Associations of life events during pregnancy with longitudinal change in symptoms of antenatal anxiety and depression.
to investigate the association of life events during pregnancy with change in antenatal anxiety and depression symptoms. We distinguished pregnancy related and non-pregnancy related events and assessed specificity of these associations for depressive or anxious symptoms. In addition, we investigated whether the associations were affected by personality or childhood adversities. observational prospective cohort study primary and secondary obstetric care centres in the Netherlands 1603 women during their first trimester of pregnancy between May 2010 and May 2012 MEASUREMENTS AND FINDINGS: we performed linear regression analyses to test the associations of pregnancy related, non-pregnancy related life events, childhood adversities and the personality traits neuroticism and extraversion with the change in symptoms of anxiety (State Trait Anxiety Inventory) and depression (Edinburgh Postnatal Depression Scale) from week 12 to week 36. Life events during pregnancy were associated with increasing antenatal symptoms of anxiety and depression. Effect sizes associated with the highest numbers of events observed ranged from 0.59 to 1.31. Pregnancy related events were specifically associated with increasing symptoms of anxiety (p=0.009), whereas non-pregnancy related events were merely associated with an increase in symptoms of depression (p<0.001). Neither personality traits nor childhood trauma influenced the associations under study. the most important finding is that pregnancy related life events during pregnancy increase levels of antenatal anxiety, whereas depression levels increase when women experience life events that are unrelated to pregnancy. Furthermore, non-pregnancy related events show stronger associations with increases in symptoms of anxiety or depression compared to pregnancy related events. our findings may help midwives to tailor psychosocial care to the specific risks of the pregnant woman which may eventually have a positive impact on the health of mother and child.


Hepatobiliary tuberculosis in western India.
Tuberculous involvement of liver as a part of disseminated tuberculosis is seen in up to 50-80% cases, but localized hepatobiliary tuberculosis (HBTB) is uncommonly described. During 6 years, a total of 280 consecutive patients with TB were evaluated prospectively for the presence and etiology of liver involvement. Cases with miliary TB or immunosuppression and cases receiving anti-tuberculosis drugs prior to presentation to our unit were excluded (38 cases). Details of clinical, biochemical and imaging findings and histology/microbiology were noted. Of 242 included cases, 38 patients (15.7%; age 38.1 +/- 12.5 years; sex ratio 2.5:1) had HBTB, whereas 20 patients (9%; age 39.3 +/- 16.3 years; sex ratio 2.1:1) had other liver diseases. Diagnosis of HBTB was based on caseating granuloma on histology (18/23 procedures), positive smear/culture for acid-fast bacilli (21/39 procedures) and positive polymerase chain reaction for Mycobacterium tuberculosis (28/29 procedures) when diagnostic procedures were guided by imaging results. Thirty-eight cases with HBTB were classified as follows [patients (n), (%)]: (A) hepatic TB [20 (52.6%)]: (1) granulomatous hepatitis - 10 (26.3%), (2) liver abscesses or pseudotumors - 10 (26.3%) and (3) calcified hepatic granuloma - 0 (0%); (B) biliary TB [15 (39.4%)]: (1) biliary strictures - 2 (5.2%), (2) gall bladder involvement - 1 (2.6%) and (3) biliary obstruction due to lymph node masses - 12 (31.5%); (C) mixed variety [3 (7.8%)]: (1) simultaneous granulomatous hepatitis and biliary stricture - 1 (2.6%) and (2) simultaneous lymph node involvement and calcified hepatic granuloma - 2 (5.2%). All the cases responded well to standard anti-tuberculosis therapy. HBTB forms an important subgroup in TB cases. It requires a combination of imaging, histological and microbiological procedures to define the diagnosis. HBTB responds well to treatment.


The human U6 snRNA intramolecular helix: structural constraints and lack of sequence specificity.
Splicing of mRNA precursors occurs in a massive structure known as the spliceosome and requires the function of several small nuclear RNAs (snRNAs). A number of studies have suggested potentially important roles for two snRNAs, U2 and U6, in splicing catalysis. These two RNAs interact extensively with each other, as well as with the pre-mRNA, and possible similarities with catalytic RNAs have been noted. An important feature of the U2-U6 complex is an intramolecular helix in U6, which forms in conjunction with activation of the spliceosome. Here we describe a detailed genetic analysis of residues that make up this helix in human U6 snRNA, using an in vivo assay in which splicing of a test pre-mRNA is dependent on exogenous U6 snRNA. Our results show that many, but not all, positions tested are sensitive to mutation. Unexpectedly, base pairing is fully compatible with function at all positions, and at many is both necessary and sufficient. For example, conversion of two noncanonical A-C pairs to G-C pairs did not affect splicing, nor did conversion of an A-G to C-G. Extension of the helix by a base pair was also tolerated, provided that base pairing was maintained. Most notable was the behavior of a bulged U (U74), which has been suggested previously to be of particular importance. Although U74 was sensitive to substitution or deletion, incorporation into the helix by insertion of an A across from it was without effect, even in the context of a second helix-stabilizing mutation. We discuss these results in terms of possible mechanisms by which U6 snRNA might function in splicing catalysis.


Effects of cationized ferritin and neuraminidase on invasion of cultured cells by Eimeria meleagrimitis sporozoites.
Primary turkey kidney cells and Eimeria meleagrimitis sporozoites were treated with cationized ferritin (CF) or neuraminidase ( NANase ), and the effects on the invasion of the cells by the sporozoites were measured. Cultures of host cells pretreated with either compound contained significantly fewer intracellular sporozoites than did control cultures. There was little additive effect if cultures were first treated with NANase and then with CF. In contrast, pretreatment of sporozoites with CF or low concentrations of NANase had no effect on invasion. The inhibition of invasion was apparently due to an interaction between treatment substances and host cell surface rather than to direct effect on the sporozoites. The CF bound to the randomly distributed anionic sites on the surfaces of both host cells and sporozoites and then rapidly aggregated. Sporozoites, probably in the process of invading cells, were invariably found with the conoid in close association with aggregates of CF on the host cell membrane. The CF on the sporozoites was apparently shed before or during invasion because all intracellular sporozoites were completely devoid of the label.


The Effect of Schwann Cells/Schwann Cell-Like Cells on Cell Therapy for Peripheral Neuropathy.
Peripheral neuropathy is a common neurological issue that leads to sensory and motor disorders. Over time, the treatment for peripheral neuropathy has primarily focused on medications for specific symptoms and surgical techniques. Despite the different advantages of these treatments, functional recovery remains less than ideal. Schwann cells, as the primary glial cells in the peripheral nervous system, play crucial roles in physiological and pathological conditions by maintaining nerve structure and functions and secreting various signaling molecules and neurotrophic factors to support both axonal growth and myelination. In addition, stem cells, including mesenchymal stromal cells, skin precursor cells and neural stem cells, have the potential to differentiate into Schwann-like cells to perform similar functions as Schwann cells. Therefore, accumulating evidence indicates that Schwann cell transplantation plays a crucial role in the resolution of peripheral neuropathy. In this review, we summarize the literature regarding the use of Schwann cell/Schwann cell-like cell transplantation for different peripheral neuropathies and the potential role of promoting nerve repair and functional recovery. Finally, we discuss the limitations and challenges of Schwann cell/Schwann cell-like cell transplantation in future clinical applications. Together, these studies provide insights into the effect of Schwann cells/Schwann cell-like cells on cell therapy and uncover prospective therapeutic strategies for peripheral neuropathy.


[Health care financing models].
The functioning of health care depends mainly on the level and method of financing. Countries choose between different models. Bismarck's model is financing based mainly on the contributions that are obligatory for employers and employees, decentralized model of managing and contracting services. Beveridge's model is financed mostly from the government taxes, it allows contributing to the cost of benefits for patients and participation by private sector. Residual model is based on the optional and private health insurances, supplemented only by National Health Service. Siemaszko's model in his assumption is based on the financing of benefits by the state budget, provides permanent control of the state and equal access to all the benefits for citizens. Choice of a specific financing model entails certain impact on all of the system's participants. The purpose of this article is to introduce subject of health care financing based on the literature and the authors' own thoughts.


Daily cyclic changes in the urinary excretion of 5-hydroxyindoleacetic acid in patients with carcinoid tumors.
Vasoactive peptides produced by neuroendocrine tumors can induce characteristic symptoms of the carcinoid syndrome (flushing, diarrhea, and wheezing). To what extent external factors provoke these symptoms and how excretion of 5-hydroxyindoleacetic acid (5-HIAA), the degradation product of serotonin, varies throughout the day remain unknown. In this study, we investigated whether symptoms and daily activity are related to 5-HIAA excretion and whether 24-h urine collection is needed. In 26 patients with metastatic carcinoid (14 men and 12 women; median age, 60 years) urine was collected in portions of 4 or 8 h during 2 days. Patients were asked to keep a diary in which they noted symptoms of flushes, consistency of stools, activities, and food intake. Excretion of 5-HIAA in 24-h urine was increased in 88% of the patients (median, 515 micromol/24 h). Overnight-collected urine appeared the most representative for 24-h collection concentrations (correlation coefficient = 0.81). We found no clear correlation between symptoms of the carcinoid syndrome and degree of activity. Watery diarrhea was reported only by patients with strong variations in 5-HIAA excretion. One-half of the patients (n = 16) exhibited a high variability in urinary 5-HIAA excretion throughout the day, with increased concentrations most prominent in morning collections (P = 0.0074) and lower concentrations in the evening (P = 0.0034). In the other patients these curves were flat. Cyclic changes in patients relate to high variability in 5-HIAA excretion. Overnight-collected urine can replace the 24-h urine collection, and marked variations in 5-HIAA excretion seem to be associated with severity of diarrhea.


