Understanding the mechanisms through which women's group community participatory intervention improved maternal health outcomes in rural Malawi: was the use of contraceptives the pathway?
Women's group intervention is a community based initiative through which rural women form groups, meet regularly to discuss maternal health issues affecting them, and come up with locally available solutions. This intervention has been associated with reduced maternal and neonatal mortality in limited resource settings. Nevertheless, the mechanisms through which women's groups influence maternal health outcomes are uncertain. Because contraception reduces the risk of maternal mortality and women's groups also tackled this issue, we speculated that contraceptive use might be the pathway. Consequently, this study investigated whether participation in women's groups was associated with contraceptive use in Malawi. We examined the use of contraceptives between women who participated in women's groups and those who did not through a community-based cross-sectional study in Mchinji, Malawi. The study involved 3,435 women of reproductive age (15-49 years) who were recruited using a multistage sampling approach. Members (treated) and non-members (control) of women's groups were matched on observed covariates using propensity scores and the counterfactual for the treated individuals was estimated. Crude analysis revealed that women's groups improved uptake of contraceptives by 26% (odds ratio (OR)=1.26; 95% confidence interval (CI)=1.03-1.56; p=0.024). However, using the matched data, uptake of contraceptives was almost the same among members and non-members of women's groups. More precisely, the likelihood of using contraceptives was not significantly different between the members and non-members of women's groups (OR=1.00; 95% CI=0.81-1.24; p=0.991). There is insufficient evidence of an association between participation in women's groups and contraceptive use among rural Malawian women. The implication is that contraception was not the mechanism through which women's groups contributed to reduced maternal mortality in Malawi. Because the effects of community interventions are usually comprehensive and sometimes difficult to demonstrate, ethnographic studies should be considered in the evaluation of women's groups and other related interventions.


The relationship between the cancer cell and the oocyte.
What causes cancer? To date, this question is left with no answer. The scientific community keeps defining cancer as a proliferation of cells in an uncontrolled and uncontrollable manner. The hypothesis developed here through an understanding of the cancer cell's behaviour led to its re-definition, providing answers to the questions arising from cancer. Through striking similarities in cell behaviour, I have concluded that the cancer cell is a reprogrammed cell with the launch of the egg cell's genetic program. The unique cell to express this program is the oocyte, therefore this oocyte cell should become the subject of significant study to understand the genesis of cancer. Above all, it will enable us to eradicate in a specific manner the cancer cell.


Ropinirole Augmentation for Depression: A Randomized Controlled Trial Pilot Study.
Evidence both from animal and human studies suggests a role for dopaminergic pathways in the treatment of depression. Ropinirole, a selective agonist of dopamine D2/D3, is in use for the treatment of parkinsonism. Preliminary evidence suggests that such agonists might be useful as antidepressants. We tested whether an add-on ropinirole is an effective in depressed patients. We conducted a double-blind, randomized, placebo-controlled trial of add-on ropinirole in depressed patients unresponsive to at least one antidepressant. We recruited 32 unipolar and bipolar patients who remained depressed (modified 21-item Hamilton Depression Rating Scale) despite at least 4 weeks of treatment with an adequate dose of antidepressant medication. Patients received either 2 mg of oral ropinirole or placebo twice daily added on to their current medication and were evaluated weekly for 7 weeks using the Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale. No difference in primary or secondary outcome measures was detected between the treatment and control groups. These results differ from previous studies and are unexpected in light of theoretical considerations. This may indicate that there are differences in pharmacological activity between ropinirole and other dopaminergic agents such as pramipexole.


[Difficult road to diagnosing dementia with lewy bodies (DLB). case report].
The main aim of the study was to present the case of a patient with neurological, depressive and psychotic symptoms, most probably connected with progressing dementia with Lewy bodies (DLB). The systematic symptom analysis based on the clinical examination and medical documentation. During the first hospitalisation, the presented patient was diagnosed with acute and transient psychotic disorders (F23). After being discharged from the ward, the patient experienced recurrence of previous symptoms with a short period of time. The two following diagnoses after hospital treatment were established as a depressive episode with psychotic symptoms. During the fourth hospitalisation, the patient was diagnosed with organic delusional (schizophrenia-like) disorder (F06.2). After six years, thorough analysis of clinical history as well as the course of existing disorder made it possible to diagnose the patient as having dementia with Lewy bodies-DLB (F02.8). Since that time, the patient has been taking rivastigmine, which has turned out to be a successful treatment. It has been 6 months since the patient left the hospital and still remains in remission. Social functioning of the woman is similar to the period before the first episode. The presented case demonstrates, that DLB symptomatology is a difficult problem in everyday psychiatric practice. A differential diagnosis of psychopathological and neurological symptoms covers many disorders, which together, with the clinical picture variation may delay effective treatment.


Monitoring of concordance in growth hormone therapy.
Concordance with growth hormone (GH) therapy in 75 children was objectively assessed using data on GP prescriptions over 12 months. 23% missed >2 injections/week. Lower concordance was associated with longer duration on GH therapy (p<0.005), lack of choice of delivery device (p<0.005) and short prescription durations (p<0.005), and predicted lower height velocities (p<0.05).


Muscle activities during asymmetric trunk angular accelerations.
The objective of this study was to characterize trunk muscle and intra-abdominal pressure behavior during extensions of the trunk when angular trunk acceleration levels and trunk twist were varied during lifting exertions. Since force is related to acceleration, it was believed that changes in trunk acceleration would cause activity changes in the muscles and abdominal cavity pressurization mechanics that load the spine during manual materials handling tasks. The electromyographic activity of 10 trunk muscles and intra-abdominal pressure were studied in 39 subjects as they moved their trunks under high, medium, and low constant angular acceleration conditions. The results indicated that almost all the muscles were affected by acceleration and asymmetry. Muscle activities of up to 50% of maximum were observed even though a minimal amount of torque was being produced by the back. Coactivation of muscles was also apparent. Muscles located at the greatest distances from the spine, such as the latissimus dorsi and oblique groups, increased their activities the most as trunk acceleration increased. Muscles located farthest from the spine also played an important role as the trunk became more asymmetric. Intra-abdominal pressure changed minimally over the test conditions. The nature of these responses and their impact on spine loading are discussed.


Optical levitation experiments to assess the validity of the generalized Lorenz-Mie theory.
Experimental near-forward-scattering diagrams obtained with one particle in optical levitation are recorded and compared with scattering diagrams computed by using the generalized Lorenz-Mie theory. Comparisons concern the particular case of an off-axis location of the particle. Agreement between experimental and computed diagrams is found to be satisfactory.


Rapid Fluorescence Quenching Detection of Escherichia coli Using Natural Silica-Based Nanoparticles.
The development of fluorescent silica nanoparticles (SNP-RB) from natural amorphous silica and its performance as an Escherichia coli (E. coli) biosensor is described in this paper. SNP-RB was derived from silica recovered from geothermal installation precipitation and modified with the dye, Rhodamine B. The Fourier Infrared (FTIR) confirms the incorporation of Rhodamine B in the silica matrix. Transmission Electron Microscopy (TEM) micrographs show that the SNP-RB had an irregular structure with a particle diameter of about 20-30 nm. The maximum fluorescence spectrum of SNP-RB was recorded at 580 nm, which was further applied to observe the detection performance of the fluorescent nanoparticles towards E. coli. The sensing principle was based on the fluorescence-quenching mechanism of SNP-RB and this provided a wide linear E. coli concentration range of 10-105 CFU/mL with a limit detection of 8 CFU/mL. A rapid response time was observed after only 15 min of incubation of SNP-RB with E. coli. The selectivity of the biosensor was demonstrated and showed that the SNP-RB only gave quenching response only to live E. coli bacteria. The use of SNP-RB as a sensing platform reduced the response time significantly compared to conventional 3-day bacterial assays, as well having excellent analytical performance in terms of sensitivity and selectivity.


Key Advances in MIP-based Sensors Applied for Cancer and Cardiovascular Biomarkers Detection.
Cancer and cardiovascular diseases have become one of the leading causes of death worldwide. Therefore, early detection of these diseases and rapid intervention by medical staff remain a great challenge for clinicians and healthcare providers worldwide. Cancer and cardiovascular disease biomarkers are promising tools for early diagnosis before it becomes incurable at an advanced stage. They also contribute to monitoring the progress of therapy and surgical treatment. Indeed, sensors have shown great importance for detecting cancer and cardiovascular biomarkers. Sensors usually require a recognition element for the selective detection of targets. Molecularly imprinted polymer (MIP), as an artificial antibody, has been proposed as an alternative recognition element in sensing fields to overcome the main drawbacks of natural antibodies. With the high need for sensors providing results quicklyand making the early diagnosis of these diseases easier, MIP-based sensors are attracting considerable interest recently, which will undoubtedly be increased in the future due to the sustainability trend. The key aim of this review is to emphasize the recent applications of sensors based on MIP for the detection of cancer and cardiovascular biomarkers and to highlight the key advances related to MIP-based sensors. Furthermore, several key future trends about the applications of MIP-based sensors for detecting cardiovascular and cancer biomarkers are presented.


[Resolutions of the Health Council: instrument of social control or bureaucratic document].
The present study has a documentary character and analyzes the resolutions registered in minutes of meetings of a Health Council, as a form to characterize the social control in health carried through for this instance. The majority of the resolutions were referred to the approval of Programs and Projects, arising from the Secretariat of Health, regarding the reform, material and equipment acquisition for units of health, the qualification of existing services or the creation of new services. The study suggests that the practical one of this council seems to be bureaucratic, without any proposal of politics of health for the council is visualized. The way the resolutions have being legalized does not characterize its guiding not even the visibility of the actions for the population in general. In the studied case, it is signaled that the mere regular functioning of this council does not guarantee that exist effective social control.


[A case of cerebellar variant of posterior reversible encephalopathy syndrome in puerperium].
A 29-year-old woman complained of headache and nausea several hours after delivery, followed by mild disturbance of consciousness. Physical examination revealed hypertension, systemic edema, nystagmus, dysarthria, and cerebellar ataxia. Computed tomography showed low attenuation areas in the cerebellum, and MR imaging revealed vasogenic edema in the cerebellum. MR angiography and MR venography demonstrated no significant abnormalities. We diagnosed a cerebellar variant of posterior reversible encephalopathy syndrome(PRES), and treated the patient immediately with antihypertensive drug and diuretic. The symptoms dramatically improved and MR imaging ten days after admission revealed disappearance of the vasogenic edema in the cerebellum. She was discharged without any sequelae. Though a cerebellar variant of PRES is very rare, rapid diagnosis and treatment is important for good prognosis when the disease is encountered.


