Cervicogenic headache in the general population: the Akershus study of chronic headache.
The objective was to study the prevalence of cervicogenic headache (CEH) in the general population. An age- and gender-stratified random sample of 30,000 persons aged 30-44 years received a mailed questionnaire. Those with self-reported chronic headache were interviewed by neurological residents. The criteria of the Cervicogenic Headache International Study Group and the International Classification of Headache Disorders, second edition, were applied. The questionnaire response rate was 71% and the participation rate of the interview was 74%. The prevalence of CEH was 0.17% in the general population, with a female preponderance. Fifty per cent had co-occurrence of medication overuse and 42% had co-occurrence of migraine. The pericranial muscle tenderness score was significantly higher on the pain than non-pain side (p < .005). The cervical range of motion was significantly reduced compared to healthy controls (p < .005). The mean duration of CEH was eight years. Based on patients' self-reports, greater occipital nerve (GON) blockage and cryotherapy was reported effective in 90% of those who had this procedure, while other treatment alternatives were reported less effective.


Rapamycin suppresses axon sprouting by somatostatin interneurons in a mouse model of temporal lobe epilepsy.
In temporal lobe epilepsy many somatostatin interneurons in the dentate gyrus die. However, some survive and sprout axon collaterals that form new synapses with granule cells. The functional consequences of γ-aminobutyric acid (GABA)ergic synaptic reorganization are unclear. Development of new methods to suppress epilepsy-related interneuron axon sprouting might be useful experimentally. Status epilepticus was induced by systemic pilocarpine treatment in green fluorescent protein (GFP)-expressing inhibitory nerurons (GIN) mice in which a subset of somatostatin interneurons expresses GFP. Beginning 24 h later, mice were treated with vehicle or rapamycin (3 mg/kg intraperitoneally) every day for 2 months. Stereologic methods were then used to estimate numbers of GFP-positive hilar neurons per dentate gyrus and total length of GFP-positive axon in the molecular layer plus granule cell layer. GFP-positive axon density was calculated. The number of GFP-positive axon crossings of the granule cell layer was measured. Regression analyses were performed to test for correlations between GFP-positive axon length versus number of granule cells and dentate gyrus volume. After pilocarpine-induced status epilepticus, rapamycin- and vehicle-treated mice had approximately half as many GFP-positive hilar neurons as did control animals. Despite neuron loss, vehicle-treated mice had over twice the GFP-positive axon length per dentate gyrus as controls, consistent with GABAergic axon sprouting. In contrast, total GFP-positive axon length was similar in rapamycin-treated mice and controls. GFP-positive axon length correlated most closely with dentate gyrus volume. These findings suggest that rapamycin suppressed axon sprouting by surviving somatostatin/GFP-positive interneurons after pilocarpine-induced status epilepticus in GIN mice. It is unclear whether the effect of rapamycin on axon length was on interneurons directly or secondary, for example, by suppressing growth of granule cell dendrites, which are synaptic targets of interneuron axons. The mammalian target of rapamycin (mTOR) signaling pathway might be a useful drug target for influencing GABAergic synaptic reorganization after epileptogenic treatments, but additional side effects of rapamycin treatment must be considered carefully.


Human natural killer cells: origin, receptors, function, and clinical applications.
Natural killer (NK) cells are important effectors playing a relevant role in innate immunity, primarily in tumor surveillance and in defenses against viruses. Human NK cells recognize HLA class I molecules through surface receptors (KIR and NKG2A) that inhibit NK cell function and kill target cells that have lost (or underexpress) HLA class I molecules as it occurs in tumors or virus-infected cells. NK cell activation is mediated by an array of activating receptors and co-receptors that recognize ligands expressed primarily on tumors or virus-infected cells. In vivo anti-tumor NK cell activity may be suppressed by tumor or tumor-associated cells. Alloreactive NK cells (i.e. those that are not inhibited by the HLA class I alleles of the patient) derived from HSC of haploidentical donors play a major role in the cure of high-risk leukemia, by killing leukemia blasts and patient's DC, thus preventing tumor relapses and graft-versus-host disease. The expression of the HLA-C2-specific activating KIR2DS1 may also contribute to NK alloreactivity in patients expressing C2 alleles. A clear correlation has been proven between the size of the alloreactive NK cell population and the clinical outcome. Recently, haplo-HSCT has been further improved with the direct infusion, together with HSC, of donor-derived, mature alloreactive NK cells and TCRγδ(+) T cells - both contributing to a prompt anti-leukemia effect together with an efficient defense against pathogens during the 6- to 8-week interval required for the generation of alloreactive NK cells from HSC.


The dynamics of the microcirculation in the subcutaneous adipose tissue is impaired in the postprandial state in type 2 diabetes.
Postprandially, the blood flow and uptake of non-esterified fatty acids increase concomitantly in the abdominal subcutaneous adipose tissue in healthy subjects. In insulin-resistant subjects, this postprandial blood flow increase is blunted. We have previously found that the postprandial adipose tissue blood flow (ATBF) increase is accompanied by capillary recruitment in healthy subjects. The aim of the present study was to investigate whether the postprandial capillary recruitment in adipose tissue is affected in type 2 diabetes mellitus. Eight type 2 diabetic overweight male subjects and eight age- and weight-matched healthy subjects were studied. Contrast-enhanced ultrasound imaging was applied to study the microvascular volume in abdominal subcutaneous adipose tissue and in forearm skeletal muscle in the fasting state and 60, 120 and 180 min after a 75-g oral glucose load. Abdominal subcutaneous ATBF was measured using (133) Xenon washout technique, and forearm skeletal muscle blood flow was assessed by venous occlusion plethysmography. In the healthy, overweight subjects, ATBF increased and concomitantly capillary recruitment took place after glucose ingestion. No significant changes were found in the ATBF or in capillary recruitment in the type 2 diabetic subjects. There was no significant blood flow or microvascular blood volume changes in forearm skeletal muscle in either of the groups. After an oral glucose load, the abdominal ATBF and microvascular blood volume changes in abdominal subcutaneous adipose tissue are impaired in overweight type 2 diabetic subjects compared to weight-matched healthy subjects.


Gas chromatographic negative ion mass spectrometric assay of 2-dicyclopropylmethylamino-2-oxazoline (S-3341), a new antihypertensive drug.
The quantification in plasma and urine of 2-dicyclopropylmethylamino-2-oxazoline (S-3341), a new antihypertensive drug is described using a sensitive gas chromatographic negative ion mass spectrometric method with ammonia as moderating gas. After a two-step extraction, derivatization is carried out with 3,5-bis(trifluoromethyl)benzoyl chloride and the abundance of the molecular ion (m/z 420) obtained is compared with that of the tetradeuterated standard (m/z 424). The low background due to the high mass and negative ion detection provides a detection limit of about 1 pg per injection. Oral administration of 1 or 2 mg S-3341 to patients gives a maximum concentration of 3.3 +/- 0.7 ng ml-1 and 7.6 +/- 2.0 ng ml-1 at 1.8 +/- 0.6 h and 1.4 +/- 0.7 h and an average elimination half-life of 6.7 h.


Growth control and cell wall signaling in plants.
Plant cell walls have the remarkable property of combining extreme tensile strength with extensibility. The maintenance of such an exoskeleton creates nontrivial challenges for the plant cell: How can it control cell wall assembly and remodeling during growth while maintaining mechanical integrity? How can it deal with cell wall damage inflicted by herbivores, pathogens, or abiotic stresses? These processes likely require mechanisms to keep the cell informed about the status of the cell wall. In yeast, a cell wall integrity (CWI) signaling pathway has been described in great detail; in plants, the existence of CWI signaling has been demonstrated, but little is known about the signaling pathways involved. In this review, we first describe cell wall-related processes that may require or can be targets of CWI signaling and then discuss our current understanding of CWI signaling pathways and future prospects in this emerging field of plant biology.


In vivo volumetric intravascular ultrasound visualization of early/inflammatory arterial atheroma using targeted echogenic immunoliposomes.
This study aimed to demonstrate three-dimensional (3D) visualization of early/inflammatory arterial atheroma using intravascular ultrasound (IVUS) and targeted echogenic immunoliposomes (ELIP). IVUS can be used as a molecular imaging modality with the use of targeted contrast agents for atheroma detection. Three-dimensional reconstruction of 2-dimensional IVUS images may provide improved atheroma visualization. Atheroma were induced in arteries of Yucatan miniswine (n = 5) by endothelial cell denudation followed by a 4-week high cholesterol diet. The contralateral arteries were left intact and served as controls. Anti-intercellular adhesion molecule-1 (ICAM-1) and generic gammaglobulin (IgG) conjugated ELIP were prepared. Arteries were imaged using IVUS before and after ELIP injection. Images were digitized, manually traced, segmented, and placed in tomographic sequence for 3D visualization. Atheroma brightness enhancement was compared and reported as mean gray scale values. Plaque volume was quantified both from IVUS and histologic images. Anti-ICAM-1 ELIP highlighting of the atheroma in all arterial segments was different compared with baseline (P < 0.05). There was no difference in the mean gray scale values with IgG-ELIP. Arterial 3D IVUS images allowed visualization of the entire plaque distribution. The highlighted plaque/atheroma volume with anti-ICAM-1 ELIP was greater than baseline (P < 0.01). This study demonstrates specific highlighting of early/inflammatory atheroma in vivo using anti-ICAM-1 ELIP. Three-dimensional IVUS reconstruction provides good visualization of plaque distribution in the arterial wall. This novel methodology may help to detect and diagnose pathophysiologic development of all stages of atheroma formation in vivo and quantitate plaque volume for serial and long-term atherosclerotic treatment studies.


