to December 2011 was done. Mean age at presentation was 5.8 days and mean weight was 1.94 kg. Mean number of attempts was 1.14, mean duration of insertion 8.4 min and mean duration of patency of catheter 3.14 days. Most common site of catheter insertion was upper extremity (basilic followed by cephalic). Overall complications were seen in 47 (23%) cases. Infectious complications were seen in 22 (10.7%) and non-infectious in 25 (12.2%) cases. Significant correlation existed between non-infective complications and insertion site (P = 0.03) and duration of PICC (P = 0.04). Precautions should be taken and position must be confirmed during and after PICC insertion to avoid undue complications.


Modeling light adaptation in circadian clock: prediction of the response that stabilizes entrainment.
Periods of biological clocks are close to but often different from the rotation period of the earth. Thus, the clocks of organisms must be adjusted to synchronize with day-night cycles. The primary signal that adjusts the clocks is light. In Neurospora, light transiently up-regulates the expression of specific clock genes. This molecular response to light is called light adaptation. Does light adaptation occur in other organisms? Using published experimental data, we first estimated the time course of the up-regulation rate of gene expression by light. Intriguingly, the estimated up-regulation rate was transient during light period in mice as well as Neurospora. Next, we constructed a computational model to consider how light adaptation had an effect on the entrainment of circadian oscillation to 24-h light-dark cycles. We found that cellular oscillations are more likely to be destabilized without light adaption especially when light intensity is very high. From the present results, we predict that the instability of circadian oscillations under 24-h light-dark cycles can be experimentally observed if light adaptation is altered. We conclude that the functional consequence of light adaptation is to increase the adjustability to 24-h light-dark cycles and then adapt to fluctuating environments in nature.


O(6)-allyl protected deoxyguanosine adducts of polycyclic aromatic hydrocarbons as building blocks for the synthesis of oligonucleotides.
We describe a synthetic strategy for the preparation of oligonucleotides using N(2)-alkylated and O(6)-allyl protected deoxyguanosine phosphoramidite building blocks derived from cis- and trans-opened (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and (+/-)-7beta,8alpha-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and from trans-opened (+/-)-3alpha,4beta-dihydroxy-1alpha,2alpha-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene. The appropriately blocked phosphoramidite building blocks were obtained as mixtures of the cis- and trans-opened diol epoxide adducts upon initial reaction of the diol epoxides with O(6)-allyl-3',5'-di-O-(tert-butyldimethylsilyl)-2'-deoxyguanosine. Key to the present approach is the removal of the O(6)-allyl protecting group utilizing a palladium catalyst prior to release of the constructed oligonucleotide with ammonia from the solid support. The methodology described enables a very convenient access to oligonucleotides containing cis- and trans-N(2)-deoxyguanosine adducts of polycyclic aromatic hydrocarbons in different sequence contexts.


Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus nasal carriage in the West of Iran: a population-based cross-sectional study.
Several reports designate the recent increase in community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) nasal carriage. Because of the scanty information regarding the nasal carriage sate of MRSA in the west of Iran, the purpose of the present study was to determine the frequency of CA-MRSA in Sanandaj city. Swabs collected from anterior nares of 600 volunteers were analyzed for the presence of S. aureus. The isolates were further investigated for methicillin resistance by using the cefoxitin disk diffusion test, followed by PCR-amplification of the mecA gene. SCCmec types and the presence of the Panton-Valentine Leukocidin (pvl) encoding genes were determined through PCR. Finally, the antimicrobial susceptibility of the isolates was determined by the agar diffusion method. Nasal screening identified 181 S. aureus, of which 55 isolates were MRSA. SCCmec types IV and V were detected in MRSA at frequencies of 80 and 20%, respectively. The overall frequency of pvl genes among the MRSA isolates was 14.54%. MRSA isolates were highly susceptible (98.18%) to mupirocin, gentamicin, and fusidic acid. The high prevalence of CA-MRSA carriage in the population could pose a serious public health concern for the region. Additionally, advent of drug-resistant pvl-positive strains demands continuous surveillance on the colonization state of CA-MRSA in order to prevent dissemination of the bacterium in the community.


Isolation of Phenolic Compounds from Raspberry Based on Molecular Imprinting Techniques and Investigation of Their Anti-Alzheimer's Disease Properties.
Alzheimer's disease is the most common neurodegenerative disease, characterized by memory loss and cognitive dysfunction. Raspberry fruits contain polyphenols which have antioxidant and anti-inflammatory properties. In this study, we used molecular imprinting technology to efficiently isolate phenolic components from the raspberry ethyl acetate extracts. Six phenolic components (ellagic acid, tiliroside, kaempferol-3-o-rutoside, gallic acid, ferulic acid and vanillic acid) were identified by UPLC-Q-TOF-MS analysis. Molecular docking was used to predict the anti-inflammatory effects and anti-Alzheimer's potential of these isolated compounds, which showed a good binding ability to diseases and related proteins. However, the binding energy and docking fraction of ellagic acid, tiliroside, and kaempferol-3-o-rutoside were better than those of gallic acid, ferulic acid and vanillic acid. Additionally, by studying the effects of these six phenolic components on the LPS-induced secretion of inflammatory mediators in murine microglial (BV2) cells, it was further demonstrated that they were all capable of inhibiting the secretion of NO, IL-6, TNF-α, and IL-1β to a certain extent. However, ellagic acid, tiliroside, and kaempferol-3-o-rutoside have better inhibitory effects compared to others. The results obtained suggest that the phenolic components extracted from ethyl acetate extracts of raspberry by molecularly imprinted polymers have the potential to inhibit the progression of Alzheimer's disease.


