Continuous enriched environment improves learning and memory in adult NMRI mice through theta burst-related-LTP independent mechanisms but is not efficient in advanced aged animals

Introduction

Effects of 3-month continuous environmental enrichment (EE) on cognitive abilities and on theta burst-related synaptic plasticity of CA1 hippocampal neuronal networks have been assessed in 6- and 20-month old NMRI female mice.

Results

EE decreased anxiety-like behavior and improved learning and memory performances in adult but not in aged mice. Electrophysiological results in CA1 hippocampal slices showed that basal synaptic transmission was not affected by EE in adult mice whereas it was partially improved in aged animals, even though not sufficient to rescue the decrease related to aging. Besides, no effect of EE on N-methyl-d-aspartate receptor activation and theta-burst-induced long-term potentiation was found in adult or aged animals.

Discussion

These results indicate that continuous EE is able to improve cognitive abilities in adult NMRI female mice, that does not correlate with changes in theta burst-related synaptic plasticity within neuronal networks. In addition, the lack of effects in aged animals suggests the existence of a critical delay for the beneficial effects of EE on cognitive aging.     

β-d-Xylosides Stimulate GAG Synthesis in Chondrocyte Cultures Due to Elevation of the Extracellular GAG Domains,Accompanied by the Depletion of the Intra–pericellular GAG Pools,with Alterations in the GAG Profiles

The familial disease of hereditary multiple exostoses is characterized by abnormal skeletal deformities requiring extensive surgical procedures. In hereditary multiple exostoses patients there is a shortage in the pericellular glycosaminoglycan (GAG) of heparan sulfate (HS), related to defective activity of HS glycosyltransferases, mainly in the pericellular regions of chondrocytes. This study searched for a novel approach employing xylosides with different aglycone groups priming a variety of GAG chains, in attempting to alter the GAG compositional profile. Cell cultures of patients with osteochondroma responded to p-nitrophenyl β-d-xyloside by a significant increase in total GAG synthesis, expressed mainly in the extracellular domains, limited to chondroitin sulfate). The different β-d-xylosides, in addition to increasing the synthesis of extracellular GAGs, led to a significant depletion of the intracellular GAG domains. In mouse chondrocyte cultures, β-d-xylosides with different aglycones created a unique distribution of the GAG pools. Of special interest was the finding that the naphthalene methanol β-d-xyloside showed the highest absolute levels of HS-GAGs in both extracellular and intra–pericellular moieties compared with other β-d-xylosides and with controls without xyloside. In summary, β-d-xylosides can be utilized in chondrocyte cultures to modify the distribution of GAGs between the extracellular and intracellular compartments. In addition, xylosides may alter the profile of specific GAG chains in each moiety.     

Granulocyte macrophage colony–stimulating factor is required for cytokine induction by a highly 6-branched 1,3-β-d-glucan from Aureobasidium pullulans in mouse-derived splenocytes

We have previously obtained and elucidated the precise structure of a highly branched 1,3-β-d-glucan (with 6-monoglucopyranosyl side chains), Aureobasidium pullulans-fermented β-d-glucan (AP-FBG), from the fungus A. pullulans. However, the mechanism(s) of the effects of AP-FBG on in vitro mouse primary cells have not been analyzed in detail. Herein, we report that the induction of cytokines by AP-FBG was dependent on the existence of a granulocyte macrophage colony–stimulating factor (GM-CSF); this is similar way to be a typical 1,3-β-d-glucan from Sparassis crispa (SCG), which is a 1,3-β-d-glucopyranosyl backbone with single 1,6-β-d-glucopyranosyl side branching units every three residues. In other words, the production of cytokines in DBA/2-mouse-derived splenocytes by AP-FBG was completely hampered by an anti-GM-CSF neutralizing monoclonal antibody. Furthermore, the addition of exogenous GM-CSF to C57BL/6-derived splenocytes, which are less sensitive to AP-FBG, induced the production of cytokines by AP-FBG. Therefore, GM-CSF is indispensable for the induction of cytokines by AP-FBG in mouse-derived splenocytes. This finding has provided a new insight into our understanding of the actions of β-d-glucan but will also aid in the design and development of more effective β-d-glucan agents.     

