Successful treatment of radiation-induced proctitis pain by blockade of the ganglion impar in an elderly patient with prostate cancer: a case report.
Chronic rectal pain secondary to radiation-induced proctitis is fast-becoming a leading cause of chronic pain, especially for prostate cancer survivors. Currently, many elderly patients resort to increased opioid intake to alleviate the pain. However, this increase in opioid consumption often leads to constipation and further aggravates the anorectal pain, thus leading to a perpetual, vicious cycle. We reasoned that blocking the ganglion impar could attenuate this sympathetically maintained pain, which would lead to a reduction in the consumption of opioids, lessen constipation, and lead to an improvement in the patient's quality of life. Case report. An academic tertiary pain management clinic. The authors report the case of a 73-year-old African American man with a history of prostate cancer who presented to the pain management clinic for evaluation and treatment of his chronic anorectal pain secondary to radiation-induced proctitis. The patient underwent a ganglion impar block, using the transcoccygeal technique, and consequently reported excellent pain relief with little or no use for opioid pain medications at a 2-month follow-up. Ultimately, this approach led to improved mobility and an increase in the patient's quality of life. Based on this case's success, a prospective study or randomized control trial evaluating the efficacy of the ganglion impar block as a treatment option for chronic anorectal pain secondary to radiation-induced proctitis appears warranted.


Gastrointestinal Cryptococcosis Associated with Intestinal Lymphangiectasia.
Intestinal lymphangiectasia is a pathological dilation of enteric lymphatic vessels resulting in lymph leakage to the intestinal lumen. This chronic lymph leakage leads to a state of immunosuppression secondary to the loss of humoral and cellular components of the immune system and represents a potential risk factor for opportunistic infections. We report a case of protein-losing enteropathy in a seemingly immunocompetent patient. An intestinal histopathological study revealed the unusual association of lymphangiectasia and intestinal cryptococcosis. Although cryptococcal infection is common in immunocompromised patients, intestinal involvement is rarely reported. We found no reports on the association of intestinal cryptococcosis in patients with lymphangiectasia. This case report is the first to describe intestinal cryptococcosis associated with intestinal lymphangiectasia.


The supplementary use of XP-endo Finisher R after Reciproc enhances the removal of a bioceramic sealer in oval root canals.
This study compared the performance of Reciproc and Reciproc Blue endodontic files in retreatment time and re-establishment of apical patency, plus removal of a bioceramic sealer from the canal surface with the supplementary use of the XP-endo Finisher R. Following preparation, slightly curved oval root canals in mandibular incisors were filled using a corresponding gutta-percha point and a bioceramic sealer. Apical patency achievement was assessed and the time required to reach the original working length was recorded. The samples were split longitudinally and were photographed to assess the material remaining on the canal walls. No significant differences were observed regarding patency achievement or retreatment times when comparing Reciproc and Reciproc Blue. Significant less material remained on the canal walls when Reciproc was followed by XP-endo compared with Reciproc alone, and when the data for Reciproc and Reciproc Blue were pooled.


Sternoclavicular joint involvement in rheumatoid arthritis: clinical and ultrasound findings of a neglected joint.
To describe the prevalence of sternoclavicular (SC) joint involvement and the relationship between clinical and ultrasound (US) findings in patients with rheumatoid arthritis (RA). One hundred three consecutive patients with RA and 103 age- and sex-matched healthy individuals were enrolled. Clinical evaluation and blinded US examinations of the SC joint were performed bilaterally in both groups. The presence of gray-scale synovitis, osteophytes, erosions, and intraarticular power Doppler (PD) was recorded. Interobserver agreement was calculated. A total of 412 SC joints were evaluated: 206 from patients with RA and 206 from healthy controls. In the RA group, 39 joints (19%) were found to be clinically involved (pain/swelling), in contrast to only 4 (1.9%) in the control group (P = 0.0001). In the RA group, US abnormalities were recorded in 89 SC joints (43%) compared with 36 (17%) in the healthy control group (P = 0.0001), comprising osteophytes in 59 (29%) versus 25 (12%; P = 0.0001), synovitis in 31 (15%) versus 5 (2%; P = 0.0001), erosions in 23 (11%) versus none (P = 0.0001), and intraarticular PD in 5 (2%) versus none (P = 0.03). Furthermore, a correlation between the presence of US synovitis (P < 0.001) and intraarticular PD (P < 0.0001) with a higher Disease Activity Score in 28 joints (DAS28) was found. In patients with RA, US detected a higher number of involved SC joints than with clinical assessment. Our results indicate that both gray-scale and PD US findings were more prevalent in patients with RA than in healthy controls. US synovitis and synovial hyperperfusion correlated with the DAS28, suggesting that SC joints actively participate in the systemic inflammatory process of RA.


Use of new automated biopsy device for percutaneous testicular biopsy. A preliminary clinical experience.
Testicular biopsy is indicated in the azoospermic patients to determine if the cause of azoospermia is ductal obstruction or testicular pathology and in certain patients who have severe oligozoospermia. The technique traditionally used is an open testicular biopsy. New Automated Biopsy Device has been used successfully for renal diseases. This instrument is now used by the urologist for transrectal prostate biopsy. The aim of this study was to evaluate whether percutaneous testicular needle biopsy with new automated device can replace open testis biopsy or not. 90 testes of 48 patients between 22 and 43 years olf underwent percutaneous testicular biopsy with a new 18-gauge automated biopsy device. Adequate samples were recovered from 90% cases (average 24.77 tubule sections per testis). When needle biopsy and open biopsy samples were compared in 30 testes of 15 patients, complete agreement was obtained in 93%, whereas slight differences in 7%. These results show that percutaneous needle biopsy with new automated systems is cost-effective, quick, safe, repeatable, relatively painless and effective way to obtain largest possible cores through full cut technique. No serious complications were encountered during or after the procedure. The diagnosis were found to be comparable to those obtained by open biopsy. For these reasons, it is concluded that this new technique can replace the open biopsy.


Disadvantaged black and coloured infants in two urban communities in the Western Cape, South Africa differ in micronutrient status.
To determine the nutritional and health status of urban infants in two disadvantaged communities in the Western Cape, South Africa with special reference to micronutrient status. The results of this study will serve to plan an intervention study in these communities in the same age group. Cross-sectional study. Two disadvantaged urban black and 'coloured' communities in the Western Cape, South Africa. Sixty infants aged 6-12 months from each community. Dietary intake, anthropometric measurements, micronutrient status and psychomotor development. Stunting and underweight were more prevalent in coloured infants (18% and 7%, respectively) than in black infants (8% and 2%, respectively). Anaemia (haemoglobin (Hb) < 11 g dl(-1) was prevalent in 64% of coloured and 83% of black infants. Iron-deficiency anaemia (Hb < 11 g dl(-1) and ferritin < 10 ng ml(-1) was found in 32% of coloured infants and in 46% of black infants. Zinc deficiency was prevalent in 35% and 33% of the coloured and black infants, respectively. Marginal vitamin A deficiency (serum retinol < 20 microg dl(-1) was observed in 23% of black infants compared with 2% of coloured infants. Of black infants, 43% and of coloured infants 6% were deficient in two or more micronutrients. Six per cent of coloured infants had C-reactive protein concentrations above 5 mg l(-1) compared with 38% of the black infants. The dietary intake of micronutrients was in general lower in black infants than in coloured infants. The overall psychomotor development, assessed by the Denver Developmental Screening Test, was different between the two groups. The coloured infants scored higher in three out of the four categories as well as in their overall score. This study shows that information on stunting and wasting only in urban disadvantaged infants is not sufficient to make recommendations about specific community intervention programmes. Information on the micronutrient status, independent of wasting and stunting, is necessary to design nutrition programmes for different communities. The study also showed a substantially higher prevalence of micronutrient deficiencies among black infants.


The transformation of adult but not newborn human lymphocytes by Epstein Barr virus and phytohemagglutinin is inhibited by interferon: the early suppression by T cells of Epstein Barr infection is mediated by interferon.
In a previous study, it was demonstrated that T cells from adult individuals were able to suppress the transformation of B cells after infection by EBV. In this paper, it is shown that this suppression is mediated by interferon. Thus, the suppression is abrogated by anti-interferon serum and mimicked by human leukocyte interferon. Furthermore, the interferon is released in response to the virus-infected B cell, not the virus alone. The relevance of these results to previous clinical evidence, indicating a role for interferon in recovery from EBV infection, is discussed. Interferon will also suppress the transformation of adult B lymphocytes by the mitogen phytohemagglutinin (PHA). However, interferon at concentrations 2 to 3 orders of magnitude higher was unable to suppress the transformation of neonatal B lymphocytes by either EBV or PHA. These experiments suggest that EBV and PHA induced transformation share a common interferon sensitive step. Lastly, the resistance of newborn lymphocytes to the protective effect of interferon may be an important consideration in the application of interferon as an antiviral or anti-tumor agent.


Family health conversations versus support group conversations when a family member has been critically ill: A mixed methods study.
Introduction: When a family member has been critically ill and cared for at an intensive care unit the individual family member as well as the family system are affected and in need of support. The aim of this study was to compare and contrast the responses from 2 different types of follow-up interventions for families of critically ill persons, focusing on individual hopes, health-related quality of life, family functioning and ability to cope with challenges. Method: Adult family members from 3 hospitals attended 1 of 2 interventions 2 months after intensive care. The family health conversation included the family. The support group conversation included just family members and not the patient who had experienced intensive care. Data were collected via self-reported questionnaires and follow-up interviews with family members. Quantitative and qualitative data were first analyzed separately, and the results were then integrated through mixed methods analysis. Results: A total of 38 family members took part in the interventions. Family members in the 2 intervention groups talked about how they had more hope for the future, and about how talking within the family and the group had helped them justify their feelings, which empowered them in the transition toward a healthier quality of life. Comparisons of the interventions show a higher significance of family function and hope in the family health conversation. Discussion: The article illustrates a disparity between how family members function and the needs they have for follow-up. We discuss what kind of follow-up these persons need. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


SSDesign: Computational metabolic pathway design based on flux variability using elementary flux modes.
Metabolic pathway modification based on the stoichiometric model has been an effective approach for enhancing microbial bio-production. The network of optimal pathways for "growth-associated" and "non-growth-associated" production can be designed from the flux variability (solution space). The present study introduces a new computational method (solution space design [SSDesign]) that visually designs the gene knockout solution space. The smallest reaction sets that satisfy the mass balances of intermediates are called elementary flux nodes (EFMs). Because some of the EFMs necessarily occupy the outer boundary nodes of the flux solution space, the proposed SSDesign determines the area over which EFMs should be removed from the solution space of the parent strain, and explores the gene knockouts that will eliminate these undesirable EFMs. To evaluate the performance of SSDesign, the model was applied to growth-associated and non-growth-associated succinate production in Escherichia coli. In the growth-associated case, the deletion mutants that promoted succinate production at maximum biomass yield were predicted, and a candidate of ΔptsG ΔpykA,F ΔpflA has been experimentally confirmed as a succinate producer. Simply by changing the parameters, the gene knockout combinations yielding high growth yield were successfully predicted by SSDesign. In the non-growth-associated case, strong candidates for succinate production were the deletion mutants ΔpntAB ΔsfcA ΔpykA,F and ΔsfcA ΔmaeB ΔpykA,F Δzwf. According to the solution spaces, these strains allow high growth yield and inevitably produce succinate at zero biomass yield, since their metabolic pathways cannot sustain steady-state without discarding succinate from the cell.


