A coding single nucleotide polymorphism in the interleukin-6 receptor enhances IL-6 signalling in CD4 T cells and predicts treatment response to tocilizumab in giant cell arteritis.

Objectives: The study objective was to determine if a common single nucleotide polymorphism in the interleukin 6 (IL-6) receptor (rs2228145, p.Asp358Ala) predicted treatment response to tocilizumab in giant cell arteritis (GCA).

Methods: Genetic sequencing of the rs2228145 locus was performed in 2 independent cohorts of patients with GCA.

Single-cell profiling identifies a CD8 CD244 Natural Killer cell subset that reflects disease activity in HLA-A29-positive birdshot chorioretinopathy.

Birdshot chorioretinopathy is an inflammatory eye condition strongly associated with MHC-I allele HLA-A29. The striking association with MHC-I suggests involvement of T cells, whereas natural killer (NK) cell involvement remains largely unstudied. Here we show that HLA-A29-positive birdshot chorioretinopathy patients have a skewed NK cell pool containing expanded CD16 positive NK cells which produce more proinflammatory cytokines.

Predictors of Retirement Voluntariness Using Canadian Longitudinal Study on Aging Data.

Involuntary exit from the labor force can lead to poor health and well-being outcomes. Therefore, the purpose of this research is to better understand the factors that contribute to perceived retirement voluntariness. We conducted descriptive and multivariable logistic regression analyses using a sample of recent retirees ( = 2080) from the Canadian Longitudinal Study on Aging (CLSA).

Eye movements disrupt EEG alpha-band coding of behaviorally relevant and irrelevant spatial locations held in working memory.

Oscillations in the alpha frequency band (∼8-12 Hz) of the human electroencephalogram play an important role in supporting selective attention to visual items and maintaining their spatial locations in working memory (WM). Recent findings suggest that spatial information maintained in alpha is modulated by interruptions to continuous visual input, such that attention shifts, eye closure, and backward masking of the encoded item cause reconstructed representations of remembered locations to become degraded. Here, we investigated how another common visual disruption-eye movements-modulates reconstructions of behaviorally relevant and irrelevant item locations held in WM.

Habituation of the stress response multiplex to repeated cold pressor exposure.

Humans show remarkable habituation to aversive events as reflected by changes of both subjective report and objective measures of stress. Although much experimental human research focuses on the effects of stress, relatively little is known about the cascade of physiological and neural responses that contribute to stress habituation. The cold pressor test (CPT) is a common method for inducing acute stress in human participants in the laboratory; however, there are gaps in our understanding of the global state changes resulting from this stress-induction technique and how these responses change over multiple exposures.

Prevalence and Correlates of Military Sexual Trauma in Service Members and Veterans: Results From the 2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey.

Introduction: Military sexual trauma (MST) is an ongoing problem. We used a 2002 population-based sample, followed up in 2018, to examine: (1) the prevalence of MST and non-MST in male and female currently serving members and veterans of the Canadian Armed Forces, and (2) demographic and military correlates of MST and non-MST.

Methods: Data came from the 2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (n = 2,941, ages 33 years + ).

Lessons Learned From Presumptive Condition Lists in Veteran Compensation Systems.

Presumptive condition lists formally accept connections between military factors and veteran health conditions. An environmental scan of such lists and their evidentiary basis was conducted across four veterans' administrations to inform other administrations considering the development of such lists. Information on included conditions, qualifying military factors, and scientific processes was obtained through targeted internet searches and correspondence with veterans' administrations.

Affecting the effectors: JAK inhibitors modulation of immune cell numbers and functions in patients with rheumatoid arthritis.

Introduction: The Janus kinase family includes four members - JAK1, JAK2, JAK3, TYK2 - that are selectively associated with type I and II cytokine receptors. Jak-inhibitors (Jakinibs) are a new class of drugs for treating inflammatory diseases. Five Jakinibs are currently available for Rheumatoid Arthritis (RA): tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib.

Evaluation of the in vitro susceptibility of various filarial nematodes to emodepside.

Filariae are vector-borne nematodes responsible for an enormous burden of disease. Human lymphatic filariasis, caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori, and onchocerciasis (caused by Onchocerca volvulus) are neglected parasitic diseases of major public health significance in tropical regions. To date, therapeutic efforts to eliminate human filariasis have been hampered by the lack of a drug with sufficient macrofilaricidal and/or long-term sterilizing effects that is suitable for use in mass drug administration (MDA) programs, particularly in areas co-endemic with Loa loa, the causative agent of loiasis.

Health care access and use among male and female Canadian Armed Forces veterans.

Background: Veterans are more likely than other Canadians to have chronic health conditions, making access to health care an important issue. However, little research has addressed health care access and use among veterans. This paper examines access and use among veterans compared with other Canadians.

Lifetime Prevalence and Comorbidity of Mental Disorders in the Two-wave 2002-2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (CAFVMHS): Prévalence et Comorbidité de Durée de vie Des Troubles Mentaux Dans l'Enquête de Suivi Sur la Santé Mentale Auprès des Membres des Forces Armées Canadiennes et Des ex-Militaires (ESSMFACM) en Deux Cycles de 2002 à 2018.

Objective: The current study used the Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (CAFVMHS) to (1) examine the incidence and prevalence of mental disorders and (2) estimate the comorbidity of mental disorders over the follow-up period.