Sensory feedback prosthesis reduces phantom limb pain: proof of a principle

Background

Constrained functionality and phantom limb pain (PLP) are major concerns for forearm amputees. Neuroscientific investigations of PLP suggest that behaviorally relevant stimulation of the stump can decrease PLP. Furthermore the prosthesis user could use feedback information of the prosthesis hand for optimizing prosthesis motor control when handling soft and fragile objects. Somatosensory feedback information from a prosthetic hand may therefore help to improve prosthesis functionality and reduce phantom limb pain.

Objectives

We wanted to find out whether a two weeks training on a hand prosthesis that provides somatosensory feedback may help to improve prosthesis functionality and reduce phantom limb pain.

Methods

Eight forearm amputees with phantom limb pain were trained for two weeks to use a hand prosthesis with somatosensory feedback on grip strength.

Results

The current study demonstrates a significant increase of functionality of the prosthesis in everyday tasks. Furthermore, the study shows that usage of a prosthesis that provides somatosensory feedback on the grip strength is effective to reduce phantom limb pain.

Conclusions

A prosthesis with a feedback function appears to be a promising therapeutic tool to reduce phantom limb pain and to increase functionality in everyday tasks. Future studies should further investigate the scope of application of that principle.     

“Michael's Game,” a card game for the treatment of psychotic symptoms

Objective

“Michael's Game” is a card game which aims at familiarizing healthcare professionals and patients with cognitive therapy of psychotic symptoms. The present study tests the feasibility and the impact of the intervention in naturalistic settings.

Methods

135 patients were recruited in 11 centres. They were assessed pre- and post-tests with the Beck Cognitive Insight Scale (BCIS) and the Peters Delusion Inventory-21 items (PDI-21).

Results

Data about 107 patients were included in the entire analyses. Significant improvements were observed on BCIS subscales as well as a reduction of severity of conviction and preoccupation scores on the PDI-21. The intervention has a moderate effect on the PDI-21 preoccupation and conviction as well as the BCIS subscales. Patients who benefit the most from the program are patients who have a low degree of self-reflectiveness and patients who are concomitantly preoccupied by their symptoms.

Conclusion

The present study supports the feasibility and effectiveness of “Michael's Game” in naturalistic settings.

Practical implications

The game seems to be a useful tool for patients with psychotic disorders.     

The effect of conflicting medication information and physician support on medication adherence for chronically ill patients

Objective

This article explores the effect of conflicting information, defined as contradictory information about medication topics from different sources, on medication adherence in a sample of chronically ill patients. We specifically investigate whether conflicting information and physician support directly affect medication adherence or whether the effect is mediated by adherence self-efficacy and outcome expectations for medications.

Methods

Vasculitis patients (n = 228) completed two on-line questionnaires which contained measures of conflicting information, adherence self-efficacy, outcome expectations, physician support, and medication adherence. We conducted a mediation analysis using a bootstrapping approach to generate point estimates and 95% confidence intervals to test the significance of each mediated effect.

Results

A majority of patients (51.3%) received conflicting medication information. Conflicting information had a direct negative effect on medication adherence, which was not mediated by self-efficacy or outcome expectations. Alternatively, self-efficacy mediated the positive effect of physician support on medication adherence.

Conclusion

Patients who encounter conflicting medication information are less adherent to their medications. The presence of a supportive physician may counteract the negative effect of conflicting medication information.

Practice implications

Physicians should initiate conversations about conflicting medication information with their patients. Consensus-based guidelines that address medication discrepancies may also reduce the availability of conflicting information.     

A new computer-based counselling system for the promotion of physical activity in patients with chronic diseases—Results from a pilot study

Objective

To develop a computer-based counselling system (CBCS) for the improvement of attitudes towards physical activity in chronically ill patients and to pilot its efficacy and acceptance in primary care.

Methods

The system is tailored to patients’ disease and motivational stage. During a pilot study in five German general practices, patients answered questions before, directly and 6 weeks after using the CBCS. Outcome criteria were attitudes and self-efficacy. Qualitative interviews were performed to identify acceptance indicators.