Hybrid CMOS detectors for high-speed X-ray imaging.
Hybrid CMOS (hCMOS) x-ray framing cameras are a new and powerful detector option for experiments in the fields of Inertial Confinement Fusion (ICF) and High Energy Density Physics (HEDP). These digital cameras capture multiple images along a single line-of-sight with a time resolution as short as 1.5 ns and with high quantum efficiency. To manage the high data rate, an image sequence is acquired in a short burst of time and subsequently read out on a much longer time scale. The technology is well suited for operating in high radiation environments, including fusion ignition experiments. Diagnostics using hCMOS cameras are now deployed in experiments on major laser and pulsed-power ICF facilities around the world. Continued advances in microelectronics technologies will enable faster and more capable detectors well into the future. This paper reviews this detector technology with a focus on application to ICF and HEDP experiments.


Cellular strategies of protein quality control.
Eukaryotic cells must contend with a continuous stream of misfolded proteins that compromise the cellular protein homeostasis balance and jeopardize cell viability. An elaborate network of molecular chaperones and protein degradation factors continually monitor and maintain the integrity of the proteome. Cellular protein quality control relies on three distinct yet interconnected strategies whereby misfolded proteins can either be refolded, degraded, or delivered to distinct quality control compartments that sequester potentially harmful misfolded species. Molecular chaperones play a critical role in determining the fate of misfolded proteins in the cell. Here, we discuss the spatial and temporal organization of cellular quality control strategies and their implications for human diseases linked to protein misfolding and aggregation.


Effect of Electrolytes on Solution and Interfacial Behaviors of Double Chain Cationic-Nonionic Surfactant Mixtures for Hydrophobic Surface Wetting and Oil/Water Emulsion Stability Applications.
The solution behaviors of the binary mixture of double chain cationic surfactant didodecyldimethylammonium bromide (DDAB) with nonionic surfactants of varied head groups, EO-9 and EO-40, in the presence and absence of electrolytes were studied and found nonideal behavior. The different physicochemical properties such as Gibb's surface excess (Γ), minimum area per molecule (Amin), and interaction parameters at bulk (βM) and interface (βσ) were calculated. In the presence of nonionic surfactants, lowering of CMC, CVC, and surface tension at these two concentrations of DDAB were observed. The βM and βσ values indicate strong interaction between DDAB and EO-40 mixed system. Further, addition of electrolytes to the mixed systems show increased interaction and change of physicochemical properties because of the combination of electrical and salting out effects.


Importance of Universal screening for thyroid disorders in first trimester of pregnancy.
To determine the importance of screening for Thyriod disorders in the first trimester of pregnancy. The Study was conducted on 305 patients which were were randomly selected and screened on OPD basis by TSH levels (cut off level 0.10-2.50 mIU/ml). In the 305 women screened mean age was 24.46 years, mean gestational age was 9.09 weeks, 89.83% were euthyroid, 9.8%were hypothyroid, 0.32% were hyperthyroid. Incidence of hypothyroidism in high risk population was 20.58% and in normal population was 6.7%. There was significant association of thyroid disorders with high risk factors (P < 0.001). In hypothyroid women 46% had adverse perinatal outcomes and 53.33% had normal outcomes. This shows statistically significant association abnormal TSH values with adverse pregnancy outcomes (P < 0.001). In abnormal perinatal outcomes 6.2% women had Caesarean section out of them 73.68% were euthyroid, 26.31% were hypothyroid 1.9% had preterm labour, out of them 50% were euthyroid, 50% were hypothyroid. Out of 2.2% spontaneous abortions 28.5% were in euthyroid group while 71.4% were in hypothyroid group. There was 1 term stillbirth in hypothyroid group. This study showed significant association between abnormal thyroid stimulating hormone (TSH) values and adverse perinatal outcomes (P < 0.001). There is significant correlation between risk factors and hypothyroidism. So high risk screening is mandatory in early pregnancy. But if we screen only high risk population we would miss 4.6% cases which could have been diagnosed and treated earlier. Therefore it is important to screen all pregnant women in the first trimester, it should be made mandatory.


circALPL Sponges miR-127 to Promote Gastric Cancer Progression by Enhancing MTDH Expression.
Background: CircRNA plays an important role in cancer progression. However, the potential mechanism of circRNA in gastric cancer remains unknown. In this study, we aimed to investigate the specific mechanism of circALPL in gastric cancer. Methods: Using a high-throughput microarray, we found that circALPL was upregulated in gastric cancer cell lines. RT-qPCR was used to measure the circALPL expression level in gastric cell lines and tissue. Transwell, CCK-8, and metastasis assays were performed to learn the function after circALPL was inhibited. Results: circALPL downregulation suppresses the invasion and proliferation ability of gastric cancer cells. Additionally, the underlying pathway of circALPL was studied using luciferase reporter assays and RNA immunoprecipitation assays. The results showed that circALPL promotes gastric cancer progression by sponging miR-127, thus upregulating MTDH. Conclusion: The circALPL-miR-127-MTDH pathway plays a vital role in gastric cancer proliferation and metastasis. circALPL might be a new therapeutic target in gastric cancer.


Molecular characterization and antibiotic resistance profiling of Salmonella isolated from retail Turkey meat products.
Contaminated poultry meat has been identified as one of the principal foodborne sources of Salmonella. Molecular characterization of Salmonella is important in addressing methods to control this pathogen. Seventy-four retail turkey meat samples were collected from various stores in Fargo, North Dakota in the fall of 2003. Salmonella was recovered from 30 samples using the standard conventional culture method (FSIS, USDA). Isolated Salmonella were characterized by serotyping, pulsed-field gel electrophoresis (PFGE) analysis, plasmid analysis, and antibiotic resistance profiling. Five serotypes were identified among the isolates: Newport (n = 12), Hadar (n = 8), Heidelberg (n = 7), 4,12:nonmotile (n = 2), and Reading (n = 1). XbaI PFGE analysis revealed 13 PFGE types and succeeded in grouping the isolates according to their serotypes. Plasmid profiling identified 5 plasmid types (with 1 or 2 plasmids) among eleven isolates that harbored plasmids. Seventeen isolates were resistant to antibiotics. The Heidelberg serotype showed resistance to multiple antibiotics: 1 isolate had resistance to gentamicin, sulfamethoxazole, and streptomycin, and 6 isolates had resistance to tetracycline, gentamycin, sulfamethoxazole, kanamycin, and streptomycin. The Hadar serotype isolates were resistant to 2 or 3 antibiotics: tetracycline and streptomycin (1 isolate); tetracycline and kanamycin (1 isolate); and tetracycline, kanamycin, and streptomycin (6 isolates). The 4,12:nonmotile serotype isolates showed resistance to tetracycline only. The Newport and the Reading serotypes were susceptible to all 16 of the antimicrobials tested.


Epilepsy in institutionalized patients with encephalopathy: clinical aspects and nosological considerations.
This study was designed to correlate the prevalence of epilepsy with the severity and type of encephalopathy of 1,023 institutionalized patients and tentatively classify each according to the Proposals of the Commission on Classification and Terminology of the International League Against Epilepsy. Of this sample, 326 individuals were diagnosed with epilepsy. Sex distribution and mean age in the epilepsy and no epilepsy groups were similar, but degree of handicap was higher for those with epilepsy. Of these individuals 32.5% had a partial form. Of the 204 patients with generalized epilepsy (62.5%), 64 had a form with electroclinical characteristics of the idiopathic type; 57, a syndromic form (53 cases with a Lennox-Gastaut syndrome); and 83, a nonsyndromic form. Degree of handicap and frequency of seizures were lower in subjects with partial epilepsy and with those having electroclinical characteristics of the idiopathic type.


Fermentation kinetics of recombinant yeast in batch and fed-batch cultures.
Fed-batch cultures of recombinant microorganisms have attracted attention as they can separate cell growth stage from cloned-gene expression phase during fermentations. In this work, the effect of different glucose feeding strategies on cell growth and cloned gene expression was studied during aerobic fed-batch fermentations of recombinant yeast, containing the plasmid pRB58. The plasmid contains the yeast SUC2 gene, which codes for the enzyme invertase. Some feeding policies resulted in a constant glucose concentration inside the fermentor, while others deliberately introduced a cyclic variation. The cell mass yield was found to be higher at low glucose concentrations, thus indicating a shift to the more energy-efficient respiratory pathway. The SUC2 gene expression was derepressed at glucose levels below 2 g/L. The response of specific invertase activity to changes in the medium glucose concentration was found to be almost immediate.


Depressive symptoms in women experiencing intimate partner violence.
The study was a cross-sectional examination of African American women positive for intimate partner violence (IPV) who presented to the medical or psychiatric emergency department (ED) for treatment. African American women with a recent history of IPV who presented following an attempted suicide (n = 100) were compared to demographically comparable African American women who were IPV positive who had not attempted suicide and presented for treatment of another condition(n= 100). Women completed face-to-face interviews on several measures, including demographics and the Beck Depression Inventory-II (BDI-II). Overall, there were no demographic differences between cases and controls. Attempters reported statistically significant higher scores on all 21 BDI-II items than did nonattempters. Four BDI-II items had effect size values in the medium range: sadness, self-dislike, suicidal thoughts, and feelings of worthlessness. These four items can be used as a brief screen in the ED to detect female patients positive for IPV at increased risk for suicidal behavior.