The yeast activator HAP1--a GAL4 family member--binds DNA in a directly repeated orientation.
The yeast transcriptional activator HAP1 contains a DNA-binding domain homologous to GAL4, PPR1, and related factors. By selecting random HAP1-binding sites, we found that HAP1, like GAL4, binds to two CGG triplets. Unlike GAL4, the CGGs in the HAP1 consensus are in a direct and not inverted orientation. Sites with inverted CGGs were not recovered, and mutations converting the direct repeat of CGGs to an inverted repeat greatly reduce HAP1-binding affinity. Also, the 6-bp spacer between the CGGs contains a consensus TA that is positioned asymmetrically. Dimethylsulfate protection patterns on six of these sites show protections and enhancements that also lie in a directly repeated orientation, suggesting that the two HAP1 DNA recognition domains of a HAP1 homodimer are oriented in a directly repeated configuration on the DNA. Moreover, substitution of the HAP1 dimerization domain with that of PPR1, which forms coiled-coils and dimerizes symmetrically, did not diminish the ability of the protein to bind selectively to a direct repeat. This result suggests that one DNA-binding domain of the HAP1 homodimer must be able to swivel 180 degrees relative to the dimerization domain to make specific contacts with the second CGG triplet. Our results present a novel example of domain swiveling in one of the two identical subunits of a homodimer to accommodate specific DNA contacts to both CGG triplets of a direct repeat.


Special evolution of neurohypophysial hormones in cartilaginous fishes: asvatocin and phasvatocin, two oxytocin-like peptides isolated from the spotted dogfish (Scyliorhinus caniculus).
In contrast to most vertebrate species that possess one oxytocin-like hormone and one vasopressin-like hormone, a few groups, such as marsupials or cartilaginous fishes, are endowed with two peptides of either or both types, suggesting possible gene duplications. We have now isolated two oxytocin-like hormones from the pituitary of the spotted dogfish Scyliorhinus caniculus (suborder Galeoidei). Microsequencing as well as chromatographic and pharmacological comparisons with synthetic peptides show that these peptides are [Asn4,Val8]oxytocin (asvatocin) and [Phe3,Asn4,Val8]-oxytocin (phasvatocin). Asvatocin and phasvatocin display oxytocic activity on rat uterus, about 80 and 5 milliunits per nmol, respectively, and virtually no pressor activity on anesthetized rats. They occur in roughly equal molar amounts in the gland; vasotocin is also present in a proportional amount that is lower by about a factor of 20. In addition to the duality, conservative amino acid substitutions are observed in the two oxytocic peptides in positions 4 (Gln-4-->Asn) and 8 (Leu-8-->Val), when compared with oxytocin. Furthermore, replacement of the isoleucine residue found in position 3 of all other oxytocin-like hormones by phenylalanine in phasvatocin is exceptional; it determines a dramatic decrease of the oxytocic activity. Preservation of the C-terminal-amidated nonapeptide pattern in the 12 vertebrate neurohypophysial hormones known to date suggests that both precursors and processing enzymes have coevolved tightly. On the other hand, whereas the great evolutionary stability of the mature hormones (generally observed in vertebrates) suggests a strict messenger-receptor coevolution, the exceptional diversity found in cartilaginous fishes (six oxytocin-like peptides identified out of eight known) might be due to a looseness of selective constraints, perhaps in relationship with their specific urea osmoregulation.


Effects of air pollution on respiratory parameters during the wheat-residue burning in Patiala.
Effects of pollution produced by wheat-residue burning on respiratory parameters of healthy inhabitants were investigated for two consecutive wheat cultivation periods (February-July in 2007 and 2008) at Patiala city of Punjab, India. A total of 51 selected subjects of the age group 13-53 were selected from five sites of Patiala for pulmonary function tests (PFTs), including force vital capacity (FVC), force expiratory volume in one second (FEV(1)), peak expiratory flow (PEF) and force expiratory flow between 25 to 75% of FVC (FEF(25-75%)) using a spirometer. High volume samplers (HVS) and an Andersen cascade impactor were also used to measure the concentration of suspended particulate matter (SPM) and particulate matter (PM) of size less than 10 mum. PFTs show significant decrease and particulate matter shows a significant increase during the burning period of wheat residue. Decrease in FVC and FEV(1) did not recover even after completion of the exhaustive burning period this is a more serious concern then PEF and FEF(25-75%). The results showed that the public exposure to relatively high levels of pollutants during the exhaustive burning period of wheat residue influences the PFTs of even healthy inhabitants.


Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma.
To evaluate the possibility of treatment with antiepidermal growth factor receptor (EGFR) mAb, Cetuximab against esophageal squamous cell carcinoma (SCC), we performed detail analysis of the antibody-dependent cellular cytotoxicity (ADCC) mediated by Cetuximab against esophageal SCC. Esophageal SCC cell lines with various levels of EGFR (n = 8) were evaluated for their Cetuximab-mediated ADCC by (51)Cr-release assay. As a result, Cetuximab was able to induce ADCC against EGFR-expressing esophageal SCC and the activities reflected the degree of EGFR expression on the esophageal SCC. The activities of Cetuximab-mediated ADCC by patients' PBMC were impaired in comparison with those by healthy donors' PBMC. Moreover, the inhibition of transforming growth factor (TGF)-beta could enhance Cetuximab-mediated ADCC against TGF-beta-producing SCC. In conclusion, Cetuximab was able to induce ADCC against EGFR-expressing esophageal SCC. Some modalities aiming at enhancing the Cetuximab-mediated ADCC may be necessary for successful Cetuximab treatment of patients with esophageal SCC.


Wastewater treatment in tsunami affected areas of Thailand by constructed wetlands.
The tsunami of December 2004 destroyed infrastructure in many coastal areas in South-East Asia. In January 2005, the Danish Government gave a tsunami relief grant to Thailand to re-establish the wastewater management services in some of the areas affected by the tsunami. This paper describes the systems which have been built at three locations: (a) Baan Pru Teau: A newly-built township for tsunami victims which was constructed with the contribution of the Thai Red Cross. Conventional septic tanks were installed for the treatment of blackwater from each household and its effluent and grey water (40 m3/day) are collected and treated at a 220 m2 subsurface flow constructed wetland. (b) Koh Phi Phi Don island: A wastewater collection system for the main business and hotel area of the island, a pumping station and a pressure pipe to the treatment facility, a multi-stage constructed wetland system and a system for reuse of treated wastewater. The constructed wetland system (capacity 400 m3/day) consists of vertical flow, horizontal subsurface flow, free water surface flow and pond units. Because the treatment plant is surrounded by resorts, restaurants and shops, the constructed wetland systems are designed with terrains as scenic landscaping. (c) Patong: A 5,000 m2 constructed wetland system has been established to treat polluted water from drainage canals which collect overflow from septic tanks and grey water from residential areas. It is envisaged that these three systems will serve as prototype demonstration systems for appropriate wastewater management in Thailand and other tropical countries.


Time-dependent plasma protein changes in streptozotocin-induced diabetic rats before and after fungal polysaccharide treatments.
Previous studies about protein modulation with chemically induced models of diabetes in animals have yielded conflicting results, in that many investigators have reported different regulation patterns for the same proteins. Therefore, it is reasonable to determine biomarkers for prognosis and diagnosis of diabetes with time profiling for the candidate proteins. In this regard, we examined the influence of hypoglycemic fungal polysaccharides (EPS) on the time-dependent plasma protein alterations in streptozotocin-induced diabetic rats. The 2-DE analysis of rat plasma demonstrated that about 50 proteins from about 900 visualized spots were found to be differentially regulated, of which 20 spots were identified as principal diabetes-associated proteins. The results of time profiling revealed that most of the identified proteins showed significant alterations in a time-dependent manner during 14 days, with notable trends. Nine out of the twenty proteins displayed very similar time profiles between normal healthy and EPS-treated diabetic rats. Interestingly, the altered profiles of several proteins by diabetes induction almost returned to control levels after EPS treatments. In particular, we found a clear distinction in differential expression of oxidative stress proteins (ceruloplasmin and transferrin) and lipid metabolism related proteins (Apo A-I, Apo A-IV, and Apo E) in the STZ-induced diabetic rats. The data presented here have identified and characterized the time-dependent changes in plasma proteins associated with EPS treatment in STZ-induced diabetic rats, thereby leading to the discovery of early-response and late-response biomarkers in diabetic and EPS-treated states.


Relationships among obstructive sleep apnea, anthropometric measures, and neurocognitive functioning in adolescents with severe obesity.
To explore associations between measures of obstructive sleep apnea (OSA) and sleep quality, anthropometrics, and neurocognitive functioning in severely obese adolescents. This was a cross-sectional pilot study performed at an academic medical center in 37 severely obese (body mass index [BMI] >97th percentile) adolescents. Study evaluations included polysomnography, BMI, waist circumference, and standardized neurocognitive tests to assess memory, executive functioning, psychomotor efficiency, academic achievement, and an approximation of full-scale IQ. Outcome data were evaluated categorically, based on clinical criteria for the diagnosis of OSA, and continuously to quantify associations between sleep parameters, anthropometrics, and neurocognitive test results. Sleep fragmentation and poorer sleep quality were associated with reduced psychomotor efficiency, poorer memory recall, and lower scores on standardized academic tests. Having evidence of OSA was associated with lower math scores, but not with other neurocognitive measures. BMI and waist circumference were negatively associated with oxygen saturation. Our pilot study findings suggest that sleep fragmentation and poorer sleep quality have implications for neurocognitive functioning in obese adolescents. The epidemic of childhood obesity has dire implications, not only for increasing cardiometabolic pathology, but also for possibly promoting less readily apparent neurologic alterations associated with poor sleep quality.


