Chlamydia trachomatis Infection and Seropositivity in Women Reporting Sexual Contact to a Chlamydia-Infected Partner.

ABSTRACT: Among 73 women presenting to a sexually transmitted infection (STI) clinic in Birmingham, Alabama for reported sexual contact to a chlamydia-infected partner, Chlamydia trachomatis was detected in genital specimens in 24 (32.8%), less often in women reporting prior chlamydial infection ( P = 0.001). Most women (93.2%) were C. trachomatis seropositive.

Vulnerability of the spinal motor neuron presynaptic terminal sub-proteome in ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, characterised by the loss of motor neurons and subsequent paralysis. Evidence indicates that synaptic alterations are associated with the early stages of ALS pathogenesis. A hallmark of ALS postmortem tissue is the presence of proteinaceous inclusions, indicative of disturbed protein homeostasis, particularly in spinal cord motor neurons. We recently demonstrated that spinal cord motor neurons contain a supersaturated proteome, as they possess proteins at concentrations that exceed their solubility limits, resulting in a metastable proteome conducive to protein misfolding and aggregation. Recent evidence indicates metastable sub-proteomes within neuronal compartments, such as the synapse, may be particularly vulnerable and underlie their involvement in the initial stages of neurodegenerative diseases. To investigate if the motor neuron presynaptic terminal possesses a metastable sub-proteome, we used human and mouse spinal cord motor neuron expression data to calculate supersaturation scores. Here, we found that both the human and mouse presynaptic terminal sub-proteomes have higher supersaturation scores than the entire motor neuron proteome. In addition, we observed that proteins down-regulated in ALS were over-represented in the synapse. These results provide support for the notion that the metastability of the sub-proteome within the motor neuron presynaptic terminal may be particularly susceptible to protein homeostasis disturbances in ALS, and may contribute to explaining the observed synaptic dysfunction in ALS.

CuATSM improves motor function and extends survival but is not tolerated at a high dose in SOD1G93A mice with a C57BL/6 background.

The synthetic copper-containing compound, CuATSM, has emerged as one of the most promising drug candidates developed for the treatment of amyotrophic lateral sclerosis (ALS). Multiple studies have reported CuATSM treatment provides therapeutic efficacy in various mouse models of ALS without any observable adverse effects. Moreover, recent results from an open label clinical study suggested that daily oral dosing with CuATSM slows disease progression in patients with both sporadic and familial ALS, providing encouraging support for CuATSM in the treatment of ALS. Here, we assessed CuATSM in high copy SOD1G93A mice on the congenic C57BL/6 background, treating at 100 mg/kg/day by gavage, starting at 70 days of age. This dose in this specific model has not been assessed previously. Unexpectedly, we report a subset of mice initially administered CuATSM exhibited signs of clinical toxicity, that necessitated euthanasia in extremis after 3-51 days of treatment. Following a 1-week washout period, the remaining mice resumed treatment at the reduced dose of 60 mg/kg/day. At this revised dose, treatment with CuATSM slowed disease progression and increased survival relative to vehicle-treated littermates. This work provides the first evidence that CuATSM produces positive disease-modifying outcomes in high copy SOD1G93A mice on a congenic C57BL/6 background. Furthermore, results from the 100 mg/kg/day phase of the study support dose escalation determination of tolerability as a prudent step when assessing treatments in previously unassessed models or genetic backgrounds.

Age over 25 years, but not plasma adrenocorticotropic hormone con-cen-tration above the seasonally adjusted reference range is predictive for radio-graphically assessed changes of chronic laminitis in elderly horses.