Duodenal infusion of fatty acids differentially affects plasma glucagon-like peptide-1 and ghrelin concentrations in sheep.
The aim of this study was to investigate how intraduodenal infusions of fatty acids (FA) affect appetite-related gut peptides such as glucagon-like peptide-1 (GLP-1) and ghrelin in sheep. We hypothesized that these peptides can be highly reactive to unsaturated long-chain FA, because they are well known to decrease dry matter intake (DMI). Four ewes were fitted with a duodenal cannula and a jugular vein catheter for a 6-h duodenal infusion of the 9 FA (C8:0, C10:0, C12:0, C14:0, C16:0, C18:0, C18:1, C18:2, and C18:3) and water (control). The concentration of each FA was 1.6 g per metabolic body weight (BW), approximately corresponding to the amount of supplemented fat in a standard dairy cow diet. Each infusion was separated by at least 2 d. During the infusion period, blood samples were collected periodically to determine changes in plasma GLP-1, ghrelin, and metabolite concentrations. Duodenal infusions of C18:1, C18:2, and C18:3 led to higher plasma GLP-1 (P < 0.05) and lower glucose (P < 0.05) than control. Plasma ghrelin concentrations were greater in C18:1 and C18:3 infusions than control (P < 0.05). Plasma ketone bodies were higher in C8:0 and C10:0 infusions (P < 0.05), but plasma triglyceride concentrations were lower in C8:0, C10:0, C12:0, and C16:0 infusions (P < 0.05) than control. Fatty acid infusions except for C18:3 led to higher plasma NEFA concentrations than control (P < 0.05). These results confirmed that the hypophagic effect of dietary unsaturated long-chain FA is mediated by GLP-1 (an anorexigenic effect) secretion. However, we also observed higher plasma ghrelin (an orexigenic effect) partially by unsaturated long-chain FA. Thus, the gut peptide secretions when ruminant animals ingest FA supplements would complexly affect satiety and further studies are needed to determine their each impact on DMI.


Ischemia-modified albumin concentrations in patients with peripheral vascular disease and exercise-induced skeletal muscle ischemia.
Ischemia-modified albumin (IMA) is a new marker of myocardial ischemia, there is concern that IMA concentrations may be affected by ischemia occurring in tissues other than the myocardium. We assessed 23 consecutive patients (15 males; mean age, 67 years) with typical leg claudication and documented peripheral vascular disease (PVD). All patients underwent both treadmill-exercise stress testing to induce leg ischemia and dobutamine stress echocardiography 1 week apart for the assessment of myocardial ischemia. Blood samples for IMA measurements were obtained at baseline, immediately after peak exercise/stress, and 1 h after exercise/stress. Statistical analysis was performed with the ANOVA repeated-measures test. Compared with baseline, mean (SD) IMA was significantly lower after the induction of skeletal muscle ischemia and returned to baseline values at 1 h: baseline, 74.6 (15.6) kilounits/L; peak stress, 69.5 (14.0) kilounits/L (P <0.0001 vs baseline); 1 h after stress, 75.9 (15.7) kilounits/L (P <0.0001 vs peak stress; P = 0.3 vs baseline). Baseline, peak stress, and 1-h poststress IMA concentrations were inversely correlated with the ankle-brachial index after exercise (r = -0.4; P <0.05). None of the patients showed regional wall motion abnormalities during dobutamine stress echocardiography, and IMA concentrations remained unchanged from baseline. There were no differences in baseline [74.6 (15.6) vs 72.7 (11.5) kilounits/L; P = 0.6], peak stress, or poststress IMA concentrations when exercise testing and dobutamine stress echocardiography values were compared. The relationship between disease severity (of a noncardiac origin) and baseline IMA values is an important and novel finding. IMA is significantly lower immediately after exercise-induced leg ischemia in patients with PVD and is related to disease severity. IMA concentrations can therefore be affected by the development of skeletal muscle ischemia, and this may have implications regarding the ability of IMA to detect myocardial ischemia in PVD patients.


Use of a novel carbon fibre composite material for the femoral stem component of a THR system: in vitro biological assessment.
A novel, low elastic modulus femoral component for THR has been developed using a composite of polyetheretherketone and carbon fibre. The objectives of this study were to investigate human osteoblast-like cell and macrophage responses to this material in vitro. Cells were grown on composite discs and controls. Osteoblast attachment and proliferation was not significantly different to that on Ti6Al4V. The levels of alkaline phosphatase activity, Type I collagen production and osteocalcin production were not significantly different to that on Ti6Al4V by the end of the experimental period. Hydrogen peroxide production by macrophages was significantly less than that detected for cells cultured on copper, but was still greater than that detected for cells cultured on tissue culture plastic and Ti6Al4V. Beta-glucoronidase activity was not significantly different to that detected for cells cultured on tissue culture plastic. The in vitro biocompatibility assessment of this composite undertaken in this study showed initial osteoblast attachment at least comparable to that of the tissue culture plastic and Ti6Al4V controls, with proliferation similar to the controls at all time points up to 11 days. Alkaline phosphatase activity was similar to that of Ti6Al4V but reduced compared to tissue culture plastic controls. Whilst hydrogen peroxide production by macrophages was raised on composite surfaces compared to controls, beta-glucoronidase activity and osteoblastic production of Type I collagen and osteocalcin were similar to levels detected on Ti6Al4V.


Characterization of khaya gum as a binder in a paracetamol tablet formulation.
The influence of khaya gum, a binding agent obtained from Khaya grandifolia (Meliaceae family), on the bulk, compressional, and tabletting characteristics of a paracetamol tablet formulation was studied in comparison with the effects of two standard binders: polyvinylpyrrolidone (PVP; molecular weight 40,000) and gelatin. The relative ability of khaya gum to destroy any residual microbial contamination in the binder or in the formulation during tabletting was also studied using Bacillus subtilis spores as a model. Formulations containing khaya gum exhibited more densification than formulations containing PVP and gelatin during die filling, but less densification due to rearrangement at low pressures. The mean yield pressure of the formulation particles obtained from Heckel plots, and another pressure term, also inversely related to plasticity, obtained from Kawakita plots, showed dependence on the nature and concentration of the binder, with formulations containing khaya gum exhibiting the lowest and highest values respectively. The values of the pressure terms suggest that the yield pressure relates to the onset of plastic deformation during compression, while the Kawakita pressure relates to the total amount of plastic deformation occurring during the compression process. Tablets made from formulations containing khaya gum had the lowest tensile strength values but also the lowest tendency to laminate or cap, as indicated by their lowest brittleness. All the tablets had friability values < 1% at higher concentrations of the three binders. In addition, khaya gum demonstrated a comparable ability to destroy microorganisms in the formulation during tabletting as the two binders. The characterization of the formulations suggests that khaya gum can be developed into a commercial binding agent for particular tablets.


Trap Profiling Based on Frequency Varied Charge Pumping Method for Hot Carrier Stressed Thin Gate Oxide Metal Oxide Semiconductors Field Effect Transistors.
In this study, pulse frequency and reverse bias voltage is modified in charge pumping and advanced technique is presented to extract oxide trap profile in hot carrier stressed thin gate oxide metal oxide semiconductor field effect transistors (MOSFETs). Carrier trapping-detrapping in a gate oxide was analyzed after hot carrier stress and the relationship between trapping depth and frequency was investigated. Hot carrier induced interface traps appears in whole channel area but induced border traps mainly appears in above pinch-off region near drain and gradually decreases toward center of the channel. Thus, hot carrier stress causes interface trap generation in whole channel area while most border trap generation occurs in the drain region under the gate. Ultimately, modified charge pumping method was performed to get trap density distribution of hot carrier stressed MOSFET devices, and the trapping-detrapping mechanism is also analyzed.


Basolateral binding and uptake of 125-I-insulin in proximal tubular cells after peritubular extraction in the avian kidney.
Several studies have suggested the existence of a renal peritubular extraction of insulin. So far, however, no conclusive evidence, as to whether insulin enters the proximal tubular cell following peritubular extraction, has been presented. In the present study we injected iodine labelled porcine insulin into the renal portal system on hens prepared according to a modified Sperber technique and followed cellular handling of the extracted 125-I-insulin using electron microscope autoradiography at 1 and 7 min after injection. The results showed that at 1 min after injection, peritubular extraction of 125-I-insulin accounted for as much as 30% of total proximal tubular accumulation of grains. Of these grains about 40% were located over basal vesicles, lysosomers or other cell organelles with the remaining 60% located in the intercellular space, probably bound to the basolateral membrane. At 7 min after injection the distribution of grains subsequent to peritubular extraction of 125-I-insulin was unchanged. In contrast, very few grains were located over distal tubules at 1 or 7 min. Thus, the results demonstrate a sizable peritubular extraction of 125-I-insulin in the avian kidney with subsequent uptake into the proximal tubular cells of about one third of the extracted insulin.


Evaluation of endovascular abdominal aortic aneurysm repair in nonagenarians.
The aim of this study was to investigate the safety and efficacy of endovascular abdominal aortic aneurysm repair (EVAR) in nonagenarians. From May 2003 to March 2011, 12 nonagenarian abdominal aortic aneurysm patients were treated with endovascular repair including two emergencies. The mean age of patients was 92.5 ± 1.6 years (range: 90-95 years), and 11 of the patients (91.7%) were men. Technical success, perioperative complications, and mortality were evaluated. The follow-up protocol consisted of computed tomography angiograms or ultrasounds performed at 3, 6, 9, and 12 months, and annually thereafter. Seven patients were operated under general anesthesia and five under local anesthesia. There was 100% technical success with no need for open conversion. The endografts used included two Endurant endografts, four Talent endografts, and six Zenith endografts. The mean operative time was 3.4 ± 1.3 h, mean procedural blood loss was 150.5 ± 60.5 mL, and mean postoperative length of stay was 8.4 ± 2.3 days. Mortality rates were 8.3% at 30 days, 16.7% at 1 year, 41.7% at 3 years, and 75% at 5 years. The mean survival of the 11 patients who expired beyond the first 30 days was 28.5 months (range: 9-73 months). Overall, EVAR in nonagenarians was associated with acceptable procedural success and perioperative morbidity and mortality. The medium and long-term results suggested that EVAR may be of limited benefit in some patients who are aged >90 years. Therefore, individual patient selection is very important.


Immunogenicity of a hybrid Plasmodium falciparum malaria antigen.
A recombinant baculovirus-expressed hybrid protein containing epitopes for the C-terminal fragment of the Plasmodium falciparum precursor to the major merozoite surface antigens (PMMSA) and the tetrapeptide repeats of the circumsporozoite protein (CSP) was assessed for its immunogenicity. Murine MHC-II restriction of the antibody response to the CSP repeats was not overcome by the PMMSA component, the response to which showed no restriction. In an adjuvant trial the highest antibody titres in rabbits to both components of the hybrid were obtained using Freund's adjuvant. Lack of a boosting antibody response to the CSP repeats appeared to be linked to the conformation of the PMMSA component. Formulation of the hybrid protein into Iscoms gave antibody titres of only short duration to both components.