Results

Seventy-nine patients participated (mean age: 64.5 years, 53% males; 38% without previous computer experience). Patients’ affective and cognitive attitudes changed significantly, self-efficacy showed only minor changes. Patients mentioned no difficulties in interacting with the CBCS. However, perception of the system's usefulness was inconsistent.

Conclusion

Computer-based counselling for physical activity related attitudes in patients with chronic diseases is feasible, but the circumstances of use with respect to the target group and its integration into the management process have to be clarified in future studies.

Practice implication

This study adds to the understanding of computer-based counselling in primary health care. Acceptance indicators identified in this study will be validated as part of a questionnaire on technology acceptability in a subsequent study.     

Counselling in infertility: individual, couple and group interventions

Objective

Infertility is considered a biopsychosocial crisis and infertility counselling is recommended as an integral part of a multidisciplinary approach. This article will outline the theoretical background and describe common interventions used in infertility counselling for individuals, couples and in a group setting.

Methods

This article summarizes the proceedings of the first campus workshop of the Special interest group of Psychology and Counselling of the European Society for Human Reproduction and Embryology (ESHRE).

Results

Infertility counselling offers the opportunity to explore, discover and clarify ways of living more satisfyingly and resourcefully when fertility impairments have been diagnosed. The Heidelberg Fertility Consultation Service is presented as a framework for individual and couples counselling and highlights important issues in counselling patients. For group work a number of steps to set up a group within an infertility framework are discussed.

Conclusion

In recent years, infertility counselling has become a specialist form of counselling requiring professional expertise and qualification. Key issues and common interventions are presented to raise awareness for the specific counselling needs of individuals and couples experiencing infertility and undergoing medical treatment.

Practice implications

Mental health professionals new to the field of reproductive technologies as well as those in other areas of mental health counselling clients with fertility disorders can benefit from the topics addressed.     

The Effect of Poly(d,l-Lactide-co-Glycolide)-Alendronate Conjugate Nanoparticles on Human Osteoclast Precursors

Abstract

Nanoparticles (NPs) formed from polymers conjugated with bisphosphonates (BPs) allow the bone targeting of loaded drugs, such as doxorubicin, for the treatment of skeletal tumours. The additional antiosteoclastic effect of the conjugated BP could contribute to the inhibition of tumour-associated bone degradation. With this aim, we have produced NPs made of poly(d,l-lactide-co-glycolide) (PLGA) conjugated with alendronate (ALE). To show if ALE retained the antiosteoclastic properties after the conjugation with PLGA and the production of NPs, we treated human osteoclasts, derived from circulating precursors, with PLGA–ALE NPs and compared the effects on actin ring generation, apoptosis and type-I collagen degradation with those of free ALE and with NPs made of pure PLGA. PLGA–ALE NPs disrupted actin ring, induced apoptosis and inhibited collagen degradation. Unexpectedly, also NPs made of pure PLGA showed similar effects. Therefore, we cannot exclude that in addition to the observed antiosteoclastic activity dependent on ALE in PLGA–ALE NPs, there was also an effect due to pure PLGA. Still, as PLGA–ALE NPs are intended for the loading with drugs for the treatment of osteolytic bone metastases, the additional antiosteoclastic effect of PLGA–ALE NPs, and even of PLGA, may contribute to the inhibition of the disease-associated bone degradation.     

Isolation of Coxsackievirus A24 variant from patients with hemorrhagic conjunctivitis in Cuba, 2008-2009

Background

An outbreak of acute hemorrhagic conjunctivitis occurred in Cuba in 2008 and 2009.

Objective

To determinate the etiological agent associated with the Cuban outbreaks of acute hemorrhagic conjunctivitis during 2008 and 2009.

Study design

Conjunctival swabs and/or faecal samples from 382 patients with clinical diagnosis suggestive of acute hemorrhagic conjunctivitis were subject to viral culture in HEp-2 human laryngeal epidermoid carcinoma cells. Positive samples were identified by a specific Coxsackievirus A24 variant PCR and the 3C protease region of 16 isolates was sequenced for phylogenetic analysis.

