Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

The role of the dentist and the orthodontist in early diagnosis of Gorlin-Goltz syndrome: a cephalometric and photometric study.

AIM: The aim of this study was to analyse the facial characteristics and the craniofacial morphology in GGS patients in order to enable an early diagnosis. BACKGROUND: Gorlin-Goltz syndrome (GGS) is a autosomic dominant disease, characterised by basal cell carcinoma, palmar/plantar pits, maxillary and mandibular keratocysts and dental abnormalities. METHODS: Nine out of a sample of 24 GGS patients had complete cephalometric and photographic records at an average age of 8.7 years. Cephalometric and photometric analysis were carried out with standard analyses and compared with healthy patients matched for sex and age. CONCLUSION: Early diagnosis of GGS based on clinical features could be useful to identify the presence of keratocysts through x-ray examination proceeding with surgical removal at an early stage, limiting space occupying damages.

The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

Nasoalveolar molding and skeletal development in patients with bilateral cleft lip and palate: A retrospective cephalometric study at the completion of growth.

The aim of this retrospective long-term study was to assess the influence of primary columella lengthening and presurgical nasoalveolar molding (NAM) on the skeletal development at the completion of growth in patients with bilateral cleft lip and palate (BCLP). Lateral cephalometric radiographs at the completion of growth of consecutively treated patients BCLP patients, operated by the same surgeon, who had undergone NAM were compared with a second group of BCLP patients who were not treated with NAM. The groups were matched for sex and age. Independent samples t tests were carried out. 23 Lateral cephalometric radiographs of BCLP patients (mean age 18.2 ± 1.3 years) who had undergone NAM were compared with a second group of 23 BCLP patients (mean age 18.4 ± 1.3 years) who were not treated with NAM. The only two significant differences were observed in Ans-Me/N-Me (control group = 0.6 ± 0.02; sample group = 0.57 ± 0.05; p = 0.019) and ILs^AnsPns (control group = 105.5 ± 7.9; sample group = 112.4 ± 8.6; p = 0.007). No other significant differences were observed in terms of facial skeletal development between the two groups. Presurgical NAM performed during infancy in BCLP patients does not seem to have negative effects on the skeletal development at the completion of craniofacial growth compared to the group of patients treated without NAM.

Non-surgical treatment of vertical excess of the premaxilla in growing bilateral cleft lip and palate patients.

Patients with bilateral complete cleft lip and palate (BCLP) may present a vertical excess of the premaxilla in childhood. This is a severe functional and aesthetic problem, where bone grafting is more challenging. The aim of this study was to describe a simple and reproducible non-surgical orthopaedic treatment for vertical excess of the premaxilla in the deciduous/early mixed dentition phase in BCLP patients. Six growing patients with complete BCLP with a severe vertical excess of the premaxilla were included. An intrusion device associated with a bonded rapid palatal expander was applied to intrude the premaxilla. Radiographic and photographic records obtained before and at the end of the orthodontic intrusion, at short- and long-term follow-up, were available. A flattening of the occlusal plane was achieved in all patients. Normalization of the position of the maxillary incisors and gingival display in relation to the upper lip was obtained, and an improvement in anterior nasal spine position was also observed in all cases. The novel technique described might be of assistance in treating BCLP children with vertical excess of the premaxilla during the deciduous/early mixed dentition phase. This simplified, easily reproducible method may allow the burden of care of this rare but complex problem affecting BCLP patients to be reduced significantly.

Targeted differential illumination improves reproductive traits of broiler breeder males.

