[Brexpiprazole for treatment of schizophrenia: a critical literature study]. / Brexpiprazol voor de behandeling van schizofrenie: een kritische literatuurstudie.

Background Brexpiprazole has been registered in the Netherlands and Belgium for the treatment of schizophrenia since 2019. It is a third-generation antipsychotic drug with a number of pharmacological similarities to aripiprazole and cariprazine. Aim To critically evaluate the pharmacology, effectiveness and side effects of brexpiprazole in the treatment of schizophrenia using the hitherto available double-blind, placebo-controlled study. Method A clinically oriented study of the literature. Results Brexpiprazole is effective in the treatment of schizophrenia and has few extrapyramidal side effects, metabolic side effects and moderate weight gain, no QTc prolongation, no sedation, and little influence on blood prolactin levels. Limited dose titration is required when initiated on brexpiprazole. Conclusion Brexpiprazole is a treatment option for schizophrenia, with a relatively favorable side effect profile. The position of brexpiprazole within the current treatment algorithm should become clear through future research and clinical experience. Tijdschrift voor Psychiatrie 63(2021)1, 48-55.

Lateralized EEG mu power during action observation and motor imagery in typically developing children and children with unilateral Cerebral Palsy.

OBJECTIVE: During motor execution (ME), mu power is diminished over the contralateral hemisphere and increased over the ipsilateral hemisphere, which has been associated with cortical activation of the contralateral motor areas and inhibition of the ipsilateral motor areas respectively. The influence of action observation (AO) and motor imagery (MI) on mu power is less clear, especially in children, and remains to be studied in children with unilateral cerebral palsy (uCP). METHODS: We determined mu power during ME, AO, and MI of 45 typically developing (TD) children and 15 children with uCP over both hemispheres, for each hand. RESULTS: In TD children, over the left hemisphere mu power was lowered during ME when the right hand was used. In line, over the right hemisphere mu power was lowered when the left hand was addressed. In addition, during AO and MI increased mu power was observed when the right hand was addressed. In children with uCP, over the spared hemisphere mu power was diminished during ME when the less-affected hand was used. However, over the lesioned hemisphere, no mu changes were observed. CONCLUSIONS: The results of TD children fit the activation/inhibition model of mu power. SIGNIFICANCE: The results of children with uCP suggest that the lesioned hemisphere is unresponsive to the motor tasks.

Experience with and amount of postpartum maternity care: Comparing women who rated the care they received from the maternity care assistant as 'good' or 'less than good care'.

OBJECTIVE: The postpartum period is an important time in the lives of new mothers, their children and their families. The aim of postpartum care is 'to detect health problems of mother and/or baby at an early stage, to encourage breastfeeding and to give families a good start' (Wiegers, 2006). The Netherlands maternity care system aims to enable every new family to receive postpartum care in their home by a maternity care assistant (MCA). In order to better understand this approach, in this study we focus on women who experienced the postpartum care by the MCA as 'less than good' care. Our research questions are; among postpartum women in the Netherlands, what is the uptake of MCA care and what factors are significantly associated with women's rating of care provided by the MCA. Design and setting This study uses data from the 'DELIVER study', a dynamic cohort study, which was set up to investigate the organization, accessibility and quality of primary midwifery care in the Netherlands. Participants In the DELIVER population 95.6% of the women indicated that they had received postpartum maternity care by an MCA in their home. We included the responses of 3170 women. MEASUREMENTS AND FINDINGS: To assess the factors that were significantly associated with reporting 'less than good (postpartum) care' by the MCA, a full cases backward logistic regression model was built using the multilevel approach in Generalized Linear Mixed Models. FINDINGS: The mean rating of the postpartum care by the MCA was 8.8 (on a scale from 1-10), and 444 women (14%) rated the postpartum maternity care by the MCA as 'less than good care'. In the full cases multivariable analysis model, odds of reporting 'less than good care' by the MCA were significantly higher for women who were younger (women 25-35 years had an OR 1.32, CI 0.96-1.81 and women 35 years), multiparous (OR 1.27, CI 1.01-1.60) and had a higher level of education (women with a middle level had an OR 1.84,CI 1.22-2.79, and women with a high level of education had an OR 2.11, CI 1.40-3.18 compared to women with a low level of education). Odds of reporting 'less than good care' were higher for women who, received the minimum amount of hours (OR 1.86, CI 1.45-2.38), in their opinion received not enough or too many hours maternity care assistance (OR 1.47, CI 1.01-2.15 and OR 5.15, CI 3.25-8.15, respectively), received care from two or more different MCAs (2 MCAs OR 1.61 CI 1.24-2.08, ≥3 MCAs OR 3.01, CI 1.98-4.56 compared to 1 MCA) and rated the care of the midwife as less than good care (OR 4.03, CI 3.10-5.25) . The odds of reporting 'less than good care' were lower for women whose reason for choosing maternity care assistance was to get information and advice (OR 0.52, CI 0.41-0.65). KEY CONCLUSIONS: We conclude that (the postpartum) MCA care is well utilised, and highly rated by most women. IMPLICATIONS FOR PRACTICE: The approach to care in the Netherlands addresses the needs as outlined by NICE and WHO. Although no data exists around the impact of use on maternal infant outcomes, this approach might be useful in other jurisdictions. MCA care might be improved if the hours of MCA care were tailored, and care by multiple MCAs minimised.

