Cytotoxicity of a vanadyl(IV) complex with a multidentate oxygen donor in osteoblast cell lines in culture.
Strong chelating ligands as oxodiacetate (oda) are model systems to study the process of metal trapping by living organisms. Vanadium compounds display interesting biological and pharmacological actions. In vertebrates, vanadium is stored mainly in bones. In the present study we report the effects of the complex of oda with vanadyl(IV) cation, VO(oda), on two osteoblast cell lines, one normal (MC3T3E1) and the other tumoral (UMR106). VO(oda) exerted cytotoxic actions in osteoblasts as it was determined through a dose-dependent decrease in cell proliferation, and morphological and actin alterations. The putative mechanisms underlying VO(oda) deleterious effects were also investigated. The complex increased the level of ROS which correlated with a decreased in GSH/GSSG ratio. Besides, VO(oda) induced a dissipation of the mitochondria membrane potential (MMP) and promoted an increase in ERK cascade phosphorylation, which is involved in the regulation of cellular death and survival. All the effects were more pronounced in MC3T3-E1 than in UMR106 cells. ERK activation was inhibited by PD98059, Wortmanin and the ROS scavenger NAC (N-acetyl cysteine). These results suggest that VO(oda) stimulated ERKs phosphorilation by induction of free radicals involving kinases upstream of ERK pathway. The inhibitory effect of the complex on cell proliferation was partially reversed in both cell lines by NAC. Moreover, PD98059 and Wortmanin also partially reversed the inhibition of cell proliferation in the tumoral osteoblasts. The use of specific inhibitors and ROS scavengers suggested the involvement of oxidative stress, MMP alterations and ERK pathway in the apoptotic actions of this complex.


Combined use of in ovo electroporation and cultured neurons for gene function analysis of embryogenesis in the chicken optic tectum.
Chicken embryos are used widely in the fields of developmental biology and neurobiology. The chicken embryo also serves as a model to analyze gene expression and function using in ovo electroporation. Plasmids may be injected into the spinal cord or tectum of the chicken central nervous system by microinjection for electroporation. Here, we developed a novel method that combines in ovo electroporation and neuronal culturing to study gene function in the chicken tectum during embryo development. Our method can be used to study in-vivo and in-vitro exogenous genes' function. In addition, live cell imaging microscopy, immunostaining, and transfection can be used with our method to study neuronal growth, development, neurite growth and retraction, and axonal pathfinding. Our result showed that axons were present in isolated neurons after culturing for 24 h, and cell debris was low after replacing the media at 48 h. Many GFP-expressing neurons were observed in the cultured cells after 48 h. We successfully cultured the neurons for 3 weeks. Together, this method combines in ovo electroporation and neuronal culturing advantages and is more convenient for the gene function analysis.


Molecular analysis of interleukin-25 exons 1 and 2 and its serum levels in Iranian patients with multiple sclerosis.
Overexpression of Interleukin-17 (IL-17) family has been shown in a variety of autoimmune diseases. IL-25 (IL-17E), as a member of this family of cytokines, induces the overexpression of IL-13 and impedes Th17/IL-17 responses. In the present study potential single nucleotide polymorphisms (SNP) of IL-25, its serum level in Multiple Sclerosis (MS) patients have been surveyed. Blood samples were obtained from 100 Relapsing-Remitting MS cases, and 100 healthy controls. Serum levels of IL-25 were measured by ELISA. IL-25 exons 1 and 2 were sequenced. IL-25 serum levels investigation showed significant association in cases compared to controls. Molecular analysis of IL-25exons 1 and 2 depicted significant differences in polymorphisms of exon 2 between two groups of study. However, no significant differences were found in polymorphisms for IL-25 exon. These results demonstrate that serum levels of IL-25 are reduced in MS patients compared to controls. This is the first study in Iran that shows polymorphisms in IL-25 among MS patients. Considering the role of IL-25 in suppression of the effects of IL-17A and active phase of Experimental Autoimmune Encephalomyelitis (EAE) in vivo, this cytokine seems to have therapeutic potentials for autoimmune diseases like MS.


Core-Shell Molecularly Imprinted Polymer Nanocomposites for Biomedical and Environmental Applications.
Core-shell polymers represent a class of composite particles comprising of minimum two dissimilar constituents, one at the center known as a core which is occupied by the other called shell. Core-shell molecularly imprinting polymers (CSMIPs) are composites prepared via printing a template molecule (analyte) in the coreshell assembly followed by their elimination to provide the everlasting cavities specific to the template molecules. Various other types of CSMIPs with a partial shell, hollow-core and empty-shell are also prepared. Numerous methods have been reported for synthesizing the CSMIPs. CSMIPs composites could develop the ability to identify template molecules, increase the relative adsorption selectivity and offer higher adsorption capacity. Keen features are measured that permits these polymers to be utilized in numerous applications. It has been developed as a modern technique with the probability for an extensive range of uses in selective adsorption, biomedical fields, food processing, environmental applications, in utilizing the plant's extracts for further applications, and sensors. This review covers the approaches of developing the CSMIPs synthetic schemes, and their application with special emphasis on uses in the biomedical field, food care subjects, plant extracts analysis and in environmental studies.


Doxycycline-induced dizziness in a dental patient.
Many dentists are unaware of the documented adverse drug reaction of doxycycline-induced dizziness. Because doxycycline is frequently prescribed in dentistry, it is important for dentists and patients to be aware of this significant adverse reaction to prevent medical complications. A clinical case is reported in which a patient developed dizziness after taking doxycycline that was prescribed following periodontal surgery. The dizziness resolved when the doxycycline was stopped. Patients and dentists should be educated to recognize the signs and symptoms of doxycycline's adverse reactions.


Influenza and influenza-like illness in general practice: drawing lessons for surveillance from a pilot study in Paris, France.
There are two types of inflenza surveillance techniques: qualitative laboratory-based surveillance and quantitative medical practice-based surveillance. The former is of great importance in isolating new strains of the virus, which helps in the decision-making process concerning the composition of the vaccine, and the latter provides estimates of morbidity, mortality or economic impact as a result of infection from the influenza virus. Rapid methods such as immunoflourescence (IF) or immunocapture assays (ICA) are now available for diagnosis of influenza infections. However, little is known about the use of these methods for influenza surveillance purposes. To evaluate the feasibility of a rapid influenza diagnosis in ambulatory conditions, and to investigate the therapeutical outcomes of patients suffering from influenza-like illness (ILI) in relation to the virological diagnoses. During the 1994-1995 influenza season, 130 patients presenting with ILI symptoms (< 36 hours) to 33 general practitioners (GPs) were included in a prospective study. Two nasal swabs and one throat swab per patient were collected and sent to the laboratory within 12 hours. Information concerning therapeutical outcomes was recorded during examination. Specimens were analysed using the immunofluorescence (IF) method and antigen immunocapture assay (ICA). Sixteen influenza A (12%) and 19 influenza B (15%) infections were diagnosed. The overall rate of influenza positive specimens was 17% in the pre-epidemic period and 31% during the epidemic (P = 0.1). The rates of usable specimens for IF assay, nasal ICA and throat ICA were 46%, 100% and 99% respectively. The combination of these three collections ensured a highly sensitive influenza virological diagnosis. There were no differences in therapeutical outcomes between the influenza positive and negative cases. The GPs prescribed antibiotics in 60% of the cases for a mean duration of 7 days (+/- 1.2). The mean duration of sick leave was 3.4 days (+/- 1.6). Twelve patients (four influenza positive, eight influenza negative) had been vaccinated at the beginning of the winter. The practitioner's intuition concerning 'which patient should be tested for influenza virus' did not prove useful in improving the aptness of virological diagnoses in the field of influenza surveillance. The only way to estimate the true impact of influenza is to carry out a systematic virological sampling based on a sensitive clinical definition and using sensitive laboratory methods.


Functional plasminogen activator inhibitor 1 is retained on the activated platelet membrane following platelet activation.
Platelets harbor the primary reservoir of circulating plasminogen activator inhibitor 1 (PAI-1), but the reportedly low functional activity of this pool of inhibitor has led to debate over its contribution to thrombus stability. Here we analyze the fate of PAI-1 secreted from activated platelets and examine its role in maintaining thrombus integrity. Activation of platelets results in translocation of PAI-1 to the outer leaflet of the membrane, with maximal exposure in response to strong dual agonist stimulation. PAI-1 is found to co-localize in the cap of PS-exposing platelets with its cofactor, vitronectin, and fibrinogen. Inclusion of tirofiban or Gly-Pro-Arg-Pro significantly attenuated exposure of PAI-1, indicating a crucial role for integrin αIIbβ3 and fibrin in delivery of PAI-1 to the activated membrane. Separation of platelets post-stimulation into soluble and cellular components revealed the presence of PAI-1 antigen and activity in both fractions, with approximately 40% of total platelet-derived PAI-1 remaining associated with the cellular fraction. Using a variety of fibrinolytic models we found that platelets produce a strong stabilizing effect against tPA-mediated clot lysis. Platelet lysate, as well as soluble and cellular fractions stabilize thrombi against premature degradation in a PAI-1 dependent manner. Our data show for the first time that a functional pool of PAI-1 is anchored to the membrane of stimulated platelets and regulates local fibrinolysis. We reveal a key role for integrin αIIbβ3 and fibrin in delivery of PAI-1 from platelet α-granules to the activated membrane. These data suggest that targeting platelet-associated PAI-1 may represent a viable target for novel profibrinolytic agents.


[Support and guidance in driving for patients with (or suspected of having) Alzheimer's disease or related diseases: position paper].
New ministerial decree restricts driving motorized vehicles for patients with Alzheimer's disease and related disorders. Reisberg stage 3, threshold used to contraindicate driving, appears to correspond to a mild stage of major neurocognitive impairment. A single scale gives an idea of the level of risk but does not provide a holistic assessment. The aim of this consensus is to put forward recommendations from several French learned societies for individualized cognitive assessments to minimize the risks associated with driving and its cessation. Fitness to drive should be raised at the earliest stages of the diagnostic process, and regularly throughout the follow-up. Consult a registered doctor is recommended to all patients wishing to continue driving. All documents must be given to the patient only. An alternative must always be offered to patients who are recommended a modal shift.


