Position statement for the diagnosis and management of anogenital warts.

BACKGROUND: Anogenital warts (AGW) can cause economic burden on healthcare systems and are associated with emotional, psychological and physical issues. OBJECTIVE: To provide guidance to physicians on the diagnosis and management of AGW. METHODS: Fourteen global experts on AGW developed guidance on the diagnosis and management of AGW in an effort to unify international recommendations. Guidance was developed based on published international and national AGW guidelines and an evaluation of relevant literature published up to August 2016. Authors provided expert opinion based on their clinical experiences. RESULTS: A checklist for a patient's initial consultation is provided to help physicians when diagnosing AGW to get the relevant information from the patient in order to manage and treat the AGW effectively. A number of frequently asked questions are also provided to aid physicians when communicating with patients about AGW. Treatment of AGW should be individualized and selected based on the number, size, morphology, location, and keratinization of warts, and whether they are new or recurrent. Different techniques can be used to treat AGW including ablation, immunotherapy and other topical therapies. Combinations of these techniques are thought to be more effective at reducing AGW recurrence than monotherapy. A simplified algorithm was created suggesting patients with 1-5 warts should be treated with ablation followed by immunotherapy. Patients with >5 warts should use immunotherapy for 2 months followed by ablation and a second 2-month course of immunotherapy. Guidance for daily practice situations and the subsequent action that can be taken, as well as an algorithm for treatment of large warts, were also created. CONCLUSION: The guidance provided will help physicians with the diagnosis and management of AGW in order to improve the health and quality of life of patients with AGW.

Anti-predator behaviour of adult red-legged partridge (Alectoris rufa) tutors improves the defensive responses of farm-reared broods.

The aim of this work was to improve natural anti-predator behaviour of farm-reared gamebirds. We evaluated the anti-predator behaviour of reared red-legged partridge Alectoris rufa chicks kept in brooder houses in large groups (>350 chicks), trained and not trained by parent red-legged partridges acting as experienced tutors. The experiment consisted of two conditioned tests (a raptor model and a human) and two control tests, which were conducted during three consecutive phases of life (1-4, 15-17 and 30-32 d after hatching). The motor anti-predator behaviour, its duration, the intensity of response in chicks and alarm calls elicited by adults were recorded. Tutors elicited aerial alarm calls (76% of tests) and showed prolonged crouching (59% of tests) in response to the raptor model whereas uttering the ground alarm call (73% of tests) and showing vigilance behaviour (78% of tests) was the main pattern during the human test. Trained and not trained chicks showed similar motor behaviour in response to the raptor model (crouching) and the human test (escaping), but frequency of strong responses (all chicks responding) from chicks trained with tutors was double that of chicks trained without them, and chicks trained with tutors showed a higher frequency of long responses (41-60 s). This study indicates that anti-predator training programmes before release may improve behaviour of farm-reared partridges which may confer benefits to survival of birds.

Autoantibodies against TIF-1-γ and CADM-140 in Spanish patients with clinically amyopathic dermatomyositis (CADM): clinical significance and diagnostic utility.

BACKGROUND: Patients with clinically amyopathic dermatomyositis (CADM) appear to be at risk for developing cancer and interstitial lung diseases, but population data to confirm this hypothesis are limited. Moreover, CADM presents cutaneous and histological findings that may overlap with subacute cutaneous lupus erythematosus (SCLE). OBJECTIVES: To determine the association between myositis-specific autoantibodies, myositis-associated autoantibodies and CADM in Spanish patients. In addition, to study the usefulness of these autoantibodies in the differential diagnosis between CADM and SCLE. METHODS: Serum samples were tested for myositis-specific autoantibodies and myositis-associated autoantibodies through immunoprecipitation and other standardized methods. RESULTS: Anti-CADM-p140 and anti-p155 antibodies were the only myositis-specific autoantibodies found and were associated with interstitial lung diseases and cancer respectively. No myositis-associated autoantibodies were found in CADM. Moreover, clinical subsets and proportions seemed to differ from Asian cohorts, where anti-CADM-p140 is considered a CADM hallmark antibody and a risk factor for the development of interstitial lung disease. Interestingly, anti-SSA was highly associated with SCLE, whereas no myositis-specific autoantibodies were found in this entity. LIMITATIONS OF THE STUDY: Association between CADM and myositis-specific autoantibodies and differences between CADM and SCLE were tested on a relatively small cohort of patients. CONCLUSION: There is an association between cancer-associated myositis and interstitial lung diseases and their hallmark autoantibodies in our cohort. In addition, the combined determination of myositis-specific autoantibodies and SSA autoantibodies may help to accurately discriminate SCLE from CADM.

