Machine learning approach to assess the association between anthropometric, metabolic, and nutritional status and semen parameters.

ABSTRACT: Many lifestyle factors, such as nutritional imbalance leading to obesity, metabolic disorders, and nutritional deficiency, have been identified as potential risk factors for male infertility. The aim of this study was to evaluate the relationship between semen parameters and anthropometric, metabolic and nutritional parameters. Relationship was first assessed individually, then after the application of a previously constructed and validated machine learning score that allows their combination. Anthropometric, metabolic, antioxidant, micronutrient, and sperm parameters from 75 men suffering from idiopathic infertility from four infertility centers in France (Jean-Verdier ART Center Hospital, Bondy; North Hospital ART Center, Saint-Étienne; Navarre Polyclinic ART Center, Pau; and Cochin Hospital ART Center, Paris) between September 2009 and December 2013 were collected. After assessing standard correlation analysis, a previously built machine learning model, providing a score ranging from 0 (the poorest) to 1 (the most favorable), was calculated for each man in the study cohort. This machine learning model, which separates infertile/fertile men with unexplained infertility on the basis of their bioclinical signature, provides a more holistic evaluation of the influence of the considered markers (anthropometric, metabolic, and oxidative status). We observed a significant correlation of some anthropometric, metabolic, and nutritional disorders with some sperm characteristics. Moreover, an unfavorable machine learning score was associated with a high level of sperm DNA fragmentation. Favorable anthropometric, metabolic, and oxidative patterns, which may reflect an appropriate lifestyle, appear to positively impact overall health, in particular reproductive function. This study, consistent with previous publications, suggests that beyond semen quality parameters, in an essential assessment of male fertility, other key factors should be taken into account. In this regard, the application of emerging artificial intelligence techniques may provide a unique opportunity to integrate all these parameters and deliver personalized care.

Effectiveness of the miWe Simulator Training on Powered Wheelchair-driving Skills: A Randomized Controlled Trial.

OBJECTIVES: To evaluate the effectiveness of a home-based simulator training, in comparison with a videogame-based training, in terms of powered wheelchair driving skills, skills use in a real-world setting, and driving confidence. DESIGN: Single-blinded randomized controlled trial. SETTING: Community. PARTICIPANTS: New powered wheelchair users (N=47) randomly allocated to simulator group (n=24, 2 drop-out) and control group (n=23, 3 drop-out). INTERVENTIONS: The miWe wheelchair simulator (simulator group) or a kart driving videogame (control group) was setted-up at participants' homes (computer + joystick). They were instructed to use it at least 20 minutes every 2 days, during a period of 2 weeks. PRIMARY OUTCOME MEASURE(S): Assessments were done at baseline (T1) and post-training (T2) using the Wheelchair Skills Test Questionnaire (WST-Q, version 4.1), Wheelchair Confidence Scale (WheelCon), Assistive Technology Outcomes Profile for Mobility, and Life-Space Assessment (LSA). The time necessary to complete 6 WST tasks was measured with a stopwatch. RESULTS: Participants of the simulator group significantly increased their WST-Q capacity score at T2 by 7.5% (P<.05), whereas the control group remained at the same score (P=.218). Participants of both groups rolled backward and went through a door significantly faster at T2 (P=.007; P=.016), but their speed did not change for the other skills. The WheelCon score significantly increased after training (+4% for the control group and +3.5% for the simulator group, P=.001). There was no T1-T2 difference between groups for the WST-Q performance scores (P=.119), the ATOP-Activity (P=.686), the ATOP-Participation scores (P=.814), and the LSA score (P=.335). No adverse events or side effects were reported during data collection or training. CONCLUSIONS: Participants of both groups improved some skills and their wheelchair driving confidence. The simulator training group also demonstrated a modest post-training gain in their WST-Q capacity, but more studies would be needed to explore the long-term effects of the McGill immersive wheelchair simulator (miWe) simulator on driving skills.

A systematic review of the determinants of implementation of a locomotor training program using a powered exoskeleton for individuals with a spinal cord injury.