Results

Enterovirus cytopathic effect was observed in 138 cases (36%). A higher percent of CA24v was recovered from faecal samples, 19 out of 45 cases (42.2%), than from conjunctival swabs, 127 out of 355 samples (35.8%). All isolates were identified as Coxsackievirus A24 variant. Phylogenetic analysis revealed that 2008 and 2009 Cuban outbreaks were caused by the same virus strains and that isolates were closely related to those from Taiwan (2006-2007), China (2007-2008) and Singapore (2005) with a bootstrap value of 71%.

Conclusions

Outbreaks of acute hemorrhagic conjunctivitis occurred in Cuba in 2008 and 2009 were caused by Coxsackievirus A24 variant. The faecal-oral route is another mode of transmission of CA24v in the acute hemorrhagic conjunctivitis outbreaks. Phylogenetic analysis of Cuban CA24v strains involved in an acute hemorrhagic conjunctivitis outbreak in 2008 and 2009 confirms a new introduction of the CA24 variant into the Americas from South-east Asia.     

Can private pharmacy providers offer comprehensive reproductive health services to users of emergency contraceptives? Evidence from Nairobi, Kenya

Objective

To evaluate the provision of reproductive health information and services to users of emergency contraceptives (ECs) by private pharmacists.

Methods

The study involved intervention (9) and control (8) pharmacies, with baseline and endline assessments of EC provision through the use of mystery clients. Intervention pharmacies received weekly updates on EC, fliers with three key messages on EC, and information, education, and communication materials. Logistic regression models are estimated to predict the provision of reproductive health services to EC clients.

Results

The differences between the control and intervention pharmacies with respect to the provision of additional information on EC and regular family planning services are in the expected direction but statistically insignificant. In contrast, the likelihood of providing information or referral for counseling or testing for sexually transmitted infections or HIV was lower in the intervention than in the control pharmacies but the difference was also not statistically significant.

Conclusion

Pharmacy providers in the country face institutional challenges in providing reproductive health services to EC clients.

Practice implications

The challenges could be addressed through pre-service training, targeted in-service training, sensitization of clients, and point-of-sale materials such as brochures, posters and package inserts.     

Organizational factors affecting successful adoption of innovative eHealth services: a case study employing the FITT framework

Objective

The paper presents an application of the “Fit between Individuals, Task and Technology” (FITT) framework to analyze the socio-organizational-technical factors that influence IT adoption in the healthcare domain.

Method

The FITT framework was employed as the theoretical instrument for a retrospective analysis of a 15-year effort in implementing IT systems and eHealth services in the context of a Regional Health Information Network in Crete. Quantitative and qualitative research methods, interviews and participant observations were employed to gather data from a case study that involved the entire region of Crete.

Results

The detailed analysis of the case study based on the FITT framework, showed common features, but also differences of IT adoption within the various health organizations. The emerging picture is a complex nexus of factors contributing to IT adoption, and multi-level interventional strategies to promote IT use.

Conclusion

The work presented in this paper shows the applicability of the FITT framework in explaining the complexity of aspects observed in the implementation of healthcare information systems. The reported experiences reveal that fit management can be viewed as a system with a feedback loop that is never really stable, but ever changing based on external factors or deliberate interventions. Management of fit, therefore, becomes a constant and complex task for the whole life cycle of IT systems.     

Efficacy of ongoing group based diabetes self-management education for patients with type 2 diabetes mellitus. A randomised controlled trial

Objective

To evaluate the efficacy of ongoing group based diabetes self-management education (DSME) for patients with type 2 diabetes.

Methods

146 patients were randomised to either group education or waiting list control. Primary outcomes were A1C and patient activation measured with patient activation measure (PAM).

Results

There were no differences in the primary outcomes between the groups at 12 months, but the control group had an increase in A1C of 0.3% points during follow-up. Diabetes knowledge and some self-management skills improved significantly in the intervention group compared to the control group. A sub group analysis was conducted for the quartile with the highest A1C at baseline (>7.7, n = 18 in both groups). There were significant improvements within the intervention group at 12 month follow-up for both A1C and PAM and a trend for better outcome in the intervention group compared to the control.

Conclusions

The locally developed ongoing diabetes self-management education programs prevented an increase in A1C and can have an effect on A1C in patients with higher A1C level.