The Case to Case Comparison of Hormone Receptors and HER2 Status between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis.
Nowadays, the adjuvant treatment for breast cancer patients chosen depends on immunohistochemical pattern of Estrogen receptor(ER), Progesterone receptor(PR) and HER2 status of primary breast tumor. Several retrospective studies showed significant discordance in receptor expression between primary and metastatic tumors. The objective of this research was to determine discordant rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis of individual breast cancer patients in Thammasat University Hospital. A prospective observational study of all breast cancer patients who have axillary metastasis and underwent surgery at Thammasat Hospital between January 2011 to December 2015. Tumor staging, ER, PR, and HER2 status on primary breast tumor were recorded. Synchronous axillary lymph node metastasis was evaluated with immunohistochemistry for ER, PR, and HER2. The ER-positive rate from primary tumor to synchronous axillary lymph node metastasis decreased from 74.7% to 71.7%; the HER2 overexpression rate was decreased from 26% to 24%. In contrast, PR positive rate were 71% in both primary tumor and synchronous axillary lymph node metastasis. In case to case comparison, discordance rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis were 11.1%, 20.2% and 10.1%, respectively. Furthermore, the tumor staging was not significant associated with discordance of ER, PR and HER2. ER, PR and HER 2 biomarkers showed significant concordance between primary tumor and synchronous axillary lymph node metastasis. Hence, if we cannot assess the ER, PR and HER2 status in primary tumor, then synchronous axillary lymph node metastasis can be studied instead. However, the repeat of biomarker testing in node-positive breast cancer patients may be beneficial for tailored adjuvant therapy, especially for patients with negative hormone receptor and/or HER2 profile on primary tumor.


Gloves and socks syndrome associated with parvovirus B19 infection.
The spectrum of disease caused by parvovirus B19 infection ranges from asymptomatic to a serious disease. Parvovirus B19 plays a role in the pathomechanism of gloves and socks syndrome, erythema infectiosum, acute polyarthralgia, aplastic crisis in persons with hemolytic anemia, and birth defects. Gloves and socks syndrome has an acute febrile course. Painful edema of hands and feet, and numerous small confluent petechiae in the same localization are the most characteristic signs. Blisters and erosions may occur in oral mucosa. General discomfort and arthralgia accompany skin lesions. The disease tends to be self-limiting. A typical case of gloves and socks syndrome in a 36-year-old woman is reported. Serological tests disclosed the parvovirus B19 infection, confirming the causal relationship between the syndrome and this infection.


Context dependence of receptive field remapping in superior colliculus.
Our perception of the positions of objects in our surroundings is surprisingly unaffected by movements of the eyes, head, and body. This suggests that the brain has a mechanism for maintaining perceptual stability, based either on the spatial relationships among visible objects or internal copies of its own motor commands. Strong evidence for the latter mechanism comes from the remapping of visual receptive fields that occurs around the time of a saccade. Remapping occurs when a single neuron responds to visual stimuli placed presaccadically in the spatial location that will be occupied by its receptive field after the completion of a saccade. Although evidence for remapping has been found in many brain areas, relatively little is known about how it interacts with sensory context. This interaction is important for understanding perceptual stability more generally, as the brain may rely on extraretinal signals or visual signals to different degrees in different contexts. Here, we have studied the interaction between visual stimulation and remapping by recording from single neurons in the superior colliculus of the macaque monkey, using several different visual stimulus conditions. We find that remapping responses are highly sensitive to low-level visual signals, with the overall luminance of the visual background exerting a particularly powerful influence. Specifically, although remapping was fairly common in complete darkness, such responses were usually decreased or abolished in the presence of modest background illumination. Thus the brain might make use of a strategy that emphasizes visual landmarks over extraretinal signals whenever the former are available.


Retinoblastoma cells in tissue culture.
This review summarizes and discusses research on retinoblastoma (Rb) cells in tissue culture. Retinoblastoma is an intraocular tumor of early childhood which is believed to originate from the primitive multipotential neuroectoderm of the optic cup region. The application of tissue culture techniques to the study of Rb cells permits detailed studies of the biology of this tumor. Classic studies have primarily focussed on growth and metastatic potential of Rb cells. Y-79 Rb cells, for example, have a short doubling time in vitro as well as aggressively growing in the anterior chambers of athymic 'nude' mice. Such active growth may result from secretion of a Retinoblastoma Derived Growth Factor (RDGF) by the cells. Several natural agents have now been shown to halt Rb cell growth in vitro. Among these are the fatty acid, butyrate, and two retinoids: retinol and retinoic acid. Interestingly, the retinoids have different mechanisms of action. Cultured Y-79 and WERI cells appear to be multipotential in that they exhibit both neuronal- and glial-like characteristics. Natural agents such as cyclic AMP and butyrate can induce the cells to differentiate along either neuronal or glial cell lines as assessed morphologically and immunocytochemically. Of interest is that combination of agents such as butyrate and laminin, an extracellular attachment protein, yield totally different morphologies, in this case, pigment epithelial in nature. Tissue culture studies thus not only show the primitive, multipotential nature of the Rb cells but their great plasticity as well. Such studies are also useful in elucidating the multiple factors (e.g., substrata and soluble agents) which code for normal retinal development from embryo to adult.


Characteristics of aerobic gram-negative bacteria colonizing critically ill patients.
Adherence of gram-negative bacteria (GNB) to epithelial surfaces is important for GNB colonization to occur. Pili, rodlike structures projecting from the outer membrane of GNB, and GNB surface hydrophobicity have been shown to enhance GNB adherence. We investigated the types of pili and the hydrophobicity of aerobic GNB colonizing the stomach, oropharynx, and trachea of critically ill patients. Piliation and hydrophobicity of oral, tracheal, and gastric GNB were compared with that of commensal GNB isolated from patients' rectums. Significantly more oropharyngeal than rectal GNB were piliated, and the most common type of pili present was type 1, or mannose-sensitive pili. Mannose-resistant and P pili were present less often, and no colonizing GNB had S pili. Colonizing GNB were hydrophilic rather than hydrophobic, and no differences in hydrophobicity were noted between colonizing GNB and rectal isolates. Our results suggest that pili may be important for oropharyngeal GNB colonization.


GM1-Modified Lipoprotein-like Nanoparticle: Multifunctional Nanoplatform for the Combination Therapy of Alzheimer's Disease.
Alzheimer's disease (AD) exerts a heavy health burden for modern society and has a complicated pathological background. The accumulation of extracellular β-amyloid (Aβ) is crucial in AD pathogenesis, and Aβ-initiated secondary pathological processes could independently lead to neuronal degeneration and pathogenesis in AD. Thus, the development of combination therapeutics that can not only accelerate Aβ clearance but also simultaneously protect neurons or inhibit other subsequent pathological cascade represents a promising strategy for AD intervention. Here, we designed a nanostructure, monosialotetrahexosylganglioside (GM1)-modified reconstituted high density lipoprotein (GM1-rHDL), that possesses antibody-like high binding affinity to Aβ, facilitates Aβ degradation by microglia, and Aβ efflux across the blood-brain barrier (BBB), displays high brain biodistribution efficiency following intranasal administration, and simultaneously allows the efficient loading of a neuroprotective peptide, NAP, as a nanoparticulate drug delivery system for the combination therapy of AD. The resulting multifunctional nanostructure, αNAP-GM1-rHDL, was found to be able to protect neurons from Aβ(1-42) oligomer/glutamic acid-induced cell toxicity better than GM1-rHDL in vitro and reduced Aβ deposition, ameliorated neurologic changes, and rescued memory loss more efficiently than both αNAP solution and GM1-rHDL in AD model mice following intranasal administration with no observable cytotoxicity noted. Taken together, this work presents direct experimental evidence of the rational design of a biomimetic nanostructure to serve as a safe and efficient multifunctional nanoplatform for the combination therapy of AD.


Efficacy of raltegravir-containing regimens in antiretroviral-naïve and -experienced individuals in routine clinical practice.
Raltegravir is one of the standard antiretroviral therapy (ART) options in treatment-experienced and -naïve patients. However, efficacy data from clinical practice are scarce. Therefore, the efficacy of raltegravir-containing ART in clinical practice was investigated retrospectively. In all, 295 treatment-naïve and -experienced patients were analysed using two different cut-offs for virological failure (200 or 50 copies/ml). The response at week 24 and onwards was evaluated as a 'time to loss of virological response' analysis and estimated as a survival function. Additionally, dual therapy regimens (raltegravir plus boosted protease inhibitor) were compared to standard combinations in experienced patients performing a snapshot analysis at weeks 24 and 48, as well as a time to loss of virological response analysis. A total of 86.2% of the 64 treatment-naïve patients maintained virological suppression using a cut-off of 200 copies/ml (c/ml), while 67.7% maintained virological suppression with a 50 copies/ml cut-off from week 24 until the end of observation. Among the 231 treatment-experienced patients, 84.8% maintained virological suppression from week 24 onwards using a cut-off of 200 copies/ml; and 71.0% using 50 copies/ml, respectively. In the subgroup snapshot analysis at week 24, 98.3% (86.7% using a cut-off of 50 copies/ml) and at week 48, 93.3% (80.0%) of patients responded to dual therapy. Patients who were receiving a standard background therapy responded in 88.3% (81.3%) at week 24 and in 86.0% (80.7%) at week 48. Differences were not significant. This study shows again the overall long-term efficacy of raltegravir-based ART and furthermore gives reference for a comparable efficacy of dual and standard nucleos(t)ide reverse transcriptase inhibitor-backbone regimens in experienced patients on raltegravir over a period of 48 weeks in a real-life cohort where patients with severe comorbidities were included.


Incidence and diagnosis of acute rheumatic fever in Denmark, 1980 and 1983. A retrospective analysis of the fulfillment of the revised Jones criteria in hospitalized patients.
A review of 1547 official hospital record summaries concerning discharges during the period 1980 through 1983 of patients whose diagnoses had been coded as acute rheumatic fever revealed that in only 61% of the cases had this illness been diagnosed or suspected. A substantial proportion of the remaining patients had had acute non-rheumatic pericarditis diagnosed. The medical records were analyzed for 141 patients diagnosed in 1980 or 1983 by hospital departments as having acute rheumatic fever with regard to the revised Jones criteria. They were fulfilled in 47 patients, 23 of whom were considered unlikely cases of rheumatic fever. Eight patients were considered possible cases, although they did not fulfill the revised Jones criteria. The current annual incidence of acute rheumatic fever was estimated to be at most 0.3 per 100,000 inhabitants.


