Motivations and personality characteristics of candidate sperm and oocyte donors according to parenthood status: a national study from the French CECOS network.

STUDY QUESTION: In a non-commercial national gamete donation programme, do the motivations and personality characteristics of candidate sperm and oocyte donors differ according to their parenthood status? SUMMARY ANSWER: Moderate differences exist between non-parent and parent candidate donors in motivations for gamete donation and representations as well as in personality characteristics. WHAT IS KNOWN ALREADY: Several studies have analysed the motivations and experiences of oocyte or sperm donors, but mainly in countries where gamete donation is a commercial transaction, and very few studies have reported results of personality traits using personality inventory tests. No study has specifically investigated the motivations and personality characteristics of candidate gamete donors according to parenthood status. STUDY DESIGN SIZE DURATION: A prospective study was carried out including 1021 candidate donors from 21 centres (in university hospitals) of the national sperm and egg banking network in France between November 2016 and December 2018. PARTICIPANTS/MATERIALS SETTING METHODS: In total, 1021 candidate gamete donors were included in the study. During their first visit, male (n = 488) and female candidate donors (n = 533) completed a questionnaire on sociodemographic characteristics, their motivations for donation and their representations of donation, infertility and family. Secondly, a NEO Personality Inventory (NEO-PI-R) exploring the Big Five personality traits was completed online. Results were compared between parent and non-parent candidate donors. MAIN RESULTS AND THE ROLE OF CHANCE: Altruistic values were the principal motive for donation irrespective of parenthood status. Reassurance about their fertility or preservation of sperm for future use was more often reported in non-parent than in parent candidate donors. With regard to representation of gamete donation or of the family, independently of their parenthood status, candidate donors more frequently selected social rather than biological representations. Mean personality characteristics were in the normal range. Non-parent candidate donors had higher scores on openness and depression than parents, while parent candidate donors appeared more social than non-parents. LIMITATIONS REASONS FOR CAUTION: The personality characteristics inventory was not completed by all candidate donors included in the study. However, family status did not differ between the two groups (NEO-PI-R completed (n = 525) or not), while the group who completed the NEO-PI-R had a higher educational level. This national study was performed in a country where gamete donation is subject to strict legislation. WIDER IMPLICATIONS OF THE FINDINGS: In a global context where reproductive medicine is commercialized and gamete donor resources are limited, this study found that altruism and social representations of gamete donation and family are the main motivations for gamete donation in a country which prohibits financial incentive. These findings are relevant for health policy and for gamete donation information campaigns. STUDY FUNDING/COMPETING INTERESTS: Grant from the Agence de la Biomédecine, France. The authors have nothing to disclose related to this study. TRIAL REGISTRATION NUMBER: N/A.

Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott-Aldrich syndrome.

Patients with Wiskott-Aldrich syndrome (WAS) lacking a human leukocyte antigen-matched donor may benefit from gene therapy through the provision of gene-corrected, autologous hematopoietic stem/progenitor cells. Here, we present comprehensive, long-term follow-up results (median follow-up, 7.6 years) (phase I/II trial no. NCT02333760 ) for eight patients with WAS having undergone phase I/II lentiviral vector-based gene therapy trials (nos. NCT01347346 and NCT01347242 ), with a focus on thrombocytopenia and autoimmunity. Primary outcomes of the long-term study were to establish clinical and biological safety, efficacy and tolerability by evaluating the incidence and type of serious adverse events and clinical status and biological parameters including lentiviral genomic integration sites in different cell subpopulations from 3 years to 15 years after gene therapy. Secondary outcomes included monitoring the need for additional treatment and T cell repertoire diversity. An interim analysis shows that the study meets the primary outcome criteria tested given that the gene-corrected cells engrafted stably, and no serious treatment-associated adverse events occurred. Overall, severe infections and eczema resolved. Autoimmune disorders and bleeding episodes were significantly less frequent, despite only partial correction of the platelet compartment. The results suggest that lentiviral gene therapy provides sustained clinical benefits for patients with WAS.