Serum protein profiling for diagnosis of breast cancer using SELDI-TOF MS.
In search for novel markers for breast cancer, we aimed to identify and validate novel serum protein profiles specific for breast cancer, and assess the influence of clinical (subjects age) and pre-analytical (sample storage duration) variables on the constructed classifiers. To this end, sera of breast cancer patients (n=152) and healthy controls (n=129), randomly divided into a training and test set, were analysed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS). In the training set, 14 peak clusters were found to differ significantly in expression between cases and controls. None of the peak clusters were influenced by subjects age and sample storage duration. Ten peak clusters were also found significantly discriminative in the test set. Peak clusters were structurally identified as C3a des-arginine anaphylatoxin, (tentative) inter-alpha-trypsin inhibitor heavy chain 4 fragments and a fibrinogen fragment. Logistic regression analyses on the training set yielded a classification model with a moderate performance on the test set, corresponding to those reported in previously performed validation studies. Most likely originating from the highly heterogeneous nature of breast cancer, selection of breast cancer subgroups for comparison with healthy controls is expected to improve results of future diagnostic SELDI-TOF MS studies.


Till death do us pair: Co-evolution of plant-necrotroph interactions.
Plants use programmed cell death as a potent defense response against biotrophic pathogens that require living host cells to thrive. However, cell death can promote infection by necrotrophic pathogens. This discrepancy creates specific co-evolutionary dynamics in the interaction between plants and necrotrophs. Necrotrophic pathogens produce diverse cell death-inducing effectors that act redundantly on several plant targets and sometimes suppress plant immune responses as an additional function. Plants use surface receptors that recognize necrotrophic effectors to increase quantitative disease resistance, some of which evolved independently in several plant lineages. Co-evolution has shaped molecular mechanisms involved in plant-necrotroph interactions into robust systems, relying on degenerate and multifunctional modules, general-purpose components, and compartmentalized functioning.


Quantifying Queensland patients with cancer health service usage and costs: study protocol.
The overall mortality rate for cancer has declined in Australia. However, socioeconomic inequalities exist and the out-of-pocket costs incurred by patients in Australia are high compared with some European countries. There is currently no readily available data set to provide a systematic means of measuring the out-of-pocket costs incurred by patients with cancer within Australia. The primary aim of the project is to quantify the direct out-of-pocket healthcare expenditure of individuals in the state of Queensland, who are diagnosed with cancer. This project will build Australia's first model (called CancerCostMod) of out-of-pocket healthcare expenditure of patients with cancer using administrative data from Queensland Cancer Registry, for all individuals diagnosed with any cancer in Queensland between 1 July 2011 and 30 June 2012, linked to their Admitted Patient Data Collection, Emergency Department Information System, Medicare Benefits Schedule and Pharmaceutical Benefits Scheme records from 1 July 2011 to 30 June 2015. No identifiable information will be provided to the authors. The project will use a combination of linear and logistic regression modelling, Cox proportional hazards modelling and machine learning to identify differences in survival, total health system expenditure, total out-of-pocket expenditure and high out-of-pocket cost patients, adjusting for demographic and clinical confounders, and income group, Indigenous status and geographic location. Results will be analysed separately for different types of cancer. Human Research Ethics approval has been obtained from the Townsville Hospital and Health Service Human Research Ethics Committee (HREC/16/QTHS/110) and James Cook University Human Research Ethics Committee (H6678). Permission to waive consent has been sought from Queensland Health under the Public Health Act 2005.


Reliability of Handheld Blood Glucose Monitors in Neonates: Trustworthy Arterial Readings but Capillary Results Warrant Caution for Hypoglycemia.
Accurate glucose monitoring is vitally important in neonatal intensive care units (NICUs) and clinicians use blood glucose monitors (BGM), such as the Inform II, for bedside glucose monitoring. Studies on BGM use in neonates have demonstrated good reliability; however, most studies only included healthy-term neonates. Therefore, the applicability of results to the preterm and/or ill neonate is limited. In preterm and ill neonates, quantify differences in glucose concentrations between (1) capillary glucose (measured by BGM) and arterial glucose (measured by YSI 2300 Stat Plus) and (2) between aliquots from the same arterial blood sample, one measured by BGM versus one by YSI. Forty neonates were included in the study. Using Inform II, we measured glucose concentrations on blood samples simultaneously collected from capillary circulation via heel puncture and from arterial circulation via an umbilical catheter. Plasma was then separated from the remainder of the arterial whole blood sample and a YSI 2300 Stat Plus measured plasma glucose concentration. The dominant majority of arterial BGM results met the Clinical and Laboratory Standard Institute (CLSI) and Food and Drug Administration (FDA) tolerance criteria. Greater discrepancy was observed with capillary BGM values with an average of 27.5% of results falling outside tolerance criteria. Blood glucose monitor testing provided reliable results from arterial blood. However, users should interpret hypoglycemic results obtained from capillary blood with caution.


Patient experiences following acute HIV infection diagnosis and counseling in South Africa.
Individuals in the acute stage of HIV infection (AHI) have an elevated potential to transmit HIV and play a critical role in the growth of the epidemic. Routine identification and counseling of individuals during AHI could decrease transmission behavior during this key period. However, diagnosis of AHI may present challenges distinct from those experienced through diagnosis of established HIV infection. A study was conducted in a public youth clinic outside of Cape Town, South Africa, to identify and counsel individuals with acute stage HIV infection. In-depth interviews were conducted with patients following diagnosis. After counseling, patients were accepting of the testing regimen used to diagnose AHI. They used the knowledge of having been recently infected to identify the source of their infection, but did not retain or place importance on information regarding the increased ability to transmit HIV during the acute stage. Future interventions directed at the reduction of HIV transmission following diagnosis with AHI will need to find ways of making this information more salient, possibly through more culturally meaningful educational approaches.


Dynamic polyhedral models of globular proteins.
We have devised several mechanical models of globular proteins by approximating them to various polyhedra (dodecahedron, truncated octahedron, icosahedron, truncated icosahedron). The models comprise hollow blocks linked together in a flexible chain. Between blocks there is a set of several reversible, weak magnetic interactions such that when the chain is agitated, it will fold into a stable polyhedral structure about the size of a hand. Folding may be followed in real time with a video camera. Key to the success of the folding process is the lightness of the chain. Several side chains may also be added to the blocks such that they come together to create a polyhedral core when the chain folds. The models have a number of similarities to globular proteins: each chain folds into a unique, but dynamic, three-dimensional structure; the instructions that determine this structure are built into the configuration of blocks; and it is difficult to predict this structure given the unfolded block configuration. Furthermore, the chains fold quickly, generally in less than a minute, several pathways are involved, and these pathways progress through elements of "native" structure. In particular, the models emphasize the importance of restricted conformational mobility in assisting the chain to fold, and also in eliminating undesirable interactions. Because of these similarities to globular proteins, we believe that the polyhedral models will, with continued development, be helpful in understanding the protein folding process, while at the same time acting as valuable educational visual aids. They might also inspire the construction of new types of microscopic, self-assembling devices.


Race-Specific Spirometry Equations Do Not Improve Models of Dyspnea and Quantitative Chest CT Phenotypes.
Race-specific spirometry reference equations are used globally to interpret lung function for clinical, research, and occupational purposes, but inclusion of race is under scrutiny. Does including self-identified race in spirometry reference equation formation improve the ability of predicted FEV1 values to explain quantitative chest CT abnormalities, dyspnea, or Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification? Using data from healthy adults who have never smoked in both the National Health and Nutrition Survey (2007-2012) and COPDGene study cohorts, race-neutral, race-free, and race-specific prediction equations were generated for FEV1. Using sensitivity/specificity, multivariable logistic regression, and random forest models, these equations were applied in a cross-sectional analysis to populations of individuals who currently smoke and individuals who formerly smoked to determine how they affected GOLD classification and the fit of models predicting quantitative chest CT phenotypes or dyspnea. Race-specific equations showed no advantage relative to race-neutral or race-free equations in models of quantitative chest CT phenotypes or dyspnea. Race-neutral reference equations reclassified up to 19% of Black participants into more severe GOLD classes, while race-neutral/race-free equations may improve model fit for dyspnea symptoms relative to race-specific equations. Race-specific equations offered no advantage over race-neutral/race-free equations in three distinct explanatory models of dyspnea and chest CT scan abnormalities. Race-neutral/race-free reference equations may improve pulmonary disease diagnoses and treatment in populations highly vulnerable to lung disease.


The involvement of TNF-alpha-related apoptosis-inducing ligand in the enhanced cytotoxicity of IFN-beta-stimulated human dendritic cells to tumor cells.
TNF-alpha-related apoptosis-inducing ligand (TRAIL) is characterized by its preferential induction of apoptosis of tumor cells but not normal cells. Dendritic cells (DCs), besides their role as APCs, now have been demonstrated to exert cytotoxicity or cytostasis on some tumor cells. Here, we report that both human CD34(+) stem cell-derived DCs (CD34DCs) and human CD14(+) monocyte-derived DCs (MoDCs) express TRAIL and exhibit cytotoxicity to some types of tumor cells partially through TRAIL. Moderate expression of TRAIL appeared on CD34DCs from the 8th day of culture and was also seen on freshly isolated monocytes. The level of TRAIL expression remained constant until DC maturation. TRAIL expression on immature CD34DCs or MoDCs was greatly up-regulated after IFN-beta stimulation. Moreover, IFN-beta could strikingly enhance the ability of CD34DCs or MoDCs to kill TRAIL-sensitive tumor cells, but LPS did not have such an effect. The up-regulation of TRAIL on IFN-beta-stimulated DCs partially contributed to the increased cytotoxicity of DCS: Pretreatment of TRAIL-sensitive tumor cells with caspase-3 inhibitor could significantly increase their resistance to the cytotoxicity of IFN-beta-stimulated DCS: In contrast, NF-kappaB inhibitor could significantly increase the sensitivity of tumor cells to the killing by nonstimulated or LPS-stimulated DCS: Our studies demonstrate that IFN-beta-stimulated DCs are functionally cytotoxic. Thus, an innate mechanism of DC-mediated antitumor immunity might exist in vivo in which DCs act as effectors to directly kill tumor cells partially via TRAIL. Subsequently, DCs act as APCs involved in the uptake, processing, and presentation of apoptotic tumor Ags to cross-prime CD8(+) CTL cells.