What I wish I'd learned as an orthodontic trainee: an online survey of British Orthodontic Society members concerning postgraduate training experiences.
To survey the opinion of recently qualified and established orthodontists on the perceived value of their training and to identify specific areas which which were considered to be deficient, adequately covered or focussed on excessively. Descriptive cross-sectional survey. Online electronic questionnaire. Members of the British Orthodontic Society (BOS). An electronic questionnaire was circulated to members of the BOS focusing on dental education history, and opinions concerning orthodontic teaching generally and specific clinical and non-clinical subjects. Information was also obtained in terms of possible need for improvement, modification or removal of teaching on focused academic and clinical aspects. A total of 217 responses were received from 1080 emailed invitations resulting in a response rate of 20.1%. Respondents were generally satisfied with their training both in relation to theoretical, academic and practical aspects. However, training was regarded as deficient by some respondents in respect of temporary anchorage devices (38%), bonded retainers (6%), experience with lingual appliances (47%), removable aligners (44%), inter-proximal reduction (24%) and adult orthodontics (16%), working with therapists (32%), and NHS contracts (47%) and commissioning (47%). The overall satisfaction of BOS members with postgraduate orthodontic training is generally high, although both recently qualified and established practitioners emphasised the need for better exposure to training in specific practical aspects and practice management within the NHS.


Diastereoselection in the formation of contiguous quaternary carbon stereocenters by the intramolecular Heck reaction.
The second in a series of two papers, this study examines the origins of diastereoselection in the second ring closure of the highly diastereoselective double Heck cyclization of cyclohexenes 1 and 3 that form contiguous quaternary stereocenters. Seven model substrates were synthesized and cyclized to examine the structural features responsible for imparting diastereoselection in the second intramolecular Heck reaction. These studies demonstrate that stereoselection in the formation of the second spirooxindole ring results from the avoidance of steric interactions in the insertion step with the spirooxindole formed in the first Heck cyclization. An axial substituent (carbonyl or arene) is required at the allylic position for high levels of diastereoselection to be realized.


Paracorporeal Lung Devices: Thinking Outside the Box.
Extracorporeal Membrane Oxygenation (ECMO) is a resource intensive, life-preserving support system that has seen ever-expanding clinical indications as technology and collective experience has matured. Clinicians caring for patients who develop pulmonary failure secondary to cardiac failure can find themselves in unique situations where traditional ECMO may not be the ideal clinical solution. Existing paracorporeal ventricular assist device (VAD) technology or unique patient physiologies offer the opportunity for thinking "outside the box." Hybrid ECMO approaches include splicing oxygenators into paracorporeal VAD systems and alternative cannulation strategies to provide a staged approach to transition a patient from ECMO to a VAD. Alternative technologies include the adaptation of ECMO and extracorporeal CO2 removal systems for specific physiologies and pediatric aged patients. This chapter will focus on: (1) hybrid and alternative approaches to extracorporeal support for pulmonary failure, (2) patient selection and, (3) technical considerations of these therapies. By examining the successes and challenges of the relatively select patients treated with these approaches, we hope to spur appropriate research and development to expand the clinical armamentarium of extracorporeal technology.


Utility of the Rome I and Rome II criteria for irritable bowel syndrome in U.S. women.
Using interview data from a large, community-based sample of American women, we assessed the lifetime prevalence of irritable bowel syndrome (IBS) using questions consistent with the Rome II criteria, determined the sensitivity of Rome I and II in women diagnosed with IBS by their community physician, and identified whether there are differences in the patients identified by Rome I versus II. A geographically diverse national probability sample of women diagnosed with IBS was identified and interviewed by telephone screening of a national, random digit dialing sample of households. A parallel national survey of adult females was conducted to determine the lifetime prevalence of IBS in U.S. women. Screening and interviews were conducted by experienced, female interviewers. IBS was defined by variations on the Rome I/II criteria. In the national community sample, lifetime IBS prevalence was 5.4% using Rome II. Full interviews were completed in 1,014 IBS patients. In the IBS sample, Rome I was significantly more sensitive than Rome II (84% vs 49%, p < 0.001). There was 47% agreement between Rome I and II. Of patients with IBS by Rome I, 58% met Rome II. Only 17.7% did not meet either Rome I or II. Rome I was more sensitive than Rome II in this community sample of female IBS patients. Rome I/II do not necessarily identify the same IBS patients. These findings have important implications for clinical research in IBS patients and raise questions about whether the Rome II criteria are sensitive enough to be useful in clinical practice.


