Pelvic floor muscle rehabilitation for genitourinary syndrome of menopause: why, how and when?

Genitourinary syndrome of menopause (GSM) is caused by chronic deprivation of estrogen and other sex steroids during the postmenopausal period, which leads to changes in the vulvovaginal tissues. These changes cause bothersome symptoms, such as vaginal dryness, pruritus, dyspareunia, increased daytime urinary frequency, urgency and urinary incontinence, which have considerable negative effects on women's quality of life and sexual function. Recent studies have investigated a novel treatment approach for GSM. Pelvic floor muscle (PFM) rehabilitation, a low-cost conservative management with no side-effects, has been studied alone or in combination with other treatment modalities to reduce the signs and symptoms of GSM. The aim of this article is to discuss why PFM rehabilitation could be useful for women with GSM, how it may help improve signs and symptoms of GSM and when this treatment should be recommended.

CFTR pharmacological modulators: A great advance in cystic fibrosis management.

Cystic fibrosis is a severe monogenic disease that affects around 7400 patients in France. More than 2100 mutations in the cystic fibrosis conductance transmembrane regulator (CFTR), the gene encoding for an epithelial ion channel that normally transports chloride and bicarbonate, lead to mucus dehydration and impaired bronchial clearance. Systematic neonatal screening in France since 2002 has enabled early diagnosis of cystic fibrosis. Although highly demanding, supportive treatments including daily chest physiotherapy, inhaled aerosol therapy, frequent antibiotic courses, nutritional and pancreatic extracts have improved the prognosis. Median age at death is now beyond 30 years. Ivacaftor was the first CFTR modulator found to both reduce sweat chloride concentration and improve pulmonary function in the rare CFTR gating mutations. Combinations of modulators such as lumacaftor + ivacaftor or tezacaftor + ivacaftor were found to improve pulmonary function both in patients homozygous for the F508del mutation characterized by the lack of CFTR protein and those heterozygous for F508del with minimal CFTR activity. The triple combination of ivacaftor + tezacaftor + elexacaftor was recently shown to significantly improve pulmonary function and quality of life, to normalize sweat chloride concentration, and to reduce the need for antibiotic therapy in patients with at least one F508del mutation (83% in France). These impressive data, however, need to be confirmed in the long term. Nevertheless, it is encouraging to hear treated patients testify about their markedly improved quality of life and to observe that the number of lung transplants for cystic fibrosis decreased dramatically in France after 2020, despite the COVID pandemic, with no increase in deaths without lung transplant.

Radioactivity concentration measurements in fish and shellfish samples from the west coast of Canada after the Fukushima nuclear accident (2011-2018).

Radioactive contamination of the Pacific Ocean following the Fukushima nuclear accident has raised public concern about seafood safety, particularly in coastal Indigenous communities. To address this, Health Canada and partners have collected and analyzed a total of 621 samples of commonly consumed salmon, ground fish, and shellfish from the Canadian west coast from 2011 to 2018. While the vast majority of the 137Cs and 134Cs levels were below the Minimum Detectable Concentration (MDC, typically 0.7-1.0 Bq kg-1 fw for a 6 h counting), further examination of 19 fish samples revealed 137Cs concentrations of 0.17-0.53 Bq kg-1 fw with an average value and uncertainty (k = 1) of 0.29 ± 0.02 Bq kg-1 fw. Of these, only two samples were found to have trace levels of 134Cs likely derived from the Fukushima accident. The global fallout contribution from atmospheric nuclear weapons testing to the observed 137Cs in these two samples was determined to be 0.26 ± 0.08 Bq kg-1 fw (49 ± 14%) and 0.12 ± 0.02 Bq kg-1 fw (24 ± 4%) for collection years 2015 and 2016, respectively. The annual average level of 137Cs in fish and shellfish was also determined by spectral summation for collection years 2014-2018. In fish, 137Cs levels determined through spectral summation were relatively constant (0.18-0.25 Bq kg-1 fw) with an average value and uncertainty of 0.21 ± 0.02 Bq kg-1 fw. By contrast, 38 shellfish samples (bivalves) were measured and revealed no radiocesium or other anomalies in either tissue or shell. In all, measurements over eight years showed that the radioactivity in fish and shellfish was dominated by natural radionuclides and that the level of anthropogenic radionuclides, as indicated by the radioactive cesium content, remained small. An upper bound for ingested dose from 137Cs was determined to be approximately 0.26 µSv per year, far below the worldwide average annual effective dose of 2400 µSv from exposure to natural background radiation. We can therefore conclude that fish, such as salmon, ground fish, and shellfish from the Canadian west coast are of no radiological health concern despite the Fukushima Dai-ichi nuclear accident of 2011.