Antiviral action and selectivity of 6-azauridine.
6-Azauridine (AzUrd) is a broad-spectrum antimetabolite that inhibits both DNA and RNA virus multiplication. Prior work indicated that several AzUrd-sensitive viruses induced an increase in the level of uridine kinase, and this might explain the selective activity of AzUrd on such viruses. Present studies compared AzUrd sensitive and resistant viruses with respect to their orotic acid pathways by labeling cells with [14C]-orotic acid during the latent period of viral infection. No differences were detected by this method with either vaccinia, Newcastle disease, or vesicular stomatitis viruses. AzUrd inhibits transport of orotic acid into the cell by 30%, while incorporation of orotic acid into cellular RNA is inhibited by 50% (taking into consideration the 30% already noted) when the highest concentration of antimetabolite is used. This suggests that, in addition to blocking orotidylic acid decarboxylase, AzUrd may act on some other site (sites) of action in the inhibition of virus multiplication.


Web-Based Activity Within a Sexual Health Economy: Observational Study.
Regular testing for sexually transmitted infections (STIs) is important to maintain sexual health. Self-sampling kits ordered online and delivered in the post may increase access, convenience, and cost-effectiveness. Sexual health economies may target limited resources more effectively by signposting users toward Web-based or face-to-face services according to clinical need. The aim of this paper was to investigate the impact of two interventions on testing activity across a whole sexual health economy: (1) the introduction of open access Web-based STI testing services and (2) a clinic policy of triage and signpost online where users without symptoms who attended clinics for STI testing were supported to access the Web-based service instead. Data on attendances at all specialist public sexual health providers in an inner-London area were collated into a single database. Each record included information on user demographics, service type accessed, and clinical activity provided, including test results. Clinical activity was categorized as a simple STI test (could be done in a clinic or online), a complex visit (requiring face-to-face consultation), or other. Introduction of Web-based services increased total testing activity across the whole sexual health economy by 18.47% (from 36,373 to 43,091 in the same 6-month period-2014-2015 and 2015-2016), suggesting unmet need for testing in the area. Triage and signposting shifted activity out of the clinic onto the Web-based service, with simple STI testing in the clinic decreasing from 16.90% (920/5443) to 12.25% (511/4172) of total activity, P<.001, and complex activity in the clinic increasing from 69.15% (3764/5443) to 74.86% (3123/4172) of total activity, P<.001. This intervention created a new population of online users with different demographic and clinical profiles from those who use Web-based services spontaneously. Some triage and signposted users (29.62%, 375/1266) did not complete the Web-based testing process, suggesting the potential for missed diagnoses. This evaluation shows that users can effectively be transitioned from face-to-face to Web-based services and that this introduces a new population to Web-based service use and changes the focus of clinic-based activity. Further development is underway to optimize the triage and signposting process to support test completion.


Guiding Low Spatial Ability Individuals through Visual Cueing: The Dual Importance of Where and When to Look.
Research suggests that spatial ability may predict success in complex disciplines including anatomy, where mastery requires a firm understanding of the intricate relationships occurring along the course of veins, arteries, and nerves, as they traverse through and around bones, muscles, and organs. Debate exists on the malleability of spatial ability, and some suggest that spatial ability can be enhanced through training. It is hypothesized that spatial ability can be trained in low-performing individuals through visual guidance. To address this, training was completed through a visual guidance protocol. This protocol was based on eye-movement patterns of high-performing individuals, collected via eye-tracking as they completed an Electronic Mental Rotations Test (EMRT). The effects of guidance were evaluated using 33 individuals with low mental rotation ability, in a counterbalanced crossover design. Individuals were placed in one of two treatment groups (late or early guidance) and completed both a guided, and an unguided EMRT. A third group (no guidance/control) completed two unguided EMRTs. All groups demonstrated an increase in EMRT scores on their second test (P < 0.001); however, an interaction was observed between treatment and test iteration (P = 0.024). The effect of guidance on scores was contingent on when the guidance was applied. When guidance was applied early, scores were significantly greater than expected (P = 0.028). These findings suggest that by guiding individuals with low mental rotation ability "where" to look early in training, better search approaches may be adopted, yielding improvements in spatial reasoning scores. It is proposed that visual guidance may be applied in spatial fields, such as STEMM (science, technology, engineering, mathematics and medicine), surgery, and anatomy to improve student's interpretation of visual content. Anat Sci Educ. © 2018 American Association of Anatomists.


Nociceptive transmission within the spinal cord.
Pain pathways in the spinal cord transmit information about actual or impending tissue damage. There are parallel pathways to both the medial (motivational-affective) and lateral (sensory-discriminative) portions of the system. Endogenous systems modulate pain transmission and ultimately pain perception. These modulatory systems can be accessed pharmacologically by naturally occurring neurotransmitters and neuromodulators. Research is being done to identify receptor specific agents that selectively inhibit pain and do not interfere with processing of other information.


The organization of a counselling service for the families of patients undergoing bone marrow transplant.
The organisation of our Counselling Service for the relatives of patients undergoing bone marrow transplant is structured in various phases. During the first phase, contact is established with the relatives. The therapist introduces himself to the relatives when the patient is hospitalized and enters the sterile ward. The second phase consists in an illustration of the objectives and purpose of the Service. During this phase, two weekly interviews lasting approximately one hour are proposed, plus assessment tests (CFI, Camberwell Family Interview--and MMPI--Minnesota Multiphasic Personality Inventory). A third phase, which is often contextual to the presentation of the Service, consists in the recognition of the needs and suffering of the given relative. Here, the therapist acts as a receptacle for the anxieties and fear of death brought to him by the subject, thus empathetically accepting these states of mind and legitimizing them. Moreover, our model of intervention envisages the formation of support groups for the relatives of patients suffering from blood cancers. A further phase concerns the exchange of information between the two therapists helping, respectively, the relative and the patient, and also with medical and nursing staff. To further the same aims, for a number of years now, our Service has been organising intervention groups for nursing staff working at CTMO. The final phase is counselling, which takes place twice a week. There are two fundamental areas of intervention that must be taken into account for families of subjects suffering from blood cancers: providing information and offering support. From our experience, it emerges that the relatives need to obtain information on organic aspects of the illness and the transplant.


Interferon-gamma modulates human oligodendrocyte susceptibility to Fas-mediated apoptosis.
Interferon gamma (IFN-gamma) has been shown to be produced within multiple sclerosis (MS) lesions by infiltrating lymphocytes; systemic administration of this cytokine induces exacerbation of the disease. The aim of the current study was to establish the contribution of IFN-gamma to oligodendrocyte (OL) injury. Our studies utilized cultured human OLs, obtained by dissociation of surgically derived non-MS adult brain tissue. Neither cell survival nor myelin basic protein (MBP) gene expression were affected after 96 hours of treatment with IFN-gamma (100 U/ml), as assessed by LDH release, nucleosome enrichment assay, and RT-PCR. Expression of the death receptor Fas (CD95, APO-1) was, however, significantly increased. Furthermore, IFN-gamma-treated OLs became susceptible to Fas-mediated apoptosis when compared with untreated cells, and were protected by pretreatment with the caspase inhibitor ZVAD. TNF-alpha augmented the IFN-gamma-induced effect. Our results thus indicate that IFN-gamma is not directly cytotoxic for human OLs in culture, but could indirectly modulate functional injury-related responses by upregulating Fas on the cell surface.


Identification of Host Factors Involved in Human Cytomegalovirus Replication, Assembly, and Egress Using a Two-Step Small Interfering RNA Screen.
As obligate intracellular parasites, viruses are completely dependent on host factors for replication. Assembly and egress of complex virus particles, such as human cytomegalovirus (HCMV), are likely to require many host factors. Despite this, relatively few have been identified and characterized. This study describes a novel high-throughput, two-step small interfering RNA (siRNA) screen, which independently measures virus replication and virus production. By combining data from replication and virus production, multiple candidate genes were identified in which knockdown resulted in substantial loss of virus production with limited effect on primary replication, suggesting roles in later stages such as virus assembly and egress. Knockdown of the top candidates, ERC1, RAB4B, COPA, and COPB2, caused profound loss of virus production. Despite COPA and COPB2 being reported to function in the same complex, knockdown of these genes produced distinct phenotypes. Furthermore, knockdown of COPA caused increased expression of viral late genes despite substantial inhibition of viral DNA replication. This suggests that efficient viral genome replication is not required for late gene expression. Finally, we show that RAB4B relocates to the viral assembly compartment following infection with HCMV and knockdown of RAB4B reduces the release of intact virion particles, suggesting that it plays a role in virion assembly and egress. This study demonstrates a powerful high-throughput screen for identification of host-virus interactions, identifies multiple host genes associated with HCMV assembly and egress, and uncovers potentially independent functions for coatomer components COPA and COPB2 during infection.IMPORTANCE Human cytomegalovirus infection is a significant cause of disease in immunocompromised populations, individuals with heart disease, and recipients of solid organ and bone marrow transplants. HCMV is also the leading cause of infectious congenital birth defects. The majority of antivirals in clinical use target components of the virus to specifically inhibit replication. However, a major drawback of this approach is the emergence of resistance. An alternative approach is to target host factors that the virus requires for successful infection. In this study, multiple host factors were identified that were found to be essential for the production of newly infectious human cytomegalovirus. Identifying which host genes are necessary for virus replication extends our understanding of how viruses replicate and how cells function and provides potential targets for novel antivirals.


Acute and chronic musculoskeletal pain situations among the working population and their pain education needs: an exploratory study.
Pain affects a person's physical and psychological well-being, work performance and productivity. Working population bear their pain and continue to work which may contribute to the worsening of their pain condition. However, their pain situation was not well-examined. The aim of the study was to explore the prevalence of acute and chronic pain in the working population in Hong Kong, understand their pain management strategies and determine their preferences with regard to the use of electronic pain management materials. This was an exploratory online survey. The participants' pain history, their preferences in methods of pain management, the source of the pain management education that they had received, sources and preferences in relation to the use of the Internet for pain education, and the participants' demographic characteristics were collected. A total of 210 participants joined the study, 67% of whom were experiencing pain. Of the group in pain, 71.6% were in chronic pain that has persisted for 3 months or more. Pain intensities ranged from 2.82 to 3.82 on a 10-point numeric scale. Of the participants, 85.7% reported not receiving adequate pain management education, and 91.4% of those agreed pain services were inadequate. Websites and health care professionals were the sources from which they obtained their pain management education. The high prevalence of pain in the working population requires special attention. Health care professionals should be proactive and an online pain management programme can be a solution to address the critical problem of pain in the working population.


