[Male infertility, environment and lifestyle]. / Infertilité masculine, environnement et mode de vie.

BACKGROUND: Since the 1970s, there has been a quantitative and qualitative decline in sperm parameters. The main hypothesis to explain such a rapid evolution is the involvement of environmental and behavioral phenomena. METHODS: A bibliographic search limited to English and French literature in men published before 7/2023 was carried out on the links between fertility and pollution, xenobiotics, tobacco, narcotics, cannabis, alcohol, weight, sport, sedentary lifestyle, sleep and anabolics. RESULTS: Profound changes in lifestyle have occurred over the past 50 years: reduced sleep time, sedentary lifestyle, dietary changes, tobacco consumption, use of narcotics and anabolics. These changes have a proven impact on spermogram parameters, and should be corrected in an effort to optimize reproductive health. Other environmental parameters: pollution, exposure to heavy metals, exposure to xenobiotics, phthalates and pesticides… will be more difficult to exclude from patients' daily lives, but deserve to be taken more into account. CONCLUSION: This review should help the urologist to assess and counsel patients in order to improve their reproductive health. These factors should be routinely investigated in infertile men.

Prevalence and management of chronic breathlessness in COPD in a tertiary care center.

BACKGROUND: Breathlessness is the prominent symptom of chronic obstructive pulmonary disease (COPD). Despite optimal therapeutic management including pharmacological and non-pharmacological interventions, many COPD patients exhibit significant breathlessness. Chronic breathlessness is defined as breathlessness that persists despite optimal treatment of the underlying disease. Because of the major disability related to chronic breathlessness, symptomatic treatments including opioids have been recommended by several authors. The prevalence of chronic breathlessness in COPD and its management in routine clinical practice have been poorly investigated. Our aim was to examine prevalence, associated characteristics and management of chronic breathlessness in patients with COPD recruited in a real-life tertiary hospital-based cohort. METHODS: A prospective study was conducted among 120 consecutive COPD patients recruited, in stable condition, at Nancy University Hospital, France. In parallel, 88 pulmonologists of the same geographical region were asked to respond to an on-line questionnaire on breathlessness management. RESULTS: Sixty four (53%) patients had severe breathlessness (modified Medical Research Council scale≥3), despite optimal inhaled medications for 94% of them; 40% had undergone pulmonary rehabilitation within the past 2 years. The severity of breathlessness increased with increasing airflow limitation. Breathlessness was associated with increased symptoms of anxiety, depression and with osteoporosis. No relation was found with other symptoms, exacerbation rate, or cardiovascular comorbidities. Among the patients with chronic breathlessness and Hospitalized Anxiety and/or Depression score > 10, only 25% were treated with antidepressant or anxiolytic. Among the pulmonologists 46 (52%) answered to the questionnaire and expressed a high willingness to prescribe opioids forchronic breathlessness, which contrasted with the finding that none of these patients received such treatments against breathlessness. CONCLUSION: Treatment approaches to breathlessness and associated psychological distress are insufficient in COPD. This study highlights underuse of pulmonary rehabilitation and symptomatic treatment for breathlessness.

Estimation of the frequency of Q fever in sheep, goat and cattle herds in France: results of a 3-year study of the seroprevalence of Q fever and excretion level of Coxiella burnetii in abortive episodes.

