Optimization strategies to obtain smooth gait transitions through biologically plausible central pattern generators.

Central pattern generators are small networks that contribute to generating animal locomotion. The models used to study gait generation and gait transition mechanisms often require biologically accurate neuron and synapse models, with high dimensionality and complex dynamics. Tuning the parameters of these models to elicit network dynamics compatible with gait features is not a trivial task, due to the impossibility of inferring a priori the effects of each parameter on the nonlinear system's emergent dynamics. In this paper we explore the use of global optimization strategies for parameter optimization in multigait central pattern generator (CPG) models with complex cell dynamics and minimal topology. We first consider an existing quadruped CPG model as a test bed for the objective function formulation, then proceed to optimize the parameters of a newly proposed multigait, interlimb hexapod CPG model. We successfully obtain hexapod gaits and prompt gait transitions by varying only control currents, while all CPG parameters, once optimized, are kept fixed. This mechanism of gait transitions is compatible with short-term synaptic plasticity.

[Lipofilling in the management of breast cancer: An update based on a literature review and national and international guidelines]. / Le lipomodelage du sein dans un contexte cancérologique : mise au point à partir d'une revue de littérature actualisée et des référentiels nationaux et internationaux.

BACKGROUND: Lipomodelling (LM) is an increasingly used technique to reconstruct or correct an aesthetic defect linked to a loss of substance. In France, the Haute Autorité de santé (HAS) published recommendations in 2015 and 2020 concerning the conditions of use of LM on the treated and contralateral breast. These appear to be inconsistently followed. METHODS: Twelve members of the Senology Commission of the Collège national des gynécologues-obstétriciens français (French College of Gynecologists and Obstetricians) reviewed the carcinological safety of LM and the clinical and radiological follow-up of patients after breast cancer surgery, based on French and international recommendations and a review of the literature. The bibliographic search was conducted via Medline from 2015 to 2022, selecting articles in French and English and applying PRISMA guidelines. RESULTS: A total of 14 studies on the oncological safety of LM, 5 studies on follow-up and 7 guidelines were retained. The 14 studies (6 retrospective, 2 prospective and 6 meta-analyses) had heterogeneous inclusion criteria and variable follow-up, ranging from 38 to 120 months. Most have shown no increased risk of locoregional or distant recurrence after LM. A retrospective case-control study (464 LMs and 3100 controls) showed, in patients who had no recurrence at 80 months, a subsequent reduction in recurrence-free survival after LM in cases of luminal A cancer, highlighting the number of lost to follow-up (more than 2/3 of luminal A cancers). About follow-up after LM, the 5 series showed the high frequency after LM of clinical mass and radiological images (in » of cases), most often corresponding to cytosteatonecrosis. Most of the guidelines highlighted the uncertainties concerning oncological safety of LM, due to the lack of prospective data and long-term follow-up. DISCUSSION AND PERSPECTIVES: The members of the Senology Commission agree with the conclusions of the HAS working group, in particular by advising against LM "without cautionary periods", excessively, or in cases of high risk of relapse, and recommend clear, detailed information to patients before undergoing LM, and the need for postoperative follow-up. The creation of a national registry could address most questions regarding both the oncological safety of this procedure and the modalities of patient follow-up.

[Breast cancer and organ transplantation: Systematic review and meta-analysis]. / Cancer du sein et greffe d'organes : revue systématique et méta-analyse.

OBJECTIVES: Our main objective was to investigate donor-transmitted epithelial cancers of all origins in comparison with breast cancers, with analysis of the carcinological outcome of recipients. Our secondary objective was to define medical check-up to be performed before any organ procurement from a donor with a history of breast cancer. METHODOLOGY: We performed a systematic review of the literature up to June 1st 2022 by including all original articles (including clinical cases) reporting cases of epithelial cancer transmitted from donor to recipient, followed by a meta-analysis of epidemiological and survival data. RESULTS: In total, we included 52 articles (31 clinical cases and 21 cohort studies), representing 91,388 donors, 236,142 recipients, and 2591 cases of transmitted cancer. The risk of transmitted cancer was significantly higher with a history of breast cancer compared with a history of other cancer (RR=9.48 P=0.0025). In clinical cases, the pre-donation check-up was specified in only 33.3% of publications. The time between transplantation and cancer occurrence was longer in cases of breast cancer transmission compared to other epithelial cancers: 1435.8 days versus 297.6 (P<0.001). CONCLUSION: Organ donation from a person previously treated for breast cancer or having a risk of occult breast cancer is possible in some situations but requires an adapted pre-donation assessment, the respect of good practice guidelines and an expert opinion in complex situations.

