The isolation of Ant1, a transposable element from Aspergillus niger

A transposable element has been isolated from the industrially important fungus Aspergillus niger (strain N402). The element was identified as an insertion sequence within the coding region of the nitrate reductase gene. It had inserted at a TA site and appeared to have duplicated the target site upon insertion. The isolated element was found to be 4798 by in length and contained 37-bp inverted, imperfect, terminal repeats (ITRs). The sequence of the central region of the element revealed an open reading frame (designated ORF1) which showed similarity, at the amino acid level, to the transposase of the Tc1/mariner class of DNA transposons. Another sequence within the central region of the element showed similarity to the 3′ coding and downstream untranslated region of the amyA gene of A. niger. Sequence homology and structural features indicate that this element, which has been named Ant1 (A. niger transposon 1), is related to the Tc1/mariner group of DNA transposons. Ant1 is apparently present as a single copy in strain N402 of A. niger.     

Hemagglutinin of unusual specificity from Helcococcus kunzii

Helcococcus kunzii is a gram-positive, catalase-negative opportunist. The organism has been isolated from the lower extremities and breast masses of several patients. A clinical isolate of Helcococcus kunzii was shown to possess a hemagglutinin-lectin with a specificity for N-acetylglucosamine and lactose, two structurally unrelated carbohydrates. The lectin is sensitive to protease, heat and mutanolysin. Electron microscopy failed to reveal fimbriae or fibrillae, suggesting that the lectin is associated with peptidoglycan or the cytoplasmic membrane. It is likely that the lectin is involved in adhesion and colonization of H. kunzii.     

Pathogenicity of Salmonella Strains Isolated from Egg Shells and the Layer Farm Environment in Australia

In Australia, the egg industry is periodically implicated during outbreaks of Salmonella food poisoning. Salmonella enterica serovar Typhimurium and other nontyphoidal Salmonella spp., in particular, are a major concern for Australian public health. Several definitive types of Salmonella Typhimurium strains, but primarily Salmonella Typhimurium definitive type 9 (DT9), have been frequently reported during egg-related food poisoning outbreaks in Australia. The aim of the present study was to generate a pathogenicity profile of nontyphoidal Salmonella isolates obtained from Australian egg farms. To achieve this, we assessed the capacity of Salmonella isolates to cause gastrointestinal disease using both in vitro and in vivo model systems. Data from in vitro experiments demonstrated that the invasion capacity of Salmonella serovars cultured to stationary phase (liquid phase) in LB medium was between 90- and 300-fold higher than bacterial suspensions in normal saline (cultured in solid phase). During the in vivo infection trial, clinical signs of infection and mortality were observed only for mice infected with either 10³ or 10⁵ CFU of S. Typhimurium DT9. No mortality was observed for mice infected with Salmonella serovars with medium or low invasive capacity in Caco-2 cells. Pathogenicity gene profiles were also generated for all serovars included in this study. The majority of serovars tested were positive for selected virulence genes. No relationship between the presence or absence of virulence genes by PCR and either in vitro invasive capacity or in vivo pathogenicity was detected. Our data expand the knowledge of strain-to-strain variation in the pathogenicity of Australian egg industry-related Salmonella spp.     

Weight Control Behaviors Among Adult Men and Women: Cause for Concern?

NEUMARK-SZTAINER, DIANNE, NANCY E. SHERWOOD, SIMONE A. FRENCH, AND ROBERT W. JEFFERY. Weight control behaviors among adult men and women: cause for concern? Obes Res. Objectives To examine gender differences in weight control behaviors; their duration and the consistency of their use over a 3-year period; and variations of these behaviors by body mass index (BMI). Research Methods and Procedures The study population included 714 women and 229 men participating in a community-based weight gain prevention program who completed surveys about their weight control behaviors annually for 3 years. General dieting behaviors (e.g., current, regular, and past dieting), dietary restraint (using Restrained Eating subscale of the Three-Factor Eating Questionnaire), and specific weight control practices (e.g., increasing exercise, skipping meals, and taking laxatives) were assessed. Results Women were more likely than men to report weight control behaviors, with particularly strong associations found between gender and “history of dieting” (odds ratio = 8.1) and “participation in an organized weight loss program” (odds ratio = 11.7). Among both genders, exercise was the most frequently reported specific weight loss practice (66% of women and 53% of men), followed by decreasing fat intake (62% of women and 48% of men). The use of at least one unhealthy weight control behavior over the past year was reported by 22% of the women and 17% of the men. Gender differences were not found for duration of use of most of the specific weight control practices over the past year, or for consistency of general dieting behaviors and dietary restraint over time. Although both gender and BMI were strongly associated with dieting behaviors, interactions between gender and BMI on prevalence rates of dieting were not significant. Discussion Although weight control behaviors were more prevalent among women than men, in general, large gender differences were not found in the types of behaviors used and the duration and consistency of their use. The high percentages of adults using healthy methods of weight control was encouraging. However, there is still cause for concern, in that unhealthy weight control practices were also reported by a significant percentage of the population.     

