Clinicopathological relevance of antithyroglobulin antibodies in low-risk papillary thyroid cancer.

OBJECTIVE: The extent of initial surgical management in papillary thyroid cancer (PTC) is controversial. We examined whether the presence of perioperative antithyroglobulin antibodies (TGA) could predict long-term recurrence and occurrence of adverse features among a homogenous group of patients with PTC. METHODS: The clinical features of patients with PTC treated at a single institution (Jewish General Hospital, McGill University, Montreal, Canada) were obtained from the medical records, and all clinicopathologic information was reviewed. Only low-risk PTC without clinical evidence of nodal disease before surgery and treated with 30 mCi of radioactive iodine was included in the study. RESULTS: The chart review retrieved 361 patients with a median follow-up of 85.0 months (Q25-Q75 73-98). Forty-two (11.6%) patients had presence of perioperative TGA. Perioperative TGAs were associated with present extrathyroidal extension (P=.005), unsuspected nodal disease (P=.001) and autoimmune thyroiditis (P<.0001). Overall, 17 (4.7%) patients experienced locoregional recurrence. Perioperative TGAs were a significant predictor of recurrence in univariable (P=.021) but not in multivariable analysis (P=.13). CONCLUSION: Presence of perioperative TGAs is associated with aggressive histological features and the presence of thyroiditis. Detection of TGA perioperatively may encourage surgeons to consider more extensive initial surgery.

Increased upper airway cytokines and oxidative stress in severe obstructive sleep apnoea.

Inflammation may contribute to upper airway pathophysiology in obstructive sleep apnoea (OSA). Our objective was to compare upper airway pro-inflammatory cytokine expression, oxidative stress and connective tissue deposition in severe (n = 25) versus mild (n = 17) OSA patients. Upper airway surgical specimens were separated by predominance of either mucosal or muscle tissue. Expression levels of interleukin (IL)-1α, IL-6, interferon-γ, RANTES (regulated on activation, normal T-cell expressed and secreted), transforming growth factor (TGF)-ß and l-selectin were measured by ribonuclease protection assay. Oxidative stress was assessed via protein carbonyl group detection by immunoblotting. Histochemistry was employed for immunolocalisation of selected cytokines and connective tissue morphometry. In the severe OSA group, expression of IL-1α, IL-6 and TGF-ß was significantly higher in mucosa-predominant tissues, whereas in muscle-predominant specimens, RANTES expression was greater in severe OSA. Increased protein carbonylation was observed in severe OSA within both mucosal and muscle compartments. Immunohistochemistry localised TGF-ß to submucosal and perimuscular inflammatory cells, while IL-6 was primarily localised to myocytes. Consistent with the pro-fibrotic cytokine profile observed in mucosa-predominant tissue, morphometric analysis revealed greater submucosal and perimuscular connective tissue in severe OSA subjects. There is increased pro-inflammatory and pro-fibrotic cytokine expression, oxidative stress, and connective tissue deposition in upper airway tissues from severe versus mild OSA patients.

Outcome and long-term follow-up of 20 horses undergoing surgery for caecal impaction: a retrospective study (2000-2008).