Gene Therapy: A Possible Alternative to CFTR Modulators?

Cystic fibrosis (CF) is a rare genetic disease that affects several organs, but lung disease is the major cause of morbidity and mortality. The gene responsible for CF, the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, has been discovered in 1989. Since then, gene therapy i.e., defective gene replacement by a functional one, remained the ultimate goal but unfortunately, it has not yet been achieved. However, patients care and symptomatic treatments considerably increased CF patients' life expectancy ranging from 5 years old in the 1960s to 40 today. In the last decade, research works on CFTR protein structure and activity led to the development of new drugs which, by readdressing CFTR to the plasma membrane (correctors) or by enhancing its transport activity (potentiators), allow, alone or in combination, an improvement of CF patients' lung function and quality of life. While expected, it is not yet known whether taking these drugs from an early age and for years will improve the quality of life of CF patients in the long term and further increase their life expectancy. Besides, these molecules are not available (specific variants of CFTR) or accessible (national health policies) for all patients and there is still no curative treatment. Another alternative that could benefit from new technologies, such as gene therapy, is therefore still attractive, although it is not yet offered to patients. Faced with the development of new CFTR correctors and potentiators, the question arises as to whether there is still a place for gene therapy and this is discussed in this perspective.

A stable, unified model for resonant Faraday cages.

We study some effective transmission conditions able to reproduce the effect of a periodic array of Dirichlet wires on wave propagation, in particular when the array delimits an acoustic Faraday cage able to resonate. In the study of Hewett & Hewitt (2016 Proc. R. Soc. A 472, 20160062 (doi:10.1098/rspa.2016.0062)) different transmission conditions emerge from the asymptotic analysis whose validity depends on the frequency, specifically the distance to a resonance frequency of the cage. In practice, dealing with such conditions is difficult, especially if the problem is set in the time domain. In the present study, we demonstrate the validity of a simpler unified model derived in Marigo & Maurel (2016 Proc. R. Soc. A 472, 20160068 (doi:10.1098/rspa.2016.0068)), where unified means valid whatever the distance to the resonance frequencies. The effectiveness of the model is discussed in the harmonic regime owing to explicit solutions. It is also exemplified in the time domain, where a formulation guaranteeing the stability of the numerical scheme has been implemented.

[COVID-19 in children: SARS-CoV-2-related inflammatory multisystem syndrome mimicking Kawasaki disease]. / COVID-19 chez l'enfant : syndrome inflammatoire multi-systémique lié à SARS-CoV-2 mimant un syndrome de Kawasaki.