Salicylhydroxamic Acid (SHAM) Inhibition of the Dissolved Inorganic Carbon Concentrating Process in Unicellular Green Algae.
Rates of photosynthetic O(2) evolution, for measuring K(0.5)(CO(2) + HCO(3) (-)) at pH 7, upon addition of 50 micromolar HCO(3) (-) to air-adapted Chlamydomonas, Dunaliella, or Scenedesmus cells, were inhibited up to 90% by the addition of 1.5 to 4.0 millimolar salicylhydroxamic acid (SHAM) to the aqueous medium. The apparent K(1)(SHAM) for Chlamydomonas cells was about 2.5 millimolar, but due to low solubility in water effective concentrations would be lower. Salicylhydroxamic acid did not inhibit oxygen evolution or accumulation of bicarbonate by Scenedesmus cells between pH 8 to 11 or by isolated intact chloroplasts from Dunaliella. Thus, salicylhydroxamic acid appears to inhibit CO(2) uptake, whereas previous results indicate that vanadate inhibits bicarbonate uptake. These conclusions were confirmed by three test procedures with three air-adapted algae at pH 7. Salicylhydroxamic acid inhibited the cellular accumulation of dissolved inorganic carbon, the rate of photosynthetic O(2) evolution dependent on low levels of dissolved inorganic carbon (50 micromolar Na-HCO(3)), and the rate of (14)CO(2) fixation with 100 micromolar [(14)C] HCO(3) (-). Salicylhydroxamic acid inhibition of O(2) evolution and (14)CO(2)-fixation was reversed by higher levels of NaHCO(3). Thus, salicylhydroxamic acid inhibition was apparently not affecting steps of photosynthesis other than CO(2) accumulation. Although salicylhydroxamic acid is an inhibitor of alternative respiration in algae, it is not known whether the two processes are related.


Live neuron morphology automatically reconstructed from multiphoton and confocal imaging data.
We have developed a fully automated procedure for extracting dendritic morphology from multiple three-dimensional image stacks produced by laser scanning microscopy. By eliminating human intervention, we ensure that the results are objective, quickly generated, and accurate. The software suite accounts for typical experimental conditions by reducing background noise, removing pipette artifacts, and aligning multiple overlapping image stacks. The output morphology is appropriate for simulation in compartmental simulation environments. In this report, we validate the utility of this procedure by comparing its performance on live neurons and test specimens with other fully and semiautomated reconstruction tools.


Lycium barbarum polysaccharides attenuate cisplatin-induced hair cell loss in rat cochlear organotypic cultures.
The aim of the present study was to investigate the effects of Lycium barbarum polysaccharides (LBP) on cisplatin-induced hair cell damage in the organ of Corti explant. The neonatal (P2-3) rat organ of Corti explant was exposed to cisplatin (20 μM; 48 h) with or without LBP pretreatment (150 and 600 μg/mL; 24 h). Hair cell loss was indicated by FITC-labeled phalloidin staining. The level of reactive oxygen species (ROS) and alteration of mitochondrial membrane potential (ΔΨ(m)) in hair cells were analyzed using fluorescent probes 2',7'-dichlorofluorescein diacetate and JC-1, respectively. The results showed that LBP significantly attenuated hair cell loss (p < 0.01). Hair cells pretreated with LBP showed significant reduction in ROS production and the decline of ΔΨ(m) compared with cisplatin alone group (p < 0.01), indicating the protective effect of LBP on cisplatin-induced hair cell loss. Taken together, these results indicate that LBP was effective in attenuating cisplatin-induced hair cell loss by reducing the production of ROS and maintaining mitochondrial ΔΨ(m).


Managing organizational problems in alternative service organizations.
Alternative Service Organizations--hotlines, shelters, crisis centers, etc.--are a growing and essential part of the overall human service delivery system. These organizations face predictable problems which arise from their unique history, structure, and mission. Using a political economy perspective, the common issues and professionalization, funding, and formalization are discussed and procedures for effectively managing resulting problems are suggested.


Aspirin therapy for cardiovascular disease.
Aspirin is a widely used and effective antithrombotic agent. Recent studies suggest that aspirin's anti-inflammatory effects are mediated via inhibition of an inducible isoform of cyclooxygenase in inflammatory cells (COX-2) and through blockade of the nuclear transcription factor, NF-kappa B. The optimal dose of aspirin for most clinical situations is 75 to 325 mg/d, but debate continues as to whether higher doses are needed to prevent cerebral ischemia. Aspirin is very effective for inhibition of platelet-mediated thrombosis at sites of vascular injury but does not reduce restenosis after coronary angioplasty or carotid endarterectomy, nor does it prevent a first stroke. Combined therapy with warfarin and aspirin has been shown to limit systemic embolic in high-risk patients with artificial heart valves, but at the cost of increased bleeding. A new aspirin derivative is currently being developed that appears to stimulate platelet nitric oxide release, inhibit thrombin-induced platelet aggregation, and lower gastric toxicity.


miR-21 and KLF4 jointly augment epithelial‑mesenchymal transition via the Akt/ERK1/2 pathway.
miR-21 induces epithelial-mesenchymal transition (EMT) of human cholangiocarcinoma (CCA) cells. However, the mechanism by which this occurs remains unclear. In the present study, high throughput platform was employed to detect the genes that are differential expressed in QBC939 cells transfected with a hsa-miR-21 antagomir or control vectors. The EMT-related Krüppel-like factor 4 (KLF4) gene was downregulated after miR-21 was knocked down. Overexpression of miR-21 upregulated KLF4, Akt, ERK and mesenchymal cell markers (N-cadherin and vimentin), downregulated the expression of epithelial cell marker E-cadherin and reduced cell migration and invasion. Immunohistochemistry showed that KLF4, pAkt and pERK were upregulated in tumor xenografts transfected with miR-21 mimics. Inhibitors of the PI3K-Akt and ERK1/2 pathways, LY294002 and U0126, significantly suppressed the EMT phenotype. The present data demonstrated that overexpression of miR-21, accompanied with KLF4, augmented the EMT via inactivation of Akt and ERK1/2 pathways. In conclusion, we have identified a novel mechanism that may be targeted in an attempt to relieve the malignant biological behavior of CCA cells.


[Pharmacokinetics of benzimidazole derivatives].
Pharmacokinetic properties of benzimidazole derivatives drug possessing antipsychotic, actoprotector, antiarrhythmic, antiulcerogenic, antiallergic, uricosuric, anthelmintic activities have been summarized. Pharmacokinetics of benzimidazole derivatives used in veterinary practice as anthelmintic drugs is also considered. Benzimidazoles derivatives are characterised by multicompartment and ambiguous pharmacokinetic models. The derivatives of benzimidazoles are subjected to the first pass metabolism in the liver, and, therefore, they are converted to both active, and inactive metabolites. It is necessary to take into account for coadministration of benzimidazoles with other drugs. Hepatoduodenal circulation and repeated adsorption of unchanged drug and its metabolites in the gut is observed for benzimidazole. Many derivatives of benzimidazoles are characterised by rather low absolute bioavailability during peroral intake (from 2 up to 60%). Benzimidazsole derivative may bind to proteins and cell elements of blood. More often pharmacokinetic profile of benzimidazoles is linear for low doses, however, at high doses the linearity is lost. For animals and men pharmacokinetic models are always nearly identical.


Effect of Microwave Treatment of Graphite on the Electrical Conductivity and Electrochemical Properties of Polyaniline/Graphene Oxide Composites.
Polyaniline (PANI)/graphene oxide (GO) composites were synthesized via in situ polymerization of aniline in the presence of GO. The effect of microwave treatment of graphite on the electrical conductivity and electrochemical properties of PANI/GO composites was highlighted, and the morphology and microstructure were subsequently characterized using transmission electron microscopy, scanning electron microscopy, Fourier-transformed infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. The results demonstrated that microwave treatment of graphite imparted a well-dispersed, highly ordered layered structure to the as-prepared GO, and in turn facilitated strong bonding between the GO and PANI nanosheets, which may be responsible for the improved electrical conductivity and electrochemical properties of the resulting PANI/GO composites. The desired PANI/GO composites possessed an electrical conductivity of 508 S/m, an areal capacitance of 172.8 mF/cm², and a retained capacitance of 87.4% after cycling, representing percentage increases of 102, 232, and 112, respectively, as a result of the microwave treatment of graphite. The resulting composites are promising electrode materials for high-performance and ecofriendly electrical energy storage devices.


6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation.
Shogaols are reported to possess anti-inflammatory and anticancer activities. However, the antimetastatic potential of shogaols remains unexplored. This study was performed to assess the effects of shogaols against breast cancer cell invasion and to investigate the underlying mechanisms. The anti-invasive effect of a series of shogaols was initially evaluated on MDA-MB-231 breast cancer cells using the matrigel invasion assay. The suppressive effects of 6-shogaol on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 (MMP-9) gelatinolytic activity and nuclear factor-κB (NF-κB) activation were further determined. Shogaols (6-, 8- and 10-shogaol) inhibited PMA-stimulated MDA-MB-231 cell invasion with an accompanying decrease in MMP-9 secretion. 6-Shogaol was identified to display the greatest anti-invasive effect in association with a dose-dependent reduction in MMP-9 gene activation, protein expression and secretion. The NF-κB transcriptional activity was decreased by 6-shogaol; an effect mediated by inhibition of IκB phosphorylation and degradation that subsequently led to suppression of NF-κB p65 phosphorylation and nuclear translocation. In addition, 6-shogaol was found to inhibit JNK activation with no resulting reduction in activator protein-1 transcriptional activity. By using specific inhibitors, it was demonstrated that ERK and NF-κB signalling, but not JNK and p38 signalling, were involved in PMA-stimulated MMP-9 activation. 6-Shogaol is a potent inhibitor of MDA-MB-231 cell invasion, and the molecular mechanism involves at least in part the down-regulation of MMP-9 transcription by targeting the NF-κB activation cascade. This class of naturally occurring small molecules thus have potential for clinical use as antimetastatic treatments.


Structuring β-Ga2O3 photonic crystal photocatalyst for efficient degradation of organic pollutants.
Coupling photocatalysts with photonic crystals structure is based on the unique property of photonic crystals in confining, controlling, and manipulating the incident photons. This combination enhances the light absorption in photocatalysts and thus greatly improves their photocatalytic performance. In this study, Ga2O3 photonic crystals with well-arranged skeleton structures were prepared via a dip-coating infiltration method. The positions of the electronic band absorption for Ga2O3 photonic crystals could be made to locate on the red edge, on the blue edge, and away from the edge of their photonic band gaps by changing the pore sizes of the samples, respectively. Particularly, the electronic band absorption of the Ga2O3 photonic crystal with a pore size of 135 nm was enhanced more than other samples by making it locate on the red edge of its photonic band gap, which was confirmed by the higher instantaneous photocurrent and photocatalytic activity for the degradation of various organic pollutants under ultraviolet light irradiation. Furthermore, the degradation mechanism over Ga2O3 photonic crystals was discussed. The design of Ga2O3 photonic crystals presents a prospective application of photonic crystals in photocatalysis to address light harvesting and quantum efficiency problems through manipulating photons or constructing photonic crystal structure as groundwork.