Artificial targeted illumination has a pivotal role in reproductive processes of poultry. The light-absorption mechanism in birds consists of 2 main components: the eye (retinal photoreceptors) and extraretinal photoreceptors located in the brain. Previous studies conducted on hens have shown that photostimulation of brain extraretinal photoreceptors elevates reproductive activity, whereas retinal photostimulation suppresses it. We tested the effect of targeted differential photostimulation (TDP) on reproductive activities of broiler breeder males. Fifty broiler breeder roosters (Ross), 21 wk of age, were divided into 5 environmentally controlled light-treatment rooms (n = 10) equipped with individual cages. Rooms 1 and 2 had 2 parallel lighting systems consisting of red light (630 nm) and green light (514 nm), and rooms 3 and 4 had parallel red and blue (456 nm) lighting systems. Room 5, illuminated with white light, served as the control. Birds of all groups were kept under short day (6L:18D) for 2 wk with both lighting systems in each treatment room turned on. At 23 wk of age, birds were photostimulated by gradually increasing one of the lighting systems to 14 h of light in each room, while the other lighting system was left on short day (6L:18D). Weekly semen samples were collected until 65 wk of age and analyzed for volume, motility, concentration and vitality. Monthly blood samples were drawn for plasma hormone assays. At 65 wk of age, roosters were euthanized and hypothalamus, pituitary gland, retina and testes samples were taken for mRNA expression analysis. TDP using long-day red light and short-day green light significantly increased reproductive performance, manifested by higher semen volume, motility and concentration, and testis weight; furthermore, this group had higher plasma testosterone levels, higher GnRH mRNA expression in the hypothalamus, lower levels of aromatase in the testes, and lower mRNA expression of hypothalamic serotonin transporter, and of pituitary prolactin and its receptors in the testes. This is the first study showing a positive effect of TDP on reproduction of broiler breeder roosters.

In ovo green light photostimulation during the late incubation stage affects somatotropic axis activity.

Targeted green light photostimulation during the last stage of broiler incubation increases expression of the somatotropic axis. The purpose of this study was to further shorten the in ovo green light photostimulation and determine the critical age for photostimulation in broilers embryos, as a future strategy for broiler incubation. Fertile broilers eggs (n = 420) were divided into 5 treatment groups. The first group was incubated under standard conditions (in the dark) as the negative control group. The second was incubated under intermittent monochromatic green light using light-emitting diode lamps with an intensity of 0.1 W/m2 at shell level from embryonic day (ED) 0 of incubation until hatch, as a positive control. The third, fourth, and fifth groups were incubated under intermittent monochromatic green light from ED 15, 16, and 18 of incubation, respectively, until hatch. All treatment groups showed elevated somatotropic axis expression compared with the negative control, with the group incubated under monochromatic green light from ED 18 until hatch showing results closest to the positive control. This suggests that broiler embryos can be exposed to in ovo green light photostimulation from a late stage of incubation (when transferring the eggs to the hatchery) and exhibit essentially the same outcome as obtained by photostimulation during the entire incubation period.

European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

The quality of informed consent obtained for orthopedic surgeries-elective versus trauma: A prospective interview-based study.

BACKGROUND: Orthopedic surgeons routinely obtain informed consent prior to surgery. Legally adequate informed consent necessitates a thorough discussion of treatment options and risks and proper documentation. However, the quality of informed consent in orthopedic trauma patients is an under-researched area. PURPOSE: To assess the quality of the informed consent process in trauma compared with elective orthopedic patients and to assess patients' emotional state at the time of signing consent form. METHODS: Sixty-two consecutive patients undergoing either elective total joint arthroplasty ( N = 32) or orthopedic trauma surgery ( N = 30) were included. The data were collected through personal interviews using a proposed informed consent score. The interviews were held after obtaining the informed consent and before the index procedure. Patients were asked to describe their diagnosis, the surgical procedure, its' benefits, and risks as well as alternative treatments. RESULTS: Mean age differed significantly between elective and trauma group patients (66.1 vs. 51.6, respectively, p < 0.01), while gender and education level were comparable ( p = 0.075, p = 0.55, respectively). The quality of consent was significantly better for patients with post-high-school education compared to elementary education level (consent score: 16.9 ± 4.1 vs. 12.2 ± 5.5, p = 0.021). Patients in the elective group showed an overall higher quality of consent, as reflected by a mean score of 17.03 ± 4.2 versus a mean score of only 13.73 ± 4.7 in the trauma group ( p = 0.005, 95% CI: 1.02-5.57). Specifically, trauma patients demonstrated a lower comprehension of the diagnosis, the benefits of surgical treatment, the possible complications, and the expected postoperative course. CONCLUSION: Patients undergoing trauma surgery are significantly more likely to have an inadequate understanding of the proposed treatment. These findings raise questions concerning the validity of consent from trauma patients.