Event-related Potentials During Target-response Tasks to Study Cognitive Processes of Upper Limb Use in Children with Unilateral Cerebral Palsy.

Unilateral Cerebral Palsy (CP) is a neurodevelopmental disorder that is a very common cause of disability in childhood. It is characterized by unilateral motor impairments that are frequently dominated in the upper limb. In addition to a reduced movement capacity of the affected upper limb, several children with unilateral CP show a reduced awareness of the remaining movement capacity of that limb. This phenomenon of disregarding the preserved capacity of the affected upper limb is regularly referred to as Developmental Disregard (DD). Different theories have been postulated to explain DD, each suggesting slightly different guidelines for therapy. Still, cognitive processes that might additionally contribute to DD in children with unilateral CP have never been directly studied. The current protocol was developed to study cognitive aspects involved in upper limb control in children with unilateral CP with and without DD. This was done by recording event-related potentials (ERPs) extracted from the ongoing EEG during target-response tasks asking for a hand-movement response. ERPs consist of several components, each of them associated with a well-defined cognitive process (e.g., the N1 with early attention processes, the N2 with cognitive control and the P3 with cognitive load and mental effort). Due to its excellent temporal resolution, the ERP technique enables to study several covert cognitive processes preceding overt motor responses and thus allows insight into the cognitive processes that might contribute to the phenomenon of DD. Using this protocol adds a new level of explanation to existing behavioral studies and opens new avenues to the broader implementation of research on cognitive aspects of developmental movement restrictions in children.

Children with unilateral cerebral palsy show diminished implicit motor imagery with the affected hand.

AIM: Motor imagery refers to the mental simulation of a motor action without producing an overt movement. Implicit motor imagery can be regarded as a first-person kinesthetic perceptual judgement, and addresses the capacity to engage into the manipulation of one's body schema. In this study, we examined whether children with unilateral cerebral palsy (CP) are able to engage in implicit motor imagery. METHOD: A modified version of the hand laterality judgment task was employed. Erroneous responses, reaction times, and event-related potentials from the electroencephalograph were analysed. RESULTS: In 13 children with typical development (mean age 10y 7mo, SD 1y 2mo; seven male, six female), we observed the classic rotation direction effect. Specifically, when comparing outward rotated with inward rotated hand pictures, decreased accuracy and increased response times were observed. Event-related potentials analyses of the electroencephalogram revealed a more marked N1 and an enhanced rotation-related negativity. INTERPRETATION: These findings suggest that an implicit motor imagery strategy was used to solve the task. However, in 10 children with unilateral CP (mean age 10y 7mo, SD 2y 5mo; five male, five female), these effects were observed only when the less-affected hand was involved. This observation suggests that children with CP could benefit from visual training strategies.

Neglect-like characteristics of developmental disregard in children with cerebral palsy revealed by event related potentials.