Sepsis, meningitis and cerebral abscesses caused by Citrobacter koseri.
After a 36-week diamniotic dichorionic gestation, an infant was delivered by elective caesarean section due to growth restriction and altered diastolic flow in the umbilical artery. Birth weight was 2140 g. The patient was admitted for exclusive parenteral nutrition, with umbilical venous catheter placement. Sinus tachycardia and temperature instability with positive inflammatory markers occurred at 51 h. Penicillin and gentamicin were started, but 6 h later septic shock with disseminated intravascular coagulation was noted. Vancomycin and meropenem were started and penicillin suspended. Citrobacter koseri was isolated from blood culture. Generalised clonic convulsions occurred on day 4, and an electroencephalogram revealed severe encephalic dysfunction. Cerebrospinal fluid cytochemical analysis was suggestive of meningitis, although culture was negative. Cefotaxime was added to the drug regimen. Cranioencephalic MR showed a temporal abscess and diffuse hemispheric destruction, with no indications for neurosurgery. After 6 weeks of therapy, neuroimaging follow-up showed multiloculated cystic encephalomalacia. Currently, the patient is 14 months old with axial hypotonia and decreased movements. The source of infection has not been determined. Nosocomial infection cannot be excluded and vertical transmission is unlikely.


Procedure, Screening, and Cost of Fecal Microbiota Transplantation.
Fecal microbiota transplantation (FMT) is currently considered a potential treatment for various GI-related illnesses, with the goal to replenish natural healthy flora of the GI tract that has been harmed because of antibiotic use or overgrowth of harmful bacteria. Current methods of administering the processed stool include colonoscopy and enema, while an oral capsule is being developed. Each method of administration carries its own set of risks, including adverse reactions to treatment, infection following the invasive administration procedure, and flare-ups of GI-related symptoms. Current oral administration through nasoduodenal tube poses a risk for aspiration which has not been ruled out as the cause of subsequent pneumonia and death in patient trials. The development of an oral capsule could address some of the faults of the current methods, not only making treatment more affordable and accessible but also less of a risk due to its minimally invasive nature. FMT is also a treatment option to attenuate adverse effects associated with antibiotic use, including combatting the emergence of antibiotic resistance, as well as adverse effects related to other medical treatments such as chemotherapy. While FMT is an unexplored treatment option for multiple gastrointestinal disorders and is currently still largely inaccessible for many patients financially, studies have suggested that it could be a more affordable treatment option long-term for patients as aspects of the treatment become more affordable with further research.


Knowledge of neonatal danger signs and associated factors among husbands of mothers who gave birth in the last 6 months in Gurage Zone, Southern Ethiopia, 2020: a community-based cross-sectional study.
To assess knowledge of neonatal danger signs and their associations among husbands of mothers who gave birth in the last 6 months in Gurage Zone, Southern Ethiopia, from 1 February to 28 February 2020. Community-based cross-sectional study. Gurage Zone, Southern Ethiopia. The study was conducted among 633 participants living in Gurage Zone from 1 February to 28 February 2020. 618 completed the questionnaire. A multistage sampling technique was employed to obtain study participants. Data were collected through face-to-face interviews conducted by 20 experienced and trained data collectors using a pretested structured questionnaire. To assess knowledge, 10 questions were adopted from the WHO questionnaire, which is a standardised and structured questionnaire used internationally. Data were entered into EpiData V.3.1 and exported to SPSS (Statistical Package for Social Sciences) V.24 for analysis. Descriptive statistics were performed and the findings were presented in text, figures and tables. Binary logistic regression was used to assess the association between each independent variable and the outcome variable. All variables with p<0.25 in the bivariate analysis were included in the final model and statistical significance was declared at p<0.05. Voluntary consent was taken from all participants. A total of 618 participants were included in the study, with a response rate of 97.6%. Of the participants, 40.7% had good knowledge (95% CI 36.3 to 44.2). Urban residence (adjusted OR=6.135, 95% CI 4.429 to 9.238) and a primary and above educational level (adjusted OR=4.294, 95% CI 1.875 to 9.831) were some independent predictors of husbands' knowledge status. Knowledge of neonatal danger signs in this study was low. Urban residence, primary and above educational level, the husband's wife undergoing instrumental delivery and accompanying the wife during antenatal care visits were independent predictors of knowledge. Thus, strong multisectoral collaboration should target reducing the knowledge gap by improving husbands' attitude with regard to accompanying their wives during antenatal care and postnatal care visits, or create a strategy to increase husbands' participation in access to maternal and child health service since husbands are considered decision-makers when it comes to healthcare-seeking in the family. The government should come up with policies that will help promote formal education in the community and increase their media access.


In silico analysis of onion chitinases using transcriptome data.
Chitinases are glycoside hydrolase (GH) family of proteins having multifaceted roles in plants. It is of interest to identify and characterize chitinase-encoding genes from the popular bulbous plant onion (Allium cepa L.). We have used the EST sequences for onion chitinases to elucidate its functional features using sequence, structure and functional analysis. These contigs belong to the GH19 chitinases family according to domain architecture analysis. They have highly conserved chitinase motifs including motifs exclusive to plant chitinases as implied using the MEME based structural characterization. Estimation of biochemical properties suggested that these proteins have features to form stable and hydrophilic proteins capable of localizing extracellular and in vacuoles. Further, they have multiple cellular processes including defense role as inferred by DeepGO function prediction. Phylogenetic analysis grouped them as class I and class VII plant chitinase, with possible abundance of class I chitinase in onion. These observations help in the isolation and functional validation of onion chitinases.


Oxazolidinones--a new class of broad-spectrum chemotherapeutics.
The oxazolidinones are a new class of broad spectrum chemotherapeutics of antibiotic properties. These drugs have good activity against Gram-positive pathogenic bacteria. Oxazolidinones possess an unique mechanism of inhibitory bacterial protein biosynthesis. These compounds inhibit the formation of N-formylmethionyl-tRNA, which is a requisite of beginning translation process. Linezolid, the first oxazolidinone to be approved for the clinical treatment of Gram-positive bacterial infections, displays a wide spectrum of in vitro activity against many important pathogens, including for instance methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and penicillin-resistant pneumococci. Linezolid is a pararental drug that also possesses near-complete oral bioavailability and a favourable pharmacokinetic profile. In clinical trials involving hospitalised patients with skin and soft tissue infections oxazolidinones appeared to be effective treatment option, comparable in efficacy to vancomycin.


[Experiences with Ilizarov distraction osteogenesis with the AO spindle fixator].
For correction of leg length discrepancies and for the treatment of segmental bony defects we used a modular AO-fixator knowing that the principle of the distraction osteogenesis is not dependent of a special fixation device. In our small series the AO-fixator proved to be a good alternative to the ring fixator of Ilizarov for the use on the tibia but not on the femur where we noticed a relatively high incidence of complications, especially deformities of the axis. The distraction osteogenesis has proved to be an efficient technique for limb lengthening and segmental bone transport but is high demanding for the patient and the surgeon.


The role of cadmium in obesity and diabetes.
Multiple studies have shown an association between environmental exposure to hazardous chemicals including toxic metals and obesity, diabetes, and metabolic syndrome. At the same time, the existing data on the impact of cadmium exposure on obesity and diabetes are contradictory. Therefore, the aim of the present work was to review the impact of cadmium exposure and status on the risk and potential etiologic mechanisms of obesity and diabetes. In addition, since an effect of cadmium exposure on incidence of diabetes mellitus and insulin resistance was suggested by several epidemiologic studies, we carried out a meta-analysis of all studies assessing risk of prevalence and incidence of diabetes. By comparing the highest versus the lowest cadmium exposure category, we found a high risk of diabetes incidence (odds ratio=1.38, 95% confidence interval 1.12-1.71), which was higher for studies using urine as exposure assessment. On the converse, results of epidemiologic studies linking cadmium exposure and overweight or obesity are far less consistent and even conflicting, also depending on differences in exposure levels and the specific marker of exposure (blood, urine, hair, nails). In turn, laboratory studies demonstrated that cadmium adversely affects adipose tissue physiopathology through several mechanisms, thus contributing to increased insulin resistance and enhancing diabetes. However, intimate biological mechanisms linking Cd exposure with obesity and diabetes are still to be adequately investigated.


Physical activity and lymphoid neoplasms in the European Prospective Investigation into Cancer and nutrition (EPIC).
Lymphoid neoplasms are a heterogeneous group of cancers that originate in the lymphatic cells of the immune system. Several risk factors have been identified or suggested, but they all account for only a small proportion of the lymphoid neoplasm incidence. It has been hypothesised that regular exercise may modulate the immune system and thereby reduce the risk of developing the disease. The European Investigation into Cancer and Nutrition (EPIC) cohort consists of 521,457 adults, recruited by 23 centres in 10 European countries. The analytical cohort included 343,756 participants, with 778 non-Hodgkin lymphoma (NHL) cases (376 men and 402 women) and 690 B-cell non-Hodgkin lymphoma (B-NHL) cases (326 men and 364 women). Multivariate Cox regression models were used to calculate hazard ratios (HR) for the association between total, recreational, occupational, and household physical activity and NHL and B-NHL risk, as well as the risk for several B-NHL subtypes. Models were stratified by study centre and age at recruitment and adjusted for various potential confounding factors. We found no evidence of any effect of total physical activity on NHL (adjusted p-trend=0.76 and 0.30 for men and women, respectively) and B-NHL risk (adjusted p-trend=0.99 and 0.21 for men and women, respectively) for either men or women. Also no robust results were found for B-NHL subtype analyses among men or women. This study provided no consistent evidence for an association between various physical activity measures and the risk of lymphoid neoplasms or any of the B-NHL subtypes.


How mentoring education affects nurse mentors' competence in mentoring students during clinical practice - A quasi-experimental study'.
Mentors need diverse competencies, sources of motivation and characteristics to successfully mentor nursing students and support students' learning processes. Effective mentoring education can benefit future nursing professionals, students' satisfaction and learning, as well as the general perception of the nursing profession. The purpose of this study was to evaluate how an educational intervention affects nurse mentors' competence in mentoring nursing students during clinical practice. A quasi-experimental study design with pre- and post-tests was used. Educational interventions were conducted in one university hospital and two central hospitals in Finland between 2013 and 2017. The intervention was conducted twice per year with a duration of 3 months for each group. The inclusion criteria for the participants were as follows: volunteer participation to mentor education employment at the university hospital or central hospitals in Northern Finland. The intervention aimed to increase Registered Nurses' competence in mentoring nursing students. The education lasted 3 months and included online learning as well as three face-to-face teaching sessions. A total of 120 nurse mentors completed the Mentor Competence Instrument (MCI), which includes 10 subscales that describe various competence areas, before and after the education. Nurse mentors' mentoring competence increased across all mentoring competence areas after the educational intervention. More specifically, the participating nurses showed a statistically significant increase in their competence regarding knowledge of mentoring practices in the workplace, student-centred evaluation, identifying student needs, mentoring practices between mentor and student, supporting students' learning processes, goal orientation in mentoring and constructive feedback. On an international level, nurse mentors are not typically required to have completed mentoring education prior to the mentoring of nurse students. Since mentoring education increased nurses' competence at mentoring nursing students, we recommend that all nurse degree programs include mentoring education to prepare future nurses for the important future role in mentoring.


