Sleep Position Detection for Closed-Loop Treatment of Sleep-Related Breathing Disorders.

Reliable detection of sleep positions is essential for the development of technical aids for patients with position-dependent sleep-related breathing disorders. We compare personalized and generalizable sleeping position classifiers using unobtrusive eight-channel pressure-sensing mats. Data of six male patients with confirmed position-dependent sleep apnea was recorded during three subsequent nights. Personalized position classifiers trained using leave-one-night-out cross-validation on average reached an F1-score of 61.3% for supine/non-supine and an F1-score of 46.2% for supine/lateral-left/lateral-right classification. The generalizable classifiers reached average F1-scores of 62.1% and 49.1% for supine/non-supine and supine/lateral-left/lateral-right classification, respectively. In-bed presence ("bed occupancy") could be detected with an average F1-score of 98.1%. This work shows that personalized sleep-position classifiers trained with data from two nights have comparable performance to classifiers trained with large interpatient datasets. Simple eight-channel sensor mattresses can be used to accurately detect in-bed presence required for closed-loop systems but their use to classify sleep-positions is limited.

Correction to: Unexpected high frequency of neurofibroma in the celiac ganglion of German cattle.

An amendment to this paper has been published and can be accessed via the original article.

Unexpected high frequency of neurofibroma in the celiac ganglion of German cattle.

In a study originally designed to find potential risk factors for bovine spongiform encephalopathy (BSE) we examined tissues from 403 Holstein Frisian cattle in total. These included 20 BSE cattle and their 236 birth- and feeding cohort animals plus 32 offspring, 103 age, breed and district-matched control cattle and further twelve cattle with neurological signs. In addition to the obex, we examined the celiac ganglion, cervical cranial ganglion, trigeminal ganglion and proximal ganglion of the vagus nerve using histological techniques. Unexpectedly, we found a high number of neurofibroma, a benign peripheral nerve sheath tumor consisting of Schwann cells, fibroblasts and perineural cells. The neurofibroma were present only in the celiac ganglion and found during histologic examination. With a frequency of 9.91% in BSE cattle and their cohorts (case animals) and 9.09% in the age, breed and district matched control animals there seems to be no correlation between the occurrence of BSE and neurofibroma. Benign peripheral nerve sheath tumors have been described more often in cattle than in other domestic animals. Usually, they are incidental macroscopic findings in the thoracic ganglia during meat inspection. To our knowledge, there are no previous systematic histologic studies including bovine celiac ganglia at all. The high incidence of celiac ganglia neurofibroma may play a role in the frequently occurring abomasal displacements in Holstein Frisian cattle as the tumors might cause a gastrointestinal motility disorder. At present a genetic predisposition for these neoplasms cannot be ruled out.

Noninvasive assessment of the common carotid artery hemodynamics with increasing exercise work rate using wave intensity analysis.

Noninvasively determined local wave speed ( c) and wave intensity (WI) parameters provide insights into arterial stiffness and cardiac-vascular interactions in response to physiological perturbations. However, the effects of incremental exercise and subsequent recovery on c and WI have not been fully established. We examined the changes in c and WI parameters in the common carotid artery (CCA) during exercise and recovery in eight young, healthy male athletes. Ultrasound measurements of CCA diameter and blood flow velocity were acquired at rest, during five stages of incremental exercise (up to 70% maximum work rate), and throughout 1 h of recovery, and noninvasive WI analysis [diameter-velocity ( DU) approach] was performed. During exercise, c increased (+136%), showing increased stiffness with work rate. All peak and area of forward compression, backward compression, and forward expansion waves increased during exercise (+452%, +700%, and +900%, respectively). However, WI reflection indexes and CCA resistance did not significantly change from rest to exercise. Furthermore, wave speed and the magnitude of all waves returned to baseline within 5 min of recovery, suggesting that the effects of exercise in the investigated parameters of young, healthy individuals were transient. In conclusion, incremental exercise was associated with an increase in local CCA stiffness and increases in all wave parameters, indicative of enhanced ventricular contractility and improved late-systolic blood flow deceleration. NEW & NOTEWORTHY We examined hemodynamics of the common carotid artery using noninvasive application of wave intensity analysis during exercise and recovery. The hemodynamic adjustments to exercise were associated with increases in local common carotid artery stiffness and all waves' parameters, with the latter indicating enhanced ventricular contractility and improved late systolic blood flow deceleration.