Relationships between brain water content and diffusion tensor imaging parameters (apparent diffusion coefficient and fractional anisotropy) in multiple sclerosis.
Fifteen multiple sclerosis patients were examined by diffusion tensor imaging (DTI) to determine fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in a superventricular volume of interest of 8 x 8 x 2 cm(3) containing gray matter (GM) and white matter (WM) tissue. Point resolved spectroscopy 2D-chemical shift imaging of the same volume was performed without water suppression. The water contents and DTI parameters in 64 voxels of 2 cm(3) were compared. The water content was increased in patients compared with controls (GM: 244+/-21 vs. 194+/-10 a.u.; WM: 245+/-32 vs. 190+/-11 a.u.), FA decreased (GM: 0.226+/-0.038 vs. 0.270+/-0.020; WM: 0.337+/-0.044 vs. 0.402+/-0.011) and ADC increased [GM: 1134+/-203 vs. 899+/-28 (x10(-6) mm(2)/s); WM: 901+/-138 vs. 751+/-17 (x10(-6) mm(2)/s)]. Correlations of water content with FA and ADC in WM were strong (r=-0.68, P<0.02; r=0.75; P<0.01, respectively); those in GM were weaker (r=-0.50, P<0.05; r=0.45, P<0.1, respectively). Likewise, FA and ADC were more strongly correlated in WM (r=-0.88; P<0.00001) than in GM (r=-0.69, P<0.01). The demonstrated relationship between DTI parameters and water content in multiple sclerosis patients suggests a potential for therapy monitoring in normal-appearing brain tissue.


Mycobacterium avium subspecies Paratuberculosis and Crohn's regional ileitis: how strong is association?
Mycobacterium avium subsp. paratuberculosis (MAP) is a well-established etiological agent of Johne's disease in animals. In humans, similar clinical condition, first described by Crohn as regional ileitis in 1932, now known as Crohn's diseases (CD), has also been associated with this mycobacterial species. However, there are two schools of thoughts, one favoring MAP as its etiological agent while the second considers it as an immune-inflammatory condition triggered by an external factor. Onset of CD requires a series of events including predisposition of certain inherited genetic traits, associated environmental stimuli, and immune-inflammatory response. A combination of these factors probably leads to this disease. Recently, some human genes have also been identified which regulate ability to respond appropriately to the external factors. Added to these factors are concerns about the selection of clinical specimens and poor adherence to laboratory quality controls. The literature is full of contradictory findings, but there a lack of uniformity in the materials and methods used by many of these researchers. In this review, we provide our perspective under above circumstances and give our point of view which may open a platform for debate regarding the MAP as the etiological agent of human CD.


[Postoperative adhesions, the everlasting topical subject].
Creation of postoperative adhesions is a part of every abdominal operation. The authors analyse 320 patients operated for ileus in last 7 years. 118 patients were operated for adhesive ileus. Most common reoperations for ileus are after radical gynecological operations and inflammatory intraabdominal diseases. The creation of adhesiones depends on preoperative mechanical or chemical damage of tissues and peritoneum, bacterial infection and irradiation. The major complication of intraabdominal adhesions are disturbances of bowel function what leads to subileus or ileus. Authors present therapeutical possibilities and prefer laparoscopic operations.


Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Typhimurium Q1.
Here, we report the draft genome sequence of Salmonella enterica subsp. enterica serovar Typhimurium strain Q1. The draft genome contains 4,793,493 bp in 149 contigs.


Long-term results of kidney transplantation: a single center experience.
Overall, patient and renal allograft survivals after cadaveric transplantation have improved significantly since the incorporation of CsA into the standard immunosuppressive regimen. Overall, patient and renal allograft survivals were significantly better for non-diabetic recipients when compared to diabetic recipients after cadaveric transplantation. Living-donor renal transplant recipients have a better outcome than cadaveric transplant recipients. Cardiovascular disease is the leading cause of death after renal transplantation. Death on dialysis accounted for the second largest number of posttransplant mortalities. Sepsis and malignancy remained the next most important causes of death after renal transplantation.


Podoconiosis instruction at nursing schools in Kenya, Rwanda, and Uganda.
Podoconiosis is a preventable, progressive, and non-infectious form of elephantiasis that can contribute to significant disability and economic burden when not treated early. Nurses play a critical role in early detection and response in rural Africa, but it is unclear if they receive adequate training on podoconiosis. We aimed to characterize podoconiosis instruction at all government accredited, post-secondary nursing institutions in three African countries. Data for this cross-sectional study was collected through a quantitative survey with several open-answer questions. Through a rigorous online search, we identified all post-secondary institutions in Kenya, Rwanda and Uganda accredited to teach human nursing. A total of 289 accredited programs, including 85 certificate, 56 degree and 148 diploma programs were invited to participate. Respondents completed surveys online or by telephone. Measures focused on podoconiosis knowledge, perceptions of quality/quantity of podoconiosis instruction, and barriers to sufficient podoconiosis education. We obtained information about 212 curricula across 149 nursing institutions in the three countries (participation rate: 73.4%). Podoconiosis coverage was limited across programs (certificate-24.1%; diploma-55.6%; degree-30.3%). Most respondents felt that the quality and quantity of instruction were insufficient (60.6%, 62.9%), respectively. Exclusion from government curricula, low priority and faculty lack of knowledge were commonly reported barriers to podoconiosis inclusion. This study demonstrated clear gaps in podoconiosis training for nurses across the three countries and highlights a serious challenge in eliminating podoconiosis as a public health problem. Interventions to improve nurses' knowledge could include the development and free distribution of podoconiosis teaching materials, designed for integration into pre-existing courses.


Cross-talk among bone cells.
Bone cells such as osteoclasts, osteoblasts, and osteocytes 'talk' to each other throughout adult life to maintain bone integrity. This review highlights frontier areas of research on intercellular communication among bone cells. Bone cells communicate to regulate the balance between bone resorption and bone formation. Recent findings have suggested that bone remodeling compartment is critical for osteoclast-osteoblast communication during bone remodeling. New molecules and mechanisms for bone cell communication, including 'coupling' of bone formation to resorption, have been revealed. Osteoclastic regulation of pH within the bone remodeling compartment is a mechanism that has been posited to rapidly activate osteoblastic bone formation, whereas osteocytes in the bone matrix regulate osteoclasts and osteoblasts on the bone surface through the lacuno-canaliculi network. Differentiation, activation, and apoptosis of bone cells are often dependent on the status of other types of bone cells. Bone cells in different lineages achieve intercellular communication not only by ligand-receptor interactions but also by molecules and ions traveling in the extracellular space or across gap junctions, processes that depend profoundly on the four-dimensional (space and time) architecture of bone tissue.


Long-term pulmonary function after recovery from pulmonary contusion due to blunt chest trauma.
Blunt chest trauma can cause severe acute pulmonary dysfunction due to hemo/pneumothorax, rib fractures and lung contusion. To study the long-term effects on lung function tests after patients' recovery from severe chest trauma. We investigated the outcome and lung function tests in 13 patients with severe blunt chest trauma and lung contusion. The study group comprised 9 men and 4 women with an average age of 44.6 +/- 13 years (median 45 years). Ten had been injured in motor vehicle accidents and 3 had fallen from a height. In addition to lung contusion most of them had fractures of more than three ribs and hemo/pneumothorax. Ten patients were treated with chest drains. Mean intensive care unit stay was 11 days (range 0-90) and mechanical ventilation 19 (0-60) days. Ten patients had other concomitant injuries. Mean forced expiratory volume in the first second was 81.2 +/- 15.3%, mean forced vital capacity was 85 +/- 13%, residual volume was 143 +/- 33.4%, total lung capacity was 101 +/- 14% and carbon monoxide diffusion capacity 87 +/- 24. Post-exercise oxygen saturation was normal in all patients (97 +/- 1.5%), and mean oxygen consumption max/kg was 18 +/- 4.3 ml/kg/min (60.2 +/- 15%). FEV1 was significantly lower among smokers (71.1 +/- 12.2 vs. 89.2 +/- 13.6%, P = 0.017). There was a non-significant tendency towards lower FEV1 among patients who underwent mechanical ventilation. Late after severe trauma involving lung contusion, substantial recovery was demonstrated with improved pulmonary function tests. These results encourage maximal intensive care in these patients. Further larger studies are required to investigate different factors affecting prognosis.


IS1327, a new insertion-like element in the pathogenicity-associated plasmid of Erwinia herbicola pv. gypsophilae.
The pathogenicity-associated plasmid (pPATH) of Erwinia herbicola pv. gypsophilae was previously shown to be exclusively present in pathogenic strains and to contain a gene cluster encoding phytohormone biosynthesis. Sequence analysis of the DNA region located downstream from the cytokinin biosynthetic gene (etz) revealed homology to insertion sequences (IS) of the IS6 family. Southern blot analysis performed on plasmid DNA of E. herbicola pv. gypsophilae revealed the presence of six copies of this insertion-like element, which was designated as IS1327. Only pathogenic strains contained IS1327 and restriction fragment length polymorphism was observed among gypsophilae and beet pathovars of E. herbicola. Nonpathogenic deletion derivatives of pPATH contained fewer copies of IS1327, suggesting its presence in the deleted region. One copy of IS1327 (IS1327-R) was located 2.8 kb downstream from the IS element adjacent to the etz (IS1327-L) in a direct repeat.


The effects of oil sands process-affected water naphthenic acid fraction components on GDF15 secretion in extravillous trophoblast cells.
Exposure to compounds present in petroleum and wastewaters from oil and gas extraction sites in the Alberta Oil Sands Region can impair reproductive health. It has been established that acid extractable organics found in oil sands process-affected water (OSPW) such as naphthenic acids (NA-fraction components; NAFC) can adversely affect reproductive outcomes. We have shown that NAFC exposure results in a significant upregulation of GDF15 in placental trophoblasts, a cellular stress marker known to be involved in human embryonic development and necessary for the maintenance of pregnancy. However, little is known regarding the mechanism(s) underlying NAFC-induced increases in GDF15 production during early placentation. The goal of this study was to examine the effects of NAFC exposure on the regulation of critical transcription factors of GDF15 in extravillous trophoblast cells. Of these transcription factors, inflammatory mediators including prostaglandins have been reported to inhibit proliferation and migration of trophoblast cells in vitro. Hence, the secondary goal of this study was to determine whether inflammation mediated through prostaglandin production is critical to GDF15 secretion. HTR-8/SVneo cells were exposed to an NAFC for 6 and 24 h to assess the expression of key transcriptional regulators, GDF15 secretion, and prostaglandin (PGE2) output. Treatment with NAFC (125 mg/L only) significantly increased GDF15 expression and secretion in association with upregulation of the transcription factors KLF4, EGR1, ATF3 and TP53. Similarly, PTGS2 (i.e. COX2) expression and PGE2 output were significantly increased at the same concentration. However, co-treatment with a COX2 selective antagonist (SC236) only partially blocked the NAFC-induced increase in PGE2 output and did not block GDF15 expression or secretion. These findings suggest that while NAFC may affect GDF15 production, it is not exclusively a result of prostaglandin-mediated inflammation. This study provides new insights into the mechanisms by which NAFC may adversely affect placental trophoblast cell function in mammals.


