Autosomal dominant ApoA4 mutations present as tubulointerstitial kidney disease with medullary amyloidosis.

Sporadic cases of apolipoprotein A-IV medullary amyloidosis have been reported. Here we describe five families found to have autosomal dominant medullary amyloidosis due to two different pathogenic APOA4 variants. A large family with autosomal dominant chronic kidney disease (CKD) and bland urinary sediment underwent whole genome sequencing with identification of a chr11:116692578 G>C (hg19) variant encoding the missense mutation p.L66V of the ApoA4 protein. We identified two other distantly related families from our registry with the same variant and two other distantly related families with a chr11:116693454 C>T (hg19) variant encoding the missense mutation p.D33N. Both mutations are unique to affected families, evolutionarily conserved and predicted to expand the amyloidogenic hotspot in the ApoA4 structure. Clinically affected individuals suffered from CKD with a bland urinary sediment and a mean age for kidney failure of 64.5 years. Genotyping identified 48 genetically affected individuals; 44 individuals had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73 m2, including all 25 individuals with kidney failure. Significantly, 11 of 14 genetically unaffected individuals had an eGFR over 60 ml/min/1.73 m2. Fifteen genetically affected individuals presented with higher plasma ApoA4 concentrations. Kidney pathologic specimens from four individuals revealed amyloid deposits limited to the medulla, with the mutated ApoA4 identified by mass-spectrometry as the predominant amyloid constituent in all three available biopsies. Thus, ApoA4 mutations can cause autosomal dominant medullary amyloidosis, with marked amyloid deposition limited to the kidney medulla and presenting with autosomal dominant CKD with a bland urinary sediment. Diagnosis relies on a careful family history, APOA4 sequencing and pathologic studies.

A silicone-based slippery polymer coating with humidity-dependent nanoscale topography.

HYPOTHESIS: Slippery Omniphobic Covalently Attached Liquids (SOCAL) have been proposed for making omnirepellent thin films of self-assembled dimethylsiloxane polymer brushes grafted from silica surfaces. Smooth and flat at very small scale, these fluid surfaces could exhibit a more complex multiscale structure though showing very weak contact angle hysteresis (less than 5°). EXPERIMENT: In this work, coatings were deposited on glass surfaces from an acidic dimethoxydimethylsilane solution under carefully controlled relative humidity. Ellipsometry mapping was used to analyze the surface structuration with nanometric thickness sensitivity. The sliding properties were determined using a drop shape analyzer with a tilting device, and chemical analyses of the coatings were performed using on-surface techniques (XPS, ATR-FTIR spectroscopy). FINDINGS: Coated materials possessed an unexpected surface structure with multiscale semispherical-like features, which surprisingly, did not increase the contact angle hysteresis. A careful study of some parameters of the coating process and the related evolution of the surface properties allowed us to propose a new model of the chemical organization of the polymer to support this remarkable liquid-like behavior. These structures are made of end-grafted strongly adsorbed Guiselin brushes with humidity-dependent thickness: the higher the humidity, the thinner and the more slippery the coating.

Obese outbred mice only partially benefit from diet normalization or calorie restriction as preconception care interventions to improve metabolic health and oocyte quality.