BACKGROUND: Wearable powered exoskeletons represent a promising rehabilitation tool for locomotor training in various populations, including in individuals with a spinal cord injury. The lack of clear evidence on how to implement a locomotor powered exoskeleton training program raises many challenges for patients, clinicians and organizations. OBJECTIVE: To report determinants of implementation in clinical practice of an overground powered exoskeleton locomotor training program for persons with a spinal cord injury. DATA SOURCES: Medline, CINAHL, Web of Science. STUDY SELECTION: Studies were included if they documented determinants of implementation of an overground powered exoskeleton locomotor training program for individuals with spinal cord injury. DATA EXTRACTION: Eligible studies were identified by two independent reviewers. Data were extracted by one reviewer, based on constructs of the Consolidated Framework for Implementation Research, and validated by a second reviewer. RESULTS: Sixty-three articles were included. 49.4% of all determinants identified were related to the intervention characteristics, 29.6% to the individuals' characteristic and 13.5% to the inner setting. Recurrent barriers identified were the high prevalence of adverse events (e.g., skin issues, falls) and device malfunctions. Adequate training for clinicians, time and resource available, as well as discussion about patients' expectations were identified as facilitators. CONCLUSIONS: Powered exoskeleton training is a complex intervention. The limited information on the context and the implementation process domains may represent a barrier to a successful transition from knowledge to action.

Final 4-year results of the RAINBOW real-world study: intravitreal aflibercept dosing regimens in France in treatment-naïve patients with neovascular age-related macular degeneration.

PURPOSE: The purpose of this study is to evaluate real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in routine clinical practice in France. METHODS: RAINBOW (NCT02279537) was an ambispective, observational, 4-year study assessing IVT-AFL effectiveness, treatment patterns, and safety in patients with nAMD in France. Treatment-naïve patients prescribed IVT-AFL and treated according to local practice (pro re nata or treat-and-extend) were eligible. Three treatment cohorts were retrospectively identified based on their treatment pattern within the first 12 months: regular (3 initial monthly IVT-AFL injections received within 45-90 days after the first injection in month 0 and followed by injections every 2 months), irregular with the initial monthly injections, and irregular without the initial monthly injections. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to month 12. The 48-month results are described here. RESULTS: Overall, the study included 516 patients (each with one study eye), and 30.2% of patients completed 48 months of IVT-AFL treatment. Mean change in BCVA from baseline (56.5 letters) to month 48 for patients with an assessment at both time points was + 1.1 (regular cohort, n = 47), + 0.1 (irregular cohort with initial monthly injections, n = 115), and - 1.3 letters (irregular cohort without initial monthly injections, n = 26), representing a decrease from the gains achieved at month 12. Mean number of IVT-AFL injections received by month 48 in the treatment cohorts was 14.9, 13.7, and 11.9, respectively. The safety profile of IVT-AFL was consistent with previous studies. CONCLUSION: In RAINBOW, the 48-month results demonstrate a lack of long-term effectiveness of IVT-AFL treatment of nAMD due to progressive undertreatment in routine clinical practice in France. These real-world findings highlight the importance of 3 initial monthly IVT-AFL injections followed by continuous proactive treatment beyond the first year to achieve optimal functional outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02279537.

Structural and functional analysis of retinal vasculature in HANAC syndrome with a novel intronic COL4A1 mutation.

PURPOSE: Mutations of the COL4A1 gene, a major structural protein of vessels, may cause hereditary angiopathy with nephropathy, aneurysms and muscle cramps (HANAC) syndrome. The vascular structure and function of patients with HANAC is poorly known. Here, we report a family with HANAC syndrome associated to a previously unreported mutation in COL4A1. The structure and function of retinal vessels were detailed by adaptive optics ophthalmoscopy (AOO) and optical coherence tomography (OCT) angiography. METHODS: Clinical data from six affected individuals (43 to 72 years old) from a single family comprising two generations were collected. Imaging charts including conventional fundus imaging, OCT-angiography and AOO in static and dynamic (flicker) mode were reviewed. DNA sequencing was done in the proband. RESULTS: DNA sequencing of the proband revealed a heterozygous deletion of COL4A1 (NM_001845) at position 1120 in the intron 20 resulting in the loss of splicing donor site for exon 20 (c.1120 + 2_1120 + 8del heterozygote). Four patients had arterial hypertension, and three had kidney dysfunction, one of which under dialysis. By fundus examination, five had typical retinal arteriolar tortuosity with arteriolar loops. Wall-to-lumen ratio of arteries was within normal limits, that is, lower than expected for hypertensive patients. Several foci of arteriolar irregularities were noted in the two oldest patients. In three affected subjects, evaluation of the neurovascular coupling showed a higher flicker-induced vasodilation than a control population (6 % to 11 %; n < 5 %). CONCLUSIONS: Structural and dynamic analysis of retinal vessels in a HANAC family bearing a previously unreported intronic COL4 mutation was done. In addition to arteriolar tortuosity, we found reduced wall-to-lumen ratio, arteriolar irregularity and increased vasodilatory response to flicker light. These abnormalities were more marked in the oldest subjects. This abnormal flicker response affected also non-tortuous arteries, suggesting that microvascular dysfunction extends beyond tortuosity. Such explorations may help to better vascular dysfunction related to HANAC and hence better understand the mechanisms of end-organ damage.