Amalgam Phase-Down Part 1: UK-Based Posterior Restorative Material and Technique Use.

INTRODUCTION: A European Union amalgam phase-down has recently been implemented. Publicly funded health care predominates in the United Kingdom with the system favoring amalgam use. The current use of amalgam and its alternatives has not been fully investigated in the United Kingdom. OBJECTIVES: The study aimed to identify direct posterior restorative techniques, material use, and reported postoperative complication incidence experienced by primary care clinicians and differences between clinician groups. METHODS: A cross-sectional survey was distributed to primary care clinicians through British dentist and therapist associations (11,092 invitations). The questionnaire sought information on current provision of direct posterior restorations and perceived issues with the different materials. Descriptive statistical and hypothesis testing was performed. RESULTS: Dentists' response rate was 14% and therapists' estimated minimum response rate was 6% (total N = 1,513). The most commonly used restorative material was amalgam in molar teeth and composite in premolars. When placing a direct posterior mesio-occluso-distal restoration, clinicians booked on average 45% more time and charged 45% more when placing composite compared to amalgam (P < 0.0001). The reported incidences of food packing and sensitivity following the placement of direct restorations were much higher with composite than amalgam (P < 0.0001). Widely recommended techniques, such as sectional metal matrix use for posterior composites, were associated with reduced food packing (P < 0.0001) but increased time booked (P = 0.002). CONCLUSION: Amalgam use is currently high in the publicly funded sector of UK primary care. Composite is the most used alternative, but it takes longer to place and is more costly. Composite also has a higher reported incidence of postoperative complications than amalgam, but time-consuming techniques, such as sectional matrix use, can mitigate against food packing, but their use is low. Therefore, major changes in health service structure and funding and posterior composite education are required in the United Kingdom and other countries where amalgam use is prevalent, as the amalgam phase-down continues. KNOWLEDGE TRANSFER STATEMENT: This study presents data on the current provision of amalgam for posterior tooth restoration and its directly placed alternatives by primary care clinicians in the United Kingdom, where publicly funded health care with copayment provision predominates. The information is important to manage and plan the UK phase-down and proposed phase-out of amalgam and will be of interest to other, primarily developing countries where amalgam provision predominates in understanding some of the challenges faced.

Amalgam Phase-Down Part 2: UK-Based Knowledge, Opinions, and Confidence in the Alternatives.

INTRODUCTION: Amalgam use has recently been phased down, and the potential for a phase-out is being investigated. OBJECTIVES: The study aimed to identify knowledge of the phase-down and opinions of a potential phase-out of amalgam by UK primary care clinicians and assess their confidence in using different materials in different situations. METHODS: An anonymized, prepiloted cross-sectional e-survey was used to assess primary care clinicians' knowledge and opinions of the amalgam phase-down and potential phase-out and their confidence in using amalgam and the alternatives in different situations. In total, 11,902 invitations were distributed through British dentist and therapist associations. Prior hypotheses were tested alongside descriptive statistics. RESULTS: Response rate was 13% (n = 1,513). Knowledge of the amalgam phase-down was low, with just 3% clinicians correctly identifying all patient groups in whom amalgam use should be avoided in the United Kingdom. Postgraduate education on posterior composite placement was high (88%), but a large majority had personal and patient-centered concerns over the suitability of the alternatives and lacked confidence when placing composite in comparison to amalgam in difficult situations (P < 0.0001). Logistic regressions revealed that the best predictors of high confidence in placing mesio-occluso-distal composites and composites in difficult situations were being a private general dentist or being primarily a composite user. CONCLUSION: Primary care clinicians have major personal and patient-centered concerns regarding the amalgam phase-down (of which they have limited knowledge) and potential phase-out. Many lack confidence in using the alternative, composite, to restore posterior teeth in difficult situations, whereas confidence in using amalgam in similar situations is high. Effective education of clinicians and understanding patients' needs, alongside policy changes, are required to enable a successful amalgam phase-down and potential phase-out. KNOWLEDGE TRANSFER STATEMENT: This study shows that UK primary care clinicians are worried about the phase-down of amalgam for themselves and their patients. Many lack confidence in the alternative, composite, when used in difficult situations, which is in stark contrast to amalgam. Knowledge of the phase-down is limited. There is a need for more effective education of clinicians, an understanding of patients' values, and policy changes to ensure the success of the phase-down and potential phase-out of amalgam.