STUDY QUESTION: Can diet normalization or a calorie-restricted diet for 2 or 4 weeks be used as a preconception care intervention (PCCI) in Western-type diet-induced obese Swiss mice to restore metabolic health and oocyte quality? SUMMARY ANSWER: Metabolic health and oocyte developmental competence was already significantly improved in the calorie-restricted group after 2 weeks, while obese mice that underwent diet normalization showed improved metabolic health after 2 weeks and improved oocyte quality after 4 weeks. WHAT IS KNOWN ALREADY: Maternal obesity is linked with reduced metabolic health and oocyte quality; therefore, infertile obese women are advised to lose weight before conception to increase pregnancy chances. However, as there are no univocal guidelines and the specific impact on oocyte quality is not known, strategically designed studies are needed to provide fundamental insights in the importance of the type and duration of the dietary weight loss strategy for preconception metabolic health and oocyte quality. STUDY DESIGN, SIZE, DURATION: Outbred female Swiss mice were fed a control (CTRL) or high-fat/high-sugar (HF/HS) diet. After 7 weeks, some of the HF mice were put on two different PCCIs, resulting in four treatment groups: (i) only control diet for up to 11 weeks (CTRL_CTRL), (ii) only HF diet for up to 11 weeks (HF_HF), (iii) switch at 7 weeks from an HF to an ad libitum control diet (HF_CTRL) and (iv) switch at 7 weeks from an HF to a 30% calorie-restricted control diet (HF_CR) for 2 or 4 weeks. Metabolic health and oocyte quality were assessed at 2 and 4 weeks after the start of the intervention (n = 8 mice/treatment/time point). PARTICIPANTS/MATERIALS, SETTING, METHODS: Changes in body weight were recorded. To study the impact on metabolic health, serum insulin, glucose, triglycerides, total cholesterol and alanine aminotransferase concentrations were measured, and glucose tolerance and insulin sensitivity were analyzed at PCCI Weeks 2 and 4. The quality of in vivo matured oocytes was evaluated by assessing intracellular lipid droplet content, mitochondrial activity and localization of active mitochondria, mitochondrial ultrastructure, cumulus cell targeted gene expression and oocyte in vitro developmental competence. MAIN RESULTS AND THE ROLE OF CHANCE: Significant negative effects of an HF/HS diet on metabolic health and oocyte quality were confirmed (P < 0.05). HF_CTRL mice already showed restored body weight, serum lipid profile and glucose tolerance, similar to the CTRL_CTRL group after only 2 weeks of PCCI (P < 0.05 compared with HF_HF) while insulin sensitivity was not improved. Oocyte lipid droplet volume was reduced at PCCI Week 2 (P < 0.05 compared with HF_HF), while mitochondrial localization and activity were still aberrant. At PCCI Week 4, oocytes from HF_CTRL mice displayed significantly fewer mitochondrial ultrastructural abnormalities and improved mitochondrial activity (P < 0.05), while lipid content was again elevated. The in vitro developmental capacity of the oocytes was improved but did not reach the levels of the CTRL_CTRL mice. HF_CR mice completely restored cholesterol concentrations and insulin sensitivity already after 2 weeks. Other metabolic health parameters were only restored after 4 weeks of intervention with clear signs of fasting hypoglycemia. Although all mitochondrial parameters in HF_CR oocytes stayed aberrant, oocyte developmental competence in vitro was completely restored already after 2 weeks of intervention. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, we applied a relevant HF/HS Western-type diet to induce obesity in an outbred mouse model. Nevertheless, physiological differences should be considered when translating these results to the human setting. However, the in-depth study and follow-up of the metabolic health changes together with the strategic implementation of specific PCCI intervals (2 and 4 weeks) related to the duration of the mouse folliculogenesis (3 weeks), should aid in the extrapolation of our findings to the human setting. WIDER IMPLICATIONS OF THE FINDINGS: Our study results with a specific focus on oocyte quality provide important fundamental insights to be considered when developing preconception care guidelines for obese metabolically compromised women wishing to become pregnant. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Flemish Research Fund (FWO-SB grant 1S25020N and FWO project G038619N). The authors declare there are no conflicts of interest.

The Human Affectome Project: A dedication to Jaak Panksepp.

Mapping the neural basis of the Affectome was certainly the goal of Jaak Panksepp as he extended the work of a long line of thinkers from William James to Paul Maclean. Jaak's contribution was not just an incremental step, but a move to embrace feelings as a key component of affective science. His goal was to develop objective behavioral measures as he identified the neural substrates associated with affective states. He dedicated his career to studying the biological roots of emotional operating systems and his 1998 book "Affective Neuroscience" stands as a seminal accomplishment that provided a foundation for a field of research that has flourished since. His influences can be seen in many of the reviews created for this project and his early references to comfort zones are central to the human affectome. Indeed, Jaak was a tireless investigator who challenged our thinking, and he gave us many insights and gifts. We are immensely grateful for his contributions and this special issue is dedicated to his memory.

Utilizing the Consolidated Framework for Implementation Research to Explore Palliative Care Program Implementation for American Indian and Alaska Natives throughout the United States.