Two-year outcomes of the APOLLON observational study of intravitreal aflibercept monotherapy in France in patients with diabetic macular edema.

APOLLON (NCT02924311) was a prospective observational study to evaluate the effectiveness of intravitreal aflibercept (IVT-AFL) treatment of diabetic macular edema (DME) over 24 months in routine clinical practice in France. The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) by 12 months, and safety was monitored throughout the study. Of 402 patients enrolled across 61 participating clinics and hospitals in France, 168 patients were followed for at least 24 months and included in the effectiveness analyses (79 treatment-naïve and 89 previously treated). After 24 months of IVT-AFL treatment, the mean (± standard deviation [SD]) change in BCVA from baseline was + 6.5 (± 10.7) letters in treatment-naïve patients (p < 0.001) and + 1.6 (± 17.0) letters in previously treated patients (p = 0.415) from a baseline of 63.8 (± 13.6) and 60.5 (± 16.5) letters. The mean number of IVT-AFL treatments over 24 months was 11.3 (± 4.9) and 11.9 (± 4.7) for treatment-naïve and previously treated patients. This final analysis of the APOLLON study indicated that following 24 months of IVT-AFL treatment in routine clinical practice in France, treatment-naïve patients with DME achieved significant gains in visual acuity and previously treated patients maintained prior visual acuity gains.Trial registration number: NCT02924311.

Extreme Interocular Asymmetry in an Atypical Case of a Hydroxychloroquine-Related Retinopathy.

Background and Objectives: Long-term hydroxychloroquine (HCQ) therapy can lead to retinal toxicity. Typically, it is characterized by a bull's eye maculopathy. More recently, a "pericentral" form of HCQ retinopathy that predominantly affects patients of Asian descent has been described. To our knowledge, this is the first reported case where such an asymmetry between the right and the left eye in the toxicity profile is observed. Case presentation: The patient presented with a 12-year exposure to HCQ at a daily dose of 4.35 mg/kg. She presented an inferior pericentral-only phenotype of HCQ toxicity on the right eye and a perifoveal-only toxicity on the left eye. Modest progression of toxicity was observed on both eyes over the seven years of follow-up, despite drug discontinuation. Conclusions: To our knowledge, this is the first time that two different phenotypes of HCQ-related retinopathy are found in the same patient, challenging our understanding of the pathophysiology of HCQ retinal toxicity.

Association between metabolic disorders and seminal plasma miRNA levels: a pilot study.

BACKGROUND: Excess weight and metabolic disorders have a negative impact on male reproductive functions. The mechanisms involved are numerous and complex and epigenetic mechanisms may also be involved, notably through the small non-coding RNAs. Among them, microRNAs (miRNAs) are of particular interest. This preliminary study aimed to identify the miRNAs differentially enriched in seminal plasma related to metabolic disorders and if some are also associated with spermatic parameters alterations. One hundred and sixty men between 18 to 45 years, partners of infertile couple, were included in this cohort. The miRNAs associated with metabolism were selected from the literature and assayed by quantitative real-time PCR using TaqMan gene expression assays. A subset of those with an interesting profile in seminal plasma were secondarily tested in blood. RESULTS: Among the 11 selected miRNAs, seven were detected in seminal plasma (miR10b, miR19a, miR19b, miR34b, miR34c, miR133b, miRlet7c). A negative correlation was observed between seminal miR19a levels and metabolic syndrome, blood glucose and C-peptide. Seminal miR19b levels were also negatively correlated with metabolic syndrome. Seminal miR34c levels were negatively correlated with body mass index (BMI) and waist circumference. Seminal miR133b levels were positively correlated with BMI, waist circumference and leptin levels. Interestingly, modifications of miRNAs in seminal plasma seem specific since highlighted above correlations were not retrieved in the blood plasma for the miR19a, 19b, 10b, 34c. CONCLUSION: Few metabolic and anthropometric disorders are correlated with the level of specific miRNAs in seminal plasma. Further studies will be required to decipher if other small non-coding RNAs may also be correlated with metabolic and anthropometric disorders and to assess their potential implication in the alteration of reproductive functions in men with obesity or metabolic disorders. CLINICAL STUDY: Metabolic Syndrome and Male Infertility (Metasperme): Trial registration:  NCT01974947 . Registered 18 July 2013.