SARS-CoV-2 pandemics is characterized by a high level of infectivity and a high mortality among adults at risk (older than 65 years, obesity, diabetes, systemic hypertension). Following a common viral pneumonia, a multisystem inflammatory syndrome sometimes occurs, including an Acute Respiratory Distress Syndrome (ARDS) carrying a high mortality. Unlike most common respiratory viruses, children seem less susceptible to SARS-CoV-2 infection and generally develop a mild disease with low mortality. However, clusters of severe shock associated with high levels of cardiac biomarkers and unusual vasoplegia requiring inotropes, vasopressors and volume loading have been recently described. Both clinical symptoms (i.e., high and persistent fever, gastrointestinal disorders, skin rash, conjunctivitis and dry cracked lips) and biological signs (e.g., elevated CRP/PCT, hyperferritinemia) resembled Kawasaki disease. In most instances, intravenous immunoglobin therapy improved the cardiac function and led to full recovery within a few days. However, adjunctive steroid therapy and sometimes biotherapy (e.g., anti-IL-1Ra, anti-IL-6 monoclonal antibodies) were often necessary. Although almost all children fully recovered within a week, some of them developed coronary artery dilation or aneurysm. Thus, a new 'Multisystem Inflammatory Syndrome associated with SARS-CoV-2' has been recently described in children and helps to better understand Kawasaki disease pathophysiology.

Selecting sorting centres to avoid long distance transport of weaned beef calves.

The transport of weaned calves from cow-calf producers to fatteners is a general concern for the young bull industry due to its documented negative impact on the welfare, health and performance of the animals. These transfers are often managed by intermediaries who transport weaned calves to sorting centres, where they are grouped into batches before being sent to fattening units. In this study, we present an algorithm to limiting these transfer distances by appropriately selecting the sorting centre through which they must go. We tested the effectiveness of this algorithm on historical data from a French beef producer organization managing 136,892 transfers using 13 sorting centres. The results show a decrease in the transfer distances compared to the historical record, especially for the calves travelling over long distances (- 76 km, i.e. 18% on average for the 33% longest transfers). Moreover, the distribution of calves between the sorting centres proposed by the algorithm reveals differences in their efficiency in minimizing transfer distances. In addition to its usefulness as a management tool for the daily transport of cattle, this algorithm provides prospects for improving the management of the sorting centres themselves.

Sarcoidosis diagnosed in the elderly: a case-control study.

BACKGROUND: Studies on sarcoidosis in elderly patients are scarce and none have specifically evaluated patients aged ≥75 at onset. AIM: We aimed to analyse the characteristics of patients with sarcoidosis diagnosed after 75 and to compare them with those of younger patients. DESIGN: Multicenter case-control study comparing elderly-onset sarcoidosis (EOS) with young-onset sarcoidosis (YOS) seen at Lyon University Hospitals between 2006 and 2018. METHODS: Using our institutional database, we included 34 patients in the EOS group and compared them with 102 controls from the YOS group in a 1:3 ratio. Demographic characteristics, medical history, clinical presentation, laboratory and imaging findings, sites of biopsies, histological analyses, treatments and outcomes were recorded using a comprehensive questionnaire. RESULTS: There were more Caucasians in the EOS group (94.1% vs. 59.8%; P < 0.001), who had significantly more comorbidities (mean, 3.1 ± 2 vs. 1.1 ± 1.6; P < 0.001). In the EOS group, there was less pulmonary involvement (26.5% vs. 49%; P = 0.022), less lymphadenopathy (2.9% vs. 16.7%; P = 0.041), no erythema nodosum (0% vs. 12.8%; P = 0.029) and no arthralgia (0% vs. 25.5%; P = 0.001). Conversely, uveitis was more common in the EOS group (55.9% vs. 20.6%; P < 0.001). Pathological confirmation was obtained significantly less frequently in the EOS group (67.7% vs. 85.3%; P = 0.023). Corticosteroid-related side effects were significantly more common in the EOS group (100% vs. 75.9%; P = 0.030). CONCLUSION: Epidemiology and clinical presentation of EOS differs from YOS, including more comorbidities and more uveitis. Elderly patients are more prone to corticosteroid side effects.

No evidence that rapid adaptation impedes biological control of an invasive plant.