[The conduct of deaconesses during the NS-dictatorship and the efforts to overcome these experiences. A case study on historical research].
The article is an approach to the conduct of nurses organisations and their members during the time of National Socialism as well as the following attempts to come to terms with these events. Both themes are dealt with rarely. The present state of research is outlined. In a case-study, which relies on source material from an archive of a deaconesses mother house and covers the period from 1943 to 1990, central problems are discussed exemplarily. Questions for further research are formulated and methodological problems are discussed. In this connection the special relevance of the analysis of personal files of the nurses is emphasized.


Effects of the use of semipermeable membranes on fluid loss in low-birth-weight premature newborns.
Studies have shown that the application of semipermeable membranes to the skin of premature newborns (NBs) can aid in protecting the skin, reduce disturbances in fluid and electrolyte levels, and decrease neonatal mortality. The aim of this study was to verify the effect of using semipermeable membranes in low-birth-weight preterm newborns (PTNBs). A randomized controlled trial was carried out in the neonatal intensive care unit (NICU) with 42 NBs split evenly into an intervention group (IG), in which semipermeable membranes were used to cover large areas of the skin for the first 7 days of life, and a control group (CG), which received normal care. The variables investigated for the study were weight, hydration status, urinary density, glycemic control, sodium concentration, and daily hydration quota. The following variables displayed significant daily variation: weight, hydration quota, and sodium concentration. Statistically significant individual effects by day and by group were found only for sodium concentration. In the overall analysis of the intersubject effects, sodium concentration, alone, proved to be significant (p = .055). Significant effects by group in relation to the sodium concentration were found, with the IG showing a lower average sodium concentration than the CG. Thus, the use of semipermeable membranes reduced fluid loss in premature NBs in the current study, confirming the findings of previous studies. Guidelines for practice may now be warranted.


Survival and storage stability of encapsulated probiotic under simulated digestion conditions and on dried apple snacks.
The objective of the current study was to explore the probiotics carrier potential of apple dried snacks and improve the survival of probiotics under simulated gastrointestinal conditions. Purposely, the probiotics were encapsulated using two hydrogel materials (sodium alginate and carrageenan) by using encapsulator. Briefly, slices of apple were immersed in solution containing free and encapsulated probiotics and then dried by conventional drying method. The dried apple snack was analyzed for different characteristics (physiochemical and microbiological) during storage. The viability of the free and encapsulated probiotics was accessed in apple snack and under simulated gastrointestinal conditions. Apple snack rich with encapsulated probiotics showed a significant result (p < .05) regarding the survival and stability. The encapsulated probiotics decreased from 9.5 log CFU/g to 8.83 log CFU/g as compared to free probiotics that decreased to 5.28 log CFU/g. Furthermore, encapsulated probiotics exhibited a better stability under simulated gastrointestinal conditions as compared to free. During storage, an increase in phenolic content and hardness was observed while decrease in pH was noted. Results of sensory parameters indicated apple snack as potential and acceptable probiotics carrier.


[Dehydrogenases of the pentose cycle in rat liver peroxisomes].
Subcellular distribution of NADP+-dependent dehydrogenases of pentose phosphate pathway (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) in rat liver was studied, using differential and isopycnic centrifugation. The enzyme activity was detected in the purified peroxisomal fraction as well as in the cytosol. Both dehydrogenases are localized in the peroxisomal matrix. Administration of a hypolipidaemic drug clofibrate increases the amount of both enzymes in peroxisomes. The putative functional role of pentose phosphate cycle dehydrogenases in peroxisomes is discussed.


Rotation of subunits during catalysis by Escherichia coli F1-ATPase.
During oxidative and photo-phosphorylation, F0F1-ATP synthases couple the movement of protons down an electrochemical gradient to the synthesis of ATP. One proposed mechanistic feature that has remained speculative is that this coupling process requires the rotation of subunits within F0F1. Guided by a recent, high-resolution structure for bovine F1 [Abrahams, J. P., Leslie, A. G., Lutter, R. & Walker, J. E. (1994) Nature (London) 370, 621-628], we have developed a critical test for rotation of the central gamma subunit relative to the three catalytic beta subunits in soluble F1 from Escherichia coli. In the bovine F1 structure, a specific point of contact between the gamma subunit and one of the three catalytic beta subunits includes positioning of the homolog of E. coli gamma-subunit C87 (gamma C87) close to the beta-subunit 380DELSEED386 sequence. A beta D380C mutation allowed us to induce formation of a specific disulfide bond between beta and gamma C87 in soluble E. coli F1. Formation of the crosslink inactivated beta D380C-F1, and reduction restored full activity. Using a dissociation/reassembly approach with crosslinked beta D380C-F1, we incorporated radiolabeled beta subunits into the two noncrosslinked beta-subunit positions of F1. After reduction of the initial nonradioactive beta-gamma crosslink, only exposure to conditions for catalytic turnover results in similar reactivities of unlabeled and radiolabeled beta subunits with gamma C87 upon reoxidation. The results demonstrate that gamma subunit rotates relative to the beta subunits during catalysis.


[Ethical aspects of medical thought on the madness in the enlightenment].
The seventeenth century is a period of transition from religious views that are not authentic but dogmatic about demonic influences to the application of scientific and methodological criteria in science. During Enlightenment there was an approach heavily influenced by ethical issues. In this context, there is a rational recognition of the value of man free from the teleological type references. Mental illnesses are treated using scientific criteria. During the seventeenth century clinical interest is also extended to psychosis and not only to neurosis. There are several significant changes in the care of psychiatric patient, and healthcare institutions are improved and increased. Many behaviors are inspired by the values of philanthropy.


Effectively remove printing ink from plastic surface over quaternary ammonium-modified waste cooking oil.
The printing ink on the plastic surface will greatly reduce the quality of recycled plastic products. In this work, quaternary ammonium-modified waste cooking oil (WCOEQ) was fabricated using waste cooking oil, epichlorohydrin, and trimethylamine aqueous solution as raw materials, through ring-opening esterification and quaternary amination reaction. The synthesis conditions of WCOEQ were optimised, and the structure and properties of WCOEQ were characterised by Fourier transform infrared spectroscopy, zeta potential, and 1H NMR. Furthermore, WCOEQ had excellent emulsifying performance, low kraft point, low critical micelle concentration value, good foaming, and stability, which could effectively reduce the surface tension of water, showing application potential in the field of plastic deinking. Importantly, compared with the waste cooking oil without deinking effect, the WCOEQ had an excellent deinking performance on the ink on the plastic surface, and the deinking efficiency could be improved by increasing the concentration of the deinking agent, the deinking temperature, and prolonging the pre-soaking and stirring time. The results of atomic force microscope, energy-dispersive spectroscopy, optical photos, and Leica microscope showed that the roughness changed significantly and the ink molecules were gradually peeling off. This work highlighted the potential of quaternary ammonium-modified waste cooking oil for excellent removal of printing inks on the plastic surface.


Fluoridated Water Modifies the Effect of Breastfeeding on Dental Caries.
Breastfeeding is important for health and development. Yet, the interaction between breastfeeding duration and usage of fluoridated water on caries experience has not been investigated. This study examined exposure to fluoridation as an effect modifier of the association between breastfeeding duration and caries. The 2012 to 2014 national population-based study of Australian children involved parental questionnaires and oral epidemiological assessment. Children were grouped by parent-reported breastfeeding duration into minimal (none or <1 mo), breastfed for 1 to <6 mo, breastfed for 6 to 24 mo, and sustained (>24 mo). Residential history and main water source used for the first 2 y of life were collected to group children into exposed (WF) and nonexposed (NF) to fluoridation. Socioeconomic status, infant formula feeding, and sugar-sweetened beverage (SSB) consumption data were collected. The prevalence and severity of caries in children aged 5 to 6 y were primary outcomes. Multivariable regression models with robust error estimation were generated to compute prevalence ratios (PRs) and mean ratios (MRs) for 3 breastfeeding groups against the reference (breastfed for 6-24 mo). Of the 5- to 6-y-old children, 2,721 were in the WF and 1,737 were in the NF groups. The groups had comparable distributions of socioeconomic factors, infant formula feeding, and SSB consumption. There were U-shape distributions of caries experience among breastfeeding groups, being more pronounced among NF children. Among NF children, the minimal and sustained breastfeeding groups had significantly higher PR (1.4 [1.1-1.9] and 1.8 [1.4-2.4]) and MR (2.1 [1.4-3.3] and 2.4 [1.4-4.1]) than the reference group. However, among the WF children, this association between breastfeeding duration and caries attenuated after adjustment for other factors. The study contributes evidence of a nonlinear (U-shape) association between breastfeeding duration and dental caries. Early life exposure to fluoridated drinking water attenuated the potential cariogenic effect of both lack of and sustained breastfeeding.


Adenine Nucleotide Changes during Cold Acclimation of Winter Rape Plants.
During the first stage of hardening of winter rape plants (Brassica napus L. var. oleifera L., cv. Górczański), marked increase of ATP content in leaves was observed. Lowering the temperature from 5 to 0 C (the second stage of hardening) had no further effect on ATP content. In roots, not capable of hardening, pronounced decrease of ATP content was noted after prolonged exposure to cold. It was found that increased ATP content and higher energy charge in cold-treated leaves were due to light and dark processes.


Girl-trafficking, HIV / AIDS, and the position of women in Nepal.
This article focuses on trafficking of young Nepalese girls and women. Trafficking is an integral part of the social and economic fabric of Nepal, as in other parts of the world. The practice causes intolerable degradation and suffering for the girls and young women involved, who are treated as a commodity. It presents a risk to their physical and mental health, and in particular to their sexual health. The article examines the connections between coercive sex work and HIV infection, and community and government responses to HIV infection among trafficked sex workers. In particular, it considers the current AIDS prevention and control program in Nepal, and criticizes it from the feminist perspective of the authors, who are a Nepalese nurse who has undertaken academic work in New Zealand related to women's health, and a New Zealand feminist academic, who is also a nurse.