Cardiac biomarkers of disordered eating as a function of diagnostic subtypes.

OBJECTIVE: The purpose of this study was to identify cardiac biomarkers of disordered eating as a function of diagnostic subtype as assessed via self-report inventory. METHOD: Mean heart rate (HR), systolic and diastolic blood pressure, mean R wave amplitude (mV), mean T wave amplitude (mV), QTc interval (sec), Tpeak-Tend interval prolongation (sec), QTc interval prolongation (sec), QRS prolongation (sec), and spectral indicators of cardiac dysfunction (LF/HF spectral ratio, HF spectral power) were assessed via electrocardiography among women with no eating disorder symptoms (n = 32), subclinical eating disorder symptoms (n = 92), anorexia nervosa (n = 7), bulimia nervosa (n = 89), binge eating disorder (BED: n = 20), and other specified feeding and eating disorders (OSFED: n = 19). RESULTS: MANOVA results showed statistically significant group differences. Follow-up tests revealed significantly decreased mean R wave amplitude among participants with self-indicated clinical (bulimia nervosa, binge eating disorder) and subclinical forms of disordered eating compared to asymptomatic controls. DISCUSSION: Results suggest decreased mean R wave amplitude is a promising cardiac biomarker of disordered eating.

Micro- and macro-viscosity relations in high concentration antibody solutions.

Molecular crowding in highly concentrated monoclonal antibody (mAb) solutions results in significant increases in viscosity, which complicates fill-finish steps and patient administration by subcutaneous injection. As viscosity measurements for optimization of the mAb formulation require significant amounts of material not always available in early development, fluorescence correlation spectroscopy (FCS) is evaluated as a potential ultra-low volume technique for viscosity measurement of high concentration protein solutions assuming the Generalised Stokes Einstein relation (GSE) remains valid. Using like-charge fluorescent tracers of different sizes, FCS provided measurements of microviscosities which were compared to the macroviscosity. After parametrising the protein concentration dependence of the viscosity by the exponential coefficient (k) of a simple exponential model, FCS derived k-values of like-size tracer to the crowder followed the same ordering as the macroviscosity derived k-values with respect to solvent conditions. Furthermore, k and the diffusion-derived protein-protein interaction parameter, kD, are linked, and, attractive conditions for mAbs result in a stronger concentration dependence of the viscosity. For tracers and crowders of like-size, a key result is negative deviations from the GSE relation are observed in presence of strong attractive interactions between crowder molecules. These data demonstrate that FCS has application to the screening of high concentration mAb solutions for formulation selection.

Long-term implant of intramuscular sensors and nerve transfers for wireless control of robotic arms in above-elbow amputees.

Targeted muscle reinnervation (TMR) amplifies the electrical activity of nerves at the stump of amputees by redirecting them in remnant muscles above the amputation. The electrical activity of the reinnervated muscles can be used to extract natural control signals. Nonetheless, current control systems, mainly based on noninvasive muscle recordings, fail to provide accurate and reliable control over time. This is one of the major reasons for prosthetic abandonment. This prospective interventional study includes three unilateral above-elbow amputees and reports the long-term (2.5 years) implant of wireless myoelectric sensors in the reinnervation sites after TMR and their use for control of robotic arms in daily life. It therefore demonstrates the clinical viability of chronically implanted myoelectric interfaces that amplify nerve activity through TMR. The patients showed substantial functional improvements using the implanted system compared with control based on surface electrodes. The combination of TMR and chronically implanted sensors may drastically improve robotic limb replacement in above-elbow amputees.

Personalized pathology maps to quantify diffuse and focal brain damage.

