The AGE Reader: A non-invasive method to assess long-term tissue damage.

AIMS: Advanced glycation endproducts (AGEs) are sugar-modified adducts which arise during non-enzymatic glycoxidative stress. These compounds may become systemically elevated in disease states, and accumulate in tissue, especially on long-lived proteins. AGEs have been implicated in various acute, and chronic diseases, stressing the need for reliable and comprehensive measuring techniques. Measurement of AGEs in tissue such as skin requires invasive skin biopsies. The AGE Reader has been developed to assess skin autofluorescence (SAF) non-invasively using the fluorescent properties of several AGEs. RESULTS/CONCLUSION: Various studies have shown that SAF is a useful marker of disease processes associated with oxidative stress. It is prospectively associated with the development of cardiovascular events in patients with diabetes, renal or cardiovascular disease, and it predicts diabetes, cardiovascular disease, and mortality in the general population. However, when measuring SAF in individual subjects, several factors may limit the reliability of the measurement. These include endogenous factors present in the skin that absorb emission light such as melanin in dark-skinned subjects, but also factors that lead to temporal changes in SAF such as acute diseases and strenuous physical exercise associated with glycoxidative stress. Also, exogenous factors could potentially influence SAF levels inadvertently such as nutrition, and for example the application of skin care products. This review will address the AGE Reader functionality and the endogenous, and exogenous factors which potentially influence the SAF assessment in individual subjects.

Dielectric Barrier Discharge Applicator for Heating Carbon Nanotube-Loaded Interfaces and Enhancing 3D-Printed Bond Strength.

Material extrusion (ME) 3D printing is a revolutionary technique for manufacturing thermoplastic parts; however, the printed parts typically suffer from poor interlayer bonding, which causes weak tensile strength in the build direction. Many methods have been proposed to address the mechanical deficiencies of 3D-printed parts, but most fall short of a production-ready solution. Here we report the use of a dielectric barrier discharge (DBD) plasma electrode mounted concentrically around the nozzle of an ME 3D printer for in situ welding of thermoplastic parts. This is the first report of a DBD being used as a non-contact means to induce Joule heating in resistive composite materials. The polymer welding process is accomplished by coupling the DBD with the carbon nanotube-loaded interfaces between the 3D-printed layers. The current passing through the part results in rapid resistive heating of the nanotubes and thermal welding of the interfaces. We show that parts printed with this method have isotropic strength and are equivalent to their injection-molded counterparts.

Assessing recovery after cold challenge and thumb involvement can help to rule out systemic sclerosis in patients presenting with Raynaud's phenomenon.

Objective: Our aim was to study whether recovery from a Raynaud's attack and involvement of the thumb are differentiators for systemic sclerosis (SSc) in patients with Raynaud's phenomenon (RP).Method: A stepwise cooling and recovery procedure was performed, provoking an RP attack, in patients with primary Raynaud's phenomenon (PRP, n = 68) and SSc (n = 18). During the procedure, the perfusion of all five fingers during cooling and recovery was assessed by photoelectric plethysmography.Results: In SSc patients, perfusion after 10 min in one or more fingers was more frequently not restored than in PRP patients (p = 0.001), with a negative predictive value of 98%. The thumb was more frequently involved in SSc patients (p = 0.036), with a negative predictive value of 95%. Positive predictive values were low.Conclusions: In patients with RP, when there is restoration of perfusion in all fingers after 10 min or when the thumb is spared, the presence of an underlying SSc is very unlikely. Although these results need to be validated in a clinical setting in a larger prospective study, these signs can help physicians to select additional testing for SSc in RP patients.

Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy.