Are parent-reared red-legged partridges (Alectoris rufa) better candidates for re-establishment purposes?

Aiming to produce game birds suitable for re-establishment purposes, we studied the survival and behavior of 31 adult red-legged partridges reared by their natural parents in captivity (parent-reared) and 67 wild red-legs (35 adults and 32 subadults). Birds were radio-tracked and released in a game estate where management targeting small game species was conducted and shooting was not allowed. Survival of parent-reared partridges was shorter (mean 108 d) than wild adults (mean 160 d), though no significant differences were found. Parent-reared birds showed a longer escape reaction (mean 11.7 sec) than wild adults (mean 0.4 sec) and were mainly predated by terrestrial predators (52%), whereas the most important source of predation in wild red-legs was raptors (49%). The home range of parent-reared (mean 23 ha) was not significantly lower than wild adults (mean 27 ha). Nineteen percent of parent-reared and 31.4% of wild adults paired successfully, and we recorded 6 pairs in which one bird was wild and the other parent-reared and one pair in which both birds were parent-reared. A small proportion of red-legs started incubation (parent-reared 12.9%, wild 20%), and the proportion completing incubation was similar among wild and parent-reared birds. Overall, parent-reared red-legs showed similar survival and behavior compared to wild red-legs and better than intensively reared, so parent-reared red-legs should be chosen for the re-establishment of wild populations.

Do pairing systems improve welfare of captive Red-Legged partridges (Alectoris rufa) in laying cages?

Although animal welfare has become an important premise in poultry, little attention has been paid to the effects of present-day rearing methods on the welfare of game birds, species released for hunting and re-establishment purposes. This work studied the effect of pairing methods on the welfare of the Red-Legged partridge kept in laying cages (4,500 cm2), a commonly hunted game species in Western Europe. Agonistic behavior and possible injuries caused by aggression were studied during the pairing and laying period in 2 types of couples: the forced type (n=24), 1 male and 1 female randomly chosen and placed in the same cage, and the free type (n=24), where the female had the opportunity to chose between 4 males, using the time spent by the female near each male as female choice parameter. Welfare of partridges was affected by pairing system, as aggressive behavior, divorces and injuries were observed in a higher rate in forced pairs (25% of pairs did not finish the productive cycle) than in free pairs (16.6%). In addition, more females were attacked in forced pairs, whereas in free pairs, the number of attacked males and mutual aggression was increased. Males tended to display more aggressive behavior than females, pecking mainly on the head and back of females. Although injuries were observed in a minor rate in free pairs, a higher mortality was reported in females compared with males from both free and forced pairs (6 females died in total). The poor welfare in a high percentage of laying pairs hampers the development of sustainable rearing methods for the species. Thus, farmers should consider avoiding forced pairing.

Does early antipredator training increase the suitability of captive red-legged partridges (Alectoris rufa) for releasing?

This study aimed to evaluate the postrelease survival and spatial distribution of farm-bred red-legged partridges (Alectoris rufa) that were subject to a prerelease training program based on exemplary behavior and alarm calls given by adults that acted as experienced demonstrators in simulated predator encounters (wooden raptor models and humans). Two groups of partridges were released in this study: trained (intensively reared birds accompanied by tutors) and control (chicks reared without tutors). Releases were conducted in the fall and winter-spring during 2 consecutive years using a total of 44 trained and 40 control radio-tagged partridges. Trained partridges showed statistically higher mean values of survival (72.7 d), home range (13.04 ha), and dispersion (549.58 m) compared with nontrained partridges, with most nontrained birds failing to survive more than 2 wk after release. Trained adult partridges showed the best survival results (105.2 d). Taking all birds into account, causes of death were attributed to terrestrial predators (45%), raptors (18.7%), hunting (11.3%), and unknown causes (25%). Although values of variables reported here were lower than those reported in wild counterparts, survival time and spatial behavior of trained birds were close to that of previous data of parent-reared partridges and higher than that of farm-bred birds. This study aimed to confirm the potential of prerelease training techniques in present-day rearing systems. Farm-bred game birds, which normally suffer from high predation rates after release, could highly benefit from the use of cost-effective training techniques based on learning from experienced adults.