BACKGROUND AND OBJECTIVES: Quantitative MRI (qMRI) permits the quantification of brain changes compatible with inflammation, degeneration and repair in multiple sclerosis (MS) patients. In this study, we propose a new method to provide personalized maps of tissue alterations and longitudinal brain changes based on different qMRI metrics, which provide complementary information about brain pathology. METHODS: We performed baseline and two-years follow-up on (i) 13 relapsing-remitting MS patients and (ii) four healthy controls. A group consisting of up to 65 healthy controls was used to compute the reference distribution of qMRI metrics in healthy tissue. All subjects underwent 3T MRI examinations including T1, T2, T2* relaxation and Magnetization Transfer Ratio (MTR) imaging. We used a recent partial volume estimation algorithm to estimate the concentration of different brain tissue types on T1 maps; then, we computed a deviation map (z-score map) for each contrast at both time-points. Finally, we subtracted those deviation maps only for voxels showing a significant difference with healthy tissue in one of the time points, to obtain a difference map for each subject. RESULTS AND CONCLUSION: Control subjects did not show any significant z-score deviations or longitudinal z-score changes. On the other hand, MS patients showed brain regions with cross-sectional and longitudinal concomitant increase in T1, T2, T2* z-scores and decrease of MTR z-scores, suggesting brain tissue degeneration/loss. In the lesion periphery, we observed areas with cross-sectional and longitudinal decreased T1/T2 and slight decrease in T2* most likely related to iron accumulation. Moreover, we measured longitudinal decrease in T1, T2 - and to a lesser extent in T2* - as well as a concomitant increase in MTR, suggesting remyelination/repair. In summary, we have developed a method that provides whole-brain personalized maps of cross-sectional and longitudinal changes in MS patients, which are computed in patient space. These maps may open new perspectives to complement and support radiological evaluation of brain damage for a given patient.

BDA hospital dentists survey 2017.

In 2016 the BDA undertook to investigate the demographics and distribution of its hospital members alongside their morale and motivation. This is the first time the BDA had undertaken such a survey and it is the first time any workforce research into the Hospital Dental Services (HDS) has been published by any party. Subsequent freedom of information requests have suggested that BDA HDS member data is representative of the overall HDS workforce. Of particular note is the distribution of some of the 'smaller' specialties with some seemingly only existing at dental school level alongside morale and motivation levels in relation to other dental roles.

Agglutination by anti-capsular polysaccharide antibody is associated with protection against experimental human pneumococcal carriage.

The ability of pneumococcal conjugate vaccine (PCV) to decrease transmission by blocking the acquisition of colonization has been attributed to herd immunity. We describe the role of mucosal immunoglobulin G (IgG) to capsular polysaccharide (CPS) in mediating protection from carriage, translating our findings from a murine model to humans. We used a flow cytometric assay to quantify antibody-mediated agglutination demonstrating that hyperimmune sera generated against an unencapsulated mutant was poorly agglutinating. Passive immunization with this antiserum was ineffective to block acquisition of colonization compared to agglutinating antisera raised against the encapsulated parent strain. In the human challenge model, samples were collected from PCV and control-vaccinated adults. In PCV-vaccinated subjects, IgG levels to CPS were increased in serum and nasal wash (NW). IgG to the inoculated strain CPS dropped in NW samples after inoculation suggesting its sequestration by colonizing pneumococci. In post-vaccination NW samples pneumococci were heavily agglutinated compared with pre-vaccination samples in subjects protected against carriage. Our results indicate that pneumococcal agglutination mediated by CPS-specific antibodies is a key mechanism of protection against acquisition of carriage. Capsule may be the only vaccine target that can elicit strong agglutinating antibody responses, leading to protection against carriage acquisition and generation of herd immunity.

Nerve grafts bridging the thenar branch of the median nerve to the ulnar nerve to enhance nerve recovery: a report of three cases.