Gap junction-mediated regulation of endothelial cellular stiffness.
Endothelial monolayers have shown the ability to signal each other through gap junctions. Gap junction-mediated cell-cell interactions have been implicated in the modulation of endothelial cell functions during vascular inflammation. Inflammatory mediators alter the mechanical properties of endothelial cells, although the exact role of gap junctions in this process remains unclear. Here, we sought to study the role of gap junctions in the regulation of endothelial stiffness, an important physical feature that is associated with many vascular pathologies. The endothelial cellular stiffness of living endothelial cells was determined by using atomic force microscopy. We found that tumor necrosis factor-α transiently increased endothelial cellular stiffness, which is regulated by cytoskeletal rearrangement and cell-cell interactions. We explored the role of gap junctions in endothelial cellular stiffening by utilizing gap junction blockers, carbenoxolone, inhibitory anti-connexin 32 antibody or anti-connexin 43 antibody. Blockade of gap junctions induced the cellular stiffening associated with focal adhesion formation and cytoskeletal rearrangement, and prolonged tumor necrosis factor-α-induced endothelial cellular stiffening. These results suggest that gap junction-mediated cell-cell interactions play an important role in the regulation of endothelial cellular stiffness.


Troglitazone upregulates nitric oxide synthesis in vascular smooth muscle cells.
We investigated the effects of troglitazone on cytokine-stimulated nitric oxide (NO) production in cultured rat vascular smooth muscle cells (VSMC). The increase in NO formation caused by interleukin-1alpha (IL-1) was enhanced by troglitazone in a concentration-dependent manner. Bacterial lipopolysaccharide-stimulated NO synthesis was also increased by troglitazone. The combinations of IL-1, tumor necrosis factor-alpha, or lipopolysaccharide with interferon-gamma (IFN) were strong stimuli for induction of NO synthesis in VSMC, which were further potentiated by the presence of troglitazone. When troglitazone was added at increasing intervals after the stimulation of VSMC with IL-1, the enhancement in NO production decreased as the interval lengthened, suggesting that troglitazone alters NO synthase (NOS) expression by VSMC rather than having a direct affect on VSMC NOS activity. Troglitazone had no effect on IL-1-elicited or IL-1/IFN-elicited nuclear factor-kappaB activity in VSMC. Troglitazone inhibited the degradation of cytokine-induced NOS mRNA. Thus troglitazone appears to enhance IL-1-induced NOS mRNA levels by prolonging its half-life rather than activating its transcription, which is nuclear factor -kappaB-dependent. No expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) was detected in VSMC, and 15-deoxy-D12,14 prostaglandin J2, the natural ligand for the PPARgamma, did not resemble the effect of troglitazone on IL-1-induced NO synthesis. These results indicate that troglitazone upregulates cytokine-stimulated NO synthesis in VSMC through PPARgamma-independent mechanisms. Considering its inhibitory effects on the action of numerous growth factors on VSMC, the direct vascular effects of troglitazone shown in this study may have important implications for prevention of restenosis and possibly atherosclerosis.


[Application of non-steroidal anti-inflammatory drugs to enhance 5-fluorouracil efficacy in experimental systems].
The elevated cyclooxygenase-2 (COX-2) expression has been shown to affect the carcinogenesis and tumor progression processes, including cell proliferation, motility and angiogenesis. COX-2 is overexpressed in approximately 80% of sporadic colorectal carcinomas and COX-2 enzyme is the best defined target of non-steroidal anti-inflammatory drugs (NSAIDs). In the chemotherapy of colorectal carcinomas 5-fluorouracil (5-FU) has been the most important of the basic drugs for more than 40 years. In order to improve the effectiveness of 5-FU therapy different biological modifiers i.e. inhibitors of its catabolism or activators of anabolism have been studied recently. The rate-limiting enzyme of 5-FU catabolism is dihydropyrimidine dehydrogenase (DPD) since more than 80% of the administered 5-FU is catabolized by DPD. Tumoral DPD has become of clinical interest because elevated intratumoral DPD can decrease the tumor response to 5-FU therapy. The main purpose of our experiments was to investigate the effect of COX inhibitors on the efficacy of 5-FU on high and low COX-2 expressing HCA-7 and HT-29 human colon adenocarcinoma cell lines, respectively, and also on xenografts derived from HT-29 cells. The cytotoxic and antitumor effects of 5-FU in the presence of low doses of indomethacin (non-selective COX-2 inhibitor) and that of NS-398 (highly selective COX-2 inhibitor) on HT-29 and HCA-7 cells and also on the HT-29 xenograft were investigated. In addition, our intention was to understand the mechanism(s) by which NSAIDs could enhance the cytotoxic effect of 5-FU. Our data indicated that the elevated COX-2 expression of HCA-7, the collagen-induced HT-29-C cells and of the HT-29 xenograft were associated with reduced 5-FU sensitivity. Based on the fact that at the same time DPD activity was also increased it might be conceivable that a possible explanation for the decrease of 5-FU sensitivity is the co-existence of high COX-2 and DPD activity. Indomethacin or NS-398 enhanced in a simultaneous and significant manner the sensitivity and cytotoxic effect of 5-FU on high COX-2 expressing cells and xenografts through the modulation of DPD - decrease of its mRNA expression and/or enzyme activity. Based on our results it could be presumable that 5-FU efficacy is limited by the COX-2 associated high DPD expression and activity in patients with colorectal cancer as well, therefore further clinical studies are warranted to decide if NSAIDs in the therapeutic protocol might improve the antitumor potency of 5-FU. Réti A. Application of non-steroidal anti-inflammatory drugs to enhance 5-fluorouracil efficacy in experimental systems.


Antitumor activity of cobrotoxin in human lung adenocarcinoma A549 cells and following transplantation in nude mice.
The aim of the present study was to investigate cobra neurotoxin (cobrotoxin) activity in A549 cell lines transplanted into nude mice, and to explore its molecular mechanism. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was used to detect the growth inhibition rate of cobrotoxin in human lung A549 adenocarcinoma cells and HFL1 lung fibroblasts. Cell colony formation assays were performed to determine the effect of cobrotoxin on A549 cell colony formation, and transmission electron microscopy was used to detect cobrotoxin autophagy. In addition, western blot analysis was performed to determine the effect of 3-methyl adenine (3-MA) activity on the inhibition of autophagy, SB203580 inhibition of the p38-mitogen-activated protein kinase (MAPK) pathway, and Beclin 1, LC3, p62, p38 and phosphorylated (p)-p38 protein expression. Nude mice were injected with human lung A549 cells, and intervention and control groups were compared with regard to tumor suppression. The MTT assay revealed that various concentrations of cobrotoxin inhibited growth of A549 cells, but not HFL1 cells. A549 cell colony formation decreased and autophagosome activity was significantly increased compared with the controls. Following 3-MA administration, SB203580 autophagosome activity decreased, and following cobrotoxin administration, Beclin 1, p-p38, and LC3-II protein expression significantly increased, whereas p62 expression significantly decreased. Following 3-MA inhibition of autophagy, Beclin 1, LC3-II and p62 expression increased. Furthermore, following SB203580 inhibition of the p38-MAPK pathway, Beclin 1, p-p38, LC3-II and p62 protein expression increased. Cobrotoxin exhibited inhibitory activity on the human lung cancer A549 cells transplanted into the nude mice, suppressing the tumor growth rate by 43.4% (cobrotoxin 40 μg/kg group). However, following the addition of 3-MA (10 mmol/kg) and SB203580 (5 mg/kg), the suppression of the tumor growth rate decreased significantly. Cobrotoxin inhibits the growth of human lung cancer A549 cells in vitro and A549 cells transplanted into nude mice. Furthermore, the induction of autophagy may be associated with the activation of the p38-MAPK pathway.


[Brain abscesses after extracranial infections of the head and neck area].
The authors report on 20 immunocompetent patients with brain abscess after 12 cases of middle ear, seven tooth and a single frontal sinus infection. The clinical aspects, hematochemical and microbiological data, the role of imaging diagnostics (CT, MR) and the type of treatment are analysed. Neurosurgery was performed on 17 patients (85%), eight of whom subsequently underwent evacuation of the primary source of infection (four mastoidectomies, two timpanoplasties, two tooth extractions). Mastoidectomy was eventually carried out on one of the three patients who did not undergo neurosurgery. Microbiological diagnosis was possible in nine patients through culture examination: Proteus mirabilis in three cases, Peptostreptococcus sp. in two, Micrococcus varians, Proteus vulgaris, Streptococcus sanguis and Streptococcus viridans not typed in single cases. The pus was sterile in eight patients (47.1% of those operated). An association of two antimicrobial agents was used in 18 patients, while in two cases monotherapy was preferred, based on the isolated bacteria. Treatment lasted on average 38 days. The most frequently used therapy regimen (75%) was the association of a beta-lactam drug with chloramphenicol or metronidazole. Therapy was successful in 19/20 patients; one patient died. There was no significant difference in prognostic terms with regard to sex, age, duration of symptoms prior to diagnosis, clinical picture at onset, number and size of abscesses or type of treatment. Recognising the first clinical signs and symptoms (headache, fever, alterations in consciousness, focal neurological deficit, epileptic seizures) is extremely important for prompt diagnosis of brain abscess.


The chemical nature of a pancreatic cardiodepressant factor.
The presence of a cardiodepressant factor of pancreatic origin has been reported in the plasma of experimental animals and man in a variety of shock states. It has been suggested that the depression of developed tension of the isolated cat papillary muscle may be caused by excess NaCl in the bathing medium rather than a specific cardiodepressant peptide. Incubated pancreatic homogenate was used as a source of this factor, and after protein precipitation, ultrafiltration (10,00 and 1,000 MW), dialysis and lyophilization, the residue was applied to a Sephadex G-10 column in order to ensure the removal of all salts. The protein effluent of the Sephadex column contained all the cardiodepressant activity of the filtered, dialyzed pancreatic homogenate and none of the salt content. To further isolate this cardiodepressant factor, the active residue was applied to a cellulose column and eluted with butanol: glacial acetic acid: water (25:26 v/v/v). This elution gave 8 distinct peptide peaks, one of which, peak 4, contained significant depressant activity. Thus, a cardiodepressant peptide of approximately 250-1,000 MW exists in pancreatic homogenates and this compound is not excess NaCl in the assay system.


