Androgens, Endometriosis and Pain

The intriguing relationship between androgens, endometriosis and chronic pain continues to unfold. Determining this relationship is of crucial importance to gynecologists managing people with these conditions, as common treatments dramatically alter her hormonal profiles, with both intended and unintended consequences. Although they may be present in the same individual, there is a recognized disconnect between pain or pain-related symptoms, and the presence or extent of endometriosis lesions. Reduced androgen levels provide a potential mechanism to link the development of endometriosis lesions and the presence of chronic pain. This research paper expands the presentation of our research at the World Endometriosis Congress in 2021, subsequently published in the Journal of Pain Research which demonstrated a strong inverse relationship between androgen levels and days per month of pelvic and period pain. Here we extend and further explore the evidence for a role for androgens in the etiology and management of dysmenorrhea and pelvic pain in women, both with and without endometriosis. We explore the potential for inflammation to induce low androgen levels and consider ways in which clinicians can optimize levels of androgens when treating women with these conditions. This article prompts the question: Is it estrogens that predispose people to a life of pain, or androgens that are protective?

The impact of the regional capital on center-periphery interactions – the case of Lviv and its surrounding region

o analyse the impact of Lviv on centre-periphery interactions the authors calculated the Socio-Economic Development Index for different districts of the region and considered the distance of each district from the regional capital. The Socio-Economic Development Index (Іr) of each district was calculated as the arithmetic mean of indices of its economic (Іе) and social (Іs) development. A strong inverse relationship was found between districts’ indices and their distances from the regional capital (R = –0.69). The indices were used to classify districts into three categories: central, semi-peripheral, and peripheral. The central category includes districts located within a 50-km radius of Lviv and their indices range from 0.5 to 0.7. Semi-peripheral districts are located within the radius of 50-75 km and their Іr values range from 0.3 to 0.5. Peripheral districts are located at the furthest distance from the regional centre, and their Іr values are below 0.3. Because the correlation between the distance from the regional center and index value for some districts was not consistent with the general pattern, two subtypes of districts were also added – core and ancillary. The authors demonstrate that the impact of the regional capital on the socio-economic development of administrative districts decreases with their increasing distance from the regional center. The level of socio-economic development in districts depends, on the one hand, on the strength of impulses generated by the regional center, and on the other hand, is determined by the local economic capacity and ability to absorb the impacts of the regional center and other local growth poles.

A higher burden of multiple sclerosis genetic risk confers an earlier onset

Background: Age at onset of multiple sclerosis (MS) is an objective, influential predictor of the evolution of MS independent of disease duration. Objectives: Determine the influence of MS genetic predisposition on age of onset. Methods: We conducted a comprehensive investigation of MS risk variants and age at onset in 3495 non-Latinx white individuals, including for combinations of HLA-DRB1*15:01 alleles and quintiles of an unweighted genetic risk score (GRS) for 198 of 200 autosomal MS risk variants that reside outside the major histocompatibility complex. Results: The mean age at onset was 32 years, 29% were male, and 46% were HLA-DRB1*15:01 carriers. For those with the greatest genetic risk burden (the highest GRS quintile with two HLA-DRB1*15:01 alleles) were on average 5 years younger at onset ( p = 0.002) than those with the lowest genetic risk burden (the lowest GRS quintile with no HLA-DRB1*15:01 alleles). There was a strong inverse relationship between the MS genetic risk burden and age at onset of MS ( p < 5 × 10−8). Conclusion: We demonstrate a significant gradient between elevated MS genetic risk burden and an earlier onset of MS, suggesting that a higher MS genetic risk burden accelerates onset of the disease.

