Effects of mitochondrial ATP-sensitive potassium channel activation (nicorandil) in patients with angina pectoris undergoing elective percutaneous coronary interventions: A meta-analysis of randomized controlled trials.
Nicorandil, which is a mitochondrial ATP-sensitive potassium channel opener, is believed to improve perioperative myocardial injury (PMI) in patients undergoing percutaneous coronary intervention (PCI), but recent studies have shown that nicorandil treatment did not improve functional and clinical outcomes in patients with angina pectoris who underwent elective PCI. We performed a meta-analysis to investigate the protective effect of nicorandil on perioperative injury in patients with angina pectoris who underwent elective PCI. The Medline, EMBASE, and Cochrane databases were searched for randomized clinical trials examining the effects of nicorandil. Two investigators independently selected suitable trials, extracted data, and assessed trial quality. Seven studies of patients undergoing elective PCI, comprising a total of 979 patients, were included in this review. The results showed that nicorandil did not reduce the levels of markers of myocardial injury (standardized mean difference [SMD] 0.31 [95%CI -0.6, 1.22] for creatine kinase-MB [CK-MB] and 1.29 [95%CI -2.18, 4.76] for troponin I [TNI]), perioperative complications (relative risk [RR] 0.91 [95%CI 0.46-1.81]), target vessel revascularization (RR 0.79 [95%CI 0.50-1.25]) or major adverse cardiac events (MACE) (RR 0.83 [95%CI 0.49-1.43]). Nicorandil did reduce the corrected TIMI frame count (SMD-0.30 [95%CI -0.52, -0.09]). Although nicorandil did not reduce the overall incidence of perioperative complications and the incidence of major adverse cardiac events (MACE) in patients with angina pectoris who underwent elective PCI, it could still improve no reflow and slow coronary flow.


Polynanocrystalline Graphite: A New Carbon Anode with Superior Cycling Performance for K-Ion Batteries.
We synthesized a new type of carbon-polynanocrystalline graphite-by chemical vapor deposition on a nanoporous graphenic carbon as an epitaxial template. This carbon is composed of nanodomains being highly graphitic along c-axis and very graphenic along ab plane directions, where the nanodomains are randomly packed to form micron-sized particles, thus forming a polynanocrystalline structure. The polynanocrystalline graphite is very unique, structurally different from low-dimensional nanocrystalline carbon materials, e.g., fullerenes, carbon nanotubes, and graphene, nanoporous carbon, amorphous carbon and graphite, where it has a relatively low specific surface area of 91 m2/g as well as a low Archimedes density of 0.92 g/cm3. The structure is essentially hollow to a certain extent with randomly arranged nanosized graphite building blocks. This novel structure with disorder at nanometric scales but strict order at atomic scales enables substantially superior long-term cycling life for K-ion storage as an anode, where it exhibits 50% capacity retention over 240 cycles, whereas for graphite, it is only 6% retention over 140 cycles.


Heat effect induces production of inflammatory cytokines through heat shock protein 90 pathway in cornea cells.
Many studies have been conducted to elucidate the molecular consequences of ultraviolet irradiation, whereas little is known about the effect of infrared radiation on ocular disease. Heat is generated as a consequence of infrared irradiation, in addition to photons, and heat shock is widely considered to be an environmental stressor. Our previous study has demonstrated that heat shock (42 °C) induces apoptosis of Statens Seruminstitut Rabbit Cornea (SIRC) cells. However, the biological effect of mild heat shock (39 °C), which does not induce apoptosis, on SIRC cells has not been studied yet. The SIRC cells were treated with mild heat shock and the expression of inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6), in the mRNA and protein levels were then assayed with reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The levels of heat shock protein 90 (HSP90), phosphorylated AKT, phosphorylated IκBα and nuclear NF-κB were assessed with immunoblot assays; the involvement of these molecules in the signaling pathway were further assessed by using specific inhibitor for HSP90, AKT or NF-κB. Mild heat shock increased the production of inflammatory cytokines, IL-1β and IL-6. Mild heat shock increased expression of HSP90, which increased the phosphorylation of AKT. The activated AKT then increased the phosphorylation of IκBα, resulting in nuclear translocation of NF-κB, which up-regulated the expression of IL-1β and IL-6 in SIRC cells. These findings suggest a critical role for the HSP90-AKT-NF-κB signaling pathway in mild heat shock-induced inflammatory response of cornea cells.


Education-based, lifestyle intervention programs with unsupervised exercise improve outcomes in adults with metabolic syndrome. A systematic review and meta-analysis.
To determine whether lifestyle intervention programs comprising dietary intervention and prescribed, unsupervised exercise improve outcomes for people with metabolic syndrome. A systematic review and meta-analysis of randomised controlled trials. Online databases CINAHL, MEDLINE, PubMed and Embase were searched from the earliest date available to October 2020. Post-intervention data were pooled to calculate mean differences (MD) or standardised mean differences (SMD) and 95% confidence intervals (CI) using inverse variance methods and random effects models. Trial methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale and overall quality of each meta-analysis was assessed using the Grading of Recommendation Assessment, Development and Evaluation approach. Eleven studies from 9 randomised controlled trials with 1,835 participants were included. There was high quality evidence that lifestyle intervention programs with unsupervised exercise reduced waist circumference (MD -2.82 cm, 95%CI -5.64 to 0.00, I2 91%) and blood pressure (systolic: MD -3.89 mmHg, 95%CI -5.19 to -2.58, I2 4%; diastolic: MD -3.16 mmHg, 95%CI -4.83 to -1.49, I2 50%) and increased physical activity levels (SMD 0.47, 95%CI 0.24 to 0.70, I2 45%) when compared to usual care. There was low quality evidence that they improved quality of life (SMD 0.59, 95%CI 0.05 to 1.13, I2 84%). Unsupervised programs had no significant effect on fasting blood glucose (unless > 3 months duration), metabolic syndrome prevalence or cholesterol. Lifestyle intervention programs with prescribed, unsupervised exercise are a practical alternative to supervised programs for people with metabolic syndrome when time, access or resources are limited or when social distancing is required.


Psychosocial benefits of a novel mindfulness intervention versus standard support in distressed women with breast cancer.
It is well documented that stress is associated with negative health outcomes in cancer patients. The purpose of this study was to assess the effects of a novel mindfulness intervention called mindfulness-based art therapy (MBAT) versus standard educational support, on indices of stress and quality of life in breast cancer patients with high stress levels. A total of 191 women were enrolled, stratified by age and stress level, and randomized to receive either an 8-week MBAT intervention or a breast cancer educational support program of equal time and duration. Psychosocial stress was measured using the Symptoms Checklist-90-Revised, and quality of life was measured using the Medical Outcomes Study Short-Form Health Survey at baseline, immediately post-intervention, and at 6 months. Results showed overall significant improvements in psychosocial stress and quality of life in both the MBAT and educational support groups immediately post-intervention; however, participants with high stress levels at baseline had significantly improved overall outcomes only in the MBAT group, both immediately post-intervention and at 6 months. In addition, at 6 months follow-up, participants attending five or more sessions trended toward retaining treatment effects better in the MBAT than in the control group. Finally, black women and white women were similar in terms of how they benefited from the MBAT intervention, even though white participants tended to have higher educational level and marital status. In conclusion, MBAT is associated with significant, sustained benefits across a diverse range of breast cancer patients, particularly those with high stress levels.


Nuclear magnetic resonance relaxation and water contents in normal mouse and rat tissues and in cancer cells.
By studying nuclear magnetic resonance water proton spin-lattice relaxation times (T1 and T2) of normal mouse and rat tissues at varying water contents and by comparing the data with those obtained from five types of cancer cells in ascites form, we concluded that differences in total water contents between normal tissues and cancer cells contribute less than 10% to the differences between the longer T1 of cancer cells as compared to the T1 of normal tissues. In spite of the diverse origin of the five types of cancer cells studied, their T1 and T2 as well as water contents were confined within relatively narrow limits. We suggested that all 5 ascites tumors studied are maximally deviated and that the physical state of the water in all maximally deviated cancer cells is very similar.


Electrophysiological comparison of grammatical processing and semantic processing of single spoken nouns.
Access to meaning from speech input is a high-speed process. However, models of word comprehension stipulate that words must be analyzed at phonological, grammatical and semantic levels. Here we used event-related potentials (ERPs) to compare on-line semantic categorization (natural/manufactured) and grammatical gender categorization (masculine/feminine) of spoken monosyllabic French noun pairs. Twenty four native French speakers were instructed to spot pairs of nouns in which both stimuli pertained to a category specified prior to each block. They could make a decision either after processing the first noun (i.e., ignore the second, Release condition), or after processing both (Hold condition). Virtually identical N4 components affecting Hold and Release ERPs in relation to category expectations were elicited by the first noun in both the tasks. Their topography was intermediary between that of the N400 and that of the Left Anterior Negativity. Despite shorter Release reaction times (RTs) for gender decisions than semantic ones, Release and Hold ERPs diverged 84 ms earlier in the semantic context than in the gender context, indicating faster onset for the processing of meaning. Conversely, the offset of Hold/Release differences was observed 42 ms earlier in the gender task than in the semantic task, suggesting an earlier completion for gender categorization. In sum, electrophysiological differences induced by semantic operations commenced earlier but recovered later than those relating to grammatical gender analysis. In convergence with previous Lateralized Readiness Potential and N200 studies, our results suggest that conscious semantic access can precede access to other types of lexical information during word comprehension in highly controlled conditions.


Word length and visual-noise texture in backward masking.
Visual-noise masks composed of randomly scattered letter fragments disrupt the recognition of briefly viewed letter arrays when the masks are presented immediately after these arrays. According to the feature-similarity assumption, maximal disruption should occur when the target letters and the letter fragments comprising the mask share a common stroke width. This assumption was disconfirmed in the present experiment. Two-, four-, and six-letter arrays, whose stroke width subtended a visual angle of 3-8', were viewed tachistoscopically in conjunction with visual-noise masks whose letter fragments subtended visual angles of 1-2', 1-9', 3-8', 6-6', or 9-7'. The most effective mask for all three letter-array lengths was the one composed of letter fragments subtending 6-6'. The results, together with those of previous experiments, are accounted for in terms of a neural line-detecting mechansim.