A study was carried out, from 2012 to 2015, in 10 French départements to estimate the serological prevalence of Q fever and the frequency of abortive episodes potentially related to Coxiella burnetii in a large sample of cattle, sheep and goat herds. The serological survey covered 731 cattle, 522 sheep and 349 goat herds, randomly sampled. The frequency of abortive episodes potentially related to C. burnetii was estimated by investigating series of abortions in 2695 cattle, 658 sheep and 105 goat herds using quantitative polymerase chain reaction analyses and complementary serological results when needed. The average between-herd seroprevalence was significantly lower for cattle (36·0%) than for sheep (55·7%) and goats (61·0%) and significantly higher for dairy herds (64·9% for cattle and 75·6% for sheep) than for meat herds (18·9% for cattle and 39·8% for sheep). Within-herd seroprevalence was also significantly higher for goats (41·5%) than for cattle (22·2%) and sheep (25·7%). During the study period, we estimated that 2·7% (n = 90), 6·2% (n = 48) and 16·7% (n = 19) of the abortive episodes investigated could be 'potentially related to C. burnetii'in cattle, sheep and goat herds, respectively. Overall, strong variability was observed between départements and species, suggesting that risk factors such as herd density and farming practices play a role in disease transmission and maintenance.

In vivo exposure to benzo(a)pyrene induces significant DNA damage in mouse oocytes and cumulus cells.

STUDY QUESTION: Does in vivo exposure to benzo(a)pyrene (BaP) induce DNA damage in oocytes and cumulus cells (CCs) in mice? SUMMARY ANSWER: Significant increases in DNA strand breaks in oocytes and CCs and in BaP-induced DNA adducts in CCs were detected in exposed mice compared with controls. WHAT IS KNOWN ALREADY: BaP has well-known mutagenic and carcinogenic effects on somatic cells, and is also registered as potential reproductive toxicant by several environmental protection agencies. It has been shown to cause a significant increase in DNA adducts in ovarian tissues; however, to our knowledge, the genotoxic effects of BaP on oocytes and CCs have not been studied to date. STUDY DESIGN, SIZE, DURATION: Female CD1 mice were exposed to BaP via the oral administration of a single dose of 13 mg/kg body weight (bw); matched controls were exposed to the vehicle only (soya oil). A total of 15 groups of 6 mice (exposed or controls) were sacrificed 2, 4, 6, 15 or 22 days after BaP exposure, and after collection of oviducts, the oocyte-CC complexes (COC) were released. PARTICIPANTS/MATERIALS, SETTING, METHODS: The alkaline comet assay was used to quantify the DNA breaks in oocytes and CCs; DNA damage was expressed as the Olive Tail Moment (OTM). Immunofluorescent staining was used to quantify BaP-induced DNA adducts in CCs. Fluorescence was expressed as the average grey value (AGVA; arbitrary units). The differences between the exposed and control groups were assessed using analysis of variance (ANOVA) and the non-parametric Mann-Whitney test. MAIN RESULTS AND THE ROLE OF CHANCE: Higher levels of DNA damage were observed in the oocytes and CCs of BaP-exposed mice than in those of vehicle controls. Significant increases in OTM (mean ± SE) were detected in (i) oocytes from females exposed for 4 (10.5 ± 0.9 versus 3.1 ± 0.4, P < 0.0001) or 6 days before collection (15.6 ± 2.0 versus 3.6 ± 0.9, P < 0.0001) and (ii) CCs from females exposed 2 (6.4 ± 0.6 versus 2.1 ± 0.2, P < 0.0001), 4 (7.8 ± 0.4 versus 2.4 ± 0.1, P < 0.0001) or 6 days before collection (7.3 ± 0.3 versus 3.2 ± 0.5, P < 0.0001) compared with controls. A significant increase in benzo(a)pyrene-7,8-9,10 diol epoxide (BPDE)-DNA adducts and higher AGVA (mean ± SE) scores were observed in CCs from females exposed 2 (6.1 ± 0.3 versus 3.6 ± 0.5, P < 0.0001), 4 (7.5 ± 0.1 versus 3.4 ± 0.1, P < 0.0001) or 6 days before collection (11.6 ± 0.4 versus 3.7 ± 0.1, P < 0.0001) compared with control mice. LIMITATIONS, REASONS FOR CAUTION: Mice were given one treatment via the oral route because this dose and mode of administration have been shown to induce detectable BPDE-DNA adduct levels in mouse organs and sperm cells. Additional data are needed to assess DNA damage in oocytes and CCs after chronic exposure to BaP in vivo. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first study examining the in vivo genotoxicity of BaP in oocytes and CCs. We observed significant DNA damage in the oocytes and CCs of mice after acute BaP exposure. BPDE-DNA adducts result directly from BaP metabolism while DNA breaks could result mainly from BPDE-DNA adduct excision and repair and/or through direct genotoxicity from increased reactive oxygen species. These results add new and important insights regarding the recently suggested toxicity of chronic BaP exposure in the ovary. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant (93-CPQ 2012-05) from the DIRRECTE, Provence Alpes Côte d'Azur, France. None of the authors have any conflict of interest to declare.