BACKGROUND: Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. OBJECTIVE: We sought to delineate putative beneficial effects of the Pro251 variant of perlipin-2 on subclinical atherosclerosis and the mechanism by which it acts. METHODS: A pan-European cohort of high-risk individuals where carotid intima-media thickness has been assessed was adopted. Human primary monocyte-derived macrophages were prepared from whole blood from individuals recruited by perilipin-2 genotype or from buffy coats from the Karolinska University hospital blood central. RESULTS: The Pro251 variant of perilipin-2 is associated with decreased intima-media thickness at baseline and over 30 months of follow-up. Using human primary monocyte-derived macrophages from carriers of the beneficial Pro251 variant, we show that this variant increases autophagy activity, cholesterol efflux and a controlled inflammatory response. Through extensive mechanistic studies, we demonstrate that increase in autophagy activity is accompanied with an increase in liver-X-receptor (LXR) activity and that LXR and autophagy reciprocally activate each other in a feed-forward loop, regulated by CYP27A1 and 27OH-cholesterol. CONCLUSIONS: For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.

A Potential Role for the STXBP5-AS1 Gene in Adult ADHD Symptoms.

We aimed to detect Attention-deficit/hyperactivity (ADHD) risk-conferring genes in adults. In children, ADHD is characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity and may persists into adulthood. Childhood and adulthood ADHD are heritable, and are thought to represent the clinical extreme of a continuous distribution of ADHD symptoms in the general population. We aimed to leverage the power of studies of quantitative ADHD symptoms in adults who were genotyped. Within the SAGA (Study of ADHD trait genetics in adults) consortium, we estimated the single nucleotide polymorphism (SNP)-based heritability of quantitative self-reported ADHD symptoms and carried out a genome-wide association meta-analysis in nine adult population-based and case-only cohorts of adults. A total of n = 14,689 individuals were included. In two of the SAGA cohorts we found a significant SNP-based heritability for self-rated ADHD symptom scores of respectively 15% (n = 3656) and 30% (n = 1841). The top hit of the genome-wide meta-analysis (SNP rs12661753; p-value = 3.02 × 10-7) was present in the long non-coding RNA gene STXBP5-AS1. This association was also observed in a meta-analysis of childhood ADHD symptom scores in eight population-based pediatric cohorts from the Early Genetics and Lifecourse Epidemiology (EAGLE) ADHD consortium (n = 14,776). Genome-wide meta-analysis of the SAGA and EAGLE data (n = 29,465) increased the strength of the association with the SNP rs12661753. In human HEK293 cells, expression of STXBP5-AS1 enhanced the expression of a reporter construct of STXBP5, a gene known to be involved in "SNAP" (Soluble NSF attachment protein) Receptor" (SNARE) complex formation. In mouse strains featuring different levels of impulsivity, transcript levels in the prefrontal cortex of the mouse ortholog Gm28905 strongly correlated negatively with motor impulsivity as measured in the five choice serial reaction time task (r2 = - 0.61; p = 0.004). Our results are consistent with an effect of the STXBP5-AS1 gene on ADHD symptom scores distribution and point to a possible biological mechanism, other than antisense RNA inhibition, involved in ADHD-related impulsivity levels.

Exploring the emotional and behavioural reactions to receiving personalized melanoma genomic risk information: a qualitative study.

BACKGROUND: There is a need for greater understanding of the spectrum of emotional and behavioural reactions that individuals in the general population may experience in response to genomic testing for melanoma risk. OBJECTIVES: To explore how individuals in the general population respond to receiving personalized genomic risk of melanoma. METHODS: Semistructured interviews were undertaken with 30 participants (aged 24-69 years, 50% female, 12 low risk, eight average risk, 10 high risk) recruited from a pilot trial in which they received personalized melanoma genomic risk information. We explored participants' emotional and behavioural responses to receiving their melanoma genomic risk information. The qualitative data were analysed thematically. RESULTS: Many participants reported a positive response to receiving their melanoma genomic risk, including feelings of happiness, reassurance and gaining new knowledge to help manage their melanoma risk. Some participants reported short-term negative emotional reactions that dissipated over time. Most individuals, particularly those who received average or high-risk results, reported making positive behaviour changes to reduce their melanoma risk. Emotional and behavioural responses were linked to participants' expectations for their risk result, their pre-existing perception of their own melanoma risk, their existing melanoma preventive behaviours and their genomic risk category. CONCLUSIONS: Personalized melanoma genomic risk information alongside education and lifestyle counselling is favourably received by people without a personal history and unselected for a family history of melanoma. Participants described increased knowledge and awareness around managing skin cancer risk and improved sun protection and skin examination behaviours. Any initial feelings of distress usually dissipated over time.