Heterogeneous dynamics in columnar liquid crystals of parallel hard rods.
In the wake of previous studies on the rattling-and-jumping diffusion in smectic liquid crystal phases of colloidal rods, we analyze here for the first time the heterogeneous dynamics in columnar phases. More specifically, we perform computer simulations to investigate the relaxation dynamics of a binary mixture of perfectly aligned hard spherocylinders. We detect that the columnar arrangement of the system produces free-energy barriers that the particles should overcome to jump from one column to another, thus determining a hopping-type diffusion. This phenomenon accounts for the non-Gaussian intercolumn diffusion and shows a two-step structural relaxation that is remarkably analogous to that of out-of-equilibrium glass-forming systems and gels. Surprisingly enough, slight deviations from the behavior of simple liquids due to transient cages is also observed in the direction perpendicular to this plane, where the system is usually referred to as liquidlike.


Transition metal-free functionalized hydration of alkynes: one-pot synthesis of fluorinated β-keto-imidates using Selectfluor.
A transition metal-free, four-component one-pot synthesis of polyfunctionalized fluorinated β-keto-imidates via the functionalized hydration of alkynes has been described. The intermediate 1,3-ketoamino moiety was obtained from easily accessible arylpropioladehyde and arlyhydroxylamine and was treated with Selectfluor delivering fluorinated β-keto-imidates. A wide variety of functional groups are tolerated under mild reaction conditions and the product applicability is highlighted.


Regulation of gastric H(+)-K(+)-ATPase by cAMP-dependent protein kinase.
A functional approach was utilized to isolate protein effectors from cAMP-stimulated rabbit gastric microsomes capable of stimulating H(+)-K(+)-ATPase activity. These studies have resulted in isolation of a cAMP-dependent protein kinase product from rabbit gastric microsomes which is capable of stimulating the proton pump of the parietal cell, H(+)-K(+)-ATPase, in inhibited gastric microsomes. This protein is membrane-bound and may be extracted from gastric microsomes only in the phosphorylated state. This phosphoprotein has at least 20 phosphorylation sites and produces enhancement of H(+)-K(+)-ATPase activity which equals that induced by the K+ ionophore, valinomycin. It would appear, therefore, that cAMP-mediated acid secretion involves phosphorylation of a membrane-bound cAMP-dependent protein kinase substrate in close proximity to the proton pump which produces K+ conductance and thereby controls the rate of acid secretion. The degree of phosphorylation of this protein is probably controlled by the activities of cAMP-dependent protein kinase and phosphoprotein phosphatase.


Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells (NF-AT) complex.
The lymphoid-specific transcription complex, NF-AT, is involved in early gene activation in T cells and is assembled from a pre-existing, T cell restricted cytoplasmic factor and an inducible ubiquitous nuclear component within 30 min after activation through the antigen receptor. Recent studies have implicated the family of AP1 factors as components of the murine NF-AT complex. Evidence is provided here that the nuclear component of human NF-AT contains the phorbol ester-inducible transcription factor AP1 (Jun/Fos). We further characterize which AP1 family members can assume this role. Antisera to Fos inhibits NF-AT DNA binding as does an oligonucleotide containing a binding site for AP1. Constitutive expression in vivo of Fos, and to a lesser extent Fra-1, eliminates the requirement for phorbol 12-myristate 13-acetate (PMA) stimulation, leaving NF-AT-directed transcription responsive to calcium ionophore alone. Overexpression of cJun or JunD, but not JunB, also eliminates the requirement for PMA, indicating that many but not all Jun- and Fos-related proteins functionally activate NF-AT-dependent transcription in the presence of the cytoplasmic component. NF-AT DNA binding can be reconstituted in vitro using semi-purified AP1 proteins mixed with cytosol from T lymphocytes. Fos proteins are not needed for this reconstitution, and although JunB is not functional, it can participate in the NF-AT DNA binding complex. Finally, we have partially purified the cytoplasmic component of NF-AT and show by elution and renaturation from SDS-polyacrylamide gel electrophoresis gels that it has a molecular mass between 94 and 116 kDa and may have multiple differentially modified forms.


Cloning, characterization and localization of three novel class III peroxidases in lignifying xylem of Norway spruce (Picea abies).
Plant class III peroxidases (POXs) take part in the formation of lignin and maturation of plant cell walls. However, only a few examples of such peroxidases from gymnosperm tree species with highly lignified xylem tracheids have been implicated so far. We report here cDNA cloning of three xylem-expressed class III peroxidase encoding genes from Norway spruce (Picea abies). The translated proteins, PX1, PX2 and PX3, contain the conserved amino acids required for heme-binding and peroxidase catalysis. They all begin with putative secretion signal propeptide sequences but diverge substantially at phylogenetic level, grouping to two subclusters when aligned with other class III plant peroxidases. In situ hybridization analysis on expression of the three POXs in Norway spruce seedlings showed that mRNA coding for PX1 and PX2 accumulated in the cytoplasm of young, developing tracheids within the current growth ring where lignification is occurring. Function of the putative N-terminal secretion signal peptides for PX1, PX2 and PX3 was confirmed by constructing chimeric fusions with EGFP (enhanced green fluorescent protein) and expressing them in tobacco protoplasts. Full-length coding region of px1 was also heterologously expressed in Catharanthus roseus hairy root cultures. Thus, at least the spruce PX1 peroxidase is processed via the endoplasmic reticulum (ER) most likely for secretion to the cell wall. Thereby, PX1 displays correct spatiotemporal localization for participation in the maturation of the spruce tracheid secondary cell wall.


Pentane-1,5-diaminium dibromide.
The crystal structure of the title salt, C5H16N2(2+)·2Br(-), with Z = 12 and more unusually Z' = 3, forms part of a small group of crystal structures in the Cambridge Structural Database that are ammonium bromide salts. One of the diaminium cation chains in the asymmetric unit exhibits positional disorder, which was modelled using a suitable disorder model. This compound also exhibits organic-inorganic layering in its packing arrangement that is typical of this class of compound. An extensive complex three-dimensional hydrogen-bonding network is also identified. The hydrogen bonds evident in this crystal structure were identified as being most likely strong charge-assisted hydrogen bonds.


Nursing roles and functions in the inpatient neurorehabilitation of stroke patients: a literature review.
Stroke is a major cause of morbidity and mortality in the world. In the United States, it was estimated that approximately 750,000 patients had a stroke annually. Denmark, with a population of 5.5 million, had about 12,500 cases of hospitalizations from stroke in 2009. Despite the patient's obvious need for complex nursing care and a common recognition of the nurse's central role in rehabilitation after a stroke, a description of their specific contributions appeared sparse. Therefore, a literature review was conducted using the matrix method. The purpose was to explore the nursing roles and functions identified in empirical research and to discern any possible evolution in the nursing roles and functions during a span of years. The rehabilitation literature related to inpatient rehabilitation after stroke during the period from 1997 to 2010 was reviewed. The total number of identified citations was 1,529. After screening for relevancy, 134 eligible articles remained. Of these, 30 articles were extracted into a table and formed the basis for the conclusion. We found that four nursing roles and functions described in 1997 still accommodated central aspects of the current nursing practice but also emerging changes reflecting a development in the nurses' responsibilities and contributions in conducting rehabilitation after a stroke. These changes seemed mainly to be shaped instigated by changes in the (1) patient role, (2) increasing interdisciplinary teamwork, and (3) focus on rehabilitation efforts conducted in the patient's environment.


Operads for complex system design specification, analysis and synthesis.
As the complexity and heterogeneity of a system grows, the challenge of specifying, documenting and synthesizing correct, machine-readable designs increases dramatically. Separation of the system into manageable parts is needed to support analysis at various levels of granularity so that the system is maintainable and adaptable over its life cycle. In this paper, we argue that operads provide an effective knowledge representation to address these challenges. Formal documentation of a syntactically correct design is built up during design synthesis, guided by semantic reasoning about design effectiveness. Throughout, the ability to decompose the system into parts and reconstitute the whole is maintained. We describe recent progress in effective modelling under this paradigm and directions for future work to systematically address scalability challenges for complex system design.


Asymptomatic Fungemia Due to Rhodotorula spp. Caused by a Subcutaneously Implanted Central Venous Port Catheter.
A 66-year-old man was admitted to our hospital for gastrointestinal perforation. He had a history of surgery and chemotherapy for colorectal cancer and had a subcutaneously implanted central venous port catheter. After surgery for gastrointestinal tract perforation, he developed an intra-abdominal abscess, which was treated with broad-spectrum antimicrobial agents and improved. Following this improvement, Rhodotorula spp. was detected in a blood culture and at the catheter tip. He was asymptomatic despite having fungemia. His condition improved after the removal of the catheter and the administration of antifungal drugs. Fungemia due to Rhodotorula spp. is rare, and asymptomatic fungemia is even rarer.


Lithiophilic Zn3N2-Modified Cu Current Collectors by a Novel FCVA Technology for Stable Anode-Free Lithium Metal Batteries.
Anode-free lithium metal batteries (AFLMBs) offer high-energy-density battery systems, but their commercial viability is hindered by irregular lithium dendrite growth and "dead Li" formation caused by current collector defects. This study employed filtered cathode vacuum arc (FCVA) technology to fabricate Cu current collectors (CCs) with a lithiophilic Zn3N2 film. This advanced preparation process ensures an evenly distributed film that reduces the nucleation overpotential, homogenizes the interfacial electric field during plating/stripping processes, inhibits lithium dendrite growth, and forms a stable solid-electrolyte interphase (SEI). Our results show that the advanced Zn3N2@Cu CCs exhibit superior performance with a high CE of above 99.3% after 230 cycles at a current density of 0.5 mA cm-2 and an area capacity of 1 mAh cm-2. Additionally, Li-Zn3N2@Cu||Li-Zn3N2@Cu symmetrical cells had a longer stable cycle time of over 1000 h than that of Li||Li and Li-Cu||Li-Cu symmetrical cells at a current density of 1 mA cm-2 and an area capacity of 2 mAh cm-2. Compared with bare Cu CCs, the capacity retention rate is increased from 14.9 to 63.1% after 100 cycles with a 0.5C rate in the AFLMBs with LFP as the cathode. This work provides a pioneering, eco-friendly, and effective solution for the fabrication of anode CCs in AFLMBs, addressing a significant challenge in their commercial application.