Recovery of ammonium from aqueous solutions using ZSM-5.

The demand of reactive nitrogen (N), such as ammonium (NH4+) and nitrate (NO3-), continues to increase for fertilizer applications as the population grows, but the Haber Bosch (HB) process currently employed for industrial N fixation is challenged by low efficiency and high energy consumption. Here we report on the investigation of ZSM-5 as a superior sorbent for the recovery of ammonium from aqueous solutions. Fast capture and release of ammonium (NH4+) have been achieved with >90% overall efficiency of recovery using synthetic solutions of NH4Cl and NaCl, respectively. The ZSM-5 sorbent has also been found to be recyclable and sustain high recovery efficiencies after multiple capture-release cycles. The capture of N has been further studied systematically in dependence of the dose of sorbent and reaction temperature, based on which the mechanism, thermodynamics and kinetics of ion exchange are discussed. Compared to other ion-exchange materials, the ZSM-5 sorbent exhibits superior selectivity for capturing ammonium in the presence of competing cations (NH4+ ¼ Ca2+ > Mg2+ > K+ > Na+) and demonstrates high efficiency of ammonium recovery from real wastewater streams.

Morgagnian cataract resulting from a naturally occurring nonsense mutation elucidates a role of CPAMD8 in mammalian lens development.

To investigate the genetic basis of hereditary lens opacities we analyzed 31 cases of bilateral congenital cataract in Red Holstein Friesian cattle. A genome-wide association study revealed a significant association on bovine chromosome 7 at positions 6,166,179 and 12,429,691. Whole genome re-sequencing of one case and four relatives showed a nonsense mutation (g.5995966C>T) in the PZP-like, alpha-2-macroglobulin domain containing 8 (CPAMD8) gene leading to a premature stop codon (CPAMD8 p.Gln74*) associated with cataract development in cattle. With immunohistochemistry we confirmed a physiological expression of CPAMD8 in the ciliary body epithelium of the eye in unaffected cattle, while the protein was not detectable in the ciliary body of cattle with cataracts. RNA expression of CPAMD8 was detected in healthy adult, fetal and cataractous lenses.

A genome-wide association study reveals a locus for bilateral iridal hypopigmentation in Holstein Friesian cattle.

BACKGROUND: Eye pigmentation abnormalities in cattle are often related to albinism, Chediak-Higashi or Tietz like syndrome. However, mutations only affecting pigmentation of coat color and eye have also been described. Herein 18 Holstein Friesian cattle affected by bicolored and hypopigmented irises have been investigated. RESULTS: Affected animals did not reveal any ophthalmological or neurological abnormalities besides the specific iris color differences. Coat color of affected cattle did not differ from controls. Histological examination revealed a reduction of melanin pigment in the iridal anterior border layer and stroma in cases as cause of iris hypopigmentation. To analyze the genetics of the iris pigmentation differences, a genome-wide association study was performed using Illumina BovineSNP50 BeadChip genotypes of the 18 cases and 172 randomly chosen control animals. A significant association on bovine chromosome 8 (BTA8) was identified at position 60,990,733 with a -log10(p) = 9.17. Analysis of genotypic and allelic dependences between cases of iridal hypopigmentation and an additional set of 316 randomly selected Holstein Friesian cattle controls showed that allele A at position 60,990,733 on BTA8 (P = 4.0e-08, odds ratio = 6.3, 95% confidence interval 3.02-13.17) significantly increased the chance of iridal hypopigmentation. CONCLUSIONS: The clinical appearance of the iridal hypopigmentation differed from previously reported cases of pigmentation abnormalities in syndromes like Chediak-Higashi or Tietz and seems to be mainly of cosmetic character. Iridal hypopigmentation is caused by a reduced content of melanin pigment in the anterior border layer and iridal stroma. A single genomic position on BTA8 was detected to be significantly associated with iridal hypopigmentation in examined cattle. To our knowledge this is the first report about this phenotype in Holstein Friesian cattle.

Correction: The Holstein Friesian Lethal Haplotype 5 (HH5) Results from a Complete Deletion of TBF1M and Cholesterol Deficiency (CDH) from an ERV-(LTR) Insertion into the Coding Region of APOB.

[This corrects the article DOI: 10.1371/journal.pone.0154602.].