Isolation from predators: a key factor in the failed release of farmed red-legged partridges (Alectoris rufa) to the wild?

1. The effects of predation isolation were studied in two lines of 10 month-old farmed red-legged partridges (Alectoris rufa). Birds came from bred generations in captivity (F) and directly from wild parents (W). 2. Releases were carried out in March for two consecutive years on private farmland with a stable population of wild red-legged partridge using 68 tagged birds (36 F, 32 W). 3. No statistical differences were found in survival time (mean 18 d) or home range values (mean 7·38 ha); 49% of mortality was attributable to raptors, 36% to wild canids and 15% had doubtful causes of death. F birds suffered more predation by raptors and W partridges more by mammalian carnivores. 4. A statistical difference was found in post-release dispersion: the means were 243·4 m in F and 593·3 m in W. 5. The result of predation isolation was similar in both groups, which confirms the adverse effects of current production systems on anti-predator behaviour. Farmers should consider the introduction of new rearing techniques with the aim of improving survival after release.

[Copeman nodules, a frequent but little known cause of low back pain; case report]. / Nódulos de Copeman, una causa frecuente pero poco conocida de dolor lumbar: presentación de un caso.

Copeman nodules or episacral lipomas are a very prevalent entity in the general population. They consist of subfascial fat herniations at the episacral region, through weakened areas of the overlying thoracodorsal fascia. They are usually bilateral and symmetric. Only in rare cases they are the cause of clinical manifestations. We present the case of a 63-year-old woman who presents with lumbar pain refractory to conventional treatments. Ultrasound examination suggests the diagnosis of Copeman nodules. The treatment of the patient is approached from a multidisciplinary perspective, finally deciding to operate the patient. After the intervention, the symptoms remitted shortly, allowing the patient to continue a normal life without discomfort or analgesic treatment.

Influence of the breeding system on the escape response of red-legged partridges (Alectoris rufa).

This study aimed to determine the influence of the breeding system on the escape response of red-legged partridges comparing 147 free-born partridges captured in the wild (W) and 164 partridges from a commercial hunting farm with an intensive production system (F). All birds were individually released to the natural environment using wooden cages; the escape response was recorded with a high resolution video camera and 4 behavior parameters were analyzed: reaction time or latency, escape type, angle at the moment of flight start, and distance flown. There were significant differences on the mean reaction time depending on the origin of the partridges: 0.43 s, with a maximum of 9 s, for the W and 52.90 s, with a maximum of 120 s, in 32.3% of the F birds. Only one of the W partridges (0.68%) escaped by walking, whereas all the other W birds, and 69.5% of the F partridges, flew; the differences in the type of escape reaction between origins were significant. Considering the angle of flight start, the differences were also significant because 98.6% of W partridges showed less than 45 degrees angles, whereas 37.7% of F birds showed angles of more than 45 degrees. Thus, we can conclude that the breeding system has a great influence on the escape response of the red-legged partridges. The intensive management production systems used on the commercial game farms produced obvious changes in the escape reaction of the red-legged partridges, and this could explain the low ability of these birds to integrate and to survive in the wild due to the high predation pressure they undergo when they are used in repopulation processes.

Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14.

Linkage analysis was used to search the genome for chromosomal regions harboring familial Alzheimer's disease genes. Markers on chromosome 14 gave highly significant positive lod scores in early-onset non-Volga German kindreds; a Zmax of 9.15 (theta = 0.01) was obtained with the marker D14S43 at 14q24.3. One early-onset family yielded a lod score of 4.89 (theta = 0.0). When no assumptions were made about age-dependent penetrance, significant results were still obtained (Zmax = 5.94, theta = 0.0), despite the loss of power to detect linkage under these conditions. Results for the Volga German families were either negative or nonsignificant for markers in this region. Thus, evidence indicates a familial Alzheimer's disease locus on chromosome 14.

Relationships between eye fluids and blood values after exercise in lidia cattle: mineral parameters.