RéSUMé: CONTEXTE: L'excès de poids et les troubles métaboliques ont un impact négatif sur les fonctions de reproduction masculine. Les mécanismes impliqués sont nombreux et complexes, et des mécanismes épigénétiques peuvent également intervenir, notamment par le biais des petits ARN non codants. Parmi eux, les microRNAs (miRNAs) présentent un intérêt particulier. Cette étude préliminaire visait à identifier les miRNAs différentiellement enrichis dans le plasma séminal en relation avec des troubles métaboliques et si certains étaient également associés à des altérations des paramètres spermatiques. Cent soixante hommes âgés de 18 à 45 ans, partenaires de couple infertile, ont été inclus dans cette cohorte. Les miRNAs associés au métabolisme ont été sélectionnés dans la littérature et analysés par PCR quantitative en temps réel à l'aide de tests d'expression génique TaqMan. Un sous-ensemble de ceux présentant un profil intéressant dans le plasma séminal ont été secondairement testés dans le sang. RéSULTATS: Parmi les 11 miRNAs sélectionnés, sept ont été détectés dans le plasma séminal (miR10b, miR19a, miR19b, miR34b, miR34c, miR133b, miRlet7c). Une corrélation négative a été observée entre les niveaux du miR19a séminal et le syndrome métabolique, la glycémie et le C-peptide. Les niveaux de miR19b séminaux étaient également corrélés négativement avec le syndrome métabolique. Les niveaux de miR34c séminaux étaient négativement corrélés avec l'IMC et le tour de taille. Les niveaux de miR133b séminaux étaient positivement corrélés avec l'IMC, le tour de taille et les niveaux de leptine. Il est intéressant de noter que les modifications des miRNA dans le plasma séminal semblent spécifiques puisque les corrélations mises en évidence ci-dessus n'ont pas été retrouvées dans le plasma sanguin pour les miR19a, 19b, 10b, 34c. CONCLUSION: Quelques désordres métaboliques et anthropométriques ont été observés corrélés avec le niveau de certains miRNAs dans le plasma séminal. Des études complémentaires sont nécessaires pour déterminer si d'autres petits ARN non codants sont corrélés aux troubles métaboliques et anthropométriques et pour évaluer leur implication potentielle dans l'altération des fonctions de reproduction chez les hommes souffrant d'obésité ou de troubles métaboliques.

Walking aid training as a clinical competence in Canadian entry-to-practice professional academic programs.

PURPOSE: Multiple healthcare professionals fit walking aids (WA) and train individuals on their use. The purpose of this investigation was to describe curricula on WA fitting and training in Canadian entry-to-practice professional programs. MATERIALS AND METHODS: An online survey was administered to leads from all accredited programs (n = 199). Seventeen questions asked about the importance of WA education, instructional methods and time dedicated to WA fitting and skills training, and how the pandemic had affected WA curriculum delivery. RESULTS: Responses were received from 97 programs. While most occupational therapy (OT, 8/15), physiatry (PM&R, 5/9), and physical therapy (PT, 12/19) trainees received more than 3 h of instruction on WA fitting, most nursing (29/40) and pharmacy (7/8) programs spent less than 3 h on this topic. Most OT (9/15) and PT (15/19) programs spent more than 3 h on WA skills training whereas most nursing (25/40), pharmacy (4/8), and PM&R (5/9) programs spent less than 3 h on this subject. Across all programs, 52% educated students on adapting activities of daily living for WA while 18% provided education on WA maintenance and repair. Only 19/89 programs consulted a formal WA skills training resource for curriculum development. Seventeen of 55 programs modified their WA curricula due to the pandemic. CONCLUSIONS: There is a wide range in curricular approaches to WA education in Canadian professional programs. This highlights the need for a standardised WA education program to guide curricular development to ultimately improve safe WA use for clients with short- and long-term mobility impairments.IMPLICATIONS FOR REHABILITATIONCurricula on walking aids is extremely variable within and between programs.Navigating terrains, adapting activities of daily living, and maintenance are poorly taught.There is a need for a national standardized curriculum on walking aids.This curriculum should be modular and designed for practitioners, students, and patients.