REASONS FOR PERFORMING STUDY: If untreated, caecal impaction may progress to rupture of the caecum and reports of long-term outcome for horses undergoing surgery for caecal impaction are required. OBJECTIVES: To describe short- and long-term complication rates for horses undergoing surgery for caecal impaction in an otherwise life-threatening gastrointestinal condition. METHODS: Case records were reviewed for horses undergoing surgery for caecal impaction. Horses were included in the study if an abnormally large, fluid-distended or feed-impacted caecum was the primary diagnosis at surgery and excluded if the caecum had already ruptured upon opening the abdomen, necessitating euthanasia. Short-term follow-up data were obtained from clinical records; and included complications, repeat celiotomy and survival to discharge. Long-term survival was defined as survival for >1 year post operatively. Long-term follow-up data were obtained through telephone interviews with owners and referring veterinary surgeons. Survival, occurrence of post operative colic and subsequent use of the horse were recorded. RESULTS: Twenty horses underwent surgery for caecal impaction: 16 horses underwent caecal bypass (typhlotomy and removal of caecal contents, ileal transection followed by ileocolostomy); 3 underwent typhlotomy alone; and one horse underwent typhlotomy followed by a second procedure where caecal bypass was performed. Five horses (25%) were admitted for colic evaluation with primary caecal impactions, in 10/20 (50%) of cases the impaction was secondary to previous orthopaedic surgery and in 5/20 (25%) caecal impaction was identified at repeat celiotomy following a previous colic surgery. Sixty-five percent (13/20) of horses survived to discharge; 11/13 (85%) of horses discharged survived long term; 100% (3/3) horses that received typhlotomy alone were discharged and survived long term. CONCLUSIONS: The prognosis following caecal impaction surgery is fair, if the horse survives to discharge then prognosis for long-term survival is good. POTENTIAL RELEVANCE: Surgery for caecal impaction carries a fair prognosis for a potentially life threatening disease, in particular where caecal dysfunction is suspected.

Seasonal dispersal of pests: one surge or two?

Many agricultural pest species occur in seasonal metapopulations with a period of asexual reproduction. We use evolutionary theory to predict timing of dispersal for such species, and identify four sequential phases: no dispersal, dispersal from initially occupied patches, dispersal from later colonized patches, and no dispersal. The third type of phase occurs only when reproductive rates are relatively high; we speculate that this could explain why among aphids there can be either one or two waves of dispersal during a season, depending on the species. Our model also explains other features of aphid biology, including a summer crash in colony size, and a decline in the number of colonies towards the end of each reproductive season. The presence of an additional surge of dispersal becomes more likely as season length increases, and does not require further evolution. This could have profound implications for pest management during future climatic warming.

Re-visiting the ATA 2015 sonographic guidelines - who are we missing?: A retrospective review.

BACKGROUND: The American Thyroid Association published revised guidelines in 2015 on the management of differentiated thyroid cancer in adults. One of the key changes introduced in the revision proposes that diagnostic biopsy be based on ultrasound findings (i.e. size and nodule characteristics). The overall effect of these changes results in fewer nodules requiring biopsy. This study was conducted to determine if the changes to the guidelines will result in overlooked thyroid cancers, specifically malignancies with aggressive characteristics measuring between 1 and 1.49 cm. METHODS: Patients (n = 2083) with thyroid nodules who underwent total or subtotal/hemi thyroidectomy with or without neck dissection by a single surgeon between 2006 and 2016 were retrospectively enrolled. Demographic information and nodule characteristics were collected for all patients. Ultrasonography and final pathology reports were reviewed for patients with thyroid nodules between the sizes of 1-1.49 cm (n = 155). RESULTS: 45% (n = 70) of patients with nodules between 1 and 1.49 cm were "low suspicion" nodules according to ultrasound. 47 of these nodules contained malignancies on final histopathological examination, 100% of which were of the papillary subtype. 21% (n = 10) of these malignant nodules demonstrated extrathyroidal extension and 34% (n = 16) were associated with regional metastases. CONCLUSIONS: Reliance on sonographic patterns alone could result in missed cancer diagnoses in patients with thyroid nodules measuring between 1 and 1.49 cm. Moreover, a portion of these malignancies may be associated with aggressive features. The effect of this finding on long-term outcomes is unclear.

Fracture of the medial intercondylar eminence of the tibia in horses treated by arthroscopic fragment removal (21 horses).

