Canine pseudopregnancy: an evaluation of prevalence and current treatment protocols in the UK

Background: There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised for diagnosis, and which management or treatment protocols are used. Results: The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months. Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52% of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on duration and severity of physical and behavioural signs, owners’ preference, cost, concurrent disease, drug availability and previous history. Conclusions: This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in spayed and entire bitches has been made, further studies are warranted

Split tendon transfers for the correction of spastic varus foot deformity: a case series study

<p>Abstract</p> <p>Background</p> <p>Overactivity of anterior and/or posterior tibial tendon may be a causative factor of spastic varus foot deformity. The prevalence of their dysfunction has been reported with not well defined results. Although gait analysis and dynamic electromyography provide useful information for the assessment of the patients, they are not available in every hospital. The purpose of the current study is to identify the causative muscle producing the deformity and apply the most suitable technique for its correction.</p> <p>Methods</p> <p>We retrospectively evaluated 48 consecutive ambulant patients (52 feet) with spastic paralysis due to cerebral palsy. The average age at the time of the operation was 12,4 yrs (9-18) and the mean follow-up 7,8 yrs (4-14). Eigtheen feet presented equinus hind foot deformity due to gastrocnemius and soleus shortening. According to the deformity, the feet were divided in two groups (Group I with forefoot and midfoot inversion and Group II with hindfoot varus). The deformities were flexible in all cases in both groups. Split anterior tibial tendon transfer (SPLATT) was performed in Group I (11 feet), while split posterior tibial tendon transfer (SPOTT) was performed in Group II (38 feet). In 3 feet both procedures were performed. Achilles tendon sliding lengthening (Hoke procedure) was done in 18 feet either preoperatively or concomitantly with the index procedure.</p> <p>Results</p> <p>The results in Group I, were rated according to Hoffer's clinical criteria as excellent in 8 feet and satisfactory in 3, while in Group II according to Kling's clinical criteria were rated as excellent in 20 feet, good in 14 and poor in 4. The feet with poor results presented residual varus deformity due to intraoperative technical errors.</p> <p>Conclusion</p> <p>Overactivity of the anterior tibial tendon produces inversion most prominent in the forefoot and midfoot and similarly overactivity of the posterior tibial tendon produces hindfoot varus. The deformity can be clinically unidentifiable in some cases when Achilles shortening co-exists producing foot equinus. By identifying the muscle causing the deformity and performing the appropriate technique, very satisfying results were achieved in the majority of our cases. In three feet both muscles contributed to a combined deformity and simultaneous SPLATT and SPOTT were considered necessary. For complex foot deformities where the component of cavus co-exists, supplementary procedures are required along with the index operation to obtain the best result.</p

Receptor-Mediated Enhancement of Beta Adrenergic Drug Activity by Ascorbate In Vitro and In Vivo

RATIONALE: Previous in vitro research demonstrated that ascorbate enhances potency and duration of activity of agonists binding to alpha 1 adrenergic and histamine receptors. OBJECTIVES: Extending this work to beta 2 adrenergic systems in vitro and in vivo. METHODS: Ultraviolet spectroscopy was used to study ascorbate binding to adrenergic receptor preparations and peptides. Force transduction studies on acetylcholine-contracted trachealis preparations from pigs and guinea pigs measured the effect of ascorbate on relaxation due to submaximal doses of beta adrenergic agonists. The effect of inhaled albuterol with and without ascorbate was tested on horses with heaves and sheep with carbachol-induced bronchoconstriction. MEASUREMENTS: Binding constants for ascorbate binding to beta adrenergic receptor were derived from concentration-dependent spectral shifts. Dose- dependence curves were obtained for the relaxation of pre-contracted trachealis preparations due to beta agonists in the presence and absence of varied ascorbate. Tachyphylaxis and fade were also measured. Dose response curves were determined for the effect of albuterol plus-and-minus ascorbate on airway resistance in horses and sheep. MAIN RESULTS: Ascorbate binds to the beta 2 adrenergic receptor at physiological concentrations. The receptor recycles dehydroascorbate. Physiological and supra-physiological concentrations of ascorbate enhance submaximal epinephrine and isoproterenol relaxation of trachealis, producing a 3-10-fold increase in sensitivity, preventing tachyphylaxis, and reversing fade. In vivo, ascorbate improves albuterol's effect on heaves and produces a 10-fold enhancement of albuterol activity in "asthmatic" sheep. CONCLUSIONS: Ascorbate enhances beta-adrenergic activity via a novel receptor-mediated mechanism; increases potency and duration of beta adrenergic agonists effective in asthma and COPD; prevents tachyphylaxis; and reverses fade. These novel effects are probably caused by a novel mechanism involving phosphorylation of aminergic receptors and have clinical and drug-development applications

Membrane-Anchored HIV-1 N-Heptad Repeat Peptides Are Highly Potent Cell Fusion Inhibitors via an Altered Mode of Action

