Evaluation of in vivo anti-hyperglycemic and antioxidant potentials of α-santalol and sandalwood oil.
Sandalwood finds numerous mentions across diverse traditional medicinal systems in use worldwide. The objective of this study was to evaluate the in vivo anti-hyperglycemic and antioxidant potential of sandalwood oil and its major constituent α-santalol. The in vivo anti-hyperglycemic experiment was conducted in alloxan-induced diabetic male Swiss albino mice models. The in vivo antioxidant experiment was performed in d-galactose mediated oxidative stress induced male Swiss albino mice models. Intraperitoneal administration of α-santalol (100mg/kg BW) and sandalwood oil (1g/kg BW) for an week modulated parameters such as body weight, blood glucose, serum bilirubin, liver glycogen, and lipid peroxides contents to normoglycemic levels in the alloxan-induced diabetic mice. Similarly, intraperitoneal administration of α-santalol (100mg/kg BW) and sandalwood oil (1g/kg BW) for two weeks modulated parameters such as serum aminotransferases, alkaline phosphatase, bilirubin, superoxide dismutase, catalase, free sulfhydryl, protein carbonyl, nitric oxide, liver lipid peroxide contents, and antioxidant capacity in d-galactose mediated oxidative stress induced mice. Besides, it was observed that the beneficial effects of α-santalol were well complimented, differentially by other constituents present in sandalwood oil, thus indicating synergism in biological activity of this traditionally used bioresource.


Memories of colonoscopy: a randomized trial.
Patients' memories of the past may influence their decisions about the future, yet memories are imperfect and susceptible to bias. We tested whether a memory failure observed in psychology experiments could be applied in a clinical setting to lessen patients' memories of the pain of an unpleasant medical procedure. We studied consecutive outpatients undergoing colonoscopy who were medically stable, mentally competent, and able to speak English (n=682). By random assignment, half the patients had a short interval added to the end of their procedure during which the tip of the colonoscope remained in the rectum. Pain during the procedure was measured with a ten point intensity scale. Memory following the procedure was measured using both a rating scale and a ranking task. Randomization resulted in two similar groups. As theorized, patients who underwent the extended procedure experienced the final moments as less painful (1.7 vs. 2.5 on a ten point intensity scale, P<0.001), rated the entire experience as less unpleasant (4.4 vs. 4.9 on a 10 cm visual analogue scale, P=0.006), and ranked the procedure as less aversive compared to seven other unpleasant experiences (4.1 vs. 4.6 with eight as the worst, P=0.002). Rates of returning for a repeat colonoscopy (median duration of follow-up 5.3 years) averaged 50.4% and were slightly higher (odds ratio=1.41, P=0.038) for those who underwent the longer procedure controlling for prior colonoscopy, procedure indications, and abnormal findings. Memory failures observed in experimental conditions can be found in clinical settings involving awake patients and may offer opportunities for improving patients' willingness to undergo future unpleasant medical procedures.


Triplet chemotherapy combination with cisplatin, gemcitabine and docetaxel in patients with chemotherapy-naive advanced non-small cell lung cancer.
The synergistic effects of new generation chemotherapeutics when combined with cisplatin have encouraged the development of new triplet combination regimens in the treatment of advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the feasibility of triplet chemotherapy using weekly cisplatin-gemcitabine-docetaxel (CGD) for patients with chemotherapy-naive NSCLC. Twenty-seven patients with stage IIIB/IV disease and performance status of 0 to 2 were included in this prospective trial. A combination of gemcitabine 750 mg/m2, cisplatin 25 mg/m2 and docetaxel 25 mg/m2 was administered on days 1, 8 and 15, with cycles repeated every 3 weeks. Leucopenia and/or neutropenia and to a lesser extent thrombocytopenia were the main dose-limiting toxicities. Grade III-IV neutropenia and thrombocytopenia occurred in 26 and 7% of the patients, respectively. Only one patient developed febrile neutropenia. Dose reductions were required in 26% of patients, delays in 44% of patients and early treatment discontinuation in 15% of patients. The overall response rate was 52% and all of them experienced a partial response. The median progression-free (PFS) and overall survival (OS) times were 6 and 13 months, respectively. The one-year survival rate was 46%. In conclusion, weekly administration of CGD is an active first-line therapy with acceptable toxicity in advanced NSCLC patients.


Protective capacity of antibodies to outer-membrane components of Escherichia coli in a systemic mouse peritonitis model.
Antibody-mediated protection was studied in an experimental murine model of peritonitis-septicaemia with Escherichia coli O18:K1. Protection from lethal intraperitoneal challenge was achieved by passive immunisation with horse anti-K1 capsular antiserum (H46) or rabbit antiserum to the homologous O18 antigen. The maximum increase in LD50 achieved with anti-K1 and anti-O18 antibodies was 10- and 5-fold, respectively. The protective capacity of the anti-O serum was found to be in the IgG fraction. Rabbits were also immunised with various semi-purified or purified outer-membrane-protein preparations (porins and OmpA protein) from rough E. coli or Salmonella strains or with whole E. coli J5 bacteria. Although this immunisation resulted in high antibody titres to homologous and, to a lesser extent, also to heterologous antigens, none of the antisera protected against challenge with the capsulate E. coli O18:K1 bacteria.


Differentiation of primary from nonprimary genital herpes infections by a herpes simplex virus-specific immunoglobulin G avidity assay.
An immunoglobulin G (IgG) antibody avidity assay which uses protein-denaturing agents and a modification of an enzyme-linked immunosorbent assay have been investigated for their usefulness in distinguishing primary genital herpes simplex virus (HSV) infections from nonprimary infections. Forty-nine serum specimens from patients with primary, recurrent, and nonprimary first-episode genital herpes were studied. The clearest separation was obtained with 6 M urea treatment, giving mean avidity indices of 0.398 for sera < or = 100 days after the infection and 0.879 for sera > 100 days after the infection (P < 0.001). No significant difference in avidity indices was observed between the recurrent and nonprimary first-episode infections. Determination of the avidity of HSV-specific IgG will improve the diagnostic potential of HSV serology.


Amyloid fibril formation by pentapeptide and tetrapeptide fragments of human calcitonin.
The process of amyloid fibril formation by the human calcitonin hormone is associated with medullary thyroid carcinoma. Based on the effect of pH on the fibrillization of human calcitonin, the analysis of conformationally constrained analogues of the hormone, and our suggestion regarding the role of aromatic residues in the process of amyloid fibril formation, we studied the ability of a short aromatic charged peptide fragment of calcitonin (NH(2)-DFNKF-COOH) to form amyloid fibrils. Here, using structural and biophysical analysis, we clearly demonstrate the ability of this short peptide to form well ordered amyloid fibrils. A shorter truncated tetrapeptide, NH(2)-DFNK-COOH, also formed fibrils albeit less ordered than those formed by the pentapeptide. We could not detect amyloid fibril formation by the NH(2)-FNKF-COOH tetrapeptide, the NH(2)-DFN-COOH tripeptide, or the NH(2)-DANKA-COOH phenylalanine to the alanine analogue of the pentapeptide. The formation of amyloid fibrils by rather hydrophilic peptides is quite striking, because it was speculated that hydrophobic interactions might play a key role in amyloid formation. This is the first reported case of fibril formation by a peptide as short as a tetrapeptide and one of very few cases of amyloid formation by pentapeptides. Because the aromatic nature seems to be the only common property of the various very short amyloid-forming peptides, it further supports our hypothesis on the role of aromatic interactions in the process of amyloid fibril formation.


Iron Chelators: Development of Novel Compounds with High and Selective Anti-Tumour Activity.
Targeting essential nutrients (eg., those required for DNA synthesis) to inhibit cancer cell growth is a well established therapeutic strategy. A good example is the highly successful folate antagonist, methotrexate. However, up until recently, strategies to target iron which is also crucial for DNA synthesis have not been systematically explored to develop agents for the treatment of cancer. Over the last 15 years, our laboratory has embarked upon structure-activity studies designed to develop novel Fe chelators with anti-cancer efficacy. These studies have led to the development of the dipyridyl thiosemicarbazone chelators that show potent and selective anti-cancer activity and which overcome resistance to other cytotoxic agents. This class of compounds include the chelator, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), which at optimal doses markedly inhibits tumour growth and is well tolerated. Moreover, this ligand does not induce overt Fe-depletion in vivo, probably because very low doses (0.4 mg/kg) are effective at inhibiting tumour growth. Importantly, our compounds are far more active and less toxic than the chelator, Triapine®, that is being assessed in a wide variety of international clinical trials. A vital part of the mechanism of action of these compounds is their ability to form a redox-active Fe complex that generates radicals to inhibit tumour growth. Due to their relatively high lipophilicity and low molecular weight of this class of compounds, oral activity may be expected in addition to their well known efficacy via the intravenous route.


Tumor cell lines established in vitro: an independent prognostic factor for survival in non-small-cell lung cancer.
To determine the relation between in-vitro establishment of tumor cell lines and survival in patients with non-small-cell lung cancer. Cohort study. Single-institution tertiary care center. One hundred twenty-three consecutive patients with non-small-cell lung cancer from whom a viable tumor specimen could be obtained. Tumor tissue was removed at the time of entry into a therapeutic protocol. The tumor tissue was processed in the laboratory for attempted cell-line establishment. Patients classified as potentially curable (stages I, II, and IIIA) were treated with surgical resection, radiation therapy, or a combination. Patients suitable for palliative therapy only (stages IIIB and IV) were treated with radiation therapy with or without chemotherapy. Chemotherapy was based on in-vitro drug sensitivity when available. Cell-line establishment was correlated to clinical outcome. Univariate analysis of survival was done using the log-rank test; multivariate analysis was done by Cox modeling step-up and step-down techniques. Cell lines were established from the tumor specimens of 25 patients (20%). Those patients experienced a median survival of 7 months compared with 18 months in patients from whom cell lines could not be established (P less than 0.001). In the 61 patients with potentially curable disease, 8 patients (13%) with cell lines established had a median survival of 8 months compared with 32 months for those without cell lines established (P = 0.001). In the 62 palliative group patients, the median survival of the 17 patients (27%) from whom tumor cell lines were established was 5 months compared with 7 months for those without cell lines (P = 0.15). Multivariate analysis in both groups showed cell-line establishment to be a significant indicator of prognosis (P less than 0.0001 for curable group; P less than 0.01 for palliative group). In-vitro tumor growth is related to decreased patient survival, which in turn reflects the biologic aggressiveness of cancers giving rise to these tumor cell lines.