HAIR DYE-INDUCED RETINOPATHY MIMICKING MEK-INHIBITOR RETINOPATHY.

PURPOSE: To report a new toxic retinopathy related to the use of hair dye. METHODS: Case reports of three patients with follow-up after exposure and until resolution. RESULTS: There were three middle-aged women (32-66 year old) all of whom had bilateral moderate to severe vision loss and normal slit-lamp examination at presentation. Fundus examination showed bilateral multiple serous retinal detachments predominantly located in the posterior pole, with some pigment epithelial hypertrophy in chronic cases. Optical coherence tomography showed similar features as in MEK-inhibitor retinopathy. Electrooculogram performed in one patient showed abnormal Arden ratio. During follow-up, visual acuity improved with regression of the serous retinal detachments. The speed of resolution was proportional to the acuteness of the exposure to aromatic amines. CONCLUSION: Hair dyes containing aromatic amines can be responsible for bilateral toxic retinopathy mimicking MEK-inhibitor retinopathy.

Didanosine-induced Retinopathy: New Insights with Long-term Follow-up.

INTRODUCTION: Didanosine is an adenosine analog, part of the nucleoside reverse-transcriptase inhibitor family. Since the description of didanosine-induced retinopathy in the early 1990s, little is known about the progression of this toxic retinopathy and the putative underlying mitochondrial defect. OBJECTIVES: We report long-term follow-up for cases of didanosine-induced retinopathy and discuss a new hypothesis for pathophysiology based on the alteration of endogenous adenosine on the photoreceptor outer segment turnover and phagocytosis by the retinal pigment epithelium. METHODS: Ophthalmic data from six cases (12 eyes) of didanosine-induced retinopathy from a single institution were retrospectively analyzed. RESULTS: All patients displayed bilateral retinal alterations in the mid-periphery. Despite didanosine discontinuation, patients with advanced areas of patchy chorioretinal atrophy appeared to have a faster progression than those with limited lesions. Full-field electroretinogram revealed generalized rod-cone dysfunction in most cases that remained stable over time. CONCLUSION: We propose new guidelines including early screening and long-term observations.

Adolescents and adults with Fontan circulation: insights from the PREpArE-Fontan registry.

The Patient Registry for Adolescents and Adults with Stable Fontan Circulation aims to describe a contemporary cohort of Fontan patients who could be eligible for a clinical trial investigating macitentan, an endothelin receptor antagonist. This international, non-interventional, multicentre, cross-sectional, observational registry enrolled patients with "stable" Fontan circulation ≥10 years following extra-cardiac conduit or lateral tunnel procedure. Main exclusion criteria were NYHA functional class IV, reoperation of Fontan circulation, or signs of disease worsening. Patient characteristics at enrolment are described; available data were collected during a single registration visit. Of the 266 screened patients, 254 were included in this analysis. At enrolment, median (interquartile range) age was 24 (20;30) years, 37%/63% of patients were from the USA/Europe, 54% were male, 54%/47% had undergone extra-cardiac conduit/lateral tunnel procedures, and 95% were in NYHA functional class I or II. History of arrhythmia was more common in older patients and patients with lateral tunnel; overall prevalence was 19%. Most laboratory values were within the normal range but mean creatinine clearance was abnormally low (87.7 ml/min). Angiotensin-converting enzyme inhibitors were used by 48% of patients and their use was associated with creatinine clearance <90 ml/min (p = 0.007), as was Fontan completion at an older age (p = 0.007). 53.4% of patients had clinical characteristics that could potentially meet an endothelin receptor antagonist trial's eligibility criteria. The PREpArE-Fontan registry describes a cohort of patients who could potentially participate in an endothelin receptor antagonist trial and identified early subtle signs of Fontan failure, even in "stable" patients.