Peroxidase-Like Activity of Magnetic Nanoparticles in the Presence of Blood Proteins.
The generation of hydroxyl radicals from hydrogen peroxide in aqueous solutions containing magnetic nanoparticles (MNPs), hemoglobin (Hb), immunoglobulin G (IgG), and human serum albumin (HSA) was determined. The dependence of the rate of formation of the oxidized product of o-phenylenediamine (o-PDA) on the concentration of MNPs in solution, as well as on the concentration of proteins, was obtained. The peroxidase-like activity of MNPs was shown to decrease in the presence of HSA and IgG, while the addition of Hb to the reaction mixture led to its decrease and increase depending on protein concentration. The obtained effects can be used in the engineering of systems based on MNPs for theranostics (in particular, for suppression of tumor growth) and in predicting the ability of particles to catalyze the generation of reactive oxygen species (ROS) in vivo.


Ethnic diversity in type 2 diabetes.
The present review assesses published data relating to the main ethnic groups in the UK Prospective Diabetes Study (UKPDS), namely White Caucasians (WC; 82% of the cohort), Indian-Asians (IA; 10%) and Afro-Caribbeans (AC; 8%). At entry, the IA patients were younger than WC and AC patients, had a greater waist-hip ratio and more sedentary lifestyle, but had the lowest prevalence of hypertension and current smoking. The AC patients had the poorest glycaemic control but the most favourable lipid profile. The differences in modifiable vascular risk factors did not change over 9 years of follow-up. Consistent with UKPDS exclusion criteria, few patients had complications at baseline and there were no between-group differences. An interim analysis of incident fatal/non-fatal myocardial infarction (median follow-up 8.7 years) showed that the AC patients had a 70% lower risk than WC after adjustment for explanatory variables and that IA patients had a similar risk to WC. An analysis of complete albuminuria and renal failure data (median follow-up 15 years) showed that IA ethnicity was independently associated with an increased risk. There are sustained ethnic differences in the nature of diabetes, including vascular risk factors. AC patients had a substantially reduced risk of myocardial infarction that was not explained by their more favourable lipid profile, while IA patients were more likely to develop nephropathy than WC and IA patients. Longer follow-up is needed to determine whether the increased macrovascular risk observed in IA patients in other studies is replicated in the UKPDS cohort.


Hypoxia inducible factor-1 improves the actions of nitric oxide and natriuretic peptides after simulated ischemia-reperfusion.
Ischemia-reperfusion reduces the negative functional effects of cyclic GMP in cardiac myocytes. In this study, we tested the hypothesis that upregulation of hypoxic inducible factor-1 (HIF-1) would improve the actions of cyclic GMP signaling following simulated ischemia-reperfusion. HIF-1 alpha was increased with deferoxamine (150 mg/kg for 2 days). Rabbit cardiac myocytes were subjected to simulated ischemia [15 min 95% N(2)-5% CO(2)] and reperfusion [reoxygenation] to produce myocyte stunning. Cell function was measured utilizing a video-edge detector. Shortening was examined at baseline and after brain natriuretic peptide (BNP, 10(-8), 10(-7)M) or S-nitroso-N-acetyl-penicillamine (SNAP, 10(-6), 10(-5)M) followed by KT5823 (cyclic GMP protein kinase inhibitor, 10(-6)M). Kinase activity was measured via a protein phosphorylation assay. Under control conditions, BNP (-30%) and SNAP (-41%) reduced percent shortening, while KT5823 partially restored function (+18%). Deferoxamine treated control myocytes responded similarly. In stunned myocytes, BNP (-21%) and SNAP (-25%) reduced shortening less and KT5823 did not increase function (+2%). Deferoxamine increased the effects of BNP (-38%) and SNAP (-41%) in stunning and restored the effects of KT5823 (+12%). The cyclic GMP protein kinase increased phosphorylation of several proteins in control HIF-1 +/- cells. Phosphorylation was reduced in stunned cells and was restored in deferoxamine treated stunned cells. This study demonstrated that simulated ischemia-reperfusion reduced the negative functional effects of increasing cyclic GMP and this was related to reduced effects of the cyclic GMP protein kinase. Increased HIF-1 alpha protects the functional effects of cyclic GMP thorough maintenance of cyclic GMP protein kinase activity after ischemic-reperfusion.


Digital contact-tracing and pandemics: Institutional and technological preparedness in Africa.
Several countries in Africa have either deployed or considering using digital contact-tracing (DCT) as part of their Covid-19 containment strategy, amidst calls for the use of technology to improve the efficiency of traditional contact-tracing. We discuss some of the complexities entailed in using DCT in Africa. Adopting a socio-technical perspective, we argue that if DCT design and deployment are not well thought out, it can lead to unintended consequences, particularly in a continent like Africa with disproportionate levels of digital divides and other structural inequalities. We suggest that any adoption of DCT by African countries must take account of their compatibility with local resources, values, social structure, and domestic political factors. Accordingly, we propose a process of translation whereby DCT adaptation is made to accommodate the unique institutional and technological characteristics of African countries by leveraging local practices learned from previous pandemics like Ebola to develop a blended epidemiological approach to (digital) contact-tracing.


Management in severe dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.
Alzheimer's disease (AD) and other neurodegenerative dementias have a progressive course, impairing cognition, functional capacity, and behavior. Most studies have focused on AD. Severe dementia is associated with increased age, higher morbidity-mortality, and rising costs of care. It is fundamental to recognize that severe dementia is the longest period of progression, with patients living for many years in this stage. It is the most heterogeneous phase in the process, with different abilities and life expectancies. This practice guideline focuses on severe dementia to improve management and care in this stage of dementia. As it is a long period in the continuum of dementia, clinical practice should consider non-pharmacological and pharmacological approaches. Multidisciplinary interventions (physical therapy, speech therapy, nutrition, nursing, and others) are essential, besides educational and support to caregivers.


Trends in diagnostic tests ordered for children: a retrospective analysis of 1.7 million laboratory test requests in Oxfordshire, UK from 2005 to 2019.
To better understand testing patterns in children, we measured temporal trends in paediatric testing from 2005 to 2019 in Oxfordshire, UK. Descriptive study of population-based secondary data. Oxfordshire University Hospitals National Health Service Trust laboratories. Children aged 0-15 years in Oxfordshire who received at least one blood test. We estimated average annual percentage changes (AAPCs) in test use using joinpoint regression models. Temporal changes in age-adjusted rates in test use were calculated overall and stratified by healthcare setting, sex, and age. Between 2005 and 2019, 1 749 425 tests were performed among 113 607 children. Overall test use declined until 2012, when test rates appeared to increase (AAPC 1.5%, 95% CI -0.8% to 3.9%). Most tests were performed in inpatient settings, where testing rates stayed steady (AAPC -0.6%, 95% CI -2.1% to 0.9%). Increases were highest in females, those aged 6-15 years and in the outpatient setting. The greatest increase in testing was for vitamin D (AAPC 26.5%), followed by parathyroid hormone (9.8%), iron studies (9.3%), folate (8.4%), vitamin B12 (8.4%), HbA1c (8.0%), IgA (7.9%) and coeliac (7.7%). After an initial decline, laboratory test use by children in Oxfordshire demonstrated an apparent increase since 2012. Test use increased in outpatient and general practice settings, however remained steady in inpatient settings. Further research should examine the root causes and implications for test increases, and whether these increases are warranted. We encourage clinicians to consider the individual and systemic implications of performing blood tests in children.


[Aerosol therapy in infants].
Infants are a unique subpopulation with regard to aerosol therapy. There are various anatomical, physiological and emotional factors peculiar to infants that present significant difficulties and challenges for aerosol delivery. Most studies about the factors determining lung deposition of therapeutic aerosols are based on data from adults or older children which cannot simply be extrapolated directly to infants. The present review describes why infants/toddlers are very different with respect to two major issues--namely their anatomy/physiology and their behaviour. We suggest possible solutions and future research directions aimed at improving clinical outcomes in this age group.


Dissecting the presence of malignant squamous cells in pancreatic cytopathology: A case series.
The presence of malignant squamous cells in pancreatic cytopathology is a rare phenomenon that results either from a primary or a metastatic process. Pancreatic adenosquamous carcinoma (PASC) represents the most common variant of pancreatic ductal adenocarcinoma and is associated with a dismal prognosis. Within the period of 2013-2018, the archives of "Hygeia and Mitera Hospital" were searched for pancreatic cytopathology-related diagnoses that included the interpretation of "malignant squamous cells present." All fine needle aspirations (FNAs) of pancreatic lesions, including liver metastases in patients with known pancreatic primaries, were retrieved along with their relevant clinical information. Five pancreatic and two liver FNAs acquired from a total of six patients were reexamined. None of these patients had any documented history of primary squamous malignancy elsewhere. All pancreatic and one of the two liver FNAs showed malignant squamous cells, identified based on either morphology or immunochemistry. The other liver FNA represented a metastatic deposit which comprised of only a glandular component, whereas the associated pancreatic FNA exhibited both squamous and glandular counterparts. Most cases characteristically showed necrosis and keratinization. Of interest, two cases revealed the presence of tumor-associated giant cells. In conclusion, the presence of malignant squamous cells in pancreatic FNAs could mean the presence of PASC, especially when there is no documented history of a primary malignancy and a complete clinical and imaging workup has been performed. Immunochemistry on cell block material could help to confirm squamous differentiation in the absence of overt keratinization.