Impact of QuickFISH in addition to antimicrobial stewardship on vancomycin use and resource utilization in cancer patients with coagulase-negative staphylococcal blood cultures.

OBJECTIVE: To evaluate the impact of rapidly identifying coagulase-negative staphylococci (CoNS) from positive blood cultures combined with an established antimicrobial stewardship (AS) programme at a tertiary cancer centre. METHODS: We compared cancer patients ≥18 years old who between 01/1/13 and 12/31/13 had one or more positive CoNS blood culture(s) identified by Staphylococcus QuickFISH® (a peptide nucleic acid fluorescence in situ hybridization assay) with cancer patients ≥18 years old who had CoNS identified by standard microbiological techniques between 01/01/11 and 12/31/11 (baseline). Positive blood culture results were reported to the clinician by microbiology staff; restricted antibiotics (e.g., vancomycin) required approval by the AS team. RESULTS: There were 196 baseline and 103 QuickFISH patients. Faster median time to organism identification (33 (IQR 27-46) versus 49 (IQR 39-63) hours, p < 0.001), more vancomycin avoidance (51/103 (50%) versus 60/196 (31%), p 0.002), shorter median antibiotic duration (1 (IQR 0-3) versus 2 (IQR 0-6) days, p 0.019), fewer central venous catheter (CVC) removals (14/78 (18%) versus 57/160 (36%), p 0.004), and reduced vancomycin level monitoring (16/52 (31%) versus 71/136 (52%), p 0.009) were observed in the QuickFISH group. QuickFISH implementation was predictive of a lower likelihood of antibiotic therapy prescription (OR 0.35, 95%CI 0.20-0.62, p < 0.001). Prior transplant (RR 1.47, 95%CI 1.13-1.92, p 0.004), neutropenia (RR 1.47, 95%CI 1.09-1.99, p 0.012), multiple positive blood cultures (RR 4.23, 95%CI 3.23-5.54, p < 0.001), and CVC (RR 1.60, 95%CI 1.02-2.53, p 0.043) were independent factors for antibiotic duration. CONCLUSIONS: QuickFISH implementation plus AS support leads to greater avoidance of vancomycin therapy and improved resource utilization in cancer patients with CoNS blood cultures.

The Prostate Cancer Rehabilitation Clinic: a biopsychosocial clinic for sexual dysfunction after radical prostatectomy.

Purpose: The most prevalent intervention for localized prostate cancer (pca) is radical prostatectomy (rp), which has a 10-year relative survival rate of more than 90%. The improved survival rate has led to a focus on reducing the burden of treatment-related morbidity and improving the patient and partner survivorship experience. Post-rp sexual dysfunction (sdf) has received significant attention, given its substantial effect on patient and partner health-related quality of life. Accordingly, there is a need for sdf treatment to be a fundamental component of pca survivorship programming. Methods: Most research about the treatment of post-rp sdf involves biomedical interventions for erectile dysfunction (ed). Although findings support the effectiveness of pro-erectile agents and devices, most patients discontinue use of such aids within 1 year after their rp. Because side effects of pro-erectile treatment have proved to be inadequate in explaining the gap between efficacy and ongoing use, current research focuses on a biopsychosocial perspective of ed. Unfortunately, there is a dearth of literature describing the components of a biopsychosocial program designed for the post-rp population and their partners. Results: In this paper, we detail the development of the Prostate Cancer Rehabilitation Clinic (pcrc), which emphasizes multidisciplinary intervention teams, active participation by the partner, and a broad-spectrum medical, psychological, and interpersonal approach. Conclusions: The goal of the pcrc is to help patients and their partners achieve optimal sexual health and couple intimacy after rp, and to help design cost-effective and beneficial rehabilitation programs.