Distribution of calmodulin-stimulated ca transport into membrane vesicles from green spinach leaves.
A microsomal fraction isolated from green spinach leaves exhibited a Mg(2+) and ATP-dependent (45)Ca(2+) uptake. Addition of 10 micromolar carbonyl cyanide m-chlorophenylhydrazine had no effect. The cationophore A23187 (10 micromolar) induced the release of (45)Ca(2+) accumulated by membrane vesicles. Membranes prepared from lower epidermis showed the highest Ca(2+) accumulation activity. Microsomal fractions from petiole, lamina, and midrib were less active. The stimulation by bovine brain calmodulin was about 30% for the lower epidermis, 23.5% for midrib, and below 20% for petiole and lamina.


Hidden fungi, emergent properties: endophytes and microbiomes.
Endophytes are microorganisms that live within plant tissues without causing symptoms of disease. They are important components of plant microbiomes. Endophytes interact with, and overlap in function with, other core microbial groups that colonize plant tissues, e.g., mycorrhizal fungi, pathogens, epiphytes, and saprotrophs. Some fungal endophytes affect plant growth and plant responses to pathogens, herbivores, and environmental change; others produce useful or interesting secondary metabolites. Here, we focus on new techniques and approaches that can provide an integrative understanding of the role of fungal endophytes in the plant microbiome. Clavicipitaceous endophytes of grasses are not considered because they have unique properties distinct from other endophytes. Hidden from view and often overlooked, endophytes are emerging as their diversity, importance for plant growth and survival, and interactions with other organisms are revealed.


Rapid one-step inactivation of single or multiple genes in Escherichia coli.
Gene knockout experiments are frequently performed for both fundamental and applied biological research. We developed an integration helper plasmid-based knockout system for more efficient and rapid engineering of Escherichia coli. The integration helper plasmid, pCW611, contains two recombinases that are expressed in the reverse direction by two independent inducible systems. One is Red recombinase under the control of the arabinose-inducible system to induce a recombination event by using the linear gene knockout DNA fragment, while the other is Cre recombinase, which is controlled by the isopropyl β-D-1-thiogalactopyranoside-inducible system to obtain markerless mutant strains. The time and effort required can be reduced with this system because iterative transformation and curing steps are not required. We could delete one target gene in three days by using pCW611. To verify the usefulness of this system, deletion experiments were performed to knock out four target genes individually (adhE, sfcA, frdABCD, and ackA) and two genes simultaneously for two cases (adhE-aspA and sfcA-aspA). Also, sequential deletion of four target genes (fumB, iclR, fumA, and fumC) was successfully performed to make a fumaric acid producing strain. This successfully developed and validated rapid and efficient gene manipulation system should be useful for the metabolic engineering of E. coli.


Expectancies specific to condom use mediate the alcohol and sexual risk relationship.
The present study tested the role of alcohol expectancies for condom use in mediating the alcohol and risky sex relationship. Expectancies for condom use are specific anticipations for alcohol's effect on one's ability to use a condom. College students (N = 563) reported on beliefs, intentions and actual sexual and drinking behavior. Among the sexually active, alcohol was directly related to future intention to use a condom in drinking situations for men, but not for women. In the men, alcohol expectancies for condom use mediated the relationship between drinking and condom intention. Beliefs that alcohol negatively impacts one's ability to use condoms were associated with more drinking and lower intentions to use a condom. These expectancies may help explain how alcohol affects risky sex in men. Gender differences and implications are discussed.


Characterisation of the Immunomodulatory Effects of Meningococcal Opa Proteins on Human Peripheral Blood Mononuclear Cells and CD4+ T Cells.
Opa proteins are major surface-expressed proteins located in the Neisseria meningitidis outer membrane, and are potential meningococcal vaccine candidates. Although Opa proteins elicit high levels of bactericidal antibodies following immunisation in mice, progress towards human clinical trials has been delayed due to previous findings that Opa inhibits T cell proliferation in some in vitro assays. However, results from previous studies are conflicting, with different Opa preparations and culture conditions being used. We investigated the effects of various Opa+ and Opa- antigens from N. meningitidis strain H44/76 in a range of in vitro conditions using peripheral blood mononuclear cells (PBMCs) and purified CD4+ T cells, measuring T cell proliferation by CFSE dilution using flow cytometry. Wild type recombinant and liposomal Opa proteins inhibited CD4+ T cell proliferation after stimulation with IL-2, anti-CD3 and anti-CD28, and these effects were reduced by mutation of the CEACAM1-binding region of Opa. These effects were not observed in culture with ex vivo PBMCs. Opa+ and Opa- OMVs did not consistently exert a stimulatory or inhibitory effect across different culture conditions. These data do not support a hypothesis that Opa proteins would be inhibitory to T cells if given as a vaccine component, and T cell immune responses to OMV vaccines are unlikely to be significantly affected by the presence of Opa proteins.


The efficiency of acute infection of CD4+ T cells is markedly enhanced in the setting of antigen-specific immune activation.
Human immunodeficiency virus (HIV) disease in sub-Saharan Africa generally differs from that observed in the United States and other developed countries in that the risk of seroconversion after exposure is greater and the rate of disease progression to AIDS and death is faster. One theory that could in part explain this difference is the increased state of immune activation associated with a relatively high rate of parasite infestation and other infections among inhabitants of these regions. Using a model based on the cellular microenvironment of lymphoid organs, the role of exposure to HIV during a state of antigen-specific immune activation was investigated. Dendritic cells and CD4+ T cells are the major cellular components of the paracortical region of lymphoid tissue, the primary site of HIV replication. We analyzed cocultures of HIV-pulsed dendritic cells that had matured in the presence of tetanus toxoid and CD4+ T cells before and after inducing an antigen-specific response by in vivo immunization with tetanus toxoid. During antigen-specific immune activation, 100 times less HIV was needed to initiate a productive infection. These findings provide a model system to further delineate the relationship between immune activation and the propagation of HIV infection and suggest a mechanism for the epidemiologic observations of an increased ease of developing HIV infection and faster progression for HIV disease in geographic areas where immune activation is prevalent.


Modification by MK-801 (dizocilpine), a noncompetitive NMDA receptor antagonist, of morphine sensitization: evaluation by ambulation in mice.
The effects of five administrations (3- to 4-day intervals) of morphine (MOR: 10 and 20 mg/kg, s.c.) alone, MK-801 (dizocilpine: 0.03, 0.1, 0.3 and 1 mg/kg, i.p.) alone, and combinations of MOR with MK-801 on the ambulation in mice were investigated. MK-801 at 0.3 and 1 mg/kg, but not at 0.03 and 0.1 mg/kg, significantly increased the ambulation of mice. Although the mice given repeated administrations of MK-801 (0.3 and 1 mg/kg) exhibited enhancement and reduction, respectively, in the ambulation-increasing effect of the individual doses, they showed significantly higher sensitivity than the saline-treated mice to the challenge with MOR (10 mg/kg). The repeated administrations of MOR (10 and 20 mg/kg) induced a progressive enhancement of the ambulation-increasing effect. The mice repeatedly given MOR (10 mg/kg) exhibited significant increase in the sensitivity to MK-801 (0.03-0.3 mg/kg). The coadministrations of MOR with MK-801 intensified the ambulation-increasing effect, and repeated coadministrations induced progressive enhancement of the effect, except for the combinations of MOR (10 or 20 mg/kg) with MK-801 (1 mg/kg). However, the induction of MOR sensitization was not modified by any doses of MK-801, except for the case of combination of MOR (20 mg/kg) with MK-801 (1 mg/kg) which was highly toxic (i.e., eliciting death or a moribund condition). On the other hand, simultaneous treatment with SCH 23390 (0.05 mg/kg, s.c.) or nemonapride (0.05 mg/kg, s.c.), or 4-hr pretreatment with reserpine (1 mg/kg, s.c.) strongly, and 4-hr pretreatment with alpha-methyl-p-tyrosine (200 mg/kg, i.p.) partially reduced the ambulation-increasing effect of both MOR (10 mg/kg) and MK-801 (0.3 mg/kg). Simultaneous treatment with naloxone (1 mg/kg, sc) selectively reduced the effect of MOR. However, simultaneous treatment with apomorphine (0.1 mg/kg, s.c.) did not modify the effects of either drug. These results suggest that the characteristics of the ambulation-increasing effects of MOR and MK-801 are similar to each other, and that the repeated treatments with MK-801 induce a cross-sensitization to MOR and vice versa.


Status of Corynosoma (Acanthocephala: Polymorphidae) based on anatomical, ecological, and phylogenetic evidence, with the erection of Pseudocorynosoma n. gen.
The possession of genital spines has been considered as a key taxonomic trait to differentiate Corynosoma from other genera of the Polymorphidae. However, Corynosoma currently consists of 2 groups of species with clear ecological and morphological divergences: the "marine" group (with ca. 30 species) infects mammals and piscivorous birds in the marine realm, whereas the "freshwater" group (with ca. 7 species) infects waterfowl in continental waters. Species from these groups differ in shape of body and neck, trunk spination, lemnisci length and shape, testes arrangement, and number and shape of cement glands. We tested whether species from these 2 groups formed a monophyletic assemblage based on a phylogenetic analysis by using 15 morphological characters. We also included species of Andracantha, Polymorphus, and Hexaglandula with which potential taxonomic conflicts could most likely arise. We obtained 108 equally most parsimonious trees of 32 steps, with a consistency index (CI) = 0.59, and a retention index (RI) = 0.82. The strict consensus tree indicated that the "freshwater" species of Corynosoma form a monophyletic assemblage closely related to some species of Polymorphus, whereas the "marine" species of Corynosoma are grouped together with Andracantha. Accordingly, Corynosoma is not a monophyletic assemblage, and Pseudocorynosoma n. gen. is proposed for the "freshwater" species of Corynosoma. This decision was strongly supported by (1) a functional comparison of foretrunk muscles between species of Polymophus, Andracantha, and Corynosoma; (2) a multivariate morphometric study of proboscis characters and egg size; and (3) an analysis of ecological patterns of host-parasite relationships.


