Interactions between Manipulation Induced Pain Modulation and Conditioned Pain Modulation Analgesia

The overall objective of this thesis was to improve our understanding of two forms of endogenous analgesia induced by conditioned pain modulation and manipulation induced pain modulation. The studies presented in this thesis have shown a significant association and a comparable increase in CPM and MIPM analgesia in response to enhanced empathetic interaction and aerobic exercise. This suggests that both forms of EA are potentially mediated by a common neuro-physiological mechanism

The influence of a positive empathetic interaction on conditioned pain modulation and manipulation induced analgesia in people with lateral epicondylalgia

Objective: Conditioned pain modulation (CPM) and manipulation induced analgesia (MIA) are two forms of endogenous analgesia. Many forms of analgesia can be influenced by the nature of the patient clinician interaction. The aim of this study was to evaluate the influence of an empathetic and supportive interaction on CPM and MIA in people with Lateral Epicondylalgia (LE). Methods: In a double-blind, randomised, controlled trial, 68 participants with LE were assigned to two groups: the empathetic and neutral interaction groups. The interactions were carried out by a trained, professional role play actor, playing the part of a research assistant (RA). The RA actor spent 15min prior to CPM and MIA assessment interacting with the participants in an empathetic or neutral manner. Immediately after the interaction, a blinded assessor measured pressure pain threshold (PPT) at the symptomatic elbow and ipsilateral wrist during CPM and MIA testing. Linear mixed models were used to evaluate differences in CPM and MIA responses between the interaction groups. Results: There was a significant difference in CARE scores between the groups (p\u3c0.001), indicating that the intervention group experienced a more empathic interaction. Both groups showed a significant increase in PPT measures, indicative of a CPM and MIA analgesic response (p\u3c0.001), however the analgesic responses were greater in the group that had experienced a supportive, empathetic interaction (post CPM, wrist: p\u3c0.001; elbow: p=0.001), (post MIA wrist: p=\u3c0.001; elbow: p=0.001). Discussion: A single session of empathetic interaction positively influenced both CPM and MIA responses in people with LE

Anthropogenic waste indicators (AWIs), particularly PAHs and LABs, in Malaysian sediments: application of aquatic environment for identifying anthropogenic pollution

Polycyclic aromatic hydrocarbons (PAHs) and linear alkylbenzenes (LABs) were used as anthropogenic markers of organic chemical pollution of sediments in the Selangor River, Peninsular Malaysia. This study was conducted on sediment samples from the beginning of the estuary to the upstream river during dry and rainy seasons. The concentrations of ƩPAHs and ƩLABs ranged from 203 to 964 and from 23 to 113 ng g− 1 dry weight (dw), respectively. In particular, the Selangor River was found to have higher sedimentary levels of PAHs and LABs during the wet season than in the dry season, which was primarily associated with the intensity of domestic wastewater discharge and high amounts of urban runoff washing the pollutants from the surrounding area. The concentrations of the toxic contaminants were determined according to the Sediment Quality Guidelines (SQGs). The PAH levels in the Selangor River did not exceed the SQGs, for example, the effects range low (ERL) value, indicating that they cannot exert adverse biological effects

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Solving first-order delay differential equation by symmetry lie group

The use of delay differential equations has become more popular among researches in the modeling of natural phenomena. A general solution for such models is still largely lacking. This paper develops a symmetry Lie groups method to find a general solution of first order delay differential equation of the form x'(t) = F(t; x(ґ)) + G(t; x(t-ґ)), where ґ is constant and ґ > 0. In this method a symmetry condition is applied on the given equation and some assumptions on infinitesimals are made to find the general solution. After the new coordinate system is found in which the solution depends on only one of the variables, the solution is then expressed in the original coordinates. The paper further generalizes this method to non-linear delay differential equations. At the end we applied these concept on Houseflies model, on which analysis of this model has not been carried out. It is thus shown that the symmetry Lie groups method is valid and feasible to the study of linear and non-linear delay differential equations