Surgical correction of mandibular hypoplasia in hemifacial microsomia: A retrospective study in 39 patients.

PURPOSE: Repair of the mandibular deformity in hemifacial microsomia (HFM) remains controversial, and there is scant information in the literature regarding the late outcomes. The aim of this study was to evaluate architectural and aesthetic long-term outcomes for primary mandibular surgery in patients with HFM. MATERIALS AND METHODS: Thirty-nine patients with types II and type III HFM were included in this retrospective study. Depending on the nature of the mandibular deformity, patients were treated using a costochondral graft (CCG) or a vertical ramus osteotomy (VRO). Architectural and aesthetic parameters were evaluated preoperatively, postoperatively, and at the end of the follow-up period. RESULTS: The architectural analysis revealed the restoration of a level occlusal canting at the end of the follow-up period (p < 0.0001); the chin deviation was corrected immediately by the surgery, although a trend to recurrence was noted at the last follow-up evaluation (p < 0.0001). The aesthetic assessment revealed a significant improvement of the chin deflection, and correction of the lip commissural line tilt (p < 0.0001). Twenty-three percent of the patients required an additional orthognathic revision. CONCLUSION: CCG and VRO continue to be suitable and safe procedures with good outcomes that allow a single-stage correction of occlusion and preservation of mandibular growth in young patients with type II and type III HFM.

Fibroblasts drive an immunosuppressive and growth-promoting microenvironment in breast cancer via secretion of Chitinase 3-like 1.

Cancer-Associated Fibroblasts (CAFs) are the most prominent stromal cell type in breast tumors. CAFs promote tumor growth and metastasis by multiple mechanisms, including by mediating tumor-promoting inflammation. Immune modulation in the tumor microenvironment plays a central role in determining disease outcome. However, the functional interactions of CAFs with immune cells are largely unknown. Here we report a novel signaling axis between fibroblasts, cancer cells and immune cells in breast tumors that drives an immunosuppressive microenvironment, mediated by CAF-derived Chi3L1. We demonstrate that Chi3L1 is highly upregulated in CAFs isolated from mammary tumors and pulmonary metastases of transgenic mice, and in the stroma of human breast carcinomas. Genetic ablation of Chi3L1 in fibroblasts in vivo attenuated tumor growth, macrophage recruitment and reprogramming to an M2-like phenotype, enhanced tumor infiltration by CD8+ and CD4+ T cells and promoted a Th1 phenotype. These results indicate that CAF-derived Chi3L1 promotes tumor growth and shifts the balance of the immune milieu towards type 2 immunity. Taken together, our findings implicate fibroblast-derived Chi3L1 as a novel key player in the complex reciprocal interactions of stromal cells that facilitate tumor progression and metastasis, and suggest that targeting Chi3L1 may be clinically beneficial in breast cancer.

EACR-MRS conference on Seed and Soil: In Vivo Models of Metastasis.

New experimental tools are urgently required to better understand the metastatic process. The importance of such tools is underscored by the fact that many anti-cancer therapies are generally ineffective against established metastases. This makes a major contribution to the fact that metastatic spread is responsible for over 90% of cancer patient deaths. It was therefore timely that the recent "Seed and Soil: In Vivo Models of Metastasis" conference held in Berlin, Germany (27-29 of November 2017) aimed to give an in-depth overview of the latest research models and tools for studying metastasis, and to showcase recent findings from world-leading metastasis researchers. This Meeting Report summarises the major themes of this ground-breaking conference.

Dynamic analysis of immune and cancer cell interactions at single cell level in microfluidic droplets.