The role of articular cartilage in patellofemoral pain.
This article describes a conservative program of treatment for patellofemoral pain of chondromalacic origin. It has become obvious that patellofemoral pain syndromes are derived from cartilage degradation and from soft-tissue changes, including tendinitis and neuromatous degeneration.


Calcium-sensitivity of inositol 1,4,5-trisphosphate metabolism in exocrine cells from the avian salt gland.
The generation of inositol phosphates upon muscarinic-receptor activation was studied in [3H]inositol-loaded exocrine cells from the nasal salt glands of the duck Anas platyrhynchos, and the metabolism of different inositol phosphates in vitro was studied in tissue homogenates, with particular reference to the possible interaction of changes in intracellular [Ca2+] ([Ca2+]i) with the metabolic processes. In intact cells, there was a rapid (within 15 s) generation of Ins(1,4,5)P3 and Ins(1,3,4,5)P4, followed by an accumulation of their breakdown products, Ins(1,3,4)P3 and inositol bis- and monophosphates. Ca(2+)-sensitivity of the Ins(1,4,5)P3 3-kinase was demonstrated in tissue homogenates, with the rate of phosphorylation increasing 2-fold at free Ca2+ concentrations greater than 1 microM. However, addition of calmodulin or the presence of the calmodulin inhibitor W-7 (up to 100 microM) had no effect. 3-Kinase activity increased proportionally with the initial Ins(1,4,5)P3 concentration up to 1 microM, but a 10-fold higher substrate concentration produced only a doubling in the phosphorylation rate. Ins(1,3,4,5)P4 was dephosphorylated to Ins(1,3,4)P3, which accumulated in the homogenate assays as well as in intact cells. Depending on its concentration, Ins(1,3,4)P3 was phosphorylated [in part to Ins(1,3,4,6)P4] or dephosphorylated. To investigate the Ca(2+)-sensitivity of the 3-kinase in intact cells, excess quin2 was used to buffer the receptor-mediated transient changes in [Ca2+]i in [3H]inositol-loaded cells. These experiments revealed that increasing [Ca2+]i from less than 100 to approx. 400 nM (i.e. within the physiological range) has no effect on the partitioning of Ins(1,4,5)P3 metabolism (phosphorylation versus dephosphorylation) and on the accumulation of Ins(1,4,5)P3 and Ins(1,3,4,5)P4. This indicates that activation of the 3-kinase by physiologically relevant Ca2+ concentrations may not play a major role in the generation of Ins(1,3,4,5)P4 signals upon receptor activation in these cells. The latter are mainly achieved by the receptor-mediated increase in Ins(1,4,5)P3 in the cell and its phosphorylation by the 3-kinase in a substrate-concentration-dependent manner.


The (minimal) persuasive advantage of political video over text.
Concerns about video-based political persuasion are prevalent in both popular and academic circles, predicated on the assumption that video is more compelling than text. To date, however, this assumption remains largely untested in the political domain. Here, we provide such a test. We begin by drawing a theoretical distinction between two dimensions for which video might be more efficacious than text: 1) one's belief that a depicted event actually occurred and 2) the extent to which one's attitudes and behavior are changed. We test this model across two high-powered survey experiments varying exposure to politically persuasive messaging (total n = 7,609 Americans; 26,584 observations). Respondents were shown a selection of persuasive messages drawn from a diverse sample of 72 clips. For each message, they were randomly assigned to one of three conditions: a short video, a detailed transcript of the video, or a control condition. Overall, we find that individuals are more likely to believe an event occurred when it is presented in video versus textual form, but the impact on attitudes and behavioral intentions is much smaller. Importantly, for both dimensions, these effects are highly stable across messages and respondent subgroups. Moreover, when it comes to attitudes and engagement, the difference between the video and text conditions is comparable to, if not smaller than, the difference between the text and control conditions. Taken together, these results call into question widely held assumptions about the unique persuasive power of political video over text.


A Diagnostic Algorithm Combining Immunohistochemistry and Molecular Cytogenetics to Diagnose Challenging Melanocytic Tumors.
Some melanocytic tumors are diagnostic challenges and require ancillary tools in helping the pathologists to determine their potential of malignancy. We intend to propose a diagnostic algorithm in helping to classify challenging melanocytic tumors combining histology, immunohistochemistry, and cytogenetics. We report on 24 spitzoid and/or misdiagnosed melanocytic tumors studied with a triple p16, Ki-67, and HMB45 immunohistochemistry score, fluorescent in situ hybridization (FISH) with melanoma-dedicated and non-melanoma-dedicated probes and comparative genomic hybridization on DNA microarray (CGH array). Melanoma-dedicated FISH probe classified as favor malignant 8/8 melanomas, 1/2 atypical spitzoid tumor, and 4/14 nevi with polyploidy. Only 10 CGH array assays were contributive and concluded in complex chromosomal patterns as hallmarks of malignancy in 5 melanomas, single isolated imbalances in 3 nevi, and no chromosomal gain or loss in 2 nevi. The p16-Ki-67-HMB45 immunohistochemistry score was favor benign (ie, 0 to 3) in 13/14 nevi and in the favor benign atypical spitzoid tumor according to FISH analyses. The FISH-favor malignant atypical spitzoid tumor, 8/8 melanomas, and 1 tumor initially diagnosed as a Spitz nevus had favor malignant p16-Ki-67-HMB45 immunohistochemistry scores (ie, 4 to 9). Additional FISH analyses detected a 9p21/CDKN2A double deletion, frequently reported in melanomas but not in nevi, in the tumor initially diagnosed as a Spitz nevus with a favor malignant p16-Ki-67-HMB45 score. To conclude, in our opinion, histology and p16-Ki-67-HMB45 immunohistochemistry could consist in first-line tools to diagnose a difficult melanocytic tumor, followed by cytogenetics analyses in cases of discrepancies between histology and immunohistochemistry.


A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure.
Disassembly of apoptotic cells into smaller fragments (a form of extracellular vesicle called apoptotic bodies) can facilitate removal of apoptotic debris and intercellular communication. However, the mechanism underpinning this process is unclear. While observing monocytes undergoing apoptosis by time-lapse microscopy, we discovered a new type of membrane protrusion that resembles a 'beads-on-a-string' structure. Strikingly, the 'beads' are frequently sheared off the 'string' to form apoptotic bodies. Generation of apoptotic bodies via this mechanism can facilitate a sorting process and results in the exclusion of nuclear contents from apoptotic bodies. Mechanistically, generation of 'beads-on-a-string' protrusion is controlled by the level of actomyosin contraction and apoptopodia formation. Furthermore, in an unbiased drug screen, we identified the ability of sertraline (an antidepressant) to block the formation of 'beads-on-a-string' protrusions and apoptotic bodies. These data uncover a new mechanism of apoptotic body formation in monocytes and also compounds that can modulate this process.


Safety and feasibility of a CT protocol for acute stroke: combined CT, CT angiography, and CT perfusion imaging in 53 consecutive patients.
By combining non-contrast-enhanced CT imaging, CT perfusion imaging, and cranial-to-chest CT angiography (CTA), the entire cerebrovascular axis can be imaged during acute stroke. To our knowledge, the safety and feasibility of this technique have not been previously reported. In a consecutive series of 53 patients with suspected acute stroke, renal failure was not observed. Median imaging time was 27 minutes (range, 9-67 minutes). Image quality was degraded by motion in 1.3% of vessels studied. Dynamic CT perfusion data were successfully obtained in 52 patients (98% of patients). High-speed, multisection, helical CT scanners allow rapid, safe imaging of the entire neurovascular axis in patients with acute stroke by use of combined CT imaging, CT perfusion imaging, and CTA.


The clonal evolution of leukemic stem cells in T-cell acute lymphoblastic leukemia.
Recent genome sequencing studies have identified a broad spectrum of gene mutations in T-cell acute lymphoblastic leukemia (T-ALL). The purpose of this review is to outline the latest advances in our understanding of how these mutations contribute to the formation of T-ALL. Aberrant expression of transcription factors that control hematopoiesis can induce an aberrant stem cell-like program in T-cell progenitors, allowing the emergence of an ancestral or preleukemic stem cell (pre-LSC). In contrast, gain-of-function mutations of genes involved in signaling pathways regulating T-cell development, such as NOTCH1, interleukin-7, KIT and FLT3, are insufficient per se to initiate T-ALL but promote pre-LSC growth independent of the thymic niche. Loss-of-function mutations of epigenetic regulators, such as DNMT3A, have been identified in T-ALL, but their role in leukemogenesis remains to be defined. Relapse is associated with clonal evolution from a population of pre-LSCs that acquire the whole set of malignant mutations leading to a full-blown T-ALL. Understanding the genetic events that underpin the pre-LSC will be crucial for reducing the risk of relapse.


Cell cycle phase-specific death response of tobacco BY-2 cell line to cadmium treatment.
The character of programmed cell death (PCD) in plants differs in connection with the context, triggering factors and differentiation state of the target cells. To study the interconnections between cell cycle progression and cell death induction, we treated synchronized tobacco BY-2 cells with cadmium ions that represent a general abiotic stressor influencing both dividing and differentiated cells in planta. Cadmium induced massive cell death after application in all stages of the cell cycle; however, both the progression and the forms of the cell death differed pronouncedly. Apoptosis-like PCD induced by cadmium application in the S and G2 was characterized by pronounced internucleosomal DNA fragmentation. In contrast, application of cadmium in M and G1 phases was not accompanied by DNA cleavage, indicating suppression of autolysis and non-programmed character of the death. We interpret these results in the context of the situation in planta, where the induction of apoptosis-like PCD in the S and G2 phase might be connected with a need to preserve genetic integrity of dividing meristematic cells, whereas suppression of PCD response in differentiated cells (situated in G1/G0 phase) might help to avoid death of the whole plant, and thus enable initiation of the recovery and adaptation processes.