Eye fluids (aqueous humour and vitreous humour) may be helpful in estimating ante-mortem blood levels, since some parameters measured in these fluids have proved to be stable or to change in a predictable way after death. This would help in diagnosing the cause of death in some diseases or to evaluate ante-mortem blood levels in certain animals not easy to handle or with difficult access. In order to establish reference values of some parameters in blood and eye fluids (aqueous humour and vitreous humour), as well as the possible correlation among these three different fluids, various minerals and electrolytes (Ca, P, Mg, K, Na, Fe, Cr, Co, Ni, Cu, Zn, Se and Mo) were measured in 15 four to five year-old Lidia bulls, all dying after a period of significant stress and major exertion. Plasmatic values of Mg and P were much greater than reported in the literature. In general, mineral plasmatic values were greater than those found in ocular fluids (aqueous and vitreous), while Na, K and Cr were similar in the three fluids. We have verified the existence of correlations in P, Co and Mo among the three fluids measured, and between Se of plasma and vitreous humour. But the most marked correlations were observed in Mo (plasma -aqueous humour, r = 0.893, plasma-vitreous humour, r = 0.945, HA -HV, r = 0.849), in P (plasma-vitreous humour, r = 0.726) and in Co (plasma-vitreous humour, r = 879).

Humoral immune response against epidermal growth factor encapsulated in dehydration rehydration vesicles of different phospholipid composition.

We investigated the influence of dehydration-rehydration vesicles (DRV) phospholipid composition and the addition of other components on human recombinant epidermal growth factor (hrEGF) encapsulation efficiency and its release from liposomes. Encapsulation of EGF into DRV composed of phosphatidylcholine with different unsaturation levels was around 20-35%. The best result was obtained with dipalmitoyl phosphatidylcholine: cholesterol (DPPC:Ch) liposomes (35%) corresponding to the lowest hrEGF release during one month of storage. Even with this phospholipid composition, modification of the DRV procedure by including an extrusion step did not improve hrEGF encapsulation efficiency, rendering less stable particles. The inclusion of recombinant P64k from Neisseria meningitidis (rP64k), as such or conjugated to hrEGF, decreased the encapsulation efficiency of the latter protein into DRV or freeze and thaw multilamellar vesicles (FATMLV). The hrEGF release from liposomes could be related to the interaction between this polypeptide and the bilayer, as evidenced by increased carboxyfluorescein release from hrEGF-DRV; less susceptibility to fluorescence quenching by acrylamide in the presence of liposomes; and a measurable decrease of phospholipid phase transition Delta enthalpy (DeltaH). DRV comprising saturated phospholipids (DPPC:Ch or distearoyl phosphatidylcholine [DSPC]:Ch) and containing the conjugate EGF-P64k induced a more efficient immune response against hrEGF than unsaturated phospholipid and alum in terms of total IgG, IgG(2a), and IgG(2b) subclasses and the ability of antibody to inhibit the interaction of the EGF receptor with hrEGF.

Evolution of the corpus luteum volume determined ultrasonographically and its relation to the plasma progesterone concentration after artificial insemination in pregnant and non-pregnant dairy cows.

The aim of this study was to assess the relationship of the evolution of the corpus luteum (CL) volume that was determined ultrasonographically with the pregnancy status in lactating dairy cows during early pregnancy. Ultrasound examinations were carried out on 76 cows following artificial insemination (AI). Plasma concentrations of progesterone were determined from blood samples collected at each ultrasound examination. Conception was confirmed by ultrasonography on day 30 after AI. Around day 14 post-insemination (p.i.), the CL volume tended to decrease in pregnant and non-pregnant cows, and, after day 19 p.i., both groups differed significantly, indicating the luteal regression in non-pregnant cows. Reaching signification on day 20. The diminution in CL volume was also reflected in the plasma progesterone concentration. However, the patterns of CL volume, estimated by ultrasonography, differed more evidently and earlier between both groups (around 1 week p.i., at day 9 p.i. P < 0.05, whereas progesterone started to differ around 2 weeks p.i., at day 14 p.i, P < 0.05). These results indicate that the estimation of the CL volume by ultrasonography could be useful for assessing the presence of a functional CL.

Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR.