Oral hygiene practices and periodontitis in health care professionals.
One in 3 adults in the United States has periodontitis, yet there are few widely applied methods for its prevention. Few studies have assessed oral hygiene practices related to periodontitis. There were 533 participants in this study (14.8% male dentists; 13.7% male non-dentist health care professionals; and 71.5% female nurses), all of whom are enrolled in ongoing cohort studies in the United States which have inquired about their oral hygiene practices and whether they have professionally diagnosed periodontitis. We studied the relationship between oral hygiene practices and periodontitis, controlling for potential confounders. The participants were 69 years old on average, 84.2% white, 12.4% current smokers, and 8.3% diabetic. Seventy percent of the dentists and nurses brushed at least twice a day compared to 56% of the other health professionals. Two-thirds of the nurses, 56.3% dentists, and 36.4% other health professionals flossed at least once daily. Persons brushing twice daily were as likely to have periodontitis as those brushing once or less daily (odds ratio [OR] = 1.16; 95% confidence interval [CI]: 0.64 to 2.10); persons flossing less than once a day were as likely to have periodontitis as those who flossed daily (OR = 1.16, 95% CI: 0.63 to 2.13) after controlling for profession, age, gender, smoking, diabetes, coronary heart disease, history of periodontal surgery, and number of teeth present. People who reported better oral hygiene practices did not report less periodontitis, after controlling for potential confounders. Oral hygiene practices were not associated with periodontitis in this population.


Selective recognition and extraction of KBr via cooperative interactions with a urea functionalized crown ether dual-host.
Selective solid-liquid extraction of KBr is demonstrated for the first time with a crown ether based pentafluorophenyl urea functionalized dual-host receptor. (1)H-NMR and ITC studies have been carried out to illustrate the effect of cooperativity towards the recognition of alkali metal salts.


The haem-haemopexin utilization gene cluster (hxuCBA) as a virulence factor of Haemophilus influenzae.
Haemophilus influenzae has an absolute growth requirement for a porphyrin source, which can be supplied in vitro by haem, haemoglobin, or the haemoglobin-haptoglobin, haem-haemopexin and haem-albumin complexes. Utilization of the haem-haemopexin complex is known to be mediated by the products of the hxuCBA gene cluster. It was demonstrated that hxuC, but not hxuA or hxuB, is also essential for the utilization of haem from haem-albumin complexes. Mutants of the type b strain E1a lacking genes in the hxuCBA gene cluster were examined for their ability to cause bacteraemia in rat models of invasive disease. In 5-day-old rats, mutants in the hxuCBA genes yielded a significantly reduced bacteraemic titre compared to the wild-type strain. In addition, 5-day-old rats infected with the hxuCBA mutant strains exhibited significantly improved survival rates compared to those infected with the wild-type strain. Mutations in the haemoglobin/haemoglobin-haptoglobin-binding protein genes (hgps), either alone or in combination with the hxuCBA mutations, had no impact on virulence in 5-day-old rats. In 30-day-old rats infected with either the hxuCBA mutants or the wild-type strains, there was no significant difference in the ability to establish bacteraemia although bacterial titres were lower in rats infected with the hxuCBA mutants than in those infected with the wild-type strain. These age-related differences in the impact of mutations in the hxuCBA gene cluster may be related to changes in levels of host haem-binding proteins during development of the rat.


Sunflower Honey-Evaluation of Quality and Stability during Storage.
Honey's unique qualities should last for several years when properly stored. Therefore, it is up to manufacturers to choose the right shelf life for their product while also considering the product's nature. Physicochemical parameters (water content, electrical conductivity, free acidity, pH, ash, water-insoluble matter, hydroxymethylfurfural (HMF), sugar content and composition, and diastase activity) were analyzed in 24 samples of sunflower honey collected from several localities in Vojvodina, Serbia. Crystallization indices were also calculated. Furthermore, the impact of eighteen months of room temperature storage (22 ± 2 °C) in a dark place on selected physicochemical parameters (water, HMF, diastase activity, pH value, and free acidity) was investigated. The results of the initial test indicated that the tested samples of sunflower honey from Vojvodina is of good quality because the parameters under examination revealed results that were within the legal bounds of both national and European legislations. Eighteen months of storage at room temperature reduced diastase activity by 2 times, increased HMF content by about 17 times, and decreased the pH value of honey from a mean value of 3.66 to 3.56. The water content was relatively stable at 17.01% before storage and 16.29% after storage. The storage of sunflower honey did not have an impact on the free acidity.


Antibody production and tolerance to the α-gal epitope as models for understanding and preventing the immune response to incompatible ABO carbohydrate antigens and for α-gal therapies.
This review describes the significance of the α-gal epitope (Galα-3Galβ1-4GlcNAc-R) as the core of human blood-group A and B antigens (A and B antigens), determines in mouse models the principles underlying the immune response to these antigens, and suggests future strategies for the induction of immune tolerance to incompatible A and B antigens in human allografts. Carbohydrate antigens, such as ABO antigens and the α-gal epitope, differ from protein antigens in that they do not interact with T cells, but B cells interacting with them require T-cell help for their activation. The α-gal epitope is the core of both A and B antigens and is the ligand of the natural anti-Gal antibody, which is abundant in all humans. In A and O individuals, anti-Gal clones (called anti-Gal/B) comprise >85% of the so-called anti-B activity and bind to the B antigen in facets that do not include fucose-linked α1-2 to the core α-gal. As many as 1% of B cells are anti-Gal B cells. Activation of quiescent anti-Gal B cells upon exposure to α-gal epitopes on xenografts and some protozoa can increase the titer of anti-Gal by 100-fold. α1,3-Galactosyltransferase knockout (GT-KO) mice lack α-gal epitopes and can produce anti-Gal. These mice simulate human recipients of ABO-incompatible human allografts. Exposure for 2-4 weeks of naïve and memory mouse anti-Gal B cells to α-gal epitopes in the heterotopically grafted wild-type (WT) mouse heart results in the elimination of these cells and immune tolerance to this epitope. Shorter exposures of 7 days of anti-Gal B cells to α-gal epitopes in the WT heart result in the production of accommodating anti-Gal antibodies that bind to α-gal epitopes but do not lyse cells or reject the graft. Tolerance to α-gal epitopes due to the elimination of naïve and memory anti-Gal B cells can be further induced by 2 weeks in vivo exposure to WT lymphocytes or autologous lymphocytes engineered to present α-gal epitopes by transduction of the α1,3-galactosyltransferase gene. These mouse studies suggest that autologous human lymphocytes similarly engineered to present the A or B antigen may induce corresponding tolerance in recipients of ABO-incompatible allografts. The review further summarizes experimental works demonstrating the efficacy of α-gal therapies in amplifying anti-viral and anti-tumor immune-protection and regeneration of injured tissues.


International pediatric perfusion practice: 2011 survey results.
New cardiopulmonary bypass devices and new innovative methods are frequently reported in the literature; however, the actual extent to which they are adopted into clinical practice is not well known. We distributed an electronic survey to 289 domestic and international pediatric congenital surgery centers in an effort to measure attributes of current clinical practice. The survey consisted of 107 questions relating to program demographics, equipment, and techniques. Responses were received from 146 (51%) of queried centers and were stratified into five distinct geographic regions (North America, Central and South America, Oceana, Europe, and Asia). Most of the responding centers reported use of hard shell venous reservoirs. Closed venous systems were used at 50% of reporting centers in Central and South America as compared with only 3% in North America and 10% in Asia. Seventy-one percent of the programs used some form of modified ultrafiltration. Use of an arterial bubble detection system varied between 50% use (Central and South America) vs. 100% (North America and Oceana). "Del Nido" cardioplegia is more common in North America (32%) than any other continent, whereas Custodial HTK solution is much more prevalent in Europe (31%). Wide variation in practice was evident across geographic regions, suggesting opportunities for further investigation and improvement.


The concept of apolipoprotein-defined lipoprotein families and its clinical significance.
Classification of plasma lipoproteins on the basis of apolipoprotein (apo) composition recognizes two lipoprotein (Lp) classes, one of which is characterized by apoA-I and the other by apoB as major protein constituents. The former lipoprotein class consists of three major subclasses referred to (according to their apolipoprotein constituents) as Lp-A-I, Lp-A-I:A-II, and Lp-A-II, and the latter one of five subclasses called Lp-B, Lp-B:E, Lp-B:C, Lp-B:C:E, and Lp-A-II:B:C:D:E. As polydisperse systems of particles, the apoA-I-containing lipoproteins overlap in high-density segments and apoB- containing lipoproteins in low-density segments of the density gradient. Each subclass is characterized by a specific chemical composition and metabolic property. Normolipidemia and dyslipoproteinemias are characterized by quantitative rather than qualitative differences in the levels of apoA- and apoB-containing subclasses. Furthermore, apoA-containing subclasses seem to differ with respect to their relative antiatherogenic capacities, and apoB-containing subclasses regarding their relative atherogenic potentials. Whereas Lp-A-I may have a greater antiatherogenic capacity than other apoA-containing subclasses, the cholesterol-enriched Lp-B:C appears to be the most atherogenic subclass among apoB-containing lipoprotein families. The use of pharmacologic and/or dietary interventions to treat dyslipoproteinemias has already shown that these therapeutic modalities may affect selectively individual apolipoprotein-defined lipoproteins, and thus allow the selection of individualized treatments targeted at decreasing harmful and/or increasing beneficial lipoprotein subclasses.


Dermatoglyphics in childhood leukaemia: a guide to prognosis and aetiology?
The results of analysis of the dermatoglyphics of 152 children with acute lymphoblastic leukaemia (ALL) (and the first-degree relatives of 54 of them) contrast with those of 31 children with acute myeloblastic leukaemia (AML) (and the first-degree relatives of 25 of them). In ALL our findings suggest that neither genetic susceptibility nor an environmental factor, effective during the early antenatal period, is of aetiological importance; but the response to treatment, assessed as length of first remission, was found to be related to the amount of fingertip pattern. This may have clinical application. In AML there is evidence of a genetically determined factor carrying a high risk of the development of the disease, in that a member of each of 5 different families of the 25 studied bore a rare hypothenar pattern, compared with none in 75 control families. No dermatoglyphic features were of prognostic significance in AML.