Epidermal growth factor and transforming growth factor-beta differently modulate the acute phase response elicited by interleukin-6 in cultured liver cells from man, rat and mouse.
1. Complex effects of principal inflammatory cytokines (IL-6, IL-1, TNF, IFN-gamma) on acute phase protein synthesis and other metabolic processes in cultured liver cells are briefly reviewed. 2. Molecular properties and biological functions of transforming growth factor-beta and epidermal growth factor are compared. 3. The effects of these factors with respect to both amino acid uptake and acute phase protein synthesis are described in detail. The results are found to be different for rat or mouse hepatocytes and human hepatoma cells.


Impact of Diverse Data Sources on Computational Phenotyping.
Electronic health records (EHRs) are widely adopted with a great potential to serve as a rich, integrated source of phenotype information. Computational phenotyping, which extracts phenotypes from EHR data automatically, can accelerate the adoption and utilization of phenotype-driven efforts to advance scientific discovery and improve healthcare delivery. A list of computational phenotyping algorithms has been published but data fragmentation, i.e., incomplete data within one single data source, has been raised as an inherent limitation of computational phenotyping. In this study, we investigated the impact of diverse data sources on two published computational phenotyping algorithms, rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM), using Mayo EHRs and Rochester Epidemiology Project (REP) which links medical records from multiple health care systems. Results showed that both RA (less prevalent) and T2DM (more prevalent) case selections were markedly impacted by data fragmentation, with positive predictive value (PPV) of 91.4 and 92.4%, false-negative rate (FNR) of 26.6 and 14% in Mayo data, respectively, PPV of 97.2 and 98.3%, FNR of 5.2 and 3.3% in REP. T2DM controls also contain biases, with PPV of 91.2% and FNR of 1.2% for Mayo. We further elaborated underlying reasons impacting the performance.


Induced resistance of cotton seedlings to mites.
Mite populations grew more rapidly on new growth of cotton seedlings that had never been exposed to mites than on new growth of plants whose cotyledons had been previously exposed to them. Experiments in which a second mite introduction on the exposed plants involved a different mite species produced this same result. The substance or substances responsible for the response are transported systemically among leaves of cotton seedlings.


The impact of the National Treatment Purchase Fund on numbers of core urology training cases at University Hospital Galway.
Since the National Treatment Purchase Fund (NTPF) scheme was introduced in 2002, public patients waiting longer than three months for investigations and treatment are offered care in the private medical sector. Our aim was to assess the impact of the NTPF scheme on the number of training cases performed at University Hospital Galway (UHG). The number and type of urological procedures performed in the private medical sector under the NTFP scheme in 2008 were obtained from the UHG waiting list office. The number of these procedures performed on public patients by trainees at UHG in 2008 was determined retrospectively by reviewing theatre records. A significant number of core urology procedures were performed in the private sector via the NTPF scheme. Cancer centre designation and implementation of the EWTD will also place further pressures on urological training opportunities in Ireland.


Abrogation of DEN/Fe-NTA induced carcinogenic response, oxidative damage and subsequent cell proliferation response by Terminalia chebula in kidney of Wistar rats.
In an effort to identify a new chemopreventive agent, the present study was conducted to investigate the role of T. chebula in the prevention of ferric nitrilotriacetic acid (Fe- NTA) induced oxidative stress and renal tumorigenesis in Wistar rats. A single application of Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) significantly induced oxidative stress and elevated the marker parameters of tumor promotion. However, the pretreatment of animals with different doses of T. chebula extract (25 and 50 mg/kg body weight) restored the levels of reduced glutathione (GSH) and cellular protective enzymes (p < 0.05). Concomitantly, malondialdehyde (MDA) formation and hydrogen peroxide content were also reduced significantly (p < 0.05) at both the doses. The promotion parameters tested (ornithine decarboxylase activity and DNA synthesis) were also significantly suppressed (p < 0.05). T. chebula also inhibited N-diethyl nitrosamine initiated renal carcinogenesis by showing reduction in the number of animals with renal cell tumors and percentage incidence of tumor as compared to the DEN initiated and Fe-NTA promoted rats. The study was further histologically confirmed. These results suggest a potential role of T. chebula in protection from Fe-NTA-induced renal carcinogenesis and oxidative damage.


Probable false positive coccidioidal serologic results in patients with cystic fibrosis.
Coccidioidomycosis is an acquired fungal infection that afflicts primarily the respiratory tract. Cystic fibrosis patients who are being treated with glucocorticoids and immunosuppressed organ recipients may be at risk for infection with Coccidiodes immitis or reactivation of latent infection. The diagnosis is best made by demonstration of the organism in pathologic specimens or by culture. Serologic screening is another method that is reliable in most patients. We studied 98 patients who had serologic screening for Coccidiodes immitis performed as part of their evaluation for lung transplantation. This study revealed that approximately 15% of the cystic fibrosis patients screened had putative coccidioidal IgM, in the absence of an IgG response. None of the patients studied had a positive fungal culture for the organism. None of the non-cystic fibrosis patients screened had detectable coccidioidal IgG or IgM. We hypothesize that cystic fibrosis patients may have hyperimmune sera which interferes with serologic screening tests. We would recommend repeat serologic testing and attempts to identify the organism in tissue or by culture to confirm the diagnosis in these patients.


Riboflavin-dependent expression of flavoenzymes of the nicotine regulon of Arthrobacter oxidans.
In cells of an Arthrobacter oxidans riboflavin-dependent mutant the specific activity of the DL-nicotine-inducible nicregulon enzymes nicotine dehydrogenase (NDH, EC 184.108.40.206), 6-hydroxy-L-nicotine oxidase (6-HLNO, EC 184.108.40.206) and 6-hydroxy-D-nicotine oxidase (6-HDNO, EC 184.108.40.206) was shown to be dependent on the supply of the vitamin in the growth medium. Experiments designed to identify at which level riboflavin directs the biosynthesis of these flavoenzymes revealed that the steady-state levels of enzyme protein analysed on Western blots correlated directly with riboflavin supply from the minimal concentration of 0.5 microns-riboflavin required for growth up to 8 microns-riboflavin. Mutant cells grown at the higher riboflavin concentration showed on dot-blots increased levels of RNA which hybridized to 32P-labelled probes derived from the nic-regulon genes. When cells grown at 2 microns-riboflavin were shifted to 8 microns-riboflavin, 6-HDNO expression increased as indicated by elevated enzyme and RNA levels. When the rates of synthesis of the 6-HDNO and 6-HLNO polypeptides after DL-nicotine induction was analysed in cells grown at 0.5 microns and 8 microns-riboflavin, only cells grown at the higher riboflavin concentration showed on Western blots an accumulation of the polypeptides. No 6-HDNO or 6-HLNO polypeptide was identified in cell extracts from cells grown on 0.5 microns-riboflavin. Pulse-chase experiments with [35S]methionine showed that 6-HDNO- and 6-HLNO synthesis was prevented in cells grown at the low riboflavin concentration. The absence of detectable enzyme levels seemed not to be caused by proteolytic breakdown. Incubation in vitro of apo-6HDNO with low- or high-riboflavin-grown-cell extracts showed no increased proteolytic activity in 0.5 microns-riboflavin-grown cells. From these results it is concluded that riboflavin supply co-regulates the expression of the nicregulon genes at the level of transcription and/or mRNA turnover.


Breastfeeding and Overweight in European Preschoolers: The ToyBox Study.
The benefits of breastfeeding (BF) include risk reduction of later overweight and obesity. We aimed to analyse the association between breastfeeding practices and overweight/obesity among preschool children participating in the ToyBox study. Data from children in the six countries, participating in the ToyBox-study (Belgium, Bulgaria, Germany, Greece, Poland, and Spain) 7554 children/families and their age is 3.5-5.5 years, 51.9% were boys collected cross-sectionally in 2012. The questionnaires included parents' self-reported data on their weight, height, socio-demographic status, and infant feeding practices. Measurements of preschool children's weight and height were done by trained researchers using standard protocols and equipment. The ever breastfeeding rate in the total sample was 85.0% (n = 5777). Only 6.3% (n = 428) of the children from the general sample were exclusively breastfed (EBF) for the duration of the first six months. EBF for four to six months was significantly (p < 0.001) less likely among mothers with formal education < 12 years (adjusted Odds Ratio (OR) = 0.61; 95% Confidence interval (CI) 0.44-0.85), smoking throughout pregnancy (adjusted OR = 0.39; 95% CI 0.24-0.62), overweight before pregnancy (adjusted OR = 0.67; 95%CI 0.47-0.95) and ≤25 years old. The median duration of any breastfeeding was five months. The prevalence of exclusive formula feeding during the first five months in the general sample was about 12% (n = 830). The prevalence of overweight and obesity at preschool age was 8.0% (n = 542) and 2.8% (n = 190), respectively. The study did not identify any significant association between breastfeeding practices and obesity in childhood when adjusted for relevant confounding factors (p > 0.05). It is likely that sociodemographic and lifestyle factors associated with breastfeeding practices may have an impact on childhood obesity. The identified lower than desirable rates and duration of breastfeeding practices should prompt enhanced efforts for effective promotion, protection, and support of breastfeeding across Europe, and in particular in regions with low BF rates.


Differentiation of myoglobin and hemoglobin in biological fluids.
The use of several methods to differentiate myoglobin from hemoglobin has been investigated. The immunochemical methods, particularly those of hemagglutination inhibition and radioimmunoassay, are the most useful. This report summarizes work in the Ames Research Laboratory over the past 17 years with the several methods.


Spermatid translocation in the rat seminiferous epithelium: coupling membrane trafficking machinery to a junction plaque.
In this study, we demonstrate that specialized junction plaques that occur between Sertoli cells and spermatids in the rat testis support microtubule translocation in vitro. During spermatogenesis, Sertoli cells are attached to spermatids by specialized adhesion junctions termed ectoplasmic specializations (ESs). These structures consist of regions of the plasma membrane adherent to the spermatid head, a submembrane layer of tightly packed actin filaments, and an attached cistern of endoplasmic reticulum. It has been proposed that motor proteins on the endoplasmic reticulum interact with adjacent microtubules to translocate the junction plaques, and hence the attached spermatids, within the epithelium. If this hypothesis is true, then isolated junctions should support microtubule transport. To verify this prediction, we have mechanically isolated rat spermatids, together with their attached ESs, and tested them for their ability to transport microtubules in vitro. Most assays were done in the presence of 2 mg/ml testicular cytosol and at room temperature. ESs attached to spermatids supported microtubule translocation. In some cases in which motility events were detected, microtubules moved smoothly over the junction site. In others, the movement was slow but progressive, saltatory and "inch-worm-like." No motility was detected in the absence of exogenous ATP or in the presence of apyrase (an enzyme that catalyses the breakdown of ATP). Our results are consistent with the microtubule-based motility hypothesis of spermatid translocation.