[Hyperthyroid and acute tonsillitis in a 23-year-old woman]. / Hyperthyreose und akute Tonsillitis bei einer 23-jährigen Patientin.

A 23-year-old woman with preexisting Graves' disease who received thiamazole treatment presented with fever, dysphagia, hyperthyroidism and leukopenia. With suspicion of thyreotoxicosis accompanied by drug-induced agranulocytosis she was successfully managed by plasmapheresis, G­CSF administration and inhibition of periphereal conversion of thyroid hormones. In due course she underwent thyroidectomy. Thiamazole is frequently associated with drug-induced agranulocytosis. Long-term therapy with thiamazole requires critical evaluation and alternatives should be considered early. Plasmapheresis is an adequate treatment option to achieve normal thyroid hormonal status.

The Holstein Friesian Lethal Haplotype 5 (HH5) Results from a Complete Deletion of TBF1M and Cholesterol Deficiency (CDH) from an ERV-(LTR) Insertion into the Coding Region of APOB.

BACKGROUND: With the availability of massive SNP data for several economically important cattle breeds, haplotype tests have been performed to identify unknown recessive disorders. A number of so-called lethal haplotypes, have been uncovered in Holstein Friesian cattle and, for at least seven of these, the causative mutations have been identified in candidate genes. However, several lethal haplotypes still remain elusive. Here we report the molecular genetic causes of lethal haplotype 5 (HH5) and cholesterol deficiency (CDH). A targeted enrichment for the known genomic regions, followed by massive parallel sequencing was used to interrogate for causative mutations in a case/control approach. METHODS: Targeted enrichment for the known genomic regions, followed by massive parallel sequencing was used in a case/control approach. PCRs for the causing mutations were developed and compared to routine imputing in 2,100 (HH5) and 3,100 (CDH) cattle. RESULTS: HH5 is caused by a deletion of 138kbp, spanning position 93,233kb to 93,371kb on chromosome 9 (BTA9), harboring only dimethyl-adenosine transferase 1 (TFB1M). The deletion breakpoints are flanked by bovine long interspersed nuclear elements Bov-B (upstream) and L1ME3 (downstream), suggesting a homologous recombination/deletion event. TFB1M di-methylates adenine residues in the hairpin loop at the 3'-end of mitochondrial 12S rRNA, being essential for synthesis and function of the small ribosomal subunit of mitochondria. Homozygous TFB1M-/- mice reportedly exhibit embryonal lethality with developmental defects. A 2.8% allelic frequency was determined for the German HF population. CDH results from a 1.3kbp insertion of an endogenous retrovirus (ERV2-1-LTR_BT) into exon 5 of the APOB gene at BTA11:77,959kb. The insertion is flanked by 6bp target site duplications as described for insertions mediated by retroviral integrases. A premature stop codon in the open reading frame of APOB is generated, resulting in a truncation of the protein to a length of only <140 amino acids. Such early truncations have been shown to cause an inability of chylomicron excretion from intestinal cells, resulting in malabsorption of cholesterol. The allelic frequency of this mutation in the German HF population was 6.7%, which is substantially higher than reported so far. Compared to PCR assays inferring the genetic variants directly, the routine imputing used so far showed a diagnostic sensitivity of as low as 91% (HH5) and 88% (CDH), with a high specificity for both (≥99.7%). CONCLUSION: With the availability of direct genetic tests it will now be possible to more effectively reduce the carrier frequency and ultimately eliminate the disorders from the HF populations. Beside this, the fact that repetitive genomic elements (RE) are involved in both diseases, underline the evolutionary importance of RE, which can be detrimental as here, but also advantageous over generations.

Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: the early intervention in cystic fibrosis exacerbation (eICE) trial.