Background: A significant shortage of palliative care (PC) services exists for American Indian and Alaska Native people (AI/ANs) across the United States. Using an implementation science framework, we interviewed key individuals associated with AI/AN-focused PC programs to explore what is needed to develop and sustain such programs. Objectives: To identify facilitators of implementation and barriers to sustainability associated with the development of PC programs designed for AI/ANs across the United States. Methods: We interviewed 12 key individuals responsible for the implementation of AI/AN-focused PC services. The Consolidated Framework for Implementation Research (CFIR) guided data coding and interpretation of themes. Results: We identified nine themes that map to CFIR constructs. Facilitators of implementation include high tension for change and respecting cultural values. Barriers to program sustainability include a lack of administrative leadership support. Discussion: AI/AN-focused PC programs should be congruent with community needs. PC program developers should focus on sustainability well before initial implementation.

Maternal metabolic health and fertility: we should not only care about but also for the oocyte!

Metabolic disorders due to obesity and unhealthy lifestyle directly alter the oocyte's microenvironment and impact oocyte quality. Oxidative stress and mitochondrial dysfunction play key roles in the pathogenesis. Acute effects on the fully grown oocytes are evident, but early follicular stages are also sensitive to metabolic stress leading to a long-term impact on follicular cells and oocytes. Improving the preconception health is therefore of capital importance but research in animal models has demonstrated that oocyte quality is not fully recovered. In the in vitro fertilisation clinic, maternal metabolic disorders are linked with disappointing assisted reproductive technology results. Embryos derived from metabolically compromised oocytes exhibit persistently high intracellular stress levels due to weak cellular homeostatic mechanisms. The assisted reproductive technology procedures themselves form an extra burden for these defective embryos. Minimising cellular stress during culture using mitochondrial-targeted therapy could rescue compromised embryos in a bovine model. However, translating such applications to human in vitro fertilisation clinics is not simple. It is crucial to consider the sensitive epigenetic programming during early development. Research in humans and relevant animal models should result in preconception care interventions and in vitro strategies not only aiming at improving fertility but also safeguarding offspring health.

Video assisted thoracoscopy or laparoscopy for enucleation of esophageal leiomyoma: A seven-year single center experience of 75 cases.

OBJECTIVE: Leiomyoma is the most common benign tumor of the esophagus. Extra mucosal enucleation is the standard treatment. Herein we evaluated the feasibility and the outcomes of Minimally Invasive Surgery (MIS) using video-assisted thoracoscopic (VATS) or laparoscopic surgery (VALS) for esophageal leiomyoma enucleation. SUBJECTS AND METHODS: Retrospective study of patients who were treated via VATS or VALS for esophageal leiomyoma enucleation in "Hanoi Viet Duc Hospital" from 2010 to 2017 by the same operator. The operative approach, tumor size, complications and outcomes after surgery were recorded. RESULTS: Seventy-five patients were included. Mean age was 41.9 (range 20-68) years. The male/female sex ratio was 2.1:1. Fifty-five patients had clinical symptoms (73.3%). Tumors were identified in the upper third (12%), middle third (51%), and lower third (37%) of the esophagus. Mean tumor size was 3.7 (range 2-11) cm. VALS enucleation was performed in 23 patients who had leiomyoma located near the cardia (gastroesophageal junction or abdominal esophagus). The remaining 52 patients underwent right (n=42) or left VATS (n=10). Five patients (6.7%) sustained esophageal mucosa injury during dissection, repaired by MIS without late morbidity. A mini-incision (2 mini-laparotomies and 1 thoracotomy) was required in three patients (4%) due to large tumor size or mucosal injury. The mean operative time was 105min in VATS and 174min in VALS. No major perioperative surgical or medical complications were reported. The mean duration of hospital stay was 7.2 (range 5-12) days. CONCLUSIONS: MIS enucleation of esophageal leiomyoma is technically safe and associated with a high therapeutic success rate with low medico-surgical morbidity. VATS could be applied for almost all esophageal leiomyoma tumors; however, the VALS approach was preferred for tumors located near the gastroesophageal junction in order to create an anti-reflux valve after enucleation.

[Impact of the Lubrizol Rouen plant fire of September 26, 2019 on ophthalmic emergency room visits]. / Impact de l'incendie de l'usine Lubrizol à Rouen le 26 septembre 2019 sur la fréquentation des urgences ophtalmologiques.