Accumulation of advanced glycation end products is associated with macrovascular events and glycaemic control with microvascular complications in Type 2 diabetes mellitus.

AIM: The United Kingdom Prospective Diabetes Study (UKPDS) study showed that glycaemic control (HbA1c ) can predict vascular complications in Type 2 diabetes mellitus. The Diabetes Control and Complications Trial (DCCT) study showed that accumulation of advanced glycation end products (AGEs) from skin biopsies predicts vascular complications in Type 1 diabetes. Previously, we showed that tissue AGEs can be measured non-invasively using skin autofluorescence (SAF). The aim of this study was to compare the predictive value of HbA1c and SAF for new macrovascular events and microvascular complications in people with Type 2 diabetes. METHODS: A prospective cohort study of 563 participants, median age 64 years [interquartile range (IQR) 57-72], diabetes duration of 13 years, from five Dutch hospitals was performed. RESULTS: After a median follow-up of 5.1 (IQR 4.3-5.9) years, 79 (15%) participants had died and 49 (9%) were lost to follow-up. Some 133 (26%) developed a microvascular complication and 189 (37%) a macrovascular event. Tertiles of HbA1c were significantly associated with development of microvascular complications (log rank P = 0.022), but not with macrovascular events. Tertiles of SAF were significantly associated with macrovascular events (log rank P = 0.003). Cox regression analysis showed SAF was associated with macrovascular events: crude hazard ratio (HR) 1.53 (P < 0.001) per unit increase, HR 1.28 (P = 0.03) after correction for UKPDS score. HbA1c was predictive for microvascular complications: crude HR 1.20 (P = 0.004), HR 1.20 (P = 0.004) after correction for UKPDS score. CONCLUSION: This study shows that tissue accumulation of AGEs, assessed by SAF, is associated with development of macrovascular events in people with Type 2 diabetes, whereas HbA1c is associated with the development of microvascular complications.

Tailored Network Formation in Graphene Oxide Gels.

Graphene oxide (GO)-based gels are attractive because of their ability to retain individual nanosheet properties in a three-dimensional (3D) bulk material. The final morphology and properties of these 3D gel networks depend strongly on the type and density of cross-links, and these gels can be dried and annealed to form aerogels with both high conductivity (560 S/m) and high surface area (1700 m2/g). The results show that both ammonia content and the parent nanosheet morphology (crumpled vs flat) have a strong influence on the cross-linked structure and composition; notably, nitrogen is found in the gels, suggesting that ammonia actively participates in the reaction rather than as a mere catalyst. The GO nanosheet morphology may be altered using spray-drying to obtain crumpled GO (cGO) nanosheets and form cGO gels; this allows for an additional handle in the creation of GO-based gels with tunable density, electrical conductivity, and surface area.

Trophic Transfer and Accumulation of Multiwalled Carbon Nanotubes in the Presence of Copper Ions in Daphnia magna and Fathead Minnow (Pimephales promelas).