Detecting objective and subjective cognitive effects of electroconvulsive therapy: intensity, duration and test utility in a large clinical sample.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for depression but the extent and persistence of cognitive side-effects remain uncertain. It has been reported that there is little evidence that impairments last longer than up to 15 days post-ECT. However, relatively few studies have followed patients for even as long as 1 month post-ECT. Here we report results from a brief cognitive battery given prior to ECT and repeated five times up to 6 months post-ECT. METHOD: In a retrospective case-note study of routinely collected clinical data 126 patients treated with ECT completed two neuropsychological tests [Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial recognition memory (SRM) and Mini Mental State Examination (MMSE)] and two subjective reports of memory function, prior to ECT. Patients were reassessed following ECT and at 1, 3 and 6 months post-ECT although not all patients completed all assessments. RESULTS: Performance relative to pre-ECT baseline was significantly poorer at each post-ECT assessment up to 3 months post-ECT using the CANTAB SRM, but was improved at 6 months. Conversely, MMSE score showed improvements relative to baseline from 1 month post-ECT. Mood and subjective memory scores improved following ECT and were correlated with one another, but not with either neuropsychological measure. CONCLUSIONS: The CANTAB SRM task revealed reversible cognitive deficiencies relative to a pre-ECT baseline for at least 3 months following ECT, while MMSE score and patients' subjective reports showed only improvement. Visuospatial memory scores eventually exceeded baseline 6 months post-ECT.

Temporal and spatial variability of organotins in an intermittent Mediterranean river.

Organotin compounds (OTs) are exclusively anthropogenic and have been widely used for their biocidal properties and as stabilizers in various industrial applications. Hence organotins are common pollutants. Their high toxicity has led to their entry on the EU water framework's priority substances' list. However, few studies are available regarding their behaviour in surface waters, in particular, in intermittent Mediterranean rivers. The Vène is an intermittent river located in Languedoc-Roussillon, southern France. It is the main tributary of an important shellfish farming site: the Thau lagoon. The present study aims at establishing the presence of OTs on a 1.5 km long reach of the river into which a waste water treatment plant (WWTP) discharges. The study is carried out during steady-state flow conditions over two consecutive years and investigates potential OTs sources in everyday domestic activities. Routine field monitoring was carried out over a 5 month period during the springs of 2008 and 2009. The results establish the presence of butyltins and octyltins throughout the 1.5 km long reach at concentrations exceeding the maximum allowable concentration levels imposed by the water framework directive. The WWTP is recognized as an important OTs point source; however, using trace and rare earth elements as tracers, an urban stormwater sewage gutter is identified as a secondary source. Its impact on the river's pollutant loads is however variable in time because of flow intermittency. The paper discusses the need for specific monitoring and management schemes for intermittent rivers.

Sperm cryopreservation before cancer treatment: a 15-year monocentric experience.