INTRODUCTION: A fire at the Lubrizol chemical factory in Rouen on September 26, 2019 generated a huge column of smoke directed northeast toward the city. As the eye might be particularly affected by the smoke and other toxic emissions from the fire, we assessed the impact of this industrial and ecological disaster on irritative eye surface disease in the week following the accident. MATERIALS AND METHODS: We retrospectively collected the medical data of the patients who presented to the Ophthalmology Emergency Department (OED) of Rouen University Hospital (the only OED open during the days following the accident) during the week following the fire (W1). We compared these data with those of patients who presented during the week before the fire (W-1). We also collected data on patients presenting to the ED in general during W-1 and W1, including the number of visits directly related to the fire. RESULTS: 361 patients presented to the OED during W1 following the fire, compared with 384 in W-1. Of these patients, 83 (23%) had ocular surface disease in W1, versus 76 (20%) in W-1. Conjunctivitis was found in 54 patients in W1 (39 viral, 9 allergic, 6 undetermined) versus 44 in W-1 (27 viral, 12 allergic, 5 undetermined). A dry irritative syndrome was present in 29 patients in W1 versus 32 in W-1. Only 4 patients directly attributed their symptoms to the fire: 2 viral conjunctivitis, 1 allergic conjunctivitis and 1 worried patient (at D2, D5, D7 and D7 following the fire respectively). DISCUSSION: The number of emergency eye consultations did not change in the week following the Lubrizol factory fire (except for a decrease the day of the accident, related to the lock-down). There was a higher number of consultations in W1 for conjunctivitis, mostly viral in appearance and probably not directly related to the fire. The number of consultations for dry irritative syndrome was comparable between the two periods. Despite major media coverage of the event at the national level and a very high level of concern among the population, the fire does not seem to have had an effect on OED activity at Rouen University Hospital, nor on general ED visits. The stay-at-home order on the first day may have had a protective effect, avoiding direct exposure to smoke. The long-term consequences of the soot deposits on the ground as the smoke cloud passed over remain undetermined and are under surveillance. A review of the literature on the ocular consequences of industrial accidents is presented. CONCLUSION: The Ophthalmology Emergency Department did not record increased activity in the week following the Lubrizol Rouen fire, and ocular surface disease did not give rise to more consultations than the week before the fire. This suggests that there was no or minimal immediate ocular toxicity of the smoke from the fire.

Effect of overconditioning on the hepatic global gene expression pattern of dairy cows at the end of pregnancy.

Overconditioning is a risk factor for upregulated pre- and postpartum fat mobilization. Therefore, we hypothesized that overconditioning at the end of pregnancy leads to the accumulation of lipids in the liver and modifications of the hepatic gene expression pattern. The aim of this study was to evaluate the effect of normal- versus overconditioning on the hepatic transcriptomic profile of dairy cows at the end of pregnancy. Ten dry multiparous Holstein cows were killed 2 wk before expected calving. Body condition score (BCS) and backfat thickness (BFT) were evaluated, and blood samples for nonesterified fatty acids (NEFA) were taken before cows were killed. After cows were killed, liver biopsy samples were collected for further assessment of total lipids and RNA sequencing. Five cows were classified as normal-conditioned (median BCS = 3, range 2.75-3.5) and 5 as overconditioned (median BCS = 4, range 4-5). Regression models confirmed that normal-conditioned cows had lower BFT (1.29 ± 0.29 cm; least squares means ± standard error) and serum NEFA (0.16 ± 0.04 mmol/L) in comparison to overconditioned cows (3.14 ± 0.43 cm and 0.38 ± 0.07 mmol/L for BFT and NEFA, respectively). Total liver lipid percentage tended to be lower in normal- versus overconditioned cows (4.63 ± 0.40% and 6.06 ± 0.44%, respectively). In comparison to the mean liver lipid percentage of the normal- and overconditioned cows, 1 overconditioned cow had a relatively low (5.21%) and 1 normal-conditioned cow had a relatively high (6.07%) liver lipid percentage. Differentially expressed genes analysis (edgeR quasi-likelihood method) showed that normal-conditioned cows presented 11 upregulated and 12 downregulated genes in comparison to overconditioned cows. Linear discriminant analysis effects size revealed 133 differentially expressed genes between normal- versus overconditioned cows. Notably, the liver of normal-conditioned cows had upregulated genes associated with liver functionality (ALB, SELENOP, IGF1, and IGF2). On the other hand, overconditioned cows had upregulated genes associated with the acute-phase response (C3, HPX, and, LBP). High basal lipolysis in overconditioned cows at the end of pregnancy increased liver lipid content, and this may alter the hepatic gene expression pattern to a pro-inflammatory state.