Gastrojejunocolic fistula as a complication of Billroth II gastrectomy: a case report.
Gastrojejunocolic fistula is a late, severe complication of a stomal ulcer, which develops as a result of inadequate resection of the stomach or incomplete vagotomy. It is uncommon and in our century is reported only sporadically in medical literature The authors report a case of benign gastrojejunocolic fistula, diagnosed by barium based contrast radiography, which demonstrated reflux of contrast from the transverse colon to the stomach and jejunum via a fistulous tract. Therapy of the gastrojejunal fistula is always radical and comprises en bloc resection of the fistula and revision of gastrectomy, partial resection of the jejunum and the colon, which is involved in the fistula, and restoration of continuity of the digestive tract by gastrojejunostomy, jejunojejunostomy and colocolostomy. If trunkal vagotomy has not previously been completed, it is advisable to perform it nonetheless.


[Cognitive disturbances in cerebellum infarctions].
The influence of the cerebellum on cognitive functions (CF) is poorly known and understudied so far. Neurological, neuropsychological and neuroimaging non-randomized study was carried out in 25 patients (14 women, 11 men, mean age 51.8 +/- 18.0 years) with isolated cerebellum infarctions. Cognitive disturbances (CD) were detected in 22 (88%) patients. They included impairment of attention, planning, control, abstract reasoning, memory; speech (naming, fluency, agrammatism, dysprosodia), special visual, quasi-spatial and counting disorders that indicated dysfunction of the anterior and posterior associative areas of the brain cortex. The expression of CD was different: being clinically obvious in 6 patients (24%), they were found only by neuropsychological methods in 16 patients (64%). Clinically significant CD developed in the lesions of certain areas (posterior-lower- lateral and posterior-medial) of the cerebellum hemisphere related to the dominant brain hemisphere. The presence of these CD did not depend on infarctions size: in expressed CD it was smaller (mean 5.65 cm3) than in other cases (mean 12.8 cm3). Typical appearances of cerebellum infarction (ataxia, vertigo, vomiting) were observed in all the patients with clinically non-significant CD and only in 2 out of 6 with clinically significant CD. The study demonstrated a role of the cerebellum in CF modulation. The expression of CD in cerebellum infarctions depends on their localization. Topic localization of the cerebellum areas, controlling CD and movement, is different.


Development of Risk Indices for Neonatal Respiratory Extracorporeal Membrane Oxygenation.
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has saved thousands of newborns. Population comparisons for research and quality initiatives require risk-matching, but no indices exist for this population. We sought to create a pre-ECMO risk index using the registry data from the Extracorporeal Life Support Organization. We analyzed 5,455 neonatal (<30 days old) respiratory VA-ECMO patients for the period 2000-2010. Multivariate regression examining the impact of pre-ECMO variables on survival to hospital discharge was performed to create the Pittsburgh Index for Pre-ECMO Risk (PIPER), which was ultimately was based on seven pre-ECMO variables. Each PIPER quartile demonstrated increasing mortality by 15% (R = 0.98) and was associated with increased complications on ECMO. Further modeling to include on-ECMO complications (PIPER), including complications and length of time on ECMO, increased the predictive power of the model, with 21% increases in mortality per PIPER quartile (R = 0.97). Our developed indices provide the first steps towards risk-adjusting patients for meaningful comparisons amongst patient populations. There may be additional clinically relevant measures, both pre- and on-ECMO, which could provide better predictive capability. Future work will focus on finding these additional measures and expansion of our techniques to include other patient populations.


Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+, CD40L+ T cells by producing CCL22.
The natural history of B-chronic lymphocytic leukemia (CLL) is not entirely explained by intrinsic defects of the neoplastic cell, but is also favored by microenvironmental signals. As CLL cells retain the capacity to respond to CD40 ligand (CD40L) and as CD4(+) T cells are always present in involved tissues, we asked whether malignant CLL cells might produce T cell-attracting chemokines. We studied the chemokine expression of CD19(+)/CD5(+) malignant B cells from peripheral blood (PB), lymph nodes (LN) or bone marrow (BM) of 32 patients and found a major difference. LN- and BM-, but not PB-derived cells, expressed a readily detectable reverse transcription-PCR band for CCL22 and one for CCL17 of variable intensity. CD40 ligation of PB cells induced the mRNA expression of both CCL22 and CCL17. CCL22 was also released in the culture supernatants. These supernatants induced the migration of activated CD4(+), CD40L(+) T cells expressing the CCL22 receptor, CCR4. T cell migration was abrogated by anti-CCL22 antibodies. Immunohistochemistry and cytofluorography studies revealed that a proportion of CD4(+) T cells in CLL LN and BM expressed CD40L. Our data demonstrate that malignant CLL cells chemo-attract CD4(+) T cells that in turn induce a strong chemokine production by the leukemic clone, suggesting a vicious circle, leading to the progressive accumulation of the neoplastic cells.


Suppression of histone deacetylation promotes the differentiation of human pluripotent stem cells towards neural progenitor cells.
Emerging studies of human pluripotent stem cells (hPSCs) raise new prospects for neurodegenerative disease modeling and cell replacement therapies. Therefore, understanding the mechanisms underlying the commitment of neural progenitor cells (NPCs) is important for the application of hPSCs in neurodegenerative disease therapies. It has been reported that epigenetic modifications of histones play important roles in neural differentiation, but the exact mechanisms in regulating hPSC differentiation towards NPCs are not fully elucidated. We demonstrated that suppression of histone deacetylases (HDACs) promoted the differentiation of hPSCs towards NPCs. Application of HDAC inhibitors (HDACi) increased the expression of neuroectodermal markers and enhanced the neuroectodermal specification once neural differentiation was initiated, thereby leading to more NPC generation. Similarly, the transcriptome analysis showed that HDACi increased the expression levels of ectodermal markers and triggered the NPC differentiation related pathways, while decreasing the expression levels of endodermal and mesodermal markers. Furthermore, we documented that HDAC3 but not HDAC1 or HDAC2 was the critical regulator participating in NPC differentiation, and knockdown of HDAC3's cofactor SMRT exhibited a similar effect as HDAC3 on NPC generation. Our study reveals that HDACs, especially HDAC3, negatively regulate the differentiation of hPSCs towards NPCs at an earlier stage of neural differentiation. Moreover, HDAC3 might function by forming a repressor complex with its cofactor SMRT during this process. Thus, our findings uncover an important epigenetic mechanism of HDAC3 in the differentiation of hPSCs towards NPCs.


A case of scurvy rarely encountered in Japan.
We report a case of scurvy, which is rarely encountered in Japan. A 75-year-old male was hospitalized with diffuse subcutaneous hemorrhaging of both feet, pain on walking, and shortness of breath. A remarkably low serum level of vitamin C was confirmed. Administration of ascorbic acid dramatically improved his clinical symptoms. Improvement paralleled the increase of serum vitamin C level. This case underscores the important role of vitamin C on the integrity function of the vessel wall.


Z plasty closure of lower lip defects after tumor excision.
Reconstruction of the defects of the lower lip should provide a sensate, functional, and aesthetic lip structure. Defects of the lower lip, up to 30% of the total width, can be closed primarily, which gives a better result than any known flap operation unless the contracture of the linear scar tissue distorts the anatomic landmarks. Taking this possibility into consideration and to prevent scar contracture, we have performed Z plasty to the skin component while closing the resultant central defects of the lower lip after tumor excision. This modification improved our cosmetic results.


Weeding atypical glandular cell look-alikes from the true atypical lesions in liquid-based Pap tests: a review.
The purpose of this review is to identify features that separate atypical glandular cells (AGC) associated with glandular neoplasia from its mimickers, both benign and neoplastic. We reviewed cases of AGC diagnosed on liquid-based Pap tests (LBP) for which corresponding histological follow-up was available. A review of the literature for similar studies in LBP tests was also conducted. We find that certain benign mimics can be reliably separated from AGC, but recommend caution in attempting to increase specificity at the risk of losing sensitivity. Although accounting for only a small percentage of diagnoses AGC require a thorough clinical evaluation, including colposcopy. Most cases are ultimately found to be benign. When evaluating smears suspicious for AGC, it is important to examine the subtle features which make truly atypical cells discernible from their numerous benign mimickers.


Rho-kinase regulates thrombin-stimulated interleukin-6 synthesis via p38 mitogen-activated protein kinase in osteoblasts.
We have previously reported that thrombin stimulates synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the mechanism of thrombin in the thrombin-stimulated IL-6 synthesis and the involvement of Rho-kinase in MC3T3-E1 cells. Thrombin time-dependently induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and myosin phosphatase targeting subunit-1 (MYPT-1), a Rho-kinase substrate. While SP600125, an inhibitor of SAPK/JNK, failed to reduce IL-6 synthesis, PD98059, a specific inhibitor of MEK, and SB203580 and BIRB0796, potent inhibitors of p38 MAP kinase, suppressed the IL-6 synthesis induced by thrombin. Y27632, a specific Rho-kinase inhibitor, significantly reduced thrombin-stimulated IL-6 synthesis as well as the MYPT-1 phosphorylation. Fasudil, another inhibitor of Rho-kinase, suppressed thrombin-stimulated IL-6 synthesis. Y27632 and fasudil failed to affect thrombin-induced phosphorylation of p44/p42 MAP kinase. Y27632 as well as fasudil attenuated thrombin-induced phosphorylation of p38 MAP kinase. These results strongly suggest that Rho-kinase regulates thrombin-stimulated IL-6 synthesis via p38 MAP kinase activation in osteoblasts.


Metal nanoparticle pollutants interfere with pulmonary surfactant function in vitro.
Reported associations between air pollution and pulmonary and cardiovascular diseases prompted studies on the effects of gold nanoparticles (Au NP) on pulmonary surfactant function. Low levels (3.7 mol % Au/lipid, 0.98% wt/wt) markedly inhibited adsorption of a semisynthetic pulmonary surfactant (dipalmitoyl-phosphatidylcholine (DPPC)/palmitoyl-oleoyl-phosphatidylglycerol/surfactant protein B (SP-B); 70:30:1 wt %). Au NP also impeded the surfactant's ability to reduce surface tension (gamma) to low levels during film compression and to respread during film expansion. Transmission electron microscopy showed that Au NP generated by a seed-growth method were spherical with diameters of approximately 15 nm. Including palmitoyl-oleoyl-phosphatidylglycerol appeared to coat the NP with at least one lipid bilayer but did not affect NP shape or size. Similar overall observations occurred with dimyristoyl phosphatidylglycerol. Dipalmitoyl-phosphatidylglycerol was less effective in NP capping, although similar sized NP were formed. Including SP-B (1% wt/wt) appears to induce the formation of elongated strands of interacting threads with the fluid phosphatidylglycerols (PG). Including DPPC resulted in formation of aggregated, less spherical NP with a larger size distribution. With DPPC, strand formation due to SP-B was not observed. Agarose gel electrophoresis studies demonstrated that the aggregation induced by SP-B blocked migration of PG-coated NP. Migration was also influenced by the fluidity of the PGs. It is concluded that Au NP can interact with and sequester pulmonary surfactant phospholipids and, if inhaled from the atmosphere, could impede pulmonary surfactant function in the lung.