[A Resected Case of UR-LA Pancreatic Tail Cancer with Aortic Invasion after Chemoradiotherapy].
A 70-year-old male was referred to our hospital because of weight loss and epigastric discomfort. CT showed an irregularshaped, low-density tumor, 12 cm in diameter in the tail of the pancreas. This tumor widely invaded to the left kidney and to the anterior and left lateral sides of the aorta in spite of no involvement of celiac and superior mesenteric arteries. Moreover, it closely contacted with the stomach and the spleen. EUS-fine-needle aspiration biopsy of the tumor detected adenocarcinoma. Thus, he was diagnosed with UR-LA pancreatic cancer with aortic invasion. He received combination chemotherapy(S-1 plus gemcitabine[GEM])and 50.4 Gy 3-dimensional conformal radiation therapy, but this therapy had no expected effect. We changed the regimen to GEM plus nab-PTX. After 1 course of changed regimen, the tumor ruptured into the stomach and endoscopic debridement of the necrotic tissue was performed. Twenty-six days later, We performed distal pancreatectomy with splenectomy, total gastrectomy, left nephrectomy, left adrenalectomy, and segmental resection of the colon. The tumor was detached from the aorta as much as possible. The final diagnosis was pT3N0M0, pStage II A. Fifty-nine days after operation, we restarted GEM plus nab-PTX therapy. However, a cerebral infarction suddenly occurred, and we discontinued the chemotherapy. Five months after the operation, he died of cancerous peritonitis.


A Novel Variant in the PAH Gene Causing Phenylketonuria in an Iranian Pedigree.
Phenylalanine hydroxylase (PAH) gene is the well-known causative gene for classic Phenylketonuria (PKU) (OMIM#261600) disease, with more than 500 reported mutations. Through this study, a novel mutation in the PAH gene in an Iranian pedigree with phenylketonuria was introduced. A consanguineous family with a 10-year old affected girl was referred for genetic analysis. Mutation screening of all exons and exon-intron boundaries was performed by Sanger sequencing, and mini haplotype analysis was carried out by genotyping of Short Tandem Repeat (STR) and Variable Number Tandem Repeat (VNTR) alleles. Mutation analysis revealed a novel homozygous insertion of a single adenine nucleotide at position 335 in exon 3 of the PAH gene. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the change is interpreted as a pathogenic mutation which produces a premature termination signal (TAA) at codon 113 according to in silico assessments. The mini haplotype analysis showed that this mutation was linked to STR (15) -VNTR (3). In this study, a novel mutation was reported in a patient who had PKU symptoms without any previously reported mutations in the PAH gene (NM_000277.1:p.Asp112Glufs*2) that can be responsible for the classical PKU phenotype in the Iranian population. Detection of novel mutations indicates notable allelic heterogeneity of the PAH locus among this population.


Morphology and ultrastructure of Neolecta species.
Several independent molecular phylogenetic analyses have indicated that the genus Neolecta has a unique position within the Ascomycota. It is the only taxon outside the core-group of filamentous, ascoma-forming ascomycetes that also has the ability to form ascomata. Light and electron microscope studies indicate that hymenial structure and development in Neolecta spp. are unique. Ascogenous hyphae in N. vitellina branched repeatedly and successively to produce asci. Non-ascogenous hyphae were multinucleate, often with nuclei in pairs. Nuclear pairing was particularily prominent in the ascogenous hyphae. A basal septum delimited the dikaryotic ascus. Ascosporogenesis was initiated by nuclear fusion followed by a meiotic and mitotic division to form eight nuclei. The ascus apex was thin with an annular subapical thickening. Ascospores were forcibly released through a 'split' in the ascus apex. Woronin bodies were frequently associated with hyphal septa. Attempts to culture N. vitellina and to obtain molecular information from the type species, N. flarovirescens, were unsuccessful. However, N. flavovirescens showed several microscopic characters that indicated close relationships with the two other species in the genus, N. vitellina and N. irregularis. The position of Neolecta spp. within the Ascomycota is discussed.


Rh(II)-Catalyzed Denitrogenative Reaction of N-Sulfonyl-1,2,3-triazoles with Quinolones and Isoquinolones.
Herein, we developed an efficient approach to access biologically relevant 2-aminoquinolines and 1-aminoisoquinolines from readily available N-sulfonyl-1,2,3-triazoles and 2-quinolones or 1-isoquinolones. This transformation involves the selective O-H insertion of these derivatives onto the in situ generated Rh-azavinyl carbenes (Rh-AVC) followed by rearrangement. The reaction proceeds smoothly under operationally simple conditions and the protocol was found to be scalable.


Characterization of two forms of acetolactate synthase from barley.
Acetolactate synthase (ALS) catalyzes the first common step in the biosynthesis of valine, leucine, and isoleucine. ALS is the target site for several classes of herbicides, including sulfonylureas, imidazolinones, and triazolopyrimidines. Two forms of ALS (designated ALS I and ALS II) were separated from barley shoots by heparin affinity column chromatography. The molecular masses of native ALS I and ALS II were determined to be 248 kDa and 238 kDa by nondenaturing gel electrophoresis and activity staining. Similar molecular masses of two forms of ALS were confirmed by a Western blot analysis. SDS-PAGE and Western blot analysis showed that the molecular masses of the ALS I and ALS II subunits were identical--65 kDa. The two ALS forms exhibited different properties with respect to the values of K(m), pI and optimum pH, and sensitivity to inhibition by herbicides sulfonylurea and imidazolinone as well as to the feedback regulation by the end-product amino acids Val, Leu, and Ile. These results, therefore, suggest that the two ALS forms are not different polymeric forms of the same enzyme, but isozymes.


Mindsets May Matter in Nursing Education.
Nursing education needs innovative and effective teaching models that are easily conveyed and economical. Dweck's mindset model harnesses the predictive power of noncognitive factors such as motivation, perseverance, effort, and academic tenacity to shape the learner's perceptions of intelligence for competency development. All individuals possess perceptions of intelligence; however, the mindset model demonstrates the immense potential associated with endorsement of the growth mindset and student success.


Primitive, quiescent and difficult to kill: the role of non-proliferating stem cells in chronic myeloid leukemia.
Recent studies have identified primitive, malignant stem cells which have entered the G0-phase of the cell cycle to become 'quiescent' and which are present, in small numbers, in all chronic myeloid leukaemia (CML) patients. These cells have attracted intense scrutiny because they are proving exceptionally refractory to attempts to kill them, in vitro, using imatinib mesylate, the current first-line therapy for CML, or conventional chemotherapeutic agents, such as cytosine arabinoside. This insensitivity, or resistance, to drug treatment is ominous and has important implications for the clinical management of CML, particularly with regard to relapse following an imatinib-induced remission. In this review, we consider the known properties of this cell population, including recent evidence which suggests that transcription of BCR-ABL occurs at an exceptionally high level in these cells despite them having only a single copy of the oncogene. We also discuss possible alternative, Bcr-Abl-independent, mechanisms for the insensitivity of these cells to agents which promote apoptosis, including the putative role of transporter proteins in causing abnormal drug influx or efflux.


Beyond the Bragg peak: hyperthermal heavy ion damage to DNA components.
We have observed the destruction of fundamental building blocks of DNA (nucleoside, base, and sugar) by hyperthermal (0.25-1.75 eV/amu) heavy ion impact. Nucleoside damage pathways include base or sugar loss, and complete disintegration of either moiety. Sugar damage dominates, and in DNA will yield a complex strand break. Our results suggest that (a) heavy particle damage to biological media may extend to ion track ends beyond the Bragg peak, and (b) the nascent damage by hyperthermal secondary heavy particles, formed along the primary ion tracks, may be equally complex.


Understanding Dielectrics: Impact of External Salt Water Bath.
As predicted by the theory of super dielectric materials, simple tests demonstrate that dielectric material on the outside of a parallel plate capacitor dramatically increases capacitance, energy density, and power density. Simple parallel plate capacitors with only ambient air between the plates behaved as per standard theory. Once the same capacitor was partially submerged in deionized water (DI), or DI with low dissolved NaCl concentrations, still with only ambient air between the electrodes, the capacitance, energy density, and power density, at low frequency, increased by more than seven orders of magnitude. Notably, conventional theory precludes the possibility that material outside the volume between the plates will in any fashion impact capacitive behavior.


Distinct Role of Striatal Functional Connectivity and Dopaminergic Loss in Parkinson's Symptoms.
Degeneration of dopaminergic neurons is a hallmark of Parkinson's disease. However, its link to Parkinson's disease symptoms remains unclear. Striatal resting state functional connectivity differentiates between Parkinson's disease patients and healthy controls and might be a potential mediator of the effects of striatal dopaminergic degeneration onto Parkinson's disease symptoms. Here, we evaluated the relationship between dopaminergic deficits, striatal functional connectivity (SFC) at rest and different Parkinson's disease clinical symptoms in the largest currently established cohort of de novo Parkinson's disease patients. We show that SFC is an independent predictor of symptom severity in Parkinson's disease in addition to striatal dopaminergic deficits. Furthermore, we find that distinct SFC networks are associated with symptoms reflecting the ability to perform daily routine automatized motor tasks and clinician-rated Parkinson's disease motor symptoms. We find that reduced SFC is a major and independent predictor of Parkinson's disease symptoms going beyond the mere reflection of striatal dopaminergic input loss. These findings indicate the high value of SFC as a clinically relevant biomarker in Parkinson's disease.


Housing and dementia care - a scoping review of the literature.
This paper reports the findings of a scoping study designed to describe the evidence base with regard to housing provision for elderly people with dementia with the aim of identifying gaps in existing knowledge. This report from the scoping study findings covers studies of housing and accommodation in relation to dementia that have been published in the UK since the early 1980s, although we draw on limited aspects of overseas research to illuminate issues missing from the UK research agenda. The results reveal a significant number of research gaps in the UK context, most notably in relation to end-of-life care for people with dementia and the effectiveness of integrated and segregated facilities. UK policy regarding the development of extra-care housing also neglects the long-term future of people with dementia. A more robust evidence base will be required, combining a variety of methodological approaches, if UK dementia research is to contribute to future housing policy developments.


Highlights of the 14th Japan Bioanalysis Forum Symposium.
The 14th Japan Bioanalysis Forum Symposium was held at Tower Hall Funabori, Japan from 1-3 March 2023. The conference theme, 'Bringing Together - the Expertise of Bioanalysis', aimed to enable people from various fields to gather, learn and collaborate together for the common goal of delivering medicines to patients faster. Approximately 360 participants from various fields, including pharmaceutical industries, contractors, academia and regulatory authorities, gathered at an in-person symposium which had an online participation option, for the first time in 4 years. The symposium offered a wide range of topics including ICH M10, new modalities, biomarkers, immunogenicity, electronization and patient-centric sampling. The latest research results were provided from domestic and overseas scientists. This report summarizes the major topics.