Late Contralateral Recurrence of Unilateral Acute Idiopathic Maculopathy: Adaptive Optics Findings.

PURPOSE: To report a case of late contralateral recurrence of unilateral acute idiopathic maculopathy (UAIM) and its sequelae by using adaptive optics. METHODS: A 46-year-old woman positive for coxsackie virus presented with a typical UAIM, followed 3 years later by a recurrence in the fellow eye. At an early stage, spectral domain-OCT showed a localized loss of the inner segment/outer segment and cone outer segment tips lines, while flood-illumination adaptive optics displayed pigment clumpings and transient small hard exudates, associated with a persistent blurring of the cone mosaic. RESULTS: These findings support the hypothesis of an outer retinal blood-barrier breakdown, inducing a disruption limited to the outer segment of the photoreceptors, followed by a progressive though incomplete normalization of the cone mosaic characterized by a persistent misalignment of outer segment tips. CONCLUSION: This would explain the acute clinical presentation of UAIM, followed by a spontaneous, partial, recovery, with a relative scotoma remaining over time.

Proof of concept and development of a couple-based machine learning model to stratify infertile patients with idiopathic infertility.

We aimed to develop and evaluate a machine learning model that can stratify infertile/fertile couples on the basis of their bioclinical signature helping the management of couples with unexplained infertility. Fertile and infertile couples were recruited in the ALIFERT cross-sectional case-control multicentric study between September 2009 and December 2013 (NCT01093378). The study group consisted of 97 infertile couples presenting a primary idiopathic infertility (> 12 months) from 4 French infertility centers compared with 100 fertile couples (with a spontaneously conceived child (< 2 years of age) and with time to pregnancy < 12 months) recruited from the healthy population of the areas around the infertility centers. The study group is comprised of 2 independent sets: a development set (n = 136 from 3 centers) serving to train the model and a test set (n = 61 from 1 center) used to provide an unbiased validation of the model. Our results have shown that: (i) a couple-modeling approach was more discriminant than models in which men's and women's parameters are considered separately; (ii) the most discriminating variables were anthropometric, or related to the metabolic and oxidative status; (iii) a refined model capable to stratify fertile vs. infertile couples with accuracy 73.8% was proposed after the variables selection (from 80 to 13). These influential factors (anthropometric, antioxidative, and metabolic signatures) are all modifiable by the couple lifestyle. The model proposed takes place in the management of couples with idiopathic infertility, for whom the decision-making tools are scarce. Prospective interventional studies are now needed to validate the model clinical use.Trial registration: NCT01093378 ALIFERT https://clinicaltrials.gov/ct2/show/NCT01093378?term=ALIFERT&rank=1 . Registered: March 25, 2010.

Did the COVID-19 Pandemic Increase the Incidence of Acute Macular Neuroretinopathy?

BACKGROUND: Acute macular neuroretinopathy (AMN) is an increasingly diagnosed disorder associated with several diseases. The aim of this study was to report the incidence of AMN cases diagnosed during the 2020 coronavirus disease 2019 (COVID-19) pandemic year in a French hospital, and to describe their different forms. METHODS: All patients diagnosed between 2019 and 2020, in Paris Rothschild Foundation Hospital, with AMN, paracentral acute middle maculopathy (PAMM) and multiple evanescent white dot syndrome (MEWDS) were retrospectively collected using the software Ophtalmoquery® (Corilus, V1.86.0018, 9050 Gand, Belgium). Systemic and ophthalmological data from AMN patients were analyzed. RESULTS: Eleven patients were diagnosed with AMN in 2020 vs. only one patient reported in 2019. The incidence of AMN significantly increased from 0.66/100,000 visits in 2019 to 8.97/100,000 visits in 2020 (p = 0.001), whereas the incidence of PAMM and MEWDS remained unchanged. Four (36%) of these AMN patients were tested for COVID-19 and received positive polymerase chain reaction (PCR) tests. CONCLUSIONS: The incidence of AMN cases increased significantly in our institution in 2020, which was the year of the COVID-19 pandemic. All AMN-tested patients received a positive COVID PCR test, suggesting a possible causative link. According to the different clinical presentations, AMN may reflect different severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pathogenic mechanisms.