NADH:ubiquinone oxidoreductase of Vibrio alginolyticus: purification, properties, and reconstitution of the Na+ pump.
The Na+-activated NADH:ubiquinone oxidoreductase of Vibrio alginolyticus was extracted from the membranes with lauryldimethylamine-N-oxide and purified by two successive anion exchange columns. This preparation, yielding four major and several minor stained bands after SDS-PAGE, retained the NADH-dehydrogenase activity (with menadione as an artificial electron acceptor) and ubiquinone-1 (Q) reductase activity. On further fractionation of the enzyme, the Q-reductase activity essentially disappeared. Chemical analyses revealed the presence of FAD but not FMN, of non-heme iron and of acid-labile sulfur and tightly-bound ubiquinone-8 in the purified Q-reductase preparation. The participation of an iron-sulfur cluster of the [2Fe-2S] type in the electron translocation was demonstrated by the appearance of a typical EPR signal for this prosthetic group after the reduction of Q-reductase with NADH. A strong EPR signal typical for a radical observed upon reduction of the enzyme might arise from the formation of quinone radicals. In the absence of Na+, the path of the electrons apparently ends with the reduction of ubiquinone-1 to the semiquinone derivative which in the presence of O2 becomes reoxidized with concomitant formation of superoxide radicals. In the presence of Na+, these oxygen radicals are not formed and the semiquinone is further reduced to the quinol derivative. These results indicate that the Na+-dependent step in the electron transfer catalyzed by NADH:ubiquinone oxidoreductase is the reduction of ubisemiquinone to ubiquinol. After reconstitution of the purified Q-reductase into proteoliposomes, NADH oxidation by ubiquinone-1 was coupled to Na+ transport with an apparent stoichiometry of 0.5 Na+ per NADH oxidized. The transport was stimulated by valinomycin (+ K+) or by the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP). The transport of Na+ is therefore a primary event and does not involve the intermediate formation of a proton gradient.


Associations of Salivary Total Antioxidant Capacity With Cortical Amyloid-Beta Burden, Cortical Glucose Uptake, and Cognitive Function in Normal Aging.
Determining susceptibility to Alzheimer's disease (AD) in asymptomatic individuals requires from noninvasive, simple, and inexpensive markers that can be easily obtained in primary care settings. While saliva meets all these requirements, there is a lack of evidence linking salivary constituents to in vivo AD pathology in aging. We examined the potential of salivary total antioxidant capacity (TAC) for identifying global cortical amyloid-beta (Aβ) burden, deficits in regional glucose uptake, and poorer cognition in 71 cognitively normal older adults. We further assessed whether salivary TAC-related cognitive performance was associated with higher Aβ load and lower cortical glucose consumption. Linear regression analyses adjusted by age, sex, years of education, and ApoE4 status showed that salivary TAC was associated with slower processing speed and poorer sustained attention, as well as with higher Aβ load and lower glucose metabolism in cortical regions vulnerable to cognitive aging and AD. Results also revealed that lower scores in processing speed and sustained attention were associated with greater Aβ burden and lower regional glucose consumption, respectively. Together, these findings support the use of salivary TAC for preventive screening and detection of cerebral vulnerability to AD. Further research is needed to evaluate the utility of salivary TAC as a clinical marker.


Magnesium ions and opioid agonist activity in streptozotocin-induced hyperalgesia.
Streptozotocin-induced hyperglycemia accompanied by a chronic decrease in the nociceptive threshold is considered a useful model of experimental hyperalgesia. We examined (1) the effect of the opioid receptor agonists and (2) the effect of the magnesium ions (Mg(2+)) on the antinociceptive action of opioid agonists in a diabetic neuropathic pain model. When administered alone, opioid agonists like morphine (5 mg/kg i.p.) and fentanyl (0.0625 mg/kg i.p.), as well as the partial agonist buprenorphine (0.075 mg/kg) had only little effect on streptozotocin-induced hyperalgesia. However, pretreatment with Mg(2+) at a dose of 40 mg magnesium sulfate/kg i.p. markedly enhanced the analgesic activity of all three investigated opioids. Practical aspects of co-administration of magnesium and opioids in diabetic neuropathy are discussed.


Evidence for the occurrence of, and possible physiological role for, cyanobacterial calmodulin.
Phosphate uptake by the blue-green alga Oscillatoria limnetica Lemmerman is stimulated by micromolar concentrations of Ca(2+). The calmodulin antagonists 4-(3-[2(trifluoromethyl)phenylthiazin-10-yl]propyl)-1-piperazine ethanol-HCl and its monofluoro-analog inhibit orthophosphate uptake of Oscillatoria limnetica by over 97% implying involvement of calmodulin in this process. A calmodulin-like protein was quantitated in cell-free extracts from O. limnetica by radioimmunoassay.


Lipid peroxidation, assessed with BODIPY-C11, increases after cryopreservation of stallion spermatozoa, is stallion-dependent and is related to apoptotic-like changes.
Lipid peroxidation (LPO) of stallion spermatozoa was assessed in fresh semen and in samples of the same ejaculates after freezing and thawing. Particular attention was paid to individual differences in the susceptibility to LPO and its possible relationship with freezability. Innate levels of LPO were very low in fresh spermatozoa but increased after thawing, a change that was largely stallion-dependent. The level of LPO in fresh spermatozoa was not correlated with that of the thawed spermatozoa. Negative correlations existed between LPO and intact membranes post-thaw (r=-0.789, P<0.001), and also between LPO and spermatozoa with high mitochondrial membrane potential (Deltapsim) post-thaw (r=-0.689, P<0.001). LPO was also highly and significantly correlated with caspase activity. The correlation between caspase activity in ethidium positive cells and LPO was r=0.772, P<0.001. This LPO is unlikely to represent, per se, a sign of cryopreservation-induced injury, but it is apparently capable of triggering 'apoptotic-like changes' that could result in the sub-lethal cryodamage often seen among surviving spermatozoa.


Peculiarities of molecular events in human glial tumors revealed by serial analysis of gene expression (SAGE).
To enhance glioblastoma (GB) marker discovery we compared gene expression in glioblastoma with human normal brain (NB). Serial analysis of gene expression (SAGE) was used to determine the genes differentially expressed between glioblastoma and human NB by accessing SAGEmap NCBI web site. Of 117 genes with more than 5-fold difference (P less, not similar 0.05) found by comparison of five GB vs. two NB SAGE libraries, 24 had an increased expression in GB. High expression of 10 genes in GB as well as in GB cell lines suggested that expression in the bulk tumors originated from transformed cells. Since the highest expression levels of these 24 genes were mostly found in GB, they can be viewed as molecular markers in the analysis of malignant progression of astrocytic tumors.


The "unclear problem" category: an analysis of its patient and dispatch characteristics and its trend over time.
An effective emergency medical dispatch process is vital to provide appropriate prehospital care to patients. It increases patient safety and ensures the sustainable use of medical resources. Although Copenhagen has a sophisticated emergency medical services (EMS) system with a significant focus on public welfare, more than 10% of emergency cases are still being categorized as an "unclear problem category" (UPC) and are thus not categorized as "symptom-specific". Therefore, the objective of this research is to gain a better understanding of the patient and dispatch characteristics of emergency cases categorized as "unclear". This register-based study based on medical emergency cases data describes patient and dispatch characteristics of emergency cases categorized as "unclear" through the use of numbers and proportions. Moreover, these cases were compared to non UPC cases. Use of UPC was stratified by month to determine the impact of alerting medical dispatchers to reduce its use. From 296,398 included cases UPC accounted for 11.4% of the cases. The median age of those triaged with the UPC was 66 years vs 58 years for individuals triaged with other symptom-specific categories. Moreover, after having been triaged with the UPC, 9,661 (34.7%) of the dispatched EMS vehicles ended up being cancelled. Sensitizing medical dispatchers about the use of the UPC likely contributed to the decreased use of the UPC over time. The UPC has different dispatch characteristics than the symptom-specific categories, with potential negative effects on the medical dispatch process. Moreover, the median age of individuals triaged with the UPC is higher than those triaged with symptom-specific categories. Nonetheless, the use of the UPC decreased throughout the study period after the medical dispatchers were alerted about the implications of its use.


Primula obconica--is contact allergy on the decline?
Primula obconica, a member of the Primulaceae family, was introduced to Britain from China in 1880. P. obconica cultivars, which are reputed to contain less primin, have been developed over the past number of years in an attempt to reduce the incidence of allergic contact dermatitis. Primin (2-methoxy-6-pentyl-1,4-benzoquinone) is the main sensitizer, although other allergens have been postulated. We believe the incidence of primula allergic contact dermatitis has fallen since the introduction of primin-free P. obconica into the European market and thus the aims of this study were twofold. First, to determine whether the incidence of primula allergic contact dermatitis was truly on the decline and, second, to confirm the presence of primin-free P. obconica in the UK. We surveyed the incidence of primula allergic contact dermatitis in the UK and compared the incidence in the period between 1995 and 2000 with a subsequent follow-up study looking at the incidence for 2002. The results showed a significant fall in primin-positive patch tests from 1995 to 2000. The follow-up results for 2002 showed a further reduction in the number of primin-positive patch tests. The yearly incidence of contact allergy to primin has fallen from 0.785% in 1995/1996 to 0.429% in 2002. This downward trend was statistically significant (P = 0.001). A telephone survey of UK seed suppliers and selected plant retailers was also undertaken to clarify what types of P. obconica were available for sale and to assess suppliers' and retailers' knowledge of the primin-free varieties. This survey showed that 50% of suppliers were selling primin-free varieties but that the majority of surveyed retailers were not currently selling any variety of P. obconica. Our study suggests that although the yearly incidence of contact allergy to primin has fallen significantly over the past 8 years, it is still an important allergen, and thus its inclusion in the standard series remains justified for the foreseeable future.