Protein kinase C activation by iridal type triterpenoids.
Eleven iridal type triterpenoids from Iris tectorum and Belamcanda chinensis were examined for protein kinase C (PKC) activation and binding activity to PKC. Among the tested compounds, nine iridals showed dose-dependent activities, and a mutual relation between the two activities was also observed. 28-Deacetylbelamcandal, which has been found to be a new class 12-O-tetradecanoylphorbol 13-acetate type tumor promoter, showed the most potent activity in both tests. The structural requirements of the iridals inducing these activities were as follows: 1) a hydrophobic side-chain, 2) an E-methylidene aldehyde group at the C-1 position, and 3) a hydroxyl group at the C-26 position.


miR-223 Inhibits the Polarization and Recruitment of Macrophages via NLRP3/IL-1β Pathway to Meliorate Neuropathic Pain.
miRNA is an essential factor in neuropathic pain. However, the underlying mechanism of miRNA in neuropathic pain remains unclear. To explore the potential role of miR-223 in neuropathic pain in a mice model of chronic sciatic nerve injury. Mice were divided into the sham group, CCI group, CCI + Lenti-vector group, and CCI + Lenti-miR-223 group. Flow cytometry was used to detect the neuronal apoptosis and the proportion of M1/M2 macrophages in each group. Western blot was used to detect the protein expression levels of ASC, caspase-1, IL-1β, and IL-18 in each group. Luciferase activity assay detects the binding of miR-223 and NLRP3. Macrophage chemotaxis experiments verified the anti-inflammatory effect of miR-223 in vitro. The overexpression of miR-233 significantly reduced the neuropathic pain caused by CCI and reduced the apoptosis and inflammatory factor expression. miR-223 inhibits the expression of NLRP3 by directly binding to the 3'-untranslated region. Overexpression of miR-223 reduces the protein levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in the spinal cord of CCI mice, increases the proportion of M2-type macrophages, and reduces the proportion of M1-type macrophages. miR-223 may facilitate the development of neuropathic pain in CCI mice by inhibiting NLRP3-mediated neuroinflammation.


Occupational exposure and respiratory health problems among nutmeg production workers in Grenada, the Caribbean.
The nutmeg industry is a major contributor to the Grenadian economy. However, workers in the industry face many environmental and occupational health risks. The goal of this study was to investigate respiratory health problems and possible related occupational exposures among nutmeg production workers. A questionnaire, spirometry and allergen skin-prick test was given to 92 nutmeg workers. Samples for measurement of airborne dust, mold, and phosphine were also collected from work environments. Approximately half of the workers with lower respiratory symptoms such as dry cough (49.4%) and shortness of breath (42.9%) reported that their symptoms were work related. Spirometry results showed that 18.8% of workers had obstruction. Area geometric mean (GM) inhalable dust concentrations, GM personal concentrations, and total mold spores during work activities were found to be high. High prevalence of respiratory symptoms among workers in this facility was consistent with measured levels of dust and mold, and was widespread over all work areas.


Nature and Utilization of Civil Commitment for Substance Abuse in the United States.
Substance abuse is a leading cause of morbidity and mortality in the United States. Although civil commitment has been used to address substance abuse for more than a century, little is known today about the nature and use of substance-related commitment laws in the United States. We examined statutes between July 2010 and October 2012 from all 50 states and the District of Columbia for provisions authorizing civil commitment of adults for substance abuse and recorded the criteria and evidentiary standard for commitment and the location and the maximum duration of commitment orders. High-level state representatives evaluated these data and provided information on the use of commitment. Thirty-three states have statutory provisions for the civil commitment of persons because of substance abuse. The application of these statutes ranged from a few commitment cases to thousands annually. Although dangerousness was the most common basis for commitment, many states permitted it in other contexts. The maximum duration of treatment ranged from less than 1 month to more than 1 year for both initial and subsequent civil commitment orders. These findings show wide variability in the nature and application of civil commitment statutes for substance abuse in the United States. Such diversity reflects a lack of consensus on the role that civil commitment should play in managing substance abuse and the problems associated with it.


Prevalence and Burden of Self-Reported Health Problems in Junior Male Elite Ice Hockey Players: A 44-Week Prospective Cohort Study.
Little is known about the burden of overuse injuries and illnesses in junior elite ice hockey. To describe the prevalence and burden of all health problems in junior male elite ice hockey players in Norway during 1 school year. Descriptive epidemiological study. A total of 206 junior male ice hockey players (mean age, 17 years; range, 15-20 years) attending specialized sports academy high schools in Norway reported all health problems, acute injuries, overuse injuries, and illnesses, weekly during the 2018-2019 school year (44 weeks). The players self-reported injuries and illnesses using the Oslo Sports Trauma Research Center Questionnaire on Health Problems. Of the players included, 25% (95% CI, 23%-27%) reported at least 1 health problem at any given time, while 16% (95% CI, 14%-17%) experienced health problems with a substantial negative effect on training and performance. Of the total burden of health problems, acute injuries accounted for 44%, overuse injuries 31%, and illnesses 25%. For acute injuries, the greatest burden was caused by injuries to the ankle, knee, and hand, whereas for overuse injuries the most burdensome location was the hip/groin and knee. This study documented that while acute injuries did represent the greatest problem among junior elite ice hockey players, overuse injuries, especially to the knee and hip/groin, also had a substantial effect.


Pancreatic duct stent insertion for functional smoldering pancreatitis.
Some patients with smoldering pancreatitis in the absence of necrosis, pseudocyst, and ductal disruption experience unremitting abdominal pain caused by persistent pancreatic inflammation. Experience with the use of pancreatic duct stents in this patient population was reviewed. Data for 11 patients with smoldering pancreatitis who underwent ERCP with pancreatic duct stent placement were reviewed retrospectively. All patients had severe, daily pain that worsened with ingestion of food, had required narcotic analgesics for control of pain, had lost weight, and had persistently elevated serum levels of pancreatic enzymes as well as pancreatic inflammatory changes on CT (without necrosis or pseudocyst). Six patients were being treated with parenteral nutrition. The mean duration of symptoms from the onset of pancreatitis until pancreatic duct stent insertion was 74 days (range 14-151 days). Stents were placed for a mean of 7 weeks (range 2-19 weeks). Pancreatic stent placement provided permanent pain relief in 10 (91%) patients within a mean of 9 days (range 3-20 days); one patient had persistent symptoms requiring celiac plexus blockade after 5 months. Parenteral nutrition and treatment with narcotic agents were discontinued for 10 patients within a mean of 15 days (range 7-39 days) after pancreatic duct insertion. Smoldering pancreatitis may result from functional obstruction, possibly caused by edema or spasm, of the papillary orifice. Insertion of a stent into the pancreatic duct alleviates pain, enables early resumption of oral intake of food, and facilitates pancreatic duct drainage. It also may help to prevent complications arising from persistent pancreatic inflammation.


Surprising complete response of intramedullary spinal cord metastasis from breast cancer: a case report and literature review.
Intramedullary spinal cord metastases (ISCM) are considered rare but their incidence is rising. Most ISCM cases are recognized to occur in patients with stage IV lung cancer or breast cancer (BC). We report a rare case of cervical BC-ISCM in 60-year-old woman, documented by magnetic resonance imaging and positron emission tomography-computed tomography and treated with volumetric modulated arc therapy with daily image-guided radiation therapy (VMAT/IGRT). An unexpected clinical and radiologic complete response in absence of neurologic side effects was recorded 4 months after VMAT/IGRT. The present case report shows the feasibility of advanced RT and its optimal response in a case of ISCM from BC. Despite the short follow-up, in comparison with available literature data concerning the management of BC-ISCM, we found an early complete response, in contrast with other reported experiences.


Cardiac troponin I is present in plasma of type 1 myocardial infarction patients and patients with troponin I elevations due to other etiologies as complex with little free I.
Cardiac troponin (cTn) is a complex of three subunits (T, I, and C), with some studies reporting that ~5-10% is cytosolic and unbound ('free'). It has been hypothesized that free cTn is released before complex and before or without cell death dependent on the severity of ischemia. In this context, new generation assays that can discriminate free, binary (IC) and ternary (TIC) complex forms may aid to differentiate between type 1 myocardial infarction (MI) and cTn elevations due to different etiologies, e.g. demand ischemia and type 2 MI. Serial plasma samples from six type 1 MI patients and twenty-seven patients with other cTnI elevations, e.g. due to demand ischemia and type 2 MI, were analyzed using high-sensitivity ET Healthcare Pylon assays for total cTnI, complex cTnI (IC and TIC), and cTnTIC. The specificity of the anti-cTnT antibody in the cTnTIC assay was such that only full-size cTnTIC is detected. In vitro stability of different cTnI forms was assessed by spiking free cTnI and cTnTIC in cTnI-free serum, incubating at 4 or 37 °C, and measuring different cTnI forms over 0-182 h. Presence of cytosolic free cTnI was evaluated on fixed rat cardiac tissue using an antibody against free cTnI. Pylon assays for total and complex cTnI tracked well over time with each other and gave similar results, both for type 1 MI and non-type 1 MI patients, indicating that the vast majority was complex cTnI. As a minority of complex cTnI was full-size cTnTIC, this indicated that complex cTnI mainly consisted of a degraded form of cTnTIC (low-molecular weight cTnTIC) and/or cTnIC. Full-size cTnTIC was more abundant in early compared to late samples. In vitro studies indicated that free cTnI and cTnTIC are not stable at 37 °C (28% and 11% recovery after 24 h, respectively) and this is also true to some extent for cTnTIC at 4 °C (60% recovery after 24 h). Free cTnI was not readily detected in rat cardiac tissue. In agreement with type 1 MI, cTnI in samples of patients with cTnI elevations due to other etiologies is found predominantly as complex cTnI, of which some is full-size cTnTIC. In most cases, assays for total and complex cTnI indicated there was little free cTnI; however, its presence cannot be completely excluded, due to the inability of its direct measurement and limited stability.