INTRODUCTION: Endocrinopathic laminitis occurs as a consequence of hormonal derangements like pituitary pars intermedia dysfunction (PPID). The objective of the present study was to assess the occurrence of radiographic changes associated with chronic laminitis in elderly, clinically sound horses. Fifty-one horses were included in the study. Horses were assigned to different age groups, in groups according to their BCS and CNS as well as to groups with different ACTH concentrations in order to assess their risk of chronic laminitis (reported as odds ratios (OR) and confidence intervals (CI)). Horses assigned to an older age group (26-32 years) were significantly more likely to have radiographically assessed changes of chronic laminitis than horses in a younger age group (15-25 years) (OR 3.33; CI 1.05-10.59). The other variables (body condition score, cresty neck score, ACTH concentration) were not associated with an increased risk of having laminitic changes in these horses.

INTRODUCTION: La fourbure endocrinopathique survient à la suite de troubles hormonaux tels que le dysfonctionnement de la pars intermedia de l'hypophyse (DPIH). L'objectif de la présente étude était d'évaluer les changements radiographiques associés à la fourbure subclinique chez les chevaux âgés cliniquement sains. Cinquante et un chevaux ont été inclus dans l'étude. Les chevaux ont été assignés à différents groupes d'âge, en groupes en fonction de leur Body Condition Score (BCS) et de leur Cresty Neck Score (CNS) ainsi que des groupes avec différentes concentrations d'ACTH afin d'évaluer leur risque de fourbure chronique (rapportés sous forme de rapports de cotes (Odds-Ratio, OR) et d'intervalles de confiance (IC)). Les chevaux faisant partie d'un groupe d'âge plus avancé (26 à 32 ans) étaient significativement plus susceptibles de présenter des signes radiographiques de fourbure chronique que les chevaux d'un groupe d'âge plus jeune (15 à 25 ans) (OR 3,33; IC 1,05­10,59). Les autres variables (BCS, CNS, concentration d'ACTH) n'étaient pas associées à un risque accru de modifications de type fourbure chez ces chevaux.

Ubiquitin Homeostasis Is Disrupted in TDP-43 and FUS Cell Models of ALS.

A major feature of amyotrophic lateral sclerosis (ALS) pathology is the accumulation of ubiquitin (Ub) into intracellular inclusions. This sequestration of Ub may reduce the availability of free Ub, disrupting Ub homeostasis and ultimately compromising cellular function and survival. We previously reported significant disturbance of Ub homeostasis in neuronal-like cells expressing mutant SOD1. Here, we show that Ub homeostasis is also perturbed in neuronal-like cells expressing either TDP-43 or FUS. The expression of mutant TDP-43 and mutant FUS led to UPS dysfunction, which was associated with a redistribution of Ub and depletion of the free Ub pool. Redistribution of Ub is also a feature of sporadic ALS, with an increase in Ub signal associated with inclusions and no compensatory increase in Ub expression. Together, these findings suggest that alterations to Ub homeostasis caused by the misfolding and aggregation of ALS-associated proteins play an important role in the pathogenesis of ALS.

[Professional entry into equine medicine]. / Berufseinstieg von Staatsabgängern in die Pferdemedizin.

INTRODUCTION: In the present study phone interviews on working hours, salary, professional satisfaction and other topics were carried out with 30 equine veterinarians. None of the participants had more than five years of work experience. The gross annual wages ranged from CHF 36'400 to CHF 91'500. The study participants worked 42 to 93 hours per week. Only 13% were moderately satisfied with the job, the remaining participants were satisfied to highly satisfied. Sixty percent of the study participants were dissatisfied with their wages and wished to be paid according to the Swiss Veterinary Association (GST) salary recommendations. Five out of 27 wages were within the recommended ranges. The lowest wages were paid at the universities. Sixteen people worked more than the legal maximum of 50 hours a week. A big difference in total working hours per week existed. Especially since part-time workers had more working hours than participants in a full-time job. The study reflects the situation before 2018 and especially at the universities, before the introduction of a new employment contracts with a 50h week, wage adjustments and defined times for further training.