Sperm banking is an important procedure to preserve fertility before cancer therapy. The aim of this study was to comprehensively analyse cryopreservation activity retrospectively for 1080 patients referred to the sperm bank for sperm cryopreservation before cancer treatment. This study included 1007 patients diagnosed with testicular cancer (TC) (41.7%), lymphoma (26%), other haematological cancers (9.4%) or other types of cancer (22.8%); of these, 29 patients did not produce any semen sample and cryopreservation was impossible for 67 patients. Semen characteristics before treatment were within normal ranges, except moderate asthenospermia. Sperm concentration was significantly lower in TC than in non-TC. Straws from 57 patients (6.3%) were used in assisted reproductive technologies, which led to a 46.8% cumulative birth rate. Straws were destroyed for 170 patients (18.7%) and 140 patients performed semen analyses after cancer therapy. After an average delay of 22.5 months after the end of therapy, 43 patients (30.7%) exhibited azoospermia. This study of a large population of cancer patients revealed a high level of successful sperm storage. Utilization of cryopreserved spermatozoa led to good chances of fatherhood. Nevertheless, sperm banks should be aware of the low rates of straw use and straw destruction by cancer patients.

[Stability of Le Fort I impaction osteotomies]. / Stabilité osseuse des ostéotomies de Le Fort I d'impaction.

INTRODUCTION: Long-term results of Le Fort I osteotomy with vertical impaction for maxillary vertical excess may be not stable. We had for aim to analyze postoperative maxillary and dental displacement after a Le Fort I vertical impaction osteotomy, to identify causes of relapse. PATIENTS AND METHODS: A clinical and radiological evaluation was made on postoperative occlusion (early and late). The position of three bone (O: lower orbit; P: greatest palatine convexity; T: lowest part of the mandibular foramen) and of three dental landmarks (I: occlusal edge of the upper incisor; i: occlusal edge of the lower incisor; m: first molar distal vestibular cuspid) was measured in a standardized method on pre-surgical, early and late (1 to 2.5 years) postoperative cephalometric X rays. Eighteen patients were operated by the same surgeon for maxillary anterior vertical excess and underwent Le Fort I impaction osteotomy, alone or associated with a mandibular osteotomy. Stability was defined by a postoperatory displacement smaller than 1mm. RESULTS: All patients had stable bone landmarks. Three patients had unstable dental landmarks due to relapse. DISCUSSION: Impaction maxillary osteotomy provides stable bone results for maxillary facial height excess. Unsatisfactory outcome is always due to postoperative dental and alveolar displacement. These results correlate to published data.

Application of a Model of Workforce Resilience to the Education Workforce: Expanding Opportunities for Support.

The current study analyzed 502 responses from members of the education workforce on the Resilience at Work (RAW) scale and other measures of health and job satisfaction as part of an initiative offering training and technical assistance to support student and staff well-being. A latent profile analysis using scores on components of the RAW identified three resilience profiles: lower, moderate, and higher capacities for resilience. Profiles were differentiated across components related to resilience capacity including alignment of work and personal values, level of social support, and ability to manage stress. Differences between profiles were observed across days of poor physical health, days of poor mental health, days of activity restriction, general health rating, and domains of burnout, compassion satisfaction, and secondary traumatic stress. These findings reinforce calls to support the education workforce through changes that allow access to meaningful work, an evaluation of demands including workload, relevant training on emotional wellness, positive experiences, connections with others, and stress management.

Ischaemic stroke and essential thrombocythemia: a series of 14 cases.

BACKGROUND: Essential thrombocythemia (ET) is considered as a rare cause of stroke, partially because of difficulties to identify it when platelet count is not greatly elevated. However, early detection of ET is important because, without adapted treatment, recurrent thromboses are frequent. METHOD: We collected, retrospectively, data from 14 cases of stroke patients with ET. Clinical characteristics, ischaemic stroke, laboratory data (platelet and leucocyte count, haemoglobin, JAK2 V617F mutation, culture of haematopoietic progenitors) and treatment were reviewed. Every patient has been interviewed by phone to evaluate outcome. RESULTS: The population consisted of nine women and five men with ages ranging from 40 to 87 years. Most of the patients (12) had atherosclerotic risk factors and two presented a thrombus in the internal carotid. ET was diagnosed early after the onset of stroke except in two patients. The platelet count was under 600*10(9) /L for five patients. Mutation JAK2 V617F was found for eight patients. Thirteen patients were treated with an association between antiplatelet and cytoreductive treatment and did not present further thrombosis. Median follow-up is 2.8 years. CONCLUSION: These cases emphasize the problems of diagnosing ET at the onset of the stroke. Complete blood count has to be carefully read and ET can be suspected even if platelet count is not greatly increased. Diagnosis must be confirmed by haematologist to initiate appropriate treatment.