Capacity of Trolox to improve the development and quality of metabolically compromised bovine oocytes and embryos invitro during different windows of development.

Trials to improve oocyte developmental competence under metabolic stress by using antioxidants may start before or after oocyte maturation. In the present conceptual study, we aimed to identify the most efficient timing of antioxidant application in relation to a metabolic insult using a bovine invitro embryo production model. Pathophysiological concentrations of palmitic acid (PA) were used to induce metabolic stress during oocyte maturation or embryo development. Trolox (TR; antioxidant) treatment prior to, during or after the PA insult was tested to evaluate the protective, neutralising and rescuing capacity of TR respectively. Changes in embryo developmental competence, mitochondrial activity, reactive oxygen species (ROS) concentrations, blastocyst cell allocation and apoptosis and cell stress-related gene expression were monitored. The improvement in developmental capacity was most obvious when oocytes were preloaded with TR before the PA insult. This protective effect could be explained by the observed combination of increased mitochondrial activity with reduced ROS production. This resulted in blastocysts with normal cell counts and apoptosis, as well as increased nuclear factor erythroid 2-related factor 2 (NRF2) expression (a marker for redox regulatory processes) and normalised the expression of the mitochondrial transcription factor A (TFAM), a marker of mitochondrial biogenesis. These results indicate that 'pretreatment' of oocytes with antioxidants produces embryos that seem to be more resilient to a metabolic stress insult.

Invasive rhino-orbital-cerebral aspergillosis in an immunocompetent patient.

INTRODUCTION: Rhino-orbital-aspergillosis (ROA) is a rare but serious disease in immunocompetent patients. Diagnosis is often delayed due to the absence of specific clinical symptoms. We describe the case of a patient who presented initially with ROA which spread progressively to the right ethmoid-sphenoid sinuses and then to the brain. OBSERVATION: A 61-year-old patient with a history of well-controlled diabetes presented with a sudden severe decrease in right visual acuity. Cerebral MRI showed the presence of an infiltrate in the right orbital apex extending to the homolateral cavernous sinus without any cerebral involvement. A diagnosis of right orbital myositis was made and corticosteroid therapy was started. His symptoms worsened progressively leading to quasi-blindness. A new MRI showed the development of right sphenoid-ethmoid osteolytic lesions. A fungal aetiology was suspected and tests for fungal biomarkers found a ß-(1-3)-D-glucan level of 99pg/ml but negative galactomannan. An ethmoid biopsy was performed for histological and mycological investigations, including the detection of Aspergillus DNA by qPCR. qPCR was positive and culture resulted in the isolation of multi-sensitive Aspergillus fumigatus. Treatment was initiated with voriconazole. Due to persistence of blindness and the appearance of a lesion extending to the right frontal lobe, surgical excision was performed followed by antifungal treatment for a total duration of 1year. The patient is currently stable, but has persistence of blindness in the right eye. CONCLUSION: Invasive ROA is a rare but serious disease in immunocompetent patients which should be evoked in the differential diagnosis of a tumour or vasculitis. Early diagnosis is essential for optimal management.

Altered embryotrophic capacities of the bovine oviduct under elevated free fatty acid conditions: an in vitro embryo--oviduct co-culture model.

Maternal metabolic stress conditions are of growing importance in both human and dairy cattle settings as they can have significant repercussions on fertility. Upregulated lipolysis is a common trait associated with metabolic disorders and results in systemically elevated concentrations of non-esterified fatty acids (NEFAs). The effects of high NEFA concentrations on the follicular environment, oocyte and embryo development is well documented. However, knowledge on the effects of NEFAs within the oviduct, representing the initial embryonic growth environment, is currently lacking. Therefore, the experiments outlined here were designed to obtain fundamental insights into both the direct and indirect interactions between NEFAs, bovine oviductal cells and developing zygotes. Hence, zygotes were co-cultured with NEFA-pre-exposed bovine oviductal cells or subjected to simultaneous NEFA exposure during the co-culture period. The outcome parameters assessed were embryo development with cleavage (48h post insemination (pi)), morula (120-126h pi) and blastocyst (192h pi) rates, as well as morula intracellular lipid content and blastocyst quality using Bodipy and differential staining respectively. Our data suggest a direct embryotoxicity of NEFAs as well as impaired embryo development through a reduced oviductal ability to support and protect early embryo development.