Cell-cell communication mediates immune responses to physiological stimuli at local and systemic levels. Intercellular communication occurs via a direct contact between cells as well as by secretory contact-independent mechanisms. However, there are few existing methods that allow quantitative resolution of contact-dependent and independent cellular processes in a rapid, precisely controlled, and dynamic format. This study utilizes a high-throughput microfluidic droplet array platform to analyze cell-cell interaction and effector functions at single cell level. Controlled encapsulation of distinct heterotypic cell pairs was achieved in a single-step cell loading process. Dynamic analysis of dendritic cell (DC)-T cell interactions demonstrated marked heterogeneity in the type of contact and duration. Non-stimulated DCs and T cells interacted less frequently and more transiently while antigen and chemokine-loaded DCs and T cells depicted highly stable interactions in addition to transient and sequential contact. The effector function of CD8+ T cells was assessed via cytolysis of multiple myeloma cell line. Variable cell conjugation periods and killing time were detected irrespective of the activation of T cells, although activated T cells delivered significantly higher cytotoxicity. T cell alloreactivity against the target cells was partially mediated by secretion of interferon gamma, which was abrogated by the addition of a neutralizing antibody. These results suggest that the droplet array-based microfluidic platform is a powerful technique for dynamic phenotypic screening and potentially applicable for evaluation of novel cell-based immunotherapeutic agents.

Erdheim-Chester disease: 25-year history with early CNS involvement.

We report a case of Erdheim-Chester disease (ECD) with a 25-year history following initial presentation with diabetes insipidus and brainstem involvement. The exceptionally long history is particularly notable, given that ECD is a life-threatening disorder and there is a recognised association between central nervous system involvement and poor outcome. The case is a timely reminder of the presenting features of the condition, given the emergence of potential new treatment options.

Generation and functional assessment of 3D multicellular spheroids in droplet based microfluidics platform.

Here we describe a robust, microfluidic technique to generate and analyze 3D tumor spheroids, which resembles tumor microenvironment and can be used as a more effective preclinical drug testing and screening model. Monodisperse cell-laden alginate droplets were generated in polydimethylsiloxane (PDMS) microfluidic devices that combine T-junction droplet generation and external gelation for spheroid formation. The proposed approach has the capability to incorporate multiple cell types. For the purposes of our study, we generated spheroids with breast cancer cell lines (MCF-7 drug sensitive and resistant) and co-culture spheroids of MCF-7 together with a fibroblast cell line (HS-5). The device has the capability to house 1000 spheroids on chip for drug screening and other functional analysis. Cellular viability of spheroids in the array part of the device was maintained for two weeks by continuous perfusion of complete media into the device. The functional performance of our 3D tumor models and a dose dependent response of standard chemotherapeutic drug, doxorubicin (Dox) and standard drug combination Dox and paclitaxel (PCT) was analyzed on our chip-based platform. Altogether, our work provides a simple and novel, in vitro platform to generate, image and analyze uniform, 3D monodisperse alginate hydrogel tumors for various omic studies and therapeutic efficiency screening, an important translational step before in vivo studies.

Phenotypic drug profiling in droplet microfluidics for better targeting of drug-resistant tumors.

Acquired drug resistance is a key factor in the failure of chemotherapy. Due to intratumoral heterogeneity, cancer cells depict variations in intracellular drug uptake and efflux at the single cell level, which may not be detectable in bulk assays. In this study we present a droplet microfluidics-based approach to assess the dynamics of drug uptake, efflux and cytotoxicity in drug-sensitive and drug-resistant breast cancer cells. An integrated droplet generation and docking microarray was utilized to encapsulate single cells as well as homotypic cell aggregates. Drug-sensitive cells showed greater death in the presence or absence of Doxorubicin (Dox) compared to the drug-resistant cells. We observed heterogeneous Dox uptake in individual drug-sensitive cells while the drug-resistant cells showed uniformly low uptake and retention. Dox-resistant cells were classified into distinct subsets based on their efflux properties. Cells that showed longer retention of extracellular reagents also demonstrated maximal death. We further observed homotypic fusion of both cell types in droplets, which resulted in increased cell survival in the presence of high doses of Dox. Our results establish the applicability of this microfluidic platform for quantitative drug screening in single cells and multicellular interactions.