Layered double hydroxide-carbon dot composite: high-performance adsorbent for removal of anionic organic dye.
It would be of significance to design a green composite for efficient removal of contaminants. Herein, we fabricated a facile and environmentally friendly composite via direct assembly of surface passivated carbon dots with abundant oxygen-containing functional groups on the surface of the positively charged layered double hydroxide (LDH). The resulting LDH-carbon dot composites were characterized by X-ray diffraction (XRD), Fourier transformed infrared (FTIR) spectroscopy, high resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and N2 adsorption-desorption technique. The adsorption performances of the resulting LDH-carbon dot composites were evaluated for the removal of anionic methyl blue dye. Taking advantage of the combined benefits of LDH and carbon dots, the as-prepared composites exhibited high uptake capability of methyl blue (185 mg/g). The adsorption behavior of this new adsorbent fitted well with Langmuir isotherm and the pseudo-second-order kinetic model. The reasons for the excellent adsorption capacity of methyl blue on the surface of the LDH-carbon dot hybrid were further discussed. A probable mechanism was speculated to involve the cooperative contributions of hydrogen bonding between methyl blue and carbon dots and electrostatic attraction between methyl blue and LDH, in the adsorption process. This work is anticipated to open up new possibilities in fabricating LDH-carbon dot materials in dealing with anionic dye pollutants.


[Life just is not fair - and statistics do not make it any better].
We have all tried it: it is pouring down with rain, we reach for the keys, and choose the wrong one. The mathematical probability for choosing the correct key - out of two - is 50%. During the 1990s, candy.scient. Jarle Gundersson (JG) proposed a mathematically unexplainable factor of uncertainty. He used the above example with the keys and concluded that the real, or observed, probability for choosing the correct key was 5-10%. The discrepancy between the mathematical and real probability was, according to JG, caused by The Awfulness of Being Concept. In this article, we present the results from a study and demonstrate the difference between the mathematical and the observed probability of success in two different scenarios (winning a coin toss and choosing the correct key in the first attempt). Questionnaire survey performed at the Regional Hospital of Esbjerg 18-19 September 2009 using staff as questionnaire respondents. We found a discrepancy between the mathematical and observed probability in both scenarios, 64% and 68% of the cases in the two scenarios, respectively. We also found that there is a negative correlation between age and the probability that one will win a coin toss, but a positive correlation between age and choosing the correct key. The results lacked any statistical significance. We hypothesised that you will always loose in a coin toss and never choose the correct key when there are two choices. The study demonstrated that this was incorrect, but there was a difference between the mathematical and the observed probabilities in most of the cases.


Efficacy of COVID-19 vaccine booster doses in older people.
We provide here an updated analysis on efficacy of COVID-19 vaccine booster doses in older people (i.e., aged ≥ 80 years) based on ongoing Italian nationwide COVID-19 vaccination campaign. Data were obtained from the COVID-19 national integrated surveillance program, made available and regularly updated by the Italian National Institute of Health. Compared to those who completed the COVID-19 vaccination cycle for ≥ 5 months (n = 2,385,897), those receiving booster doses (n = 1,549,747) had 75% lower risk of SARS-CoV-2 infection, 82-83% lower risk of COVID-19 hospitalization and ICU admission, and 81% lower risk of death. Administration of COVID-19 vaccine boosters generated also greater protection (between 63 and 87% higher) against all these same endpoints compared to early completing (i.e., < 5 months; n = 335,458) a primary COVID-19 vaccination cycle. The administration of COVID-19 vaccine booster doses is advisable for reducing the risk of morbidity and mortality in older people.


[Investigation of cardiovascular adaptation to postural passive test in the course of selecting candidates for special contingent].
Selection of candidates for special contingent is made with the focus on evaluation of cardiovascular functioning and adaptability to stresses, and detection of pre-disease shifts in CV regulation. Hemodynamics regulation was assessed by tilt testing of 15 essentially healthy men at the age of 18 to 34. The tilt table was initially at 0 degrees (baseline), turned at +75 degrees (20 min), and then back to 0 degrees for 5-min recovery. Simultaneously with the standard measurements of ECG and blood pressure, the myocardium state was registered with the use of KardioVizor-06; cerebral circulation was evaluated using rheoencephalography and microcirculation vessels, -ultrasonic Doppler. Three human subjects exhibited hypotensive reactions to the tilt test and two showed hypertensive reactions. However, no changes were present on ECG records. Hence, in-depth investigation of the CV reaction to tilt test is capable to reveal incipient regulatory disorders and their trend, and to assess adaptability to stresses.


HMOs and PPOs in review.
The significance of the growth of health maintenance organizations (HMOs) and preferred provider organizations (PPOs) hinges on the reliability of the reported figures, which may not be accurate. The greatest changes in the industry over the past 3 months were evidenced in the areas of federal legislation regarding Medicare beneficiaries and military personnel, and within the industry itself, with numerous joint ventures and acquisitions. Dynamic changes continue, and the actors are becoming more clearly defined.


Separation of Storage and Loss Modulus of Polyelectrolyte Multilayers on a Nanoscale: A Dynamic AFM Study.
Atomic force microscopy (AFM) is used to carry out rheology measurements on the nanoscale and to determine the mechanical properties of poly(l-lysine) (PLL)/hyaluronic acid (HA) multilayer films. Storage (G') and loss modulus (G″) of the films are calculated and compared with the values obtained from quartz crystal microbalance with dissipation monitoring measurements (QCM-D). A predominant elastic behavior independently of the applied frequencies (5-100 Hz) is observed for native HA/PLL films consisting of 36 double layer. If the layers are cross-linked, the value of G' increases by 2 orders of magnitude, while the loss modulus becomes negligible, making these films a purely elastic chemical gel. The values of G' and G'' extracted from QCM-D measurements on native films are much higher, due to the different frequency regime of the applied shear stress. However, the viscoelastic ratio from the two methods is the same and proves the elastic dominated response of the multilayer in both frequency regimes.


Salivary CPLANE1 Levels as a Biomarker of Oral Squamous Cell Carcinoma.
This study aimed to identify novel biomarkers for oral squamous cell carcinoma (OSCC) screening to improve the survival rate of patients with oral cancer. We investigated differential salivary gene expression in patients with OSCC, those with oral potentially malignant disorders (OPMDs), and healthy volunteers (HVs). CPLANE1 was selected for further investigation by microarray analysis. We used quantitative reverse transcription PCR (qRT-PCR) to determine CPLANE1 expression levels in the saliva. The expression of CPLANE1 in normal and oral cancer tissues was analyzed using the Gene Expression database of Normal and Tumor tissues. qRT-PCR analysis of saliva samples showed that CPLANE1 expression levels were significantly higher in OSCC patients than in HVs and OPMDs patients. Furthermore, we developed a screening test for OSCC using CPLANE1 and showed that it had good accuracy. Salivary CPLANE1 could be a useful biomarker for OSCC screening and early detection.


Lateral Translation of the Patella in MPFC Reconstruction: A Biomechanical Study of Three Approaches.
The purpose of this study was to investigate whether differences exist in preventing lateral patellar translation between three distinct medial patellofemoral complex (MPFC) reconstruction procedures at varying knee flexion angles. Six cadaveric knee specimens were dissected, potted, and placed in a customized jig for testing. Lateral patellar displacement was measured at intervals between 0 and 90 degrees of knee flexion using a tensile testing machine with a 20 N lateral force applied to the patella. Each specimen was tested with the MPFC intact, sectioned, and after each of the three reconstruction techniques: MPFL, hybrid, and medial quadriceps-tendon femoral (MQTFL) reconstructions. There was significantly increased lateral patellar displacement following MPFC sectioning when compared with the intact state in early degrees of flexion (10-30 degrees) (p < 0.05). All three reconstruction groups restored patella stability and reduced lateral patellar displacement following sectioning from 0 to 30 degrees of flexion (p < 0.05). When compared with the intact group, all three reconstruction groups demonstrated reduced patella translation at full knee extension, while the MPFL and hybrid reconstruction groups additionally demonstrated significant reduction in patella translation at 10 degrees of flexion (p < 0.05). No significant differences were observed between the three reconstruction groups. This biomechanical study demonstrates the efficacy of three MPFC reconstruction techniques in patella stabilization following sectioning. Our results suggest that MPFL reconstruction may provide the most robust patella stabilization, whereas MQTFL reconstruction may be the most forgiving construct. This study suggests that MQTFL and hybrid reconstructions provide adequate resistance to lateral translation and may be used as an alternative to MPFL reconstruction.


Relationships Between Oral Microecosystem and Respiratory Diseases.
Oral microecosystem is a very complicated ecosystem that is located in the mouth and comprises oral microbiome, diverse anatomic structures of oral cavity, saliva and interactions between oral microbiota and between oral microbiota and the host. More and more evidence from studies of epidemiology, microbiology and molecular biology is establishing a significant link between oral microecosystem and respiratory diseases. Microbiota settling down in oral microecosystem is known as the main source of lung microbiome and has been associated with the occurrence and development of respiratory diseases like pneumonia, chronic obstructive pulmonary disease, lung cancer, cystic fibrosis lung disease and asthma. In fact, it is not only indigenous oral microbes promote or directly cause respiratory infection and inflammation when inhaled into the lower respiratory tract, but also internal environment of oral microecosystem serves as a reservoir for opportunistic respiratory pathogens. Moreover, poor oral health and oral diseases caused by oral microecological dysbiosis (especially periodontal disease) are related with risk of multiple respiratory diseases. Here, we review the research status on the respiratory diseases related with oral microecosystem. Potential mechanisms on how respiratory pathogens colonize oral microecosystem and the role of indigenous oral microbes in pathogenesis of respiratory diseases are also summarized and analyzed. Given the importance of oral plaque control and oral health interventions in controlling or preventing respiratory infection and diseases, we also summarize the oral health management measures and attentions, not only for populations susceptible to respiratory infection like the elderly and hospitalized patients, but also for dentist or oral hygienists who undertake oral health care. In conclusion, the relationship between respiratory diseases and oral microecosystem has been established and supported by growing body of literature. However, etiological evidence on the role of oral microecosystem in the development of respiratory diseases is still insufficient. Further detailed studies focusing on specific mechanisms on how oral microecosystem participate in the pathogenesis of respiratory diseases could be helpful to prevent and treat respiratory diseases.