Biological control is a popular tool for invasive species management, but its success in nature is difficult to predict. One risk is that invasive plants, which may have adapted to lower herbivore pressure in the introduced range, could rapidly evolve defences upon re-association with their biocontrol agent(s). Previous studies have demonstrated that populations of the invasive plant purple loosestrife (Lythrum salicaria) exposed to biocontrol exhibit traits consistent with the rapid evolution of defence. However, to date, no one has tested this hypothesis under field-natural levels of herbivory. Using seed from 17 populations of purple loosestrife growing in eastern Canada, that varied in their history of exposure to their biocontrol agent, the leaf beetle Neogalerucella spp., we transplanted 1,088 seedlings from 136 maternal families into a common garden under ambient herbivory. Over the following three and half years, we assessed plant performance in the face of biocontrol by measuring early-season plant size, defoliation, flowering, and season-end biomass. We discovered that a population history with biocontrol explained little variation in herbivory or plant performance, suggesting that adaptation is not hindering biocontrol effectiveness. Instead, plant size, subsequent defoliation, and spatio-temporal variables were the main predictors of plant growth and flowering during the study. The high individual variability we observed in plant performance underscores that flexible strategies of allocation and phenology are important contributors to the persistence of invasive plants. Our findings suggest that plant adaptation to biocontrol is unlikely to be a strong impediment to biological control in this species, however, the high survival and variable defoliation of plants in our study also indicate that biocontrol alone is unlikely to result in significant population decline. We recommend that the application of multiple forms of control simultaneously (e.g. thinning plus biocontrol) could help to prevent the existence of refuges of large, reproductive individuals.

Risks of severe hyponatremia in children receiving hypotonic fluids.

Intravenous fluids are frequently used in hospitalized children. Hypotonic fluids have been the standard of care in pediatrics for many years. This might be explained by the empiricism of early recommendations favoring fluids with dextrose, but an insufficient amount of sodium. The risk of hyponatremia (<135mmol/L) might be increased by the occurrence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in the course of common acute diseases (e.g., bronchiolitis, acute gastroenteritis, encephalitis, meningitis) in children. Severe hyponatremia (<130mmol/L) is often associated with neurologic complications leading to sequelae or even death. Over the last few years, hyponatremia induced by hypotonic fluids has been increasingly reported, and significant progress has been made in the understanding of cerebral edema and osmotic demyelination. Several randomized clinical trials have shown weak but significant evidence that isotonic fluids were superior to hypotonic solutions in preventing hyponatremia. However, clinical practices have not changed much in France, as suggested by the analysis of intravenous fluids ordered from the Assistance Publique-Hôpitaux de Paris (AP-HP) central pharmacy (PCH) in 2017. Therefore, it would be advisable that national guidelines be released under the French Health Authorities regarding the safe infusion of infants and children.

Bilateral sagittal split osteotomy training on mandibular 3-dimensional printed models for maxillofacial surgical residents.

Complications with bilateral sagittal split osteotomy (BSSO) can sometimes result from surgical inexperience. Our aim was to present a 3-dimensional printed mandibular model for BSSO training in a maxillofacial surgical education programme. A polymethacrylate mandibular model obtained from mandibular cone-beam computed tomographic (CT) images was designed and printed for use in training. Twenty-four residents were each asked to do a BSSO according to the Epker/Dal-Pont technique. The session was conducted as a simulation course with a final debriefing. A questionnaire before and after the test was filled in using a 10-point Likert scale to assess the participants' knowledge. The mandibular model provided a realistic way of handling the trabecular bone after cortical osteotomy, as well as in the splitting phase. Significant increases in knowledge and surgical skills were noted for all steps of the BSSO, particularly regarding the use of the piezoelectric device for osteotomy, and for management of wisdom teeth in the splitting zone (3.00 ±2.16 to 6.95 ±2.06 and 2.73 ±1.91 to 5.75 ±2.63, respectively; p1=0.0002 and p2=0.0003). We think that this is a valuable printed mandibular model for the development of surgical skills for BSSO in maxillofacial surgical residents.

Effects of an individualized exercise training program on severity markers of obstructive sleep apnea syndrome: a randomised controlled trial.