Tissue growth into three-dimensional composite scaffolds with controlled micro-features and nanotopographical surfaces.
Controlling topographic features at all length scales is of great importance for the interaction of cells with tissue regenerative materials. We utilized an indirect three-dimensional printing method to fabricate polymeric scaffolds with pre-defined and controlled external and internal architecture that had an interconnected structure with macro- (400-500 μm) and micro- (∼25 μm) porosity. Polycaprolactone (PCL) was used as model system to study the kinetics of tissue growth within porous scaffolds. The surface of the scaffolds was decorated with TiO2 and bioactive glass (BG) nanoparticles to the better match to nanoarchitecture of extracellular matrix (ECM). Micrometric BG particles were also used to reveal the effect of particle size on the cell behavior. Observation of tissue growth and enzyme activity on two-dimensional (2D) films and three-dimensional (3D) scaffolds showed effects of nanoparticle inclusion and of surface curvature on the cellular adhesion, proliferation, and kinetics of preosteoblastic cells (MC3T3-E1) tissue growth into the pore channels. It was found that the presence of nanoparticles in the substrate impaired cellular adhesion and proliferation in 3D structures. Evaluation of alkaline phosphate activity showed that the presence of the hard particles affects differentiation of the cells on 2D films. Notwithstanding, the effect of particles on cell differentiation was not as strong as that seen by the curvature of the substrate. We observed different effects of nanofeatures on 2D structures with those of 3D scaffolds, which influence the cell proliferation and differentiation for non-load-bearing applications in bone regenerative medicine.


A comparison of sampling methods with respect to cattle-visiting Muscidae and their nematode infections.
Cattle-visiting Muscidae were sampled with a handnet from a blood-smeared Masonite panel as well as grazing heifers and dairy cows in south-central Sweden. All flies were examined in search of nematodes. Only Musca autumnalis was infected with nematodes (Parafilaria bovicola, Thelazia spp. and Heterotylenchus autumnalis). The only mixed infections found involved P. bovicola and Thelazia spp. Most M. autumnalis infected with P. bovicola and Thelazia spp. were found during the two first months of the grazing season, whereas the prevalence of specimens infected with H. autumnalis remained about the same throughout the sampling period. Musca autumnalis was caught in significantly smaller numbers from heifers (P < 0.05) than from panel and cows. The catches of nematode-infected M. autumnalis were similarly distributed. Catches of other cattle-visiting Muscidae did not differ significantly among the methods used. Handnet sampling off a panel is therefore considered to be a convenient and accurate method when investigating the abundance of cattle-visiting Muscidae and the prevalence of their nematode infections.


Eosinophils utilize multiple chemokine receptors for chemotaxis to the parasitic nematode Strongyloides stercoralis.
Protective innate immunity to the nematode Strongyloides stercoralis requires eosinophils in the parasite killing process. Experiments were performed to determine if an extract of S. stercoralis would trigger eosinophil chemotaxis, and to then compare the chemotactic migration response, including second messenger signals and receptors, to those mechanisms triggered by host chemoattractants. Eosinophils undergo both chemotaxis and chemokinesis to soluble parasite extract in transwell plates. Pretreatment of eosinophils with pertussis toxin, a G protein-coupled receptor inhibitor, inhibited migration of the eosinophils to the parasite extract. Likewise, blocking PI3K, tyrosine kinase, p38 and p44/42 inhibited eosinophil chemotaxis to parasite extract. Furthermore, CCR3, CXCR4 or CXCR2 antagonists significantly inhibited eosinophil chemotaxis to the parasite extract. Molecular weight fractionation of parasite extract revealed that molecules attracting eosinophils were present in several fractions, with molecules greater than 30 kDa being the most potent. Treating the extract with proteinase K or chitinase significantly inhibited its ability to induce chemotaxis, thereby demonstrating that the chemoattractants were both protein and chitin. Therefore, chemoattractants derived from parasites and host species stimulate similar receptors and second messenger signals to induce eosinophil chemotaxis. Parasite extract stimulates multiple receptors on the eosinophil surface, which ensures a robust innate immune response to the parasite.


Increased miR-155 expression in peripheral blood mononuclear cells of primary immune thrombocytopenia patients was correlated with serum cytokine profiles.
We investigated the possible pathogenic role of a microRNA (miR-155) in primary immune thrombocytopenia (ITP). We used quantitative real-time PCR to determine the relative expression of miR-155 and SOCS1 (suppressor of cytokine signaling) mRNA in peripheral blood mononuclear cells (PBMCs) from 28 ITP patients and 28 healthy controls. Cytokine plasma levels were determined by ELISA. Possible associations between miR-155 levels and serum cytokine concentrations were assessed using Spearman or Pearson correlation analysis. Seven naive ITP patients were followed and the effects of medical treatment on miR-155 levels were assessed. Compared to healthy controls, ITP patients had increased miR-155 and decreased SOCS1 mRNA levels. ITP patients also had increased plasma IL-17A and decreased IL-4, IL-10 and TGF-β1 levels. miR-155 levels were negatively correlated with platelet counts, SOCS1 mRNA levels, and the plasma levels of IL-4, IL-10 and TGF-β1, but positively correlated with plasma IL-17A levels. Medical treatment for ITP decreased miR-155 levels. Thus, our results suggest that miR-155 might be involved in the pathogenesis of ITP by regulating cytokine profiles, which may be mediated by miR-155 targeting SOCS1.


[Angiotensin I-converting enzyme in cerebrospinal fluid and neurosarcoidosis].
Sarcoidosis is a disease of unknown aetiology. This granulomatous disease is essentially localized in lung and skin, but many other localizations are possible, such as in nervous system. Sometimes the neurological involvement is alone leading to a differential diagnosis from other neurological diseases. Angiotensin I-converting enzyme (ACE) is synthesized by sarcoidotic granulomas and diffuses in various biological fluids. The determination of ACE activity in cerebrospinal fluid (CSF) can help for the diagnosis of neurosarcoidosis, associated or not to its determination in serum. We developed a radiometric assay for the determination of ACE activity in CSF since the methods for serum cannot be used because ACE activity is low in CSF, as well as in pathological situations. At the analytical point of view this assay is sensitive, specific and reproducible. We established a normal range and yielded recommendations to give the results, particularly in function of the aspect of the CSF and the proteinorrachia. But increased level of ACE in CSF is not specific of neurosarcoidosis since elevations were also shown in meningitis. We can claim for the routine use of ACE assay in CSF for differential diagnosis by eliminating neurosarcoidosis, as well as for positive diagnosis of this disease, but in both cases with the confrontation to other parameters.


Second-step reconcentration of environmental samples by ammonium sulfate flocculation of beef extract.
Some enteric viruses are sensitive to the acid environment utilized during the concentration of viruses from water. The use of a neutral flocculant, neutralized ammonium sulfate at 50% saturation, permitted the recovery of 97% of the simian rotavirus SA-11, 87% of Coxsackievirus B-4, and 88% of poliovirus type 1. This method should permit a better recovery of enteric viruses from the environment.


Two-dimensional organization of mono- and bisurea supramolecular polymers studied by scanning tunneling microscopy.
Scanning tunneling microscopy (STM) of mono- and bisurea-functionalized oligo(p-phenylenevinylene)s at solid/liquid interface visualized two-dimensionally-ordered double columnar structures of pi-conjugated segments scaffolded by one-dimensional supramolecular polymerization of urea hydrogen-bonding units. In contrast to a persistent alignment of the bisurea compound supported by twofold intermolecular urea-urea hydrogen-bonding, the building blocks in the monourea double columns shows dynamic fluctuation and defects because of their rotational motion around urea-urea hydrogen-bonding axis and/or adsorption-desorption of the individual molecules from the surface. Self-assembled structures of mono- and bisurea compounds at solid/liquid interface revealed by STM can be related to their gelation abilities in organic solvents.


Abrogated cryptic activation of lentiviral transfer vectors.
Despite significant improvements in lentivirus (LV) vector-based gene therapy there are still several safety risks using LV vectors including the potential formation of replication-competent LV particles. To address this shortcoming, we constructed a novel and safer gene transfer system using modified SIN-based LV gene transfer vectors. Central to our approach is a conditional deletion of the Ψ packaging signal after integration in the target genome. Here we demonstrate that after transduction of target cells, conventional SIN-based LV transfer vectors can still be mobilized. However mobilization is rendered undetectable if transductions are followed by a Cre/loxP-mediated excision of Ψ. Thus conditional elimination of the packaging signal may represent another advance in increasing the safety of LV vectors for gene therapeutic treatment of chronic diseases.


Incomplete quality of life data in lung transplant research: comparing cross sectional, repeated measures ANOVA, and multi-level analysis.
In longitudinal studies on Health Related Quality of Life (HRQL) it frequently occurs that patients have one or more missing forms, which may cause bias, and reduce the sample size. Aims of the present study were to address the problem of missing data in the field of lung transplantation (LgTX) and HRQL, to compare results obtained with different methods of analysis, and to show the value of each type of statistical method used to summarize data. Results from cross-sectional analysis, repeated measures on complete cases (ANOVA), and a multi-level analysis were compared. The scores on the dimension 'energy' of the Nottingham Health Profile (NHP) after transplantation were used to illustrate the differences between methods. Compared to repeated measures ANOVA, the cross-sectional and multi-level analysis included more patients, and allowed for a longer period of follow-up. In contrast to the cross sectional analyses, in the complete case analysis, and the multi-level analysis, the correlation between different time points was taken into account. Patterns over time of the three methods were comparable. In general, results from repeated measures ANOVA showed the most favorable energy scores, and results from the multi-level analysis the least favorable. Due to the separate subgroups per time point in the cross-sectional analysis, and the relatively small number of patients in the repeated measures ANOVA, inclusion of predictors was only possible in the multi-level analysis. Results obtained with the various methods of analysis differed, indicating some reduction of bias took place. Multi-level analysis is a useful approach to study changes over time in a data set where missing data, to reduce bias, make efficient use of available data, and to include predictors, in studies concerning the effects of LgTX on HRQL.


Numerical analysis of brilliance and coherent photon flux of segmented undulator radiation based on statistical optics.
A method based on wave optics together with electron tracking is used to analyze synchrotron radiation from a segmented undulator in a double or multi mini-β function lattice storage ring. Radiation brilliance and transverse coherence features are investigated, where the former is calculated with the Wigner distribution function and the latter is evaluated by integrating the photon flux and cross-spectral density to exhibit the coherent flux and overall degree of coherence. To be specific, radiation properties for a single undulator in a typically single mini-β function and a tandem undulator in a double mini-βy lattice are compared in this work. As a result, both, brilliance and coherent flux can be enhanced by a second tandem undulator at the Taiwan Photon Source.