Peptides-Derived from Thai Rice Bran Improves Endothelial Function in 2K-1C Renovascular Hypertensive Rats.
In recent years, a number of studies have investigated complementary medical approaches to the treatment of hypertension using dietary supplements. Rice bran protein hydrolysates extracted from rice is a rich source of bioactive peptides. The present study aimed to investigate the vasorelaxation and antihypertensive effects of peptides-derived from rice bran protein hydrolysates (RBP) in a rat model of two kidney-one clip (2K-1C) renovascular hypertension. 2K-1C hypertension was induced in male Sprague-Dawley rats by placing a silver clip around the left renal artery, whereas sham-operated rats were served as controls. 2K-1C and sham-operated rats were intragastrically administered with RBP (50 mg kg(-1) or 100 mg kg(-1)) or distilled water continuously for six weeks. We observed that RBP augmented endothelium-dependent vasorelaxation in all animals. Administration of RBP to 2K-1C rats significantly reduced blood pressure and decreased peripheral vascular resistance compared to the sham operated controls (p < 0.05). Restoration of normal endothelial function and blood pressure was associated with reduced plasma angiotensin converting enzyme (ACE), decreased superoxide formation, reduced plasma malondialdehyde and increased plasma nitrate/nitrite (p < 0.05). Up-regulation of eNOS protein and down-regulation of p47phox protein were found in 2K-1C hypertensive rats-treated with RBP. Our results suggest that RBP possesses antihypertensive properties which are mainly due to the inhibition of ACE, and its vasodilatory and antioxidant activity.


Bringing memories to life.
Age Exchange is a charity based in south London that uses reminiscence-based creative activities to engage older people with dementia and mental health problems. The charity celebrates its 30th anniversary this year. It provides training for health and social care staff in the practical application of reminiscence work and programmes designed to promote learning, creativity and understanding between generations.


Physician assistants as administrators. Opportunities in management. Panel discussion.
Physician assistants' involvement in administration focused on educational programs early in the profession's history. Recently, PAs have begun to work as administrators in hospitals and other settings. Preparation for management positions varies from on-the-job training to graduate degrees in business administration and public health. Clinical experience as a PA increases marketability in health care administration. Physician assistants who work as clinicians and administrators may find it difficult to balance responsibilities. In this forum, four PAs who helped pioneer this role explain how they became administrators and answer questions raised by other PAs interested in this growing job opportunity.


Sequential study of myeloid differentiation antigens of neutrophil granulocytes in different phases of chronic myeloid leukaemia: natural history and prognostic significance.
In an attempt to contribute to the knowledge of the natural history of Philadelphia-chromosome-positive chronic myeloid leukaemia (CML) and its prognosis, we analyzed sequentially the myeloid differentiation antigens of peripheral blood neutrophil granulocytes (NG) in different evolutive stages of the disease. Four monoclonal antibodies (CD15, CD24, 31D8, and 13F6) were used, and a total number of 116 sequential studies were performed in 43 patients. At diagnosis, there is a significant decrease of NG expressing myeloid differentiation antigens, which recover to nearly normal levels after initial control of the disease. The onset reduction is probably due to the circulation of incompletely mature NG. In accelerated/blastic phase NG expressing myeloid differentiation antigens decrease again, probably due to a true antigen loss. This reduction could herald by a few months the development of accelerated/blastic phase. In such a case, its predictive strength is higher than that of the well recognized initial prognostic parameters in CML. These results indicate that the sequential study of NG myeloid differentiation antigens may contribute to both a better understanding of the natural history of CML and the evolutive prognosis of this disease.


CYP2A6 polymorphisms in Malays, Chinese and Indians.
The genetically polymorphic cytochrome P450 (CYP) 2A6 is the major nicotine-oxidase in humans that may contribute to nicotine dependence and cancer susceptibility. The authors investigated the types and frequencies of CYP2A6 alleles in the three major ethnic groups in Malaysia and CYP2A6*1A, CYP2A6*1B, CYP2A6*1x2, CYP2A6*2, CYP2A6*3, CYP2A6*4, CYP2A6*5, CYP2A6*7, CYP2A6*8 and CYP2A6*10 were determined by allele-specific polymerase chain reaction (PCR) in 270 Malays, 172 Chinese and 174 Indians. Except for CYP2A6*2 and *3 that were not detected in the Malays and Chinese, all the other alleles were detected. Frequencies for the CYP2A6*4 allele were 7, 5 and 2%, respectively, in Malays, Chinese and Indians. A statistically significant high frequency of the duplicated CYP2A6*1x2 allele occurred among Chinese. Among Malays and Chinese, the most common allele was CYP2A6*1B, but it was CYP2A6*1A among Indians. These ethnic difference in frequencies suggested that further studies are required to investigate the implications on diseases such as cancer and smoking behaviour among these major ethnic groups in Malaysia.


Aerial drones for blood delivery.
Aerial drone technology is now in use to improve medical care, especially blood delivery. The use of aerial drones is broader than just this and includes aerial photography, express shipping and delivery, disaster management, search and rescue operations, crop monitoring, weather tracking, law enforcement, and structural assessment. This wide use promises to accelerate and, ideally, reduce the cost of technological advances of drones. By doing so, drone use offers the opportunity of improving health care, particularly in remote and/or underserved environments by decreasing lab testing turnaround times, enabling just-in-time lifesaving medical supply/device delivery, and reducing costs of routine prescription care in rural areas.


Dysplastic nevus--risk factor or disguise for melanoma.
Dysplastic nevus is an acquired or hereditary nevus that clinically seems atypical and pathohistologically dysplastic. The term of dysplastic nevus has changed through history and even until now the dermatologists and pathologists have not found the same conclusion for name and definition of dysplastic nevus. Epidemiology of dysplastic nevus is different depending on geographic lattitude, being three times higher in Australia than in Great Britain. Genetic factors play a role in etiology of dysplastic nevus but are still not well defined. UV radiation is indisputable main etiological factor in developing dysplastic nevus. Many studies confirm that children who have been using sun protection creams with SPF have less dysplastic nevi than those who did not. Nevus with geographic shape and muddy borders, dominately macular, red to brown colored and has 5 mm or more in diameter is clinically dysplastic nevus. ABCDE rules count for dysplastic nevus as well as for melanoma but prefferable diagnostic criteria for dysplastic nevus would be "ugly duckling sign". Pathohistologic analysis is the key in confirming the diagnosis of dysplastic nevus. Great experience and knowledge in dermatopathology field is essential for pathologists to make a distinction between dysplastic nevus and melanoma in situ. Likewise great experience in dermatooncology field is essential in differentiating dysplastic nevus from other nevi. Surgical excision is the only therapy that should be done for dysplastic nevus. Regular follow up is highly recommended for patients with dysplastic nevus and syndroma naevi dysplastic. Education about sun protection measures and self-examination techniques is essential for all patients with dysplastic nevi and their family.


[Value of combinational detection by IgH and IgL primers in improving detection rate of lymphoma gene in paraffin-embedded tissue].
Clonality detection through amplifying immunoglobulin heavy chain (IgH) by polymerase chain reaction (PCR) is a useful tool in diagnosis of lymphoma, but the false negative rate is high, especially in paraffin-embedded tissues. This study was to explore the value of tumor tissue microdissection and combinational detection of IgH and immunoglobulin light chain (Ig kappa or Ig lambda) in diagnosis of non-Hodgkin's lymphoma (NHL). Two pairs of conventional primers for IgH and T-cell receptor gamma (TCRgamma), 2 novel designed pairs of primers for Ig kappa and Ig lambda were used to detect 58 paraffin-embedded blocks, which had been diagnosed by pathology and histochemistry. Of the 58 cases of lymph node tissues, 39 were B-cell lymphoma, 16 were T-cell lymphoma, and 3 were reactive proliferative lymph node tissue. Lymphoma cell lines DG75 and Jurkat were used as control. The positive rates of IgH primers (P1) and IgL primers (P kappa/P lambda) were 79.5% and 71.8% in the 39 cases of B-cell lymphoma (P>0.05), 6.3% and 12.5% in the 16 cases of T-cell lymphoma, respectively. The positive rate was greatly increased to 92.3% in combinationally detecting the primers for IgH and P kappa/P lambda. There was no positive detection among the reactive proliferative lymph node tissues. B-cell lymphoma detection rate can be significantly improved by the combination of IgH and IgL gene rearrangement primers, which provides efficient assistant method for the diagnosis and differential diagnosis of lymphoma.


Patient and public involvement in primary care research - an example of ensuring its sustainability.
The international literature on patient and public involvement (PPI) in research covers a wide range of issues, including active lay involvement throughout the research cycle; roles that patients/public can play; assessing impact of PPI and recommendations for good PPI practice. One area of investigation that is less developed is the sustainability and impact of PPI beyond involvement in time-limited research projects. This paper focuses on the issues of sustainability, the importance of institutional leadership and the creation of a robust infrastructure in order to achieve long-term and wide-ranging PPI in research strategy and programmes. We use the case of a Primary Care Research Centre to provide a historical account of the evolution of PPI in the Centre and identified a number of key conceptual issues regarding infrastructure, resource allocation, working methods, roles and relationships. The paper concludes about the more general applicability of the Centre's model for the long-term sustainability of PPI in research.


Dopa-responsive parkinsonism phenotype of spinocerebellar ataxia type 2.
We report on 2 brothers, Patients 1 and 2, who presented with a similar clinical syndrome consisting of resting tumor, bradykinesia, rigidity, and dysarthria at the ages of 40 and 43 years, respectively. An excellent response to levodopa therapy was observed throughout the disease course. No gait or limb ataxia, slow saccades, or decreased tendon reflexes were detected, but unsteadiness of gait with propulsion developed recently in Patient 1 approximately 25 years after disease onset. Magnetic resonance imaging demonstrated mild atrophy of the pons and cerebellum in Patient 1 and cerebellar atrophy in Patient 2. Expanded CAG repeats, numbering 36, in one allele of the ataxin-2 gene were identified in Patient 1 only; his brother was not available for this investigation. With [(99m)Tc]TRODAT-1 single photon emission computed tomography of the brain, a significant bilateral and asymmetrical reduction of striatal dopamine transporters was found in Patient 1 compared to healthy controls. This bilateral reduction of striatal dopamine transporters resembled that observed in a set of controls with Parkinson's disease who had asymmetrical impairment. These results suggest that patients with familial parkinsonism who present with typical Parkinson's disease should be screened for the genetic defect of spinocerebellar ataxia type 2. The presynaptic impairment of nigrostriatal function is very likely to be the reason for levodopa responsiveness.