Ion selective phosphotungestate and beta-cyclodextrin based membrane electrodes for stability-indicating determination of midodrine hydrochloride.
This paper reports the construction and evaluation of two ion selective electrodes for the determination midodrine hydrochloride (MD) by direct potentiometry in pure drug substance and in tablet formulations. Precipitation based technique was used for fabrication of the first membrane sensor (sensor 1) using phosphotungestate (PT) and dioctylphthalate (DOP) as cation exchanger and solvent mediator, respectively. beta-cyclodextrin (beta-CD)-based technique with PT as a fixed anionic site in PVC matrix was used for fabrication of the second membrane sensor (sensor 2). The proposed sensors showed fast, stable Nernstian responses of 54 and 56 mV/decade for sensors 1 and 2, respectively, across a relatively wide MD concentration range (1x 10(-4) to 1 x 10(-1) mol/L and 5 x 10(-5) to 1 x 10(-1) mol/L for sensor 1 and 2, respectively) in the pH range of 5-7. Sensor I and sensor 2 can be used for three and two weeks, respectively without any measurable change in sensitivity. The suggested electrodes succeeded to determine intact MD in the presence of up to 10% of its degradation product and displayed good selectivity in presence of common inorganic and organic species.


L-aspartic acid and urea supplementation of low-protein layer diets.
1. Urea supplementation of low-protein (125 g/kg) conventional-type diets for layers, whether containing fish meal or not, did not appear advantageous. 2. Supplementation of the low-protein diet with aspartic acid did not affect egg production rate of efficiency. 3. Soyabean meal supplementation of the low-protein diet increased egg weight significantly whereas aspartic acid did not.


CCL2 promotes osteogenesis by facilitating macrophage migration during acute inflammation.
Novel minimally invasive strategies are needed to obtain robust bone healing in complex fractures and bone defects in the elderly population. Local cell therapy is one potential option for future treatment. Mesenchymal stromal cells (MSCs) are not only involved in osteogenesis but also help direct the recruitment of macrophages during bone regeneration via MSC-macrophage crosstalk. The C-C motif chemokine ligand 2 (CCL2) is an inflammatory chemokine that is associated with the migration of macrophages and MSCs during inflammation. This study investigated the use of CCL2 as a therapeutic target for local cell therapy. MSCs and macrophages were isolated from 10 to 12 week-old BALB/c male mice. Genetically modified CCL2 over-expressing MSCs were produced using murine CCL2-secreting pCDH-CMV-mCCL2-copGFP expressing lentivirus vector. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture. Cell migration assays were also performed. MSCs transfected with murine CCL2-secreting pCDH-CMV-mCCL2-copGFP expressing lentivirus vector showed higher levels of CCL2 secretion compared to unaltered MSCs (p < 0.05). Genetic manipulation did not affect cell proliferation. CCL2 did not affect the osteogenic ability of MSCs alone. However, acute (1 day) but not sustained (7 days) stimulation with CCL2 increased the alizarin red-positive area when MSCs were co-cultured with macrophages (p < 0.001). Both recombinant CCL2 (p < 0.05) and CCL2 released from MSCs (p < 0.05) facilitated macrophage migration. We demonstrated that acute CCL2 stimulation promoted subsequent osteogenesis in co-culture of MSCs and macrophages. Acute CCL2 stimulation potentially facilitates osteogenesis during the acute inflammatory phase of bone healing by directing local macrophage migration, fostering macrophage-MSC crosstalk, and subsequently, by activating or licensing of MSCs by macrophage pro-inflammatory cytokines. The combination of CCL2, MSCs, and macrophages could be a potential strategy for local cell therapy in compromised bone healing.


Potential drug targets in Mycobacterium tuberculosis through metabolic pathway analysis.
The emergence of multidrug resistant varieties of Mycobacterium tuberculosis has led to a search for novel drug targets. We have performed an insilico comparative analysis of metabolic pathways of the host Homo sapiens and the pathogen M. tuberculosis. Enzymes from the biochemical pathways of M. tuberculosis from the KEGG metabolic pathway database were compared with proteins from the host H. sapiens, by performing a BLASTp search against the non-redundant database restricted to the H. sapiens subset. The e-value threshold cutoff was set to 0.005. Enzymes, which do not show similarity to any of the host proteins, below this threshold, were filtered out as potential drug targets. We have identified six pathways unique to the pathogen M. tuberculosis when compared to the host H. sapiens. Potential drug targets from these pathways could be useful for the discovery of broad spectrum drugs. Potential drug targets were also identified from pathways related to lipid metabolism, carbohydrate metabolism, amino acid metabolism, energy metabolism, vitamin and cofactor biosynthetic pathways and nucleotide metabolism. Of the 185 distinct targets identified from these pathways, many are in various stages of progress at the TB Structural Genomics Consortium. However, 67 of our targets are new and can be considered for rational drug design. As a case study, we have built a homology model of one of the potential drug targets MurD ligase using WHAT IF software. The model could be further explored for insilico docking studies with suitable inhibitors. The study was successful in listing out potential drug targets from the M. tuberculosis proteome involved in vital aspects of the pathogen's metabolism, persistence, virulence and cell wall biosynthesis. This systematic evaluation of metabolic pathways of host and pathogen through reliable and conventional bioinformatic methods can be extended to other pathogens of clinical interest.


The Schiff base bond configuration in bacteriorhodopsin and in model compounds.
The Schiff base linkage bond configuration of bacteriorhodopsin was studied using model compounds consisting of all-trans- and 13-cis-retinal-protonated Schiff bases bearing C = N anti and syn bond configurations. The C = N configuration was analyzed using a combination of Fourier transform infrared spectroscopy and isotopically labeled chromophores. It was found that, in the model compounds, the coupling between the C14--C15 stretching frequency and the N--H rock is weak in the all-trans-retinal-protonated Schiff base in both the anti and syn C = N configurations. However, this coupling is relatively strong in the 13-cis-retinal-protonated Schiff base in both the anti and syn C = N configurations. Thus, it is concluded that, in model compounds, the C14--C15 mode can serve as a marker for the C13 = C14 bond configuration but not for the C = N. A different situation may prevail in bacteriorhodopsin due to different conformations of the retinal chromophore in the protein binding site and in solution. This difference suggests that the C14--C15/NH coupling in retinal-protonated Schiff bases is affected by the retinal conformation.


Child with dengue haemorrhagic fever complicated by ileocaecal intussusception.
Dengue fever is one of the most common neglected tropical diseases with an increasing trend seen in Sri Lanka and many other tropical countries. A number of unusual presentations and complications of dengue fever have been reported, and acute abdomen is one such presentation. However, intussusception as the cause of acute abdomen in a patient with dengue haemorrhagic fever has not been previously reported. The authors report a child who was diagnosed to have intussusception during the critical phase of dengue haemorrhagic fever while having a platelet count of 15×103/cumm. The child had initial point-of-care ultrasound followed by detailed ultrasound of the abdomen by the radiologist, and the diagnosis of ileocaecal intussusception was confirmed. Intussusception was relieved by saline reduction and without needing laparotomy. Early diagnosis and non-operative management prevented emergency laparotomy.


[Posterior lamellar keratoplasty with DSEK technique and use of the Tan EndoGlide - short-term results].
To present the differences in surgical technique of DSEK (Descemet's Stripping Endothelial Keratoplasty) with the use of Tan EndoGlide (Coronet, UK) and Busin Glide (Moria, FR). Short-term results will also be presented, DSEK was performed in 24 eyes, in 8 cases the surgery was combined with cataract phacoemulsification and lOL implantation. Surgery course and 6 months postoperative results of first 12 eyes performed with the use of Tan EndoGlide were compared with 12 consecutive eyes preformed with Busin Glide. Tan EndoGlide provided much more stable anterior chamber, donor tissue unfolding process was better controlled but the incision was wider incision. Surgically induced mean refractory cylinder 6. months after the surgery was 1.56 - 1.15 Dsph in Tan EndoGlide group and 1.18 +/- 1.10 Dsph in Busin Glide group (P <0.05). The endothelial cell loss was 20.5% and 21.12% respectively (P>0.05). Mean CDVA was 0.65+/- 0.27 and 0.63 +/- 0.25, respectively (P>0,05). Statistically significant differences in intra- and post-operative complications between both groups were not found. The Tan EndoGlide used during posterior lamellar keratoplasty with DSEK technique is a good alternative to currently used methods. It provides better stabilization of the anterior chamber, however its use is linked with higher postoperative astigmatism in comparison with Busin Glide. The visual outcomes and endothelial cell loss 6 months after the surgery were similar in both groups.


Pseudomonas aeruginosa exoenzyme S is an adhesion.
Exoenzyme S from Pseudomonas aeruginosa has been studied as an adhesion for glycosphingolipids and buccal cells. Binding of exoenzyme S to gangliotriosylceramide (GalNAc beta 1-4Gal beta 1-4Glc beta 1-1Cer), gangliotetraosylceramide (Gal beta 1-3 GalNAcT beta 1-4 Gal beta 1-4Glc beta 1-1Cer), and lactosylceramide (Gal beta 1-4Glc beta 1-1Cer) separated on thin-layer chromatograms was observed. Binding curves for exoenzyme S with dilutions of gangliotetraosylceramide immobilized on plastic plates were similar to previously reported results for the intact bacteria. Binding of exoenzyme S to sialylated counterparts of these glycosphingolipids was not seen, indicating that the addition of a sialic acid residue interferes with binding. Exoenzyme S and monoclonal antibody to exoenzyme S inhibit the binding of P. aeruginosa to buccal cells. The presence of exoenzyme S on the surface of P. aeruginosa was detected by immunogold labeling of bacteria with antibodies to exoenzyme S. Results of these studies led us to conclude that exoenzyme S is an important adhesion of P. aeruginosa.