The increase in use of nanomaterials such as multiwalled carbon nanotubes (MWCNTs) presents a need to study their interactions with the environment. Trophic transfer was measured between Daphnia magna and Pimephales promelas (fathead minnow, FHM) exposed to MWCNTs with different outer diameter (OD) sizes (MWCNT1 = 8-15 nm OD and MWCNT2 = 20-30 nm OD) in the presence and absence of copper. Pristine FHM were fed D. magna, previously exposed for 3 d to MWCNT1 or MWCNT2 (0.1 mg/L) and copper (0.01 mg/L), for 7 d. D. magna bioaccumulated less MWCNT1 (0.02 µg/g) than MWCNT2 (0.06 µg/g), whereas FHM accumulated more MWCNT1 (0.81 µg/g) than MWCNT2 (0.04 µg/g). In the presence of copper, MWCNT bioaccumulation showed an opposite trend. Mostly MWCNT1 (0.03 µg/g) bioaccumulated in D. magna, however less MWCNT1 (0.21 µg/g) than MWCNT2 (0.32 µg/g) bioaccumulated in FHM. Bioaccumulation factors were higher for MWCNT1s than MWCNT2. However, an opposite trend was observed when copper was added. Plasma metallothionein-2 was measured among treatments; however concentrations were not statistically different from the control. This study demonstrates that trophic transfer of MWCNTs is possible in the aquatic environment and further exploration with mixtures can strengthen the understanding of MWCNT environmental behavior.

The effect of side of implantation on unilateral cochlear implant performance in patients with prelingual and postlingual sensorineural hearing loss: A systematic review.

OBJECTIVE: Cerebral lateralisation of language processing leads to a right ear advantage in normal hearing subjects. The aim of this study was to present a systematic overview of the effect of implantation side on postoperative cochlear implant performance in patients with symmetrical severe to profound sensorineural hearing loss. DATA SOURCES: PubMed, Embase and The Cochrane Library databases. RESEARCH METHODS: Databases were searched from database inception up to 9 January 2017 for cochlear implant and side and all synonyms. Title, abstract and full-text of retrieved articles were screened for eligibility. Then, directness of evidence and risk of bias were assessed. For the included articles, study characteristics and outcome data (hearing and language development) were extracted. RESULTS: 2541 unique articles were screened, of which twenty were eligible for critical appraisal. No randomised controlled trials were identified. Twelve studies with a high directness of evidence remained for data extraction. Four of six studies including children with pre-lingual sensorineural hearing loss and four of seven studies investigating adults with postlingual sensorineural hearing loss found a right ear advantage in at least one outcome measurement related to cochlear implant performance. CONCLUSION: The available evidence on the effect of side of implantation is of low quality, as study populations and outcome measures are heterogeneous. The majority of studies reveals evidence for a right ear advantage in prelingually deafened children as well as postlingually deafened adults. In view of the present evidence and as no left ear advantage was identified, we cautiously advise implanting the cochlear implant in the right ear when other prognostic factors do not favour the left ear and sensorineural hearing loss is symmetrical.

Cochlear implant performance in children deafened by congenital cytomegalovirus-A systematic review.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is a major cause of sensorineural hearing loss in children. OBJECTIVE OF REVIEW: The objective of this systematic review was to compare performance in paediatric cochlear implant users with SNHL caused by cCMV compared to non-cCMV implantees. TYPE OF REVIEW: Systematic review SEARCH STRATEGY: PubMed, EMBASE and the Cochrane databases were searched from inception up to 15 May 2017 for children, cochlear implant, performance and their synonyms. EVALUATION METHODS: Titles, abstracts and full texts were screened for eligibility. Directness of evidence and risk of bias were assessed. From the included studies, study characteristics and outcome data (speech perception, speech production, receptive language and auditory performance of cCMV groups and non-cCMV groups) were extracted. RESULTS: A total of 5280 unique articles were screened of which 28 were eligible for critical appraisal. After critical appraisal, 12 studies remained for data extraction. Seven of 12 studies showed worse performance after cochlear implantation in cCMV children compared to non-cCMV children. Worse performance in cCMV children was attributed to cCMV-related comorbidities in six of these studies. Available data on asymptomatic cCMV children compared to non-cCMV children did not reveal an unfavourable effect on cochlear implant performance. CONCLUSIONS: The available evidence reveals that cCMV children often have worse cochlear implant performance compared to non-cCMV children, which can be attributed to cCMV related comorbidities. We urge physicians to take into account the cCMV related comorbidities in the counselling of paediatric CI users deafened by cCMV.