Effects of Chronic Viral Infection on Lymphocyte Populations in Middle‑aged Baboons (Papio anubis)

Aging of the immune system is characterized by the loss of naïve T-cells, increased inflammation, and immune function impairment. Chronic infection with cytomegalovirus is thought to play a role in age-related changes in immunity. Therefore, to assess the effect of pathogens such as cytomegalovirus on the immune system, we determined lymphocyte populations and inflammatory markers over a 3-y period in captive, middle-age baboons, with various exposure to pathogens and shedding pressure. Groups included SPF (i.e., pathogen-negative; n = 14); large-group, conventionally housed (CONV LG; pathogen-positive; n = 14), and small-group, conventionally housed (CONV SM; pathogen-positive; n = 7). All baboon groups showed a decrease in CD45RA+ CD28+ (i.e., naive) cells over time during middle age, but the rate of decline appeared faster in CONV LG baboons than in the other groups. In addition, the reduction in CD45RA+ CD28+ cells in the CONV LG baboons coincided with higher IgG levels against baboon cytomegalovirus, increased serum cortisol concentration, and a greater inflammatory phenotype. The results of this project support a role for cytomegalovirus infection in immune system alterations in middle-aged baboons.

In 2010, an estimated 8% of the world''s population was 65 y or older, and by 2050 the world''s aged population is estimated to reach 16%.²⁹ As people live longer, age-related diseases and conditions place an increased burden on public health and may place tremendous hardship on individual families. Aging is the number one risk factor for numerous diseases, including Alzheimer disease, cardiovascular disease, cancer, and diabetes.³⁰ Practices that improve wellbeing and allow for extended periods of productivity in the aged population will help lower the costs of long-term care for individual families and to society as a whole.²⁹ Further complicating matters, many older adults have multiple, concurrent age-related diseases, making specific disease-targeted treatment approaches less efficient. Treatments targeting the deficiencies underlying aging diseases would therefore be preferable. The increased susceptibility to disease in the elderly is due, in part, to a progressive weakening of the immune system, a process known as immunosenescence. Understanding how age affects immunity may offer more broad-reaching therapeutic targets to reduce the cost of long-term care while it helps to improve health and wellbeing among aged populations.Aging is associated with an altered immune system that includes loss of naïve T lymphocytes, accumulation of T lymphocytes negative for the costimulatory receptor CD28, altered cytokine expression, and increased inflammatory markers.^7,16,28,39 Evidence indicates that immunosenescence reduces overall health and contributes to a rise of disease in the elderly.^7,8,10 Infection with chronic pathogens has been implicated in the aging of immune function.^32,39 Antigenic stress from chronic viruses, particularly cytomegalovirus, is thought to contribute to age-related changes in the immune system.¹ Cytomegalovirus is a β-herpesvirus that rarely causes symptoms in healthy individuals despite establishing a lifelong infection in its host.⁶ Starting in middle age and accumulating over a lifetime, the constant immune response to cytomegalovirus viral antigens is thought to significantly reduce the overall efficiency of the immune system.¹³Chronic infection with pathogens like cytomegalovirus has been suggested to contribute to immunosenescence by causing decreases in naïve cells and increases in late-differentiated memory lymphocytes.^1,6,32 Naive lymphocytes are an essential defense against infection by new pathogens. Some direct evidence in other species suggests that decreases in the naive T-cell pool could limit the ability of the elderly to respond to a novel immune stimulus appropriately.³⁶ Naive lymphocytes are activated through a process that involves the costimulatory receptor, CD28.²⁴ High numbers of lymphocytes negative for CD28 are linked to a reduced response to influenza vaccines and increased inflammatory diseases in the elderly.^35,38,41 Although correlations between chronic viruses and aging of the immune system have been identified in several species, critical questions regarding the direct effects of chronic viruses on the immune system changes remain unanswered.To better determine the role of chronic viruses in age-related changes in the immune system, appropriate animal models are necessary. The genetics and physiology of NHP are similar to those in humans and, therefore, these species have distinct advantages over other animal models. In addition, NHP carry viruses that are closely related to viruses naturally infecting humans. However, little research examining the general effects of age on immunocompetence in NHP is available. Previous studies by our laboratory found that olive baboons (Papio anubis) show age-associated alterations in the immune system.^26,46 In conventionally raised baboons 6 to 26 y old, we discovered that T cells aged in a manner like what has been described in people.⁴⁶ In addition, aged baboons were found to exhibit a proinflammatory state.²⁶ Although the cited study²⁶ supports the idea that aging causes impairment of cell-mediated immunity and a proinflammatory phenotype, the cause of these changes was not addressed. Therefore, in the current study, we sought to test the hypothesis that baboons with the most exposure to chronic pathogens, particularly baboon cytomegalovirus (BaCMV), will show the most profound changes in the immune system, whereas animals lacking exposure to chronic pathogens will have better preservation of immune function over time.     