BACKGROUND: Children with unilateral Cerebral Palsy (CP) often show diminished awareness of the remaining capacity of their affected upper limb. This phenomenon is known as Developmental Disregard (DD). DD has been explained by operant conditioning. Alternatively, DD can be described as a developmental delay resulting from a lack of use of the affected hand during crucial developmental periods. We hypothesize that this delay is associated with a general delay in executive functions (EF) related to motor behavior, also known as motor EFs. METHODS: Twenty-four children with unilateral CP participated in this cross-sectional study, twelve of them diagnosed with DD. To test motor EFs, a modified go/nogo task was presented in which cues followed by go- or nogo-stimuli appeared at either the left or right side of a screen. Children had to press a button with the hand corresponding to the side of stimulus presentation. Apart from response accuracy, Event-Related Potentials (ERPs) extracted from the ongoing EEG were used to register covert cognitive processes. ERP N1, P2, N2, and P3 components elicited by cue-, go-, and nogo-stimuli were further analyzed to differentiate between different covert cognitive processes. RESULTS: Children with DD made more errors. With respect to the ERPs, the P3 component to go-stimuli was enhanced in children with DD. This enhancement was related to age, such that younger children with DD showed stronger enhancements. In addition, in DD the N1 component to cue- and go-stimuli was decreased. CONCLUSIONS: The behavioral results show that children with DD experience difficulties when performing the task. The finding of an enhanced P3 component to go-stimuli suggests that these difficulties are due to increased mental effort preceding movement. As age in DD mediated this enhancement, it seems that this increased mental effort is related to a developmental delay. The additional finding of a decreased N1 component in DD furthermore suggests a general diminished visuo-spatial attention. This effect reveals that DD might be a neuropsychological phenomenon similar to post-stroke neglect syndrome that does not resolve during development. These findings suggest that therapies aimed at reducing neglect could be a promising addition to existing therapies for DD.

Unravelling developmental disregard in children with unilateral cerebral palsy by measuring event-related potentials during a simple and complex task.

BACKGROUND: In a subset of children with unilateral Cerebral Palsy (CP) a discrepancy between capacity and performance of the affected upper limb can be observed. This discrepancy is known as Developmental Disregard (DD). Though the phenomenon of DD has been well documented, its underlying cause is still under debate. DD has originally been explained based on principles of operant conditioning. Alternatively, it has been proposed that DD results from a diminished automaticity of movements, resulting in an increased cognitive load when using the affected hand. To investigate the amount of involved cognitive load we studied Event-Related Potentials (ERPs) preceding task-related motor responses during a single-hand capacity and a dual-hand performance task. It was hypothesised that children with DD show alterations related to long-latency ERP components when selecting a response with the affected upper limb, reflecting increased cognitive load in order to generate an adequate response and especially so within the dual-hand task. METHODS: Fifteen children with unilateral CP participated in the study. One of the participants was excluded due to major visual impairments. Seven of the remaining participants displayed DD. The other seven children served as a control group. All participants performed two versions of a cue-target paradigm, a single-hand capacity and a dual-hand performance task. The ERP components linked to target presentation were inspected: the mid-latency P2 component and the consecutive long-latency N2b component. RESULTS: In the dual-hand performance task children with DD showed an enhancement in mean amplitude of the long-latency N2b component when selecting a response with their affected hand. No differences were found regarding the amplitude of the mid-latency P2 component. No differences were observed regarding the single-hand capacity task. The control group did not display any differences in ERPs linked to target evaluation processes between both hands. CONCLUSION: These electrophysiological findings show that DD is associated with increased cognitive load when movements are prepared with the affected hand during a dual-hand performance task. These findings confirm behavioural observations, advance our insights on the neural substrate of DD and have implications for therapy.

Effects of hand orientation on motor imagery--event related potentials suggest kinesthetic motor imagery to solve the hand laterality judgment task.