Recent advances in post autologous transplantation maintenance therapies in B-cell non-Hodgkin lymphomas.
Lymphomas constitute the second most common indication for high dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT). The intent of administering HDT in these heterogeneous disorders varies from cure (e.g., in relapsed aggressive lymphomas) to disease control (e.g., most indolent lymphomas). Regardless of the underlying histology or remission status at transplantation, disease relapse remains the number one cause of post auto-HCT therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at prevention of post auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. In relapsed, chemosensitive diffuse large B-cell lymphoma (DLBCL), although post auto-HCT maintenance rituximab seems to be safe and feasible, it does not provide improved survival outcomes and is not recommended. The preliminary results with anti- programmed death -1 (PD-1) antibody therapy as post auto-HCT maintenance in DLBCL is promising but requires randomized validation. Similarly in follicular lymphoma, maintenance therapies including rituximab following auto-HCT should be considered investigational and offered only on a clinical trial. Rituximab maintenance results in improved progression-free survival but has not yet shown to improve overall survival in mantle cell lymphoma (MCL), but given the poor prognosis with post auto-HCT failure in MCL, maintenance rituximab can be considered on a case-by-case basis. Ongoing trials evaluating the efficacy of post auto-HCT maintenance with novel compounds (e.g., immunomodulators, PD-1 inhibitors, proteasome inhibitors and bruton's tyrosine kinase inhibitors) will likely change the practice landscape in the near future for B cell non-Hodgkin lymphomas patients following HDT and auto-HCT.


Pituitary and ovarian hormone levels in unexplained menorrhagia.
To compare pituitary and ovarian hormone levels in women complaining of unexplained menorrhagia with objectively heavy menstrual blood loss (greater than 80 mL) to those with normal loss, and to determine whether there is any relation between menstrual volume and important cyclic endocrine events. Over the course of 1 month, daily plasma LH, FSH, and estradiol (E2), and salivary progesterone concentrations were determined in 20 women with a measured menstrual loss exceeding 80 mL. These were compared with values in 22 women whose loss was less than 80 mL. For all participants, we calculated correlation coefficients for measured menstrual blood loss and the mean LH peak concentration, the mean FSH peak concentration, the mean of plasma E2 concentrations from day LH -3 to +1, and the mean of salivary progesterone concentrations from day LH +2 to +10. There were no significant differences in the plasma concentrations of LH, FSH, or E2 or in the salivary concentrations of progesterone between those with objectively heavy loss and those with normal loss. We did not find significant relations between the measured menstrual blood loss and the mean LH and FSH peak concentrations, the plasma E2 concentrations daily around ovulation, or the salivary progesterone concentrations during the luteal phase. There does not appear to be a relation between ovarian and pituitary hormones and menstrual loss.


Allopurinol-Induced Drug Reaction With Eosinophilia and Systemic Symptoms: A Case Report.
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon yet serious adverse cutaneous drug reaction that results from a hypersensitivity reaction. Drug reaction with eosinophilia and systemic symptoms is often misdiagnosed because of vague and confounding signs and symptoms. The most common clinical manifestations of DRESS are shared with many other diseases and include rash, lymphadenopathy, and fever. Because the syndrome can be difficult to diagnose, patients are often in the late stages of the disease process before treatment is initiated. The mainstay of treatment is stopping the culprit medication. Drug reaction with eosinophilia and systemic symptoms is associated with a high mortality rate, most often from liver failure and failure to diagnose. Emergency providers should be able to recognize the clinical manifestations of DRESS, know what diagnostic studies are indicated, and be familiar with the appropriate treatment.


Plasma CX3CL1 levels and long term outcomes of patients with atrial fibrillation: the West Birmingham Atrial Fibrillation Project.
There is growing evidence that chemokines are potentially important mediators of the pathogenesis of atherosclerotic disease. Major atherothrombotic complications, such as stroke and myocardial infarction, are common among atrial fibrillation (AF) patients. This increase in risk of adverse events may be predicted by a score based on the presence of certain clinical features of chronic heart failure, hypertension, age 75 years or greater, diabetes and stroke (the CHADS2 score). Our objective was to assess the prognostic value of plasma chemokines CCL2, CXCL4 and CX3CL1, and their relationship with the CHADS2 score, in AF patients. Plasma CCL2, CXCL4 and CX3CL1 were measured in 441 patients (59% male, mean age 75 years, 12% paroxysmal, 99% on warfarin) with AF. Baseline clinical and demographic factors were used to define each subject's CHADS2 score. Patients were followed up for a mean 2.1 years, and major adverse cardiovascular and cerebrovascular events (MACCE) were sought, being the combination of cardiovascular death, acute coronary events, stroke and systemic embolism. Fifty-five of the AF patients suffered a MACCE (6% per year). Those in the lowest CX3CL1 quartile (≤ 0.24 ng/ml) had fewest MACCE (p = 0.02). In the Cox regression analysis, CX3CL1 levels >0.24 ng/ml (Hazard ratio 2.8, 95% CI 1.02-8.2, p = 0.045) and age (p = 0.042) were independently linked with adverse outcomes. The CX3CL1 levels rose directly with the CHADS2 risk score (p = 0.009). The addition of CX3CL1 did not significantly increased the discriminatory ability of the CHADS2 clinical factor-based risk stratification (c-index 0.60 for CHADS2 alone versus 0.67 for CHADS2 plus CX3CL1 >0.24 ng/ml, p = 0.1). Aspirin use was associated with lower levels of CX3CL1 (p = 0.0002) and diabetes with higher levels (p = 0.031). There was no association between CXCL4 and CCL2 plasma levels and outcomes. There is an independent association between low plasma CX3CL1 levels and low risk of major cardiovascular events in AF patients, as well as a linear association between CX3CL1 plasma levels and CHADS2-defined cardiovascular risk. The potential for CX3CL1 in refining risk stratification in AF patients merits consideration.


Mechanical property of a TIM-barrel protein.
The mechanical response of a TIM-barrel protein to an applied pressure has been studied. We generated structures under an applied pressure by assuming the volume change to be a linear function of normal mode variables. By Delaunay tessellation, the space occupied by protein atoms is divided uniquely into tetrahedra, whose four vertices correspond to atomic positions. Based on the atoms that define them, the resulting Delaunay tetrahedra are classified as belonging to various secondary structures in the protein. The compressibility of various regions identified with respect to secondary structural elements in this protein is obtained from volume changes of respective regions in two structures with and without an applied pressure. We found that the beta barrel region located at the core of the protein is quite soft. The interior of the beta barrel, occupied by side chains of beta strands, is the softest. The helix, strand, and loop segments themselves are extremely rigid, while the regions existing between these secondary structural elements are soft. These results suggest that the regions between secondary structural elements play an important role in protein dynamics. Another aspect of tetrahedra, referred to as bond distance, is introduced to account for rigidities of the tetrahedra. Bond distance is a measure of separation of the atoms of a tetrahedron in terms of number of bonds along the polypeptide chain or side chains. Tetrahedra with longer bond distances are found to be softer on average. From this behavior, we derive a simple empirical equation, which well describes the compressibilities of various regions.


Do Tonic Itch and Pain Stimuli Draw Attention towards Their Location?
Although itch and pain are distinct experiences, both are unpleasant, may demand attention, and interfere with daily activities. Research investigating the role of attention in tonic itch and pain stimuli, particularly whether attention is drawn to the stimulus location, is scarce. In the somatosensory attention task, fifty-three healthy participants were exposed to 35-second electrical itch or pain stimuli on either the left or right wrist. Participants responded as quickly as possible to visual targets appearing at the stimulated location (ipsilateral trials) or the arm without stimulation (contralateral trials). During control blocks, participants performed the visual task without stimulation. Attention allocation at the itch and pain location is inferred when responses are faster ipsilaterally than contralaterally. Results did not indicate that attention was directed towards or away from the itch and pain location. Notwithstanding, participants were slower during itch and pain than during control blocks. In contrast with our hypotheses, no indications were found for spatial attention allocation towards the somatosensory stimuli. This may relate to dynamic shifts in attention over the time course of the tonic sensations. Our secondary finding that itch and pain interfere with task performance is in-line with attention theories of bodily perception.


Effect of somatostatin-28 on growth hormone response to growth hormone-releasing hormone--impact of aging and lifelong dietary restriction.
The present study was designed to investigate the modulating effect of aging and lifelong dietary restriction (DR), a powerful anti-aging intervention in laboratory rodents, on growth hormone (GH) secretion from pituitary cells in response to GH-releasing hormone (GHRH) in the presence of somatostatin (SS)-28. Dispersed pituitary cells from 6- and 24-month-old rats fed ad libitum (AL-Y, AL-O, respectively) and 24-month-old rats dietary restricted from 6 weeks of age (DR-O) were subjected to a reverse hemolytic plaque assay under variable conditions including GHRH (0, 1, 10 nM) and SS-28 (0, 10 nM). The proportion of GH plaque-forming cells in dispersed pituitary cells increased by GHRH and decreased by SS-28. The proportion of these cells was lowest in AL-O rats; it was lower in DR-O than in AL-Y rats, particularly in the presence of SS-28. The reduction in these cells by SS-28 was greatest in Group AL-O. The mean area of these plaques, reflecting the amount of GH released from individual cells, was not different among the three rat groups in the absence of SS-28. In contrast, SS-28 produced a significantly higher reduction in the plaque area in Group AL-O compared with AL-Y and DR-O rats. Our results indicated that: (1) aging did not alter the responsiveness of GH-secreting cells to GHRH for GH secretion, while increased sensitivity of GH-secreting cells to SS-28 was noted in aged rats; (2) lifelong dietary restriction did not modulate the responsiveness to GHRH but partially inhibited the age-related increase in the sensitivity to SS-28 of GH-secreting cells, and (3) the major impact of the dietary regimen may include modulation of the number of pituitary cells, which leads to a high proportion of GH-secreting cells compared with that in AL rats at the same chronological age.


Granuloma pyogenicum as a complication of flashlamp-pumped pulsed dye laser.
The flashlamp-pumped pulsed dye laser (FPDL) is a dye laser with 585-nm wavelength and 300- to 450-microseconds pulse width and has been demonstrated to effectively and safely treat port-wine stains, telangiectases and superficial hemangiomas. We report 2 cases of pyogenic granuloma following the treatment with FPDL.


The Effect of Artificial Mowing on the Competition of Phragmites australis and Spartina alterniflora in the Yangtze Estuary.
Spartina alterniflora Loisel. is one of the most invasive species in the world. However, little is known about the role of artificial mowing in its invasiveness and competiveness. In this work, we studied the effect of mowing on its interspecific interactions with native species Phragmites australis (Cav.) Trin ex Steud of the Yangtze Estuary, China. We calculated their relative neighbor effect (RNE) index, effect of relative crowding (Dr ) index, and interaction strength (I) index. The results showed that the RNE of Phragmites australis and Spartina alterniflora was 0.354 and 0.619, respectively, and they have competitive interactions. The mowing treatments can significantly influence the RNE of Phragmites australis and Spartina alterniflora on each other. Concretely, the RNE of Spartina alterniflora in the removal treatments was significantly higher than the value in the controls. But the RNE of Phragmites australis in the removal treatments was significantly lower than the value in the controls. Meanwhile, Dr of the two species on the targets was higher in the removal treatments than that in the controls, and the opposite was for I. We concluded that artificial mowing could promote the invasion of Spartina alterniflora by increasing its competitive performance compared with native species.