Peptide inhibitors derived from HIV-gp41 envelope protein play a pivotal role in deciphering the molecular mechanism of HIV-cell fusion. According to accepted models, N-heptad repeat (NHR) peptides can bind two targets in an intermediate fusion conformation, thereby inhibiting progression of the fusion process. In both cases the orientation towards the endogenous intermediate conformation should be important. To test this, we anchored NHR to the cell membrane by conjugating fatty acids with increasing lengths to the N- or C-terminus of N36, as well as to two known N36 mutants; one that cannot bind C-heptad repeat (CHR) but can bind NHR (N36 MUTe,g), and the second cannot bind to either NHR or CHR (N36 MUTa,d). Importantly, the IC50 increased up to 100-fold in a lipopeptide-dependent manner. However, no preferred directionality was observed for the wild type derived lipopeptides, suggesting a planar orientation of the peptides as well as the endogenous NHR region on the cell membrane. Furthermore, based on: (i) specialized analysis of the inhibition curves, (ii) the finding that N36 conjugates reside more on the target cells that occupy the receptors, and (iii) the finding that N36 MUTe,g acts as a monomer both in its soluble form and when anchored to the cell membrane, we suggest that anchoring N36 to the cell changes the inhibitory mode from a trimer which can target both the endogenous NHR and CHR regions, to mainly monomeric lipopetides that target primarily the internal NHR. Besides shedding light on the mode of action of HIV-cell fusion, the similarity between functional regions in the envelopes of other viruses suggests a new approach for developing potent HIV-1 inhibitors

Predicting the Impact of Climate Change on Threatened Species in UK Waters

Global climate change is affecting the distribution of marine species and is thought to represent a threat to biodiversity. Previous studies project expansion of species range for some species and local extinction elsewhere under climate change. Such range shifts raise concern for species whose long-term persistence is already threatened by other human disturbances such as fishing. However, few studies have attempted to assess the effects of future climate change on threatened vertebrate marine species using a multi-model approach. There has also been a recent surge of interest in climate change impacts on protected areas. This study applies three species distribution models and two sets of climate model projections to explore the potential impacts of climate change on marine species by 2050. A set of species in the North Sea, including seven threatened and ten major commercial species were used as a case study. Changes in habitat suitability in selected candidate protected areas around the UK under future climatic scenarios were assessed for these species. Moreover, change in the degree of overlap between commercial and threatened species ranges was calculated as a proxy of the potential threat posed by overfishing through bycatch. The ensemble projections suggest northward shifts in species at an average rate of 27 km per decade, resulting in small average changes in range overlap between threatened and commercially exploited species. Furthermore, the adverse consequences of climate change on the habitat suitability of protected areas were projected to be small. Although the models show large variation in the predicted consequences of climate change, the multi-model approach helps identify the potential risk of increased exposure to human stressors of critically endangered species such as common skate (Dipturus batis) and angelshark (Squatina squatina)

Functional identity versus species richness: herbivory resistance in plant communities

The resistance of a plant community against herbivore attack may depend on plant species richness, with monocultures often much more severely affected than mixtures of plant species. Here, we used a plant–herbivore system to study the effects of selective herbivory on consumption resistance and recovery after herbivory in 81 experimental grassland plots. Communities were established from seed in 2002 and contained 1, 2, 4, 8, 16 or 60 plant species of 1, 2, 3 or 4 functional groups. In 2004, pairs of enclosure cages (1 m tall, 0.5 m diameter) were set up on all 81 plots. One randomly selected cage of each pair was stocked with 10 male and 10 female nymphs of the meadow grasshopper, Chorthippus parallelus. The grasshoppers fed for 2 months, and the vegetation was monitored over 1 year. Consumption resistance and recovery of vegetation were calculated as proportional changes in vegetation biomass. Overall, grasshopper herbivory averaged 6.8%. Herbivory resistance and recovery were influenced by plant functional group identity, but independent of plant species richness and number of functional groups. However, herbivory induced shifts in vegetation composition that depended on plant species richness. Grasshopper herbivory led to increases in herb cover at the expense of grasses. Herb cover increased more strongly in species-rich mixtures. We conclude that selective herbivory changes the functional composition of plant communities and that compositional changes due to selective herbivory depend on plant species richness

Small-molecule targeting of brachyury transcription factor addiction in chordoma.

Chordoma is a primary bone cancer with no approved therapy1. The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutations in chordoma tumors2,3. Here we describe the discovery of therapeutically targetable chordoma dependencies via genome-scale CRISPR-Cas9 screening and focused small-molecule sensitivity profiling. These systematic approaches reveal that the developmental transcription factor T (brachyury; TBXT) is the top selectively essential gene in chordoma, and that transcriptional cyclin-dependent kinase (CDK) inhibitors targeting CDK7/12/13 and CDK9 potently suppress chordoma cell proliferation. In other cancer types, transcriptional CDK inhibitors have been observed to downregulate highly expressed, enhancer-associated oncogenic transcription factors4,5. In chordoma, we find that T is associated with a 1.5-Mb region containing 'super-enhancers' and is the most highly expressed super-enhancer-associated transcription factor. Notably, transcriptional CDK inhibition leads to preferential and concentration-dependent downregulation of cellular brachyury protein levels in all models tested. In vivo, CDK7/12/13-inhibitor treatment substantially reduces tumor growth. Together, these data demonstrate small-molecule targeting of brachyury transcription factor addiction in chordoma, identify a mechanism of T gene regulation that underlies this therapeutic strategy, and provide a blueprint for applying systematic genetic and chemical screening approaches to discover vulnerabilities in genomically quiet cancers