High pretreatment systemic immune-inflammation index values are associated with diminished short-term success after temporomandibular joint arthrocentesis procedure

Background The systemic immune-inflammation index (SII) has been demonstrated to be a valid biomarker of a patient's immunological and inflammatory state, with the ability to accurately predict outcomes in a variety of disease conditions. In the absence of comparable studies, we intended to examine the relevance of pretreatment SII in predicting the success rates of temporomandibular joint arthrocentesis (TMJA) at 1-week, 1-month, and 6-month periods, defined as maximum mouth opening (MMO) > 35 mm and VAS ≤ 3. Methods A sum of 136 patients with disc displacement without reduction (DDwo-red) who underwent TMJA was included. For each patient, pre-TMJA SII was calculated as; SII = Platelets × neutrophils/lymphocytes. Additionally, baseline MMO and VAS measurements were recorded for each patient. The success criteria of TMJA included MMO > 35 mm and VAS ≤ 3. The optimal pre-TMJA SII cutoff that predicts TMJA success was determined using receiver operating characteristic (ROC) curve analysis. The primary endpoint was the link between the pre-treatment SII and TMJA success (simultaneous achievement of MMO > 35 mm and VAS ≤ 3). Results The median pre-TMJA jaw locking duration, maximum mouth opening (MMO), and visual analog score (VAS) were 7 days, 24 mm, and 8, respectively. The overall TMJA success rates were determined as 80.1%, 91.9%, and 69.1% at 1-week, 1-month, and 6-months, respectively. The results of ROC curve analysis exhibited the optimal SII cutoff at 526 (AUC: 67.4%; sensitivity: 66.7%; specificity: 64.2%) that grouped the patients into two subgroups: Group 1: SII ≤ 526 (N = 81) and SII > 526 (N = 55), respectively. Spearman correlation analysis revealed a strong inverse relationship between the pretreatment SII values and the success of TMJA 1-week (rs: − 0.83; P = 0.008) and 1-month, (rs: − 0.89; P = 0.03). Comparative analyses displayed that TMJA success rates at 1-week (87.7% vs. 69.1%; P = 0.008) and 1-month (96.2% vs. 80%; P = 0.03) were significantly higher in the SII ≤ 526 than SII > 526 group, respectively, while the 6-month results favored the SII ≤ 526 group with a trend approaching significance (P = 0.084). Conclusion The current study's findings suggested the SII as a unique independent prognostic biomarker that accurately predicts treatment outcomes for up to 6 months. Trial registration The results of this research were retrospectively registered.

High Pretreatment Systemic Immune-Inflammation Index Values are Associated with Diminished Short-term Success After Temporomandibular Joint Arthrocentesis Procedure

Background To retrospectively assess the significance of the pretreatment systemic immune-inflammation index (SII) in predicting the success of temporomandibular joint arthrocentesis (TMJA) at 1-week, 1- month, and 6-month time points. Methods A sum of 136 patients with disc displacement without reduction (DDwo-red) who underwent TMJA was included. For each patient, pre-TMJA SII was calculated as; SII = Platelets × neutrophils/lymphocytes. The success criteria of TMJA included MMO > 35 mm and VAS ≤ 3. The optimal pre-TMJA SII cutoff that predicts TMJA success was determined using receiver operating characteristic (ROC) curve analysis. The primary endpoint was the link between the pre-treatment SII and TMJA success. Results The median pre-TMJA jaw locking duration, maximum mouth opening (MMO), and visual analog score (VAS) were 7 days, 24 mm, and 8, respectively. The overall TMJA success rates were determined as 80.1%, 91.9%, and 69.1% at 1-week, 1-month, and 6-months, respectively. The results of ROC curve analysis exhibited the optimal SII cutoff at 526 (AUC:67.4%; sensitivity:66.7%; specificity:64.2%) that grouped the patients into two subgroups: Group 1: SII ≤ 526(N = 81) and SII > 526(N = 55), respectively. Spearman correlation analysis revealed a strong inverse relationship between the pretreatment SII values and the success of TMJA 1-week (rs: -0.83; P = 0.008) and 1-month, (rs:-0.89; p = 0.03). Comparative analyses displayed that TMJA success rates at 1-week (87.7% versus 69.1%; P = 0.008) and 1-month (96.2% versus 80%; p = 0.03) were significantly higher in the SII ≤ 526 than SII > 526 group, respectively, while the 6-month results favored the SII ≤ 526 group with a trend approaching significance (p = 0.084). Conclusion The current study's findings suggested the SII as a unique independent prognostic biomarker that accurately predicts treatment outcomes for up to 6 months. Trial registration: The results of this research were retrospectively registered.