Autosomal dominant hypohidrotic ectodermal dysplasia in a large family.
We have studied an autosomal dominant hypohidrotic ectodermal dysplasia in 38 individuals over six generations in one family. Thirty-two affected individuals in four generations are still living. Questionnaire responses were received from 21 of the affected relatives and some of the individuals were examined by one of the authors. Smooth, dry, thin skin is seen in most affected individuals. Nearly all have fine, slow-growing scalp and body hair and all have sparse eyebrows and short eyelashes. Nearly all show a decrease in sweating, with some only sweating under the arms and/or on the palms and soles. All affected individuals lacked some deciduous teeth and some permanent teeth. Some teeth are abnormally shaped. Nail abnormalities are more variable and may occur more frequently with increasing age. No other abnormalities are seen in affected individuals in this family. We reviewed 40 autosomal dominant ectodermal dysplasia syndromes. This family bears some resemblance to a family described by Jorgensen et al. [1987]; however, it appears to represent a disorder that has not been described previously.


The Emerging Role of Drug-Induced Sleep Endoscopy in the Management of Obstructive Sleep Apnea.
Obstructive sleep apnea is a prevalent sleep disorder characterized by partial or complete obstruction of the upper airway. Continuous positive airway pressure is the first-line therapy for most patients, but adherence is often poor. Alternative treatment options such as mandibular advancement devices, positional therapy, and surgical interventions including upper airway stimulation target different levels and patterns of obstruction with varying degrees of success. Drug-induced sleep endoscopy enables the visualization of upper airway obstruction under conditions mimicking sleep. In the era of precision medicine, this additional information may facilitate better decision-making when prescribing alternative treatment modalities, with the hope of achieving better adherence and/or success rates. This review discusses the current knowledge and evidence on the role of drug-induced sleep endoscopy in the non-positive airway pressure management of obstructive sleep apnea.


Job satisfaction of health care staff employed at health centres in Turkey.
The objective of the study was to identify job satisfaction levels and their causes among health care workers employed at public health centres. A survey was therefore carried out of health care workers in 21 health centres in Konya, Turkey. The Minnesota Satisfaction Questionnaire was used to investigate job satisfaction. The satisfaction score and proportion of those satisfied were determined according to demographic features. The percentage of satisfied health care workers was 60% and the satisfaction score was 3.8 +/- 0.5. Midwives had the lowest satisfaction scores. Working environment and income were the most important factors for dissatisfaction. There was no correlation between global satisfaction and other demographic variables. These results showed that the health care workers at public health centres in the province have low satisfaction scores. Improving working conditions and income may improve the overall quality of health care provision.


Helium ion microscopy based wall thickness and surface roughness analysis of polymer foams obtained from high internal phase emulsion.
Due to their wide range of applications, porous polymers obtained from high internal phase emulsions have been widely studied using scanning electron microscopy. However, due to their lack of electrical conductivity, quantitative information of wall thicknesses and surface roughness, which are of particular interest to tissue engineering, has not been obtained. Here, Helium Ion Microscopy is used to examine uncoated polymer foams and some very strong but unexpected contrast is observed, the origin of which is established here. Based on this analysis, a method for the measurement of wall thickness variations and wall roughness measurements has been developed, based on the modeling of Helium ion transmission. The results presented here indicate that within the walls of the void structure there exist small features with height variations of ~30 nm and wall thickness variations from ~100 nm to larger 340 nm in regions surrounding interconnecting windows within the structure. The suggested imaging method is applicable to other porous carbon based structures with wall thicknesses in the range of 40-340 nm.


Alterations of adrenergic systems in thyroid slices from patients with Graves' disease.
The responses to TSH of tissue cAMP levels in thyroid slices from patients with Graves' disease were significantly lower than those in normal thyroid slices. Conversely, tissue cAMP levels in thyroid slices from these patients were greatly increased by beta-adrenergic agonists, either isoproterenol or norepinephrine compared with those in normal thyroid slices. The elevation of cAMP levels induced by TSH in normal thyroid slices was significantly reduced by norepinephrine via alpha-adrenergic action as reported previously in canine thyroid slices, while such an elevation by TSH of cAMP levels in slices of Graves' disease thyroids was not inhibited, or rather increased by norepinephrine. These results indicate that, in addition to low responses to TSH, alpha- and beta-adrenergic systems were functionally altered in thyroid tissues of patients with Graves' disease.


Mapping of evoked magnetic field with visual stimulation: a secondary projection and processing area.
Visual evoked fields (VEFs) were measured in four subjects, using magnetoencephalography (MEG) and a flashed checkerboard pattern stimulation with a duration of 20 ms. The left hemisphere was searched for the primary and the secondary projection areas with a full-field stimulus. Typical VEFs were found in the occipital area, which is considered to be the primary projection; and a secondary projection area was found in the dorsal temporal area in all subjects. The negative VEF in the secondary projection area was robust and stable, with a range of latencies from 200 to 230 ms. The amplitude was more than -400 femtotesla (fT), as high as the VEF in the occipital area. However, we were unable to localize the position of a dipole, since only one amplitude maxima was found.


Apparent total tract nutrient digestibility and metabolizable energy estimation in commercial fresh and extruded dry kibble dog foods.
Commercial fresh cooked foods have started gaining popularity among American dog owners in recent years. However, nutrient digestibility and the estimation of metabolizable energy (ME) of commercial fresh dog foods remain inadequately understood, even though both measures are critical to provide the intended calories for the target animal. In this preliminary study, different cohorts of normal-weight dogs were fed one of five test diets of comparable macronutrient composition: a chicken-based extruded dry kibble diet (n = 12), and chicken- (n = 12), beef- (n = 6), pork- (n = 6), or turkey-based fresh food (n = 6) for 10 d. Daily food intake and fecal characteristics were recorded, and fecal samples were collected for nutrient analysis. Despite comparable dry matter (DM) and caloric intakes between the two chicken-based diets, the fresh diet led to lower defecation frequency (1.2 ± 0.2 vs. 1.7 ± 0.5 times/d, adjusted P < 0.001), lower fecal DM (24 ± 8 vs. 47 ± 10 g/d, adjusted P < 0.001), and lower fecal calories (92 ± 31 vs. 189 ± 43 kcal/d, adjusted P < 0.001) than the kibble diet. The apparent total tract digestibility of DM, protein, fat, nitrogen-free extract, and calories of the kibble diet were all significantly lower than any of the fresh diets (adjusted P < 0.001 for all). Measured ME per food DM in all of the fresh diets, except the pork-based recipe, was significantly higher than that of the kibble diet (adjusted P < 0.001 for all). For the kibble diet, the modified Atwater calculation underestimated the ME and the NRC 2006 calculation was the most accurate predictor of ME. The standard Atwater calculation performed best for the two fresh diets that had the highest fat content (chicken, beef) and the NRC 2006 calculation performed best for the fresh diet that had the highest protein content (pork). ME of the turkey-based diet was equally overestimated and underestimated with the standard Atwater and NRC 2006 methods, respectively. We propose that commercial and home-prepared fresh diets should be assessed using standard Atwater factors as commonly done in human nutrition, or preferably for commercial products, by direct measurement in conforming feeding trials.


Efficient Accessible Bounds to the Classical Capacity of Quantum Channels.
We present a method to detect lower bounds to the classical capacity of quantum communication channels by means of few local measurements (i.e., without complete process tomography), reconstruction of sets of conditional probabilities, and classical optimization. The method does not require any a priori information about the channel. We illustrate its performance for significant forms of noisy channels.


Economic evaluations: a new avenue of outcome assessment in spinal disorders.
The number of economic evaluations in the field of spinal disorders and methodological studies have increased in the last decade. The objective of this paper is to provide an overview of current views on economic evaluations in the field of spinal disorders and to facilitate clinicians to interpret and use results from these studies. A full economic evaluation compares both costs and effects of two or more interventions. Key elements of economic evaluations such as identifying adequate alternatives, analytical perspective, cost methodology, missing values and sensitivity analyses are addressed. Further emphasis is placed on the interpretation of results of economic evaluations conducted alongside randomised clinical trials. Incremental cost-effectiveness ratios, cost-effectiveness planes, acceptability curves and cost-effectiveness thresholds are discussed. The contents may aid in taking the efficacy 'hurdle' in the field of spinal disorders.


Acetylation-dependent function of human single-stranded DNA binding protein 1.
Human single-stranded DNA binding protein 1 (hSSB1) plays a critical role in responding to DNA damage and maintaining genome stability. However, the regulation of hSSB1 remains poorly studied. Here, we determined that hSSB1 acetylation at K94 mediated by the acetyltransferase p300 and the deacetylases SIRT4 and HDAC10 impaired its ubiquitin-mediated degradation by proteasomes. Moreover, we demonstrated that the hSSB1-K94R mutant had reduced cell survival in response to DNA damage by radiation or chemotherapy drugs. Furthermore, the p300/CBP inhibitor C646 significantly enhanced the sensitivity of cancer cells to chemotherapy drugs, and a positive correlation between hSSB1 and p300 level was observed in clinical colorectal cancer samples. Acetylation, a novel regulatory modification of hSSB1, is crucial for its function under both physiological and pathological conditions. This finding supports the notion that the combination of chemotherapy drugs with acetylation inhibitors may benefit cancer patients.


A family with gastrointestinal amyloidosis associated with variant lysozyme.
Hereditary nonneuropathic systemic lysozyme amyloidosis is a very rare form of amyloidosis, and only 4 families with this condition have been detailed until now in the literature. Clinical manifestations of lysozyme amyloidosis observed until now mainly concerned the kidneys, liver, and digestive tract. We report here a new family with hereditary lysozyme amyloidosis who presented predominantly with gastrointestinal involvement. The proband, a middle-aged woman, underwent partial gastrectomy for a hemorrhagic "gastric peptic ulcer" in 1984. Gastrointestinal amyloidosis was diagnosed in 1998 on biopsies performed on the gastroduodenal anastomosis, which appeared to be very congestive at presentation. Immunohistochemical stainings in tissue sections were positive for lysozyme. Amyloid was also observed in the colonic mucosa. The patient had a mutation in the lysozyme gene characterized by substitution of the amino acid at position 64 in the mature protein from tryptophan to arginine, previously described in only 1 French family with prominent nephropathy. It is interesting to note that her father had died many years before with an uncharacterized digestive amyloidosis. Our observation shows that a search for gastrointestinal amyloidosis is important, particularly when physicians are faced with congestive mucosa, unexplained abdominal hemorrhage, or abdominal symptoms. When gastrointestinal amyloidosis is diagnosed, it is important to determine with precision the nature of the amyloid fibril proteins, because various types of amyloidosis can involve the gastrointestinal tract.