3D-printed simulator for nasopharyngeal swab collection for COVID-19.

OBJECTIVES: Diagnosis of COVID-19 is essential to prevent the spread of SARS-CoV-2. Nasopharyngeal swabs (NPS) remain the gold standard in screening, although associated with false negative results (up to 30%). We developed a 3D simulator of the nasal and pharyngeal cavities for the learning and improvement of NPS collection. PATIENTS AND METHODS: Simulator training sessions were carried out in 11 centers in France. A questionnaire assessing the simulator was administered at the end of the sessions. The study population included both healthcare workers (HCW) and volunteers from the general population. RESULTS: Out of 589 participants, overall satisfaction was scored 9.0 [8.9-9.1] on a scale of 0 to 10 with excellent results in the 16 evaluation items of each category (HCWs and general population, NPS novices and experienced). The simulator was considered very realistic (95%), easy to use (97%), useful to understand the anatomy (89%) and NPS sampling technique (93%). This educational tool was considered essential (93%). Participants felt their future NPS would be more reliable (72%), less painful (70%), easier to perform (88%) and that they would be carried out more serenely (90%). The mean number of NPS conducted on the simulator to feel at ease was two; technical fluency with the simulator can thus be acquired quickly. CONCLUSION: Our simulator, whose 3D printing can be reproduced freely using a permanent open access link, is an essential educational tool to standardize the learning and improvement of NPS collection. It should enhance virus detection and thus contribute to better pandemic control.

[Techniques and complications of non-genetic risk reducing mastectomies: Guidelines of the National College of French Gynecologists and Obstetricians (CNGOF)]. / Modalités et morbidité des mastectomies de réduction de risque en dehors du risque avéré de prédisposition héréditaire : recommandations du Collège national des gynécologues et obstétriciens français (CNGOF).

OBJECTIVE: Based on an updated review of the international literature covering the different surgical techniques and complications of risk reducing mastectomies (RRM) in non-genetic context, the Commission of Senology (CS) of the College National des Gynécologues Obstétriciens Français (CNGOF) aimed to establish recommendations on the techniques to be chosen and their implementation. DESIGN: The CNGOF CS, composed of 24 experts, developed these recommendations. A policy of declaration and monitoring of links of interest was applied throughout the process of making the recommendations. Similarly, the development of these recommendations did not benefit from any funding from a company marketing a health product. The CS adhered to and followed the AGREE II (Advancing guideline development, reporting and evaluation in healthcare) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method to assess the quality of the evidence on which the recommendations were based. The potential drawbacks of making recommendations in the presence of poor quality or insufficient evidence were highlighted. METHODS: The CS considered 6 questions in 4 thematic areas, focusing on oncologic safety, risk of complications, aesthetic satisfaction and psychological impact, and preoperative modalities. RESULTS: The application of the GRADE method resulted in 7 recommendations, 6 with a high level of evidence (GRADE 1±) and 1 with a low level of evidence (GRADE 2±). CONCLUSION: There was significant agreement among the CS members on recommendations for preferred surgical techniques and practical implementation.

[Connected bras for breast cancer detection in 2021: Analysis and perspectives]. / Détection du cancer du sein à l'aide de soutiens-gorge connectés en 2021 : analyses et perspectives.