Vaccines for Prevention of Bluetongue and Epizootic Hemorrhagic Disease in Livestock: A North American Perspective.
Bluetongue (BT) and epizootic hemorrhagic disease (EHD) are noncontagious, insect-transmitted diseases of domestic and wild ruminants caused by related but distinct viruses. There are significant gaps in our scientific knowledge and available countermeasures to control an outbreak of orbivirus-induced disease, whether BT or EHD. Both BT virus (BTV) and EHD virus (EHDV) cause hemorrhagic fevers in susceptible ruminants; however, BT is principally a disease of domestic livestock whereas EHD is principally a disease of certain species of wild, non-African ungulates, notably white-tailed deer. The live-attenuated (modified live virus [MLV]) vaccines available in the United States for use in small ruminant livestock do provide good protection against clinical disease following infection with the homologous virus serotype. Although there is increasing justification that the use of MLV vaccines should be avoided if possible, these are the only vaccines currently available in the United States. Specifically, MLVs are used in California to protect sheep against infection with BTV serotypes 10, 11, and 17, and a MLV to BTV serotype 10 is licensed for use in sheep throughout the United States. These MLV vaccines may need to continue to be used in the immediate future for protective immunization of sheep and goats against BT. There are currently no licensed vaccines available for EHD in the United States other than autogenous vaccines. If there is a need to rapidly develop a vaccine to meet an emerging crisis associated with either BTV or EHDV infections, development of an inactivated virus vaccine in a conventional adjuvanted formulation will likely be required. With two doses of vaccine (and in some instances just one dose), inactivated vaccines can provide substantial immunity to the epizootic serotype of either BTV or EHDV. This strategy is similar to that used in the 2006-2008 BTV serotype 8 outbreaks in northern Europe that provided vaccine to the field within 2 years of the initial incursion (by 2008). Further research and development are warranted to provide more efficacious and effective vaccines for control of BTV and EHDV infections.


[Homeostasis and paravasal damper structures in intact and damaged nerves and long tubular bones].
Sciatic and tibial nerves and a femoral osteotomic area were investigated in experiments on 36 adult mongrel dogs during neutral and distractional osteosynthesis. Histological and X-ray studies, computer-assisted image analysis, and statistical methods were used. The morphological basis of hemodynamic features of the nerves and long tubular bones was characterized. The mechanisms responsible for perivascular osteogenesis in the bone marrow cavity and for hypertrophy of perineural cell paravasal spongy structures in the nerves were studied as compensatory and adaptive responses to changes in the hemodynamical components of homeostasis after bone injury and during extremity stretching.


Immobilization of Sertoli cells on islets of Langerhans.
Sertoli cells play a crucial role in creating the immunoprivileged environment of the testis. We examined the survival of islets of Langerhans after co-transplantation with Sertoli cells. Sertoli cells near islets should protect the graft from rejection. In this study, conjugates of single stranded oligonucleotides, poly(ethylene glycol) and phospholipids (ssDNA-PEG-DPPE) were used to immobilize Sertoli cells on islets. The 20-mer of deoxyadenylic acid (oligo(dA)20) and 20-mer of deoxythymidylic acid (oligo(dT)20) were presented as ssDNAs on the surfaces of Sertoli cells and islets, respectively, through the hydrophobic interaction between a lipid unit of the conjugates and the cell membrane. The Sertoli cells were immobilized on the islets through hybridization between oligo(dA)20 and oligo(dT)20. When Sertoli cell-immobilized islets were infused into the liver of mice through the portal vein, the Sertoli cells remained around the islets.


Kinesin's light chains inhibit the head- and microtubule-binding activity of its tail.
Kinesin-1 is a microtubule-based motor comprising two heavy chains (KHCs) and two light chains (KLCs). Motor activity is precisely regulated to avoid futile ATP consumption and to ensure proper intracellular localization of kinesin-1 and its cargoes. The KHC tail inhibits ATPase activity by interacting with the enzymatic KHC heads, and the tail also binds microtubules. Here, we present a role for the KLCs in regulating both the head- and microtubule-binding activities of the kinesin-1 tail. We show that KLCs reduce the affinity of the head-tail interaction over tenfold and concomitantly repress the tail's regulatory activity. We also show that KLCs inhibit tail-microtubule binding by a separate mechanism. Inhibition of head-tail binding requires steric and electrostatic factors. Inhibition of tail-microtubule binding is largely electrostatic, pH dependent, and mediated partly by a highly negatively charged linker region between the KHC-interacting and cargo-binding domains of the KLCs. Our data support a model wherein KLCs promote activation of kinesin-1 for cargo transport by simultaneously suppressing tail-head and tail-microtubule interactions. KLC-mediated inhibition of tail-microtubule binding may also influence diffusional movement of kinesin-1 on microtubules, and kinesin-1's role in microtubule transport/sliding.


Neurodevelopmental outcome at 5.5 years in Dutch preterm infants born at 24-26 weeks' gestational age: the EPI-DAF study.
After lowering the Dutch threshold for active treatment from 25 to 24 completed weeks' gestation, survival to discharge increased by 10% in extremely preterm live born infants. Now that this guideline has been implemented, an accurate description of neurodevelopmental outcome at school age is needed. Population-based cohort study. All neonatal intensive care units in the Netherlands. All infants born between 240/7 and 266/7 weeks' gestation who were 5.5 years' corrected age (CA) in 2018-2020 were included. Main outcome measure was neurodevelopmental outcome at 5.5 years. Neurodevelopmental outcome was a composite outcome defined as none, mild or moderate-to-severe impairment (further defined as neurodevelopmental impairment (NDI)), using corrected cognitive score (Wechsler Preschool and Primary Scale of Intelligence Scale-III-NL), neurological examination and neurosensory function. Additionally, motor score (Movement Assessment Battery for Children-2-NL) was assessed. All assessments were done as part of the nationwide, standardised follow-up programme. In the 3-year period, a total of 632 infants survived to 5.5 years' CA. Data were available for 484 infants (77%). At 5.5 years' CA, most cognitive and motor (sub)scales were significantly lower compared with the normative mean. Overall, 46% had no impairment, 36% had mild impairment and 18% had NDI. NDI-free survival was 30%, 49% and 67% in live born children at 24, 25 and 26 weeks' gestation, respectively (p<0.001). After lowering the threshold for supporting active treatment from 25 to 24 completed weeks' gestation, a considerable proportion of the surviving extremely preterm children did not have any impairment at 5.5 years' CA.


Promoter elements and transcription factors involved in differentiation-dependent human chorionic gonadotrophin-alpha messenger ribonucleic acid expression of term villous trophoblasts.
Differentiation of primary villous cytotrophoblasts into syncytia is associated with increasing production of alpha and beta human CG subunits, which is predominantly governed at the level of messenger RNA expression. Here, we present a detailed study on the mechanisms involved in the differentiation-dependent regulation of the trophoblast-specific CGalpha gene promoter. Site-directed mutations in each of the five DNA-elements of the composite enhancer were performed to investigate the contribution of the individual regulatory sequences to the overall transcriptional activity of the promoter at two different stages of trophoblast in vitro differentiation. We show that deletion of one cyclic AMP response element (CRE) did not affect CGalpha promoter activity in cytotrophoblasts; however, it reduced transcription by 33% in differentiating cultures. Removal of both CREs almost abolished transcription at early and later stages of in vitro differentiation. Upon mutation the enhancer elements alphaACT, JRE, and CCAAT significantly decreased luciferase reporter transcription; however their contribution to the total promoter activity did not change during in vitro differentiation. Contrary to that, mutated TSE diminished promoter activity by 19% during 12 and 48 h of cultivation but reduced luciferase expression by 78% between 48 and 84 h of differentiation. In electrophoretic mobility shift assay, the TSE interacted with activating protein (AP)-2alpha in both primary trophoblasts and choriocarcinoma cells. While CRE-interacting proteins were detectable 12 h after isolation, the TSE-binding complex did not appear before 36 h of in vitro differentiation. During syncytium formation increasing protein expression of activating transcription factor (ATF)-1, cAMP response element-binding protein (CREB)-1, and AP-2alpha was observed on Western blots. Moreover, phosphorylated CREB-1 and ATF-1 accumulated between 24 and 78 h of trophoblast cultivation. By fluorescence immunohistochemistry, we show that CREB-1 was predominantly expressed in syncytiotrophoblasts, whereas ATF-1 and AP-2alpha localized to the syncytium and some cytototrophoblasts as well as to stromal and endothelial cells of the placental villus. Phosphorylated CREB-1/ATF-1 and the coactivator protein CBP were primarily detected in syncytial nuclei, suggesting the presence of functional, cAMP-dependent transcriptional complexes in the differentiated tissue. In agreement to the in vivo situation, phosphorylated CREB-1/ATF-1 were observed in nuclei of the differentiated trophoblast cultures. The activity of the CGalpha promoter as well as CREB-1/ATF-1 phosphorylation increased upon elevation of cAMP levels and overexpression of the catalytic subunit of protein kinase A. Additionally, we demonstrate that overproduction of the enzyme enhanced protein expression and binding of AP-2alpha to the TSE. We conclude that differentiation-dependent transcription of the CGalpha gene in villous trophoblasts is mainly governed by increasing expression of AP-2alpha and PKA-dependent phosphorylation of CREB-1 and ATF-1.


Health-related quality-of-life assessment in surgical patients with papillary thyroid carcinoma: A single-center analysis from Mainland China.
Even with a favorable prognosis, the health-related quality of life (HRQoL) of papillary thyroid carcinoma (PTC) patients remains unclear and conflicting. Thus, in the present study, we compared the HRQoL of PTC patients with that of the general population (GP).The study was performed in our thyroid and parathyroid surgery department, and 186 PTC patients who had undergone thyroidectomy were included. The exclusion criteria were an age < 18 years, no follow-up, and the presence of other malignant neoplasms. The control group included 186 volunteers who were matched by age, gender, and socioeconomic status. The survivor and control groups were asked to complete the Chinese version of the SF-36 questionnaire.The 186 volunteers from the GP were well matched to PTC patients with respect to the baseline demographic characteristics. PTC patients showed significantly lower scores than those of the control group in 7 domains of the HRQoL: role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH). PTC was a risk factor for a low Physical Component Summary (PCS) score and a low Mental Component Summary (MCS) score (all P values were less than .05). Significant reductions in the scores of all 8 domains were observed at 1 month after the operation, and obvious recovery was noted at 6 months according to the PCS and MCS scores (all P values were less than .05). However, even 2 years after surgery, few domain scores had recovered to levels found in the GP, including the PCS and MCS scores (all P values were less than .05).Due to the decreased preoperative and postoperative HRQoL scores, much attention should be given to and more long-term observation should be performed for PTC patients, even those who have undergone surgery.