Variations in elemental composition of rice (Oryza sativa L.) with different cultivation areas of Ethiopia.
Variations in the elemental composition of rice (Oryza sativa L.) grains, and the link with the growing soil, were investigated across the major production areas of Ethiopia (Fogera, Metema and Pawe). The elements (Ca, Mg, Fe, Zn, Mn, Cu, Ni, Cr, Cd and Pb) were determined by using flame atomic absorption spectroscopy (FAAS), after digesting samples through an optimized procedure with respect to volumes of reagents (HNO3, HClO4 and H2O2), temperature and time. The accuracy of the FAAS method was in the range of 87‒113%. The most abundant element in rice was Mg (414‒561 mg kg-1) followed by Fe (49.4‒168 mg kg-1), while in soil was Fe (11674‒12917 mg kg-1) followed by Mg (619‒709 mg kg-1). Chromium, Cd and Pb were all below the limit of quantitation of the method. The concentrations of the elements, except Zn in rice and Fe in soil, varied significantly (p < 0.05) with the growing region. Notably, rice from Fogera contained more than double Fe, while from Pawe less than half Cu than from the other region. Soils from the rice fields of Pawe, generally, had lower levels of the elements than from the other regions. The order of the abundances of the elements in soil was reflected in the rice grains, except for the reversal between Fe and Mg. However, elemental concentrations were higher in soil than in rice, indicating the absence of bioaccumulation by the rice grains. Furthermore, only copper exhibited a strong positive correlation (r = 0.991) between the rice grain and soil.


Mechanism of resistance to an antitubercular 2-thiopyridine derivative that is also active against Burkholderia cenocepacia.
The discovery of new compounds that are able to inhibit the growth of Burkholderia cenocepacia is of primary importance for cystic fibrosis patients. Here, the mechanism of resistance to a new pyridine derivative already shown to be effective against Mycobacterium tuberculosis and to have good activity toward B. cenocepacia was investigated. Increased expression of a resistance-nodulation-cell division (RND) efflux system was detected in the resistant mutants, thus confirming their important roles in B. cenocepacia antibiotic resistance.


Computerized tomography scan in acute appendicitis with eventual negative appendectomy.
Acute appendicitis (AA) is traditionally considered a clinical diagnosis and negative appendectomy (NA) rates vary across health-care systems. Computed tomography (CT) scans have been shown to aid in the reduction of NA rates. Our study aimed to determine the pre-operative imaging characteristics in patients undergoing appendectomy with eventual normal histology. An audit of all patients with a discharge diagnosis of AA was conducted from January 2011 to December 2015. Histology reports of all patients who underwent appendectomies were reviewed, and medical records of patients with NA were included in the study. To study the impact of CT scan reporting in NA patients, CT scan images of patients with NA were reviewed retrospectively by two blinded radiologists. A total of 2603 patients underwent appendectomy for suspected AA, and NA rate was 3.34% (n=87). The mean age of patients with NA was 30.3 (14.8-69.8) years with no gender difference (51.7% male). Sixty-six (75.9%) patients had laparoscopic appendectomy with 3.5% open conversion rate. CT scans were done in 47 patients. Pre-operative CT scan report was more likely to report dilated appendix (n=26 [55.3%] vs. n=7 [14.9%], P=0.0001). Post-operative blinded radiology review was more like to report other pathology (n=27 [57.4%] vs. n=2 [4.3%], P=0.0001) and normal appendix (n=26 [55.3%] vs. n=5 (10.6%), P=0.0001). The NA rate is low. There needs to be standardized reporting for imaging features of prominent/dilated appendix. Appendectomy must be avoided in patients with a normal CT scan and when another pathological diagnosis is established. Liberal imaging policy assists to reduce NA rates. Imaging features of prominent or dilated appendix can be subjective and international collaboration is needed to define thresholds for imaging diagnosis of AA.


The standard of care debate: can research in developing countries be both ethical and responsive to those countries' health needs?
To avoid exploitation of host communities, many commentators argue that subjects must receive the best methods available worldwide. Others worry that this requirement may block important research intended to improve health care, especially in developing countries. To resolve this dilemma, we propose a framework for the conditions under which it is acceptable to provide subjects with less than the best methods. Specifically, institutional review boards should assume a default of requiring the "worldwide best" methods, meaning the best methods available anywhere in the world, in all cases.However, institutional review boards should be willing to grant exceptions to this default for research studies that satisfy the following 4 conditions: (1) scientific necessity, (2) relevance for the host community, (3) sufficient host community benefit, and (4) subject and host community non-maleficence.


Pegulated liposomal doxorubicin and cisplatin given concurrently with conventional radiotherapy: a phase I dose-escalation trial for patients with squamous cell carcinoma of head and neck and lung.
This is a phase I study of concurrent chemoradiation with pegulated liposomal doxorubicin (PLDH) and cisplatin for patients with squamous non-small cell lung cancer (NSCLC) and head and neck carcinoma (SCCHN). Nine patients with NSCLC and 9 with SCCHN were recruited in two phase I dose-escalation trials. The starting dose of PLDH was 7 mg/m2 once a week and was increased by 5 mg/m2 dose increments for every 3 patients. The standard dose of cisplatin was 20 mg/m2 once a week for 6.5-7 weeks of conventional external irradiation. The total tumor dose was 64 and 70 Gy for NSCLC and SCCHN patients respectively. The maximum tolerated dose of PLDH was 12 mg/m2 for the two cohorts of patients. Grade 3 mucositis was the dose limiting toxicity for NSCLC and SCCHN patients, at the 17 mg/m2 dose level. Three chemoradiation delays of 7 days were confirmed. The median time of follow-up was 17.9 months (range 3-36 months). Four patients died due to local-regional failure combined with distant metastases (3 patients) and pericardial effusion (1 patient). In total, there were 6/18 (33%) CRs (95% confidence interval, 11-55%), and 10/18 (55%), PRs (95% confidence interval, 32-78%). The recommended phase II PLDH dose combined to cisplatin and external irradiation is 12 mg/m2/week. The incorporation of PLDH in concomitant chemoradiation regimens for future treatment of squamous cell carcinoma of the lung and head and neck is warranted.


Changes in peripheral immune cell numbers and functions in octogenarian walkers - an acute exercise study.
Age-related changes of the immune system, termed immunosenescence, may underlie the increased risk of infections and morbidity in the elderly. Little is known about the effects of acute exercise on peripheral immune parameters in octogenarians. Therefore, we investigated acute exercise-induced changes in phenotype and function of the immune system in octogenarians participating in the 2013 edition of the Nijmegen Four Days Marches. Blood sampling was performed at baseline and immediately after 4 days of the walking exercise (30 km/day). A comprehensive set of adaptive and innate immune traits were enumerated and analyzed by flow-cytometry. Peripheral blood mononuclear cells, isolated before and after walking were stimulated with LPS and supernatants were analysed for IL-1β, IL-6, IL-8 and TNF-α concentrations by ELISA. CMV serostatus was determined by ELISA. The walking exercise induced a clear leucocytosis with numerical increases of granulocytes, monocytes and lymphocytes. These exercise-induced changes were most profound in CMV seropositive subjects. Within lymphocytes, numerical increases of particularly CD4+ T cells were noted. Further T cell differentiation analysis revealed profound increases of naïve CD4+ T cells, including naïve Treg. Significant increases were also noted for CD4+ memory T cell subsets. In contrast, only slight increases in naïve and memory CD8+ T cell subsets were detected. Exercise did not affect markers of immune exhaustion in memory T cell subsets. NK cells demonstrated a numerical decline and a change in cellular composition with a selective decrease of the mature CD56dim NK cells. The latter was seen in CMV seronegative subjects only. Also, a higher IL-6 and IL-8 production capacity of LPS-stimulated PBMC was seen after walking. In this exceptional cohort of octogenarian walkers, acute exercise induced changes in immune cell numbers and functions. A clear response of CD4+ T cells, rather than CD8+ T cells or NK cells was noted. Remarkably, the response to exercise within the CD4+ T cell compartment was dominated by naïve CD4+ subsets.


Pathophysiological characteristics, diagnostic problems and assessment of sinus node dysfunction.
Based on clinical and experimental experience, sick sinus syndrome can be divided into two groups: intrinsic and autonomic neurovegetative pacemaker dysfunction. Sinus node activity is characterized electrophysiologically by automaticity, recovery and sinoatrial conduction. The automaticity of the sinus pacemaker cell groups and sinus recovery can be differentiated properly under experimental conditions. Studies of the electrophysiological characteristics showed the basic functional parameters to be normal in autonomic sinus dysfunction. Diagnosis is either based on clinical observation or on the data of Holter monitoring, the electrophysiological methods being inadequate for diagnosing this neurovegetative form of sick sinus syndrome. On the other hand, intrinsic-organic sinus dysfunction can be diagnosed by electrophysiological tests. If completed by complex pharmacological studies, in this organic form of sick sinus syndrome, even the severity of the intrinsic injuries can be assessed quantitatively. This division provides a logical basis for a proper selection and evaluation of the differential diagnostic procedures, while information on the aetiopathology of sinus dysfunction and on the degree of the functional injuries of the electrophysiological structure of the heart provides an adequate basis for therapy.