We report a nerve graft procedure bridging the thenar branch of the median nerve to the ulnar nerve in three patients with ulnar nerve transection and defect at the mid-forearm. Ulnar nerve function was evaluated with electroneurography and quantitative sensory-motor testing before and after surgery, and at a 6-year follow-up. After surgery all patients showed electroneurographic evidence of median nerve innervation of the intrinsic muscles normally innervated by the ulnar nerve. The average strength was Grade 4 in the intrinsic muscles originally supplied by the ulnar nerve at the final follow-up. Our results indicate that the thenar branch of the median nerve may support ulnar nerve regeneration and so help prevent intrinsic muscles from irreversible atrophy, but our report is preliminary. This procedure should be validated by future clinical data, especially those with complete ulnar nerve transection at or above the elbow. LEVEL OF EVIDENCE: IV.

Acinic Cell Carcinoma of the Parotid Gland with Four Morphological Features.

Acinic cell carcinoma arising in salivary glands is a rare tumor, accounting for 2% to 5% of the primary neoplasms of the parotid gland. When these tumors are well-differentiated, the neoplasia has innocuous aspect, due to the similarity to normal parotid tissue. This makes the diagnosis difficult. Initially the malignancy of this tumor was uncertain; however, recent studies have declared it as malignant. The female / male ratio is 3:2. The nodule usually presents as solitary and well defined shape. Several authors have used different terms to describe histomorphological patterns of these tumors. Four descriptive categories (solid, microcystic, papillary-cystic and follicular) are useful for pathologists. Here we report a case of a 49 yr old man with a left parotid nodule of 5 cm. Parotidectomy was performed at the Hospital Universitario Miguel Servet, in Zaragoza (Spain). The microscopy showed a tumor with acinic semblance, having the four morphologic patterns previously described. The morphological and immunohistochemical study was consistent with the diagnosis of acinic cell carcinoma.

Is there still room for additional common susceptibility alleles for venous thromboembolism?

UNLABELLED: Essentials Genetic architecture of venous thromboembolism (VTE) remains to be fully disentangled. 11 newly discovered candidate polymorphisms were genotyped in 3019 VTE cases and 2605 controls. None of the 11 polymorphisms were significantly associated with VTE risk. Additional major efforts are needed to identify VTE-associated genetic variants. SUMMARY: Background Through a meta-analysis of 12 genome-wide association studies, the International Network against VENous Thrombosis (INVENT) consortium identified two novel susceptibility loci for venous thromboembolism (VTE). This project has also generated other candidates that need to be confirmed. Objectives To assess the association with VTE of common single-nucleotide polymorphisms (SNPs) that demonstrated strong statistical, but not genome-wide, significance in the INVENT cohorts. Patients/methods Eleven SNPs were genotyped and tested for association with VTE in three case-control studies totaling 3019 patients and 2605 healthy individuals. Results and conclusions None of the tested SNPs showed evidence for association with VTE. Different strategies are needed to decipher the whole spectrum of common and rare genetic variations associated with VTE risk.

Hand Transplantation Versus Hand Prosthetics: Pros and Cons.

Composite tissue transplantation and new developments in the field of prosthetics have opened new frontiers in the restoration of function among upper limb amputees. It is now possible to restore hand function in affected patients; however, the indications, advantages, and limitations for either hand transplantation or prosthetic fitting must be carefully considered depending on the level and extent of the limb loss. Hand transplantation allows comprehensive hand function to be restored, yet composite tissue transplantation comes with disadvantages, making this method a controversial topic in the hand surgical community. Alternatively, prosthetic limb replacement represents the standard of care for upper limb amputees, but results in the known limitations of function, sensation, and usage. The indication for hand transplantation or prosthetic fitting strongly depends on the level of amputation, as well as on the extent (unilateral/bilateral) of the amputation. In this review, we discuss the advantages and disadvantages of hand transplantation and prosthetic replacement for upper limb amputees in general, as well as in regard to the different levels of amputation.

Laser treatment for female facial hirsutism: are quality-of-life benefits sustainable?