Practice implications

Locally developed programs may be less effective than programs developed for studies.     

Incidence of cytomegalovirus UL97 and UL54 amino acid substitutions detected after 100 or 200 days of valganciclovir prophylaxis

Background

The IMPACT study was a randomized, double-blind study comparing 100 to 200 days of VGCV prophylaxis (900 mg once daily) in D+/R− kidney transplant recipients. Although extending the duration of prophylaxis resulted in a significant reduction in confirmed cytomegalovirus (CMV) disease (100-day: 36.8% vs 200-day: 16.1%¹), the consequence of extending the duration of prophylaxis on the development of viral resistance remains unknown.

Objective

To determine whether extending valganciclovir prophylaxis from 100 days to 200 days increased the incidence of ganciclovir resistance.

Study design

Genotypic analysis of CMV UL97 and UL54 was conducted on virus isolated from patients meeting the predefined resistance analysis criteria (RAC).

Results

A greater number of patients met the RAC in the 100 day prophylaxis arm (50/163; 31%) compared to the 200 day prophylaxis arm (22/155; 14%). Sequence data were successfully generated for all 200-day patients and 48/50 100-day patients. Three patients in each treatment arm (100 day: 3/163 (1.8%) vs 200 day: 3/155 (1.9%)) had a single known valganciclovir resistance mutation detected (100 day: UL97 gene: M460V, C592G twice; 200 day: UL97 gene: C603W, M460V and UL54 gene: P522S). Overall, a resistance mutation was more likely to be detected if the patient met the RAC during prophylaxis (5/12 (42%)) compared to post-prophylaxis (1/58 (2%)). All six patients with known ganciclovir resistance mutations cleared the virus; three cleared virus without treatment and three cleared virus following treatment.

Conclusions

Extending valganciclovir prophylaxis from 100 days to 200 days did not significantly affect the incidence of ganciclovir resistance.     

Molecular characterization of methicillin-resistant Staphylococcus aureus isolates in Algeria

Introduction

The epidemiology of Staphylococcus aureus has changed radically since 1999, in particular, methicillin-resistant S. aureus (MRSA), originally restricted to hospital, has emerged as a significant pathogen in the community, and true community-acquired MRSA (CA-MRSA) infections have been reported in patients with no clear risk factors. CA-MRSA strains frequently produce Panton-Valentine leukocidin (PVL).

Objectives

The objectives of this study were: (i) to monitor the prevalence of PVL and toxic shock syndrome toxin-1 (TSST-1) isolates MRSA; (ii) to identify the staphylococcal cassette chromosome (SCCmec) types of MRSA isolates.

Material and methods

Sixty-four isolates, collected between 2005 and 2007 in Didouche Mourad hospital of Algeria. The isolates were identified by conventional methods. The antibiotic susceptibility of the isolates was performed using the disk diffusion method and automat Vitek2. The presence of gene mecA, the genes encoding SCCmec type, PVL and TSST-1 toxins were investigated by real-time PCR.

Results

All strains were gene mecA positives, 32 (50%) harboured SCCmec IV type, 28 (43.75%) harboured SCCmec V type. 19 (29.68%) have been identified positive for the leukocidin toxin (PVL), they harboured SCCmec type IV. The virulence factor TSST-1 was not present among these isolates.

Conclusion

These results show a high prevalence of PVL-positive H-MRSA in our wards.     

Factor structure and dimensionality of the two depression scales in STAR*D using level 1 datasets

Background

The factor structure and dimensionality of the HAM-D₁₇ and the IDS-C₃₀ are as yet uncertain, because psychometric analyses of these scales have been performed without a clear separation between factor structure profile and dimensionality (total scores being a sufficient statistic).

Methods

The first treatment step (Level 1) in the STAR*D study provided a dataset of 4041 outpatients with DSM-IV nonpsychotic major depression. The HAM-D₁₇ and IDS-C₃₀ were evaluated by principal component analysis (PCA) without rotation. Mokken analysis tested the unidimensionality of the IDS-C₆, which corresponds to the unidimensional HAM-D_6.