Interferon-γ promotes phagocytosis of Cryptococcus neoformans but not Cryptococcus gattii by murine macrophages.
Among invasive fungal infections, cryptococcosis caused by inhalation of Cryptococcus neoformans or Cryptococcus gattii is particularly dangerous because it can disseminate to the central nervous system and cause life-threatening meningitis or meningoencephalitis. Previous reports described significant differences in the histopathological features of C. neoformans and C. gattii infection, such as greater pathogen proliferation and a limited macrophage response in mouse lung infected by C. gattii. To elucidate the difference in pathogenicity of these two Cryptococcus species, we investigated the interaction of C. neoformans and C. gattii with murine macrophages, the first line of host defense, by confocal laser microscopy. Only thin-capsulated, and not thick-capsulated C. neoformans and C. gattii were phagocytosed by macrophages. Preactivation with interferon-γ increased the phagocytic rate of thin-capsulated C. neoformans up to two-fold, but did not promote phagocytosis of thin-capsulated C. gattii. Lipopolysaccharide preactivation or Aspergillus fumigatus conidia co-incubation had no effect on internalization of thin-capsulated C. neoformans or C. gattii by macrophages. Phagocytosis of live thin-capsulated C. neoformans, but not that of live thin-capsulated C. gattii, induced interleukin-12 release from macrophages. However, phagocytosis of heat-killed or paraformaldehyde-fixed thin-capsulated C. neoformans did not increase IL-12 release, showing that the internalization of live yeast is important for initiating the immune response during C. neoformans-macrophage interactions. Our data suggest that macrophage response to C. gattii is limited compared with that to C. neoformans and that these results may partially explain the limited immune response and the greater pathogenicity of C. gattii.


Re-evaluation of cefepime or piperacillin/tazobactam to decrease use of carbapenems in ESBL-producing Enterobacterales urinary tract infections (REDUCE-UTI).
To re-examine the use of non-carbapenems (NCBPs), specifically piperacillin/tazobactam and cefepime, for ESBL-producing Enterobacterales (ESBL-E) urinary tract infections (UTIs). Retrospective cohort study of adults hospitalized between January 2016 and June 2020 with pyuria on urinalysis, a urine culture positive for ESBL-E treated with a study antibiotic (meropenem, ertapenem, cefepime or piperacillin/tazobactam) and did not meet criteria for study exclusion. To compare carbapenems (CBPs) with cefepime or piperacillin/tazobactam for the treatment of ESBL-E UTI. The primary outcome was clinical cure, defined as complete resolution of signs and symptoms of infection. Secondary outcomes included in-hospital mortality, recurrence within 30 days and resistance emergence within 30 days. One-hundred and thirty-three patients were included, based on definitive therapy received; 69 (51.9%) received CBP and 64 (48.1%) received NCBP therapy. Of the total patient population, 17 (12.8%) were admitted to the ICU, 84 (63.1%) had a complicated UTI and 64 (48.1%) had pyelonephritis. There was no difference in clinical cure between the CBP and NCBP groups (95.7% versus 96.9%, P = 0.999). Additionally, no differences in secondary outcomes were observed. When compared with CBPs, cefepime and piperacillin/tazobactam resulted in similar clinical cure, in-hospital mortality, recurrence and resistance emergence in the treatment of ESBL-E UTI.


Diabetes Insipidus Complicating Management in a Child with COVID-19 and Multiorgan System Failure: A Novel Use for Furosemide.
Judicious balance of fluids is needed for optimal management of acute respiratory distress syndrome (ARDS). Achieving optimal fluid balance is difficult in patients with disorders of fluid homeostasis such as diabetes insipidus (DI). There is little data on the use of Furosemide to aid in balancing fluid and electrolytes in patients with DI. Here, we present a critically ill 11-year-old female with developmental delay, septo-optic dysplasia, central DI, and respiratory failure secondary to COVID-19 ARDS. She required careful titration of a Vasopressin infusion in addition to IV Furosemide for successful management of fluid and electrolyte derangements. On admission, she demonstrated high-volume urine output with mild hypernatremia (serum sodium 156 mmol/L). Despite her maximum Vasopressin infusion rate of 8 mU/kg/hr, by day two of admission, she voided a total of 4 L resulting in severe hypernatremia (serum sodium 171 mmol/L). With continually high Vasopressin infusion rates, her overall fluid balance became increasingly net positive, although her hypernatremia persisted. Her ARDS continued to worsen. After 48 hours of the addition of intermittent Furosemide, successful diuresis along with resolution of hypernatremia was achieved. The combination of IV Furosemide with Vasopressin infusion resulted in tailored diuresis and more controlled titration of serum sodium levels than adjustment in Vasopressin and fluids alone. These results are in contradistinction to the published literature, which focuses on the use of thiazide diuretics in managing DI. This experience highlights the potential for loop diuretics to aid in establishing a desired fluid and electrolyte status in managing patients with both DI and ARDS.


Tainted blood: Probing safety practices in the Danish blood system.
The existing literature on donor screening in transfusion medicine tends to distinguish between social concerns about discrimination and medical concerns about safety. In this article, we argue that the bifurcation into social and medical concerns is problematic. We build our case on a qualitative study of the historical rise and current workings of safety practices in the Danish blood system. Here, we identify a strong focus on contamination in order to avoid 'tainted blood', at the expense of working with risks that could be avoided through enhanced blood monitoring practices. Of further significance to this focus are the social dynamics found at the heart of safety practices aimed at avoiding contamination. We argue that such dynamics need more attention, in order to achieve good health outcomes in transfusion medicine. Thus, we conclude that, to ensure continuously safe blood systems, we need to move beyond the bifurcation of the social and medical aspects of blood supply as two separate issues and approach social dynamics as key medical safety questions.


Molecular mechanisms involved in fruit cracking: A review.
Several fleshy fruits are highly affected by cracking, a severe physiological disorder that compromises their quality and causes high economical losses to the producers. Cracking can occur due to physiological, genetic or environmental factors and may happen during fruit growth, development and ripening. Moreover, in fleshy fruits, exocarp plays an important role, acting as a mechanical protective barrier, defending against biotic or abiotic factors. Thus, when biochemical properties of the cuticle + epidermis + hypodermis are affected, cracks appear in the fruit skin. The identification of genes involved in development such as cell wall modifications, biosynthesis and transport of cuticular waxes, cuticular membrane deposition and associated transcription factors provides new insights to better understand how fruit cracking is affected by genetic factors. Amongst the major environmental stresses causing cracking are excessive water during fruit development, leading to imbalances in cations such as Ca. This review focus on expression of key genes in these pathways, in their influence in affected fruits and the potential for molecular breeding programs, aiming to develop cultivars more resistant to cracking under adverse environmental conditions.


Application of bovine microsatellite markers for genetic diversity analysis of European bison (Bison bonasus).
In this study, the cross-amplification of a commercial multiplex set of 11 cattle (Bos taurus) microsatellites was tested on a panel of 35 European bison (Bison bonasus) individuals. After polymerase chain reaction optimization, all loci cross-amplified successfully in investigated bisons. Number of alleles and observed and expected heterozygosity per locus are in the range of 2-4, 0.086-0.629 and 0.288-0.621 respectively. The availability of a heterologous set of multiplexed microsatellite markers derived from cattle opens an avenue for collecting profound genetic data for efficient conservation management strategies of the European bison.


Agency and market area factors affecting home health agency supply changes.
To use the natural experiment created by the Medicare interim payment system (IPS) to study supply change behavior of home health agencies (HHAs) in local market areas. One hundred percent Medicare home health claims for 1996 and 1999, linked with Medicare Provider of Service and Denominator files, and the Area Resource File. Medicare home health care (HHC) claims data were used to distinguish HHAs that changed the local market supply of Medicare HHC by their market exit or by significant expansion or contraction of their geographic service area between 1996 and 1999 from other HHAs. Multinomial logit models were estimated to analyze how characteristics of agencies and the market areas in which they served were associated with these different agency-level supply changes. Changes in local HHA supply stemming from geographic service area expansions and contractions rivaled those owing to agency closures and market entries. Agencies at greater risk of closure and service area contraction tended to be smaller, newer, freestanding agencies, operating with more visit-intensive practice styles in markets with more competitor agencies. Except for having much less visit-intensive practice styles, similar attributes characterized agencies that increased local supply through service area expansion. Supply changes by HHAs largely reflected rational market responses by agencies to significant changes in financial incentives associated with the Medicare IPS. Recently certified agencies were among the most dynamic providers. Supply changes were more likely among agencies operating in more competitive market environments.


Tuning the viscoelastic response of hydrogel scaffolds with covalent and dynamic bonds.
The processes of growth, proliferation and differentiation of stem cells encapsulated in 3D hydrogel microenvironments are strongly affected by the viscoelastic properties of the platforms. As the viscoelastic response of a hydrogel is determined by the rates of thermally induced dissociation of reversible cross-links, its modulation by introduction of several types of supramolecular and/or dynamic covalent bonds with different characteristic lifetimes has recently become a hot topic. To reduce the number of experiments needed for design of hydrogel microenvironments with required mechanical properties, a model is developed for the viscoelastic and viscoplastic responses of hydrogels with multiple networks bridged by covalent and physical bonds. An advantage of the model is that it (i) involves a small number of material parameters, (ii) describes observations in rheological and mechanical tests in a unified manner, and (iii) predicts conventional measures of viscoelasticity used in the analysis of viability of cells.


Predictors of poor hospital discharge outcome in acute stroke due to atrial fibrillation.
Atrial fibrillation (AF) is a frequent cause of acute ischemic stroke that results in severe neurological disability and death despite treatment with intravenous thrombolysis (intravenous recombinant tissue plasminogen activator [rtPA]). We performed a retrospective review of a single-center registry of patients treated with intravenous rtPA for stroke. The purposes of this study were to compare intravenous rtPA treated patients with stroke with and without AF to examine independent predictors of poor hospital discharge outcome (in-hospital death or hospital discharge to a skilled nursing facility, long-term acute care facility, or hospice care). A univariate analysis was performed on 144 patients receiving intravenous rtPA for stroke secondary to AF and 190 patients without AF. Characteristics that were significantly different between the two groups were age, initial National Institutes of Health Stroke Scale score, length of hospital stay, gender, hypertension, hyperlipidemia, smoking status, presence of large cerebral infarct, and hospital discharge outcome. Bivariate logistic regression analysis indicated that patients with stroke secondary to AF with a poor hospital discharge outcome had a greater likelihood of older age, higher initial National Institutes of Health Stroke Scale scores, longer length of hospital stay, intubation, and presence of large cerebral infarct compared with those with good hospital discharge outcome (discharged to home or inpatient rehabilitation or signed oneself out against medical advice). A multivariate logistic regression analysis showed that older age, longer length of hospital stay, and presence of large cerebral infarct were independent predictors of poor hospital discharge outcome. These predictors can guide nursing interventions, aid the multidisciplinary treating team with treatment decisions, and suggest future directions for research.