BACKGROUND: Facial hirsutism in women impairs quality of life (QoL). Laser hair removal (LHR) has been shown to confer significant improvements in QoL for up to 6 months after treatment, but the longer-term benefits have not been investigated. AIM: To assess the sustainability of LHR benefits to the QoL of hirsute women up to 30 months after treatment. METHODS: Hirsute women about to undergo National Health Service (NHS)-funded LHR in 2010-2012 (n = 142) completed proforma questionnaires quantifying the burden of hirsutism on their QoL. These included: the Dermatology Life Quality Index (DLQI) (assessing functional impact on QoL), the number of days spent removing hair per week and a 10-point scale assessing how much their condition bothered them (emotional burden on QoL). Postal questionnaires recorded QoL changes up to 30 months after LHR. Improvements in QoL scores for each woman were compared. Responses were then grouped into periods of 0-6, 6-12 and 12-30 months post-treatment, and the magnitude of change between these time groups was compared for each QoL measure. RESULTS: In total, 63 women responded to the post-LHR questionnaire. QoL was severely affected, but improved with LHR. The number of days spent removing hair reverted to baseline at 12-30 months post-LHR, and a significant decline was seen in the magnitude of improvement in emotional burden on QoL over time (P = 0.04). However, no significant difference existed between improvements in DLQI scores (P = 0.12). CONCLUSION: LHR supplies some functional QoL benefits up to 30 months post-treatment. Emotional benefits are less sustainable. Further LHR treatment is required to maintain QoL benefits.

Prosthetic reconstruction to restore function in transcarpal amputees.

Mutilated hands at the distal level may pose a challenge for reconstruction. Biological treatment options may require multiple surgical interventions and a long rehabilitation course with little hope of good functional outcome. Standard hand prostheses are also not an ideal solution, as they are too long and cumbersome for partial hand injuries. This paper outlines the functional outcomes of prosthetic reconstruction with devices customized for the transcarpal amputation levels. The functional outcome was evaluated with the Action Research Arm Test (ARAT), Southampton Hand Assessment Procedure (SHAP), and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH). Functional evaluation was performed at least 12 months after final fitting. Psychological assessment was performed with the Short Form-36. The three patients achieved a mean ARAT score of 35.67 ± 0.58. The average SHAP score was 74 ± 7.81. The average DASH score was found to be 16.11 ± 12.03. The reconstructed hand achieved a score of 75.27 ± 8.16% in SHAP and 62.57 ± 1.02% in ARAT in relation to the healthy hand. All patients exhibited average physical and mental component summary scales in the Short Form-36. The majority of transcarpal amputations are seen in manual laborers due to work-related trauma. Returning to work is the main goal in such young and otherwise-healthy patients. As shown with this study, prosthetic fitting results in quick and reliable functional reconstruction. Therefore, this treatment should be considered as an option during the initial decision-making process of reconstructing difficult traumatic injuries of the hand.

A multi-contrast MRI study of microstructural brain damage in patients with mild cognitive impairment.

OBJECTIVES: The aim of this study was to investigate pathological mechanisms underlying brain tissue alterations in mild cognitive impairment (MCI) using multi-contrast 3 T magnetic resonance imaging (MRI). METHODS: Forty-two MCI patients and 77 healthy controls (HC) underwent T1/T2* relaxometry as well as Magnetization Transfer (MT) MRI. Between-groups comparisons in MRI metrics were performed using permutation-based tests. Using MRI data, a generalized linear model (GLM) was computed to predict clinical performance and a support-vector machine (SVM) classification was used to classify MCI and HC subjects. RESULTS: Multi-parametric MRI data showed microstructural brain alterations in MCI patients vs HC that might be interpreted as: (i) a broad loss of myelin/cellular proteins and tissue microstructure in the hippocampus (p ≤ 0.01) and global white matter (p < 0.05); and (ii) iron accumulation in the pallidus nucleus (p ≤ 0.05). MRI metrics accurately predicted memory and executive performances in patients (p ≤ 0.005). SVM classification reached an accuracy of 75% to separate MCI and HC, and performed best using both volumes and T1/T2*/MT metrics. CONCLUSION: Multi-contrast MRI appears to be a promising approach to infer pathophysiological mechanisms leading to brain tissue alterations in MCI. Likewise, parametric MRI data provide powerful correlates of cognitive deficits and improve automatic disease classification based on morphometric features.