Early augmentation of interleukin (IL)-12 level in the airway of mice administered orally with clarithromycin or intranasally with IL-12 results in alleviation of influenza infection.
The protective role of interleukin (IL)-12 against influenza infection was assessed by analyzing the efficacies of orally administered clarithromycin (CAM) as an immunomodulator and intranasal administration of recombinant IL-12 in intranasally influenza virus-infected mice. In infected mice, CAM at 20 mg/mouse/day significantly elevated the levels of IL-12 and interferon-gamma on days 2 and 3, respectively, after infection in the bronchoalveolar lavage fluid (BALF), but the levels in the sera were not affected. The levels of IL-4, -6, and -10 were not significantly affected in the sera and BALF. Corresponding with the local elevation of IL-12 level, CAM reduced virus yield and the number of infiltrated cells in the BALF, the severity of pneumonia, and mortality of the treated mice. The potential activity of CAM as an experimental immunomodulator was verified at a dose of 20 mg/mouse/day. Intranasal administration of the optimal dose (20 ng/mouse) of IL-12 on day 2 significantly reduced virus yield in the BALF after infection. The loss of body weight was significantly suppressed by IL-12 administration. The local elevation of IL-12 level at the optimal dose and timing in influenza infection was confirmed to be effective in alleviating the influenza infection in mice treated with the two different ways. Thus, the augmentation of IL-12 production or administration of supplementary IL-12 in the respiratory tract was essential in reducing virus yield in the early phase of influenza and may be crucial for recovery from influenza infection.


Drug responses in antigen-induced contractions of tracheal strips of ovalbumin-sensitized guinea pigs.
Guinea pig trachea strips were isolated after 21 d of ovalbumin-sensitization. Challenging the preparations with antigen induced a double-phase contractile response (DPCR) which consisted of a rapid contraction (RC) and a tonic contraction (TC). The effects of tetrodotoxin (TTX), atropine, hexamethonium, diphenhydramine and a substance P (SP) antagonist on the DPCR were observed. DPCR was insensitive to atropine or hexamethonium at 1 mumol/L. Diphenhydramine 2 mumol/L abolished RC, and inhibited TC by 48.0 +/- 5.6%. TTX 1 mumol/L and lidocaine 2 mumol/L almost completely abolished TC and reduced RC by 49.6 +/- 6.7% and 44.6 +/- 8.4%, respectively. The substance P antagonist, (D-Arg1, D-2,4-diCl2-Phe5, Asp6, D-Trp7,9, Nle11)-SP 10 mumol/L, inhibited RC by 49.9 +/- 6.1% and TC by 90.7 +/- 9.3%. The results suggest that SP sensory nerve fibers in respiratory tract play an important role in the pathogenesis of DPCR, especially in that of TC.


Structural basis of lectin-carbohydrate recognition.
Lectins are responsible for cell surface sugar recognition in bacteria, animals, and plants. Examples include bacterial toxins; animal receptors that mediate cell-cell interactions, uptake of glycoconjugates, and pathogen neutralization; and plant toxins and mitogens. The structural basis for selective sugar recognition by members of all of these groups has been investigated by x-ray crystallography. Mechanisms for sugar recognition have evolved independently in diverse protein structural frameworks, but share some key features. Relatively low affinity binding sites for monosaccharides are formed at shallow indentations on protein surfaces. Selectivity is achieved through a combination of hydrogen bonding to the sugar hydroxyl groups with van der Waals packing, often including packing of a hydrophobic sugar face against aromatic amino acid side chains. Higher selectivity of binding is achieved by extending binding sites through additional direct and water-mediated contacts between oligosaccharides and the protein surface. Dramatically increased affinity for oligosaccharides results from clustering of simple binding sites in oligomers of the lectin polypeptides. The geometry of such oligomers helps to establish the ability of the lectins to distinguish surface arrays of polysaccharides in some instances and to crosslink glycoconjugates in others.


Unprecedented H-atom transfer from water to ketyl radicals mediated by Cp(2)TiCl.
The H-atom transfer (HAT) from water to ketyl radicals, mediated by titanocene(iii) aqua-complexes, can explain the Ti(III)-promoted reduction of ketones in aqueous medium better than the conventional House mechanism. Moreover, we also report novel evidences supporting the existence of these titanocene(iii) aqua-complexes.


Intraoperative augmented reality for laparoscopic colorectal surgery by intraoperative near-infrared fluorescence imaging and optical coherence tomography.
Advances in imaging quality and capability have been the major driver of the laparoscopic revolution that has dramatically impacted upon operative strategies and surgical patient care in recent years. Increasingly now the technological capacity is becoming available to supraselect or extend the useful clinical range of the electromagnetic spectrum beyond visible or white light. This has markedly broadened the intraprocedural optical information available at intraluminal endoscopy and there is likely to be considerable similar benefit for laparoscopy. Rather than narrow band or ultraviolet imaging however, it is the near infrared (NIR) spectrum that seems of most potential to exploit during intra-abdominal endoscopy in particular as this energy range is capable of penetrating relatively deeply into tissues such as the mesentery and bowel wall without inducing thermal damage due to heat dissipation or indeed the intracellular effects associated with higher energy, shorter wavelength energies. By incorporating the NIR spectrum alongside more conventional laparoscopic imaging, a greater appreciation of tissue architecture, character and quality is possible in particular with respect to lymphatic and vascular channel anatomy and flow dynamics and also real-time optical histology (by NIR optical coherence tomography). Such a facility may significantly aid critical intraoperative decision making during colorectal operations by informing the surgeon regarding the most biologically relevant lymphatic basin and lymph nodes for any target area of interest (especially important if considering tailored operative extent for colorectal neoplasia), the sufficiency and quality of arterial supply (and hence inform re the perfusion of stapled intestinal ends prior to reanastomosis) and perhaps even in situ pathological assessment. This article provides a state of art overview of the fascinating potential of this emergent technological capability.


Central projections of auditory nerve fibers in the barn owl.
The central projections of the auditory nerve were examined in the barn owl. Each auditory nerve fiber enters the brain and divides to terminate in both the cochlear nucleus angularis and the cochlear nucleus magnocellularis. This division parallels a functional division into intensity and time coding in the auditory system. The lateral branch of the auditory nerve innervates the nucleus angularis and gives rise to a major and a minor terminal field. The terminals range in size and shape from small boutons to large irregular boutons with thorn-like appendages. The medial branch of the auditory nerve conveys phase information to the cells of the nucleus magnocellularis via large axosomatic endings or end bulbs of Held. Each medial branch divides to form 3-6 end bulbs along the rostrocaudal orientation of a single tonotopic band, and each magnocellular neuron receives 1-4 end bulbs. The end bulb envelops the postsynaptic cell body and forms large numbers of synapses. The auditory nerve profiles contain round clear vesicles and form punctate asymmetric synapses on both somatic spines and the cell body.


Characterization of acute and delayed ocular lesions induced by sulfur mustard in rabbits.
To establish an experimental model for sulfur mustard-induced acute and delayed ocular lesions in rabbits. Rabbit eyes were exposed to sulfur mustard (HD) vapor (370, 420 microg/l) for a period of two minutes. A three months follow-up study was carried out, based on the evaluation of clinical, biochemical and histological parameters. HD exposure initiated typical clinical symptoms within 2-6 hrs, characterized by eye closure, eyelid swelling, conjunctival hyperemia, corneal erosions and inflammation. The clinical signs were significantly dose-dependent and reached a peak at 24--72 hrs post exposure. Biochemical evaluation of the aqueous humor exhibited an inflammatory reaction and oxidative stress at 4 hrs after exposure, subsiding at 28 hrs after exposure. Histological examination of corneas at 48 hrs revealed epithelial denudation and marked stromal edema, accompanied by cellular infiltration. Epithelial regeneration started after 72 hrs, and recovery was almost completed within 1--2 weeks, depending on the HD dose. A second phase of pathological processes started as early as two weeks post exposure and was characterized by corneal edema, opacity, recurrent erosions and neovascularization. The delayed injuries were found in 25 and 40% of the eyes respectively, and when appearing, were more severe than the initial ones. The development of HD-induced ocular lesions in rabbits is similar to the lesions described in human casualties. Quantitative analysis of the various clinical parameters emphasizes the contribution of each tissue to the overall toxic picture. Our experimental model is useful for studying the pathological mechanisms of HD-ocular lesions, and may serve for testing potential therapies.


[Establishment of liver metastasis model of human primary colonic lymphoma by orthotopic transplantation].
To provide an ideal animal model for exploring pathogenesis and experimental treatment of primary colonic lymphoma. Primary colonic and liver metastatic lymphoma tissues were obtained from the surgical specimens,and transplanted into colonic mucosa of nude mice respectively. The tumorigenesis, invasion, metastasis and morphology of the transplanted tumor were observed. Karyotype was analyzed and DNA content was measured. According to the new WHO classification of malignant lymphoma, two high metastatic models (HCBL-0303 from primary lymphoma and HCBL-0304 from live metastatic lesion) of human primary colonic non-Hodgkin's B cell lymphoma in nude mice were established successfully by orthotopic transplantation. Pathological examination showed poorly differentiated non-Hodgkin's B cell lymphoma of the transplanted tumors, and immunohistochemical staining showed positive expressions of CD19, CD20 and CD22, and negative expressions of CD3 and CD7. The number of chromosome ranged from 55 to 59, and DNA index (DI) was 1.59 - 1.71 (i.e. heteroploid). In HCBL-0303,liver metastasis rate was 63.7% and lymph node metastasis rate was 56.4%. However, in HCBL-0304, both metastasis rates of liver and lymph node were 100%. The transplanted tumors grew autonomously and invasively in nude mice, and further developed hematogenous, lymphatic metastasis and intraperitoneal seeding. HCBL-0303 and HCBL-0304 are the first established high metastatic models of primary colonic lymphoma, and can be applied to the research on pathogenesis, invasion,metastasis and experimental therapy of human primary colonic lymphoma.