Is There an Association of Being Breastfed as an Infant and Fertility Status as an Adult?

Background: Breastfeeding has many short-term and long-term health benefits for infants. Short-term benefits include protection against childhood infections and mortality in low-income countries. The adult long-term effects usually emphasized are a reduction of excess weight and type 2 diabetes. However, there is a lack of available data on the impact of having been breastfed on adult fertility. Indeed, infertility probably has a multifactorial origin, including an environmental origin. The aim of this study was to investigate whether having been breastfed could be associated with unexplained infertility. Materials and Methods: This research is an ancillary study of the case-control study ALIFERT, for which both fertile and infertile couples were recruited. Breastfeeding statuses, collected from childhood health records, were compared among fertile and infertile individuals. Anthropometrics parameters were also used for analysis. Results: About 65.6% of infertile women and 63.3% of fertile women were breastfed, and 69% of infertile men and 67.4% of fertile men were breastfed. There was no statistically significant difference between fertile and infertile groups. Nevertheless, infertile women who were not breastfed had a significantly higher body mass index than those who were breastfed (25.8 kg/m2 vs. 23.2 kg/m2). Conclusion: In our study, we did not observe any association between having been breastfed and fertility in adulthood. However, we observed that, in infertile women, having not been breastfed may influence weight in adulthood. Trial registration: NCT01093378 ALIFERT. Registered: March 25, 2010.

Adding Haptic Feedback to Virtual Environments With a Cable-Driven Robot Improves Upper Limb Spatio-Temporal Parameters During a Manual Handling Task.

Physical interactions within virtual environments are often limited to visual information within a restricted workspace. A new system exploiting a cable-driven parallel robot to combine visual and haptic information related to environmental physical constraints (e.g. shelving, object weight) was developed. The aim of this study was to evaluate the impact on user movement patterns of adding haptic feedback in a virtual environment with this robot. Twelve healthy participants executed a manual handling task under three conditions: 1) in a virtual environment with haptic feedback; 2) in a virtual environment without haptic feedback; 3) in a real physical environment. Temporal parameters (movement time, peak velocity, movement smoothness, time to maximum flexion, time to peak wrist velocity) and spatial parameters of movement (maximum trunk flexion, range of motion of the trunk, length of the trajectory, index of curvature and maximum clearance from the shelf) were analysed during the reaching, lowering and lifting phases. Our results suggest that adding haptic feedback improves spatial parameters of movement to better respect the environmental constraints. However, the visual information presented in the virtual environment through the head mounted display appears to have an impact on temporal parameters of movement leading to greater movement time. Taken together, our results suggest that a cable-driven robot can be a promising device to provide a more ecological context during complex tasks in virtual reality.

Impact of intravitreal aflibercept dosing regimens in treatment-naïve patients with neovascular age-related macular degeneration in routine clinical practice in France: results from the RAINBOW study.

OBJECTIVE: To evaluate 12-month outcomes in treatment-naïve patients with neovascular (wet) age-related macular degeneration (AMD) stratified by intravitreal aflibercept (IVT-AFL) regimen. METHODS AND ANALYSIS: Patients included in the 12-month interim analysis of Real life of intravitreal Aflibercept In FraNce: oBservatiOnal Study in Wet AMD (RAINBOW), a 4-year, ongoing observational study conducted in France, were stratified by IVT-AFL dosing regimen. Safety (n=593) and effectiveness (n=428) data were analysed. Regimens included a regular cohort (three initial monthly IVT-AFL injections and ≥6 injections) and irregular cohorts (<6 injections) with and without three initial monthly injections. The main outcome measure was mean gain in best-corrected visual acuity (BCVA) at 12 months. RESULTS: Mean number of IVT-AFL injections was 6.0 (all patients, n=513), 7.2 (regular cohort, n=102), 6.1 (irregular cohort with three initial monthly injections, n=266) and 5.2 (irregular cohort without three initial monthly injections, n=60). Overall mean gain in BCVA at 12 months was 5 letters; +7.1 letters (regular cohort) and +5.6 letters (irregular cohort with three initial monthly injections), both p<0.001 versus baseline, and -1.1 letters (irregular cohort without three initial monthly injections), p=0.669. Improvements in BCVA were also significantly greater in the regular cohort (p<0.001) and irregular cohort with three initial monthly injections (p=0.003) compared with the irregular cohort without three initial monthly injections. Ocular and non-ocular adverse events were reported in 14.7% and 17.4% of all patients, respectively. CONCLUSION: Treatment-naïve patients with neovascular AMD receiving three initial monthly injections followed by regular or irregular injections over 12 months experienced better visual acuity outcomes than those receiving irregular treatment without three initial monthly injections. TRIAL REGISTRATION NUMBER: NCT02279537.