Inhibitory effect of PMC, a potent hydrophilic α-tocopherol derivative, on vascular smooth muscle cell proliferation: the pivotal role of PKC-α translocation.
Vascular smooth muscle cells (VSMCs) play a major role in the pathogenesis of atherosclerosis and restenosis, and thus the excessive proliferation of VSMCs contributes to neointimal thickening during atherosclerosis and restenosis. PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane) is the most potent hydrophilic derivative of the alpha-tocopherols; it acts as a potent anti-inflammatory and free-radical scavenger. The present study was designed to examine the inhibitory mechanisms of PMC in VSMC proliferation. VSMC proliferation and cytotoxicity were measured by MTT and LDH assays, respectively. The cell cycle and translocation of PKC-alpha in VSMCs were used by flow cytometry and confocal microscope, respectively. To detect PKC-alpha translocation and activation in VSMCs, immunoblotting was performed in the present study. In this study, we demonstrate an anti-proliferative effect of PMC in VSMCs. Concentration-dependent inhibition of serum-induced VSMC proliferation was observed in PMC (20 and 50 muM)-treated cells. PMC pretreatment also arrested VSMC cell cycle progression at the G2/M phase. Furthermore, PMC exhibited obvious inhibitory effects on phorbol 12-myristate 13-acetate (PMA)-induced protein kinase C (PKC)-alpha translocation and phospho-(Ser/Thr) substrate phosphorylation. The inhibitory mechanisms of PMC on VSMC proliferation is mediated, at least in part, by inhibition of PKC-alpha translocation and causes cell cycle arrest in the G2/M phase. PMC treatment may represent a novel approach for lowering the risk of or improving function in abnormal VSMC proliferation-related vascular diseases.


Validity and reliability of self-assessment of sexual maturity in elite adolescent athletes.
The variability along the progression of different stages of maturation during puberty suggests that chronological age is not the best indicator in assessing biological status during adolescence. This is particularly relevant for adolescents involved in high level of sports competitions, which implies greater physiological and biomechanical demands to the body. Therefore, monitoring physical changes during this period may help the coaching and medical staff to construct and adapt on an individual basis, better training programs and, then, improve performance while preventing injuries. Thus, the aim of this study was to evaluate the validity and the reliability of self-assessment of sexual maturity among elite adolescent athletes. Using the Tanner sexual maturity method, 24 male and 23 female athletes aged 12 to 17 years, were assessed by a physician, and, then, self-assessed for sexual maturity. Agreement with the physician ratings was high (k coefficients of 0.79 for pubic hair and 0.67 for genital development for boys and 0.75 and 0.85 for pubic hair and breast development for girls, respectively). Spearman correlations ranged from 0.86 to 0.97 (P= or <0.05). The self-assessment is a valid and reliable method to assess sexual maturity in elite adolescent athletes.


Innate Immunity and CKD: Is There a Significant Association?
Chronic kidney disease (CKD) constitutes a worldwide epidemic, affecting approximately 10% of the global population, and imposes significant medical, psychological, and financial burdens on society. Individuals with CKD often face elevated morbidity and mortality rates, mainly due to premature cardiovascular events. Chronic inflammation has been shown to play a significant role in the progression of CKD, as well as in the acceleration of CKD-related complications, including atherosclerosis, cardiovascular disease (CVD), protein-energy wasting, and the aging process. Over the past two decades, a substantial body of evidence has emerged, identifying chronic inflammation as a central element of the uremic phenotype. Chronic inflammation has been shown to play a significant role in the progression of CKD, as well as in the acceleration of CKD-related complications in dialysis patients, including atherosclerosis, CVD, protein-energy wasting, and the aging process. Remarkably, chronic inflammation also impacts patients with CKD who have not yet required renal replacement therapy. While extensive research has been conducted on the involvement of both the adaptive and innate immune systems in the pathogenesis of CKD-related complications, this wealth of data has not yet yielded well-established, effective treatments to counteract this ongoing pathological process. In the following review, we will examine the established components of the innate immune system known to be activated in CKD and provide an overview of the current therapeutic approaches designed to mitigate CKD-related chronic inflammation.


A tertiary structure model of the internal ribosome entry site (IRES) for methionine-independent initiation of translation.
Cricket paralysis-like viruses have a dicistronic positive-strand RNA genome. These viruses produce capsid proteins through internal ribosome entry site (IRES)-mediated translation. The IRES element of one of these viruses, Plautia stall intestine virus (PSIV), forms a pseudoknot immediately upstream from the capsid coding sequence, and initiates translation from other than methionine. Previously, we estimated that the IRES element of PSIV consists of seven stem-loops using the program MFOLD; however, experimental evidence of the predicted structures was not shown, except for stem-loop VI, which was responsible for formation of the pseudoknot. To determine the whole structure of the PSIV-IRES element, we introduced compensatory mutations into the upstream MFOLD-predicted helical segments. Mutation analysis showed that stem-loop V exists as predicted, but stem-loop IV is shorter than predicted. The structure of stem-loop III is different from predicted, and stem-loops I and II are not necessary for IRES activity. In addition, we identified two new pseudoknots in the IRES element of PSIV. The complementary sequence segments that are responsible for formation of the two pseudoknots are also observed in cricket paralysis virus (CrPV) and CrPV-like viruses such as Drosophila C virus (DCV), Rhopalosiphum padi virus (RhPV), himetobi P virus (HiPV), Triatoma virus (TrV), and black queen-cell virus (BQCV), although each sequence is distinct in each virus. Considering the three pseudoknots, we constructed a tertiary structure model of the PSIV-IRES element. This structural model is applicable to other CrPV-like viruses, indicating that other CrPV-like viruses can also initiate translation from other than methionine.


Comparative analysis of the quality of life for patients prior to and after heart transplantation.
The aim of this study was to assess the quality of life of patients before and after heart transplantation (HTX). We included 63 patients after a heart transplant under the care of the Transplantation Clinic. The authors' questionnaire was used, which consisted of 2 parts: questions concerning the life of patients before and after a heart transplant. The significance level was p<0.05. In the group before the heart transplant, average quality of life (on a 10-point scale) was 3.16 ± 1.47 and in the group after the heart transplant this factor increased to 7.60 ± 1.21 (p<0.00001). Our study shows that after the heart transplant people consider their physical health to be better. In the group before the heart transplant, the average assessment of physical health on a scale from 1 to 5 was 2.079 ± 0.79 and after the heart transplant it was 4.10 ± 0.39 (p<0.0001). No statistically significant correlations were indicated between the quality of life after the heart transplant and the quality of life before the transplant, age, sex, and time elapsed after the heart transplant. There was a positive correlation between the assessment of quality of life and that of physical (r=0.53; p<0.05) and mental health (r=0.45; p<0.05). The study shows that the quality of life of patients after the heart transplant was significantly improved in all spheres of life under analysis: physical, mental, social, and family. The results of the study indicate that patients associated the quality of life with their physical and mental health status.


New directions in the irritable bowel syndrome.
The irritable bowel syndrome (IBS) is an umbrella for the diagnosis of heterogeneous conditions that are awaiting better identification of specific manometric causes. This article focuses on the concept that future therapy for IBS will rely on identification of subgroups and in turn tailor the specific therapeutic approaches to an appreciation of the pathophysiology and symptom predominance of these subgroups. Future therapies will rely on the following principles: (1) prokinetic agents to coordinate upper gastrointestinal and colonic motility as well as improve the propulsive nature of colonic contractions; (2) gastrointestinal hormone agonists such as erythromycin and antagonists such as sandostatin and cholecystokinin antagonists; (3) spasmolytic therapy incorporating calcium channel blocking and anticholinergic agents; (4) inhibition of ovulatory cycle changes in circulating concentrations of gonadal hormones in women, who tend to dominate the IBS population; (5) incorporation of concepts relating to the role of subtypes of 5-hydroxytryptamine receptors in control of neural and myogenic function; (6) reassessment of food intolerance and sensitivity; and (7) incorporation of concepts relating to psychologic profiles and psychologic treatment approaches. IBS is a rich and fertile area for application of the exciting new pharmacologic advances relating to gastrointestinal smooth-muscle and neural innervation of the gut. Improvement in the understanding and treatment of IBS will be one of the major accomplishments of this decade.


Quality of life of elderly ischaemic stroke patients one year after thrombolytic therapy. A comparison between patients with and without thrombolytic therapy.
An observational study to examine whether thrombolytic therapy in stroke patients realizes better quality of life outcomes compared to patients without thrombolytic therapy one year after stroke. We also examined whether daily functioning, mental functioning and activities improved after thrombolytic treatment. A total of 88 stroke patients were interviewed at home one year post-stroke. Health-related quality of life (HRQOL) was assessed using the RAND-36, disability with the Barthel Index, depression and anxiety with the Hospital Anxiety and Depression Scale, and a questionnaire about patient way of life was completed. People aged under 60, moving to a nursing home or with a haemorrhage were excluded. The thrombolysis group (TG) had more severe stroke (higher NIHSS) scores and were younger than the group without thrombolytic therapy (WTG). The primary outcome was HRQOL, which was high and nearly identical in both groups, however the TG had significantly better HRQOL for the 'mental health' and 'vitality' scales. Patients who stopped or reduced their hobbies because of stroke had a significantly worse HRQOL. One year after stroke, more patients in the TG were totally or severely ADL dependent (12% TG and 0% WTG, p = 0.022). The level of dependence decreased in the TG (p = 0.042) and worsened in the WTG (p < 0.001) after one year. Being more dependent is related to diminishing daily occupations in both groups. In the TG the level of dependence had less impact on visiting family and friends and going on holiday. The prevalence of anxiety disorder and depression was low compared to other studies and there is no significant difference between the two groups. No major differences in the primary outcome (HRQOL) could be found between the two groups. In addition, no essential difference could be found in mental functioning and participation. We expected that patients undergoing thrombolytic therapy would have worse quality of life because of the greater initial severity of their stroke. Therefore, thrombolytic therapy seems to be of great importance in achieving better quality of life in ischemic stroke patients who respond to this therapy.