BACKGROUND: Acute pulmonary exacerbations are central events in the lives of individuals with cystic fibrosis (CF). Pulmonary exacerbations lead to impaired lung function, worse quality of life, and shorter survival. We hypothesized that aggressive early treatment of acute pulmonary exacerbation may improve clinical outcomes. PURPOSE: Describe the rationale of an ongoing trial designed to determine the efficacy of home monitoring of both lung function measurements and symptoms for early detection and subsequent early treatment of acute CF pulmonary exacerbations. STUDY DESIGN: A randomized, non-blinded, multi-center trial in 320 individuals with CF aged 14 years and older. The study compares usual care to a twice a week assessment of home spirometry and CF respiratory symptoms using an electronic device with data transmission to the research personnel to identify and trigger early treatment of CF pulmonary exacerbation. Participants will be enrolled in the study for 12 months. The primary endpoint is change in FEV1 (L) from baseline to 12 months determined by a linear mixed effects model incorporating all quarterly FEV1 measurements. Secondary endpoints include time to first acute protocol-defined pulmonary exacerbation, number of acute pulmonary exacerbations, number of hospitalization days for acute pulmonary exacerbation, time from the end of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation, change in health related quality of life, change in treatment burden, change in CF respiratory symptoms, and adherence to the study protocol. CONCLUSIONS: This study is a first step in establishing alternative approaches to the care of CF pulmonary exacerbations. We hypothesize that early treatment of pulmonary exacerbations has the potential to slow lung function decline, reduce respiratory symptoms and improve the quality of life for individuals with CF.

[Kyphoplasty in combination with intraoperative radiotherapy. Technical and regulatory characteristics of a concept for treatment of vertebral metastases]. / Kyphoplastie in Kombination mit intraoperativer Radiotherapie. Technische und regulatorische Besonderheiten eines Konzepts zur Behandlung von Wirbelkörpermetastasen.

BACKGROUND: Operative and radiotherapeutic procedures are available for the treatment of symptomatic vertebral metastases. The method for treatment of vertebral metastases presented in this article involves a combination of intraoperative radiotherapy (IORT) and kyphoplasty. METHODS AND RESULTS: Kyphoplasty-IORT allows treatment of symptomatic vertebral metastases between vertebrae T3 and L5. With the patient under intubation narcosis an extrapedicular or bipedicular access to the vertebra is selected as for conventional kyphoplasty. This is followed by insertion of special sheaths of the radiation applicator and radiation therapy is intraoperatively administered via a radiation generator (Intrabeam®, Carl Zeiss Surgical, Oberkochen, Germany). The radiation dose is 8 Gy at a depth of 5-10 mm depending on the study protocol (50 kV X-radiation). Following radiation a conventional kyphoplasty procedure (Medtronic, USA) is carried out and the vertebra stabilized with cement. CONCLUSIONS: The procedure presented demonstrates a new approach to treatment of vertebral metastases and represents a valuable alternative to previously established methods.

Short, natural, and extended photoperiod response in BC2F4 lines of bread wheat with different photoperiod-1 (Ppd-1) alleles.

Flowering is a critical period in the life cycle of flowering plant species, resulting in an irreversible commitment of significant resources. Wheat is photoperiod sensitive, flowering only when daylength surpasses a critical length; however, photoperiod insensitivity (PI) has been selected by plant breeders for >40 years to enhance yield in certain environments. Control of flowering time has been greatly facilitated by the development of molecular markers for the Photoperiod-1 (Ppd-1) homeoloci, on the group 2 chromosomes. In the current study, an allelic series of BC2F4 lines in the winter wheat cultivars 'Robigus' and 'Alchemy' was developed to elucidate the influence on flowering of eight gene variants from the B- and D-genomes of bread wheat and the A-genome of durum wheat. Allele effects were tested in short, natural, and extended photoperiods in the field and controlled environments. Across genetic background and treatment, the D-genome PI allele, Ppd-D1a, had a more potent effect on reducing flowering time than Ppd-B1a. However, there was significant donor allele effect for both Ppd-D1a and Ppd-B1a, suggesting the presence of linked modifier genes and/or additional sources of latent sensitivity. Development of Ppd-A1a BC2F4 lines derived from synthetic hexaploid wheat provided an opportunity to compare directly the flowering time effect of the A-genome allele from durum with the B- and D-genome variants from bread wheat for the first time. Analyses indicated that the reducing effect of Ppd-A1a is comparable with that of Ppd-D1a, confirming it as a useful alternative source of PI.