Histamine H(1)-receptor activation of nuclear factor-kappa B: roles for G beta gamma- and G alpha(q/11)-subunits in constitutive and agonist-mediated signaling.
Nuclear factor kappa B (NF-kappa B) is an important transcription factor in inflammation that has obtained a great interest as a drug target for the treatment of various allergic conditions. In this study, we show that the histamine H(1) receptor, which is also an important player in allergic and inflammatory conditions, activates NF-kappa B in both a constitutive and agonist-dependent manner. Moreover, the observed constitutive NF-kappa B activation is inhibited by various H(1)-receptor antagonists, suggesting that inverse agonism may account, at least in part, for their ascribed antiallergic properties. Investigation of the H(1) receptor-mediated NF-kappa B activation in transfected COS-7 cells indicates that the level of the observed constitutive activity of the H(1) receptor can be modulated by the expression levels of either G alpha-proteins or G beta gamma-heterodimers. Members of the G alpha(q/11)-family of G alpha-proteins are most effective in increasing H(1) constitutive activity. Also, coexpression of G beta(2) in combination with either G gamma(1) or G gamma(2) results in an increased constitutive activity of the H(1) receptor, whereas scavenging of G beta gamma-subunits by coexpression of G alpha(t) completely neutralizes the constitutive, but not the agonist-induced, NF-kappa B activity. Our data suggest that both G alpha(q/11)- and G beta gamma-subunits play a role in the agonist-induced, H(1) receptor-mediated NF-kappa B activation, but that constitutive NF-kappa B activation by the H(1) receptor is primarily mediated through G beta gamma-subunits.


Guided bone regeneration-assisted orthodontic treatment for closing the space of missing central incisors.
Long-term missing teeth can lead to alveolar bone loss in the edentulous area. Guided bone regeneration (GBR) is a bone augmentation method. It is widely used in clinical practice and broadens the indications of orthodontic treatment to a certain extent. This article reports a case of an adult patient with edentulous space in the maxillary central incisor, which was successfully closed through orthodontic treatment combined with GBR. This study will provide a re-ference for future clinical work.


Migration of mitochondrial DNA in the nuclear genome of colorectal adenocarcinoma.
Colorectal adenocarcinomas are characterized by abnormal mitochondrial DNA (mtDNA) copy number and genomic instability, but a molecular interaction between mitochondrial and nuclear genome remains unknown. Here we report the discovery of increased copies of nuclear mtDNA (NUMT) in colorectal adenocarcinomas, which supports link between mtDNA and genomic instability in the nucleus. We name this phenomenon of nuclear occurrence of mitochondrial component as numtogenesis. We provide a description of NUMT abundance and distribution in tumor versus matched blood-derived normal genomes. Whole-genome sequence data were obtained for colon adenocarcinoma and rectum adenocarcinoma patients participating in The Cancer Genome Atlas, via the Cancer Genomics Hub, using the GeneTorrent file acquisition tool. Data were analyzed to determine NUMT proportion and distribution on a genome-wide scale. A NUMT suppressor gene was identified by comparing numtogenesis in other organisms. Our study reveals that colorectal adenocarcinoma genomes, on average, contains up to 4.2-fold more somatic NUMTs than matched normal genomes. Women colorectal tumors contained more NUMT than men. NUMT abundance in tumor predicted parallel abundance in blood. NUMT abundance positively correlated with GC content and gene density. Increased numtogenesis was observed with higher mortality. We identified YME1L1, a human homolog of yeast YME1 (yeast mitochondrial DNA escape 1) to be frequently mutated in colorectal tumors. YME1L1 was also mutated in tumors derived from other tissues. We show that inactivation of YME1L1 results in increased transfer of mtDNA in the nuclear genome. Our study demonstrates increased somatic transfer of mtDNA in colorectal tumors. Our study also reveals sex-based differences in frequency of NUMT occurrence and that NUMT in blood reflects NUMT in tumors, suggesting NUMT may be used as a biomarker for tumorigenesis. We identify YME1L1 as the first NUMT suppressor gene in human and demonstrate that inactivation of YME1L1 induces migration of mtDNA to the nuclear genome. Our study reveals that numtogenesis plays an important role in the development of cancer.


The efficacy of posterior scleral contraction in controlling high myopia in young people.
To investigate the clinical effectiveness and safety of posterior scleral contraction (PSC) surgery in controlling high myopia in young people. Twenty patients with high myopia (30 eyes) were treated with PSC. The average age for the patients was 11.45 ± 5.17 years old (range 3-22). A genipin cross-linked sclera was implanted to the posterior sclera in PSC surgery. Axial length and myopia progression rates were measured at least two years before and after PSC surgery. Prior to surgery, the mean AL progression was 0.73 ± 0.33 mm, compared to -0.08 ± 0.31 mm (P=0.00) post-surgery; the degree of myopia increased was -1.40 ± 0.95 D, compared to 0.18 ± 1.10 D post-surgery (P=0.00). The best corrected visual acuity (BCVA, in LogMAR) improved from 0.21 ± 0.16 preoperatively to 0.13 ± 0.13 two years after PSC (P=0.014). PSC can restrict AL extension and safely control high myopia progression in young people.


Comparative analysis of the effects of Copaifera multijuga oil-resin and nitrofurazona in the cutaneous wound healing process.
to evaluate, histologically and macroscopically, the influence of Copaifera multijuga (Copaíba) oil-resin on the healing process of cutaneous wounds, comparing it with nitrofurazone. we divided 36 rats into three groups of 12 animals, according to the treatment to be administered. Group SL (control) received saline on the lesion; the Group OIL received topical treatment with Copaíba oil; and the Group NITRO was treated with Nitrofurazone. We inflicted a circular wound of 8mm in diameter on the back of each animal. We subdivided each of the three groups of 12 animals into three subgroups, according to treatment time and euthanasia (7, 14 and 21 days). All animals received the proposed treatment daily. We photographed the lesions for area measurement, as well as for evaluation of macroscopic aspects. We resected and stained the scars to quantify and qualify elastic fibers, collagen, degree of epithelization, neovascularization and inflammation. although the saline solution provided a faster wound closure in its initial phase, after 14 days the wound size of the three groups tested was the same. Levels of inflammation and neovascularization were similar in all three groups. The amount of collagen and elastic fibers was higher in the Nitrofurazone and Copaíba oil groups. in male Wistar rats, Copaifera multijuga oil-resin positively influences the healing process, but it is less effective than nitrofurazone in healing by secondary intention.


Suppression of castor oil-induced diarrhoea by alpha 2-adrenoceptor agonists.
The effects of systemic administration of alpha 2-adrenoceptor agonists on migrating myoelectric complexes and castor oil-induced diarrhoea of the small intestine were studied in conscious rats. Castor oil (1 mg/kg, intraduodenally) disrupted the migrating myoelectric complexes and induced irregular spiking activity with sporadic bursts of myoelectric activity. This change of motility pattern was present concomitant with diarrhoea 1-2 h after instillation of castor oil and during the whole period of diarrhoea. Pre-treatment with clonidine (5-10 micrograms/kg i.v.) or oxymetazoline (5.6-11.2 micrograms/kg i.v.), a peripherally active alpha 2-agonist, inhibited the irregular spiking induced by castor oil and no diarrhoea occurred during the experimental period of 6 h. Thus, the antidiarrhoeal action of peripherally acting alpha 2-adrenoceptor agonists such as oxymetazoline, may be of clinical value in the treatment of diarrhoea.


Exposures to near-to-maximal speed running bouts during different turnarounds in elite football: association with match hamstring injuries.
To describe the occurrence of near-to-maximal sprinting speed (near-to-MSS) running bouts during training and hamstring injuries during the consecutive match of the same turnaround in elite football (soccer). Retrospective data from 36 team-seasons (16 elite teams performing in top European leagues) were analyzed (627 players, 96 non-contact time loss match hamstring injuries). We described 1) the occurrence of > 85%, > 90% or > 95% MSS exposures during training within each turnaround and match hamstring injuries and 2) whether the above-mentioned injury occurrences differed depending on the day(s) of the turnarounds (i.e., the period separating two consecutive matches, which is generally from 3 to 8 days) when these speed exposures occurred. The longer the length of the turnarounds and the lower the speed thresholds, the greater the number (and proportion) of near-to-MSS exposures (e.g., 18%, 45% and 72% of turnarounds with > 85% runs for 3, 5 and 7-turnarounds, respectively). For half of the turnarounds examined, there were no match hamstring injuries when players were exposed to running bouts > 95% MSS during training (e.g., injury rates: 0; CI: 0-15). Injuries still occurred during 85% of the turnarounds when there were no or lower relative speed exposures (i.e., > 85 or > 90%, injury rates: 2-5, CI: 0-6). Finally, irrespective of the turnaround length, there were no match hamstring injuries when > 95% MSS exposures occurred at D-2, while in contrast, injuries still happened when players were not exposed at all, or when these exposures occurred at D-3 and/or earlier within the turnaround. While the present observational study design precludes the examination of causal relationships, the programming of > 95% MSS exposures at D-2 may help mitigate match hamstring injury occurrences in elite football.


An unusual organelle in the pineal gland of the rat.
An electron microscopic survey of pinealocytes from normal rats revealed a highly organized arrangement of cytoplasmic tubules. Such tubules had been previously observed in normal rats (Lin, 1967) and in rats after melatonin administration or two weeks exposure to darkness (Freire and Cardinali, 1975). In a later publication the presence of the tubules was attributed to experimental manipulation resulting in infertility (Gusek, 1976). The present study resolves the discrepancy in the literature by establishing that the tubular organelle does indeed occur in untreated male rats, but rather rarely.


[Benign mesenchymal stromal tumor of the breast simulating benign schwannoma in an 81-year-old male--a case report].
Presented is an unusual case of a benign mesenchymal stromal tumor of the breast in an 81-year-old male. The basic appearance of the lesion simulated benign schwannoma and was misinterpreted as a low-grade myxoid liposarcoma initially. Well-circumscribed, gray-white mass measuring 35 mm in maximum diameter was discovered deep in the parenchyma of the completely removed breast. Microscopically, the lesion consisted of myxoid, richly vascular background where dominated oval or spindle cells with impressive palisading replicating that of benign schwannoma. Rarely, the large multinucleated (floret-like type) cells were visible; no nuclear atypia or mitotic figures were found. Immunohistochemical examination confirmed expression of estrogen and progesterone receptors, antigen Bcl2 and also focal desmin positivity. Clinical examinations disclosed no objective reason for possible hyperestrinism; no other therapy followed and the patient is free of disease 19 months after operation. On the background of both detailed review and differential diagnosis of benign, so-called stromal tumor of the female breast, the rarity of this microscopic finding in male is documented.