Smear technique in the intra-operative brain tumor diagnosis: its advantages and limitations.
The role of intra-operative pathological diagnosis increases along with a development of minimally invasive neurosurgery, especially stereotactic and endoscopic techniques. The authors present their own experience with the cytological method and evaluate its usefulness in intra-operative diagnosis of brain tumors. Brain tumor biopsy specimens obtained during craniotomy from 217 patients were examined. The cytological preparations (smears) were stained with 1% toluidin blue and/or with May-Grünwald-Giemsa stain. In 199 cases (92%) the cytological diagnosis was consistent with the histopathological one. A 99% sensitivity and 69% specificity were obtained. The histogenesis of gliomas was correctly established in 90% and their grade in 73% of cases. The most frequent diagnostic errors were: undergrading of gliomas (20), incorrect assessment of their histogenesis (10), diagnosis of low grade astrocytoma in a case of gliosis (3) and diagnosis of glioblastoma multiforme instead of metastatic carcinoma (2 cases). The most important advantages of cytological examination are rapidity, simplicity and relatively high diagnostic efficacy. Even very tiny specimens, especially of soft consistency are suitable for this technique, which is extremely important in operations of brain tumors localized in functionally important brain areas. In the authors' opinion this method still merits wider popularization in neurosurgical centers.


Elevated triglycerides levels in two infants with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia and receiving parenteral nutrition.
Therapeutic hypothermia has been widely applied to improve the survival/neurodevelopmental outcomes among infants with moderate-to-severe hypoxic ischemic encephalopathy (HIE). Due to their critical condition and concerns over feeding tolerance, it is not uncommon to withhold enteral feeds and provide parenteral nutrition (PN) during hypothermia and early rewarming. Here we report 2 infants with HIE undergoing therapeutic hypothermia, and receiving PN, who exhibited early elevated triglyceride levels. Hypertriglyceridemia can be associated with neurologic complications, ranging from altered mental status, or irritability to seizures. Given the possible altered lipid metabolism under hypothermic conditions, we advocate close monitoring of lipid tolerance and conducting further prospective trials to elucidate lipid metabolism in these infants.


Early illness features associated with mortality in the juvenile idiopathic inflammatory myopathies.
Because juvenile idiopathic inflammatory myopathies (IIMs) are potentially life-threatening systemic autoimmune diseases, we examined risk factors for juvenile IIM mortality. Mortality status was available for 405 patients (329 with juvenile dermatomyositis [DM], 30 with juvenile polymyositis [PM], and 46 with juvenile connective tissue disease-associated myositis [CTM]) enrolled in nationwide protocols. Standardized mortality ratios (SMRs) were calculated using US population statistics. Cox regression analysis was used to assess univariable associations with mortality, and random survival forest (RSF) classification and Cox regression analysis were used for multivariable associations. Of 17 deaths (4.2% overall mortality), 8 (2.4%) were in juvenile DM patients. Death was related to the pulmonary system (primarily interstitial lung disease [ILD]) in 7 patients, gastrointestinal system in 3, and multisystem in 3, and of unknown etiology in 4 patients. The SMR for juvenile IIMs overall was 14.4 (95% confidence interval [95% CI] 12.2-16.5) and was 8.3 (95% CI 6.4-10.3) for juvenile DM. The top mortality risk factors in the univariable analysis included clinical subgroup (juvenile CTM, juvenile PM), antisynthetase autoantibodies, older age at diagnosis, ILD, and Raynaud's phenomenon at diagnosis. In multivariable analyses, clinical subgroup, illness severity at onset, age at diagnosis, weight loss, and delay to diagnosis were the most important predictors from RSF; clinical subgroup and illness severity at onset were confirmed by multivariable Cox regression analysis. Overall mortality was higher in juvenile IIM patients, and several early illness features were identified as risk factors. Clinical subgroup, antisynthetase autoantibodies, older age at diagnosis, and ILD are also recognized as mortality risk factors in adult myositis.


Preparation of doxorubicin-hydrochloride nanoliposomes by ethanol injection-pH gradient method and their safety evaluation.
A new type of ethanol injection-pH gradient method was established to produce Doxorubicin-Hydrochloride Nanoliposome (DHNP). The characteristics of DHNP were examined by Zetasizer. The acute toxicity and chronic toxicity trials were conducted in Kuming mice with different doses of DHNP. The results showed that the DHNP had the uniform distribution size, diameter ranged in 140-170 nm, its entrapment rate could reach as high as 99.85%, and it was relatively stable in low temperature. The LD50 of the DHNP is 31.69 mg/kg. In the chronic toxicity study, body weight, hematocrit, the mean red blood cell volume, platelets counts and percentage of eosinophil at the dose of 6 mg/kg and 9 mg/kg groups were significantly different (p < 0.05) compared with control group, while the other parameters had no significantly difference. In the tissue analysis, pathological change was found in the lung at the treated group, and its pathological degree increased as the dose increased, while there were no other pathological changes detected in other tissues. This study demonstrates that the DHNP prepared by ethanol injection-pH gradient method possesses the advantage of uniform distribution size, high encapsulation efficiency, big drug loading rate, and its toxicity is lower than free doxorubicin.


The diversity of conjugative relaxases and its application in plasmid classification.
Bacterial conjugation is an efficient and sophisticated mechanism of DNA transfer among bacteria. While mobilizable plasmids only encode a minimal MOB machinery that allows them to be transported by other plasmids, conjugative plasmids encode a complete set of transfer genes (MOB1T4SS). The only essential ingredient of the MOB machinery is the relaxase, the protein that initiates and terminates conjugative DNA processing. In this review we compared the sequences and properties of the relaxase proteins contained in gene sequence databases. Proteins were arranged in families and phylogenetic trees constructed from the family alignments. This allowed the classification of conjugative transfer systems in six MOB families:MOB(F), MOB(H), MOB(Q), MOB(C), MOB(P) and MOB(V). The main characteristics of each family were reviewed. The phylogenetic relationships of the coupling proteins were also analysed and resulted in phylogenies congruent to those of the cognate relaxases. We propose that the sequences of plasmid relaxases can be used for plasmid classification. We hope our effort will provide researchers with a useful tool for further mining and analysing the plasmid universe both experimentally and in silico.


Pressure-support ventilation in children with severe asthma.
To review the efficacy of pressure-support ventilation in the management of children with status asthmaticus requiring mechanical ventilation. A case series. A university hospital. Children requiring mechanical ventilation due to respiratory failure despite medical therapy during an episode of acute asthma. Mechanical ventilation with pressure-support ventilation. Respiratory parameters (ventilatory settings, minute ventilation, respiratory rate, airway pressures) and blood gases were determined before, on initiation, and for 6 hrs after pressure-support ventilation. Spontaneous ventilation with an initial respiratory rate of 45 breaths/min (range 31 to 46) and an inspiration/expiration ratio (I/E) of 1:1.2 (range 1:1.1 to 1:2) was readily established in each patient. Arterial pH normalized (7.41, range 7.39 to 7.43) within 6 hrs (4.25, range 2 to 6) of the time at which ventilation was begun and the Paco2 decreased (p < .02) to 44 torr (range 39 to 47) (5.9 kPa, range 5.2 to 6.3) during pressure support ventilation. Pressure-support ventilation permitted patient-cycled spontaneous ventilation in children with asthma. The ability of patients to determine their own respiratory pattern and to maintain forced exhalation during pressure-support ventilation may have important advantages in children with severe asthma who require mechanical ventilation.


Diabetic neuropathy: a cross-sectional study of the relationships among tests of neurophysiology.
To determine the relationships among large, small, and autonomic fiber neurophysiological measures in a cross-sectional study of patients with diabetes. We assessed 130 individuals: 25 healthy subjects and 105 subjects with diabetes. Subjects were classified by the presence or absence of neuropathy by physical examination. All subjects underwent autonomic testing, nerve conduction studies, quantitative sensory testing, and nerve-axon reflex vasodilation in addition to quantifiable neurological examination and symptom scores. Correlation and cluster analysis were used to determine relationships between and among different neurophysiological testing parameters. Results of neurophysiological tests were abnormal in patients with clinical evidence of diabetic neuropathy compared with results in healthy control subjects and in those without neuropathy (P < 0.01, all tests). The correlations among individual tests varied widely, both within (r range <0.5->0.9, NS to <0.001) and between test groups (r range <0.2->0.5, NS to <0.01). A two-step hierarchical cluster analysis revealed that neurophysiological tests do not aggregate by typical "small," "large," or "autonomic" nerve fiber subtypes. The modest correlation coefficients seen between the different testing modalities suggest that these techniques measure different neurophysiological parameters and are therefore not interchangeable. However, the data suggest that only a small number of neurophysiological tests are actually required to clinically differentiate individuals with neuropathy from those without. The natural clustering of both patients and healthy control subjects suggests that variations in the population will need to be considered in future studies of diabetic neuropathy.


The future of Western Samoan migration to New Zealand.
"The history of Samoan migration to New Zealand, a demographic profile of the migrants, and the future of such migration are discussed. Migration became a serious phenomenon after independence in 1962, with primarily young, unskilled workers moving to take up jobs in the agricultural and service sectors. Remaining essentially unchanged since 1962, New Zealand's immigration policy gives preferential treatment to Western Samoans and recognizes their valuable labor contribution. The future of migration to New Zealand is discussed in the context of the costs and benefits to Western Samoa.... The author argues that emigration has been beneficial rather than deleterious to Western Samoa's development...." Data are from official sources.


[Enalapril and acebutolol in essential arterial hypertension. Comparison of the 2 drugs and evaluation of their combination].
The effects of a mid-term antihypertensive treatment with Acebutolol (A) 400 mg once-daily alone, Enalapril (E) 20 mg once-daily alone and their combination (A + E) in 12 hypertensive patients (pts.) have been evaluated. The diastolic (DBP) and systolic (SBP) blood pressure values have been evaluated in supine and upright position and at the end of an exercise test. Basic values obtained after 3 weeks of treatment with placebo have been matched with values observed after 3 months of each treatment (A; A + E; E). In order to evaluate the effectiveness of the combination, pts. were divided into two groups: the first group was given A, than A + E and finally E; in the second group the order was reversed. Our findings showed a more significant reduction of DBP in supine and upright position and after exercise (p less than .05) and of SBP in supine and upright position (p less than .05) after treatment with E. The addition of A to E did not produce a further significant reduction in blood pressure values except after exercise (p less than .01).