A conserved region adjacent to the basic domain is required for recognition of an extended DNA binding site by Maf/Nrl family proteins.
The c-maf proto-oncogene and the neural retina specific gene nrl encode members of a subfamily of bZIP proteins that form heterodimers with Fos and Jun. We have determined the DNA binding specificities of various homo- and heterodimeric combinations among Nrl, Maf, Fos and Jun. Fos-Jun heterodimers and Jun homodimers bound to a palindromic TGAC(G)TCA recognition sequence as previously demonstrated. Maf and Nrl homodimers also bound to palindromic recognition sites with the consensus sequence TGC(N)6-7GCA. Fos-Nrl, Jun-Nrl and Fos-Maf heterodimers bound to nonpalindromic recognition sequences with the consensus sequence TGAC(N)3-4GCA. These results indicate that Nrl and Maf have a DNA binding specificity distinct from that of Fos and Jun, and that each subunit in the dimer independently recognizes one half of the recognition sequence. This allows combinatorial determination of target gene specificity. Specific recognition of the extended DNA binding sequence by Maf requires an ancillary DNA binding region on the amino terminal side of the basic domain that is conserved among Maf/Nrl family members. Thus, heterodimer formation among distantly related bZIP family members can generate novel DNA binding specificities and the addition of an auxiliary DNA binding domain to the simple bZIP motif can facilitate the recognition of extended binding sites.


Resilience in children with congenital heart disease: a comparative study with health counterparts.
Resilience is a complex, yet rather unexplored topic in patients with congenital heart disease (CHD). The goal of this study was to assess and compare resilience in children with CHD with healthy controls during the COVID-19 pandemic. From June 2020 to June 2021, 124 children with various CHDs (14.6±2.1 years, 49 girls) and 124 matched healthy controls (14.8±2.0 years, 49 girls) completed the Resilience Scale-11 short version. Resilience was significantly reduced in children with CHD compared with healthy controls (CHD: 59.0±10.0 vs healthy controls: 64.4±6.5, p<0.001). That reduction was prominent in all CHD subgroups except those with left heart obstruction (aortic stenosis and coarctation of the aorta) and patients with transposition of the great arteries. Complex CHD had the lowest resilience of 57.6±8.4 (p<0.001) after adjusting for age and sex according to group differences. There was no difference between native CHD and CHD with open-heart surgery (native: 59.5±12.2 vs surgery: 58.8±9.3, p=0.758). Resilience was reduced in children and adolescents with CHD compared with healthy peers during the COVID-19 pandemic. Children with complex severity appeared to be particularly affected. These findings emphasise continued efforts to provide a holistic and multidisciplinary approach in medical aftercare of these patients and their families.


Process-based costing.
Understanding how quality improvement affects costs is important. Unfortunately, low-cost, reliable ways of measuring direct costs are scarce. This article builds on the principles of process improvement to develop a costing strategy that meets both criteria. Process-based costing has 4 steps: developing a flowchart, estimating resource use, valuing resources, and calculating direct costs. To illustrate the technique, this article uses it to cost the care planning process in 3 long-term care facilities. We conclude that process-based costing is easy to implement; generates reliable, valid data; and allows nursing managers to assess the costs of new or modified processes.


Intake of a cohort study of urban factory workers in northwest Tanzania. Risk factors for HIV-1 infection.
A cohort study has been started of urban factory workers and their spouses in Tanzania, in order to 1) identify risk factors for HIV-1 seroconversion, and 2) document changes over time in risk behaviour, in particular condom use and partner change, and determine whether these are associated with a reduced incidence of HIV-1 and other sexually transmitted diseases. We report findings at intake from October 1991 to March 1992. Study participants were interviewed, examined, and screened for HIV-1 and syphilis. HIV-1 prevalence was 91/926 (10%) in males and 36/217 (17%) in females. Statistically significant risk factors for HIV-1 infection in males were age group, region of birth, not being married for more than 5 years, being uncircumcised, having had a genital ulcer in the past four months, and having received injections from medical staff in the past four months. HIV-1 incidence in this group is expected to be between 1% and 2% per year. It is concluded that a longitudinal study is needed to assess the importance of partner change. This cohort appears to be suitable for such a study as HIV-1 incidence is expected to be fairly high, HIV-1 prevalence and risk factors are comparable to those of the general population and cooperation of the factory workers is good.


Coercive field enhancement in Co nanodisks: single-domain to vortex switching.
Magnetic multi-layered nanodisks (ND) show great promise as these are relatively easy to assemble and control, facilitating biological and storage applications. In the present work, Ti/Co/Nb ND were fabricated with a varying Co layer thickness between 6 and 14 nm. Using vibrating sample magnetometry and micromagnetic simulations (OOMMF), their magnetic properties were investigated. Our results reveal a peak in coercive field at a critical thickness that separates the two magnetic phases; single domain and vortex phase. This peak is characterized by a substantially larger coercive field and allows to establish an explicit phase diagram as a function of diameter and thickness of the ND. This opens the possibility to investigate such enhancement in other ferromagnetic materials too.


A case of delayed oxaliplatin-induced pseudo-obstruction: an atypical presentation of oxaliplatin neurotoxicity.
Chemotherapy-induced neurotoxicity is a serious complication of cancer treatment. Oxaliplatin, a third-generation platinum drug, has become one of the first-line therapies used in the treatment of metastatic colorectal cancer. Peripheral neuropathy is a common complication of platinum-based chemotherapy. Most commonly a sensory neuropathy occurs with cold-triggered symptoms in the acute phase and numbness and painful paresthesias as a late presentation. Autonomic neurotoxicity and late presentation, months after cessation of the therapy, has rarely been described. We report a patient who clinically presented with a pseudo-obstruction months after treatment with oxaliplatin for metastatic colorectal cancer. Intestinal adhesions and relapsing malignancy were carefully excluded. By exclusion the pseudo-obstruction was attributed to a toxic oxaliplatin-induced autonomic neuropathy which slowly improved during months of follow-up.


Histone Lys demethylase KDM3C demonstrates anti-inflammatory effects by suppressing NF-κB signaling and osteoclastogenesis.
Histone Lys-specific demethylases (KDMs) play a key role in many biological processes through epigenetic mechanisms. However, the role of KDMs in inflammatory responses to oral bacterial infection is poorly understood. Here, we show a novel regulatory role of KDM3C in inflammatory responses to oral bacterial infection. KDM3C expression is transiently suppressed in human and mouse macrophages exposed to LPS from Porphyromonas gingivalis (Pg LPS). Loss of KDM3C in both human and mouse macrophages led to notable induction of proinflammatory cytokines in response to Pg LPS stimulation. Also, KDM3C depletion led to strong induction of p65 phosphorylation and accelerated nuclear translocation in cells exposed to Pg LPS. Kdm3C knockout (KO) in mice led to increased alveolar bone destruction upon induction of experimental periodontitis or pulp exposure compared with those of the wild-type (WT) littermates. The Kdm3C KO mice also revealed an increased number of osteoclasts juxtaposed to the bony lesions. We also confirmed enhanced osteoclastogenesis by bone marrow-derived macrophages isolated from the Kdm3C KO compared with the WT controls. These findings suggest an anti-inflammatory function of KDM3C in regulating the inflammatory responses against oral bacterial infection through suppression of NF-κB signaling and osteoclastogenesis.-Lee, J. Y., Mehrazarin, S., Alshaikh, A., Kim, S., Chen, W., Lux, R., Gwack, Y., Kim, R. H., Kang, M. K. Histone Lys demethylase KDM3C demonstrates anti-inflammatory effects by suppressing NF-κB signaling and osteoclastogenesis.


Localization of acetylcholine receptor in excitable membrane from the electric organ of Torpedo: Evidence for exposure of receptor antigenic sites on both sides of the membrane.
Nicotinic acetylcholine receptor was localized in a receptor-rich membrane preparation from the electric organ of Torpedo californica by applying an immunoferritin technique. The membrane preparation was incubated with (Fab')2 fragments derived from specific rabbit antibodies against the purified acetylcholine receptor and subsequently with ferritin-conjugated goat antiserum to rabbit immunoglobulin. More than 50% of the vesicles were found to be labeled with ferritin while the rest remained unlabeled. Ferritin labeling on both sides of the membrane was evident in open membrane vesicles, whereas in closed vescles the labeling was confined to the outer surface due to the inability of the tracer to penetrate the membrane. These data suggest that antigenic sites of the receptor molecule are exposed on both sides of the excitable membrane, and that acetylcholine receptor may be a transmembrane protein.


Change in levels of monoamine neurotransmitters and their main metabolites of rat brain after electric acupuncture treatment.
The changes in levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE), 3-methoxy-4-hydroxyphenylethyleneglycol sulphate (MHPG-SO4) and dopamine (DA) of rat brain were studied after electric acupuncture stimulation (EAS). We found that the mean values of cerebral 5-HT and 5-HIAA after EAS were increased 16% (p less than 0.001) and 24% (p less than 0.01) respectively, significantly higher than those of controls, whereas the mean value of cerebral NE was decreased 14% (p less than 0.01), significantly lower than that of the controls. The cerebral MHPG-SO4 and DA in both groups showed no significant difference. In a second series of experiments with another group of rats, EAS was administered once a day for ten days. There was no statistical significance between the treated group and the control group in the differences in brain contents of all three monoamine neurotransmitters and 5-HIAA.


Central catheter-related Gordonia bronchialis bacteremia in an immunocompromised patient: A case report, and literature review.
Gordonia is a rarely reported organism causing central line-associated bloodstream infection (CLABSI). This article reports an acute myeloid leukemia (AML) case in which the patient developed febrile neutropenia and was later found to have Gordonia bronchialis (G. bronchialis) CLABSI. The patient received a two-week ceftriaxone regimen, based on susceptibility. The microbiologic diagnosis of this organism is considered challenging due to its resemblance with other organisms; however, more sophisticated methods of diagnosis (such as gene sequencing) can aid in differentiation.