The hypervariable regions of immunoglobulin heavy-chain (IgH) rearrangements provide a specific tumor marker in multiple myeloma (MM). Recently, real-time PCR assays have been developed in order to quantify the number of tumor cells after treatment. However, these strategies are hampered by the presence of somatic hypermutation (SH) in VDJH rearrangements from multiple myeloma (MM) patients, which causes mismatches between primers and/or probes and the target, leading to a nonaccurate quantification of tumor cells. Our group has recently described a 60% incidence of incomplete DJH rearrangements in MM patients, with no or very low rates of SH. In this study, we compare the efficiency of a real-time PCR approach for the analysis of both complete and incomplete IgH rearrangements in eight MM patients using only three JH consensus probes. We were able to design an allele-specific oligonucleotide for both the complete and incomplete rearrangement in all patients. DJH rearrangements fulfilled the criteria of effectiveness for real-time PCR in all samples (ie no unspecific amplification, detection of less than 10 tumor cells within 10(5) polyclonal background and correlation coefficients of standard curves higher than 0.98). By contrast, only three out of eight VDJH rearrangements fulfilled these criteria. Further analyses showed that the remaining five VDJH rearrangements carried three or more somatic mutations in the probe and primer sites, leading to a dramatic decrease in the melting temperature. These results support the use of incomplete DJH rearrangements instead of complete somatically mutated VDJH rearrangements for investigation of minimal residual disease in multiple myeloma.

An electrophysiological analysis of altered cognitive functions in Huntington disease.

BACKGROUND: Neuropsychological deficits are a main feature of Huntington disease (HD) with previous data suggesting involvement of memory functions and visual processing. OBJECTIVE: To increase the knowledge about cognitive malfunction in HD in the domains of visual processing and memory by the use of modern electrophysiological techniques (event-related potentials [ERPs]). DESIGN: A case-control design was used. Three ERP paradigms were used; a parallel visual search paradigm allowed for the simultaneous processing of a multi-element visual array in search of a target stimulus, while a serial search paradigm with varied numbers of distractor items necessitated a serial one by one scanning of the arrays. The third experiment was a word-recognition memory task. SETTING: The measurements were obtained in a neurophysiological laboratory of a university hospital. PATIENTS AND CONTROLS: Nine patients with HD and 9 control subjects matched for age, sex, and education were studied. MAIN OUTCOME MEASURES: Components of averaged ERPs were quantified by latency and amplitude measures and subjected to statistical analysis. Behavioral measures (search time, hit rate, and recognition accuracy) were assessed as well. RESULTS: The early visual components showed a significant latency shift (delay of about 50 milliseconds) in HD. In the search paradigms the P3 components differentiating target and standard stimuli were virtually absent in HD as was the ERP effect indexing word recognition. This was accompanied by a marked delay in search times and lower hit rates in the search tasks and a grossly reduced recognition accuracy in the memory task. CONCLUSIONS: The results suggest marked impairments of patients with HD in early visual sensory processing (early components). Deficits in visual search might be attributed to an impairment to deploy attentional resources across the visual field and/or an inability to control eye movements. The ERPs in the memory task differed grossly from similar data obtained by others in patients with Alzheimer disease, suggesting a different neural basis for the amnesia in HD.

Aberrant methylation of multiple genes in neuroblastic tumours. relationship with MYCN amplification and allelic status at 1p.

Aberrant hypermethylation occurs in tumour cell CpG islands and is an important pathway for the repression of gene transcription in cancers. We investigated aberrant hypermethylation of 11 genes by methylation-specific polymerase chain reaction (PCR), after treatment of the DNA with bisulphite, and correlated the findings with MYCN amplification and allelic status at 1p in a series of 44 neuroblastic tumours. This tumour series includes five ganglioneuromas (G), one ganglioneuroblastoma (GN) and 38 neuroblastomas (six stage 1 tumours; five stage 2 tumours; six stage 3 cases; 19 stage 4 tumours, and two stage 4S cases). Aberrant methylation of at least one of the 11 genes studied was detected in 95% (42 of 44) of the cases. The frequencies of aberrant methylation were: 64% for thrombospondin-1 (THBS1); 30% for tissue inhibitor of metalloproteinase 3 (TIMP-3); 27% for O6-methylguanine-DNA methyltransferase (MGMT); 25% for p73; 18% for RB1; 14% for death-associated protein kinase (DAPK), p14ARF, p16INK4a and caspase 8, and 0% for TP53 and glutathione S-transferase P1 (GSTP1). No aberrant methylation was observed in four control normal tissue samples (brain and adrenal medulla). MYCN amplification was found in 11 cases (all stage 4 neuroblastomas), whereas allelic loss at 1p was identified in 16 samples (13 stage 4 and two stage 3 neuroblastomas, and one ganglioneuroma). All but one case with caspase 8 methylation also displayed MYCN amplification. Our results suggest that promoter hypermethylation is a frequent epigenetic event in the tumorigenesis of neuroblastic tumours, but no specific pattern of hypermethylated genes could be demonstrated.