Gonadal development in a giant threatened reef fish, the humphead wrasse Cheilinus undulatus, and its relationship to international trade.
An opportunity arose to obtain humphead wrasse Cheilinus undulatus specimens between 2006 and 2009 from Indonesia, the major source and exporting country of this species, making study on its early gonad development possible for the first time. Protogynous hermaphroditism, previously proposed for this species, was confirmed in this study. Based on histological examination of 178 specimens, mainly <500 mm total length (L(T)) and ranging from 208 to 1290 mm L(T) (119.1 g to 43.0 kg whole body mass), the minimum body sizes for female and male sexual maturation were determined to be 650 and 845 mm L(T), respectively. Primary male development through juvenile sexual differentiation was not detected. A unique blind pouch, with a possible sperm storage function and associated with the testis, was reported for the first time in the Labridae. In Hong Kong retail markets, the global trading centre for this valuable species, live C. undulatus on sale for food were dominated by body sizes <500 mm L(T) between 1995 and 2009, reflecting an international trade largely focused on juveniles. In consideration of these findings, and given the threatened status of this species, management for C. undulatus capture and trade nationally and internationally are discussed with recommendations for ensuring sufficient spawning biomass in exploited populations and for sustainable trade.


Expression of myogenic regulatory factors in normal and dystrophic mice: effects of IGF-1 treatment.
Myogenic regulatory factors (MRFs) promote differentiation of muscle cells from fibroblasts and are induced by insulin-like growth factor I (IGF-1). Prior studies have shown synthesis of new muscle protein and improved muscle morphology when mature dy mice with muscular dystrophy are treated with IGF-1. We investigated whether these salutary effects of IGF-1 might be attributable to stimulation of MRFs. Male dy (129ReJ) mice and controls (129J) were assigned to IGF-1 treatment (10 micrograms twice daily) or non-treatment at about 5 weeks of life and sacrificed 6 weeks later. RNA was extracted from skeletal muscles, reverse transcribed, and amplified by polymerase chain reaction (PCR) using primers specific for each MRF. Competitive PCR was performed to quantify MyoD expression in response to IGF-1 treatment. Transcripts for myf-5, MRF4, and myogenin were detected in both control and dy mouse muscles; no apparent differences were observed between treatment groups. Quantitative analysis of transcripts for MyoD indicated no significant basal differences between control and dy mice. There was, however, significantly higher MyoD expression in the dy group, and a trend toward significance in the control group, following IGF-1 treatment. These data suggest that IGF-1 exerts its in vivo effects in postembryonal muscle by stimulating MRFs.


Seizure detection based on heart rate variability using a wearable electrocardiography device.
To assess the feasibility and accuracy of seizure detection based on heart rate variability (HRV) using a wearable electrocardiography (ECG) device. Noninvasive devices for detection of convulsive seizures (generalized tonic-clonic and focal to bilateral tonic-clonic seizures) have been validated in phase 2 and 3 studies. However, detection of nonconvulsive seizures still needs further research, since currently available methods have either low sensitivity or an extremely high false alarm rate (FAR). In this phase 2 study, we prospectively recruited patients admitted to long-term video-EEG monitoring (LTM). ECG was recorded using a dedicated wearable device. Seizures were automatically detected using HRV parameters computed off-line, blinded to all other data. We compared the performance of 26 automated algorithms with the seizure time-points marked by experts who reviewed the LTM recording. Patients were classified as responders if >66% of their seizures were detected. We recruited 100 consecutive patients and analyzed 126 seizures (108 nonconvulsive and 18 convulsive) from 43 patients who had seizures during monitoring. The best-performing HRV algorithm combined a measure of sympathetic activity with a measure of how quickly HR changes occurred. The algorithm identified 53.5% of the patients with seizures as responders. Among responders, detection sensitivity was 93.1% (95% CI: 86.6%-99.6%) for all seizures and 90.5% (95% CI: 77.4%-97.3%) for nonconvulsive seizures. FAR was 1.0/24 h (0.11/night). Median seizure detection latency was 30 s. Typically, patients with prominent autonomic nervous system changes were responders: An ictal change of >50 heartbeats per minute predicted who would be responder with a positive predictive value of 87% and a negative predictive value of 90%. The automated HRV algorithm, using ECG recorded with a wearable device, has high sensitivity for detecting seizures, including the nonconvulsive ones. FAR was low during the night. This approach is feasible in patients with prominent ictal autonomic changes.


Chloroquine pharmacokinetics in tissues of pyrogen treated rats and implications for chloroquine related pruritus.
The concentrations of chloroquine in the tissues and plasma of control and pyrogen treated Long Island rats were serially determined over 16 days. Significant alterations of pharmacokinetic parameters, a delayed completion of distribution with a biphasic pattern of uptake of chloroquine into peripheral organs (skin and skeletal musculature) and increased tissue uptake in visceral organs (heart, liver and kidneys) of pyrogen treated rats were found. It is suggested that the known hemodynamic changes in the febrile state produced these unusual pharmacokinetic changes in the peripheral tissues and may contribute significantly to the occurrence of pruritus and increased acute toxicity of chloroquine during a febrile illness. The uptake patterns of chloroquine into pyrogen treated rat skin and muscle strongly suggest the involvement of a blood flow-dependent process in the movement of the drug into the tissues.


Extended cardiac rehabilitation for socially vulnerable patients improves attendance and outcome.
Patients living alone or having a low socioeconomic status are likely to quit cardiac rehabilitation. We aimed to compare patients being offered extended rehabilitation (ERP) with those being offered standard rehabilitation (SRP) as concerns 1) attendance rates and 2) achievement of treatment goals at 12 months. During a five-year period, 508 consecutive myocardial infarction patients below the age of 70 years were included. In the first two years of the study, 205 patients were offered SRP (historic controls); during the last three years of the study, 303 patients were identified of whom socially non-vulnerable patients were assigned to SRP and socially vulnerable patients were assigned to ERP. Socially vulnerable patients achieved significantly higher participation rates (97.7%) than controls (75.0%), p < 0.0001, if they were offered ERP. There was no difference in cardiac rehabilitation attendance rate among socially non-vulnerable patients compared to controls (84.7% versus 82.1, p = 0.64). Socially vulnerable patients being offered ERP also had lower levels of cholesterol, systolic blood pressure and body mass index, and a higher level of compliance with medication than controls. Extended offers for socially vulnerable patients improve attendance rates for cardiac rehabilitation and seem to improve the share of patients achieving treatment goals. The Ministry of the Interior and Health, the Ministry of Social Affairs in Denmark, The Danish Heart Foundation and Aarhus University Hospital Research Initiative funded the present study. not relevant.


Postsynaptic CPG15 promotes synaptic maturation and presynaptic axon arbor elaboration in vivo.
The formation of CNS circuits is characterized by the coordinated development of neuronal structure and synaptic function. The activity-regulated candidate plasticity gene 15 (cpg15) encodes a glycosylphosphatidylinositol (GPI)-linked protein whose in vivo expression increases the dendritic arbor growth rate of Xenopus optic tectal cells. We now demonstrate that tectal cell expression of CPG15 significantly increases the elaboration of presynaptic retinal axons by decreasing rates of branch retractions. Whole-cell recordings from optic tectal neurons indicate that CPG15 expression promotes retinotectal synapse maturation by recruiting functional AMPA receptors to synapses. Expression of truncated CPG15, lacking its GPI anchor, does not promote axon arbor growth and blocks synaptic maturation. These results suggest that CPG15 coordinately increases the growth of pre- and postsynaptic structures and the number and strength of their synaptic contacts.


Lessons for the United States From Single-Payer Systems.
US political debates often refer to the experience of "single-payer" systems such as those of Canada and the United Kingdom. We argue that single payer is not a very useful category in comparative health policy analysis but that the experiences of countries such as Canada, the United Kingdom, Spain, Sweden, and Australia provide useful lessons. In creating universal tax-financed systems, they teach the importance of strong, unified governments at critical junctures-most notably democratization. The United States seems politically hospitable to creating such a system.The process of creation, however, highlights the malleability of interests in the health care system, the opportunities for creative coalition building, and the problems caused by linking health care finance and reform. In maintaining these systems, keeping the middle class supportive is crucial to avoiding universal health care that is essentially a program for the poor.For a technical term from the 1970s, "single-payer health care" has proved to have remarkable political power and persistence. We argue it is not a very useful term but the lessons from such systems can be valuable for those contemplating movement toward universal health coverage in the United States.


Binocular Function in Adults before and after Strabismus Surgery.
To evaluate the state of binocular vision, the amount and direction of the ocular deviation before and after strabismus surgery in adult patients and to monitor the occurrence of postoperative complications. The retrospective study of 58 adult patients with selected types of strabismus who were surgically treated in the Eye Department of the Tomas Bata Regional Hospital in Zlín. We evaluated the amount and the degree of the primary ocular deviation and the binocular alignment before and after surgery, as well as the state of binocular vision after surgery and the occurrence of postoperative complications. The average deviation in convergent strabismus before surgery was +23.46 degrees, after surgery +6.6 degrees, in divergent strabismus it was -21.5 degrees, after surgery -1.48 degrees, for vertical strabismus before surgery +12.5 degrees and +3.75 degrees after surgery and in paralytic strabismus +20 degrees before surgery and +3 degrees postoperatively. Preoperatively there was effectively no binocular vision in up to 63.9% of patients, superposition occurred in 31%, fusion in 5.1%. No patient had stereopsis before surgery. After surgery, superposition was present in 39.7%, fusion in 31% and stereopsis in 6.9% of patients. Only 22.4% of patients experienced no binocular vision after surgery. Of the selected 21 patients out of 58 with an observation period of at least 3 years, we observed an improvement or development of binocular vision functions after surgery in 12 patients and no improvement of binocular vision functions in 9 patients. In the first group, 58.3% had a stable deviation throughout the follow-up period. While in the second group the deviation was stable in only 33.3%. We can assume that the improvement in binocular vision function after strabismus surgery, leads to a greater longer-term stability of postoperative deviations. Strabismus surgery in adult patients is an effective and safe method, which is not only a cosmetic procedure used to adjust the position of the eyes, but also enables us to induce or improve the state of binocular vision functions.