BACKGROUND: Fractures of the medial intercondylar eminence of the tibia (MICET) are scarcely reported in horses. OBJECTIVES: To report the clinical and diagnostic findings, surgical treatment and outcome in a series of horses presented with MICET fracture and treated with arthroscopic fragment removal. STUDY DESIGN: Multicentre retrospective case series. METHODS: Case records of horses diagnosed with MICET fractures that had undergone surgical treatment were reviewed. Follow-up information was obtained from re-examination visits and/or owners. RESULTS: Twenty-one cases were identified at 9 equine hospitals between 2004 and 2016. A history of trauma and acute onset of lameness was reported in 12 horses. All cases underwent fracture removal via arthroscopy of the medial femorotibial joint. The cranial cruciate ligament was intact in 6 horses and damaged in 15 horses (damage was ≤25% [n = 9], 25-50% [n = 4] or ≥50% [n = 2] of the cross-sectional area). The cranial ligament of the medial meniscus was damaged in 11 horses (≤25% [n = 8], 25-50% [n = 3]). The medial meniscus was damaged in 5 horses and articular cartilage damage was identified in 14 horses (mild [n = 8], moderate [n = 6]). Follow-up information (median 14 months; 4 months-6 years) was available for 20 cases; 2 horses were sound but convalescing; 13 horses were sound and returned to their previous or expected use. Of the 4 horses with the most severe changes to the articular soft tissue structures, 2 remained lame and 2 were subjected to euthanasia because of persistent lameness. MAIN LIMITATIONS: The retrospective, multicentre nature of this study and the limited number of horses are the main limitations. CONCLUSIONS: Fractures of the MICET are commonly associated with a traumatic event. Prompt diagnosis and early arthroscopic removal of the fracture are recommended.

Electrosurgery as the sole means of haemostasis during the laparoscopic removal of pathologically enlarged ovaries in mares: a report of 55 cases.

REASONS FOR PERFORMING STUDY: There is little published clinical evidence on the use of a laparoscopic approach for the removal of pathologically enlarged ovaries in standing mares. OBJECTIVES: To show the orders of success and complication rates that can be expected if pathologically enlarged ovaries are removed from standing, sedated mares under laparoscopic guidance using only electrosurgical means of haemostasis. METHODS: A retrospective analysis was made of 55 mares in which the removal of an enlarged ovary was attempted by applying a standard laparoscopic procedure for routine ovariectomy in standing mares including a reliance solely on one of 2 types of electrosurgical bipolar forceps with an integrated guillotine for haemostasis and transection of the ovarian pedicle. The outcomes and complications encountered were recorded. Logistic regression analysis was performed to identify the risk of any complications associated with the size of the ovary removed and the instrument used. RESULTS: In 54 of the 55 mares, the surgery was successfully accomplished by the planned approach. In one mare there was significant intraoperative haemorrhage and this necessitated the additional use of a prosthetic haemostatic device. The only other complications encountered were post operative abdominal discomfort (n = 9), delayed incisional wound healing (n = 6) and iatrogenic uterine puncture (n = 2). One mare developed a rectal tear, but not as a direct complication of the surgical procedure. None of these prevented a long-term successful outcome. CONCLUSIONS: The removal of pathologically enlarged ovaries (up to 30 cm diameter) from mares under standing sedation can be accomplished predictably and safely by applying the standard laparoscopic approach that is established for routine laparoscopic ovariectomy, including a reliance solely on endoscopic electrosurgery instruments for haemostasis of the ovarian pedicle. POTENTIAL RELEVANCE: This study shows that the simple standing laparoscopic technique now favoured for routine ovariectomy can be used safely and reliably for the removal of pathologically enlarged ovaries. This promises to be of significant clinical advantage to mares so affected.

The cell surface mucin MUC1 limits the severity of influenza A virus infection.

Cell surface mucin (cs-mucin) glycoproteins are constitutively expressed at the surface of respiratory epithelia where pathogens such as influenza A virus (IAV) gain entry into cells. Different members of the cs-mucin family each express a large and heavily glycosylated extracellular domain that towers above other receptors on the epithelial cell surface, a transmembrane domain that enables shedding of the extracellular domain, and a cytoplasmic tail capable of triggering signaling cascades. We hypothesized that IAV can interact with the terminal sialic acids presented on the extracellular domain of cs-mucins, resulting in modulation of infection efficiency. Utilizing human lung epithelial cells, we found that IAV associates with the cs-mucin MUC1 but not MUC13 or MUC16. Overexpression of MUC1 by epithelial cells or the addition of sialylated synthetic MUC1 constructs, reduced IAV infection in vitro. In addition, Muc1-/- mice infected with IAV exhibited enhanced morbidity and mortality, as well as greater inflammatory mediator responses compared to wild type mice. This study implicates the cs-mucin MUC1 as a critical and dynamic component of the innate host response that limits the severity of influenza and provides the foundation for exploration of MUC1 in resolving inflammatory disease.