3 Different types of strength training in older women.

The objective of the present study was to evaluate and compare the neuromuscular, morphological and functional adaptations of older women subjected to 3 different types of strength training. 58, healthy women (67 ± 5 year) were randomized to experimental (EG, n=41) and control groups (CG, n=17) during the first 6 weeks when the EG group performed traditional resistance exercise for the lower extremity. Afterwards, EG was divided into three specific strength training groups; a traditional group (TG, n=14), a power group (PG, n=13) that performed the concentric phase of contraction at high speed and a rapid strength group (RG, n=14) that performed a lateral box jump exercise emphasizing the stretch-shortening-cycle (SSC). Subjects trained 2 days per week through the entire 12 weeks. Following 6 weeks of generalized strength training, significant improvements occurred in EG for knee extension one-repetition (1RM) maximum strength (+19%), knee extensor muscle thickness (MT, +15%), maximal muscle activation (+44% average) and onset latency ( -31% average) for vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) compared to CG (p<0.05). Following 6 more weeks of specific strength training, the 1RM increased significantly and similarly between groups (average of +21%), as did muscle thickness of the VL (+25%), and activation of VL (+44%) and VM (+26%). The onset latency of RF (TG=285 ± 109 ms, PG=252 ± 76 ms, RG=203 ± 43 ms), reaction time (TG=366 ± 99 ms, PG=274 ± 76 ms, RG=201 ± 41 ms), 30-s chair stand (TG=18 ± 3, PG=18 ± 1, RG=21 ± 2) and counter movement jump (TG=8 ± 2 cm, PG=10 ± 3 cm, RG=13 ± 2 cm) was significantly improved only in RG (p<0.05). At the end of training, the rate of force development (RFD) over 150 ms (TG=2.3 ± 9.8 N·s(-1), PG=3.3 ± 3.2 N·s(-1), RG=3.8 ± 6.8 N·s(-1), CG=2.3 ± 7.0 N·s(-1)) was significantly greater in RG and PG than in TG and CG (p<0.05). In conclusion, rapid strength training is more effective for the development of rapid force production of muscle than other specific types of strength training and by consequence, better develops the functional capabilities of older women.

Alpha spindles as neurophysiological correlates indicating attentional shift in a simulated driving task.

The intention of this paper is to describe neurophysiological correlates of driver distraction with highly robust parameters in the EEG (i.e. alpha spindles). In a simulated driving task with two different secondary tasks (i.e. visuomotor, auditory), N=28 participants had to perform full stop brakes reacting to appearing stop signs and red traffic lights. Alpha spindle rate was significantly higher during an auditory secondary task and significantly lower during a visuomotor secondary task as compared to driving only. Alpha spindle duration was significantly shortened during a visuomotor secondary task. The results are consistent with the assumption that alpha spindles indicate active inhibition of visual information processing. Effects on the alpha spindles while performing secondary tasks on top of the driving task indicate attentional shift according to the task modality. As compared to alpha band power, both the measures of alpha spindle rate and alpha spindle duration were less vulnerable to artifacts and the effect sizes were larger, allowing for a more accurate description of the current driver state.

Protective effect of 2,2'-dithienyl diselenide on kainic acid-induced neurotoxicity in rat hippocampus.

In this study, we investigated the effects of 2,2'-dithienyl diselenide (DTDS), an organoselenium compound, against seizures induced by kainic acid (KA) in rats. Rats were pretreated with DTDS (50 or 100 mg/kg) by oral route 1 h before KA injection (10 mg/kg, intraperitoneal). Our results showed that DTDS (100 mg/kg) was effective in increasing latency for the onset of the first clonic seizure episode induced by KA, as well as in decreasing the appearance of seizures and the Racine's score. DTDS also caused a decrease in the excitatory electroencephalographic (EEG) changes, resulting from KA exposure in hippocampus and cerebral cortex of rats. Besides, elevated reactive species (RS) and carbonyl protein levels and Na(+), K(+)-ATPase activity in hippocampus of rats treated with KA were ameliorated by DTDS (50 and 100 mg/kg). Lastly, as evidenced by Cresyl-Violet stain, DTDS (100 mg/kg) elicited a protective effect against KA-induced neurodegeneration in rat hippocampus 7 days after KA injection. In conclusion, the present study showed that DTDS attenuated KA-induced status epilepticus in rats and the subsequent hippocampal damage.

PrPSc spreading patterns in the brain of sheep linked to different prion types.