Role of the serotonergic axis in the reproductive failure associated with aging broiler breeder roosters.

Reproductive failure associated with aging is a well-known phenomenon. However, the mechanism by which this failure occurs in broiler breeder roosters is still unclear. A previous study conducted in our laboratory, comparing young and aging broiler breeder roosters, demonstrated an elevation in hypothalamic vasoactive intestinal peptide (VIP) and pituitary prolactin (PRL) gene expression accompanied by a deterioration of gonadal axis function. This resulted in a decrease in semen-quality variables as roosters aged. The objective of this study was to examine the involvement of the serotonergic axis in the age-associated reproductive failure in broiler breeder roosters. Cobb roosters aged 64 wk were divided into 3 groups (n = 20 each): parachlorophenylalanine (PCPA) administration, active immunization against chicken VIP, and controls. At 69 wk of age, each group was divided into 2 equal subgroups: 1 received ovine PRL and the other served as controls. Weekly semen volume, concentration and motility, and plasma testosterone, estradiol, and PRL concentrations were examined. At the end of the experiment, roosters were euthanized, testes were weighed, and hypothalamus and pituitary were removed to assay the expression of genes encoding hypothalamic GnRH-I, pituitary FSH, pituitary LH, hypothalamic VIP, and pituitary PRL. Both PCPA administration and active immunization against chicken VIP significantly increased testis weight, semen volume, sperm concentration, ejaculation grade, plasma testosterone level, and GnRH-I, FSH and LH gene expression compared with controls (P ≤ 0.05). In addition, a decrease in plasma estradiol and PRL concentrations and VIP and PRL gene expression was observed in PCPA- and VIP-immunized birds compared with controls (P ≤ 0.05). Administration of PRL in all groups decreased gonadal axis function and semen-quality variables (P ≤ 0.05). Collectively, these results suggest that the increasing expression levels of the serotonergic axis in aging broiler breeder roosters inhibit proper gonadal function and reproductive performance. This article establishes for the first time the inhibitory role of serotonin on reproduction in aging roosters.

Long-term tolerance and efficacy of adjunctive exenatide therapy on glycaemic control and bodyweight in type 2 diabetes: a retrospective study from a specialist diabetes outpatient clinic.

BACKGROUND: Weight gain and hypoglycaemia are common adverse effects associated with anti-diabetic treatments. AIM: Our aim was to evaluate the long-term effects of adjunctive exenatide therapy on weight loss and glycaemic control in patients with type 2 diabetes. METHODS: A review of medical records in a specialist diabetes clinic over 5 years identified 446 patients who were prescribed exenatide therapy. We examined change in glycosylated haemoglobin (HbA1c), weight, albumin-creatinine ratio and hypoglycaemic medication during 24 months follow up. RESULTS: Subjects were aged 59 ± 10 years (49% women) and received exenatide in combination with oral agents and insulin (47%). During an average of 17 ± 14 months follow up, 51% (more women than men; odds ratio 1.69, 95% confidence interval 1.14­2.49) remained on treatment. Lack of efficacy (33%) and/or gastrointestinal (27%) side-effects were the main reasons for treatment cessation. At 24 months, there was a reduction in HbA1c of 0.7 ± 1.2% and weight loss of 4.3 ± 5.2 kg. Change in HbA1c was similar regardless of concurrent insulin therapy, yet insulin was associated with greater weight reduction (4.8 ± 5.3 vs 3.8 ± 5.1 kg, P = 0.016). Independent predictors of HbA1c response were higher baseline HbA1c, longer duration of diabetes and use of insulin or sulfonylureas at study end. Predictors of weight response were baseline use of insulin or thiazolidinediones, increased age, female sex and sulfonylurea or thiazolidinediones at study end. Longer exenatide treatment duration was favourable for reducing HbA1c and weight. CONCLUSIONS: Exenatide is effective in reducing HbA1c and weight, regardless of concurrent insulin, and in a specialist diabetes outpatient clinic, is recommended for use in clinical practice.