Gunshot wounds to the right thoracoabdomen: a prospective study of nonoperative management.
Dissatisified with our unnecessary laparotomy rate in patients with gunshot wounds (GSWs) to the right thoracoabdomen (RTA), a prospective study was designed to test the hypothesis that hemodynamically stable patients without peritonitis could be managed without a surgical procedure. From 1990 through 1993, 13 consecutive patients with a GSW between the right nipple, costal margin, right posterior axillary line, and anterior midline were studied. No patient had or developed more than local wound tenderness. All patients had a right hemothorax treated with a chest tube. Computed tomographic (CT) scanning of the RTA was performed within 8 hours of admission in 12 of the 13 patients, and the following injuries were noted: pulmonary contusion (12), hepatic laceration (seven), spinal cord transection (two), and a renal laceration (one). Follow-up CT scans, 3 to 14 days after injury, in six of the seven patients with hepatic wounds showed partial or complete resolution of the injury in all. In one patient, an associated renal injury was unchanged on the follow-up CT scan. Mean length of hospitalization for the 11 patients who did not have an injury to the spinal cord was 5.1 days (3-8 days). Complications included atelectasis (four), a small persistent pneumothorax (two), and pneumonia (one).(ABSTRACT TRUNCATED AT 250 WORDS)


Novel gene sequences expressed by human melanoma cells identified by molecular subtraction.
Despite the variety of approaches used, only a limited number of tumor-associated antigens have been described for each histological type of tumor. In this report, we present a new strategy involving molecular subtraction to identify novel melanoma-associated gene sequences. Toward this end, 156 complementary DNA clones were isolated with a subtracted melanoma complementary DNA probe (melanoma minus lung carcinoma) after screening 2 x 10(4) independent recombinants of a melanoma expression library by in situ plaque hybridization. These clones were then polymerase chain reaction amplified, screened for duplication, and categorized into 53 discrete genes. By applying poissonian distribution to the numbers of duplicate isolates, we found most of the genes to be rare messages, present at less than 1 copy/200 molecules of mRNA in a typical somatic cell. Messages specific for a type of tissue are usually expressed in this range. The expression of the 53 genes was further studied in human tumor cell lines and normal tissues. Partial sequence data obtained for 20 complementary DNA clones revealed 8 novel human genes. The mRNA transcripts for 5 of the novel genes were identified by Northern blot analysis. Thus, molecular subtraction appears to be applicable for the identification of novel tumor-associated sequences. Some of the potential advantages and limitations of this technology are discussed, including its application to the molecular characterization of immunogenic melanoma-associated antigens.


Product line management.
The application of Product Line Management to the health care industry in the United States is an effort to use a management approach from the business world that aims at implementing, maintaining, and enhancing productivity without compromising quality patient care. Product Line Management is an opportunity for the nurse in management to develop a business acumen that will directly influence patient outcomes. Under this concept the product, is defined, priced, marketed and sold. The result is the ability to secure a competitive edge in the health care marketplace that not only allows us to survive, but to thrive.


Association of interleukin-33 gene polymorphisms with susceptibility to late onset Alzheimer's disease: a meta-analysis.
The association between interleukin-33 (IL-33) gene polymorphisms and late onset Alzheimer's disease (LOAD) remains controversial in previous studies. Thus, a meta-analysis was conducted to assess the association between the IL-33 polymorphisms (rs11792633 and rs7044343) and LOAD susceptibility. Crude odds ratio (OR) and 95% confidence interval (CI) were used to investigate the relationship strength. Sensitivity analysis was performed, and publication bias was estimated by the Begg's and Egger's tests. Overall, six independent studies involving 2,589 patients and 8,414 control samples met our inclusion criteria and were included in this meta-analysis. The results showed that IL-33 rs11792633 polymorphism had statistically significant correlation with a decreased risk of LOAD in heterozygous comparison model (OR =0.64, 95% CI =0.48-0.83), homozygote comparison model (OR =0.83, 95% CI =0.74-0.93), dominant model (OR =0.78, 95% CI =0.67-0.91), recessive model (OR =0.70, 95% CI =0.59-0.84), and allelic model (OR =0.79, 95% CI =0.69-0.91), which were also validated by stratified subgroup analysis. Additionally, there was an apparent association between the IL-33 rs7044343 variant and LOAD risk under four genetic models for overall population (heterozygous comparison model: OR =0.75, 95% CI =0.63-0.89; dominant model: OR =0.83, 95% CI =0.70-0.98; recessive model: OR =0.80, 95% CI =0.68-0.94; allelic model: OR =0.86, 95% CI =0.79-0.94) as well as Caucasian subgroup. In summary, our meta-analysis implicated that IL-33 gene polymorphisms rs11792633 and rs7044343 were significantly associated with the susceptibility of LOAD.