Mobile Platform for Multiplexed Detection and Differentiation of Disease-Specific Nucleic Acid Sequences, Using Microfluidic Loop-Mediated Isothermal Amplification and Smartphone Detection.

New tools are needed to enable rapid detection, identification, and reporting of infectious viral and microbial pathogens in a wide variety of point-of-care applications that impact human and animal health. We report the design, construction, and characterization of a platform for multiplexed analysis of disease-specific DNA sequences that utilizes a smartphone camera as the sensor in conjunction with a hand-held "cradle" that interfaces the phone with a silicon-based microfluidic chip embedded within a credit-card-sized cartridge. Utilizing specific nucleic acid sequences for four equine respiratory pathogens as representative examples, we demonstrated the ability of the system to utilize a single 15 µL droplet of test sample to perform selective positive/negative determination of target sequences, including integrated experimental controls, in approximately 30 min. Our approach utilizes loop-mediated isothermal amplification (LAMP) reagents predeposited into distinct lanes of the microfluidic chip, which when exposed to target nucleic acid sequences from the test sample, generates fluorescent products that when excited by appropriately selected light emitting diodes (LEDs), are visualized and automatically analyzed by a software application running on the smartphone microprocessor. The system achieves detection limits comparable to those obtained by laboratory-based methods and instruments. Assay information is combined with the information from the cartridge and the patient to populate a cloud-based database for epidemiological reporting of test results.

Integrative studies implicate matrix metalloproteinase-12 as a culprit gene for large-artery atherosclerotic stroke.

BACKGROUND: Ischaemic stroke and coronary heart disease are important contributors to the global disease burden and share atherosclerosis as the main underlying cause. Recent evidence from a genome-wide association study (GWAS) suggested that single nucleotide polymorphisms (SNP) near the MMP12 gene at chromosome 11q22.3 were associated with large-vessel ischaemic stroke. Here, we evaluated and extended these results by examining the relationship between MMP12 and atherosclerosis in clinical and experimental studies. METHODS AND RESULTS: Plasma concentrations of MMP12 were measured at baseline in 3394 subjects with high-risk for cardiovascular disease (CVD) using the Olink ProSeek CVD I array. The plasma MMP12 concentration showed association with incident cardiovascular and cerebrovascular events (130 and 67 events, respectively, over 36 months) and carotid intima-media thickness progression (P = 3.6 × 10-5 ). A GWAS of plasma MMP12 concentrations revealed that SNPs rs499459, rs613084 and rs1892971 at chr11q22.3 were independently associated with plasma MMP12 (P < 5 × 10-8 ). The lead SNPs showed associations with mRNA levels of MMP12 and adjacent MMPs in atherosclerotic plaques. MMP12 transcriptomic and proteomic levels were strongly significantly increased in carotid plaques compared with control arterial tissue and in plaques from symptomatic versus asymptomatic patients. By combining immunohistochemistry and proximity ligation assay, we demonstrated that MMP12 localizes to CD68 + macrophages and interacts with elastin in plaques. MMP12 silencing in human THP-1-derived macrophages resulted in reduced macrophage migration. CONCLUSIONS: Our study supports the notion that MMP12 is implicated in large-artery atherosclerotic stroke, functionally by enhancing elastin degradation and macrophage invasion in plaques.

Does personalized melanoma genomic risk information trigger conversations about skin cancer prevention and skin examination with family, friends and health professionals?