Scrapie in sheep and goats has been known for more than 250 years and belongs nowadays to the so-called prion diseases that also include e.g. bovine spongiform encephalopathy in cattle (BSE) and Creutzfeldt-Jakob disease in humans. According to the prion hypothesis, the pathological isoform (PrPSc) of the cellular prion protein (PrPc) comprises the essential, if not exclusive, component of the transmissible agent. Currently, two types of scrapie disease are known--classical and atypical/Nor98 scrapie. In the present study we examine 24 cases of classical and 25 cases of atypical/Nor98 scrapie with the sensitive PET blot method and validate the results with conventional immunohistochemistry. The sequential detection of PrPSc aggregates in the CNS of classical scrapie sheep implies that after neuroinvasion a spread from spinal cord and obex to the cerebellum, diencephalon and frontal cortex via the rostral brainstem takes place. We categorize the spread of PrPSc into four stages: the CNS entry stage, the brainstem stage, the cruciate sulcus stage and finally the basal ganglia stage. Such a sequential development of PrPSc was not detectable upon analysis of the present atypical/Nor98 scrapie cases. PrPSc distribution in one case of atypical/Nor98 scrapie in a presumably early disease phase suggests that the spread of PrPSc aggregates starts in the di- or telencephalon. In addition to the spontaneous generation of PrPSc, an uptake of the infectious agent into the brain, that bypasses the brainstem and starts its accumulation in the thalamus, needs to be taken into consideration for atypical/Nor98 scrapie.

EEG alpha spindle measures as indicators of driver fatigue under real traffic conditions.

OBJECTIVE: The purpose of this study is to show the effectiveness of EEG alpha spindles, defined by short narrowband bursts in the alpha band, as an objective measure for assessing driver fatigue under real driving conditions. METHODS: An algorithm for the identification of alpha spindles is described. The performance of the algorithm is tested based on simulated data. The method is applied to real data recorded under real traffic conditions and compared with the performance of traditional EEG fatigue measures, i.e. alpha-band power. As a highly valid fatigue reference, the last 20 min of driving from participants who aborted the drive due to heavy fatigue were used in contrast to the initial 20 min of driving. RESULTS: Statistical analysis revealed significant increases from the first to the last driving section of several alpha spindle parameters and among all traditional EEG frequency bands, only of alpha-band power; with larger effect sizes for the alpha spindle based measures. An increased level of fatigue over the same time periods for drop-outs, as compared to participants who did not abort the drive, was observed only by means of alpha spindle parameters. CONCLUSIONS: EEG alpha spindle parameters increase both fatigue detection sensitivity and specificity as compared to EEG alpha-band power. SIGNIFICANCE: It is demonstrated that alpha spindles are superior to EEG band power measures for assessing driver fatigue under real traffic conditions.

Evaluation of the clinical efficacy of Gonazon implants in the treatment of reproductive pathologies, behavioral problems, and suppression of reproductive function in the male dog.

Efficacy of a slow-release gonadotropin-releasing hormone (GnRH)-agonist implant (Gonazon) was assessed in 53 male dogs presented with benign prostatic hyperplasia (BPH), hypersexuality, aggressive behavior (either alone or in combination), excessive micturition, or to suppress fertility. Changes in testosterone (T) and estradiol (E2) concentrations and size of testes and prostate were monitored on Weeks 0, +8, and +26 after implantation. Additional measurements during and after this period were performed in 35 dogs. Clinical signs were assessed by the owners. All implants except one were retained throughout the study. Full downregulation of testicular function (T<0.35 nmol/L) was achieved in 46 dogs, five dogs showed partial downregulation (T = 0.36 to 0.47 nmol/L), one dog did not respond, and another one displayed a transient downregulation on Week +18. On Week +8, mean T and E2 levels were reduced by 96% and 62%, respectively, and did not further decrease. Full downregulation (T<0.35 nmol/L) lasted between 6 to >22 mo in most dogs except two. Compared with pretreatment values, mean testicular and prostatic size was reduced (P<0.00001) by 54% and 52%, respectively, on Week +8 and by 68% and 64%, respectively, on Week +26. Relative reduction of prostatic size was more marked in dogs with BPH than in healthy ones on Week +8 (P<0.05) and Week +26 (P<0.02), and clinical signs of BPH disappeared rapidly after implantation. Dogs affected with BPH were significantly older (P<0.001) than nonaffected ones (9.7 vs. 2.5 yr). Hypersexuality was more common in dogs<3 yr of age, and treatment clearly improved clinical signs. Age significantly affected the response to treatment in aggressive dogs; 75% of the cases responded with an improvement. The only minor and possibly treatment-related events observed were a short-lasting exacerbation of clinical signs of BPH (two dogs), increased weight gain (three dogs), and anxiety (three dogs) with one of these dogs developing a blunt coat. These results demonstrate the clinical efficacy and overall safety of the Gonazon implants.