INTRODUCTION: Dans cette étude, 30 vétérinaires travaillant dans des pratiques et des cliniques équines ont été interrogés par téléphone quant à leurs heures de travail, leur revenu, leur satisfaction et d'autres sujets. Ils n'avaient pas plus de cinq ans d'expérience professionnelle. Le salaire annuel brut allait de 36 400 CHF à 91 500 CHF. Les participants à l'étude ont travaillé de 42 à 93 heures par semaine. Seuls 13% étaient modérément satisfaits de leur place de travail, les autres étaient satisfaits voire entièrement satisfaits. Soixante pour cent des participants à l'étude étaient insatisfaits de leur salaire et souhaitaient être payés conformément à la recommandation salariale de la SVS. Cinq des 27 salaires se situaient dans ces fourchettes suggérées. Les salaires les plus bas étaient payés par l'université. Seize personnes travaillaient plus que le maximum légal de 50 heures par semaine. Il y avait également une grande différence dans le nombre d'heures travaillées par semaine. En particulier les travailleurs à temps partiel avaient parfois travaillé plus d'heures que ceux disposant d'un emploi à temps plein. L'étude reflète la situation, notamment dans les universités, avant l'introduction d'un nouveau contrat de travail avec la semaine de 50h, les ajustements salariaux et les horaires définis pour la formation continue à partir de janvier 2018.

HLA-DQB1*06 is a risk marker for chlamydia reinfection in African American women.

Associations between human leukocyte antigen (HLA) variants and chlamydia-related outcomes have been inconsistent. We previously identified HLA-DQB1*06 as a risk marker for chlamydia reinfection in a cohort of predominately HIV-infected adolescents. As chlamydia reinfection can lead to reproductive complications, validation of this finding in HIV-seronegative women may help reveal the underlying biology. We performed HLA-DQB1 genotyping in HIV-seronegative, chlamydia-infected African American women who were evaluated for reinfection at 3- and 6-month visits after treatment. Of 185 evaluable women for whom HLA-DQB1 genotyping was performed, only HLA-DQB1*06 was associated with chlamydia reinfection (P = 0.009), with no evidence of a dose-response effect for this allele. African American women with HLA-DQB1*06 may warrant more frequent chlamydia screening. More comprehensive genotyping of HLA class II and neighboring genes is needed to establish whether HLA-DQB1*06 is a causal variant for chlamydia reinfection or a surrogate for other causal variants in the major histocompatibility complex.

An Adaptive Chlamydia trachomatis-Specific IFN-γ-Producing CD4+ T Cell Response Is Associated With Protection Against Chlamydia Reinfection in Women.

Background: Adaptive immune responses that mediate protection against Chlamydia trachomatis (CT) remain poorly defined in humans. Animal chlamydia models have demonstrated that CD4+ Th1 cytokine responses mediate protective immunity against reinfection. To better understand protective immunity to CT in humans, we investigated whether select CT-specific CD4+ Th1 and CD8+ T cell cytokine responses were associated with protection against CT reinfection in women. Methods: Peripheral blood mononuclear cells were collected from 135 CT-infected women at treatment and follow-up visits and stimulated with CT antigens. CD4+ and CD8+ T-cells expressing IFN-γ, TNF-α, and/or IL-2 were assessed using intracellular cytokine staining and cytokine responses were compared between visits and between women with vs. without CT reinfection at follow-up. Results: A CD4+TNF-α response was detected in the majority (77%) of study participants at the treatment visit, but a lower proportion had this response at follow-up (62%). CD4+ IFN-γ and CD4+ IL-2 responses occurred less frequently at the treatment visit (32 and 18%, respectively), but increased at follow-up (51 and 41%, respectively). CD8+ IFN-γ and CD8+ TNF-α responses were detected more often at follow-up (59% for both responses) compared to the treatment visit (30% for both responses). At follow-up, a CD4+IFN-γ response was detected more often in women without vs. with reinfection (60 vs. 33%, P = 0.005). Conclusions: Our findings suggest that a CT-specific CD4+ IFN-γ response is associated with protective immunity against CT reinfection and is thus an important component of adaptive immunity to CT in women.

Performance of Chlamydia trachomatis OmcB Enzyme-Linked Immunosorbent Assay in Serodiagnosis of Chlamydia trachomatis Infection in Women.