Research on a community-based platform for promoting health and physical fitness in the elderly community.
This study aims to assess the acceptability of a fitness testing platform (iFit) for installation in an assisted living community with the aim of promoting fitness and slowing the onset of frailty. The iFit platform develops a means of testing Bureau of Health Promotion mandated health assessment items for the elderly (including flexibility tests, grip strength tests, balance tests, and reaction time tests) and integrates wireless remote sensors in a game-like environment to capture and store subject response data, thus providing individuals in elderly care contexts with a greater awareness of their own physical condition. In this study, we specifically evaluated the users' intention of using the iFit using a technology acceptance model (TAM). A total of 101 elderly subjects (27 males and 74 females) were recruited. A survey was conducted to measure technology acceptance, to verify that the platform could be used as intended to promote fitness among the elderly. Results indicate that perceived usefulness, perceived ease of use and usage attitude positively impact behavioral intention to use the platform. The iFit platform can offer user-friendly solutions for a community-based fitness care and monitoring of elderly subjects. In summary, iFit was determined by three key drivers and discussed as follows: risk factors among the frail elderly, mechanism for slowing the advance frailty, and technology acceptance and support for promoting physical fitness.


Patients transported by helicopter fare better.
The care your patients get before they arrive in your ED is critically important to their survival and well-being. View the air transport vehicle as an extension of your department. Be sure the nurses staffing the helicopter have additional training in airway management. If your program is hospital-based, be sure you have the last word on the most appropriate staffing model.


[Simplified techniques for toxoplasmosis studies (author's transl)].
Some improvements on laboratory technics for Toxoplasmosis are presented: 1--the use of serum from guinea-pigs as accessory factor (AF) on the dye-test; 2--the use of filter-paper discs for collecting and storing blood of children and small animals for the dye test; 3--conservation of Toxoplasma gondii at various media and temperatures. 1--the pool of serum from 14 guinea-pigs gave good results when diluted in 1/5 Alsever solution at the proportion of 6/10; 2--the blood from digital puncture usually could be collected on filter-paper discs of 15 mm of diameter and stored at the freezer to -23 degrees C for 3-4 weeks, protected with alumen-paper. The dilution with saline 8.5% could be made 1/2 hour before starting the procedure; 3--the Toxoplasma gondii (cysts and trophozoites) could be stored at LIT medium or saline 8.5% at refrigator a +4 degrees C for 15-22 days, with some reduction in virulence.


Relative contribution of CD2 and LFA-1 to murine T and natural killer cell functions.
We have examined the functional property of murine CD2 as an intercellular adhesion molecule by using five anti-murine CD2 mAb which were classified into two groups according to their mutual competition in binding to cell surface CD2. Hamster fibroblasts transfected with murine CD2 cDNA exhibited increased conjugate formation with a murine mastocytoma P815 which expresses the putative murine LFA-3 mRNA detected by cross-hybridization with human LFA-3 cDNA under conditions of low stringency. This increase in conjugate formation was abrogated by both groups of anti-CD2 mAb, although some differences in the extent of inhibition were observed at lower concentrations of the mAb. We then examined the involvement of CD2 in several murine T cell responses by using these mAb to abrogate CD2-mediated cellular interactions. Anti-CD2 mAb significantly inhibited mitogenic T cell responses induced by suboptimal doses of Con A and PHA. In the allogenic MLR response and in the Ag response of two KLH/I-Ak-specific Th cell clones, the inhibitory effect of anti-CD2 mAb was also greatest under suboptimal conditions, i.e., with lesser doses of the Ag. These results indicate that the contribution of CD2 as an accessory molecule is variable, depending on the Ag dose used for stimulation, and they suggest that CD2 is involved in the Ag response of murine T cells under the physiologic conditions where only a limited amount of Ag is available. We next examined the contribution of CD2 to MHC-restricted cytotoxicity by CTL and to MHC-unrestricted cytotoxicity by NK and lymphokine-activated killer cells. Only a marginal inhibition by anti-CD2 mAb alone was observed. Anti-lymphocyte function-associated Ag (LFA)-1 mAb alone exhibited greater inhibitory effects than anti-CD2 mAb in all of the cases tested. In most cases, however, substantial levels of cytotoxicity remained, even in the presence of both anti-CD2 and anti-LFA-1 mAb. These results indicate a minor contribution of CD2, as compared with LFA-1, to cytotoxicity by murine CTL, NK cells, and lymphokine-activated killer cells, and they reveal the presence of undefined cellular interaction pathways other than those mediated by CD2 and LFA-1.


Web Camera Based Eye Tracking to Assess Visual Memory on a Visual Paired Comparison Task.
Background: Web cameras are increasingly part of the standard hardware of most smart devices. Eye movements can often provide a noninvasive "window on the brain," and the recording of eye movements using web cameras is a burgeoning area of research. Objective: This study investigated a novel methodology for administering a visual paired comparison (VPC) decisional task using a web camera.To further assess this method, we examined the correlation between a standard eye-tracking camera automated scoring procedure [obtaining images at 60 frames per second (FPS)] and a manually scored procedure using a built-in laptop web camera (obtaining images at 3 FPS). Methods: This was an observational study of 54 clinically normal older adults.Subjects completed three in-clinic visits with simultaneous recording of eye movements on a VPC decision task by a standard eye tracker camera and a built-in laptop-based web camera. Inter-rater reliability was analyzed using Siegel and Castellan's kappa formula. Pearson correlations were used to investigate the correlation between VPC performance using a standard eye tracker camera and a built-in web camera. Results: Strong associations were observed on VPC mean novelty preference score between the 60 FPS eye tracker and 3 FPS built-in web camera at each of the three visits (r = 0.88-0.92). Inter-rater agreement of web camera scoring at each time point was high (κ = 0.81-0.88). There were strong relationships on VPC mean novelty preference score between 10, 5, and 3 FPS training sets (r = 0.88-0.94). Significantly fewer data quality issues were encountered using the built-in web camera. Conclusions: Human scoring of a VPC decisional task using a built-in laptop web camera correlated strongly with automated scoring of the same task using a standard high frame rate eye tracker camera.While this method is not suitable for eye tracking paradigms requiring the collection and analysis of fine-grained metrics, such as fixation points, built-in web cameras are a standard feature of most smart devices (e.g., laptops, tablets, smart phones) and can be effectively employed to track eye movements on decisional tasks with high accuracy and minimal cost.


Closure of Recalcitrant Macular Hole after Choroidal Neovascularization.
To report the closure of a recalcitrant macular hole (MH) following the development of choroidal neovascularization. A 67-year-old female patient in this case report was diagnosed with a MH and operated twice, but anatomical closure of MH could not be achieved. The patient was followed up without further treatment, as she rejected any additional procedure. Six months later, a lesion consistent with choroidal neovascularization appeared in the central macula, and the recalcitrant MH closed spontaneously. The MH defect remained closed in the following years. Besides being a new example of the presence of choroidal neovascularization after MH surgery, the most important aspect of this case report is to report the closure of a recalcitrant MH following the development of choroidal neovascularization.


Contrasting the neurologic complications of cardiac transplantation in adults and children.
The objective of this study was to evaluate neurologic complications associated with cardiac transplantation and compare the neurologic complications seen in adults and children. As advances in immunology have led to longer survival times for cardiac transplant recipients (1- and 5-year survival rates have improved to 86% and 65%, respectively), a number of neurologic complications have emerged. We performed a 14-year retrospective review of all adults and children (<18 years old) who had orthotopic cardiac transplantation at either Indiana University Hospital or James Whitcomb Riley Hospital for Children. The rates of neurologic complications involving the central and peripheral nervous systems in adults and children were assessed for differences using the chi-square test and Fisher's exact test where appropriate. A total of 191 orthotopic cardiac transplants were performed from 1986 to 2000, with follow-up available for 184, including 107 adults and 77 children. Thirty-two of 107 (30%) adults experienced a total of 47 complications, with peripheral neuropathies being the most frequent complication. Eighteen of 77 (23%) children experienced a total of 22 complications, with seizures being the most frequent complication. Other complications occurring in both groups were cerebrovascular, infectious, encephalopathies, neoplasms, and "other." Neurologic complications in children and adults after orthotopic cardiac transplantation are similar in both incidence and type. However, peripheral neuropathies tend to occur more frequently in adults than in children (P = .04), and the types of complications in the immediate post-transplant period seem to differ.


CsHCT-Mediated Lignin Synthesis Pathway Involved in the Response of Tea Plants to Biotic and Abiotic Stresses.
Many studies have shown that phenolic compounds such as lignin and flavonoids enhance plant resistance. Tea plants are rich in flavonoid compounds. Whether these compounds are related to tea plant resistance is unclear. In this study, an interesting conclusion was drawn on the basis of experimental results: in response to abiotic stress (except for sucrose treatment), gene expression was increased in the phenylpropanoid and lignin pathways and was reduced in the flavonoid pathway in tea plants. CsHCTs, the genes located at the branch point of the lignin and flavonoid pathways, are most suitable for regulating the ratio of carbon flow in the lignin pathway and flavonoid synthesis. Enzymatic and genetic modification experiments proved that CsHCTs encode hydroxycinnamoyl-coenzyme A:shikimate/quinate hydroxycinnamoyl transferase in vitro and in vivo. Furthermore, the genetic modification results showed that the contents of phenolic acids and lignin were increased in tobacco and Arabidopsis plants overexpressing CsHCTs, whereas the content of flavonol glycosides was decreased. Both types of transgenic plants showed resistance to many abiotic stresses and bacterial infections. We speculate that CsHCTs participate in regulation of the metabolic flow of carbon from the flavonoid pathway to the chlorogenic acid, caffeoylshikimic acid, and lignin pathways to increase resistance to biotic and abiotic stresses.


Infective Endocarditis Due to Abiotrophia defectiva and Its Feared Complications in an Immunocompetent Person: Rare, But Real.
Abiotrophia defectiva is nutritional deficient streptococci that cannot be cultured on routine culture medias. Even though fastidious in growth requirement, it is a virulent bacterium preferentially affecting endovascular structures and is implicated in many culture-negative endocarditis cases. Unlike other organisms, it is known for heart valve destruction leading to heart failure and excessive embolization rates. It's inherent resistance to routinely used antibiotics also contributed to increased mortality and morbidity in affected individuals and warrants timely diagnosis and prompt treatment. Our patient, a previous healthy individual, acquired this rare bacterium from intravenous drug abuse and developed infective endocarditis with valve destruction, heart failure, and distal embolization to multiple organs. He underwent multiple surgeries including mitral valve replacement and embolectomy with clinical improvement. Our case reiterates the possibility of rare cause of common diseases and raises awareness of infective endocarditis caused by A. defectiva among medical professionals.