Evidence-based patient choice: a prostate cancer decision aid in plain language

BACKGROUND: Decision aids (DA) to assist patients in evaluating treatment options and sharing in decision making have proliferated in recent years. Most require high literacy and do not use plain language principles. We describe one of the first attempts to design a decision aid using principles from reading research and document design. The plain language DA prototype addressed treatment decisions for localized prostate cancer. Evaluation assessed impact on knowledge, decisions, and discussions with doctors in men newly diagnosed with prostate cancer. METHODS: Document development steps included preparing an evidence-based DA in standard medical parlance, iteratively translating it to emphasize shared decision making and plain language in three formats (booklet, Internet, and audio-tape). Scientific review of medical content was integrated with expert health literacy review of document structure and design. Formative evaluation methods included focus groups (n = 4) and survey of a new sample of men newly diagnosed with prostate cancer (n = 60), compared with historical controls (n = 184). RESULTS: A transparent description of the development process and design elements is reported. Formative evaluation among newly diagnosed prostate cancer patients found the DA to be clear and useful in reaching a decision. Newly diagnosed patients reported more discussions with doctors about treatment options, and showed increases in knowledge of side effects of radiation therapy. CONCLUSION: The plain language DA presenting medical evidence in text and numerical formats appears acceptable and useful in decision-making about localized prostate cancer treatment. Further testing should evaluate the impact of all three media on decisions made and quality of life in the survivorship period, especially among very low literacy men

Predicted Disappearance of Cephalantheropsis obcordata in Luofu Mountain Due to Changes in Rainfall Patterns

<div><h3>Background</h3><p>In the past century, the global average temperature has increased by approximately 0.74°C and extreme weather events have become prevalent. Recent studies have shown that species have shifted from high-elevation areas to low ones because the rise in temperature has increased rainfall. These outcomes challenge the existing hypothesis about the responses of species to climate change.</p> <h3>Methodology/Principal Findings</h3><p>With the use of data on the biological characteristics and reproductive behavior of <em>Cephalantheropsis obcordata</em> in Luofu Mountain, Guangdong, China, trends in the population size of the species were predicted based on several factors. The response of <em>C. obcordata</em> to climate change was verified by integrating it with analytical findings on meteorological data and an artificially simulated environment of water change. The results showed that <em>C. obcordata</em> can grow only in waterlogged streams. The species can produce fruit with many seeds by insect pollination; however, very few seeds can burgeon to become seedlings, with most of those seedlings not maturing into the sexually reproductive phase, and grass plants will die after reproduction. The current population's age pyramid is kettle-shaped; it has a Deevey type I survival curve; and its net reproductive rate, intrinsic rate of increase, as well as finite rate of increase are all very low. The population used in the artificial simulation perished due to seasonal drought.</p> <h3>Conclusions</h3><p>The change in rainfall patterns caused by climate warming has altered the water environment of <em>C. obcordata</em> in Luofu Mountain, thereby restricting seed burgeoning as well as seedling growth and shortening the life span of the plant. The growth rate of the <em>C. obcordata</em> population is in descending order, and models of population trend predict that the population in Luofu Mountain will disappear in 23 years.</p> </div

Neutralization of Botulinum Neurotoxin by a Human Monoclonal Antibody Specific for the Catalytic Light Chain

Background: Botulinum neurotoxins (BoNT) are a family of category A select bioterror agents and the most potent biological toxins known. Cloned antibody therapeutics hold considerable promise as BoNT therapeutics, but the therapeutic utility of antibodies that bind the BoNT light chain domain (LC), a metalloprotease that functions in the cytosol of cholinergic neurons, has not been thoroughly explored. Methods and Findings: We used an optimized hybridoma method to clone a fully human antibody specific for the LC of serotype A BoNT (BoNT/A). The 4LCA antibody demonstrated potent in vivo neutralization when administered alone and collaborated with an antibody specific for the HC. In Neuro-2a neuroblastoma cells, the 4LCA antibody prevented the cleavage of the BoNT/A proteolytic target, SNAP-25. Unlike an antibody specific for the HC, the 4LCA antibody did not block entry of BoNT/A into cultured cells. Instead, it was taken up into synaptic vesicles along with BoNT/A. The 4LCA antibody also directly inhibited BoNT/A catalytic activity in vitro. Conclusions: An antibody specific for the BoNT/A LC can potently inhibit BoNT/A in vivo and in vitro, using mechanisms not previously associated with BoNT-neutralizing antibodies. Antibodies specific for BoNT LC may be valuable components o