No survival benefit with early incorporation of thoracic radiotherapy using daily fractionation in patients with limited-stage small cell lung cancer undergoing chemoradiotherapy in the modern era: A systematic review and meta-analysis.
When concurrent chemoradiotherapy (CCRT) is administered for limited-stage small cell lung cancer (LS-SCLC), the early incorporation of thoracic radiotherapy (TRT) is generally recommended. However, it is controversial if this approach is really beneficial with most commonly used daily fractionated TRT in the modern era. A systematic literature search was performed using several databases following the PRISMA guidelines from Jan 2000 to Nov 2022. We excluded twice-daily TRT-based studies. The hazard ratio (HR) for survival following late TRT as a primary effect size was pooled from comparisons within individual studies according to the timing of daily fractionated TRT (early vs. late). A total of 10 studies including 10,164 analyzable patients met all inclusion criteria. 'Early' timing usually referred to TRT within 1-2 cycles of concurrent chemotherapy. The pooled results demonstrated that the risk of death was not significantly increased following late TRT compared with early TRT (HR 1.01, 95% CI 0.84-1.20, p = 0.94). All sensitivity analysis and planned subgroup analyses showed similar results. In comparison with early TRT, late TRT did not significantly increase the risk of progression (HR 0.94, 95% CI 0.80-1.11, p = 0.48). Furthermore, late TRT was beneficial in alleviating grade 3 or higher esophagitis (OR 0.42, p = 0.01), but no significant differences was found in pneumonitis (OR 0.62, p = 0.38), and neutropenia (OR 0.57, p = 0.11). No evidence of publication bias was found. This is the first meta-analysis to support the late incorporation of TRT in managing patients with LS-SCLC undergoing daily fractionated CCRT in the modern era. This approach may not compromise survival and can prevent severe acute toxicities. Further prospective studies of the daily fractionated TRT timing are warranted.


The dual roles of a V(III) centre for substrate binding and oxygen atom abstraction; nitrite reduction mediated by a V(III) complex.
A V(iii) complex bearing a tris(thiolato)phoshine derivative mediates the reduction of nitrite without the assistance of external protons or oxophilic substrates. The metal site plays dual roles for nitrite binding and deoxygenation. The reaction is monitored by spectroscopy combined with isotopic labeling experiments. The formed product, a {VNO}4 species, is isolated and characterized.


Results of the pToWin Study: Using the pCONUS Device for the Treatment of Wide-Neck Intracranial Aneurysms.
Coil embolization has become a well-established option for the treatment of intracranial aneurysms. Yet, wide-neck bifurcation aneurysms (WNBAs) remain a challenge. The pCONUS is the first generation of a stent-like implant for the bridging of WNBAs to enable coiling. The pToWin study was a prospective, single-arm, multicenter study conducted to analyze the safety and efficacy of the pCONUS in the treatment of WNBAs. The primary effectiveness endpoint was the rate of adequate occlusion of the aneurysm at 3-6 and 7-12 months. The primary safety endpoint was the occurrence of major ipsilateral stroke or neurological death during the follow-up. A total of 115 patients were included. Aneurysm locations were the middle cerebral artery in 52 (45.2%), the anterior communicating artery in 35 (30.4%), the basilar artery in 23 (20%), the internal carotid artery terminus in three (2.6%), and the pericallosal artery in two (1.7%) patients. Treatment was successfully performed in all but one patient. The morbi-mortality rate was 1.9% and 2.3% at 3-6 and 7-12 months, respectively. Of the aneurysms, 75.0% and 65.6% showed adequate occlusion at 3-6 and 7-12 months, respectively. pCONUS offers a safe and reasonably effective treatment of WNBAs, demonstrated by acceptable adequate aneurysm occlusion and low rates of adverse neurologic events.


Tethered spinal cord following meningomyelocele repair.
Of 16 consecutive patients with tethered spinal cord studied, most had undergone repair of a meningomyelocele. All were evaluated using somatosensory evoked potentials at 6 to 12-month intervals. Other possibilities include tethered filum terminale, lipomeningocele, membrana reuniens, and miscellaneous conditions (diastematomyelia, neurenteric cysts, etc.). Metrizamide myelography with polytomography was superior to gas myelography in showing a low-lying cord, obtuse nerve root angles, and a thin subarachnoid space between the cord and the dorsal meninges cephalad to the tether. Surgery is generally helpful in these patients.


A diminished role for the sarcoplasmic reticulum in newborn myocardial contraction: effects of ryanodine.
Ryanodine, known to reduce Ca2+ release from the sarcoplasmic reticulum (SR), was used in conjunction with the single sucrose gap voltage clamp technique to study excitation-contraction coupling in papillary muscles isolated from newborn and adult rabbits. Ryanodine altered the components of voltage clamp-induced tension in the adult producing a pattern that closely resembled the normal newborn. The phasic component of tension in mature myocardium was markedly and significantly reduced by ryanodine. In addition, ryanodine significantly altered the voltage dependence of this component of tension, suggesting a change in its mechanism of generation. The appearance of a prominent phasic component of tension, absent normally, but produced in the newborn by Ca2+ loading, was also abolished by ryanodine. These results support previous proposals that the phasic component of voltage clamp-induced tension in mammalian myocardium is produced by the release of Ca2+ from the SR. In the newborn, ryanodine caused a significantly smaller decrease in the ratio of phasic to tonic tension than in the adult, suggesting a much less significant role for the SR in excitation-contraction coupling in the younger age group. Although ryanodine had a significant effect on phasic tension, no alteration in the amplitude or voltage dependence of tonic tension, generated by transmembrane Ca2+ influx, could be demonstrated in either newborn or adult heart. This investigation suggests that in newborn myocardium, Ca2+ release from the SR plays a negligible role in excitation-contraction coupling, which depends, rather, on the influx of Ca2+ from the extracellular space.