[Cephalometric study of the velocardiofacial syndrome: Impact of dysmorphosis on phonation]. / Céphalométrie du syndrome vélocardiofacial: les conséquences phonatoires de la dysmorphose.

INTRODUCTION: Velopharyngeal insufficiency is a frequent sign of the velocardiofacial syndrome (VCFS) but its origins are not well-documented. Our aim was to establish a correlation between this functional disorder and regional morphological anomalies. PATIENTS AND METHODS: Twenty-seven of 36 patients presenting with VCFS could be included retrospectively. We measured cavum depth and velum length on lateral orthodontic X-rays, and assessed the relationship between these two measures. We compared these measures to those of reference populations. Postoperative phonation was assessed with an aerophonoscope. RESULTS: The patients presented with a short velum and a deep cavum. Cranium base and upper cervical spine were malformed in 22 of the 27 patients. Seventeen of the 23 assessed patients (66%) improved their phonation after surgery. DISCUSSION: Our data suggests that velopharyngeal insufficiency in VCFS could be the result of a more global craniospinal growth disorder the functional consequences of which remain unclear. The frequent association of morphological anomalies with mental retardation is probably responsible for the failure to normalize phonation.

[Initial results of a novel technique for sperm retrieval in male infertility due to refractory retrograde ejaculation]. / Résultats préliminaires d'une nouvelle technique de recueil du sperme vésical en présence d'éjaculation rétrograde réfractaire au traitement médical.

AIMS: To describe and evaluate a novel technique of spermatozoa retrieval from patients suffering from infertility secondary to refractory retrograde ejaculation. METHOD: Prospective study to compare mobility and vitality of spermatozoa obtained from urine (U) after oral modification of chemical parameter (PH, Osmolarity) versus from endovesical instillation of sterile spermatozoa culture medium before ejaculation (F). Patients were their own controls. Twelve month prospective follow-up was achieved to document the results of assisted procreation. RESULTS: Eight patients were included and mobility and vitality were improved in all patients after F technique was compared to U technique. With U technique, eight patients on eight had negative defrost test; after F technique, seven patients on eight had a positive defrost test and could therefore have access to assisted reproduction techniques. Four couples had five ICSI and obtained three pregnancies leading to five births. CONCLUSION: Endovesical instillation of sterile spermatozoa culture medium before ejaculation was a safe and effective technique to improve spermatozoa quality in male infertility related to refractory retrograde ejaculation.

[Prognostic factors of live-birth after in vitro fertilization for unexplained infertility: A cohort study]. / Facteurs pronostiques des chances de naissance vivante en fécondation in vitro pour infertilité inexpliquée : étude de cohorte.

OBJECTIVES: For 15 to 30% of infertile couples, no etiology can be found, leading to the diagnosis of "unexplained infertility". The aim of our study was to identify prognostic factors for live birth following in vitro fertilization (IVF) for these couples. METHODS: A retrospective, monocentric study on a cohort of couples undergoing IVF for unexplained infertility with the woman aged≤40 years old. Primary analysis compared couples with a live birth following IVF versus childless couples following IVF. RESULTS: Between January 2014 and December 2018, 104 couples were included, 196 transvaginal oocyte pickup were performed, followed by 234 embryo transfers (fresh or cryopreserved) which resulted in 43 deliveries. The cumulative live birth rate was 40.4% per couple. Before IVF attempts, no clinical or paraclinical prognostic factors between the two groups was observed. However, multivariate analysis showed several biological factors of good prognosis in course of treatment, such as a higher number of mature oocytes and better quality embryos in "live birth" group. CONCLUSIONS: For a couple, the chances of having a child following IVF unexplained infertility are 40.4%. However, no clinical characteristic enabled us to identify favourable or unfavourable prognosis factors before starting ART. The prognostic factors identified during IVF cycle are interesting to advise or not to pursue IVF.