Chlamydia trachomatis serological assays with improved sensitivity over commercially available assays are needed to evaluate the burden of C. trachomatis infection and the effectiveness of prevention efforts. We evaluated the performance of a C. trachomatis outer membrane complex protein B (OmcB) enzyme-linked immunosorbent assay (ELISA) in the detection of anti-C. trachomatis antibody responses in C. trachomatis-infected women. OmcB ELISA was less sensitive than our C. trachomatis elementary body (EB) ELISA, but it was highly specific. The magnitude of the antibody response was higher in African-Americans and those with prior C. trachomatis infection. Unlike EB ELISA, the IgG1 response to C. trachomatis OmcB was short-lived and was not maintained by repeat C. trachomatis infection.

Differences in Patterns of Mortality Between Foreign-Born and Native-Born Workers Due to Fatal Occupational Injury in the USA from 2003 to 2010.

This study assesses differences mortality patterns and relative hazard due to fatal occupational injuries between native and immigrant workers in the US. Fatal occupational injury data from 2003 to 2010 were examined using survival analysis based on proportional hazards models controlling for categorical variables of race, gender, occupation, and industry. Workers are stratified based on whether they are native to the US (n = 31952) or born abroad (n = 7096). Foreign-born workers are further stratified into region of birth. Foreign-born workers had an adjusted hazard ratio of 1.148 (95 % CI 1.109:1.189) relative to native workers. Stratifying foreign-born workers into region of origin revealed significantly higher adjusted risk of work fatality relative to native workers for most foreign regions. Of fatally injured workers, foreign-born workers have shorter survival before succumbing to traumatic injury during their time of occupational 'exposure' in the workforce. Native-born workers tend to incur fatal injuries at older ages after longer 'exposure'.

T cell phenotypes in women with Chlamydia trachomatis infection and influence of treatment on phenotype distributions.

T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38+HLA-DR+), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3+CCR5+ and CCR4+, respectively), and T cell homing marker (CCR7) for both CD4+ and CD8+ T cells in CT-infected women. At follow-up after treatment of infected women, there were a lower proportion of CD4+ and CD8+ T cells expressing these markers. These findings suggest a dynamic interplay of CD4+ and CD8+ T cells in CT infection, and once the infection is treated, these cell markers return to basal expression levels. In women without reinfection, a significantly higher proportion of CD8+ T cells co-expressing CXCR3 with CCR5 or CCR4 at follow-up was detected compared to women with reinfection, suggesting they might play some role in adaptive immunity. Our study elucidated changes in T cell phenotypes during CT infection and after treatment, broadening our understanding of adaptive immune mechanisms in human CT infections.

Lower Levels of Cervicovaginal Tryptophan Are Associated With Natural Clearance of Chlamydia in Women.

Chlamydiatrachomatis (Ct) infection causes significant morbidity. In vitro studies demonstrate that Ct growth inhibition occurs by interferon-gamma (IFN-γ)-mediated depletion of intracellular tryptophan, and some Ct strains utilize extracellular indole to restore tryptophan levels. Whether tryptophan levels are associated with Ct infection clearance in humans remains unknown. We evaluated tryptophan, indole, and IFN-γ levels in cervicovaginal lavages from women with either naturally cleared or persisting Ct infection. Women who cleared infection had significantly lower tryptophan levels and trended toward lower IFN-γ levels compared to women with persisting infection. Due to its volatility, indole was not measurable in either group.

Immunoglobulin-Based Investigation of Spontaneous Resolution of Chlamydia trachomatis Infection.