Evaluating the composition and processing potential of novel sources of Brazilian biomass for sustainable biorenewables production.
The search for promising and renewable sources of carbohydrates for the production of biofuels and other biorenewables has been stimulated by an increase in global energy demand in the face of growing concern over greenhouse gas emissions and fuel security. In particular, interest has focused on non-food lignocellulosic biomass as a potential source of abundant and sustainable feedstock for biorefineries. Here we investigate the potential of three Brazilian grasses (Panicum maximum, Pennisetum purpureum and Brachiaria brizantha), as well as bark residues from the harvesting of two commercial Eucalyptus clones (E. grandis and E. grandis x urophylla) for biofuel production, and compare these to sugarcane bagasse. The effects of hot water, acid, alkaline and sulfite pretreatments (at increasing temperatures) on the chemical composition, morphology and saccharification yields of these different biomass types were evaluated. The average yield (per hectare), availability and general composition of all five biomasses were compared. Compositional analyses indicate a high level of hemicellulose and lignin removal in all grass varieties (including sugarcane bagasse) after acid and alkaline pretreatment with increasing temperatures, whilst the biomasses pretreated with hot water or sulfite showed little variation from the control. For all biomasses, higher cellulose enrichment resulted from treatment with sodium hydroxide at 130°C. At 180°C, a decrease in cellulose content was observed, which is associated with high amorphous cellulose removal and 5-hydroxymethyl-furaldehyde production. Morphological analysis showed the effects of different pretreatments on the biomass surface, revealing a high production of microfibrillated cellulose on grass surfaces, after treatment with 1% sodium hydroxide at 130°C for 30 minutes. This may explain the higher hydrolysis yields resulting from these pretreatments, since these cellulosic nanoparticles can be easily accessed and cleaved by cellulases. Our results show the potential of three Brazilian grasses with high productivity yields as valuable sources of carbohydrates for ethanol production and other biomaterials. Sodium hydroxide at 130°C was found to be the most effective pretreatment for enhanced saccharification yields. It was also efficient in the production of microfibrillated cellulose on grass surfaces, thereby revealing their potential as a source of natural fillers used for bionanocomposites production.


Quantum state engineering with nitrogen-vacancy centers coupled to low-Q microresonator.
We demonstrate efficient schemes of deterministic entanglement generation and quantum state transfer (QST) with the nitrogen-vacancy (NV) centers in diamond confined in separated microtoroidal resonators via single-photon input-output process. Assisted by the polarization of input photon pulse and the electron spin state of NV center, high fidelity NV center entangled states and photonic entangled states can be generated, respectively. The analyses of experimental feasibility show that our schemes work well with low quality resonators and weak coupling between qubits, which may be beneficial for exploring large-scale quantum information processing with diamond-based solid-state devices.


The ACA's Impact On Racial And Ethnic Disparities In Health Insurance Coverage And Access To Care.
Large disparities in health insurance coverage and access to health services have long persisted in the US health care system. We considered how the insurance coverage expansions of the Affordable Care Act have affected disparities related to race and ethnicity. In the years since the law went into effect, insurance coverage has increased significantly for all racial/ethnic groups. Because coverage increased more for non-Hispanic blacks and Hispanics than for non-Hispanic whites, disparities in coverage have decreased. Despite these improvements, a large number of adults remain uninsured, and the uninsurance rate among blacks and Hispanics is substantially higher than the rate among whites.


Cardiac effects of angiotensin I and angiotensin II: dose-response studies in the isolated perfused rat heart.
We investigated the effects of angiotensin I (4 x 10(-9), 4 x 10(-8) and 4 x 10(-7) M) on myocardial contractility, heart rate and coronary perfusion in the isolated rat heart before and after inhibition of angiotensin-converting enzyme (ACE) by captopril (4 x 10(-4) M). We also studied the post-ischaemic recovery of cardiac function in isolated hearts subjected to global myocardial ischaemia and reperfused with various doses of angiotensin II (1 x 10(-9), 1 x 10(-8) and 1 x 10(-7) M). Angiotensin I significantly reduced coronary flow, the vasoconstrictor effect of a second identical dose was attenuated after inhibition of ACE with captopril. Angiotensin II reduced coronary flow to the same extent as angiotensin I at a concentration four times lower. Left ventricular developed pressure was reduced by angiotensin I and angiotensin II in a dose-dependent manner. Heart rate was not affected by angiotensin I and was significantly lowered by the highest doses (1 x 10(-8) and 1 x 10(-7) M) of angiotensin II. Post-ischaemic recoveries of vascular and contractile function were similar in control hearts and in hearts given angiotensin II during reperfusion. However, left ventricular end-diastolic pressure was increased by the highest dose (1 x 10(-7) M) of angiotensin II throughout reperfusion compared with controls or hearts receiving lower doses (NS). In conclusion the attenuated vasoconstrictor response to angiotensin I after captopril pre-treatment confirms the existence of an intracardiac renin-angiotensin system operative in vitro. Our results also suggest that angiotensin II, at a high concentration, may play a negative role in relaxation in the ischaemic-reperfused injured heart.


Unveiling the Potential of Bioinoculants and Nanoparticles in Sustainable Agriculture for Enhanced Plant Growth and Food Security.
The increasing public concern over the negative impacts of chemical fertilizers and pesticides on food security and sustainability has led to exploring innovative methods that offer both environmental and agricultural benefits. One such innovative approach is using plant-growth-promoting bioinoculants that involve bacteria, fungi, and algae. These living microorganisms are applied to soil, seeds, or plant surfaces and can enhance plant development by increasing nutrient availability and defense against plant pathogens. However, the application of biofertilizers in the field faced many challenges and required conjunction with innovative delivering approaches. Nanotechnology has gained significant attention in recent years due to its numerous applications in various fields, such as medicine, drug development, catalysis, energy, and materials. Nanoparticles with small sizes and large surface areas (1-100 nm) have numerous potential functions. In sustainable agriculture, the development of nanochemicals has shown promise as agents for plant growth, fertilizers, and pesticides. The use of nanomaterials is being considered as a solution to control plant pests, including insects, fungi, and weeds. In the food industry, nanoparticles are used as antimicrobial agents in food packaging, with silver nanomaterials being particularly interesting. However, many nanoparticles (Ag, Fe, Cu, Si, Al, Zn, ZnO, TiO2, CeO2, Al2O3, and carbon nanotubes) have been reported to negatively affect plant growth. This review focuses on the effects of nanoparticles on beneficial plant bacteria and their ability to promote plant growth. Implementing novel sustainable strategies in agriculture, biofertilizers, and nanoparticles could be a promising solution to achieve sustainable food production while reducing the negative environmental impacts.


The Evaluation of Astaxanthin Effects on Differentiation of Human Adipose Derived Stem Cells into Oligodendrocyte Precursor Cells.
Multiple Sclerosis (MS) has been explained as an autoimmune mediated disorder in central nerve system. Since conventional therapies for MS are not able to stop or reverse the destruction of nerve tissue, stem cell-based therapy has been proposed for the treatment of MS. Astaxanthin (AST) is a red fat-soluble xanthophyll with neuroprotection activity. The aim of this study was evaluation of pre-inducer function of AST on differentiation of human Adipose-Derived Stem Cells (hADSCs) into oligodendrocyte precursor cells. After stem cell isolation, culture and characterization by flow cytometry, hanging drop technique was done for embryoid body formation. In the following, hADSCs were differentiated into oligodendrocyte cells in the presence of AST at various concentrations (1, 5, and 10 ng/ml). Finally, immunocytochemistry and real-time PCR techniques were used for assessment of oligodendrocyte differentiation. Flow cytometry results indicated that hADSCs were CD44, CD49-positive, but were negative for CD14, CD45 markers. In addition, immunocytochemistry results revealed that, in AST treated groups, the mean percentage of Olig 2 and A2B5 positive cells increased especially in 5 ng/ml AST treated group compared to control group (p<0.001). Moreover, real-time PCR analysis confirmed the results of immunocytochemistry. Since hADSCs have the potential to differentiate into multi lineage cells and due to important functions of AST in regulating various cellular processes, it seems that AST can be used as a promoter for oligodendrocyte differentiation of hADSCs for being used in cell transplantation in multiple sclerosis.


The regulation of subcutaneous adipose tissue blood flow in the ischaemic forefoot during 24 hours. Studies using the 133-xenon wash-out technique continuously over 24 hours.
A method for continuous measurement of subcutaneous adipose tissue blood flow in the forefoot during 24 hours (SBF) is described. The method is based on the radioisotope wash-out principle using 133-Xenon. A portable semiconductor detector is placed just above a local depot of 1-2 microCi 133-Xenon in 0.1 ml isotonic saline injected into the subcutaneous adipose tissue in the forefoot. The detector is connected to a memory unit allowing for storage of data. Due to the short distance, the recorded elimination rate constant must be corrected for combined convection and diffusion of the radioactive indicator. Characteristic 24-hour blood flow patterns were unveiled in patients with normal peripheral circulation and in patients having ischaemic nocturnal rest pain. In normals SBF doubled from day to night. This is ascribed to the local veno-arteriolar sympathetic axon reflex, which induces arteriolar vasoconstriction when the transmural pressure of the veins exceeds approximately 25 mmHg. In patients having ischaemic rest pains SBF was reduced by 37% on the average from day to night. This was caused by nocturnal hypotension, which is reflected proportionally in the foot. As the resistance vessels most probably are fully dilatated in feet with rest pain, the blood pressure drop during sleep causes the perfusion pressure and thus blood flow to come below a certain critical limit. There was a pronounced correlation between the reduction of systemic mean arterial blood pressure and SBF. The patients complaining of intermittent claudication, but no rest pains showed a variety of changes in SBF compatible with the continuous spectrum of the peripheral arteriosclerotic disease. After reconstructive vascular surgery, the 24-hour blood flow pattern normalized although the ankle/arm systolic blood pressure index did not come within normal range. SBF during day-time activities decreased by up to 50% postoperatively. This is caused by the reappearance of the local, sympathetic, veno-arteriolar vasoconstrictor response. During sleep SBF increased by 71%. The term postreconstructive hyperaemia seems improper, at least in a long-term context, normalization of preoperative ischaemia is a more correct notation. The coefficient of variation of nocturnal SBF was calculated to 10%. The method thus seems apt as a monitor in medical therapy for occlusive arterial disease. Changes of lambda has, however, to be considered in each study.