U.S. childhood cancer survival, 1973-1987.
The surveillance, epidemiology, and end-results (SEER) data on 5-year relative survival rates (1973-1987) for the most common pediatric tumors (ages 0-14) were analyzed. The SEER data are population based, so the observed progress in survival from childhood cancer represents the real impact that development in cancer treatment had on the population followed by the registry. The greatest increase in survival rate from 1973 until 1987 has been achieved in hematopoietic tumors such as acute lymphocytic leukemia (ALL), in which survival increased from 47.6% (1973-1977) to 60.8% (1983-1987), and Burkitt's lymphoma in which survival increased from 27.6% (1973-1977) to 68.7% (1983-1987). Solid tumors showed a less steep, but steady increase in survival rates. Flattening in the survival rates since 1978-1982 has been observed for acute leukemia, astrocytoma, medulloblastoma, and osteosarcoma. Females have better survival rates for most pediatric tumors, except Hodgkin's disease. Analysis of race of childhood leukemia confirmed that black children have worse survival than white. When solid tumors were analyzed by stage at presentation, there was no indication that diagnosis in earlier stages of disease accounted for the improved survival. Observed flattening in the survival rates since 1978-1982 of leukemia and some solid tumors warrants further follow-up.


Using mobile technology to improve healthcare service quality.
Improving healthcare service quality for illness of treatment, illness prevention and patient service is difficult for most hospitals because the hospitals are lack adequate resources and labor. In order to provide better healthcare service quality for patients, mobile technology can be used to manage healthcare in a way that provides the optimal healthcare service for patients. Pursuing utilization of mobile technology for better patient service, Taipei Medical University Municipal W. F. Teaching Hospital has implemented a mobile healthcare service (m-HS) system to increase healthcare service quality. The m-HS system improves the quality of medical care as well as healthcare service. The m-HS is a multi-functional healthcare management agent, meets the mobile tendency of the present society. This study seeks to discuss the m-HS architecture and workflow processes. We believe the m-HS does have the potential to improve healthcare service quality. Finally, the conclusions and suggestions for the m-HS are given.


RHO Family GTPases in the Biology of Lymphoma.
RHO GTPases are a class of small molecules involved in the regulation of several cellular processes that belong to the RAS GTPase superfamily. The RHO family of GTPases includes several members that are further divided into two different groups: typical and atypical. Both typical and atypical RHO GTPases are critical transducers of intracellular signaling and have been linked to human cancer. Significantly, both gain-of-function and loss-of-function mutations have been described in human tumors with contradicting roles depending on the cell context. The RAS family of GTPases that also belong to the RAS GTPase superfamily like the RHO GTPases, includes arguably the most frequently mutated genes in human cancers (K-RAS, N-RAS, and H-RAS) but has been extensively described elsewhere. This review focuses on the role of RHO family GTPases in human lymphoma initiation and progression.


[Study on the kinetics of organo-clay removing red tide organisms].
The kinetics of red tide organisms (Heterosigma akashiwo and Scrippsiella trochoidea) coagulation with clays modified by dialkyl-polyoxyethenyl quaternary ammonium compound (DPQAC) was studied using spectrophotometer and fluorometry, and the effects of different kinds and concentrations of clays, the second component DPQAC added in clays and pH on the coagulation rate were examined. When using spectrophotometer, the coagulation kinetics of red tide organism coagulation with organo-clays is well fit for the bimolecular reaction model; while using fluorometry, it is fit for the hyperbola model much better. Moreover, the results also prove that using fluorometry can avoid the great change of permeance efficiency caused by clays' sedimentation when using spectrophotometer, which has availably avoided the influence of clays' sedimentation and reflected the essential of algal coagulation and sedimentation well and truly. The results of two studying methods show that the coagulation rate is more rapid in the system of kaolin than in that of bentonite; increasing the concentration of clays and DPQAC and increasing pH all can accelerate coagulation, and among those increasing the concentration of DPQAC is the most efficient way of increasing the removal efficiency and coagulation rate.


"Prologues to a Bad Voice": Effect of Vocal Hygiene Knowledge and Training on Voice Quality Following Stage Performance.
The purpose of this investigation was to determine the effects of intensive stage rehearsal and performance on perceptual, acoustic, and aerodynamic measures of voice, and to determine the impact of knowledge and practice of vocal hygiene on measures of voice during intensive vocal performance. Nineteen stage actors who were participating in the Arkansas Shakespeare Theatre festival took part in the study. Each participant completed auditory-perceptual, acoustic, aerodynamic, and quality of life measures before and after 1 month of intensive rehearsals and stage performances. They also completed a questionnaire documenting their vocal use, vocal hygiene, and previous vocal training, if any. Subjects demonstrated statistically significant deterioration in auditory-perceptual measures and mean expiratory airflow. Other acoustic measures trended toward poorer outcomes after the performances; however, these were not statistically significant. Knowledge of vocal hygiene and vocal training did not have an impact on the change in vocal measures. Stage performances do impact vocal outcomes with reduction in quality and efficient use of airflow for voice production. Knowledge and practice of vocal hygiene have some impact on these changes; however, vocal hygiene may not be the best preventive strategy of potential phonotrauma in this subject population.


Maternal and neonatal outcomes in twin and triplet gestations in Western Saudi Arabia.
Tocompare maternal and neonatal complications in twin and triplet gestations at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Methods: Retrospective medical records of 165 women with 144 twin and 21 triplet pregnancies from 2004 to 2011 were analyzed. Comparisons were carried out for maternal complications, gestational age at birth, neonatal birth weight, and neonatal intensive care admission. Results: Most common complications were preterm birth (49%), gestational diabetes mellitus (13.3%), and premature rupture of membrane (4.8%). All triplet pregnancies and 42% twin pregnancies terminated in preterm birth. Gestational length was longer (p less than 0.001) in twin births (36.0 ± 3.05 weeks) than for triplet births (32 ± 3.81 weeks). Rates for in vitro fertilization, ovulation induction, and cesareans were higher in women with triplets than in those with twins. Neonatal intensive care unit (NICU) admission was higher (p less than 0.001) for triplets (76.2%) than for twins (23.6%). The mean weight of twins was 2333.83 ± 558.69 grams and triplets was 1553.41 ± 569.73 grams. Hyaline membrane disease, neonatal jaundice, and neonatal sepsis were most common neonatal complications. Conclusion: Neonates from triplet pregnancies were preterm, had low birth weight and needed more often NICU admission in comparison to those from twin pregnancies.


Long-term use of topical calcipotriol in chronic plaque psoriasis.
A multi-centre, open, prospective study of 12 months duration was performed to assess safety, efficacy and tolerability of topical calcipotriol in the long-term treatment of psoriasis. One hundred and sixty-seven adults with chronic plaque psoriasis who had previously responded to calcipotriol entered the study. Disease activity was monitored using the psoriasis area and severity index (PASI). Calcipotriol ointment 50 micrograms/g was applied twice daily until remission was attained. Treatment was then stopped but reinstituted in the event of relapses. Of the 167 recruited patients, 6 patients did not receive any treatment during the trial. A total of 39 patients were withdrawn: 15 due to inadequate control of their psoriasis, 9 due to irritant reactions, 7 due to defaulting and 8 for miscellaneous voluntary reasons. A further 24 patients either reached the study medication limit of 2,500 g or were considered to have completed the study a few weeks prior to the 12-month period. Accordingly, 98 patients were assessable after 12 months of therapy. Complete clearing was obtained in 26% of subjects, who then used the treatment intermittently. The remaining patients required continuous treatment for 12 months. The mean PASI fell from 8.1 (SD +/- 6.67, n = 167) at baseline to 3.90 (+/- 3.50, 136) at 2 months and 2.71 (+/- 2.12, 98) at 12 months. There was no rise in the mean serum total calcium. Calcipotriol ointment was safe, effective and well tolerated.


Simufilam suppresses overactive mTOR and restores its sensitivity to insulin in Alzheimer's disease patient lymphocytes.
Introduction: Implicated in both aging and Alzheimer's disease (AD), mammalian target of rapamycin (mTOR) is overactive in AD brain and lymphocytes. Stimulated by growth factors such as insulin, mTOR monitors cell health and nutrient needs. A small molecule oral drug candidate for AD, simufilam targets an altered conformation of the scaffolding protein filamin A (FLNA) found in AD brain and lymphocytes that induces aberrant FLNA interactions leading to AD neuropathology. Simufilam restores FLNA's normal shape to disrupt its AD-associated protein interactions. Methods: We measured mTOR and its response to insulin in lymphocytes of AD patients before and after oral simufilam compared to healthy control lymphocytes. Results: mTOR was overactive and its response to insulin reduced in lymphocytes from AD versus healthy control subjects, illustrating another aspect of insulin resistance in AD. After oral simufilam, lymphocytes showed normalized basal mTOR activity and improved insulin-evoked mTOR activation in mTOR complex 1, complex 2, and upstream and downstream signaling components (Akt, p70S6K and phosphorylated Rictor). Suggesting mechanism, we showed that FLNA interacts with the insulin receptor until dissociation by insulin, but this linkage was elevated and its dissociation impaired in AD lymphocytes. Simufilam improved the insulin-mediated dissociation. Additionally, FLNA's interaction with Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN), a negative regulator of mTOR, was reduced in AD lymphocytes and improved by simufilam. Discussion: Reducing mTOR's basal overactivity and its resistance to insulin represents another mechanism of simufilam to counteract aging and AD pathology. Simufilam is currently in Phase 3 clinical trials for AD dementia.


A density assignment method for dose monitoring in head-and-neck radiotherapy.
During head-and-neck (H&N) radiotherapy, the parotid glands (PGs) may be overdosed; thus, a tool is required to monitor the delivered dose. This study aimed to assess the dose accuracy of a patient-specific density assignment method (DAM) for dose calculation to monitor the dose to PGs during treatment. Forty patients with H&N cancer received an intensity modulated radiation therapy (IMRT), among whom 15 had weekly CTs. Dose distributions were calculated either on the CTs (CTref), on one-class CTs (1C-CT, water), or on three-class CTs (3C-CT, water-air-bone). The inter- and intra-patient DAM uncertainties were evaluated by the difference between doses calculated on CTref and 1C-CTs or 3C-CTs. PG mean dose (Dmean) and spinal cord maximum dose (D2%) were considered. The cumulated dose to the PGs was estimated by the mean Dmean of the weekly CTs. The mean (maximum) inter-patient DAM dose uncertainties for the PGs (in cGy) were 23 (75) using 1C-CTs and 12 (50) using 3C-CTs (p ≤ 0.001). For the spinal cord, these uncertainties were 118 (245) and 15 (67; p ≤ 0.001). The mean (maximum) DAM dose uncertainty between cumulated doses calculated on CTs and 3C-CTs was 7 cGy (45 cGy) for the PGs. Considering the difference between the planned and cumulated doses, 53% of the ipsilateral and 80% of the contralateral PGs were overdosed by +3.6 Gy (up to 8.2 Gy) and +1.9 Gy (up to 5.2 Gy), respectively. The uncertainty of the three-class DAM appears to be clinically non-significant (<0.5 Gy) compared with the PG overdose (up to 8.2 Gy). This DAM could therefore be used to monitor PG doses and trigger replanning.