Echocardiographic Assessment of Biventricular Function in 249 Patients During the Peri-Extracorporeal Membrane Oxygenation Period.
At a quaternary care center that regularly performs and cares for patients undergoing extracorporeal membrane oxygenation (ECMO), a database of all adult patients since 2009 was assembled with echocardiographic parameters of left (LV) and right (RV) ventricular function. From the database, 175 venoarterial (VA) and 74 venovenous (VV) ECMO patients were analyzed to compare the decannulation echocardiographic assessments of biventricular function before, during, and after ECMO in survivors and nonsurvivors. Retrospective chart review-based study. A single quaternary care center. All adult patients who received ECMO from 2009 to 2017 with both survival data and echographic studies were included in this retrospective study. When indicated, transthoracic and transesophageal echocardiograms were performed for ECMO patients. The results of these echocardiograms were reviewed retrospectively, and differences between survivors and nonsurvivors were examined. A retrospective chart review of before, during cannulation, and after decannulation echocardiographic assessments of biventricular function was performed. On average, VA ECMO survivors had better post-decannulation LV function than did nonsurvivors by a full clinical grade-mild impairment versus moderate impairment (p < 0.001). RV function comparison was similar-mild impairment in survivors versus moderate impairment in nonsurvivors (p = 0.007). LV and RV function before and during ECMO in survivors was not different from that of nonsurvivors. The change in biventricular function from before to after cannulation and during cannulation to post-cannulation was approximately a full clinical grade better in survivors than nonsurvivors (p < 0.01 in all cases). In VV ECMO patients, post-decannulation RV function was significantly worse in nonsurvivors (moderate dysfunction vs borderline normal function) (p = 0.013). Retrospective chart review of 249 patients suggests that echocardiographic assessment of biventricular function before ECMO cannulation is not prognostic in VA or VV ECMO patients. Post-decannulation assessment of biventricular function may aid in triaging more "at risk" patients because nonsurvivors have significantly worse biventricular function after decannulation. The failure to improve biventricular function from the before to after ECMO phases and the during to after ECMO phases is concerning for a poor prognosis.


TusA Is a Versatile Protein That Links Translation Efficiency to Cell Division in Escherichia coli.
To enable accurate and efficient translation, sulfur modifications are introduced posttranscriptionally into nucleosides in tRNAs. The biosynthesis of tRNA sulfur modifications involves unique sulfur trafficking systems for the incorporation of sulfur atoms in different nucleosides of tRNA. One of the proteins that is involved in inserting the sulfur for 5-methylaminomethyl-2-thiouridine (mnm5s2U34) modifications in tRNAs is the TusA protein. TusA, however, is a versatile protein that is also involved in numerous other cellular pathways. Despite its role as a sulfur transfer protein for the 2-thiouridine formation in tRNA, a fundamental role of TusA in the general physiology of Escherichia coli has also been discovered. Poor viability, a defect in cell division, and a filamentous cell morphology have been described previously for tusA-deficient cells. In this report, we aimed to dissect the role of TusA for cell viability. We were able to show that the lack of the thiolation status of wobble uridine (U34) nucleotides present on Lys, Gln, or Glu in tRNAs has a major consequence on the translation efficiency of proteins; among the affected targets are the proteins RpoS and Fis. Both proteins are major regulatory factors, and the deregulation of their abundance consequently has a major effect on the cellular regulatory network, with one consequence being a defect in cell division by regulating the FtsZ ring formation.IMPORTANCE More than 100 different modifications are found in RNAs. One of these modifications is the mnm5s2U modification at the wobble position 34 of tRNAs for Lys, Gln, and Glu. The functional significance of U34 modifications is substantial since it restricts the conformational flexibility of the anticodon, thus providing translational fidelity. We show that in an Escherichia coli TusA mutant strain, involved in sulfur transfer for the mnm5s2U34 thio modifications, the translation efficiency of RpoS and Fis, two major cellular regulatory proteins, is altered. Therefore, in addition to the transcriptional regulation and the factors that influence protein stability, tRNA modifications that ensure the translational efficiency provide an additional crucial regulatory factor for protein synthesis.


Assessment of the fear of COVID-19 and its impact on lung cancer screening participation among the Korean general population.
We aimed to assess the fear of COVID-19 and how much it affected the behaviors of the general population towards cancer screening. The Korean National Cancer Screening Survey is an annual population-based, cross-sectional survey to investigate cancer screening rates of five major malignancies. We extracted data on 3,557 cancer-free respondents aged ≥40 years in 2020, including sociodemographic characteristics, comorbidities, family history of cancer, self-perceived general health status, attitudes towards screening, and fear of COVID-19 compared with lung cancer. We collected information on health check-ups participation including cancer screening with or without schedule during the pandemic and analyzed the participation rate according to the degree of fear of COVID-19. Among 3,557 respondents, 1,066 (29.97%) people were more worried by COVID-19 than by lung cancer. 2,392 (67.25%) did not participate in health check-ups, of which 573 (24.0%) had a schedule for health check-ups but did not receive. We observed a significant increase (P<0.05) in the proportion of non-participation with schedule when the fear of COVID-19 exceeds lung cancer. In multivariate logistic analysis, the respondents with more fear of COVID-19 compared with lung cancer showed decreased likelihood of attendance in health check-ups (OR, 0.84; 95% CI: 0.71-0.98). A considerable proportion of the general population perceived more fear of COVID-19 than lung cancer, which significantly hampered their engagement in regular medical check-ups including cancer screening. This finding highlights the need for providing appropriate information to the target population of lung cancer screening to minimize disruption in cancer prevention activities.


Black-White Inequities in Kidney Disease Mortality Across the 30 Most Populous US Cities.
To examine city-level kidney disease mortality rates and Black:White racial inequities for the USA and its largest cities, and to determine if these measures changed over the past decade. We used National Vital Statistics System mortality data and American Community Survey population estimates to calculate age-standardized kidney disease mortality rates for the non-Hispanic Black (Black), non-Hispanic White (White), and total populations for the USA and the 30 most populous US cities. We examined two time points, 2008-2013 (T1) and 2014-2018 (T2), and assessed changes in rates and inequities over time. Racial inequities were measured with Black:White mortality rate ratios and rate differences. Kidney disease mortality rates varied from 2.5 (per 100,000) in San Diego to 24.6 in Houston at T2. The Black kidney disease mortality rate was higher than the White rate in the USA and all cities studied at both time points. In T2, the Black mortality rate ranged from 7.9 in New York to 45.4 in Charlotte, while the White mortality rate ranged from 2.0 in San Diego to 18.6 in Indianapolis. At T2, the Black:White rate ratio ranged from 1.79 (95% CI 1.62-1.99) in Philadelphia to 5.25 (95% CI 3.40-8.10) in Washington, DC, compared to the US rate ratio of 2.28 (95% CI 2.25-2.30). Between T1 and T2, only one city (Nashville) saw a significant decrease in the Black:White mortality gap. The largest US cities experience widely varying kidney disease mortality rates and widespread racial inequities. These local data on racial inequities in kidney disease mortality can be used by city leaders and health stakeholders to increase awareness, guide the allocation of limited resources, monitor trends over time, and support targeted population health strategies.


The Effect of Simulated In Vitro Digestion on Biological Activity of Viburnum opulus Fruit Juices.
In the present study, an in vitro digestion method has been used to assay the influence of the physiological conditions in the mouth, stomach, and intestine on the stability and activity in different cell models of the main phenolic compounds from Viburnum opulus fresh juice (FJ), phenolic-rich juice (PJ), and the bioavailable fractions (DFJ and DPJ). The data obtained indicate that the V. opulus samples achieved after in vitro digestion had an influence on cellular glucose and lipid metabolism. The bioavailable fraction of both digested juices stimulated glucose uptake and decreased lipid accumulation by L6 myoblasts and HepG2 hepatocytes. Both DFJ and DPJ reduced the secretion of inflammatory cytokines by 3T3-L1 adipocytes: interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Simultaneously, DFJ and DPJ enhanced oxidative stress in MIN6 cells and decreased glucose-stimulated insulin secretion (GSIS). UPLC-MS analysis revealed qualitative and quantitative changes in hydroxycinnamic acids. In particular, the content of chlorogenic acid decreased drastically; its content in the bioavailable fraction was almost 7 times and 30 times lower than in the FJ and PJ, respectively. Our results suggested that although the phenolic compounds of V. opulus juices undergo transformation during digestion, they are still potent antioxidant agents with biological activity.


Treating congenital hypothyroidism: maximum age limit up to which a socially compatible child is expected.
It is has been known that the treatment with thyroxine in hypothyroid children results in normal physical growth, but mental development is less predictable. A comparative study of developmental milestones, anthropometry and intelligence quotient (IQ) in congenital hypothyroid children starting thyroxine therapy before and after 6 months of age was done. Forty-eight congenital hypothyroid children were enrolled. They were given thyroxine and were followed up. In 18 cases who received thyroxine at or before 6 months of age their anthropometric measurements in majority were 50th percentile or above. Their mental age was deficient on an average by 5 months as compared to chronological age and their IQ was above 85. In rest of 30 cases where thyroxine was started after 6 months of age anthropometric measurements in majority were less than 50th percentile. Their mental age was deficient on an average by 14 months with IQ ranging between 50 and 70. Thyroxine therapy before 6 months of age considerably improved mental function so that they are educable. On the contrary those with late thyroxine therapy showed mild to moderate mental retardation and need special care. In developing country like ours if treatment of hypothyroidism can be started even by 6 months of age considerable brain function can be salvaged so that they can attain a self supportive life.


Selected Factors of Psychological Reactions Among Polish Respondents to the Outbreak of Covid-19 Pandemic.
COVID-19 global pandemic has had a profound impact on the quality of life and mental state of the community. The aim of the study was the preliminary assessment of social isolation on individual mental state due to SARS-CoV-2 pandemic. A detailed online questionnaire was conducted in the period from March 2020 to March 2021 among 587 persons from Poland. Most respondents (46.2%) expect a professional psychological support. This is followed by expectations of psychoeducation (37%) and understanding (34.4%). During the pandemic, most people deal with stress by watching TV series It is a form of escape into a different reality. Obtained results demonstrate that place of residence does not corelate with fear of coronavirus. Statistically significant differences occurred when answers regarding aspects of living during pandemic were checked against gender of respondents. Women experience pandemic-related anxiety more severely than men. This research highlights that psychological care should be part of the wider health care system in the time of crisis.