OBJECTIVES: Breast cancer is the leading cancer in women worldwide with about 2 million new cases and 685,000 deaths each year. Mammography is the most widely used screening and diagnostic method. Currently, digital technologies advances facilitate the development of connected and portable devices. To overcome some of the disadvantages of mammography (breast compression, difficulty in analyzing dense breasts, radiation, limited accessibility in some countries, etc.), portable devices, conventionally known as connected bras (CB), have been created to offer an alternative method to mammography. The objective of our review was to list all the published CBs in order to know their main characteristics, their potential indications and their possible limitations. METHOD: A bibliographical search in the PUBMED database selecting only articles written in French or English, between 2011 and 2020, found 7 CBs under development. RESULTS: These CBs use thermal, ultrasonic and impedance sensors. Their advantages are an absence of irradiation, an absence of breast compression and a flexibility of use (outside an X-ray cabinet). Mammary gland analysis times vary, depending on the device, between 30min and 24h. They are all connected to data transmission systems and models that analyze the results. DISCUSSION AND CONCLUSION: These CBs are mostly still undergoing clinical validation (only [iTBra] has been evaluated in a clinical trial) and require evaluation steps that will eventually allow their future use for breast cancer detection in high-risk women, particularly in women with dense breasts and in women between screening waves.

Towards more biologically plausible central-pattern-generator models.

Central pattern generators (CPGs) are relatively small neural networks that play a fundamental role in the control of animal locomotion. In this paper we define a method for the systematic design of CPG models able to exhibit biologically plausible gait transitions by implementing short-term synaptic plasticity mechanisms. As a case study, we focus on a simple CPG for quadruped locomotion. By applying the proposed method, three of four standard quadruped gaits were correctly reproduced by the obtained CPG model, not only in terms of the alternating sequence of the limbs but also in terms of frequency, duty cycle, and phase lags.

Generalized half-center oscillators with short-term synaptic plasticity.

How can we develop simple yet realistic models of the small neural circuits known as central pattern generators (CPGs), which contribute to generate complex multiphase locomotion in living animals? In this paper we introduce a new model (with design criteria) of a generalized half-center oscillator, (pools of) neurons reciprocally coupled by fast/slow inhibitory and excitatory synapses, to produce either alternating bursting or other rhythmic patterns, characterized by different phase lags, depending on the sensory or other external input. We also show how to calibrate its parameters, based on both physiological and functional criteria and on bifurcation analysis. This model accounts for short-term neuromodulation in a biophysically plausible way and is a building block to develop more realistic and functionally accurate CPG models. Examples and counterexamples are used to point out the generality and effectiveness of our design approach.

Breast cancer in elderly women and altered clinico-pathological characteristics: a systematic review.

PURPOSE: Breast cancer is the most common malignancy in women in terms of incidence and mortality. Age is undoubtedly the biggest breast cancer risk factor. In this study we examined clinical, histological, and biological characteristics and mortality of breast cancer in elderly women along with their changes with advancing age. METHODS: We reviewed 63 original articles published between 2006 and 2016 concerning women over 70 years with breast cancer. RESULTS: Compared to patients 70-79 years, patients aged 80 and over had larger tumor size with fewer T1 (42.9% vs 57.7%, p < 0.01) and more T2 lesions (43.5% vs 33.0%, p < 0.01). Lymph nodes and distant metastases were more frequent, with more N + (49.5% vs 44.0%, p < 0.01) and more M1 (8.0% vs 5.9%, p < 0.01). Infiltrating mucinous carcinomas were more frequent (4.3% vs 3.7%, p < 0.01). Tumors had lower grades, with more grade 1 (23.2% vs 19.8%, p = 0.01) and fewer grade 3 (21.5% vs 25.5%, p < 0.01), and were more hormone-sensitive: PR was more often expressed (72.6% vs 67.3%, p < 0.01). Lympho-vascular invasion was less frequent in the 80 years and over (22.9% vs 29.7%, p = 0.01). Breast cancer-specific mortality was higher both at 5 years (25.8% vs 17.2%, p < 0.01) and 10 years (32.7% vs 26.6%, p < 0.01). CONCLUSION: Clinico-pathological characteristics, increased incidence, and mortality associated with aging can be explained on one hand by biological changes of the breast such as increased estrogen sensitivity, epithelial cell alterations, immune senescence, and tumor microenvironment modifications. However, sociologic factors such as increased life expectancy, under-treatment, late diagnosis, and insufficient individual screening, are also involved.