Ex vivo culture of mouse skin activates an interleukin 1 alpha-dependent inflammatory response.

Ex vivo culture of mouse and human skin causes an inflammatory response characterized by production of multiple cytokines. We used ex vivo culture of mouse tail skin specimens to investigate mechanisms of this skin culture-induced inflammatory response. Multiplex assays revealed production of interleukin 1 alpha (IL-1α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), chemokine C-X-C motif ligand 1 (CXCL1), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during skin culture, and quantitative PCR revealed transcripts for these proteins were also increased. Ex vivo cultures of skin from myeloid differentiation primary response 88 deficient mice (Myd88-/- ) demonstrated significantly reduced expression of transcripts for the aforementioned cytokines. The same result was observed with skin from interleukin 1 receptor type 1 deficient mice (Il1r1-/- ). These data suggested the IL-1R1/MyD88 axis is required for the skin culture-induced inflammatory response and led us to investigate the role of IL-1α and IL-1ß (the ligands for IL-1R1) in this process. Addition of IL-1α neutralizing antibody to skin cultures significantly reduced expression of Cxcl1, Il6 and Csf3. IL-1ß neutralization did not reduce levels of these transcripts. These studies suggest that IL-1α promotes the skin the culture-induced inflammatory response.

Is the pre-antral ovarian follicle the 'holy grail'for female fertility preservation?

Fertility preservation is not only a concern for humans with compromised fertility after cancer treatment. The preservation of genetic material from endangered animal species or animals with important genetic traits will also greatly benefit from the development of alternative fertility preservation strategies. In humans, embryo cryopreservation and mature-oocyte cryopreservation are currently the only approved methods for fertility preservation. Ovarian tissue cryopreservation is specifically indicated for prepubertal girls and women whose cancer treatment cannot be postponed. The cryopreservation of pre-antral follicles (PAFs) is a safer alternative for cancer patients who are at risk of the reintroduction of malignant cells. As PAFs account for the vast majority of follicles in the ovarian cortex, they represent an untapped potential, which could be cultivated for reproduction, preservation, or research purposes. Vitrification is being used more and more as it seems to yield better results compared to slow freezing, although protocols still need to be optimized for each specific cell type and species. Several methods can be used to assess follicle quality, ranging from simple viability stains to more complex xenografting procedures. In vitro development of PAFs to the pre-ovulatory stage has not yet been achieved in humans and larger animals. However, in vitro culture systems for PAFs are under development and are expected to become available in the near future. This review will focus on recent developments in (human) fertility preservation strategies, which are often accomplished by the use of in vitro animal models due to ethical considerations and the scarcity of human research material.

The role of hedonics in the Human Affectome.

Experiencing pleasure and displeasure is a fundamental part of life. Hedonics guide behavior, affect decision-making, induce learning, and much more. As the positive and negative valence of feelings, hedonics are core processes that accompany emotion, motivation, and bodily states. Here, the affective neuroscience of pleasure and displeasure that has largely focused on the investigation of reward and pain processing, is reviewed. We describe the neurobiological systems of hedonics and factors that modulate hedonic experiences (e.g., cognition, learning, sensory input). Further, we review maladaptive and adaptive pleasure and displeasure functions in mental disorders and well-being, as well as the experience of aesthetics. As a centerpiece of the Human Affectome Project, language used to express pleasure and displeasure was also analyzed, and showed that most of these analyzed words overlap with expressions of emotions, actions, and bodily states. Our review shows that hedonics are typically investigated as processes that accompany other functions, but the mechanisms of hedonics (as core processes) have not been fully elucidated.

Impact of a long-term antibiotic stewardship program targeting fluoroquinolones in a French local hospital.