Surgery for deep endometriosis without involvement of digestive or urinary tracts: do not worry the patients!
To report postoperative outcomes after surgery for deep endometriosis without involvement of the digestive or urinary tracts. Retrospective study using data prospectively recorded in the North-West Inter Regional Female Cohort for Patients with Endometriosis (CIRENDO) database. University tertiary referral center. One hundred thirty consecutive patients whose follow-up ranged from 1 to 6 years. Laparoscopic excision of deep endometriosis nodules. Postoperative complications were recorded in the CIRENDO database and medical charts. Postoperative digestive function was assessed using standardized gastrointestinal questionnaires: the Gastrointestinal Quality of Life Index and the Knowles-Eccersley-Scott Symptom Questionnaire. Deep endometriosis nodules involved uterosacral ligaments, rectovaginal space, and vagina and spared the bowel, the bladder, and the ureters. Nodule size was <1 cm, 1-3 cm, and >3 cm in diameter in 20.8%, 64.6%, and 14.6% of cases, respectively. Clavien-Dindo 1, 2, and 3b complications occurred in 0.8%, 4.6%, and 5.4% of cases, respectively. Among Clavien-Dindo 3b complications, most involved pelvic hematoma. Gastrointestinal scores revealed significant improvement in digestive function or defecation pain at 1 and 3 years after surgery. The pregnancy rate was, respectively, 43.3% and 56.7% at 1 and 3 years postoperatively, among which 66.7% and 64.7% were spontaneous conceptions. Our data suggest that surgery for deep endometriosis without involvement of the digestive or urinary tracts provides a low rate of postoperative complications and satisfactory fertility outcomes.


Core Temperature Responses in Elite Cricket Players during Australian Summer Conditions.
This study aimed to observe core temperature responses in elite cricket players under match conditions during the summer in Australia. Thirty-eight Australian male cricketers ingested capsule temperature sensors during six four-day first-class matches between February 2016 and March 2017. Core temperature (Tc) was recorded during breaks in play. Batters showed an increase in Tc related to time spent batting of approximately 1 °C per two hours of play (p < 0.001). Increases in rate of perceived exertion (RPE) in batters correlated with smaller elevations in Tc (0.2 °C per one unit of elevation in RPE) (p < 0.001). Significant, but clinically trivial, increases in Tc of batters were found related to the day of play, wet bulb globe temperature (WBGT), air temperature, and humidity. A trivial increase in Tc (p < 0.001) was associated with time in the field and RPE when fielding. There was no association between Tc and WBGT, air temperature, humidity, or day of play in fielders. This study demonstrates that batters have greater rises in Tc than other cricket participants, and may have an increased risk of exertional heat illness, despite exposure to similar environmental conditions.


Impact of conditional and unconditional cash transfers on health outcomes and use of health services in humanitarian settings: a mixed-methods systematic review.
Cash transfers, payments provided by formal or informal institutions to recipients, are increasingly used in emergencies. While increasing autonomy and being supportive of local economies, cash transfers are a cost-effective method in some settings to cover basic needs and extend benefits of limited humanitarian aid budgets. Yet, the extent to which cash transfers impact health in humanitarian settings remains largely unexplored. This systematic review evaluates the evidence on the effect of cash transfers on health outcomes and health service utilisation in humanitarian contexts. Studies eligible for inclusion were peer reviewed (quantitative,qualitative and mixed-methods). Nine databases (PubMed, EMBAS, Medline, CINAHL, Global Health, Scopus, Web of Science Core Collection, SciELO and LiLACS) were searched without language and without a lower bound time restriction through 24 February 2021. The search was updated to include articles published through 8 December 2021. Data were extracted using a piloted extraction tool and quality was assessed using The Joanna Briggs Critical Appraisal Tool. Due to heterogeneity in study designs and outcomes, results were synthesised narratively and no meta-analysis was performed. 30 673 records were identified. After removing duplicates, 17 715 were double screened by abstract and title, and 201 in full text. Twenty-three articles from 16 countries were included reporting on nutrition outcomes, psychosocial and mental health, general/subjective health and well-being, acute illness (eg, diarrhoea, respiratory infection), diabetes control (eg, blood glucose self-monitoring, haemoglobin A1C levels) and gender-based violence. Nineteen studies reported some positive impacts on various health outcomes and use of health services, 11 reported no statistically significant impact on outcomes assessed and 4 reported potential negative impacts on health outcomes. Although there is evidence to suggest a positive relationship between cash transfers and health outcomes in humanitarian settings, high-quality empirical evidence, that is methodologically robust, investigates a range of humanitarian settings and is conducted over longer time periods is needed. This should consider factors influencing programme implementation and the differential impact of cash transfers designed to improve health versus multipurpose cash transfers. CRD42021237275.


[The use of muscle flaps in the surgical treatment of infected vascular prosthesis].
The solutions for graft infection and its complications in vascular surgery are well known. However, publications dealing with this topic do not, or just occasionally mention muscular flap plast, which is already quite widely used in other fields of surgery. The authors first used pedicled muscular flap plasty in 1996, to cover grafts that had been exposed as a result of infection. Later, this method was also applied in covering subinguinal suturelines and anastomoses respectively, to ward off impending haemorrhage. Between 1996 and 1999, 32 patients presenting with septic complications after vascular surgery were treated. Muscular flap plasty was performed in 12 of these cases. In 7 patients the exposed graftsere covered, while in 5 patients the subinguinal suture-lines and anastomoses were covered respectively with muscle flaps, 5 of the graft covering procedures were successful. In two cases of superinfection and septic progression respectively the graft had to be removed without amputation of the extremity. 3 successful operations were recorded in the cases where the covering of the subinguinal suturelines and anastomoses were the aim. 2 patients presented with erosive haemorrhage, which led to ligation of the femoral artery and consequent amputation, in view of the absence of further possibilities for reconstruction.


A hermeneutic study of integrating psychotherapist competence in postnatal Child Health Care: Parents' perspectives.
A child's emotional and social development depends on the parents' provision of optimal support. Many parents with perinatal distress experience difficulties in mastering parenthood and seek help from professionals within primary healthcare. A clinical project was launched in Stockholm, where psychodynamic psychotherapists provided short-term consultations at Child Health Centers. This study qualitatively explored parents' experiences of perinatal distress and of receiving help by nurses and therapists in the project. Thirteen parents were interviewed, and their responses were analyzed with a hermeneutical method. Three main themes crystallized; accessibility of psychological help and detection of emotional problems; experiences of therapy at the Child Health Center; and the therapists' technique. Parents were also clustered into three so-called ideal types: the insecure; parents in crisis; and parents with lifelong psychological problems. Parents experienced obstacles in accessing psychological care within primary healthcare. Psychotherapists with a holistic family perspective and who managed to oscillate between insight-promoting and supportive interventions were especially appreciated. Patient categories who benefitted from insight promotion and support, respectively, were identified.


The origins of charge separation in anisotropic facet photocatalysts investigated through first-principles calculations.
It was recently discovered that the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) can be completed on the {110} and {001} facets, respectively, of a 18-facet SrTiO3 mono-crystal. The effective charge separation is attributed to the facet junction at the interface between two arbitrary anisotropic crystal planes. Theoretical estimation of the built-in potential at the facet junction can greatly improve understanding of the mechanism. This work employs density functional theory (DFT) calculations to investigate such potential at the (110)/(100) facet junction in SrTiO3 crystals. The formation of the facet junction is verified by a calculated work function difference between the (110) and (100) planes, which form p-type and n-type segments of the junction, respectively. The built-in potential is estimated at about 2.9 V. As a result, with the ultra high built-in potential, electrons and holes can effectively transfer to different anisotropic planes to complete both photo-oxidative and photo-reductive reactions.


DNA-RNA complexes that might represent transient attachment sites of nuclear DNA to the matrix.
In this study we describe DNA-RNA complexes in matrix DNA of Friend cells. The presence of such unusual structures is confirmed by the following evidence. When a preparation of matrix DNA is electrophoresed in agarose an RNA component always migrates together with DNA. There should be a close interaction between DNA and RNA in such a preparation because the presence of the RNA component causes resistance of DNA to DNase I and Exo III. An intimate, hybrid-type association of part of the RNA component with DNA is indicated also by the fact that about 20% of this RNA is sensitive to RNase H. By specific inhibition of the RNA synthesis with alpha-amanitin and actinomycin D it was shown that the bulk of associated RNA is transcribed by RNA polymerase III. Hybridization experiments showed similarity between the DNA sequences isolated from the complexes and those from the base of dehistonized DNA loops obtained by high-salt extraction of nuclei. This observation suggests that the complexes might represent attachment sites of nuclear DNA to the matrix: possibly, the attachment is mediated via the RNA component. Experiments with induction of erythroid differentiation indicated that a profound reorganization of the nucleus, accompanying terminal differentiation, leads to a striking reduction in the number of complexes and thus in the number of attachment sites. This suggests that the complexes should function as transient attachment sites.


Determination of the gluten content of foods.
Coeliac disease affects 1:1,500 people in Europe. Treatment of the condition involves a gluten-free diet with avoidance of foods containing wheat, rye, barley or oats. Evidence suggests that individuals should adhere strictly to the diet as this reduces the increased incidence of malignancy observed in the condition. A large number of gluten-free products are currently available. Immunological assays have been developed to assess their suitability for patients with coeliac disease. Quantitative assays, based on both polyclonal antisera and monoclonal antibodies, methods of extraction and problems associated with interfering substances are reviewed in this paper.


Unusual haematological alterations in rheumatoid arthritis.
Three cases of rheumatoid arthritis (RA), presenting with refractory anaemia, thrombocytopenia and peripheral lymphocytosis respectively, were observed. In all the cases haematological manifestations were unrelated to disease activity or drug toxicity. These patients were detected to have pure red cell aplasia (PRCA) (normocytic normochromic anaemia, reticulocytopenia and absence of erythroid precursors in the bone marrow), immune thrombocytopenia (IT) (absence of splenomegaly and presence of increased megakaryocytes in the bone marrow) and multiple myeloma (MM) (lytic lesions on skull, paraproteinaemia and bone marrow plasmacytosis) respectively. PRCA and IT responded to glucocorticoids. Association with these three haematological alterations has rarely been reported. Our report highlights the need to regularly monitor blood counts in patients with RA.