Structural requirements of flavonoids to induce heme oxygenase-1 expression.

Population studies suggest cardiovascular health benefits of consuming fruits and vegetables rich in polyphenolic compounds such as flavonoids. We reported previously that the flavonoid quercetin protects arteries from oxidant-induced endothelial dysfunction and attenuates atherosclerosis in apolipoprotein E gene knockout mice, with induction of heme oxygenase-1 (Hmox1) playing a critical role. The present study investigated the structural requirements of flavonoids to induce Hmox1 in human aortic endothelial cells (HAEC). We identified ortho-dihydroxyl groups and an α,ß-unsaturated system attached to a catechol as the key structural requirements for Hmox1 induction. Active but not inactive flavonoids had a low oxidation potential and prevented ascorbate autoxidation, suggesting that Hmox1 inducers readily undergo oxidation and that oxidized, rather than reduced, flavonoids may be the biological inducer of Hmox1. To test this hypothesis, we synthesized stable derivatives of caffeic acid (3-(3,4-dihyroxyphenyl)-2-propenoic acid) containing either ortho-dihydroxy or ortho-dioxo groups. Compared with the dihydroxy compound, the quinone analog induced Hmox1 more potently in HAEC and also provided enhanced protection to arteries of wild type animals against oxidant-induced endothelial dysfunction. In contrast, the quinone analog failed to provide protection against oxidant-induced endothelial dysfunction in arteries of Hmox1-/- mice, establishing a key role for Hmox1 in vascular protection. These results suggest that oxidized forms of dietary polyphenols are the likely inducers of Hmox1 and may explain in part the protective cardiovascular effects of diets rich in these compounds.

Laser surgery as a treatment for histologically confirmed sarcoids in the horse.

REASONS FOR PERFORMING STUDY: Laser resection for the treatment of sarcoids is an established part of equine practice; however, few studies have provided long-term follow-up results. Additionally, many previous reports have evaluated several treatments concurrently or have not been able to provide a definitive histological diagnosis of sarcoid. OBJECTIVES: To establish the success rate following laser resection as a sole treatment for histologically confirmed sarcoids and evaluate risk factors for recurrence. STUDY DESIGN: Retrospective time-to-event analysis. METHODS: Horses included had laser surgery to remove at least one sarcoid between 1 July 2005 and 1 September 2012. No previous known/concurrent veterinary treatment was administered. Diagnosis was confirmed by histology in all cases. Clinical data were retrieved from the hospital database. Follow-up information was obtained by telephone questionnaire. RESULTS: Ninety-nine horses, with a total of 235 sarcoids, were included in the analysis; 82 (83%) had no recurrence of the sarcoid removed and 71 (72%) had no occurrence of any sarcoids following surgery. Horses with sarcoids on the head and neck and those with verrucose sarcoids were at increased risk of recurrence (hazard ratios of 1.61 and 4.03, and 95% confidence intervals of 1.02-2.56 and 1.11-14.7, respectively). CONCLUSIONS: Laser resection of sarcoids in the horse has a positive post operative prognosis. Further work is required to fully evaluate risk factors for recurrence fully.

Can preoperative thyroglobulin antibody levels be used as a marker for well differentiated thyroid cancer?