A new method for ultrasonographic measurement of kidney size in healthy dogs.

INTRODUCTION: The authors propose a simple method for assessment of canine kidney size derived from the radiological technique described by Finco et al in 1971. MATERIALS AND METHODS: In 26 healthy dogs ultrasonography was used to measure the length, height, and thickness of each kidney. These measurements were correlated with the lengths of the fifth and sixth lumbar vertebrae (L5 and L6), also measured by ultrasound. The resulting values were compared with the linear correlation method and the ratios defined using descriptive statistics. RESULTS: No significant differences were observed between the dimensions of the right and left kidneys. The length of both kidneys displayed significant correlation with both the length of L5 and that of L6. In both cases, the renal:vertebral length ratios ranged from 1.3 to 2.7. DISCUSSION: The ratio of kidney length to the length of L5 or L6 can be considered a useful parameter for assessing the size of the kidneys in healthy dogs. The normal range we identified in this study (from 1.3 to 2.7) is sufficiently narrow to allow sonographic detection of even limited changes in renal length.

A combined approach to investigate the toxicity of an industrial landfill's leachate: chemical analyses, risk assessment and in vitro assays.

Solid wastes constitute an important and emerging problem. Landfills are still one of the most common ways to manage waste disposal. The risk assessment of pollutants from landfills is becoming a major environmental issue in Europe, due to the large number of sites and to the importance of groundwater protection. Furthermore, there is lack of knowledge for the environmental, ecotoxicological and toxicological characteristics of most contaminants contained into landfill leacheates. Understanding leachate composition and creating an integrated strategy for risk assessment are currently needed to correctly face the landfill issues and to make projections on the long-term impacts of a landfill, with particular attention to the estimation of possible adverse effects on human health and ecosystem. In the present study, we propose an integrated strategy to evaluate the toxicity of the leachate using chemical analyses, risk assessment guidelines and in vitro assays using the hepatoma HepG2 cells as a model. The approach was applied on a real case study: an industrial waste landfill in northern Italy for which data on the presence of leachate contaminants are available from the last 11 years. Results from our ecological risk models suggest important toxic effects on freshwater fish and small rodents, mainly due to ammonia and inorganic constituents. Our results from in vitro data show an inhibition of cell proliferation by leachate at low doses and cytotoxic effect at high doses after 48 h of exposure.

Assessing the environmental risks associated with contaminated sites: Definition of an Ecotoxicological Classification index for landfill areas (ECRIS).

Assessing ecological risk in quantitative terms is a site-specific complex procedure requiring evaluation of all possible pathways taken by the chemicals from the contamination source to the targets to be protected. Unfortunately, too many cases lack of physico-chemical and ecotoxicological data makes impossible to quantify the ecological risk. We present the Ecotoxicological Classification Risk Index for Soil (ECRIS), a new classification system specific for soil risk assessment, which gives a comparative indication of the risk linked to environmental contamination by any chemical. The tool we propose is based on the integration of a data set characterizing the ecotoxicological and exposure profile of chemicals. ECRIS is a simple approach specifically set up for the landfill scenario. This index draws on the huge amount of data from our many years of leachate analysis. ECRIS is useful for a first screening of probably contaminated soil. A case study based on some Italian landfills is proposed.

[Two centers with a native fistula prevalence higher than 90%: organization and activity]. / Due centri accomunati da una prevalenza di fistole con vasi nativi maggiore del 90%: attività e modelli organizzativi a confronto.