Comparative longevity of pet dogs and humans: implications for gerontology research.
The effect of breed and body weight on longevity in the pet dog was analyzed, and a method was developed to standardize the chronological age of dogs in terms of physiological time, using human year equivalents. Mortality data from 23,535 pet dogs were obtained from a computerized data base of North American veterinary teaching hospitals, and the median age at death was determined for pure and mixed breed dogs of different body weight. Body size in the dog was inversely related to longevity. Within each body weight category, the median age at death was lower for pure breed dogs compared with mixed breed dogs. The difference between the standardized physiological ages of mixed breed dogs of the same chronological age in the smallest and largest body weight categories varied from 8 to > 15 years, and between large and small pure breed dogs, the disparity was even greater. Laboratory research to explore the biological basis for these breed and body weight specific differences in life span among dogs may provide additional clues to genetic factors influencing senescence.


Gene expression in chronic high altitude diseases.
Chronic mountain sickness (CMS) and high altitude pulmonary hypertension (HAPH) have been well described in different mountainous regions of the world as chronic high altitude (HA) diseases. This review briefly summarizes the available data from some genes known to be regulated by hypoxia-inducible factor 1 (HIF-1) and/or by hypoxia that have been studied in populations from these regions suffering from CMS and/or HAPH. Excessive erythrocytosis, caused by a lower oxygen saturation and hypoxic ventilatory response and/or ventilatory inefficiency, is the outstanding sign of CMS, and right ventricular enlargement, pulmonary hypertension, and remodeling of pulmonary arterioles are hallmarks of HAPH. Familial character and heritability studies have suggested that genetic factors could make a contribution to the pathogenesis of CMS and HAPH. Even though some alleles are more prevalent (G allele of eNOS polymorphism Glu298Asp in Sherpas and ACE I allele in HAPH Kyrgyz) or less prevalent (ACE D allele in HA Andeans) in the different high altitude populations, published data to date are insufficient for a rigorous test of any hypothesis regarding the implications of these gene polymorphims in CMS or HAPH.


Transient length responses of heart muscle in Ba2+-contracture to step tension reductions.
The transient length response of the cat papillary muscle in Ba2+-contracture to step tension reduction was found to comprise four different phases. It is tentatively suggested that the transient response is mostly determined by the kinetics of the attachment and detachment of cross-bridges between actin and myosin filaments, which vary appreciably with activation level of the muscle.


Distinct evolutionary histories of the DNA-A and DNA-B components of bipartite begomoviruses.
Viruses of the genus Begomovirus (family Geminiviridae) have genomes consisting of either one or two genomic components. The component of bipartite begomoviruses known as DNA-A is homologous to the genomes of all geminiviruses and encodes proteins required for replication, control of gene expression, overcoming host defenses, encapsidation and insect transmission. The second component, referred to as DNA-B, encodes two proteins with functions in intra- and intercellular movement in host plants. The origin of the DNA-B component remains unclear. The study described here was initiated to investigate the relationship between the DNA-A and DNA-B components of bipartite begomoviruses with a view to unraveling their evolutionary histories and providing information on the possible origin of the DNA-B component. Comparative phylogenetic and exhaustive pairwise sequence comparison of all DNA-A and DNA-B components of begomoviruses demonstrates that the two molecules have very distinct molecular evolutionary histories and likely are under very different evolutionary pressures. The analysis highlights that component exchange has played a far greater role in diversification of begomoviruses than previously suspected, although there are distinct differences in the apparent ability of different groups of viruses to utilize this "sexual" mechanism of genetic exchange. Additionally we explore the hypothesis that DNA-B originated as a satellite that was captured by the monopartite progenitor of all extant bipartite begomoviruses and subsequently evolved to become the integral (essential) genome component that we recognize today. The situation with present-day satellites associated with begomoviruses provides some clues to the processes and selection pressures that may have led to the "domestication" of a wild progenitor of the DNA-B component. The analysis has highlighted the greater genetic variation of DNA-B components, in comparison to the DNA-A components, and that component exchange is more widespread than previously demonstrated and confined to viruses from the Old World. Although the vast majority of New World and some Old World begomoviruses show near perfect co-evolution of the DNA-A and DNA-B components, this is not the case for the majority of Old World viruses. Genetic differences between Old and New World begomoviruses and the cultivation of exotic crops in the Old World are likely factors that have led to this dichotomy.


[Element composition of bacterial cells of various taxa].
The elemental compositions of cells of representatives of five bacterial genera (Hyphomonas vulgare NP-160, Caulobacter bacteroides NP-105, Flectobacillus major Mm, Escherichia coli, and Spirulina platensis) was studied by electron microscopic x-ray microanalysis. The contents of P, S, Cl, K, and Ca were determined. The bacterial species studied in this work substantially differ by the contents of these elements. A high content of K is typical of S. platensis, whereas F. major, an aquatic form, is rich in Cl. The other bacterial species were had the levels of K, Ca, and the K/Ca index, which correlated with the stability of their cell membranes and resistance to stress. In E. coli, the spectrum of the elemental composition and the values of P/S and K/Ca are indicative of high energy potential and low tolerance of membranes.


Suicide prevention through means restriction: Impact of the 2008-2011 pesticide restrictions on suicide in Sri Lanka.
To investigate the effect of 3-year phased bans of the pesticides dimethoate and fenthion in 2008-2010, and paraquat in 2009-2011, on suicide mortality in Sri Lanka. Age-standardised overall, sex-specific, and method-specific suicide rates were calculated using Sri Lankan police data (1989-2015). Using negative binomial regression models, we estimated the change in the rate and number of suicide deaths in post-ban years (2011-15) compared to those expected based on pre-ban trends (2001-10). Overall suicide mortality dropped by 21% between 2011 and 2015, from 18.3 to 14.3 per 100,000. The decline in pesticide suicides during this same period was larger than for overall suicides: from 8.5 to 4.2 per 100,000, a 50% reduction. This was accompanied by a smaller concurrent rise in non-pesticide suicide mortality with a 2% increase (9.9 to 10.1 per 100,000). In 2015, the ratio between the observed and expected pesticide suicide rates was 0.49 (95% confidence interval [CI] 0.40, 0.62), corresponding to an estimated 937 (95% CI 574, 1389) fewer pesticide suicides than expected from pre-ban suicide rates. Findings were similar in sensitivity analyses using 2008 or 2012 as commencement of the post intervention period. Bans of paraquat, dimethoate and fenthion in Sri Lanka were associated with a reduction in pesticide suicide mortality and in overall suicide mortality despite a small rise in other methods. This study provides further evidence for the effectiveness of pesticide regulation in limiting the availability of highly hazardous pesticides and thereby reducing the number of global suicides.


Pulmonary capillary hemangiomatosis imaging findings and literature update.
Pulmonary capillary hemangiomatosis (PCH) is a rare and an only recently described vascular disease. As one of the causes of primary pulmonary hypertension, the need for the establishment of helpful diagnostic radiological criteria for this condition has become imperative. However, the unstable hemodynamic condition of patients with primary pulmonary hypertension often denies pathological sampling as a definitive diagnostic tool. This diagnostic dilemma can be fatal to those patients with PCH treated for pulmonary hypertension because a fatal pulmonary edema may occur. We report a case of PCH in a 26-year-old patient who died of severe circulatory compromise while undergoing transplant evaluation. A discussion of the computed tomography findings, a review of the pathological features, and a review of the relatively limited imaging literature available on this subject are conducted.


Ras and Rab Interactor 3: From Cellular Mechanisms to Human Diseases.
Ras and Rab interactor 3 (RIN3) functions as a Guanine nucleotide Exchange Factor (GEF) for some members of the Rab family of small GTPase. By promoting the activation of Rab5, RIN3 plays an important role in regulating endocytosis and endocytic trafficking. In addition, RIN3 activates Ras, another small GTPase, that controls multiple signaling pathways to regulate cellular function. Increasing evidence suggests that dysregulation of RIN3 activity may contribute to the pathogenesis of several disease conditions ranging from Paget's Disease of the Bone (PDB), Alzheimer's Disease (AD), Chronic Obstructive Pulmonary Disease (COPD) and to obesity. Recent genome-wide association studies (GWAS) identified variants in the RIN3 gene to be linked with these disease conditions. Interestingly, some variants appear to be missense mutations in the functional domains of the RIN3 protein while most variants are located in the noncoding regions of the RIN3 gene, potentially altering its gene expression. However, neither the protein structure of RIN3 nor its exact function(s) (except for its GEF activity) has been fully defined. Furthermore, how the polymorphisms/variants contribute to disease pathogenesis remain to be understood. Herein, we examine, and review published studies in an attempt to provide a better understanding of the physiological function of RIN3; More importantly, we construct a framework linking the polymorphisms/variants of RIN3 to altered cell signaling and endocytic traffic, and to potential disease mechanism(s).


Retinoblastoma. Unusual warning and clinical signs.
Three clinical cases have been chosen to illustrate the pitfalls that can be encountered when warning signs other than leukokoria or strabismus indicate possible retinoblastoma. The first case, a four-year-old boy, was admitted to hospital after an accident, presenting uveitis, glaucoma and a subluxated lens. He was suffering from unilateral retinoblastoma, already exteriorized and the cause of death some months later. The second case, and 11-month-old female child was seen on fundus examination to present a yellowish elevated calcified mass which turned out to be tuberous sclerosis. The third patient, a 43-year-old male, father of two children suffering from retinoblastoma, was found on routine examination to be carrying a partially-calcified retinal tumour. Subsequent haemorrhaging rendered enucleation necessary and microscopic examination confirmed the diagnosis of retinoma. The diagnosis of retinoblastoma should always be kept in mind whenever an intraocular mass is revealed or where there are unexplained atypical ocular signs.


Possible role of gut microbes and host's immune response in gut-lung homeostasis.
The vast diversity of microbial communities reside in various locations of the human body, and they are collectively named as the 'Human Microbiota.' The majority of those microbes are found in the gastrointestinal and respiratory tracts. The microorganisms present in the gastrointestinal and the respiratory tracts are called the gut microbiota and the airway microbiota, respectively. These microbial communities are known to affect both the metabolic functions and the immune responses of the host. Among multiple factors determining the composition of gut microbiota, diet has played a pivotal role. The gut microbes possess enzymatic machinery for assimilating dietary fibers and releasing different metabolites, primarily short-chain fatty acids (SCFAs). The SCFAs modulate the immune responses of not only the gut but other distal mucosal sites as well, such as the lungs. Dysbiosis in normal gut flora is one of the factors involved in the development of asthma and other respiratory disorders. Of note, several human and murine studies have indicated significant cross-talk between gut microbiota and lung immunity, known as the gut-lung axis. Here, in this review, we summarize the recent state of the field concerning the effect of dietary metabolites, particularly SCFAs, on the "gut-lung axis" as well as discuss its impact on lung health. Moreover, we have highlighted the role of the "gut-lung axis" in SARS-CoV-2 mediated inflammation. Also, to analyze the global research progress on the gut-lung axis and to identify the knowledge gap in this field, we have also utilized the bibliographic tools Dimension database and VOS viewer analysis software. Through network mapping and visualization analysis, we can predict the present research trend and the possibility to explore new directions.