Multiple regulator gene control of the galactose operon in Escherichia coli K-12.
Previous studies showed that nonsense mutations in either of two genes (capR or capS) or an undefined mutation in a third gene (capT) led to pleiotropic effects: (i) increased capsular polysaccharide synthesis (mucoid phenotype); (ii) increased synthesis of enzymes specified by at least four spatially separated operons involved in synthesis of capsular polysaccharide including the product of the galE gene, UDP-galactose-4-epimerase (EC 188.8.131.52) in capR mutants. The present study demonstrated that the entire galactose (gal) operon (galE, galT, and galK) is derepressed by mutations in either the capR or the capT genes, but not by mutation in capS. Double mutants (capR9 capT) were no more derepressed than the capR9 mutant, indicating that capR9 and capT regulate the gal operon via a common pathway. Isogenic double mutants containing either galR(+), galR(-), galR(s), or galO(c) in combination with either capR(+) or capR9 were prepared and analyzed for enzymes of the gal operon. The results demonstrated that capR9 caused derepression as compared to capR(+) in all of the combinations. Strains with a galR(s) mutation are not induced, for the gal operon, by any galactose compound including d-fucose, and this was confirmed in the present study using d-fucose. Nevertheless, the derepression of galR(s) capR9 compared to galR(s) capR(+) was four- to sixfold. The same derepression was observed when galR(+)capR9 was compared to galR(+)capR(+). The data eliminate the explanation that internal induction of the gal operon by a galactose derivative was causing increased gal operon enzyme synthesis in capR or capT mutants. Furthermore, the same data suggest that the galR and capR genes are acting independently to derepress the gal operon. A modified model for the structure of the gal operon is proposed to explain these results. The new feature of the model is that two operator sites are suggested, one to combine with the galR repressor and one to combine with the capR repressor.


Molecular biology of the sea urchin embryo.
Research on the early development of the sea urchin offers new insights into the process of embryogenesis. Maternal messenger RNA stored in the unfertilized egg supports most of the protein synthesis in the early embryo, but the structure of maternal transcripts suggests that additional functions are also possible. The overall developmental patterns of transcription and protein synthesis are known, and current measurements describe the expression of specific genes, including the histone genes, the ribosomal genes, and the actin genes. Possible mechanisms of developmental commitment are explored for regions of the early embryo that give rise to specified cell lineages, such as the micromere-mesenchyme cell lineage.


Acquired hearing loss and psychiatric illness: an estimate of prevalence and co-morbidity in a geriatric setting.
Hearing impairment and mental disorders are common among residents of nursing homes and homes for the aged; however, the relationship between sensory deficit and psychiatric illness has been little investigated in this population. The prevalence of hearing impairment, psychiatric illness, and co-morbidity was investigated in a sample of 102 elderly residents from consecutive admissions to a home for the aged. Examining the coincidence of these disorders showed evidence of an association between hearing loss and paraphrenia, and hearing loss and dysphoric states, but not between hearing and cognitive impairment. The results of this survey provide only suggestive evidence regarding aetiology, but strongly support conjoint assessment of the elderly.


Prolonged epileptic blindness in an infant associated with cortical dysplasia.
We report a female infant with status epilepticus amauroticus and intractable focal motor seizures associated with congenital cortical dysplasia. EEG demonstrated persistent epileptiform discharges over the right parieto-temporal regions extending to occipital areas. She required cortical resection of the epileptic zone at age 8 months given failure of very high dose antiepileptic combinations. Histological analysis of a sample of cortex resected from the right central parieto-temporal region, identified by electrocorticography as the focus of epileptic activity, showed cortical dysplasia. The seizures ceased and the infant gained full vision after 48 hours. During an 8-year follow-up period she has had a few short-lived seizures, currently controlled with carbamazepine and vigabatrin. Her cognition and speech are intact. This case demonstrates that: (1) resection of a central temporo-parietal focus, which may have spread to the occipital regions, may result in complete visual recovery and cessation of seizures; and (2) EEG should be considered in every infant with alleged delayed visual maturation, to rule out concealed epileptic activity.


Impact of NLRP3 Depletion on Aging-Related Metaflammation, Cognitive Function, and Social Behavior in Mice.
Immunosenescence and chronic inflammation associated with old age accompany brain aging and the loss of complex behaviors. Neuroinflammation in the hippocampus plays a pivotal role in the development of cognitive impairment and anxiety. However, the underlying mechanisms have not been fully explained. In this study, we aimed to investigate the disruption of insulin signaling and the mechanisms underlying metabolic inflammation ("metaflammation") in the brains of wild-type (WT) and NLRP3 knockout (KO) mice of different ages. We found a significant upregulation of the NLRP3 inflammasome in the hippocampus during aging, leading to an increase in the expression of phosphorylated metaflammation proteinases and inflammatory markers, along with an increase in the number of senescent cells. Additionally, metaflammation causes anxiety and impairs social preference behavior in aged mice. On the other hand, deletion of NLRP3 improves some behavioral and biochemical characteristics associated with aging, such as signal memory, neuroinflammation, and metabolic inflammation, but not anxious behavior. These results are associated with reduced IL-18 signaling and the PKR/IKKβ/IRS1 pathway as well as the SASP phenotype. In NLRP3 gene deletion conditions, PKR is down-regulated. Therefore, it is likely that slowing aging through various NLRP3 inhibition mechanisms will lessen the corresponding cognitive decline with aging. Thus, the genetic knockout of the NLRP3 inflammasome can be seen as a new therapeutic strategy for slowing down central nervous system (CNS) aging.


Surface plasmon resonance image sensor module of spin-coated silver film with polymer layer.
Prism modules of 20 nm-, 40 nm-, and 60 nm-thick spin-coated silver films both without and with an upper 100 nm-thick spin-coated polymer layer were fabricated for surface plasmon resonance (SPR) image sensor applications. The prism modules were applied to an SPR image sensor system. The coefficients of determination (R2s) for the 20 nm-, 40 nm- and 60 nm-thick silver films without the polymer layer were 0.9231, 0.9901, and 0.9889, respectively, and with the polymer layer 0.9228, 0.9951, and 0.9880, respectively when standard ethanol solutions with 0.1% intervals in the range of 20.0% to 20.5% were applied. The upper polymer layer has no effect on the R2. The prism modules of the 40-nm-thick spin-coated silver films had the highest R2 value of approximately 0.99. The durability of the 40 nm-thick spin-coated silver film with the 100 nm-thick polymer layer is much better than that without the upper low-loss polymer layer. The developed SPR image sensor module of the 40 nm-thick spin-coated silver film with the upper 100 nm-thick low-loss polymer film is expected to be a very cost-effective and robust solution because the films are formed at low temperatures in a short period of time without requiring a vacuum system and are very durable.


Shrinking genomes? Evidence from genome size variation in Crepis (Compositae).
Large-scale surveys of genome size evolution in angiosperms show that the ancestral genome was most likely small, with a tendency towards an increase in DNA content during evolution. Due to polyploidisation and self-replicating DNA elements, angiosperm genomes were considered to have a 'one-way ticket to obesity' (Bennetzen & Kellogg 1997). New findings on how organisms can lose DNA challenged the hypotheses of unidirectional evolution of genome size. The present study is based on the classical work of Babcock (1947a) on karyotype evolution within Crepis and analyses karyotypic diversification within the genus in a phylogenetic context. Genome size of 21 Crepis species was estimated using flow cytometry. Additional data of 17 further species were taken from the literature. Within 30 diploid Crepis species there is a striking trend towards genome contraction. The direction of genome size evolution was analysed by reconstructing ancestral character states on a molecular phylogeny based on ITS sequence data. DNA content is correlated to distributional aspects as well as life form. Genome size is significantly higher in perennials than in annuals. Within sampled species, very small genomes are only present in Mediterranean or European species, whereas their Central and East Asian relatives have larger 1C values.


An analysis of patients receiving emergency CAG without PCI and the value of GRACE score in predicting PCI possibilities in NSTE-ACS patients.
There are patients who underwent emergency coronary angiography (CAG) but did not receive percutaneous coronary intervention (PCI). The aim of this study was to analyze these reasons. This is a single-center retrospective study. We recruited 201 consecutive patients who received emergency CAG but did not receive PCI. To investigate the value of the Global Registry of Acute Coronary Events (GRACE) score in predicting PCI possibilities in non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients, we recruited 80 consecutive patients who presented with NSTE-ACS and received emergency CAG as well as emergency PCI. Among the 201 patients who received emergency CAG but did not receive PCI, 26% patients had final diagnosis other than coronary heart disease. In the patients with significant coronary artery stenosis, 23 patients (11.5%) were recommended to coronary artery bypass grafting (CABG), one patient (0.5%) refused PCI; 13 patients (6.5%) with significant thrombus burden were treated with glycoprotein IIb/IIIa receptor antagonist; 74 patients (36.8%) were treated with drug therapy because no severe stenosis (> 70%) was present in the crime vessel. Moreover, 80 of the 201 patients were presented with NSTE-ACS (excluding those patients with final diagnosis other than coronary heart disease, excluding those patients planned for CABG treatment), referred as non PCI NSTE-ACS. When comparing their GRACE scores with 80 consecutive patients presented with NSTE-ACS who received emergency CAG as well as emergency PCI (referred as PCI NSTE-ACS), we found that PCI NSTE-ACS patients had significantly higher GRACE scores compared with non PCI NSTE-ACS patients. We then used Receiver Operator Characteristic Curve (ROC) to test whether the GRACE score is good at evaluating the possibilities of PCI in NSTE-ACS patients. The area under the curve was 0.854 ± 0.030 (P < 0.001), indicating good predictive value. Furthermore, we analyzed results derived from ROC statistics, and found that a GRACE score of 125.5, as a cut-off, has high sensitivity and specificity in evaluating PCI possibilities in NSTE-ACS patients. Our findings indicate that the GRACE score has predictive value in determining whether NSTE-ACS patients would receive PCI.