Method: The CAFVMHS (2018) is a longitudinal study with two time points of assessment. The sample is comprised of 2,941 Canadian Forces members and veterans who participated in the 2002 Canadian Community Health Survey: Canadian Forces Supplement.

The impact of COVID-19 on systemic anticancer treatment delivery in Scotland.

Understanding the impact of the COVID-19 pandemic on systemic anticancer therapy delivery (SACT) is crucial to appreciate the short- and long-term consequences for cancer patients and plan future care. Here, we report real-time national SACT delivery data from NHS Scotland. We demonstrate an initial rapid reduction in patient attendance of 28.

Considering Exposure Assessment in Epidemiological Studies of Chronic Health in Military Populations.

Exposure assessment is an important factor in all epidemiological research seeking to identify, evaluate, and control health risks. In the military and veteran context, population health research to explore exposure-response links is complicated by the wide variety of environments and hazards encountered during active service, long latency periods, and a lack of information on exposures in potentially vulnerable subgroups. This paper summarizes some key considerations for exposure assessment in long-term health studies of military populations, including the identification of hazards related to military service, characterization of potentially exposed groups, exposure data collection, and assignment of exposures to estimate health risks.

Dual Process Coding of Recalled Locations in Human Oscillatory Brain Activity.

A mental representation of the location of an object can be constructed using sensory information selected from the environment and information stored internally. Human electrophysiological evidence indicates that behaviorally relevant locations, regardless of the source of sensory information, are represented in alpha-band oscillations suggesting a shared process. Here, we present evidence from human subjects of either sex for two distinct alpha-band-based processes that separately support the representation of location, exploiting sensory evidence sampled either externally or internally.

Effects of diethylcarbamazine and ivermectin treatment on gene expression in infected gerbils ().

Lymphatic filariasis (LF) threatens nearly 20% of the world's population and has handicapped one-third of the 120 million people currently infected. Current control and elimination programs for LF rely on mass drug administration of albendazole plus diethylcarbamazine (DEC) or ivermectin. Only the mechanism of action of albendazole is well understood.

Does evaluation of in vitro microfilarial motility reflect the resistance status of Dirofilaria immitis isolates to macrocyclic lactones?

Background: Several reports have confirmed that macrocyclic lactone-resistant isolates of Dirofilaria immitis are circulating in the United States; however, the prevalence and potential impact of drug resistance is unknown. We wished to assess computer-aided measurements of motility as a method for rapidly assessing the resistance status of parasite isolates.

Methods: Blood containing microfilariae (MF) from two clinical cases with a high suspicion of resistance was fed to mosquitoes and the resultant L3 injected into dogs that were then treated with six doses of Heartgard® Plus (ivermectin + pyrantel; Merial Limited) at 30-day intervals.

Deuterium Isotope Effects in Polymerization of Benzene under Pressure.

The enormous versatility in the properties of carbon materials depends on the content of the sp and sp covalent bonds. Under compression, if intermolecular distances cross a critical threshold, then unsaturated hydrocarbons gradually transform to saturated carbon polymers. However, the mechanism of polymerization, even for benzene, the simplest aromatic hydrocarbon, is still not understood.

How do the macrocyclic lactones kill filarial nematode larvae?

The macrocyclic lactones (MLs) are one of the few classes of drug used in the control of the human filarial infections, onchocerciasis and lymphatic filariasis, and the only one used to prevent heartworm disease in dogs and cats. Despite their importance in preventing filarial diseases, the way in which the MLs work against these parasites is unclear. In vitro measurements of nematode motility have revealed a large discrepancy between the maximum plasma concentrations achieved after drug administration and the amounts required to paralyze worms.

Irrelevant learned reward associations disrupt voluntary spatial attention.

Attention can be guided involuntarily by physical salience and by non-salient, previously learned reward associations that are currently task-irrelevant. Attention can be guided voluntarily by current goals and expectations. The current study examined, in two experiments, whether irrelevant reward associations could disrupt current, goal-driven, voluntary attention.

Expression of nicotinic acetylcholine receptor subunits from parasitic nematodes in Caenorhabditis elegans.

The levamisole-sensitive nicotinic acetylcholine receptor present at nematode neuromuscular junctions is composed of multiple different subunits, with the exact composition varying between species. We tested the ability of two well-conserved nicotinic receptor subunits, UNC-38 and UNC-29, from Haemonchus contortus and Ascaris suum to rescue the levamisole-resistance and locomotion defects of Caenorhabditis elegans strains with null deletion mutations in the unc-38 and unc-29 genes. The parasite cDNAs were cloned downstream of the relevant C.

Irrelevant reward and selection histories have different influences on task-relevant attentional selection.

Task-relevant and physically salient features influence visual selective attention. In the present study, we investigated the influence of task-irrelevant and physically nonsalient reward-associated features on visual selective attention. Two hypotheses were tested: One predicts that the effects of target-defining task-relevant and task-irrelevant features interact to modulate visual selection; the other predicts that visual selection is determined by the independent combination of relevant and irrelevant feature effects.

Neural evidence reveals the rapid effects of reward history on selective attention.

Selective attention is often framed as being primarily driven by two factors: task-relevance and physical salience. However, factors like selection and reward history, which are neither currently task-relevant nor physically salient, can reliably and persistently influence visual selective attention. The current study investigated the nature of the persistent effects of irrelevant, physically non-salient, reward-associated features.