OBJECTIVE: Obstructive sleep apnea (OSA) is a high prevalent disorder with severe consequences including sleepiness, metabolic, and cardiovascular disorders. The aim of this study was to assess the effect of an individualized exercise-training (IET) program with educational sessions vs educational sessions alone on severity markers of OSA over an eight-week duration. METHODS: This was a randomised, controlled, parallel-design study. In sum, 64 patients with moderate-to-severe OSA (apnea-hypopnea index AHI 15-45/hour), low physical activity level (Voorrips<9), body-mass index (BMI) <40 kg/m2 were included in intervention group (IG) or control group (CG), and 54 patients finished the study. All underwent polysomnography (PSG), multiple sleep latency test (MSLT), constant workload exercise test, blood samples and fulfilled questionnaires twice. The primary endpoint was the change in apnea-hypopnea (AHI) at eight weeks from baseline. Main secondary endpoints were daytime sleepiness assessed by questionnaire and objective tests. RESULTS: No significant between-group differences were found for changes in AHI. A reduction in AHI was found in IG only (p = 0.005). Compared to CG, exercise training leads to a greater decrease in AHI during REM sleep (p = 0.0004), with a significant increase in mean daytime sleep latency (p = 0.02). Between-group differences were significant for weight reduction, severity of fatigue, insomnia and depressive symptoms with trend for sleepiness symptoms. CONCLUSIONS: In adult patients with moderate-to-severe OSA, IET did not decrease AHI compared to the control group but improved markers of severity of OSA, in particular AHI in rapid eye movement (REM) sleep and objective daytime sleepiness. Adding personalized exercise training to the management of patients with OSA should be considered. CLINICALTRIALS. GOV IDENTIFIER: NCT01256307.

[SLC6A14, a modifier gene in cystic fibrosis]. / SLC6A14, un gène modificateur dans la mucoviscidose.

Although cystic fibrosis is a monogenic disease, a considerable clinical phenotypic variability is observed in patients with the same CFTR mutations. Thanks to the development of new and powerful tools for carrying out genetic studies, several genes called "modifier genes" have been identified as being associated with the severity of the lung function disorder in cystic fibrosis patients. Among these genes, SLC6A14 may modulate the anti-infective response and epithelial integrity of the airways, thus providing a potential therapeutic target to improve the patient's lung function.

[Medication management of hypertension and heart failure in older patients: What happens to therapeutic changes after hospitalization?] / Prise en charge médicamenteuse de l'hypertension artérielle et de l'insuffisance cardiaque chez la personne âgée : les modifications effectuées à l'hôpital sont-elles poursuivies en ville ?

PURPOSE: The objective of this study was to objectivize if the cardiovascular therapeutic changes performed during hospitalization of older patients with hypertension and/or heart failure (HF), were maintained in ambulatory 3 month after hospitalization. METHODS: This is a longitudinal study conducted in a geriatric unit. Patients over 65 years with hypertension and/or HF, who had at least one change in cardiovascular medicaton during hospitalization, and who accepted the 3-month follow-up were included in the longitudinal study. At admission, during hospitalization and 3 months after hospitalization data concerning cardiovascular medication were collected. RESULTS: During hospitalization, 142 (73.6%) patients had at least one change in hypertension and/or HF medication. Overall, 249 changes were performed. Forty-one patients received follow-up at 3 months. At 3 months, therapeutic changes were maintained by 48.8% of the general practitioners (n=20 patients). For the rest, 41.5% of the patients had benefited from new therapeutic changes (28 changes for 10 patients) and 9.7% of the general practitioners (n=4 patients) had restored the initial prescription before hospitalization. CONCLUSIONS: Medication review performed by geriatricians and pharmacists during hospitalization resulted in 249 changes. These changes aimed at limiting iatrogenic disease, by reducing overtreatment and potentially inappropriate prescriptions. Difficulties in the patient care continuity between the hospital and ambulatory setting have been identified.