Down-regulation of murine B lymphocyte growth: arrest of B cells in G1 underlies immunosuppression induced by an IgM antibody.

Previous studies have demonstrated that culture supernatants of LPS-stimulated murine splenic B lymphocytes (BLPSSN) are able to inhibit the growth of freshly isolated B cells via an IgM antibody. In this work we investigated the progress of LPS-activated B lymphocytes through the cell cycle in the presence of this antibody. We found that the regulatory IgM did not affect the entry of LPS-stimulated B lymphocytes into G0*, as assessed by the increased expression of I-A antigens. Events that characterize the early G1 phase (G1A), such as cell enlargement and increased RNA synthesis, also occurred in the presence of the antibody. In contrast, events which mark the G1B phase, such as further cell enlargement and late RNA synthesis were inhibited. Moreover, a significant portion of the cells failed to incorporate [3H]thymidine and did not progress through S, G2, or M, as revealed by their DNA content. Therefore, our work points toward a well-defined stage of the early G1 phase at which the antibody inhibits the progression of B lymphocyte activation. This result shows a new insight into the mechanism of antibody-mediated down-regulation of polyclonal B cell responses.

Juvenile myoclonic epilepsy in chromosome 6p12-p11: locus heterogeneity and recombinations.

We recently analyzed under homogeneity a large pedigree from Belize with classic juvenile myoclonic epilepsy (JME). After a genome wide search with 146 microsatellites, we obtained significant linkage between chromosome 6p markers, D6S257 and D6S272, and both convulsive and EEG traits of JME. Recombinations in two affected members defined a 40 cM JME region flanked by D6S313 and D6S258. In the present communication, we explored if the same chromosome 6p11 microsatellites also have a role in JME mixed with pyknoleptic absences. We allowed for heterogeneity during linkage analyses. We tested for heterogeneity by the admixture test and looked for more recombinations. D6S272, D6S466, D6S294, and D6S257 were significantly linked (Zmax > 3.5) to the clinical and EEG traits of 22 families, assuming autosomal dominant inheritance with 70% penetrance. Pairwise Zmax were 4.230 for D6S294 (theta m = f at 0.133) and 4.442 for D6S466 (theta m = f at 0.111). Admixture test (H2 vs. H1) was significant (P = 0.0234 for D6S294 and 0.0128 for D6S272) supporting the hypotheses of linkage with heterogeneity. Estimated proportion of linked families, alpha, was 0.50 (95% confidence interval 0.05-0.99) for D6S294 and D6S272. Multipoint analyses and recombinations in three new families narrowed the JME locus to a 7 cM interval flanked by D6S272 and D6S257.

Autocrine regulation of murine B lymphocyte growth by an IgM antibody.

Culture supernatants of LPS-stimulated murine B lymphocytes are able to inhibit the growth of freshly isolated splenic B cells via an IgM antibody. The binding specificity of this IgM is not yet defined, but appears to be a B lymphocyte surface structure distinct from membrane immunoglobulin, MHC class II antigen, transferrin and Fc gamma receptors, and B220. The regulatory autoantibody allows the normal progression of early, but not late steps in the cycle of polyclonally-stimulated B lymphocytes and does not affect the increased antigen-presenting capacity of activated B cells. Therefore, this autoregulatory cycle is apparently ubiquitous and may be a major component of B lymphocyte homeostasis under physiological, as well as pathological conditions. Moreover, these findings bring into focus a possible regulating role of B lymphocytes in the humoral immune response.