[Genetic Diagnostics in Everyday Clinical Practice in Child and Adolescent Psychiatry: Indications, Framework Conditions, Hurdles, and Proposed Solutions].
Genetic Diagnostics in Everyday Clinical Practice in Child and Adolescent Psychiatry: Indications, Framework Conditions, Hurdles, and Proposed Solutions Abstract: Health insurance covers medically necessary genetic testing in Germany. Diagnostic genetic testing has become increasingly important for child and adolescent psychiatry (CAP), reflected by the rising number of national guidelines relevant to CAP, including genetic testing in the recommended diagnostic work-up. However, implementation of theses guidelines in routine clinical care is lacking. This article provides a concise overview of the relevance of genetic testing in CAP-related national guidelines. It outlines the legal and financial framework for genetic testing in Germany. Furthermore, it points out barriers to implementation and offers potential solutions. It then provides examples from clinical practice highlighting the potential benefits patients and their family members might have from receiving a genetic diagnosis. The article closes by outlining future CAP-relevant areas in which genetic testing may become clinically relevant.


Rehabilitation after posterolateral dislocation of the elbow in a collegiate football player: a case report.
To describe a functional rehabilitation program for a football player with a grade 2 posterolateral elbow dislocation to facilitate early return to competition. Conservative management of a posterior dislocation of the elbow is common. The elbow is the second most frequently dislocated large joint in adults. Two common mechanisms of dislocation are hyperextension and posterolateral rotation. Prolonged immobilization can be detrimental to regaining full range of motion and function of the elbow, whereas early directed rehabilitation may lead to early return to normal function. Elbow dislocation with medial collateral ligament rupture, elbow subluxation, elbow dislocation with neurovascular compromise, or supracondylar fracture. The athlete received immediate care of reduction and immobilization in a 90 degrees posterior splint followed by a radiologic evaluation. Postreduction treatment included a short immobilization period and early initiation of protected active and resistive range-of-motion exercises. The athlete was able to return to full football activities in 3 weeks. He competed for the rest of the season with the elbow braced and taped, with no recurring incidents of instability. The time to return to full participation was rapid. The medial collateral ligament was intact, as determined by magnetic resonance imaging. The athlete has since been followed for 2 football seasons and has not demonstrated any detrimental effects due to his early return. Early determination of the status of the medial collateral ligament through physical examination or imaging combined with early directed rehabilitation of a posterolateral elbow instability enabled this athlete to respond well. He regained pain-free full range of motion, strength, and function, allowing full participation in football at the Division I level with no recurring incidence of dislocation.


Projected changes to growth and mortality of Hawaiian corals over the next 100 years.
Recent reviews suggest that the warming and acidification of ocean surface waters predicated by most accepted climate projections will lead to mass mortality and declining calcification rates of reef-building corals. This study investigates the use of modeling techniques to quantitatively examine rates of coral cover change due to these effects. Broad-scale probabilities of change in shallow-water scleractinian coral cover in the Hawaiian Archipelago for years 2000-2099 A.D. were calculated assuming a single middle-of-the-road greenhouse gas emissions scenario. These projections were based on ensemble calculations of a growth and mortality model that used sea surface temperature (SST), atmospheric carbon dioxide (CO(2)), observed coral growth (calcification) rates, and observed mortality linked to mass coral bleaching episodes as inputs. SST and CO(2) predictions were derived from the World Climate Research Programme (WCRP) multi-model dataset, statistically downscaled with historical data. The model calculations illustrate a practical approach to systematic evaluation of climate change effects on corals, and also show the effect of uncertainties in current climate predictions and in coral adaptation capabilities on estimated changes in coral cover. Despite these large uncertainties, this analysis quantitatively illustrates that a large decline in coral cover is highly likely in the 21(st) Century, but that there are significant spatial and temporal variances in outcomes, even under a single climate change scenario.


A Loop-Mediated Isothermal Amplification Assay Targeting 16S rRNA Gene for Rapid Detection of Anaplasma phagocytophilum Infection in Sheep and Goats.
Anaplasma phagocytophilum is a zoonotic pathogen and the causative agent of human granulocytic anaplasmosis in humans and tick-borne fever in various kinds of animals. In the present study, a loop-mediated isothermal amplification (LAMP) assay for rapid detection of A. phagocytophilum was developed using primers specific to 16S rRNA gene of this organism. The LAMP assay was performed at 65 C for 60 min and terminated at 80 C for 10 min. The optimal reaction conditions under which no cross-reaction was observed with other closely related tick-borne parasites ( Anaplasma bovis , Anaplasma ovis , Theileria luwenshuni, Babesia motasi, and Schistosoma japonicum ) were established. The assay exhibited much higher sensitivity compared with conventional polymerase chain reaction (PCR) (1 copy vs. 1,000 copies). To evaluate the applicability of the LAMP assay, 94 field samples of sheep blood were analyzed for A. phagocytophilum infection by using LAMP, nested PCR, and conventional PCR assays at the same time. A positive LAMP result was obtained from 53 (56.4%) of the 94 samples, whereas only 12 (12.8%) and 3 (3.2%) tested positive by nested and conventional PCR, respectively. In conclusion, this LAMP assay is a specific, sensitive, and rapid method for the detection of A. phagocytophilum in sheep/goats.


Epidemiology of multiple chronic conditions: an international perspective.
The epidemiology of multimorbidity, or multiple chronic conditions (MCCs), is one of the research priority areas of the U.S. Department of Health and Human Services (HHS) by its Strategic Framework on MCCs. A conceptual model addressing methodological issues leading to a valid measurement of the prevalence rates of MCCs has been developed and applied in descriptive epidemiological studies. Comparing these results with those from prevalence studies performed earlier and in other countries is hampered by methodological limitations. Therefore, this paper aims to put the size and patterns of MCCs in the USA, as established within the HHS Strategic Framework on MCCs, in perspective of the findings on the prevalence of MCCs in other countries. General common trends can be observed: increasing prevalence rates with increasing age, and multimorbidity being the rule rather than the exception at old age. Most frequent combinations of chronic diseases include the most frequently occurring single chronic diseases. New descriptive epidemiological studies will probably not provide new results; therefore, future descriptive studies should focus on the prevalence rates of MCCs in subpopulations, statistical clustering of chronic conditions, and the development of the prevalence rates of MCCs over time. The finding of common trends also indicates the necessary transition to a next phase of MCC research, addressing the quality of care of patients with MCCs from an organizational perspective and with respect to the content of care. Journal of Comorbidity 2013;3:36-40.


Temporal trends in dioxins (polychlorinated dibenzo-p-dioxin and dibenzofurans) and dioxin-like polychlorinated biphenyls in Baltic herring (Clupea harengus).
Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyl (dl-PCBs) concentrations in Baltic herring (Clupea harengus) have been relatively stable since the mid to late 1990s. It is unclear why concentrations in Baltic herring are not following the observed decreases in other environmental matrices. Here, changes in long-term temporal trends in Baltic herring were examined. A number of biological variables were examined alongside the temporal trends to investigate whether fish biology e.g., growth (length, weight, age), lipid content, reproductive phase or fishing date may provide an explanation for the temporal trends observed. Significant (p<0.05) decreasing trends were observed for PCDD/F toxic equivalents (TEQPCDD/F) at three of the four sites (lipid weight (lw) and wet weight (ww), Swedish west coast lw only); however, other TEQ values e.g., TEQPCDD, TEQPCDF, TEQdl-PCB, TEQPCDD/F+dl-PCB were inconsistent, decreasing at some sites but not others. In the most recent 10 years of data, fewer significant decreases were seen overall. Over the examined time period, significant decreases (Bothnian Bay, p<0.01, southern Baltic Proper, p<0.02) and increases (Swedish west coast, p<0.02) in lipid content, growth dilution or lack thereof, and significant changes in age were observed. However herring were not randomly selected which biases this result. Continual efforts to decrease PCDD/F and dl-PCB emissions and to locate/reduce hotspots are necessary, while bearing in mind that herring biology may be impeding faster decreases of these chemicals.


[Treatment of serious burns].
Treatment of patients with large burns is challenging. The article is based on clinical experience, and a non-systematic review in PubMed. In patients with burns covering more than 10 - 15 % of the total body surface area, fluid resuscitation should be initiated early. Fluid induces edema, and facial burns may necessitate early orotracheal intubation to secure the airways. Reduced ventilation and-/or peripheral circulation due to deep burns should be managed by early escharotomy (and, more seldom, fasciotomy) at the primary hospital. Respiratory distress is most often due to vigorous fluid resuscitation, secretions, pneumonia and-/or sepsis. Fiber bronchoscopy may reveal inhalation injury and enables removal of secreted material from the airways. In the acute initial phase, hypotension is usually caused by hypovolemia. Subsequently a massive inflammatory response (SIRS) causes vasodilatation, hypotension and increased cardiac output. Wound and airway infections are common. SIRS may cause CRP levels above 100 and a body temperature of 38 - 39 degrees C, which makes it difficult to find the right time to start antibiotic treatment. Nevertheless, prophylactic use of antibiotics is not encouraged. Definitive surgery, excision and transplantation, should be performed early, preferably within the first week. Patients with large burns should be treated according to general principles for intensive medical care, preferably in units with special experience in treatment of burns.


Single-port transumbilical laparoscopic cholecystectomy: A prospective randomised comparison of clinical results of 140 cases.
A novel single port access (SPA) cholecystectomy approach is described in this study. We have designed a randomised comparative study in order to elucidate any possible differences between the standard treatment and this novel technique. Between July 2009 and March 2010, 140 adult patients with gallbladder pathologies were enrolled in this multicentre study. Two surgeons (RV and UB) randomised patients to either a standard laparoscopic (SL) approach group or to an SPA cholecystectomy group. Two types of trocars were used for this study: the TriPort™ and the SILS™ Port. Outcomes including blood loss, operative time, complications, length of stay and pain were recorded. There were 69 patients in the SPA group and 71 patients in the SL group. The mean age of the patients was 43.2 (17-77) for the SPA group and 42.6 (19-70) for the SL group. The mean operative time was 63.9 min in the SPA group and 58.4 min in the SL group. For one patient, the SPA procedure was converted to a standard laparoscopic technique and to open approach in the SL group. Complications occurred in eight patients: Five seromas (two in the SPA group) and three hernias (one in the SPA group).The mean hospital stay was 38.5 h in the SPA group and 24.1 h in the SL group. Pain was evaluated and was 2 in the SPA and 2.9 in the SL group, according to the visual analogue scale (VAS) after 24 h (P<0.001). The degree of satisfaction was higher in the SPA group (8.3 versus 6.7). Similar results were found for the aesthetic result (8.8 versus 7.5). (P<0.001). Single-port transumbilical laparoscopic cholecystectomy can be feasible and safe. When technical difficulties arise, early conversion to a standard laparoscopic technique is advised to avoid serious complications. The SPA approach can be undertaken without the expense of additional operative time and provides patients with minimal scarring. The cosmetic results and the degree of satisfaction appear to be significant for the SPA approach.