INTRODUCTION: Fluoroquinolones (FQs) are major antibiotics but their wide use in hospital and community settings has led to an increased bacterial resistance against this antibiotic class. We aimed to assess the efficiency of an antibiotic stewardship program targeting FQs in a local hospital, and its impact on bacterial resistance. METHODS: This observational study was conducted in the local hospital of Morteau (Franche-Comté region, East of France). The hospital has 166 beds with health and medico-social sectors and a medical home affiliated with the facility. Local guidelines on empirical treatment regimens were released in 2007 aiming to reduce the use of FQs, especially for urinary tract infections. The following monitoring indicators were assessed: total consumption of antibiotics and of FQs (DDD/1,000 hospital patient-days), and resistance to nalidixic acid among Escherichia coli strains. Changes in the number of FQ packs sold in a community pharmacy were also recorded. RESULTS: The FQ consumption decreased by 85.6% between 2006 and 2015 (from 41.1 to 5.9 DDD/1,000 patient-days). The resistance to nalidixic acid among E. coli strains substantially decreased after remaining steady until 2011 (-57.2% between 2007 and 2015). The number of norfloxacin packs sold in the assessed community pharmacy decreased by 88%. CONCLUSION: Setting up an antibiotic stewardship program in a local hospital can lead to a substantial reduction in FQ use and in E. coli resistance to FQs. It may also have a positive impact on community prescriptions.

The effect of elevated non-esterified fatty acid concentrations on bovine spermatozoa and on oocyte in vitro fertilisation.

Elevated non-esterified fatty acid (NEFA) concentrations, present in follicular and oviductal fluid, have been postulated as a causative link between metabolic disorders and subfertility. High NEFA conditions can directly disrupt oocyte maturation and developmental capacity after fertilisation. However, their influence on sperm function and the fertilisation process is not known. This study investigated the fertilisation process under high NEFA conditions. To differentiate between effects on both spermatozoa and oocytes or on spermatozoa only, different experiments were conducted. In the first experiment both gametes were simultaneously incubated during IVF under different conditions: (1) NEFA-free, solvent-free control conditions, (2) solvent control, (3) physiological concentrations of oleic (OA), palmitic (PA) and stearic (SA) acids or (4) pathophysiological concentrations of OA, PA and SA. In the second experiment spermatozoa were incubated (4h) under the same treatment conditions prior to routine IVF. Gamete co-incubation resulted in reduced fertilisation and cleavage rates and increased prevalence of polyspermy. In the second experiment embryo developmental capacity and quality were not affected, although sperm motility and plasma membrane integrity were decreased. In conclusion, lipolytic conditions affected the fertilisation process mainly through an effect on the oocyte. Spermatozoa were still able to fertilise even though these conditions reduced sperm function.

Examining the Potential for Agricultural Benefits from Pollinator Habitat at Solar Facilities in the United States.

Of the many roles insects serve for ecosystem function, pollination is possibly the most important service directly linked to human well-being. However, land use changes have contributed to the decline of pollinators and their habitats. In agricultural landscapes that also support renewable energy developments such as utility-scale solar energy [USSE] facilities, opportunities may exist to conserve insect pollinators and locally restore their ecosystem services through the implementation of vegetation management approaches that aim to provide and maintain pollinator habitat at USSE facilities. As a first step toward understanding the potential agricultural benefits of solar-pollinator habitat, we identified areas of overlap between USSE facilities and surrounding pollinator-dependent crop types in the United States (U.S.). Using spatial data on solar energy developments and crop types across the U.S., and assuming a pollinator foraging distance of 1.5 km, we identified over 3,500 km2 of agricultural land near existing and planned USSE facilities that may benefit from increased pollination services through the creation of pollinator habitat at the USSE facilities. The following five pollinator-dependent crop types accounted for over 90% of the agriculture near USSE facilities, and these could benefit most from the creation of pollinator habitat at existing and planned USSE facilities: soybeans, alfalfa, cotton, almonds, and citrus. We discuss how our results may be used to understand potential agro-economic implications of solar-pollinator habitat. Our results show that ecosystem service restoration through the creation of pollinator habitat could improve the sustainability of large-scale renewable energy developments in agricultural landscapes.

Development of a landscape integrity model framework to support regional conservation planning.

Land managers increasingly rely upon landscape assessments to understand the status of natural resources and identify conservation priorities. Many of these landscape planning efforts rely on geospatial models that characterize the ecological integrity of the landscape. These general models utilize measures of habitat disturbance and human activity to map indices of ecological integrity. We built upon these modeling frameworks by developing a Landscape Integrity Index (LII) model using geospatial datasets of the human footprint, as well as incorporation of other indicators of ecological integrity such as biodiversity and vegetation departure. Our LII model serves as a general indicator of ecological integrity in a regional context of human activity, biodiversity, and change in habitat composition. We also discuss the application of the LII framework in two related coarse-filter landscape conservation approaches to expand the size and connectedness of protected areas as regional mitigation for anticipated land-use changes.