Chlamydia trachomatis elementary body enzyme-linked immunosorbent assay (ELISA) was used to investigate serum anti-CT immunoglobulin G1 (IgG1; long-lived response) and immunoglobulin G3 (IgG3; short-lived response indicating more recent infection) from treatment (enrollment) and 6-month follow-up visits in 77 women previously classified as having spontaneous resolution of chlamydia. Of these women, 71.4% were IgG1+IgG3+, consistent with more recent chlamydia resolution. 15.6% were IgG3- at both visits, suggesting absence of recent chlamydia. Using elementary body ELISA, we demonstrated approximately 1 in 6 women classified as having spontaneous resolution of chlamydia might have been exposed to C. trachomatis but not infected. Further, we classified their possible infection stage.

The Predominant CD4+ Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women Is Tumor Necrosis Factor Alpha and Not Interferon Gamma.

Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of C. trachomatis-specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4+ T cells, in protective immunity to chlamydia. To determine the frequency and magnitude of Th1 cytokine responses elicited to C. trachomatis infection in humans, we stimulated peripheral blood mononuclear cells from 90 chlamydia-infected women with C. trachomatis elementary bodies, Pgp3, and major outer membrane protein and measured IFN-γ-, tumor necrosis factor alpha (TNF-α)-, and interleukin-2 (IL-2)-producing CD4+ and CD8+ T-cell responses using intracellular cytokine staining. The majority of chlamydia-infected women elicited CD4+ TNF-α responses, with frequency and magnitude varying significantly depending on the C. trachomatis antigen used. CD4+ IFN-γ and IL-2 responses occurred infrequently, as did production of any of the three cytokines by CD8+ T cells. About one-third of TNF-α-producing CD4+ T cells coproduced IFN-γ or IL-2. In summary, the predominant Th1 cytokine response elicited to C. trachomatis infection in women was a CD4+ TNF-α response, not CD4+ IFN-γ, and a subset of the CD4+ TNF-α-positive cells produced a second Th1 cytokine.

"It Doesn't Require Much Effort Once You Get to Know Them": Certified Nursing Assistants' Views of Communication in Long-Term Care.

Certified nursing assistants (CNAs) provide the majority of hands-on care and become highly sensitive to residents' communication behaviors. Yet, CNAs feel disempowered when communicating residents' concerns to higher levels of authority. A grounded theory approach using focus group interviews with 23 CNAs was used to describe the communication environment in long-term care (LTC) and explore CNAs' perceptions of the acceptability of communication plans, a recent Canadian intervention to facilitate resident-staff communication. Findings suggest the communication environment in LTC relates to three overlapping constructs: (a) CNA and resident communication style; (b) paradox of context; and (c) dedication to residents. Although CNAs frequently interact with residents, a division between "top and bottom staff" communication was apparent in the findings. The current study suggested that communication plans may improve the communication environment in LTC settings. [Journal of Gerontological Nursing, 42(4), 42-51.].

Retrospective evaluation of all recorded horse race starts in Switzerland during a four year period focusing on discipline-specific risk factors for clinical events.

REASONS FOR PERFORMING STUDY: Racetrack injuries are of welfare concern and the prevention of injuries is an important goal in many racing jurisdictions. Over the years this has led to more detailed recording of clinical events on racecourses. However, risk factor analyses of clinical events at race meetings have not been previously reported for Switzerland. OBJECTIVES: To identify discipline-specific factors that influence the occurrence of clinical events during race meetings with the ultimate aim of improving the monitoring and safety of racetracks in Switzerland and optimising racehorse welfare. STUDY DESIGN: Retrospective study of horse race data collected by the Swiss horse racing association. METHODS: All race starts (n = 17,670, including 6198 flat, 1257 obstacle and 10,215 trot race starts) recorded over a period of 4 years (2009-2012) were analysed in multivariable mixed effect logistic regression models including horse and racecourse related data. The models were designed to identify discipline-specific factors influencing the occurrence of clinical events on racecourses in Switzerland. RESULTS: Factors influencing the risk of clinical events during races were different for each discipline. The risk of a clinical event in trot racing was lower for racing on a Porphyre sand track than on grass tracks. Horses whose driver was also their trainer had an approximately 2-fold higher risk for clinical events. In obstacle races, longer distances (2401-3300 m and 3301-5400 m, respectively) had a protective effect compared with racing over shorter distances. In flat racing, 5 racecourses reported significantly fewer clinical events. In all 3 disciplines, finishing 8th place or later was associated with clinical events. CONCLUSIONS: Changes in management that aim to improve the safety and welfare of racehorses, such as racetrack adaptations, need to be individualised for each discipline.