Pelvic floor muscle training: mechanisms of action for the improvement of genitourinary syndrome of menopause.

Objective: This study aims to investigate the mechanism of action of pelvic floor muscle training (PFMT) for the improvement of the signs and symptoms of genitourinary syndrome of menopause (GSM) in postmenopausal women with GSM and urinary incontinence (UI).Methods: Twenty-nine women were included in the secondary analysis of a single-arm feasibility study. Using color Doppler ultrasound, the peak systolic velocity, time-averaged maximum velocity, and pulsatility index of the internal pudendal and dorsal clitoral arteries were measured at rest and after a pelvic floor muscle (PFM) contraction task. PFM function was assessed by dynamometry, and vulvovaginal tissue elasticity was measured using the Vaginal Atrophy Index.Results: PFMT significantly improved blood flow parameters in both arteries (p < 0.05) and significantly increased the speed of PFM relaxation after a contraction (p = 0.003). After the intervention, a marginally significant decrease in PFM tone was observed, as well as an increase in PFM strength (p = 0.060 and p = 0.051, respectively). Finally, improvements in skin elasticity and introitus width were observed as measured by the Vaginal Atrophy Index (p < 0.007).Conclusion: Our findings suggest that PFMT improves blood flow in vulvovaginal tissues, PFM relaxation capacity, and vulvovaginal tissue elasticity in postmenopausal women with GSM and UI.

Vertical lengthening genioplasty: A new osteotomy technique.

Vertical insufficiency of the chin imbalances the orofacial and aesthetic parameters of the lower third of the face. We here propose a new osteotomy technique for chin lengthening. Our procedure is based on a single osteotomy and it does not require any interposition of a bone graft. In our experience with seven patients, we report good aesthetic and morphometric outcomes at one year.

Conception and use of a custom-made facial mask for pressure therapy in complex facial wounds.

Pressure therapy (PT) is commonly used to manage hypertrophic scars. It is often based on the use of elastic pressure garments, which are poorly suited for a facial localization. We describe the conception, fabrication, and use of a custom-made PT facial mask for primary prevention of hypertrophic scarring of complex facial wounds. The main advantage of the device is that it is quick and easy to manufacture in a conventional prosthetics laboratory, with a good level of observance and tolerance in our experience of 20 treated patients.

[Adaptation of the General Data Protection Regulation (GDPR) to a smartphone app for rhinitis and asthma (MASK-air®)]. / Règlement général sur la protection des données pour MASK-air® (application mobile rhinite et asthme).

The General Data Protection Regulation (GDPR) regulates the processing of personal data in the European Union. The legal context is adapted to follow the evolution of technologies and of society. This new European regulation became mandatory, especially for connected devices, on May 25, 2018. An app originally known as "The Allergy Diary" is available for Android phones and iPhones. Its name was recently changed to MASK-air. The downloading and use of this app are free of charge and there are no adverts. It enables users to record their symptoms and their medications to better track the progress of their allergic rhinitis and/or asthma. It has been developed by public (Foundation FMC VIA-LR, University of Montpellier) and private (KYomed INNOV) organizations based in France and therefore falls under French jurisdiction. This article summarizes the five main principles of personal data protection to be respected during the development of the app: purpose, proportionality and relevance, limited retention period, security and confidentiality, as well as the rights of the people who are involved in the management of the personal data (including withdrawal and modification).

Enhanced resonance of sparse arrays of Helmholtz resonators-Application to perfect absorption.

The influence of the spacing on the resonance of a periodic arrangement of Helmholtz resonators is inspected. An effective problem is used which accurately captures the properties of the resonant array within a large range of frequencies, and whose simplified version leaves an impedance condition. It is shown that the strength of the resonance is enhanced when the array becomes sparser. This degree of freedom on the radiative damping is of particular interest since it does not affect the resonance frequency nor the damping due to losses within each resonator; in addition, it does not affect the total thickness of the array. It is shown that it can be used for the design of a perfect absorbing wall.