Motor imagery (MI) refers to the process of imagining the execution of a specific motor action without actually producing an overt movement. Two forms of MI have been distinguished: visual MI and kinesthetic MI. To distinguish between these forms of MI we employed an event related potential (ERP) study to measure interference effects induced by hand orientation manipulations in a hand laterality judgement task. We hypothesized that this manipulation should only affect kinesthetic MI but not visual MI. The ERPs elicited by rotated hand stimuli contained the classic rotation related negativity (RRN) with respect to palm view stimuli. We observed that laterally rotated stimuli led to a more marked RRN than medially rotated stimuli. This RRN effect was observed when participants had their hands positioned in either a straight (control) or an inward rotated posture, but not when their hands were positioned in an outward rotated posture. Posture effects on the ERP-RRN have not previously been studied. Apparently, a congruent hand posture (hands positioned in an outward rotated fashion) facilitates the judgement of the otherwise more demanding laterally rotated hand stimuli. These ERP findings support a kinesthetic interpretation of MI involved in solving the hand laterality judgement task. The RRN may be used as a non-invasive marker for kinesthetic MI and seems useful in revealing the covert behavior of MI in e.g. rehabilitation programs.

[Why do women refuse reconstructive breast surgery after mastectomy?]. / Reconstruction mammaire après cancer du sein : les motifs du refus.

The implementation of mammographic screening and neo-adjuvant therapeutics has profoundly modified breast cancer surgery, making it less aggressive. Despite these progresses, mastectomies must be performed in more than 20% of breast cancer cases. Psychological disorders following mastectomy are numerous and lead to various alterations of self-esteem, femininity and sexuality. Reconstructive breast surgery proves to be beneficial to improve these psychological disorders in about 20% of women, who accept breast mourning and appropriate their reconstructed breast. However, 80% of the patients refuse reconstructive breast surgery. Our review aims at analysing different motivations explaining reconstructive breast surgery refusal and different ways of "reconstructing psychologically" after mastectomy.

Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the existence of pre-existing heterosubtypic immunity may dampen the impact a future influenza pandemic may have.

The pitfalls of clinical case research: lessons from the Delphi Project.

Delphi is a project to make high-quality cases treated with homeopathy available for study. The project encountered a number of major difficulties including small numbers of cases submitted, ethical problems and problems of analysis. The nature of these problems and possible solutions are discussed.

The pitfalls of clinical case research: lessons from the Delphi Project

Delphi is a project to make high-quality cases treated with homeopathy available for study. The project encountered a number of major difficulties including small numbers... (AU)

Integrins and osteoclastic resorption in three bone organ cultures: differential sensitivity to synthetic Arg-Gly-Asp peptides during osteoclast formation.

We investigated possible inhibitory effects of five synthetic Arg-Gly-Asp (RGD)-containing peptides on osteoclastic resorption in three distinct in vitro resorption assays (17-day-old fetal mouse bone organ cultures) that differ in stages of osteoclast differentiation. RGD peptides, which can bind the adhesion receptors called integrins, inhibited osteoclastic resorption (45Ca release) in fetal mouse bone explants in which osteoclast precursors have yet to adhere to the mineralized matrix and develop into mature osteoclasts (metacarpals and coculture system). Treatment of metacarpals with RGD peptides inhibited the formation of multinucleated TRAP+ osteoclasts in the mineralized matrix because their mononuclear TRAP+ osteoclast precursors remained localized in the periosteum. In particular, echistatin, a viper venom protein with known affinity for alpha v beta 3 integrin, and GdRGDSP inhibited osteoclastic resorption dose dependently in these systems (ED50 10(-9) and 10(-4) M, respectively) but did not alter the activity of mature resorbing osteoclasts in radii. In addition, 45Ca release was significantly inhibited by the cyclic peptide GPenGRGDSPCA, which has a relatively higher affinity for the vitronectin than fibronectin receptor(s). In contrast, GRDGdSP, which has a much higher affinity for the fibronectin receptor (than the vitronectin receptors), had no effect on resorption at similar concentrations in any resorption system used. In summary, the data presented in this paper show that peptides with RGD motifs are capable of inhibiting osteoclastic resorption in bone organ cultures. Our studies not only support the hypothesis concerning the importance of alpha v beta 3 in osteoclastic resorption but also suggest an important role of integrin(s) in events preceding the actual resorption of calcified matrix by osteoclasts.