The Trend of β3-Adrenergic Receptor in the Development of Septic Myocardial Depression: A Lipopolysaccharide-Induced Rat Septic Shock Model.
Septic shock with low cardiac output is very common in children. However, the mechanism underlying myocardial depression is unclear. The role of β3-AR in the development of myocardial depression in sepsis is unknown. In the present study, we generated an adolescent rat model of hypodynamic septic shock induced by lipopolysaccharide (LPS). Neonatal cardiomyocytes were also treated with LPS to mimic myocardial depression in sepsis, which was confirmed via an in vivo left ventricular hemodynamic study, and measurements of contractility and the Ca2+ transient in isolated adolescent and neonatal cardiomyocytes. After 16 h of LPS treatment, cultured neonatal cardiomyocytes showed a diminished Ca2+ transient amplitude associated with an increase in the β3-AR level. With the addition of a β3-AR agonist, the Ca2+ transient in LPS-treated neonatal rat cardiomyocytes gradually decreased over time; such a change was absent in cells treated with nitric oxide synthase (NOS) inhibitors prior to treatment with a β3-AR agonist. In adolescent rats with septic myocardial depression, cardiac function declined as indicated by decreased MAP, dP/dtmax, and dP/dtmix for 6 h after LPS injection; however, the β3-AR level first increased 2 h after LPS treatment and then decreased 6 h after LPS treatment in the absence of exogenous catecholamines. The results indicate that, in vitro, at the cellular level β3-AR may be involved in the development of myocardial depression (Ca2+ transient depression) in sepsis through NOS signaling pathways; however, in vivo, a complicated mechanism for modulating β3-AR may exist.


The Effects of Anthocyanin-Rich Bilberry Extract on Transintestinal Cholesterol Excretion.
Hypercholesterolemia is one of the modifiable and primary risk factors for cardiovascular diseases (CVD). Emerging evidence suggests the stimulation of transintestinal cholesterol excretion (TICE), the nonbiliary cholesterol excretion, using natural products can be an effective way to reduce CVD. Bilberry (Vaccinium myrtillus L.) has been reported to have cardioprotective effects by ameliorating oxidative stress, inflammation, and dyslipidemia. However, the role of bilberry in intestinal cholesterol metabolism is not well understood. To examine the effects of bilberry in intestinal cholesterol metabolism, we measured the genes for cholesterol flux and de novo synthesis in anthocyanin-rich bilberry extract (BE)-treated Caco-2 cells. BE significantly decreased the genes for cholesterol absorption, i.e., Niemann-Pick C1 Like 1 and ATP-binding cassette transporter A1 (ABCA1). In contrast, BE significantly upregulated ABCG8, the apical transporter for cholesterol. There was a significant induction of low-density lipoprotein receptors, with a concomitant increase in cellular uptake of cholesterol in BE-treated cells. The expression of genes for lipogenesis and sirtuins was altered by BE treatment. In the present study, BE altered the genes for cholesterol flux from basolateral to the apical membrane of enterocytes, potentially stimulating TICE. These results support the potential of BE in the prevention of hypercholesterolemia.


Role of the specialist in the treatment of asthma.
The preponderance of literature supports the efficacy of specialist care for asthma. Not every patient with asthma needs to be treated by a specialist, however. An optimal health care delivery model for asthma (i.e. one that provides high quality care that is cost effective) requires some mix of primary and specialty services. A tiered model of care in which the primary care physician acts as the first point of contact and decision-maker with regard to referral and that includes asthma specialists, including allergists, pulmonologists, and other health care professionals with expertise in asthma, appears to be a reasonable solution. The number of studies that compare various models for organizing asthma care is limited, however. Thus, further research is needed to determine how best to align the roles of primary care physicians, allied health professionals, and subspecialists in order to ensure seamless communication and cost-effective care that is targeted to individual patient needs.


Recovery of zero-grade muscles in the zone of partial preservation in motor complete quadriplegia.
This prospective study was designed to demonstrate root level recovery in the zone of preservation by examining muscles with an initial strength of grade 0/5 in 32 motor complete (Frankel A and B) patients who had cervical spinal cord injury at the C4 through C7 levels. The biceps (C5), extensor carpi radialis (C6), triceps (C7), and flexor digitorum profundus (C8) muscles were used as key muscles when their strength at the initial manual muscle test, which was performed between three and seven days postinjury, was grade 0/5 and the muscle innervated by the cord segment directly rostral to that innervating the key muscle (grade 0/5) was grade greater than or equal to 3/5. If the biceps muscle was used, C4 pin sensation was required to be normal. Further manual muscle tests were performed weekly for four weeks, and then at 2, 3, 6, and 12 months postinjury. None, 6%, 17%, 35%, and 43% of the patients recovered to grade greater than or equal to 3/5 by 1, 2, 3, 6, and 12 months postinjury, respectively. It was also noted that in 86% of our patients, improving to grade greater than or equal to 1/5 by one month postinjury was a predictor of recovering to grade greater than or equal to 3/5 by 12 months postinjury (p less than .002). Similarly, in 100% of our patients, improving to grade greater than or equal to 2/5 by three months postinjury was a predictor of recovering to grade greater than or equal to 3/5 by 12 months postinjury (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)


Reversal of direct oral anticoagulants: Highlights from the Anticoagulation Forum guideline.
The 2019 guideline from the Anticoagulation Forum provides clear instructions on how to use 2 agents for reversing the effects of direct oral anticoagulants (DOACs): idarucizumab for dabigatran-associated bleeding and andexanet alfa for bleeding associated with rivaroxaban and apixaban. The guideline also discusses off-label use of andexanet alfa for bleeding associated with edoxaban and betrixaban and the use of hemostatic agents such as activated prothrombin complex concentrate and 4-factor prothrombin complex concentrate. Lastly, it offers approaches for building and managing stewardship programs at the health system level.


Modeling semivolatile organic aerosol mass emissions from combustion systems.
Experimental measurements of gas-particle partitioning and organic aerosol mass in diluted diesel and wood combustion exhaust are interpreted using a two-component absorptive-partitioning model. The model parameters are determined by fitting the experimental data. The changes in partitioning with dilution of both wood smoke and diesel exhaust can be described by two lumped compounds in roughly equal abundance with effective saturation concentrations of approximately 1600 microg m(-3) and approximately 20 microg m(-3). The model is used to investigate gas-particle partitioning of emissions across a wide range of atmospheric conditions. Under the highly dilute conditions found in the atmosphere, the partitioning of the emissions is strongly influenced by the ambient temperature and the background organic aerosol concentration. The model predicts large changes in primary organic aerosol mass with varying atmospheric conditions, indicating that it is not possible to specify a single value for the organic aerosol emissions. Since atmospheric conditions vary in both space and time, air quality models need to treat primary organic aerosol emissions as semivolatile. Dilution samplers provide useful information about organic aerosol emissions; however, the measurements can be biased relative to atmospheric conditions and constraining predictions of absorptive-partitioning models requires emissions data across the entire range of atmospherically relevant concentrations.


The consequences of direct versus indirect species interactions to selection on traits: pollination and nectar robbing in Ipomopsis aggregata.
Organisms experience a complex suite of species interactions. Although the ecological consequences of direct versus indirect species interactions have received attention, their evolutionary implications are not well understood. I examined selection on floral traits through direct versus indirect pathways of species interactions using the plant Ipomopsis aggregata and its pollinators and nectar robber. Using path analysis and structural equation modeling, I tested competing hypotheses comparing the relative importance of direct (pollinator-mediated) versus indirect (robber-mediated) interactions to trait selection through female plant function in 2 years. The hypothesis that provided the best fit to the observed data included robbing and pollination, suggesting that both interactors are important in driving selection on some traits; however, the direction and intensity of selection through robbing versus pollination varied between years. I then increased my scope of inference by assessing traits and species interactions across more years. I found that the potential for temporal variation in the direction and intensity of selection was pronounced. Taken together, results suggest that assessing the broader context in which organisms evolve, including both direct and indirect interactions and across multiple years, can provide increased mechanistic understanding of the diversity of ways that animals shape floral and plant evolution.


Takayasu's disease. A report of 3 cases.
Three patients with Takayasu's disease are described. In 2 cases aortography demonstrated an occlusion of the great vessels at the origin of the arch of the aorta. In 1 patient there was concomitant aneurysmal dilatation of the brachiocephalic trunk. Common and internal carotid artery stenosis occurred in 1 patient and was associated with hemiplegia and blindness. All 3 patients had constitutional symptoms and signs of the disease as well as markedly elevated erythrocyte sedimentation rates; 2 patients had moderate clinical responses to steroid administration in the short term and 1 developed bilateral calf vein thrombosis, which responded satisfactorily to conservative management.


The refined structure of bacteriophage MS2 at 2.8 A resolution.
Bacteriophage MS2 is an icosahedral virus with 180 copies of a coat protein forming a shell around a single-stranded RNA molecule. The coat protein subunits form a lattice with the triangulation number T = 3. The coat protein has a fold which is different from the fold of all other viral coat proteins so far known. It consists of a five-stranded beta sheet facing the inside of the particle, and a hairpin and two helices on the outside. The crystal structure has been refined at 2.8 A resolution. The final R-factor was 0.189 for reflections with F > 2 sigma, and the root-mean-square deviation from idealized bond lengths and bond angles was 0.015 A and 2.9 degrees, respectively. The three chemically identical conformers A, B and C are largely similar. The B conformer has a unique conformation in one loop, which is involved in 5-fold interactions, while the A and C conformers, which are involved in the quasi-6-fold contacts, are similar throughout the structure. One cis-proline has been identified in the B conformer but the corresponding prolines in A and C are of the trans isomer. This residue is conserved within small RNA coliphages and it is proposed that this isomerization enables a less elongated loop (FG) around the 5-fold axis, thus creating a channel. The extensive dimer contact supports the idea of dimers as initial building blocks. An assembly pathway is proposed where five dimers converge into a pentamer and 12 pentamers are linked together with free dimers creating a complete particle.


Ultrastructure of a bronchial mucoepidermoid tumour of a seven-year-old boy.
A bronchial mucoepidermoid tumour of a 7-year-old boy was histopathologically and electronmicroscopically studied. The light microscopy revealed an epidermoid structure in whose cells an intracellular and extracellular accumulation of acid mucopolysaccharides occurred. The origin of this transformation seems to be located within the cells of a glandular duct. Electron microscopy pointed out the main characteristics of epidermoid cells (tonofibrils, cellular junctions of desmosomal type) and the secretory transformation by the large development of polyribosomes, of the rough endoplasmic reticulum and of dilated cisternae filled with the secretory product. The prolonged evolution with repeated obstructive pneumonitides, the proliferation after partial endoscopic resection, the absence of mitoses and invasion, as well as the late evolution of the case, suggested the semi-malignancy of this tumour and the impossibility of its consideration as a mucoepidermoid carcinoma. The hypothesis of a unique class of tumours with different secretory possibility including carcinoids, cylindromas (adenocystic tumours) and mucoepidermoid tumours is sustainable.