[Evaluation of collective feeding in a group of school children with mental disability in special educating childcare centres].
The aim of the research was to estimate collective feeding way of girls and boys aged 10-15 years old with mental disability of light and moderate level, the pupils of special educating childcare centres. The assessment was based on 20 decade menus introduced in Educating Childcare Centres in two regional cities of Malopolska in late autumn period (Oct.-Dec.) 2005-2007. The quantity evaluation of decade menus showed over normal energy supply (3223.2 kcal) and non-balanced supply of basic ingredients (protein and fat surplus and shortage of carbohydrates) (suitably: 118.7 g, 113.1 g, 429.8 g). Furthermore, abnormal content of vitamin A (891 microg), shortage of vitamin C (47.3 mg) and standard supply of vitamin E (10.5 mg) and B1 (1.6 mg). Content of iron (14.9 mg) fluctuated around standard supply, but particularly non-beneficial was the relation between calcium and phosphorus.


Dual-Functionalized Mixed Keggin- and Lindqvist-Type Cu24-Based POM@MOF for Visible-Light-Driven H2 and O2 Evolution.
The development of logical visible-light-driven heterogeneous photosystems for water splitting is a subject of new research. As the first example of a noble-metal-free photocatalyst for both H2 and O2 production, a high-nuclear {CuI24(μ3-Cl)8(μ4-Cl)6}-based polyoxometalate (POM)@metal-organic framework (MOF) (ZZULI-1) is rationally designed to serve as a robust dual-functionalized photocatalyst. ZZULI-1 exhibits highly efficient photocatalytic H2 evolution (6614 μmol g-1 h-1) and O2 evolution (1032 μmol g-1 calculated for the first 6 min). The {CuI24(μ3-Cl)8(μ4-Cl)6} clusters and mixed POMs not only work as the active units for H2 and O2 production, respectively, but also improve the effective electron transfer between the photosensitizer and ZZULI-1. The highly stable dual-functionalized ZZULI-1 affords new penetrations into the development of cost-effective high-nuclear cluster-based POM@MOFs for efficient solar-to-fuel generation.


Understanding the mechanisms for COVID-19 vaccine's protection against infection and severe disease.
Multiple COVID-19 vaccines have been approved and employed in the fight against the pandemic. However, these vaccines have limited long-term effectiveness against severe cases and a decreased ability to prevent mild disease. This review discusses the relevant factors influencing the efficacy of the vaccines against mild and severe infection, analyzes the possible underlying mechanisms contributing to the different outcomes in terms of vaccine function and disease progression, and proposes improvements for the next generation of vaccines. The reduced efficacy of the COVID-19 vaccine in the prevention of viral infection is closely related to the emergence of novel SARS-CoV-2 variants and their rapid transmission ability. Fundamentally, the immune responses induced by COVID-19 vaccines cannot effectively halt virus replication in the upper respiratory tract because only a limited number of specific antibodies reach these areas and decrease in concentration over time. However, the established immune response can provide sufficient protection against severe diseases by blocking viral infection of the lower respiratory tract or lung owing to sufficient antibody repertoires and memory responses. Considering this situation, future COVID-19 vaccines should have the potential to replenish the mucosal immune response in the respiratory tract to prevent viral infection.


A nation-wide initiative against venous thromboembolism.
There is a gap between knowledge and recommendations regarding venous thromboembolism (VTE) on the one hand and daily practice on the other. This fact has prompted a Swiss multidisciplinary group consisting of angiologists, haematologists, internists, and emergency medicine and pharmaceutical medicine specialists interested in VTE, the SAMEX group, to set up a series of surveys and studies that give useful insight into the situation in our country. Their projects encompassed prophylactic and therapeutic aspects of VTE, and enrolled over 7000 patients from five academic and 45 non-academic acute care hospitals and fifty-three private practices in Switzerland. This comprehensive Swiss Clinical Study Programme forms the largest database surveying current clinical patterns of VTE management in a representative sample of the Swiss patient population. Overall the programme shows a lack of thromboprophylaxis use in hospitalised at-risk medical patients, particularly in those with cancer, acute heart or respiratory failure and the elderly, as well as under-prescription of extended prophylaxis beyond hospital discharge in patients undergoing major cancer surgery. In regard to VTE treatment, planning of anticoagulation duration, administration of LMWH for cancer-associated thrombosis, and the use of compression therapy for prevention of post-thrombotic syndrome in patients with symptomatic proximal DVT require improvement. In conclusion, this programme highlights insufficient awareness of venous thromboembolic disease in Switzerland, underestimation of its burden and inconsistent application of international consensus statement guidelines regarding prophylaxis and treatment adopted by the Swiss Expert Group.