Vascular access (AV) dysfunction is a major cause of morbidity and hospitalisation in hemodialysis population. Despite of guidelines statements which consider native arteriovenous fistula (nAVF) the gold standard, epidemiological studies still show a decline in their prevalence with an increase of central venous catheters (CVC). In this study we compared the activity of two Dialysis Units both characterized by a high prevalence (> 90%) of nAVF, in order to highlight the possible reasons. No collaboration existed between the two centres until the decision to design this work. The "policy" on creation and management of vascular access and organizational models of the two centres were assessed, in particular focusing on surgeons, presence of dedicated nephrologists, preoperatory ultrasound evaluation, follow-up and diagnosis of complications, resort to interventional radiology, complications management, in particular the timing of intervention after AVF thrombosis. Of the two dialysis populations were analysed: age, time on dialysis, coexistence of diabetes and the prevalence of various types of vascular access to 31 December 2007. It was evaluated the AV incidence in the last 4 years. The statistical analysis was performed by T student and Chi square tests. There were no substantial differences in the organizational models of the two centres, which had both a routine ECD use in preoperatory mapping and in monitoring of complications; in case of thrombosis both centres performed surgery within 12-24 hours; in case of stenosis both centres performed the correction, surgical or by angioplasty, within 15 days from the diagnosis. Another common element was the presence of a multidisciplinary team with a interventionist nephrologist, a vascular surgeon and a vascular interventional radiologist, where nephrologist has the coordination role. The data analysis showed a prevalence of nAVF in the two centres of 92.5% and 96.1%, Pescara and Lecce respectively, with a prevalence of forearm nAVF of more than 80% and 90% respectively. The analysis of incident interventions showed high percentage of forearm AVF in case of revisions for complications (stenosis, thrombosis), and a little recourse to proximal AVF and graft.

Brain magnetic resonance imaging in Wolf-Hirschhorn syndrome.

Wolf-Hirschhorn syndrome (WHS) is a rare genetic disorder, which is caused by partial deletion of the short arm of one chromosome 4. Brain magnetic resonance (MR) imaging findings are lacking. We report on brain findings in 10 children with WHS. We evaluated the MR imaging films of 10 subjects affected by WHS, which had been confirmed by genetic study. The age range at MR imaging was between 1 month and 9 years. In 9/10 cases enlargement of the third lateral ventricles was present. In 9/10 cases a global reduction of cerebral hemispheres white matter was present. In 10/10 cases diffuse thinning of the corpus callosum was visible; it was severe in 7/10 cases. In 5/10 cases small foci of T (2) hyper intense signal were visible within the subcortical white matter. In three of the six cases studied within the first year of life frontal periventricular cysts were present. In three of the four cases studied after the first year of life a squared shape of the frontal horns of the lateral ventricles was visible. The MR imaging findings reported in WHS cannot be considered pathognomonic of the syndrome, however, they may suggest WHS.

Prevalence of anti-cardiolipin, anti-beta2 glycoprotein I, and anti-prothrombin antibodies in young patients with epilepsy.

PURPOSE: To measure anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and anti-prothrombin (aPT) antibodies in young patients with epilepsy, and to correlate their presence with demographic data, clinical diagnoses, laboratory and neuroradiologic findings, and antiepileptic drugs (AEDs). METHODS: Sera from one hundred forty-two consecutive patients with epilepsy with a median age of 10 years were tested for aCL and anti-beta2GPI autoantibodies by solid-phase assays. aPT antibodies also were assayed in sera from 90 patients. Positive results were confirmed after a minimum of 6 weeks. Antinuclear antibodies (ANAs) and antibodies against extractable nuclear antigens (ENAs) also were tested. RESULTS: An overall positivity of 41 (28.8%) of 142 sera was found. Fifteen patients were positive for aCL, 25 for anti-beta2GPI, and 18 for aPT antibodies. Several patients (12%) displayed more than one specificity in their serum. Only one of these patients had a concurrent positivity for ANAs and ENAs. A predominance of younger patients was found in the antibody-positive group. All types of epilepsy were represented in the positive group. No relation between antibody positivity and AEDs was found. Diffuse ischemic lesions at computed tomography (CT)/magnetic resonance imaging (MRI) scans were present in higher percentages in patients who were antibody positive. No positive patient had a history of previous thrombosis or other features related to systemic lupus erythematosus (SLE), and no patient was born of a mother with SLE. CONCLUSIONS: Our study suggests a relation between epilepsy and aPL in young patients. A pathogenetic role for these autoantibodies cannot be excluded, and their determination might prove useful even from a therapeutic point of view.