Anti-tumor efficacy of a combination therapy with PD-L1 targeted alpha therapy and adoptive cell transfer of PD-1 deficient melanoma-specific human T-lymphocytes.

The optimization of adoptive transfer approaches of anti-tumor T cells requires both the functional improvement of the injected T cells and the modulation of the tumor microenvironment, favoring the recruitment of these T cells and their activation. We have recently shown the therapeutic benefit of two approaches tested individually in a melanoma model wich were on one hand the adoptive transfer of specific T cells deficient for the expression of the inhibitory receptor PD-1, and on the other hand PD-L1 targeted alpha therapy (TAT). In this study, we sought to investigate the efficacy of these two therapies combined, compared to each monotherapy, in order to evaluate the synergy between these two approaches, in the same melanoma model. Here we used melanoma-specific T-cell clones, previously validated for the edition of PDCD1 gene and with previously demonstrated superior anti-tumor activity than their wild-type counterparts, after adoptive transfer in NSG mice engrafted with PD-L1 expressing human melanoma tumors. We also used a previously validated TAT approach, using a 213Bi-anti-human-PD-L1 mAb, alone or in combination with adoptive cell transfer, in the same mouse model. We confirmed previous results obtained with each monotherapy and documented the safety and the superior ability of a combination between the adoptive transfer of PD-1 deficient T cells and TAT targeting PD-L1 to control the growth of melanoma tumors in NSG mice. This study provides the first proof-of-concept of the efficacy of a combination therapy using TAT, adoptive cell transfer and genomic editing of IC-coding genes.

Characterization of dentine structure in three dimensions using FIB-SEM.

All biological tissues are three dimensional and contain structures that span a range of length scales from nanometres through to hundreds of millimetres. These are not ideally suited to current three-dimensional characterization techniques such as X-ray or transmission electron tomography. Such detailed morphological analysis is critical to understanding the structural features relevant to tissue function and designing therapeutic strategies intended to address structural deficiencies encountered in pathological states. We show that use of focused ion beam milling combined with scanning electron microscopy can provide three-dimensional information at nanometre resolution from biologically relevant volumes of material, in this case dentine.

[Ileum and brain, unusual metastatic sites for a thymoma]. / Iléon et encéphale, des sites métastatiques inhabituels pour un thymome.

INTRODUCTION: Thymomas are epithelial neoplasms of thymic origin, preferentially localized in the anterior mediastinum. Recurrences after surgery are uncommon and usually occur in the intrathoracic area. The occurrence of extra-thoracic metastases is an unusual phenomenon. CASE REPORT: Here we report the case of a 61-year-old man with no special medical history. He smoked about 40 pack years but stopped in 1999. Initially he presented with a mediastinal thymoma and underwent surgical resection. One year later the development of abdominal pain and bowel disorders lead to the discovery of an ileal ulcero-necrotic tumour. After surgical resection, histological examination revealed secondary thymoma. A few months later he underwent cerebral MRI because of neurological symptoms. This revealed a second metastasis located in the brain. Stereotactic radiotherapy led to an improvement. After more than one year of follow-up the patient developed a papillary thyroid carcinoma but there were no signs of recurrence of the thymoma. CONCLUSIONS: Extra-thoracic metastases of thymoma are exceptional but their existence should not be overlooked. Their management is not standardised because of lack of data in the literature. Though surgical excision in oligo-metastatic subjects is a frequently reported therapeutic option, a radiotherapeutic approach, particularly in cerebral situations, could be a credible alternative.

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.

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.