BACKGROUND: It has been reported that thyroglobulin antibody are more frequently elevated in patients with thyroid cancercompared to general population. This study aims at evaluating whether preoperative thyroglobulin antibody (TgAb) levels increase the likelihood that a thyroid nodule is malignant. METHODS: A retrospective review of 586 patients who underwent thyroidectomy was conducted. Demographic data, TgAb levels, and final histopathology were recorded. Patients were divided into two groups: TgAb positive (defined as TgAb ≥ 30 IU/ml) and TgAb low/negative (defined as TgAb < 30). RESULTS: Preoperative TgAb levels were available in 405 patients. There were 353 (87 %) patients in the TgAblow/negative group (malignancy rate: 50.42 %) and 52 (13 %) patients in the TgAb positive group (malignancy rate: 65.38 %). The sensitivity, specificity, positive predictive value and negative predictive value of TgAb ≥ 30 IU/ml for thyroid malignancy were 16.04 %, 90.67 %, 65.38 % and 49.58 %, respectively. The relative risk of having a malignant thyroid nodule when the TgAb titers were≥30 IU/ml was 1.30 (CI1.04-1.62) and the odds ratio was 1.86 (CI 1.01-3.41). Both the Pearson chi-square test (p = 0.024) and Fisher's exact test (p = 0.017) yielded statistical significance between the two groups. CONCLUSIONS: In this study, patients with preoperative TgAb ≥ 30 IU/ml had a higher rate of malignancy when compared topatients with TgAb < 30 IU/ml. This suggests that an elevated TgAb level may indicate that a thyroid nodule is at an increased risk for malignancy.

Costs and complications of equine castration: a UK practice-based study comparing 'standing nonsutured' and 'recumbent sutured' techniques.

REASONS FOR PERFORMING STUDY: Clinicians are often asked to guide owners and trainers over the relative advantages and disadvantages of equine castration performed in either the standing horse with an open unsutured scrotal wound with healing by second intention, or a recumbent horse under general anaesthesia in aseptic conditions, with sutured scrotal skin allowing primary wound closure. OBJECTIVES: To identify types and frequency of complications following the 2 differing approaches, and to compare the financial cost associated with each procedure, based on practice charges. METHODS: Veterinary expenses of 217 horses castrated by a Newmarket equine veterinary practice over an 18-month period were analysed. Of these, Group 1 (n = 121) were castrated standing and nonsutured by one of 2 ambulatory clinicians and Group 2 (n = 96) castrated in recumbency, in aseptic equine hospital conditions. RESULTS: Group 1 had a complication prevalence of 22% with no mortalities, and Group 2 a significantly lower complication prevalence of 6% (P = 0.001) with a mortality rate of 1%. The financial cost of Group 1, without complications, was approximately one-third of the cost of uncomplicated Group 2. However, the cost of Group 1 with complications increased to approximately two-thirds of the cost of an uncomplicated Group 2 castration. CONCLUSIONS: Even though the complication prevalence for Group 1 castrations leaving an open scrotal wound was significantly higher than for a recumbent horse with a sutured scrotal wound in a hospital, the average cost of Group 1 was still less, even taking into account the additional follow-up costs associated with treating such complications. POTENTIAL RELEVANCE: This report provides a benchmark for the outcome of 2 methods of castration based on a database obtained from particular circumstances within the practice involved. Further studies are required to corroborate and take into account future development in surgical and anaesthetic techniques.

Osteoarthritis of the talocalcaneal joint in 18 horses.