BACKGROUND: Receiving information about genomic risk of melanoma might trigger conversations about skin cancer prevention and skin examinations. OBJECTIVES: To explore conversations prompted by receiving personalized genomic risk of melanoma with family, friends and health professionals. METHODS: We used a mixed-methods approach. Participants without a personal history and unselected for a family history of melanoma (n = 103, aged 21-69 years, 53% women) completed questionnaires 3 months after receiving a personalized melanoma genomic risk assessment. Semistructured interviews were undertaken with 30 participants in high, average and low genomic risk categories, and data were analysed thematically. RESULTS: From the questionnaires, 74% of participants communicated their genomic risk information with family, and 49% with friends. Communication with a health professional differed by risk level: 41%, 16% and 12% for high, average and low risk, respectively (P = 0·01). Qualitative analysis showed that perceived 'shared risk' and perceived interest of family and friends were motivations for discussing risk or prevention behaviours. The information prompted conversations with family and health professionals about sun protection and skin checks, and general conversations about melanoma risk with friends. Reasons for not discussing with family included existing personal or family health concerns, or existing high levels of sun protection behaviour among family members. CONCLUSIONS: Personalized melanoma genomic risk information can prompt risk-appropriate discussions about skin cancer prevention and skin examinations with family and health professionals. Sharing this information with others might increase its impact on melanoma prevention and skin examination behaviours, and this process could be used to encourage healthy behaviour change within families.

[Adequacy of treatment for chronic anxiety or depression; an exploratory study of treatment practice]. / Adequaatheid van de behandeling bij chronische angst en depressie; verkennende studie naar de behandelpraktijk.

BACKGROUND: Many patients with anxiety or depression receiving specialised outpatient treatment at mental health centres do not fully recover. Relapse and chronic course are common. This raises questions about the adequacy of the treatment they receive.
AIM: To obtain insight into the type and length of the treatment given to patients with chronic anxiety or depression.
METHOD: We collected data as part of a national study involving 12 mental health trusts. To be included in the study, patients had to satisfy certain criteria: they had to have received specialised treatment for anxiety or depression for at least two years and there had to be concerns whether these patients would benefit from further treatment in this setting. We gathered information about patient characteristics, diagnosis and treatment history.
RESULTS: On the basis of our selection criteria, 268 patients participated in our study; 65% of the patients were female. Patients were grouped in three categories: 67% were suffering from major depression, 25% from anxiety disorder and 8% from comorbid anxiety and depression. On average, patients had been treated for six years. More than one third of patients had received poor-quality treatment: treatment in the form of psychotherapy and/or pharmacotherapy had not been carried out in accordance with treatment guidelines.
CONCLUSION: In practice, much current treatment falls short of expectations. In particular, pharmacotherapy for depression needs to be improved. Longer periods of treatment should be evaluated at least once every six months.

HCN channels are a novel therapeutic target for cognitive dysfunction in Neurofibromatosis type 1.

Cognitive impairments are a major clinical feature of the common neurogenetic disease neurofibromatosis type 1 (NF1). Previous studies have demonstrated that increased neuronal inhibition underlies the learning deficits in NF1, however, the molecular mechanism underlying this cell-type specificity has remained unknown. Here, we identify an interneuron-specific attenuation of hyperpolarization-activated cyclic nucleotide-gated (HCN) current as the cause for increased inhibition in Nf1 mutants. Mechanistically, we demonstrate that HCN1 is a novel NF1-interacting protein for which loss of NF1 results in a concomitant increase of interneuron excitability. Furthermore, the HCN channel agonist lamotrigine rescued the electrophysiological and cognitive deficits in two independent Nf1 mouse models, thereby establishing the importance of HCN channel dysfunction in NF1. Together, our results provide detailed mechanistic insights into the pathophysiology of NF1-associated cognitive defects, and identify a novel target for clinical drug development.

Graphene reflux: improving the yield of liquid-exfoliated nanosheets through repeated separation techniques.

Scalable production of graphene through liquid-phase exfoliation has been plagued by low yields. Although several recent studies have attempted to improve graphene exfoliation technology, the problem of separating colloidal nanosheets from unexfoliated parent material has received far less attention. Here we demonstrate a scalable method for improving nanosheet yield through a facile washing process. By probing the sedimentation of liquid-phase exfoliated slurries of graphene nanosheets and parent material, we found that a portion of exfoliated graphene is entrapped in the sediment, but can be recovered by repeatedly washing the slurry of nanosheet and parent material with additional solvent. We found this process to significantly increase the overall yield of graphene (graphene/parent material) and recover a roughly constant proportion of graphene with each wash. The cumulative amount of graphene recovered is only a function of total solvent volume. Moreover, we found this technique to be applicable to other types of nanosheets such as boron nitride nanosheets.