"It Made Me Not Want to See him…": The Role of Patient-Provider Communication in Influencing Rural-Dwelling Women Veterans' Motivation to Seek Health Care for Managing Chronic Pain.
Despite being high health care utilizers, many women Veterans perceive their pain condition to be poorly understood by their providers, which can be a strong demotivator for seeking care. We set out to understand the priorities rural-dwelling women Veterans have for using health care for their chronic pain, and interviewed participants about their experiences with (and priorities for seeking) health care for their chronic pain. Self-Determination Theory identifies three sources of motivation (autonomy, competence, relatedness), all of which were represented through two themes that reflect rural women Veterans' rationale for decision-making to obtain health care for chronic pain: role of trust and competing priorities. Women described their priorities for chronic pain management in terms of their competing priorities for work, education, and supporting their family, but most expressed a desire to function in their daily life and relationships. Second, women discussed the role of trust in their provider as a source of motivation, and the role of patient-provider communication skills and gender played in establishing trust. Rural women Veterans often discussed core values that stemmed from facets of their identity (e.g. gender, military training, ethnicity) that also influenced their decision-making. Our findings provide insight for how providers may use Motivational Interviewing and discuss chronic pain treatment options so that rural-dwelling women Veterans feel autonomous, competent, and understood in their decision-making about their chronic pain. We also discuss importance of acknowledging the effects of disenfranchising talk and perpetuating gendered stereotypes related to chronic pain and theoretical implications of this work.


Educating pediatric residents about breastfeeding: evaluation of 3 time-efficient teaching strategies.
Previously reported breastfeeding curricula for residents have combined different teaching methods, have focused on knowledge and attitudes, and have been time-intensive. This study aimed to evaluate 3 time-efficient breastfeeding curricula for effectiveness in regard to pediatric residents' knowledge, confidence, and skills in managing a simulated breastfeeding scenario. First-year pediatric residents during their 4-week community hospital newborn nursery rotation were consecutively assigned to 1 of 3 groups. Group 1 shadowed an International Board Certified Lactation Consultant (IBCLC) for 1 hour; group 2 watched a 25-minute case-based breastfeeding DVD; and group 3 observed a 3-hour prenatal parent breastfeeding class (CLS). Residents were assessed by (1) a pretest and posttest evaluating their breastfeeding knowledge and confidence, and (2) a clinical skills scenario managing a breastfeeding standardized patient (SP). Thirty-nine pediatric residents participated in the study (11 in IBCLC, 16 DVD, 12 CLS) over a 1-year period. All groups significantly improved their knowledge scores and confidence in managing breastfeeding problems, with the IBCLC group showing more improvement in knowledge than the other groups (P = .02) and a higher rating of their teaching method (P = .01). All groups performed well on the SP clinical skills scenario, with no significant difference between groups. All 3 teaching methods were time-efficient and produced important gains in knowledge and confidence, with residents in the IBCLC group demonstrating greatest improvement in knowledge and a higher rating of their teaching method. Our study provides support for 3 methods of teaching residents breastfeeding management and demonstrates that IBCLCs are well-received as interprofessional educators.


Protein targeting to the plasma membrane of adult skeletal muscle fiber: an organized mosaic of functional domains.
The plasma membrane of differentiated skeletal muscle fibers comprises the sarcolemma, the transverse (T) tubule network, and the neuromuscular and muscle-tendon junctions. We analyzed the organization of these domains in relation to defined surface markers, beta-dystroglycan, dystrophin, and caveolin-3. These markers were shown to exhibit highly organized arrays along the length of the fiber. Caveolin-3 and beta-dystroglycan/dystrophin showed distinct, but to some extent overlapping, labeling patterns and both markers left transverse tubule openings clear. This labeling pattern revealed microdomains over the entire plasma membrane with the exception of the neuromuscular and muscle-tendon junctions which formed distinct demarcated macrodomains. Our results suggest that the entire plasma membrane of mature muscle comprises a mosaic of T tubule domains together with sareolemmal caveolae and beta-dystroglycan domains. The domains identified with these markers were examined with respect to targeting of viral proteins and other expresseddomain-specific markers. We found that each marker protein was targeted to distinct microdomains. The macrodomains were intensely labeled with all our markers. Replacing the cytoplasmic tail of the vesicular stomatitis virus glycoprotein with that of CD4 resulted in retargeting from one domain to another. The domain-specific protein distribution at the muscle cell surface may be generated by targeting pathways requiring specific sorting information but this trafficking is different from the conventional apical-basolateral division.


Acute percutaneous lactic acid poisoning in a child.
Percutaneous poisoning is quite rare, and in particular, topical lactic acid poisoning is even more so. We report a young girl with lamellar ichthyosis and symptoms of poisoning, with clinical signs of irritability, agitation, myoclonia, and difficulty in walking, accompanied by lactic acidosis as a result of the more frequent than recommended application of emollients containing lactic acid. The clinical symptoms resolved upon discontinuation of the topical treatment. Among the possible causes of metabolic acidosis, health care providers should be aware of the possibility of percutaneous poisoning.