Synthesis of (NHC)Pd(salicylaldimine)Cl complexes through template-directed ortho-aromatic metaloxylation of NHC-palladacycles derived from arylimines.
Reactions of imidazoliums with palladacycles afforded NHC-palladacycle complexes. The reactivity of the NHC-palladacycles was explored and the results demonstrated that they could be template-directed ortho-aromatic metaloxylated in the presence of tert-butyl hydroperoxide (TBHP), affording (NHC)Pd(salicylaldimine)Cl complexes. Furthermore, the NHC-palladacycles showed efficient catalytic activities toward the ortho-aromatic hydroxylation of arylimines.


[The possible modes of action of TNF (tumor necrosis factor)].
TNF has been characterized by the fact that it not only induces hemorrhagic necrosis in various established tumors including Meth. A in vivo but also shows antitumor activity against several transformed cell lines in vitro. However, most studies on TNF have been carried out not with purified Preparations but with mouse or rabbit serum containing other cytokines like INF or with so-called tumor necrosis serum (TNS). Therefore, it is somewhat difficult and rather early to review the action mechanisms of TNF. According to a few reports which have used TNS to study the node of he action of TNF in vitro, its activity against transformed cell lines can be tentatively summarized as follows. First, the TNF molecule binds to the corresponding receptor on the cell surface, and then is transferred to the lysosome in a similar manner to the internalization of growth hormone and insulin. The TNF on the lysosomal membrane their induces injury to the membrane as a labilizer, finally causing cell destruction. TNF seems to be a cytotoxic rather than cytolytic substance. However, this recently described mechanism in vitro is not able to explain how TNF causes the central hemorrhagic necrosis of established solid tumors in vivo. Many unknown action mechanisms of TNF still remain to be clarified.


Automated phenotype pattern recognition of zebrafish for high-throughput screening.
Over the last years, the zebrafish (Danio rerio) has become a key model organism in genetic and chemical screenings. A growing number of experiments and an expanding interest in zebrafish research makes it increasingly essential to automatize the distribution of embryos and larvae into standard microtiter plates or other sample holders for screening, often according to phenotypical features. Until now, such sorting processes have been carried out by manually handling the larvae and manual feature detection. Here, a prototype platform for image acquisition together with a classification software is presented. Zebrafish embryos and larvae and their features such as pigmentation are detected automatically from the image. Zebrafish of 4 different phenotypes can be classified through pattern recognition at 72 h post fertilization (hpf), allowing the software to classify an embryo into 2 distinct phenotypic classes: wild-type versus variant. The zebrafish phenotypes are classified with an accuracy of 79-99% without any user interaction. A description of the prototype platform and of the algorithms for image processing and pattern recognition is presented.


Clinical Risk Score for Prediction of Urgency in Carotid Cavernous Sinus Fistulas.
To develop a clinical risk score for the prediction of urgency in patients with carotid cavernous sinus fistulas (CCFs) and test for the discriminative ability of the diagnostic prediction. The medical charts of 60 patients with CCFs were retrospectively reviewed. The clinical characteristics of direct and dural CCFs were analyzed by logistic regression. The clinical risk score was developed from the coefficient in the multivariable regression model and used to predict direct CCFs which were more urgent than the dural type. The score prediction was reported as an area under the receiver operating characteristic (AuROC) curve and 95% confidence interval (95% CI). In a univariable analysis, the clinical characteristics which increased the risk of direct CCFs were age, gender, trauma, underlying diseases, visual acuity (VA) at presentation, bruit, chemosis, and dilated retinal vessels. However, in multivariable analysis, the significant predictors were limited to age, trauma, bruit, underlying diseases and logMAR VA. Regression coefficient of each predictor was converted to a risk score and summation of scores from these predictors for each patient was calculated. The total risk score predicted the urgent direct CCFs correctly with AuROC of 97.77% (95% CI; 93.57, 100). The clinical risk score for the prediction of urgent direct CCFs has been developed and used in the patients with CCFs in our setting. The discriminative ability of the score prediction is high. This simple clinical risk score may help clinicians suspect direct CCFs and urgently refer the patients to have prompt angiography and treatment.


Circulatory support in elderly chronic heart failure patients using the CircuLite® Synergy® system.
The Synergy(®) system, a miniature partial circulatory support device, is implanted with an off-pump, minimally invasive surgical approach. In our experience, implantation of this system is associated with fewer perioperative adverse events than current full support devices. This approach therefore offers the possibility of treating elderly chronic heart-failure patients who might not ordinarily be considered for long-term circulatory support. A total of 54 patients (12 patients ≥ 70 years) were implanted with the Synergy system in an off-pump minithoracotomy procedure. Mean age (54 ± 10 vs 73 ± 3), body surface area (1.9 ± 0.2 vs 1.7 ± 0.1), blood urea nitrogen (BUN) (59 ± 33 vs 91 ± 38), estimated glomerular filtration rate (eGFR) (71 ± 23 vs 50 ± 38) and haemoglobin (12.6 ± 1.9 vs 11.3 ± 1.3) differed significantly between young and old. Older patients had longer mean durations of support (337 vs 188 days). On average, both groups showed similar improvements (changes from baseline) in haemodynamics (pulmonary capillary wedge pressure -9 ± 16 vs -10 ± 8 mmHg; CO +1.0 ± 0.7 vs 0.9 ± 1.0 l/min, periferical vascular resistance (PVR) -1.2 ± 1.5 vs = 0.8 ± 1.7 Wood) and 6 min walk (107 ± 120 vs 130 ± 121 m). Older patients showed less improvement in peak VO2 (0.5 ± 2.9 vs 1.9 ± 3.0 ml/kg/min). Major adverse events (old vs young) between groups included major bleeding (75 vs 38%), infection (25 vs 38%), renal dysfunction (0 vs 17%) and device-related stroke (8 vs 10%). Mortality rate was 20% for the young and 40% for the elderly. Older patients implanted with Synergy had smaller body sizes and worse renal function than younger patients. Both groups experienced similar haemodynamic benefits and functional improvements, though peak VO2 is less improved in the elderly. Risks of bleeding and renal dysfunction appear to be increased in the elderly, though still within acceptable ranges compared with other full support devices. Minimally invasive long-term circulatory support devices, like Synergy, offer a new treatment option to the elderly chronic heart-failure population.


Recovery from contraction-induced injury is impaired in weight-bearing muscles of old male mice.
With aging, the skeletal muscles of humans sustain decreases of approximately 30% in mass and maximum force. Contraction-induced injury may contribute to these declines. When a 225 lengthening contraction protocol (LCP) was administered to small, non-weight-bearing muscles of mice, muscles of young/adult mice recovered completely, whereas those of old mice sustained permanent deficits of 20% in muscle mass and maximum force. Despite these observations, whether a large, frequently recruited, weight-bearing muscle sustains such permanent damage is not known. The hypothesis tested is that after a severe contraction-induced injury, large, weight-bearing muscles of old mice sustain permanent reductions in mass and force. The LCP was administered to plantar flexor muscles of adult and old, male C57BL/6 mice. At 3 days, 1 mo, and 2 mo after the LCP, maximum isometric forces were measured, anesthetized mice were euthanized, and muscles were removed and weighed. Two months after the LCP, the muscles of the adult mice regained control values of mass and force, whereas for muscles of old mice the mass decreased by 24% and the maximum force decreased by 32%. We conclude that a severe contraction-induced injury to large, weight-bearing muscles of old mice causes permanent deficits in mass and force.


Effects of central angiotensin II receptor antagonism on fetal swallowing and cardiovascular activity.
Fetal plasma angiotensin II levels are 10 times the levels found in adults. Despite these high levels, central injection of angiotensin II may stimulate fetal swallowing and increase fetal arterial blood pressure. We postulated that the high rate of spontaneous fetal swallowing and normal fetal pressor regulation may be dependent, in part, on central angiotensin II. In view of the potential dipsogenic role of both type 1 and type 2 angiotensin II receptors, we examined the central effect of the nonselective angiotensin II receptor antagonist saralasin on fetal swallowing and cardiovascular responses. Six time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and intracerebroventricular catheters, electrocorticograms, and esophageal electromyogram electrodes and studied at 130 +/- 1 days' gestation. After an initial 2-hour baseline period (0 to 2 hours), saralasin (1 mL, 64 microg) was injected intracerebroventricularly (2 to 4 hours). After 4 hours the dose of saralasin was repeated together with angiotensin II (1 mL, 6.4 microg), and the fetuses were monitored for a final 2 hours. Four fetuses also underwent an identical control study (on an alternate day) in which saralasin was replaced with artificial cerebrospinal fluid. Blockade of central angiotensin II receptors by intracerebroventricular saralasin significantly reduced mean (+/- SEM) spontaneous fetal swallowing (1.3 +/- 0.1 to 0.4 +/- 0.1 swallows per minute; P <.001) but did not alter fetal mean blood pressure (50 +/- 5 versus 56 +/- 5 mm Hg). Intracerebroventricular angiotensin II, in the presence of saralasin, did not affect swallowing (0.6 +/- 0.1 swallows per minute) or fetal blood pressure. In the control study, intracerebroventricular artificial cerebrospinal fluid did not change fetal swallowing (0.9 +/- 0.1 versus 1.0 +/- 0.1 swallows per minute), whereas intracerebroventricular angiotensin II significantly increased swallowing activity (1.0 +/- 0.1 versus 2.0 +/- 0.1 swallows per minute; P <.001) and fetal blood pressure (51 +/- 2 to 59 +/- 3 mm Hg; P =.003). Tonic activity of central angiotensin II receptor stimulation contributed to the high rate of basal ovine fetal swallowing but not fetal basal blood pressure. Angiotensin II-mediated fetal dipsogenic and pressor responses are a result of specific angiotensin II receptor binding in central brain regions. These results indicate that fetal exposure to angiotensin II antagonists or angiotensin-converting enzyme inhibitors may have adverse effects on fetal and amniotic fluid homeostasis.