Investigating the epidemiology of repeat Chlamydia trachomatis detection after treatment by using C. trachomatis OmpA genotyping.

Repeat Chlamydia trachomatis detection frequently occurs within months after C. trachomatis infection treatment. The origins of such infection (persistence versus reinfection from untreated or new partners) are varied and difficult to determine. C. trachomatis strains can be differentiated by sequencing the ompA gene encoding the outer membrane protein A (OmpA). We used OmpA genotyping to investigate the epidemiology of repeat C. trachomatis detection after treatment in C. trachomatis-infected subjects seen at a sexually transmitted diseases clinic. Subjects were enrolled, tested for C. trachomatis, treated with azithromycin, and scheduled for a 6-month follow-up for repeat C. trachomatis testing. OmpA genotyping was performed on C. trachomatis-positive urogenital specimens obtained from patients at enrollment and follow-up. The enrollment visit OmpA genotypes for C. trachomatis were determined for 162 subjects (92% female, 94% African American). C. trachomatis was detected at follow-up in 39 subjects (24%). The OmpA genotype distribution at enrollment did not differ in those with versus those without repeat C. trachomatis detection. Of the 35 subjects with C. trachomatis strains genotyped at enrollment and follow-up, 7 (20%) had the same ompA sequence at both visits, while 28 (80%) had discordant sequences. A new sexual partner was reported more often in subjects with discordant C. trachomatis strains than in those with concordant strains (13 [46%] versus 1 [14%]; P = 0.195). Half of the subjects with discordant C. trachomatis strains who reported sexual activity since treatment denied a new sexual partner; 62% of these subjects reported that their partner was treated. Our study demonstrates that most repeat C. trachomatis detections after treatment were new infections with a different C. trachomatis strain rather than reinfection with the same strain. OmpA genotyping can be a useful tool in understanding the origins of repeat C. trachomatis detection after treatment.

Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection.

Novel vaccines are urgently needed to reduce the burden of severe malaria. Using a differential whole-proteome screening method, we identified Plasmodium falciparum schizont egress antigen-1 (PfSEA-1), a 244-kilodalton parasite antigen expressed in schizont-infected red blood cells (RBCs). Antibodies to PfSEA-1 decreased parasite replication by arresting schizont rupture, and conditional disruption of PfSEA-1 resulted in a profound parasite replication defect. Vaccination of mice with recombinant Plasmodium berghei PbSEA-1 significantly reduced parasitemia and delayed mortality after lethal challenge with the Plasmodium berghei strain ANKA. Tanzanian children with antibodies to recombinant PfSEA-1A (rPfSEA-1A) did not experience severe malaria, and Kenyan adolescents and adults with antibodies to rPfSEA-1A had significantly lower parasite densities than individuals without these antibodies. By blocking schizont egress, PfSEA-1 may synergize with other vaccines targeting hepatocyte and RBC invasion.

Methods for analysis of calcium/calmodulin signaling in cilia and flagella.

The axonemal microtubules of cilia/flagella act as a scaffold for assembly of the protein complexes that ultimately regulate dynein activity to control the size and shape of ciliary bends. Despite our general understanding of the contribution of microtubule sliding to ciliary and flagellar motility, many questions regarding the regulation of dynein remain unanswered. For example, we know that the second messenger calcium plays an important role in modulating dynein activity in response to extracellular cues, but it remains unclear how calcium-binding proteins anchored to the axoneme contribute to this regulation. Recent work has focused on determining the identity and specific functions of these axonemal calcium-binding proteins. Here, we review our current knowledge of calcium-mediated motility and highlight key experiments that have substantially aided our understanding of calcium signaling within the axoneme.