Results

For both the HAM-D₁₇ and IDS-C₃₀, PCA identified a bi-directional factor contrasting the depressive symptoms versus the neurovegetative symptoms. The HAM-D₆ and the corresponding IDS-C₆ symptoms all emerged in the depression factor. Both the HAM-D₆ and IDS-C₆ were found to be unidimensional scales, i.e., their total scores are each a sufficient statistic for the measurement of depressive states.

Limitations

STAR*D used only one medication in Level 1.

Conclusions

The unidimensional HAM-D₆ and IDS-C₆ should be used when evaluating the pure clinical effect of antidepressive treatment, whereas the multidimensional HAM-D₁₇ and IDS-C₃₀ should be considered when selecting antidepressant treatment.     

Diversité génétique d’un génotype rare du virus de l’hépatite A

Purpose of the study

Very few is known on genotype II hepatitis A virus (HAV) since it is rarely isolated. From 2002 to 2007, the French observatory of HAV identified six sub-genotype IIA strains of which one from a patient having travelled to West Africa. To investigate the possible African origin of sub-genotype IIA, we determined its prevalence among French travellers in 2008 and characterised its genetic variability.

Patients and methods

The 2008 mandatory notification records were screened for travel to Africa. Viral genotype was determined on the nucleotide sequencing of the VP1/2A junction region. The P1 region coding for capsid proteins was used to compare the genetic diversity of IIA isolates to those of other genotypes.

Results

In 2008, five out of 54 patients returning from West Africa were infected by IIA strains and an additional “autochthonous” case was identified. Two more African cases were identified in 2009. A total of 14 IIA isolates (eight African and six “autochthonous”) were analysed. Nucleotide and amino-acid variability of IIA sequences was lower than that of the other genotypes. Phylogenetic analysis revealed the clustering of two “autochthonous” cases with African isolates whereas the other ones belonged to a different lineage.

Conclusion

Most IIA strains isolated in France are imported by travellers returning from West Africa. However, the unexplained contamination mode of some “autochthonous” cases suggests another geographical origin to discover or a French reservoir to explore.     

Moving beyond the language barrier: The communication strategies used by international medical graduates in intercultural medical encounters

Objective

To understand the communication strategies international medical graduates use in medical interactions to overcome language and cultural barriers.

Methods

In-depth interviews were conducted with 12 international physicians completing their residency training in internal medicine in a large hospital in Midwestern Ohio. The interview explored (a) barriers participants encountered while communicating with their patients regarding language, affect, and culture, and (b) communication convergence strategies used to make the interaction meaningful.

Results

International physicians use multiple convergence strategies when interacting with their patients to account for the intercultural and intergroup differences, including repeating information, changing speaking styles, and using non-verbal communication.

Practice implications

Understanding barriers to communication faced by international physicians and recognizing accommodation strategies they employ in the interaction could help in training of future international doctors who come to the U.S. to practice medicine. Early intervention could reduce the time international physicians spend navigating through the system and trying to learn by experimenting with different strategies which will allow these physicians to devote more time to patient care. We recommend developing a training manual that is instructive of the socio-cultural practices of the region where international physician will start practicing medicine.     

A nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, attenuates lipoprivic feeding in mice

Possible involvement of nitric oxide (NO) in lipoprivic feeding was investigated in nondeprived male ICR mice adapted to a high-fat diet in a within-subjects design. Lipoprivation was induced by blocking fatty acid oxidation with Na-mercaptoacetate (MA), which produces a short-term increase in feeding in mice and rats. Food intake, measured at 1, 2, and 4 h following injection of 70 mg/kg of MA, was attenuated in a dose related manner with increasing pretreatment dose (1,10, 25 and 50 mg/kg sc) of the NO-synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), reaching statistical significance at 10 mg/kg of L-NAME at h1 when compared to vehicle control condition. The inactive isomer, D-NAME, was ineffective, thereby supporting stereospecific drug action and directly implicating NO. A control experiment measured general locomotor activity (grid crossings and rears) in an open arena under 10-50 mg/kg of L-NAME in the same mice; both measures were significantly different from vehicle condition only at the highest dose. These findings support involvement of NO in lipoprivic hyperphagia; they are consistent with and extend research linking NO and ingestive behaviors through use of NOS inhibitors. Possible influences of confounds were discussed.