Mitosis and apoptosis: how is the balance set?
Anti-mitotic agents are used extensively during cancer chemotherapy. These agents target microtubules and thus block mitotic progression by activating the spindle assembly checkpoint. Following a prolonged mitotic arrest, cells either die in mitosis via apoptosis, or exit mitosis without dividing and survive, a process known as slippage. What dictates the balance between these two fates is unclear, but recent advances highlight the importance of the pro-survival Bcl2 family, with Mcl1 degradation emerging as a key determinant of mitotic cell fate. Here we review these advances, with a view towards identifying how the balance between apoptosis and slippage can be tipped in favour of death. This in turn may open up new opportunities to sensitize cancer cells to anti-mitotic agents.


Crystalloid material in cells of the murine mononuclear phagocyte system.
In an attempt to throw further light on the nature and distribution of crystalloid material in macrophages, tissues from a variety of locations in 9 normal adult mice of 36-46 g body weight were studied by light and electron microscopy. Crystalloid inclusions were widely distributed in mononuclear phagocytic cells, being present in macrophages of the bone marrow, spleen, lung and ileum and in the Kupffer cells of the liver. They were not observed in the macrophages of the thymus, parotid lymph node or skin nor were they seen within the lymphatic nodules of Peyer's patches. The observed distribution of crystalloid material seems consistent with its suggested origin from granulocyte breakdown.


CadA, the Cd2+-ATPase from Listeria monocytogenes, can use Cd2+ as co-substrate.
CadA is a membrane protein of the P-type ATPase family which is the major determinant of the resistance to Cd2+ in Listeria monocytogenes. During its catalytic cycle, CadA undergoes auto-phosphorylation from ATP at Asp398, which allows Cd2+ translocation across the membrane. In the reverse mode, Asp398 is phosphorylated from Pi. From the data obtained so far, the CadA catalytic mechanism is similar to that proposed for the sarcoplasmic reticulum Ca2+-ATPase, the model of the P-type ATPase family. We show here that CadA is sensitive to two different ranges of Cd2+ concentration. The 0.1-10 microM range of added CdCl2 corresponds to Cd2+ binding at the transport site of unphosphorylated CadA which induces the reaction of the enzyme with ATP and impairs its reaction with Pi. The 0.1-1 mM range of added CdCl2 could correspond to Cd2+ binding to the transport site accessible from the extracellular medium. In addition, although it is widely accepted that the actual substrate of P-type ATPases is the MgATP complex, we show here that CadA can also perform its cycle in the absence of Mg2+, using CdATP in the place of MgATP at the catalytic site.


The cellular immune response to cell-associated and cell-free cytomegalovirus (CMV) antigens after primary CMV-infection in non-immunocompromised hosts: development and maintenance of CMV-latency and its influence on immunocompetence.
Development and maintenance of cellular immunity to cell-associated CMV-antigens (CMVFF) was investigated in non-immunocompromised hosts during the first year (group I, n = 11) and 1 to 5 years (group II, n = 9) after a symptomatic primary CMV infection, as well as in healthy CMV-seropositive controls without a history of CMV disease (group III, n = 28). During the acute phase (0-2 months) of a primary CMV-infection CMVFF-induced lymphocyte proliferation was severely decreased compared to that in the post-illness phase (5-12 months), and to that in groups II and III. After the reconvalescent period (3-4 months) it gradually increased to levels seen in group III. In group II higher responses to CMVFF were found than in group III or during the post-illness phase of a primary infection. In general CMV-virion induced lymphocyte proliferation showed the same pattern of development as the CMVFF-induced lymphocyte response, but during the acute phase (0-2 months) a lack of correlation was observed between lymphocyte proliferation to CMVFF and CMV-virions. Lymphocyte proliferation to PHA, Con A, allogeneic lymphocytes and recall antigens were severely depressed in the acute phase of a primary CMV-infection and restored gradually to levels seen in groups II and III, with the exception of Con A-reactivity. The latter response remained depressed when compared to healthy seropositive controls, not only during the post-illness period, but also later on (group II).


Identification of an immunodominant epitope within the capsid protein of hepatitis C virus.
We have isolated cDNA clones from the 5' end of the Hutchinson strain of hepatitis C virus. Sequences encoding various segments of the HCV structural region were fused to the gene for glutathione S-transferase and analyzed for the expression of hepatitis C virus-capsid fusion proteins. With a set of these fusion proteins, both human and chimpanzee immune responses to capsid were studied. An immunodominant epitope was located within the amino-terminal portion of capsid that is preferentially recognized by antibodies in both human and chimpanzee hepatitis C virus-positive sera. In addition, analyses of sequential serum samples taken from humans and chimpanzees with either chronic or apparently self-limited infections revealed that a strong anti-capsid response develops rapidly after onset of infection.


Models of latent tuberculosis: their salient features, limitations, and development.
Latent tuberculosis is a subclinical condition caused by Mycobacterium tuberculosis, which affects about one-third of the population across the world. To abridge the chemotherapy of tuberculosis, it is necessary to have active drugs against latent form of M. tuberculosis. Therefore, it is imperative to devise in vitro and models of latent tuberculosis to explore potential drugs. In vitro models such as hypoxia, nutrient starvation, and multiple stresses are based on adverse conditions encountered by bacilli in granuloma. Bacilli experience oxygen depletion condition in hypoxia model, whereas the nutrient starvation model is based on deprivation of total nutrients from a culture medium. In the multiple stress model dormancy is induced by more than one type of stress. In silico mathematical models have also been developed to predict the interactions of bacilli with the host immune system and to propose structures for potential anti tuberculosis compounds. Besides these in vitro and in silico models, there are a number of in vivo animal models like mouse, guinea pig, rabbit, etc. Although they simulate human latent tuberculosis up to a certain extent but do not truly replicate human infection. All these models have their inherent merits and demerits. However, there is no perfect model for latent tuberculosis. Therefore, it is imperative to upgrade and refine existing models or develop a new model. However, battery of models will always be a better alternative to any single model as they will complement each other by overcoming their limitations.


Palladium(0) catalyzed 2,2'-bipyrrole syntheses.
Several 2-iodopyrroles are used in Pd(0) catalyzed homocoupling reactions at room temperature in the presence of water to efficiently synthesize 2,2'-bipyrroles. These 2,2'-bipyrroles are strongly luminous materials and have high fluorescence quantum yields.


Demise of Polymerase Chain Reaction/Electrospray Ionization-Mass Spectrometry as an Infectious Diseases Diagnostic Tool.
Although there are several US Food and Drug Administration (FDA)-approved/cleared molecular microbiology diagnostics for direct analysis of patient samples, all are single target or panel-based tests. There is no FDA-approved/cleared diagnostic for broad microbial detection. Polymerase chain reaction (PCR)/electrospray ionization-mass spectrometry (PCR/ESI-MS), commercialized as the IRIDICA system (Abbott) and formerly PLEX-ID, had been under development for over a decade and had become CE-marked and commercially available in Europe in 2014. Capable of detecting a large number of microorganisms, it was under review at the FDA when, in April 2017, Abbott discontinued it. This turn of events represents not only the loss of a potential diagnostic tool for infectious diseases but may be a harbinger of similar situations with other emerging and expensive microbial diagnostics, especially genomic tests.


Efficacy of adding activity of daily living simulation training to traditional pulmonary rehabilitation on dyspnea and health-related quality-of-life.
Exercise modalities offered as part of traditional pulmonary rehabilitation (PR) do not always translate to successful performance of Activities of Daily Living (ADL) and may hinder gains in patient's sense of well-being. Data is lacking on the efficacy of incorporation of ADL-focused training in PR. The aim of this study was to determine the impact of incorporation of ADL simulation and energy-conservation training in PR as part of a quality-initiative on health-related-quality-of-life (HRQOL), dyspnea, fatigue, and six-minute-walk-test among PR patients. Retrospective study where medical records of consecutive patients with chronic respiratory diseases who completed PR from 2016 to 2018 were reviewed. ADL-focused energy-conservation training was added to traditional PR in September 2017 by replacing three monthly sessions of traditional PR with energy-conservation training as a quality-improvement-initiative. The change from baseline on HRQOL measured by COPD assessment test (CAT), six-minute-walk-test, MMRC dyspnea score and CRQ-dyspnea and CRQ-fatigue questionnaires, were compared between patients who received traditional PR versus energy-conservation PR. Within and between group differences were calculated via repeated-measures ANOVA. The baseline characteristics of 91 patients who participated in traditional PR versus energy-conservation PR (n = 85) were similar (mean age = 68.6±10.4 years, 49% men). While improvement from baseline was similar and significant for both groups for MMRC, CRQ-dyspnea and CRQ-fatigue scores, and six-minute walk test, patients who participated in energy-conservation PR had significantly higher improvement in HRQOL CAT scores (p = 0.01) than those who completed traditional PR. Tailoring patient's training programs to include energy-conservation training exercises specific to ADL in PR improved HRQOL over traditional PR in patients with chronic respiratory diseases despite no significant change in functional status. Future randomized-controlled trials will be needed to confirm these initial findings.


Isolation and characterization of a tomato Acid phosphatase complementary DNA associated with nematode resistance.
The tomato (Lycopersicon esculentum) acid phosphatase-1 (Apase-1(1), EC 18.104.22.168) isozyme variant, genetically linked to the root-knot nematode resistance locus (Mi) on chromosome 6, has been purified by a rapid procedure from tomato cell suspension cultures. Peptide fragments of the purified enzyme were generated from trypsin and Lys-C endoprotease digests and separated by reverse-phase high-performance liquid chromatography. Amino acid sequences derived from the purified peptide fragments represented >50% of the total amino acid content of the protein and enabled the construction of degenerate oligonucleotide probes that were used to screen a tomato cell culture complementary DNA library. Clones corresponding to full-length coding sequences for Apase-1 have been isolated and sequenced. Southern blot analysis of DNA isolated from a number of tomato cultivars shows that the Apase-1(1) gene (aps1) is present at one copy per genome and that genotypes containing the aps1(1) allele have restriction fragment length polymorphisms that distinguish them from cultivars having the aps1(+) allele. Segregation analysis demonstrates that the restriction fragment length polymorphisms are associated with the aps1 locus. Tomato Apase-1(1) is also found to have significant homology at the amino acid sequence level to a class of vegetative storage proteins characterized in soybean.