Electrochemical quantification of accelerated FADGDH rates in aqueous nanodroplets

Enzymes are molecules that catalyze reactions critical to life. These catalysts are often studied in bulk water, where the influence of water volume on reactivity is neglected. Here, we demonstrate rate enhancement of up to two orders of magnitude for enzymes trapped in submicrometer water nanodroplets suspended in 1,2-dichloroethane. When single nanodroplets irreversibly adsorb onto an ultramicroelectrode surface, enzymatic activity is apparent in the amperometric current-time trace if the ultramicroelectrode generates the enzyme cofactor. Nanodroplet volume is easily accessible by integrating the current-time response and using Faraday’s Law. The single nanodroplet technique allows us to plot the enzyme’s activity as a function of nanodroplet size, revealing a strong inverse relationship. Finite element simulations confirm our experimental results and offer insights into parameters influencing single nanodroplet enzymology. These results provide a framework to profoundly influence the understanding of chemical reactivity at the nanoscale.

HISTOMORPHOMETRIC ESTIMATION OF AGE FROM BONE SAMPLES OF NIGERIANS

Background. Age estimation is crucial in creating the biological profile of unknown skeletal remains and recently there is emphasis on the need to develop population specific forensic baseline data for easy identification of these remains. Objective. The aim of this study is to estimate age from the histomorphometric features of the bones of Nigerians. Methods. Fragments of non-pathologic bone samples were collected during orthopaedic procedures. Ground sections were prepared using Modified Frost’s manual method of bone preparation to determine the following histologic parameters; haversian canal diameter (HCD), primary and secondary osteons, number of osteon fragments and non-haversian canal as well as haversian canal area (HCA). 29 subjects aged 35 to 85 years old were used for the study. Bone fragments included samples from the femur, tibia, humerus, and the vertebrae. Data obtained were subjected to descriptive statistics, Pearson’s correlation, bivariate regression equation, Student t-test and analysis of variance (ANOVA). Results. The mean age for our population was 58.86 years old. ANOVA showed significant variation in the average HCD for the various regions: humerus=8.45±2.48, femur=7.09±4.06, tibia=8.70±2.52 and verte­brae=3.69±0.73. There was a strong inverse relationship between age and primary osteons. The total number of osteon fragments increased with age while total number of primary osteons and average HCD decreased with age. The HCA, though statistically insignificant, also decreased with age. Conclusion. Our findings show that three histomorphometric parameters showed significant correlation with age: osteon fragments (OS-f), primary osteons (OS-p) and HCD. The histomorphometric parameters were therefore relevant in age estimation. Objective: The aim of this study is to estimate age from the histologic features of the bones of Nigerians. Methods: Fragments of non-pathologic bone samples were collected during orthopaedic procedures. Ground sections were prepared using Modified Frost’s manual method of bone preparation to determine the following histologic parameters; haversian canal diameter (HCD), primary and secondary osteons, number of osteon fragments and non haversian canal as well as haversian canal area (HCA). 29 subjects aged 35 to 85 years were used for the study. Bone fragments included samples from the femur, tibia, humerus, and the vertebrae. Data obtained were subjected to descriptive statistics, Pearson’s correlation, bivariate regression equation, student t-test and Analysis of variance (ANOVA). Results: The mean age for our population was 58.86 years. ANOVA shows significant variation in the average HCD for the various regions: humerus=8.45±2.48, femur=7.09±4.06, tibia=8.70±2.52 and vertebrae=3.69±0.73. There is a strong inverse relationship between age and primary osteons. The total number of osteon fragments increased with age while total number of primary osteons and average HCD decreased with age. The HCA though statistically insignificant, also decreased with age. Conclusion: Our findings show that three histomorphometric parameters showed significant correlation with age: osteon fragments (OS-f), primary osteons (OS-p) and HCD. The histomorphometric parameters are therefore relevant in age estimation. Key words: Age estimation, Histomorphometric parameters, Nigerians, Forensics