Prevalence and Correlates of Herbal Medicine Use among Women Seeking Care for Infertility in Freetown, Sierra Leone.
In resource-poor countries where access to infertility care is limited, women may turn to traditional medicine to achieve motherhood. It is unknown whether Sierra Leonean women with such condition use herbal medicine. This study investigates the prevalence and factors associated with herbal medicine use among women seeking care for infertility. This was a questionnaire-based cross-sectional study conducted among women seeking care for infertility at various clinics within Freetown, Sierra Leone. Data analysis included Chi-square tests and logistic regression. Out of the 167 women that participated, 36.5% used herbal medicine for infertility treatment. Women with no formal (AOR 4.03, CL: 1.38-11.76, p = 0.011), primary education (AOR: 6.23, CL: 2.02-19.23, p = 0.001) and those that visited a traditional medicine practitioner (AOR: 20.05, CL: 2.10-192.28, p = 0.009) as well as women suffering from other reproductive health problems (AOR: 2.57, CL: 1.13-5.83, p = 0.024) were more likely to use herbal medicines. Friends and family (n = 57, 96.7%) were the main influencers of herbal medicine use. Only (n = 12) 19.7% of users disclosed their status to their healthcare provider. Over half (n = 32, 52.5%) could not remember the name of the herb they used. Luffa acutangula (n = 29, 100%) was the herbal medicinal plant users could recall. Herbal medicine use among women seeking care for infertility in Freetown is common. Healthcare providers should be aware of the potential dyadic use of herbal and allopathic medicines by their patients and be knowledgeable about commonly used herbal remedies as well as being proactive in communicating the potential risks and benefits associated with their use.


Overexpression of the PRAD1 oncogene in a patient with multiple myeloma and t(11;14)(q13;q32).
The t(11;14)(q13;q32) chromosomal translocation is associated with several B-cell lymphoproliferative disorders and is thought to result in upregulation of expression of PRAD1/cyclin D1 proto-oncogene. A patient with multiple myeloma of IgG kappa-type with t(11;14)(q13;q32) is now shown to overexpress PRAD1. The clinical stage of the disease was advanced (IIIA), with a myeloma cell count of 94.6% in the bone marrow. Chromosomal analysis of bone marrow cells showed t(11;14)(q13;q32) in five of 20 metaphases as well as other karyotypic features. Northern blot analysis of RNA prepared from myeloma cells revealed overexpression of PRAD1. Multiple myeloma with t(11;14)(q13;q32) has been associated with an aggressive clinical course. Although neither myeloma cells in the peripheral blood nor extramedullary lesions were apparent in the present patient, the myeloma was refractory to several chemotherapeutic regimens from the beginning. Detection of PRAD1 expression may offer an easier alternative to cytogenetic analysis in myeloma and is a potentially useful indicator of a poor prognosis.


[Dynamics of morphohistochemical parameters and lipid peroxidation in the course of aging of the human cerebral hemisphere cortex].
Morphometric parameters of "neuron-capillary-glia" system, succinatedehydrogenase (SDG), NAD-diaphorase and lipid peroxidation (LPO) activities were studied in area 41 and area E of human cerebral hemisphere cortex. It was established that the aging was associated with a reduction in a portion of capillaries, decline in neuronal SDG activity and an activation of LPO. The consequences of these phenomena are the death of some part of neurons accompanied by a substitutive gliosis and an increase of glial index. Augmentation of both volumetric parameters of capillary bed and neuronal NAD-diaphorase activity, presumably, represents the compensatory reaction in human cerebral cortex in senile age. The changes described above were found to be more pronounced in auditory cortex (area 41) than in olfactory cortex (area E).


Local recurrence and metachronous multiple cancers after transoral nonrobotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study.
Late laryngopharyngeal cancers after transoral surgery include not only local recurrences but also metachronous multiple cancers. We compared clinical information, surgical outcomes, and late laryngopharyngeal cancers in patients who underwent transoral nonrobotic surgery for laryngopharyngeal squamous cell carcinoma without lymph node metastases between 2015 and 2021 in a multicenter retrospective study. Four hundred and fifty-seven patients were included. Positive surgical margins were found in 121 patients (26.5%). Twenty-two patients (4.8%) received additional treatment. Positive horizontal margins of invasive carcinoma (p = 0.003) and positive horizontal margins of carcinoma in situ only (p = 0.032) were independent risk factors for local recurrence, and prior radiotherapy (p = 0.001) for metachronous multiple cancers. Local control was significantly worse without additional treatment (p = 0.049), but there was no significant difference in survival. Patients with positive margins had an increased frequency of local recurrence, but salvage therapy was effective.


Arterio-venous differences to study macronutrient metabolism: introduction and overview.
The arterio-venous difference technique is now well established in the study of organ and tissue metabolism. This technique requires samples to be obtained of the arterial blood supplying and the venous drainage from a tissue, together with a measurement of the blood flow through the tissue. The technique is most appropriate when the arterial concentration and tissue metabolism of a substance are constant, and when the blood flow is stable. If these criteria are not satisfied, care is needed in the interpretation of the results obtained. It should be recognized that the arterio-venous difference technique only measures the net exchange of a substance with the tissue, and that tracers are needed if unidirectional flux needs to be estimated. The other factors which must be borne in mind when intending to use this technique are the transit times of blood and the substance of interest through a tissue, the volume of distribution of the substance in the tissue, and the possibility that the venous samples obtained are derived from a mixture of different tissues.


Application of electrical treatment on Euglena gracilis for increasing paramylon production.
Paramylon also called β-1,3-glucan is a value-added product produced from Euglena gracilis. Recently, researchers have developed various strategies for the enhanced paramylon production, among which electrical treatment for microbial stimulation can be an alternative owing to the applicability to large-scale cultivation. In this study, we applied the electrical treatment for enhanced paramylon production and found the proper treatment conditions. Under the treatment with platinum electrodes at 10 mA, the paramylon production of treated cells was significantly increased about 2.5-fold, compared to those of the untreated cells, although the density of cells was maintained due to considerable stress. The size of treated cells became larger, possibly due to the increased level of paramylon production within the cells. Accordingly, the contents of glucose uptake, glucose-6-phosphate (G6P), glucose-1-phosphate (G1P), and uridine diphosphoglucose (UDPG) were shifted to appropriate states for the process of paramylon synthesis under the treatment. The increased level of transcripts encoding glucan synthase-like 2 (EgGSL2) was also confirmed via droplet digital PCR (ddPCR) under the treatment. Overall, this study makes a major contribution to research on electrical stimulation and provides new insights into E. gracilis metabolism like paramylon synthesis. KEY POINTS: • Electrical treatment induced the paramylon production and morphological change of Euglena gracilis. • The glucose uptake of E. gracilis was increased during the electrical treatment, fueling the paramylon synthesis.


Discrete-time backpropagation for training synaptic delay-based artificial neural networks.
The aim of this paper is to endow a well-known structure for processing time-dependent information, synaptic delay-based ANN's, with a reliable and easy to implement algorithm suitable for training temporal decision processes. In fact, we extend the backpropagation algorithm to discrete-time feedforward networks that include adaptable internal time delays in the synapses. The structure of the network is similar to the one presented by [1], that is, in addition to the weights modeling the transmission capabilities of the synaptic connections, we model their length by means of a parameter that indicates the delay a discrete-event suffers when going from Zthe origin neuron to the target neuron through a synaptic connection. Like the weights, these delays are also trainable, and a training algorithm can be derived that is almost as simple as the backpropagation algorithm, and which is really an extension of it. We present examples of the application of these networks and algorithm to the prediction of time series and to the recognition of patterns in electrocardiographic signals. In the first case, we employ the temporal reasoning characteristics of these networks for the prediction of future values in a benchmark example of a time series: the one governed by the Mackey-Glass chaotic equation. In the second case, we provide a real life example. The problem consists in identifying different types of beats through two levels of temporal processing, one relating the morphological features which make up the beat in time and another one that relates the positions of beats in time, that is, considers rhythm characteristics of the ECG signal. In order to do this, the network receives the signal sequentially, no windowing, segmentation, or thresholding are applied.


Scaling of an antibody validation procedure enables quantification of antibody performance in major research applications.
Antibodies are critical reagents to detect and characterize proteins. It is commonly understood that many commercial antibodies do not recognize their intended targets, but information on the scope of the problem remains largely anecdotal, and as such, feasibility of the goal of at least one potent and specific antibody targeting each protein in a proteome cannot be assessed. Focusing on antibodies for human proteins, we have scaled a standardized characterization approach using parental and knockout cell lines (Laflamme et al., 2019) to assess the performance of 614 commercial antibodies for 65 neuroscience-related proteins. Side-by-side comparisons of all antibodies against each target, obtained from multiple commercial partners, have demonstrated that: (i) more than 50% of all antibodies failed in one or more applications, (ii) yet, ~50-75% of the protein set was covered by at least one high-performing antibody, depending on application, suggesting that coverage of human proteins by commercial antibodies is significant; and (iii) recombinant antibodies performed better than monoclonal or polyclonal antibodies. The hundreds of underperforming antibodies identified in this study were found to have been used in a large number of published articles, which should raise alarm. Encouragingly, more than half of the underperforming commercial antibodies were reassessed by the manufacturers, and many had alterations to their recommended usage or were removed from the market. This first study helps demonstrate the scale of the antibody specificity problem but also suggests an efficient strategy toward achieving coverage of the human proteome; mine the existing commercial antibody repertoire, and use the data to focus new renewable antibody generation efforts.