Effect of Concomitant Atrial Fibrillation on In-Hospital Outcomes of Non-ST-Elevation-Acute Coronary Syndrome-Related Hospitalizations in the United States.
Atrial fibrillation (AF) is the most common arrhythmia in patients presenting with acute coronary syndrome (ACS). The present study examined the rates and trends of clinical outcomes and management strategies of non-ST-elevation ACS (NSTE-ACS) related hospitalizations in the United States, in patients with concomitant AF compared with those in sinus rhythm (SR). We analyzed the "Nationwide Inpatient Sample" database (2004 to 2014) for patients with a primary discharge diagnosis of NSTE-ACS, and further stratified the cohort on the basis of diagnoses into SR and AF groups. Multivariate analysis was performed to examine the association between AF and major adverse cardiovascular and cerebrovascular events (composite of mortality, stroke, and cardiac complications) and its components. Of 4,668,737 NSTE-ACS hospitalizations, the proportions of SR and AF groups were 82.4% (3,848,202) and 17.6% (820,535), respectively. The incidence of AF increased significantly over time from 16.5% (2004) to 19.3% (2014). The AF group was at a greater risk of adverse outcomes with higher rates and adjusted relative risk (RR) of major adverse cardiovascular and cerebrovascular events (12.9% vs 5.3%; RR 1.74 [1.72, 1.75]), mortality (6.5% vs 3.3%; RR 1.12 [1.11, 1.13]), stroke (2.7% vs 1.5%; RR 1.32 [1.30, 1.34]), and bleeding (14.7% vs 8.8%; RR 1.42 [1.41, 1.43]). Furthermore, the AF group was less likely to receive coronary angiography (47.1% vs 58%) and percutaneous coronary intervention (18.7% vs 32.6%) in comparison to SR (p <0.001 for all outcomes). In conclusion, patients with concomitant AF and NSTE-ACS are less likely to be offered an invasive management strategy for their ACS and are associated with worse complications and higher mortality.


Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms.
The Drosophila neoplastic tumor suppressor Lethal (2) giant larvae (Lgl) controls apicobasal cell polarity and proliferation. We have previously shown that lgl(-) clones in the developing eye exhibit ectopic proliferation and suppress apoptosis without affecting apicobasal cell polarity. Ectopic expression of the apical polarity regulators atypical protein kinase C (aPKC) and Crumbs also leads to increased cell proliferation and/or survival. Here we investigate how these cell polarity regulators control proliferation and survival. We report that depletion of lgl in eye epithelial tissue, where polarity is maintained, results in upregulation of targets of the Salvador/Warts/Hippo (SWH) tumor suppressor pathway. Consistent with this, the SWH pathway transcriptional coactivator Yorkie is hyperactivated in Lgl-deficient tissue and is rate limiting for lgl(-) phenotypes. Overexpression of the apical polarity regulators Crumbs or aPKC also leads to ectopic expression of SWH pathway targets without affecting polarity. We show that Lgl depletion or aPKC overexpression results in comislocalization of Hippo and Ras-associated domain family protein (RASSF), consistent with RASSF's ability to block Hippo activation by Salvador. In contrast, Crumbs overexpression leads to mislocalization of Expanded away from the apical cortex, which is predicted to deregulate the pathway. Collectively, our data reveal that the cell polarity regulators Lgl, aPKC, and Crumbs regulate the SWH pathway by two distinct pathways: Lgl acts antagonistically to aPKC to regulate Hippo and RASSF localization, whereas Crumbs regulates Expanded localization. Thus, our study implicates Lgl, aPKC, and Crumbs as regulators of tissue growth via the SWH pathway.


Tumor lysis under anesthesia in a child.
Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency characterized by metabolic derangements caused by massive lysis and release of cellular components. TLS has been reported to occur under various circumstances. There have however, been only two reports of precipitation of TLS by anesthesia in the current medical literature. We report on the development of TLS in a 7-year-old child with a pelvic neuroectodermal tumor following induction of anesthesia and discuss the peri-operative concerns while dealing with patients with high tumor burdens.


A survey of the incidence of single-visit endodontics.
This survey was conducted to obtain answers to some basic questions regarding the timing of root canal obturation. A questionnaire was sent via e-mail to 738 randomly chosen United States endodontists listed in the 1998 to 1999 membership roster of the American Association of Endodontists. One hundred fifty-six replies were received. In pulpectomy cases, root canal obturation at the first visit was carried out by 55.8% of the responding endodontists; in infected root canal cases, the percentage was 34.4%. Of the responding endodontists, 34.2% indicated that their patients had experienced some trouble after root canal obturation at the first visit.


Functional properties of EGFP-tagged skeletal muscle calcium-release channel (ryanodine receptor) expressed in COS-7 cells: sensitivity to caffeine and 4-chloro-m-cresol.
We constructed and expressed in COS-7 cells, three E-green fluorescent protein (EGFP) tagged recombinant skeletal muscle ryanodine receptors (RYR). EGFP was tagged to (i) the NH2-terminus (nEGFP-RYR(FL)) and to (ii) the COOH-terminus (cRYR(FL)-EGFP) of the full length RYR; we also tagged the EGFP to (iii) the NH2-terminus of a truncated version of the RYR (nEGFP-RYR(Bhat)) lacking the bulk of the protein. The fluorescent pattern EGFP with all three constructs colocalize with that of an endoplasmic reticulum (ER) membrane tracker fluorescent dye, indicating that the RYR constructs are targeted to ER membranes. Our results show that: (i) COOH-terminal tagging abolishes the sensitivity of the RYR to caffeine, whereas the presence of EGFP at the NH2-terminus does not affect caffeine sensitivity and (ii) 4-Cl-m-cresol sensitivity is lost both with the truncated nEGFP-RYR(Bhat) and the nEGFP-RYR(FL), while COOH-terminal tagging does not affect sensitivity to 4-chloro-m-cresol. The dose-response curves of caffeine-induced calcium release of nEGFP-RYR(FL) differ from those of the truncated nEGFP-RYR(Bhat). Maximal calcium release was approached at 10 mM caffeine with the nEGFP-RYR(FL), while cells expressing the nEGFP-RYR(Bhat) construct displayed a bell shaped curve and the maximal concentration for caffeine-induced calcium release was 5 mM. Equilibrium [3H]-ryanodine binding confirmed the calcium photometry data. Our results demonstrate that EGFP tagging modifies the pharmacological properties of RYR, and suggest that 4-chloro-m-cresol and caffeine act through different mechanisms and probably interact with different sites on the RYR calcium release channel.


Impact of defect configuration on the clinical outcome following surgical regenerative therapy of peri-implantitis.
The present study aimed at investigating the impact of defect configuration on the clinical outcome of surgical regenerative therapy of peri-implantitis lesions using a natural bone mineral in combination with a collagen membrane (NBM+CM). Twenty-seven patients (n=27 defects) exhibited three different types of peri-implantitis lesions including either Class Ib (buccal dehiscence+semicircumferential), Class Ic (buccal dehiscence+circumferential), or Class Ie (circumferential) intra-bony defects (n=9 defects per group). All defects were treated with access flap surgery and the application of NBM+CM. At 6 and 12 months, Class Ie defects tended to reveal higher changes in the mean probing depth (PD) and clinical attachment level (CAL) values when compared with Class Ib and Class Ic groups. However, significant differences were only observed at 6 months (PD: 2.9 +/- 0.3 versus 1.4 +/- 0.5 versus 1.3 +/- 0.7 mm; CAL: 2.5 +/- 0.5 versus 0.9 +/- 0.8 versus 0.9 +/- 0.7 mm). Site-level analysis has pointed to lowest PD and CAL changes at the midbuccal aspect of Class Ib and Class Ic groups. Defect configuration may have an impact on the clinical outcome following surgical regenerative therapy of peri-implantitis lesions. While Class Ie defects seem to be promising in conjunction with NBM+CM, Class Ib and Class Ic may be considered as unfavourable.


PICALM rescues glutamatergic neurotransmission, behavioural function and survival in a Drosophila model of Aβ42 toxicity.
Alzheimer's disease (AD) is the most common form of dementia and the most prevalent neurodegenerative disease. Genome-wide association studies have linked PICALM to AD risk. PICALM has been implicated in Aβ42 production and turnover, but whether it plays a direct role in modulating Aβ42 toxicity remains unclear. We found that increased expression of the Drosophila PICALM orthologue lap could rescue Aβ42 toxicity in an adult-onset model of AD, without affecting Aβ42 level. Imbalances in the glutamatergic system, leading to excessive, toxic stimulation, have been associated with AD. We found that Aβ42 caused the accumulation of presynaptic vesicular glutamate transporter (VGlut) and increased spontaneous glutamate release. Increased lap expression reversed these phenotypes back to control levels, suggesting that lap may modulate glutamatergic transmission. We also found that lap modulated the localization of amphiphysin (Amph), the homologue of another AD risk factor BIN1, and that Amph itself modulated postsynaptic glutamate receptor (GluRII) localization. We propose a model where PICALM modulates glutamatergic transmission, together with BIN1, to ameliorate synaptic dysfunction and disease progression.


Aspiration cytology of salivary glands.
Although mass lesions of the salivary glands are readily accessible to examination by fine-needle aspiration, the use of this modality has been limited. In part, this may be related to the difficulty differentiating between benign and malignant neoplasms in some cytologic specimens. Marked atypia in reactive non-neoplastic epithelium also could result in a false-positive diagnosis. In addition, aspiration of hypocellular material from cystic neoplasms, eg, well-differentiated mucoepidermoid carcinoma, may lead to false-negative cytologic reports. However, the diagnostic specificities claimed by a number of authors for this method are excellent. Furthermore, aspirates of certain specific neoplasms may yield highly distinctive cellular samples, such as the uniform tumor cells and extracellular hyaline spheres in many adenoid cystic carcinomas. Another example is the characteristic transition between the epithelial and myoepithelial cells of pleomorphic adenomas, which may contain prominent myxoid matrical material. With the increasing recognition of such features, the reported levels of diagnostic accuracy are improving.