Factors that influence outcomes in cochlear implantation in adults, based on patient-related characteristics - a retrospective study.

OBJECTIVE: Outcomes in speech perception following cochlear implantation in adults vary widely. Many studies have been carried out to identify and quantify factors that influence outcomes. This study adds a new dimension to pre-existing literature. DESIGN: Single-centre retrospective cohort study. SETTING: University Medical Center Utrecht, the Netherlands. PARTICIPANTS: A total of 428 adults with bilateral severe-to-profound sensorineural hearing loss, unilaterally implanted between February 1988 and March 2014. MAIN OUTCOME MEASURES: Univariable and multivariable linear regression analyses were carried out to identify factors that may influence outcome after cochlear implantation. Consonant-vowel-consonant word scores were recorded pre- and post-implant and were used as outcome measure in two groups of patients (prelingually and postlingually deafened adults). As an added dimension, multiple imputation was implemented and evaluated to tackle 4% (17/407) missing data. RESULTS: For postlinguals, pre-implant speech perception score and age at onset of deafness are positive predictors and meningitis and otosclerosis as cause of deafness are negative predictors of post-implant speech perception. This model accounted for 26% of variance. For prelinguals, pre-implant speech perception score is the only strong positive predictor (ß 0.524; P < 0.001). This model accounted for 31% of variance. Age at implantation was not a significant predictor in either group. CONCLUSIONS: Speech perception is predicted by pre-implant speech perception, age at onset of deafness and aetiology (meningitis and otosclerosis) for postlinguals and solely pre-implant speech perception for prelinguals. Age at implantation is of lesser importance in predicting speech perception outcome post-implant. Multiple imputation is a useful statistical technique when analysing incomplete data sets.

[Tailored pharmacotherapy. Consultations about medication in a care programme for depression]. / Farmacotherapie op maat; medicatieconsulten in een zorgprogramma voor depressie.

BACKGROUND: Despite the increasing rationalisation of mental health care, there are no specific recommendations regarding the number of contacts between a patient and a psychiatrist for the pharmacotherapy that forms part of the combined outpatient treatment (antidepressants and psychotherapy) of depression. AIM: To consider the possibility of drawing up an advisory document regarding frequency, number and duration of consultations about medication in combined treatment for depression. METHOD: We reviewed the literature and had qualitative interviews with psychiatrists and trainees in psychiatric residency. RESULTS: The literature focuses predominantly on diagnostics and patient characteristics that determine the amount of care required. Advice on medication and pharmacotherapy is provided only by experts. According to the interviews, in psychiatric practice many factors influence the number and duration of consultations. Nevertheless, a distinctive pattern emerged. CONCLUSION: Regarding medication in the acute treatment phase, five or six visits to a psychiatrist are sufficient for most patients. Extra consultations have to be arranged for smaller groups of less stable patients and for crisis-prone patients.

The multi-faceted nature of age-associated osteoporosis.

Age-associated osteoporosis (AAOP) poses a significant health burden, characterized by increased fracture risk due to declining bone mass and strength. Effective prevention and early treatment strategies are crucial to mitigate the disease burden and the associated healthcare costs. Current therapeutic approaches effectively target the individual contributing factors to AAOP. Nonetheless, the management of AAOP is complicated by the multitude of variables that affect its development. Main intrinsic and extrinsic factors contributing to AAOP risk are reviewed here, including mechanical unloading, nutrient deficiency, hormonal disbalance, disrupted metabolism, cognitive decline, inflammation and circadian disruption. Furthermore, it is discussed how these can be targeted for prevention and treatment. Although valuable as individual targets for intervention, the interconnectedness of these risk factors result in a unique etiology for every patient. Acknowledgement of the multifaceted nature of AAOP will enable the development of more effective and sustainable management strategies, based on a holistic, patient-centered approach.