REASONS FOR PERFORMING STUDY: Talocalcaneal osteoarthritis (TO) is an uncommon cause of moderate to severe hindlimb lameness, on which only isolated case reports have been published to date. OBJECTIVES: To review the clinical features of TO and determine optimal methods for diagnosis, management and prognosis. METHODS: The case records from 4 referral centres of 18 horses showing hindlimb lameness considered, as a result of clinical investigation, to be caused by TO, were reviewed. RESULTS: TO affected mature sports and pleasure horses (age 7-16 years) and caused moderate to severe lameness, usually of sudden onset with no obvious inciting cause. There were few localising signs, other than worsening of lameness by hock flexion. Tarsocrural joint analgesia produced improvement in lameness in 6/11 horses (55%) and perineural analgesia of the tibial and fibular nerves complete soundness in 6/14 horses (43%) in which it was performed; 7/14 horses (50%) showed a further substantial improvement. Radiological findings included subchondral bone lysis and sclerosis and irregular joint space width, seen most obviously in a lateromedial view. Nuclear scintigraphy revealed marked uptake of radiopharmaceutical predominantly plantaromedially in the region of the talus in the 7 horses in which it was performed. Fourteen horses were treated conservatively with box- or pasture-rest, with or without intra-articular corticosteroids, hyaluronic acid or polysulphated glycosaminoglycan, and all remained lame. Intra-articular corticosteroids appeared to have no effect in any horse. Of 10 horses receiving conservative management only, 6 were subjected to euthanasia, 3 were retired and 1 remained in light work, but was still lame. Two horses treated by either partial tibial and fibular neurectomy or subchondral forage failed to regain soundness and were retired. Six horses were treated by surgical arthrodesis of the talocalcaneal joint with 2 or three 5.5 mm AO screws introduced obliquely across the joint from the plantarolateral aspect of the calcaneus, which resulted in improvement in lameness in all cases. CONCLUSIONS: Osteoarthritis of the talocalcaneal joint causes acute onset severe lameness, but clinical findings and diagnostic analgesia often fail to identify precisely the site of pain. Consistent radiographic changes suggested TO was contributing to the lameness and this diagnosis was supported by nuclear scintigraphy. The poor success of conservative treatment (including intra-articular medication) suggests that surgical arthrodesis is the treatment of choice, although the prognosis is still poor for a return to full soundness. POTENTIAL RELEVANCE: The clinical features described should facilitate more accurate diagnosis and prognosis. A novel surgical treatment is described which appears to offer significant improvement in the lameness. Further work is necessary to determine the causes of this condition and more effective management.

Prevalence of supporting limb laminitis in a UK equine practice and referral hospital setting between 2005 and 2013: implications for future epidemiological studies.

The electronic patient records of all equine patients of Rossdales Equine Practice between January 1, 2005 and November 1, 2013 were reviewed to determine the number of cases of supporting limb laminitis (SLL) in a large equine practice and referral hospital setting in the UK and to discuss the implications for future epidemiological studies. The clinical notes were searched electronically for a combination of 'laminitis AND (contralateral OR supporting OR overload OR weight bearing)'. The prevalence of SLL within each identified denominator population and the corresponding 95% CI were calculated. SLL developed in nine horses, one donkey and one pony. Thoroughbreds were the most commonly affected breed (72.7 per cent, CI 46.4 to 99.1 per cent), aged 2-14 years (median six years), and only mares (n=9) and stallions (n=2) were represented. SLL was not restricted to horses that were non-weightbearing lame, it developed within 4-100 days after injury (median 14.5 days) and occurred most commonly in a forelimb (54.6 per cent, CI 25.1 to 84.0 per cent). During the same time frame, a total of 65,327 horses were registered with Rossdales Equine Practice, resulting in an overall practice prevalence of SLL of 0.02 per cent (CI 0.01 to 0.03 per cent). Future epidemiological studies to investigate risk factors for SLL prevention will, therefore, be a logistical challenge.

Phage therapy: the peculiar kinetics of self-replicating pharmaceuticals.

The specter of antibiotic-resistant bacteria has provoked renewed interest in the possible use of bacteriophages to control bacterial infections. We argue that clinical application of phage therapy has been held back by a failure to appreciate the extent to which the pharmacokinetics of self-replicating agents differ from those of normal drugs. For self-replicating pharmaceutical agents, treatment outcome depends critically on various density-dependent thresholds, often with apparently paradoxical consequences. An ability to predict these thresholds and associated critical time points is a necessity if phage therapy is to become clinically practicable.

Inferring the origins of state-dependent courtship traits.