Divergent Trends of Lifespan Variation During Mortality Crises

Lifespan variation has been attracting increasingly greater attention as a measure of population health and mortality. Several studies have analysed periods of steady mortality decline, highlighting a strong inverse relationship between lifespan variation and life expectancy. Recent research has found that this association weakens, and even reverses, when mortality does not improve equally over age. However, to date no study has comprehensively explored the behaviour of lifespan variation when mortality increases significantly. Analysing three epidemics and two famines in Europe from the eighteenth to the twentieth centuries, we find that, during these events, relative lifespan variation increases, while absolute variation declines, and that subsequently both quickly revert to pre-crisis levels. Using decomposition techniques, we show that mortality at older ages leads to a temporary increase in absolute – but not relative – variation. Moreover, female lifespan variation is less affected by the crises than that of males, because of the higher impact of infant and child mortality on male lifespan variation. By underlining different trends of lifespan variation by sex and indicator, we offer new insight into the consequences of mortality crises. Contrary to what is often asserted, we also show that the choice of lifespan variation indicator is not always inconsequential.

Nephron-Deficient HSRA Rats exhibit Renal Injury with Age but have Limited Renal Damage from Streptozotocin-Induced Hyperglycemia

Hypertension and diabetes are the greatest factors influencing the progression of chronic kidney disease (CKD). Investigation into the role of nephron number in CKD alone or with hypertension has revealed a strong inverse relationship between the two; however, not much is known about the connection between nephron number and diabetic kidney disease. The HSRA rat, a novel model of nephron deficiency, provides a unique opportunity to study the association between nephron number and hypertension and diabetes on CKD. HSRA rats exhibit failure of one kidney to develop in 50-75% of offspring while remaining offspring are born with two kidneys. Rats born with one kidney (HSRA-S) develop significant renal injury with age compared to two-kidney littermates (HSRA-C). Induction of hypertension as a secondary stressor leads to significantly more renal injury in HSRA-S compared to HSRA-C and HSRA-UNX (nephrectomized HSRA-C rats). The current study sought to address the hypothesis that nephron deficiency in the HSRA rat would hasten renal injury in the presence of a secondary stressor of hyperglycemia. HSRA animals did not exhibit diabetes-related traits at any age, thus streptozotocin (STZ) was used to induce hyperglycemia in HSRA-S, HSRA-C, and HSRA-UNX. STZ and vehicle-treated animals were followed for 15 weeks. STZ animals developed robust hyperglycemia, but in contrast to the response to hypertension, HSRA-S nor HSRA-UNX animals developed proteinuria compared to vehicle. In total, our data indicates that hyperglycemia from STZ alone does not have a significant impact on the onset or progression of injury in young one kidney HSRA animals.

Assessing Environmental Attitudes and Cognitive Achievement within 9 Years of Informal Earth Education

Given the multitude of attitude scales, we examined the relationship between the 2-Major Environmental Values model (2-MEV) and the New Environmental Paradigm scale (NEP) based on a 6585 child sample over a 9-year period. The students participated in a three-day outdoor earth education program at field centers in three different US states (Arizona, Pennsylvania, and Louisiana). We further investigated the scales’ sensitivity to program effects, relating cognitive achievement and attitude with respect to a pro-environmental indicator of behavior (Y key). NEP and Preservation correlated highly, while the subscales Utilization and Preservation showed a strong inverse relationship. Based on further reliability and validity scores, and in line with the literature, this pointed to a unidimensional Preservation of Nature scale as a concise attitude measurement. In structural equation modelling, Preservation related to knowledge gains and the Y key, and effects from Preservation on knowledge held true for all three states. This suggests Preservation as one factor influencing cognitive achievement and environmentally conscious performance. Regarding program effects, the Earthkeepers program seemed to induce pro-environmental shifts based on knowledge gains and attitude changes (Preservation increasing and Utilization decreasing). Pro-environmental shifts were most prominent for those who received the Y key.