Impact of intravitreal aflibercept dosing regimens in treatment-naïve patients with neovascular age-related macular degeneration: 2-year results of RAINBOW.

BACKGROUND: To review treatment outcomes from real-world data of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) injection. METHODS: RAINBOW (ClinicalTrials.gov, NCT02279537) is an ongoing, observational, 4-year study to monitor the effectiveness and safety of IVT-AFL in patients with nAMD in clinical practice in France. Treatment-naïve patients diagnosed with nAMD who had been prescribed IVT-AFL by their treating physician were eligible. The regimens of interest were regular treatment interval cohort (patients who received three initial monthly IVT-AFL injections followed by regular injections every 2 months) and two irregular treatment interval cohorts (with and without three initial monthly injections). Here we describe results at 24 months in patients according to IVT-AFL treatment regimen. RESULTS: The mean change in best-corrected visual acuity (BCVA) with IVT-AFL from baseline to 24 months was + 3.0 letters in the overall population (P < 0.05 vs baseline). The mean change was positive for the regular and irregular treatment interval cohorts with initial doses (+ 4.9 and + 4.0 letters, respectively; P < 0.05 vs baseline) and negative for the irregular treatment interval cohort without initial doses (- 2.5 letters; P = 0.365 vs baseline) at 24 months. The mean overall number of IVT-AFL injections over 12 and 24 months was 6.0 and 8.8, respectively. The most common ocular adverse events were lack of efficacy (6.3%), vitreous floaters (2.7%), and increased lacrimation (1.7%). CONCLUSIONS: In the real-world RAINBOW study, visual outcomes observed at 24 months were consistent with results from the primary endpoint at 12 months. In this study, treatment-naïve patients who received three initial IVT-AFL doses and regular IVT-AFL treatment over the first 24 months experienced better visual outcomes than patients who received no initial doses and an irregular treatment regimen. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT02279537). Registered 29 October 2014.

Ancestral persistence of vestibulospinal reflexes in axial muscles in humans.

Most studies addressing the role of vestibulospinal reflexes in balance maintenance have mainly focused on responses in the lower limbs, while limited attention has been paid to the output in trunk and back muscles. To address this issue, we tested whether electromyographic (EMG) responses to galvanic vestibular stimulations (GVS) were modulated similarly in back and leg muscles, in situations where the leg muscle responses to GVS are known to be attenuated. Body sway and surface EMG signals were recorded in the paraspinal and limb muscles of humans (n = 19) under three complementary conditions. During treadmill locomotion, EMG responses in the lower limbs were observed only during stance, whereas responses in trunk muscles were observed during all phases of the locomotor cycle. During upright standing, a slight head contact abolished the responses in the lower limbs, while the responses remained present in back muscles. Similarly, during parabolic flight-induced microgravity, EMG responses in lower limb muscles were suppressed but remained in axial muscles despite the abolished gravitational otolithic drive. Our results suggest a differentiated control of axial and appendicular muscles when a perturbation is detected by vestibular inputs. The persistence and low modulation of axial muscle responses suggests that a hard-wired reflex is functionally efficient to maintain posture. By contrast, the ankle responses to GVS occur only in balance tasks when proprioceptive feedback is congruent. This study using GVS in microgravity is the first to present an approach delineating feedforward vestibular control in unconstrained environment.NEW & NOTEWORTHY This study addresses the extent of conservation of trunk muscle control in humans. Results show that galvanic vestibular stimulation-evoked vestibular responses in trunk muscles remain strong in conditions where leg muscle responses are downmodulated (walking, standing, microgravity). This suggests a phylogenetically conserved blueprint of sensorimotor organization, with strongly hardwired vestibulospinal inputs to axial motoneurons and a higher degree of flexibility in the later emerging limb control system.