We examine a simple model of state-dependent (indicator) traits that focuses on their evolutionary origins as courtship signals. A necessary condition for the initial evolution of signals was found: the marginal female preference for minimal traits must exceed a certain threshold, where that threshold is proportional to the marginal male fitness costs for minimal traits. We interpret a positive threshold as implying a need for preexisting sensory bias in order to overcome the threshold if indicator signals are to start to evolve. We extend the model to allow for the possibility that signal costs and female preferences may vary over evolutionary time. If there is independent information on the way that signaling costs have evolved, then one may use measurements of contemporary female preferences to make inferences concerning the presence of the ancestral threshold. It is the marginal female preferences for minimal male traits that are important, whereas reconstructing ancestral origins from measurement of average size signals is not informative. Our analyses suggest two foci for future studies: measurement of the marginal response of contemporary females to minimal male signals and reconstruction of how signaling costs have changed over evolutionary time.

The spatial dynamics of prion disease.

An important component of the latency period of the transmissible spongiform encephalopathies (prion diseases) can be attributed to delays during the propagation of the infectious prion isoform, PrPSc, through peripheral nervous tissues. A growing body of data report that the host prion protein, PrPC, is required in both peripheral and central nervous tissues for susceptibility to infection. We introduce a mathematical model, which treats the PrPSc as a mobile infectious pathogen, and show how peripheral delays can be understood in terms of the intercellular dispersal properties of the PrPSc strain, its decay rate, and its efficiency at transforming the PrPC. It has been observed that when two pathogenic strains co-infect a host, the presence of the first inoculated strain can slow down, or stop completely, the spread of the second strain. This is thought to result from a reduced concentration of host protein available for conversion by the second strain. Our model can explain the mechanisms of such interstrain competition and the time-course of the increased delay. The model provides a link between those data suggesting a role for a continuous chain of PrP-expressing tissue linking peripheral sites to the brain, and data on prion strain competition.

The evolution of virus-induced apoptosis.

Viruses from several different families are able to exploit their host's cell death programmes so as to maximize viral fitness. Consideration of the evolution of such strategies has lead to the suggestion that the virus should inhibit apoptosis, in order to prolong the life of the cell and thereby maximize the number of progeny virions. The host, on the other hand, should stimulate apoptosis thereby inhibiting viral growth and blocking viral spread. For example, the function of the latent membrane protein I (LMPI) of the Epstein-Barr virus and the bcl-2 homologue gene A179L of African swine fever virus is to inhibit apoptosis. However, in other cases it is the virus that stimulates cell death or the host that benefits from inhibiting apoptosis, such as in fatal alphavirus encephalitis. This has been explained by assuming that virus-induced apoptosis in non-regenerating cells would be detrimental to the host. We present a mathematical framework for understanding virus-induced apoptosis which accounts for these two opposite solutions to virus infection with respect to the mode of virus replication and the life cycle of the target cell.

Heavy metals have different effects on mycelial morphology of Achlya bisexualis as determined by fractal geometry.

The morphological response, as measured by changes to mycelial area, radial extension and border fractal dimension, of the oomycete Achlya bisexualis to Cu, Co, Hg, Zn and Cd at concentrations of between 0.05 and 3 mM is described. All of the metals decreased mycelial area and radial extension. Border fractal dimension increased in the presence of Cu, Co and Hg with individual hyphae extending out beyond the mycelial margin. In the presence of 3 mM Hg these hyphae displayed spiral growth. Zn and Cd had no effect on border fractal dimension. We suggest that all of the metals slow growth and that Cu, Co and Hg may also disrupt the relationship between tip growth and branching at the edge of the mycelium.

A cellular model to explain the pathogenesis of infection by the hepatitis B virus.

The natural history of infection by the hepatitis B virus (HBV) depends on many factors, including the age and immunological status of the patient, and can range from acute transient infection to subclinical chronic hepatitis. Persistent infection often leads to the development of primary hepatocellular carcinoma. We consider a cellular model of HBV infection based on the hypothesis that the liver contains two populations of cells with contrasting responses to the virus. Our findings show that the model can be used to account for the wide variety of clinical manifestations of infection and can explain the observed age dependence of the main different outcomes of the disease.