Regret,shame, and denials of women's voluntary sterilization

Women face extraordinary difficulty in seeking sterilization as physicians routinely deny them the procedure. Physicians defend such denials by citing the possibility of future regret, a well‐studied phenomenon in women's sterilization literature. Regret is, however, a problematic emotion upon which to deny reproductive freedom as regret is neither satisfactorily defined and measured, nor is it centered in analogous cases regarding men's decision to undergo sterilization or the decision of women to undergo fertility treatment. Why then is regret such a concern in the voluntary sterilization of women? I argue that regret is centered in women's voluntary sterilization due to pronatalism or expectations that womanhood means motherhood. Women seeking voluntary sterilization are regarded as a deviant identity that rejects what is taken to be their essential role of motherhood and they are thus seen as vulnerable to regret.     

Total knee replacement after high tibial osteotomy: time-to-event analysis and predictors

BACKGROUND:An important aim of high tibial osteotomy (HTO) is to prevent or delay the need for total knee replacement (TKR). We sought to estimate the frequency and timing of conversion from HTO to TKR and the factors associated with it.METHODS:We prospectively evaluated patients with osteoarthritis (OA) of the knee who underwent medial opening wedge HTO from 2002 to 2014 and analyzed the cumulative incidence of TKR in July 2019. The presence or absence of TKR on the HTO limb was identified from the orthopedic surgery reports and knee radiographs contained in the electronic medical records for each patient at London Health Sciences Centre. We used cumulative incidence curves to evaluate the primary outcome of time to TKR. We used multivariable Cox proportional hazards analysis to assess potential preoperative predictors including radiographic disease severity, malalignment, correction size, pain, sex, age, body mass index (BMI) and year of surgery.RESULTS:Among 556 patients who underwent 643 HTO procedures, the cumulative incidence of TKR was 5% (95% confidence interval [CI] 3%–7%) at 5 years and 21% (95% CI 17%–26%) at 10 years. With the Cox proportional hazards multivariable model, the following preoperative factors were significantly associated with an increased rate of conversion: radiographic OA severity (adjusted hazard ratio [HR] 1.96, 95% CI 1.12–3.45), pain (adjusted HR 0.85, 95% CI 0.75–0.96)], female sex (adjusted HR 1.67, 95% CI 1.08–2.58), age (adjusted HR 1.50 per 10 yr, 95% CI 1.17–1.93) and BMI (adjusted HR 1.31 per 5 kng/m², 95% CI 1.12–1.53).INTERPRETATION:We found that 79% of knees did not undergo TKR within 10 years after undergoing medial opening wedge HTO. The strongest predictor of conversion to TKR is greater radiographic disease at the time of HTO.