In-Hospital Postoperative Pneumonia Following Geriatric Intertrochanteric Fracture Surgery: Incidence and Risk Factors.
The in-hospital death rate in cases of hip fracture ranges from 6% to 10%. Pneumonia is a serious complication for hip fracture patients that contributes to longer hospital stays and higher mortality rates; however, the prevalence and risk factors are not well established. To address this issue, the present study investigated the incidence of and risk factors for in-hospital postoperative pneumonia (IHPOP) following geriatric intertrochanteric fracture surgery. Information on 1495 geriatric patients (>65 years) who underwent intertrochanteric fracture surgery at our hospital between October 2014 and December 2018 was extracted from a prospective hip fracture database and reviewed. Demographic information, clinical variables including surgical data, and preoperative laboratory indices that could potentially influence IHPOP were analyzed. Receiver operating characteristic curve analysis was performed and the optimum cutoff value for quantitative data was determined. Univariate and multivariate analyses were carried out to identify risk factors for IHPOP. The incidence of IHPOP following geriatric intertrochanteric fracture surgery was 3.5% (53/1495 cases). The multivariate analysis showed that age >82 years (odds ratio [OR]=2.54, p=0.004), male sex (OR=2.13, p=0.017), chronic respiratory disease (OR=5.02, p<0.001), liver disease (OR=3.39, p=0.037), urinary tract infection (OR=8.46, p=0.005), creatine kinase (CK) MB>20 U/l (OR=2.31, p=0.020), B-type natriuretic peptide (BNP) ≥75 ng/l (OR=4.02, p=0.001), and d-dimer >2.26 mg/l (OR=2.69, p=0.002) were independent risks factor for the incidence of IHPOP following geriatric intertrochanteric fracture surgery. The incidence of IHPOP was 3.5% following geriatric intertrochanteric fracture surgery; age, male sex, chronic respiratory disease, liver disease, urinary tract infection, CKMB, BNP, and d-dimer were significant risk factors. Targeted preoperative management based on these factors could reduce the risk of IHPOP and mortality in these patients.


Eco-friendly food packaging based on paper coated with a bio-based antibacterial coating composed of carbamate starch, calcium lignosulfonate, cellulose nanofibrils, and silver nanoparticles.
Traditional paper-based packaging commonly needs to be coated to achieve sufficient mechanical and barrier performances. In this research, a bio-based coating for paper was developed from carbamate starch (Sc), calcium lignosulfonate (CL), and cellulose nanofibrils (CNF). Controlling the electrostatic and hydrogen-bonding interactions among the components of the coating was conducive to tailoring the structure and performance of the coated paper. When the degree of substitution (Ds) of Sc was 0.10, the amount of CL was 1.00 g, and the amount of CNF was 0.65 % of the weight of Sc, the paper coated with the resulting 0.10Sc-1.00CL-0.65CNF coating exhibited increased hydrophobicity and excellent mechanical, air-barrier, and UV-light-barrier properties. After the addition of 0.10 % of silver nano-particles (AgNPs) to the 0.10Sc-1.00CL-0.65CNF coating, the paper coated with the resulting 0.10Sc-1.00CL-0.65CNF-0.10AgNPs coating exhibited good antibacterial activity against Escherichia coli and Staphylococcus aureus. The coated paper was used as the packaging for cherry tomatoes stored under ambient conditions. Due to the synergistic preservation effects of the Sc-CL-CNF coating and AgNPs, the shelf life of the cherry tomatoes was at least 7 days. The coated paper described herein has the potential for applications in the food packaging sector.


[Songs in music therapy with children].
For most of us, songs and nursery rhymes have a special emotional quality and, thus, are part of the basic repertoire of a music therapist. This paper outlines the meaning and applicability of songs in music therapy with children. The first part discusses the significance of songs within the context of developmental psychology, referring to the development of basic psychological functions such as motorical skills, language, cognition, emotion, mental representations, motivation and intention. The second part deals with indications and objectives as well as different applications of songs in music therapy. Traditional and new nursery rhymes, free renderings, playing songs, spontaneous tunes, welcome and farewell songs and semi-structured tunes are introduced. Finally, the article reviews the diverse therapeutical functions of songs within the process of music therapy as well as essential qualifications for a music therapist.


Genetic correlation of a mouse light chain variable region marker with a thymocyte surface antigen.
The inbred and congenic strain distribution of the I(H)-peptide marker in the variable region of mouse immunoglobulin light chains has been compared with other known genetic markers. A positive correlation was noted between the I(H)-peptide marker and expression of the Ly-3.1 thymocyte cell surface antigen. This suggests that the locus responsible for I(H)-peptide expression is genetically linked to the Ly-2 and Ly-3 loci in linkage group XI on chromsome 6 of the mouse.


Helminth parasites of the leopard frog Lithobates sp. Colima (Amphibia: Ranidae) from Colima, Mexico.
The helminth fauna inhabiting Lithobates sp. Colima from Ticuizitán, Colima, Mexico, comprises 10 species: 4 digeneans ( Clinostomum sp., Glypthelmins quieta , Haematoloechus sp., and Langeronia macrocirra ), 5 nematodes ( Aplectana itzocanensis , Cosmocerca podicipinus , Foleyellides striatus , Oswaldocruzia subauricularis , and Rhabdias sp.), and 1 cestode (Cyclophyllidea). Glypthelmins quieta , L. macrocirra , and A. itzocanensis represent new host records. These observations, added to previous records from Acapulco, Guerrero, Mexico, indicate that the helminth fauna of Lithobates sp. from Colima comprises 25 taxa. Frogs are being parasitized by 3 infection routes: ingestion of intermediate host, skin penetration by larval forms, and transmission by vectors. Species of Aplectana , Cosmocerca , Foleyellides , and Oswaldocruzia occurred in high prevalence in Colima, similar to a previous study on the same frog species from Guerrero. In Colima, Glypthelmins , Haematoloechus , and Rhabdias also occurred in high prevalence. Haematoloechus species reached the highest mean intensity in both localities. The semiaquatic habits of this species of frog and the availability of particular feeding resources appear to determine the helminth composition and infection levels; however, co-speciation events also play an important role structuring these helminth communities.


Effects of cognitive training and testing on intellectual efficacy beliefs in elderly adults.
Elderly adults (N = 116; average age = 73 years) were randomly assigned to one of four treatment groups varying in the amount of training and testing on fluid intelligence tests. They were compared before and after treatment on self-efficacy and utility beliefs for intelligence tests and everyday competence. Although both ability training and extended retest practice resulted in significant gains in objective test performance (Baltes, Kliegl, & Dittmann-Kohli, 1988), only ability training resulted in positive changes in self-efficacy. However, these changes were restricted to test-related self-efficacy. Training had no impact on perceived utility or on everyday self-efficacy beliefs. Implications of the results are discussed with regard to interventions to increase intellectual self-efficacy in elderly persons.


Patients' preoperative expectation and outcome of cataract surgery at jimma university specialized hospital -department of ophthalmology.
Patient's satisfaction for a given treatment is an important clinical outcome because a satisfied patient is more likely to comply with treatments, attend follow-ups and advocate the service to others. Therefore, knowing patients' expectations before a planned procedure or treatment and the actual level of satisfaction and fulfillment of their initial expectations thereafter is much helpful. As far as the knowledge and experience of the researchers is concerned, there has not been any study conducted in Ethiopia to find out about patients' preoperative expectations and postoperative level of satisfaction for actual outcomes. This study was therefore, conducted to describe and find out the relationship between preoperative expectations of cataract patients and the actual postoperative experience and their satisfaction level following the surgery at ophthalmology department in Jimma University Specialized Hospital. A prospective cohort study of patients undergoing first eye cataract surgery was conducted from July 10 to Oct., 10, 2007 in the Ophthalmology department of Jimma University Specialized Hospital. Detailed interviews that included general and vision specific health status measures and patients' preoperative expectations for cataract surgery outcomes were performed followed by visual acuity testing. Postoperatively, visual acuity testing was taken again and patients' level of satisfaction with attained postoperative vision was assessed. Data were collected and filled in a separate questionnaire form for each patient, and entered into a computer and analyzed using SPSS for Windows version 12.0. Of the 200 patients operated for cataract, 179 (89.5%) were followed for the whole five weeks. The average expected preoperative Visual Function-15 score was 96.3, compared to an achieved (postoperative) Visual Function-15 score of just 96.2. However, the most unrealistic expectations observed were reading small prints and doing fine handiwork. The final pinhole visual acuity postoperatively was ≤ 6/18 in 126 (70.4%) patients. Of the 78 (39%) patients who were bilaterally blind preoperatively, 5 (2.5%) patients remained blind postoperatively. Significant improvements were obtained in clinical, functional, and perceived vision by cataract surgery involving extracapsular cataract extraction with posterior chamber intraocular lens implantations. Expectations regarding visual functioning after cataract surgery were very high, and in most cases and in most cases they were fulfilled.


Direct glucose stimulation of glycogen synthase phosphatase activity in a liver glycogen particle preparation.
In glycogen particle suspensions prepared from fed rats given either glucagon or glucose in order to increase or decrease the phosphorylase a concentration, respectively, glucose stimulation of synthase phosphatase activity was observed. In preparations from glucagon-treated rats, addition of glucose stimulated synthase and phosphorylase phosphatase simultaneously and not sequentially. Synthase phosphatase stimulation was glucose concentration dependent even when phosphorylase a had been rapidly reduced to a low level. The estimated A0.5 for glucose stimulation of synthase phosphatase activity was 27 mM. An A0.5 for glucose stimulation of phosphorylase phosphatase activity could not be estimated since activity was still increasing with concentrations of glucose as high as 200 mM. In preparations from glucose-treated rats which contain virtually no phosphorylase a, glucose stimulation was still apparent but the A0.5 was increased modestly (36 mM). Stimulation of synthase phosphatase activity was specific for glucose. Several other monosaccharides and the polyhydric alcohol sorbitol were ineffective.