The burden of knee osteoarthritis (OA) on patients and health care systems is substantial and growing.¹ The current treatment strategy that relies largely on total knee replacement (TKR) for end-stage disease may not be sustainable.^2–5 Reduced quality of life and loss of productivity due to knee OA in middle-aged people in the workforce is particularly problematic.^5–8 The global prevalence of knee OA peaks at about 50 years of age.⁹ Worldwide, the estimated years lived with disability is 2.4 million for people younger than 50 years of age, the approximate age of peak prevalence for knee OA.^9,10 Accordingly, the number of middle-aged patients seeking treatment for knee OA, including TKR, is increasing. ¹¹ Joint replacement may not be the most appropriate treatment for these patients.¹² Earlier TKR is associated with prosthesis infection, ¹³ lower patient satisfaction¹⁴ and revision surgery;^15–18 about 25% of all TKRs are considered “likely inappropriate.”¹⁹ Clinicians have identified a clear treatment gap between exhausting nonoperative management and appropriateness for TKR, resulting in years of pain, decreased function, productivity losses and associated costs.^5–9,20,21 It is therefore imperative to identify additional effective treatments for the large group of patients with knee OA.Medial opening wedge high tibial osteotomy (HTO) is a limb realignment surgery intended for patients with medial compartment knee OA who are not suitable candidates for TKR because of less severe disease, younger age and greater physical demands. The purpose of HTO is to correct malalignment, thereby shifting load away from the more involved knee compartment and limit OA progression.^22,23 Substantial shifts in knee loading^24,25 have resulted in clinically important improvements in pain and function after HTO^26,27 and the procedure is cost-effective,^28,29 yet the surgery is uncommon in Canada.³⁰ Unlike the high and increasing rates of other knee surgical procedures including arthroscopy³¹ and TKR,³² rates of HTO remain low.^33,34High tibial osteotomy may help fill the treatment gap between nonsurgical treatments and definitive TKR. At the London Health Sciences Centre in London, Ontario, HTO is performed frequently with a goal of preventing or delaying the need for TKR. Thus, it is appropriate to investigate the duration of benefit of HTO, and the preoperative characteristics associated with it. When quantified as conversion from HTO to TKR, registries using administrative data enable large sample sizes (> 2500 patients) to estimate cumulative incidence of TKR.^30,35,36 However, there can be limitations in using only administrative data, including confirming the correct procedure, limb and diagnosis. Administrative data often lack detailed information assessed preoperatively, such as radiographic features (e.g., disease severity and lower limb alignment) and patient-reported outcome measures. Previously reported predictors of conversion to TKR such as female sex and greater age^30,35–39 may be influenced (perhaps confounded) by other clinical characteristics not typically included in administrative data. Therefore, our objective was to investigate the cumulative incidence of TKR after medial opening wedge HTO and potential predictors using data collected prospectively from a single Canadian centre that focuses on HTO. Specifically, we evaluated the time to conversion from HTO to TKR and investigated the association of HTO preoperative characteristics with subsequent TKR.     

Support for vicariant origins of the New Zealand Onychophora

Aim The distribution of Onychophora across the southern continents has long been considered the result of vicariance events. However, it has recently been hypothesized that New Zealand was completely inundated during the late Oligocene (25–22 Ma) and therefore that the entire biota is the result of long-distance dispersal. We tested this assumption using phylogenetic and molecular dating of DNA sequence data from Onychophora. Location New Zealand, Australia, South Africa, Chile (South America). Methods We obtained DNA sequence data from the nuclear genes 28S and 18S rRNA to reconstruct relationships among species of Peripatopsidae (Onychophora). We performed molecular dating under a Bayesian relaxed clock model with a range of prior distributions using the rifting of South America and South Africa as a calibration. Results Our phylogenetic trees revealed that the New Zealand genera Ooperipatellus and Peripatoides, together with selected Australian genera (Euperipatoides, Phallocephale and an undescribed genus from Tasmania), form a monophyletic group that is the sister group to genera from Chile (Metaperipatus) and South Africa (Peripatopsis and Opisthopatus). The relaxed clock dating analyses yielded mean divergence times from 71.3 to 78.9 Ma for the split of the New Zealand Peripatoides from their Australian sister taxa. The 0.95 Bayesian posterior intervals were very broad and ranged from 24.5 to 137.6 Ma depending on the prior assumptions. The mean divergence of the New Zealand species of Ooperipatellus from the Australian species Ooperipatellus insignis was estimated at between 39.9 and 46.2 Ma, with posterior intervals ranging from 9.5 to 91.6 Ma. Main conclusions The age of Peripatoides is consistent with long-term survival in New Zealand and implies that New Zealand was not completely submerged during the Oligocene. Ooperipatellus is less informative on the question of continuous land in the New Zealand region because we cannot exclude a post-Oligocene divergence. The great age of Peripatoides is consistent with a vicariant origin of this genus resulting from the rifting of New Zealand from the eastern margin of Gondwana and supports the assumptions of previous authors who considered the Onychophora to be a relict component of the New Zealand biota.