Higher Pain Tolerance Research Articles

How can the pain sensitivity to be affected by maximal progressive exercise test during pregnancy?

The multidimensional etiology of pain may explain the beneficial effects of regular physical activity, as evidenced by increased pain tolerance. Physically active people find it easier to exert themselves, which enables them to increase their physical activity, which in turn leads to a reduction in pain. However, no study investigated the physical activity and exercise tests as modulators of pain sensitivity in pregnant women. Therefore, this study aimed to investigate the changes in pain perception in pregnant women during pregnancy, with a particular interest in the effects of maximal progressive exercise test (CPET) and self-performed physical activity (PA). Thirty-one women with an uncomplicated singleton pregnancy (aged 23-41 years; M = 31.29, SD = 4.18) were invited to participate in pain sensitivity measurements before and after CPET twice during pregnancy (with an 8-week break). We found that pregnant women had a significantly lower pain threshold after a maximal exercise test than before, regardless of whether the test was performed in the second or third trimester of pregnancy. This effect was most pronounced in women with low levels of physical activity. Second, women with high physical activity had higher pain tolerance than women with moderate and low physical activity. In addition, physical activity levels predicted changes in pain tolerance over the course of pregnancy, with negative changes in women with low physical activity and positive changes in women with moderate physical activity. Finally, these associations were not reflected in differences in the subjective pain experience.

Soulful Rhythm, Dancing Bodies: Spirituality, Pain Tolerance, and the Risk of Lower Extremity Musculoskeletal Injuries Among Classical Kathak Dancers of India

Background: Dance and dancers reflect happiness, sadness, passion, anger, and all other emotions as every single dancing movement carries a significant signal that goes beyond words. Kathak, an Indian classical dance form, requires a divine balance between the soul and the physical body. This balance allows for a high pain tolerance of the dancers, but the spiritual nature of this dance form also generates ignorance and disinterest in their health seeking behavior towards injuries. Objectives: This comprehensive narrative review is aimed at exploring and examining the prevalence of lower extremity musculoskeletal injuries among Kathak dancers and proposes management strategies for their prevention and treatment. Methods: This review is based on a search of relevant articles, research papers, books and book chapters conducted across a wide array of online sources, utilizing the search engines like PubMed, Medline, CrossRef; etc. Considering the inclusion criterion, the review process included three stages: initial assessment of papers through title and abstract review, a detailed examination of relevant items, and systematic compilation of pertinent information into a categorized table under topical headings. Results: The review finds that the majority of injuries were reported in the foot and ankle region of dancers practicing Kathak. Conclusion: There is a need to develop supplementary exercise training programs and also spread awareness among dancers regarding their physical health and seeking medical care in time to delay/prevent lower extremity injuries.

SETBP1 haploinsufficiency and related disorders clinical and neurobehavioral phenotype study.

To comprehensively investigate the neurodevelopmental profile and clinical characteristics associated with SETBP1 haploinsufficiency disorder (SETBP1-HD) and SETBP1-related disorders (SETBP1-RD). We reported genetic results on 34 individuals, with behavior and clinical data from 22 with SETBP1-HD and 5 with SETBP1-RD, by assessing results from medical history interviews and standardized adaptive, clinical, and social measures provided from Simons Searchlight. All individuals with SETBP1-HD and SETBP1-RD exhibited neurological impairments including intellectual disability/developmental delay (IDD), attention-deficit/hyperactivity disorder, autism spectrum disorder, and/or seizures, as well as speech and language delays. While restricted interests and repetitive behaviors present challenges, a relative strength was observed in social motivation within both cohorts. Individuals with SETBP1-RD reported a risk for heart issues and compared to SETBP1-HD greater risks for orthopedic and somatic issues with greater difficulty in bowel control. Higher rates for neonatal feeding difficulties and febrile seizures were reported for individuals with SETBP1-HD. Additional prominent characteristics included sleep, vision, and gastrointestinal issues, hypotonia, and high pain tolerance. This characterization of phenotypic overlap (IDD, speech challenges, autistic, and attention deficit traits) and differentiation (somatic and heart issue risks for SETBP1-RD) between the distinct neurodevelopmental disorders SETBP1-HD and SETBP1-RD is critical for medical management and diagnosis.

"I Will Die by My Own Hand": Understanding the Development of Suicide Capability in the Narratives of Individuals Who Have Attempted Suicide.

Suicide capability is a multidimensional concept that facilitates the movement from suicidal ideation to suicide attempt. The three-step theory of suicide posits that three overarching contributors comprise suicide capability: acquired (fearlessness about death and high pain tolerance), dispositional (genetics), and practical (knowledge and access to lethal means) capability. Although extensive research has investigated relationships between individual contributors of capability and suicide attempts, little research has considered how an individual's capability for suicide develops as a combination of contributors. Given suicide is multifaceted and complex, our understanding of capability development is relatively limited. This potentially negatively impacts prevention and capacity reduction-focused intervention efficacy. Therefore, this study aimed to explore how suicide capability develops. Fourteen community-based suicide attempt survivors were recruited using convenience sampling. Individual narratives were collected using open-ended interviews, and data were analysed using narrative analysis. Results indicated that participant narratives contained two elements. The first included how capability development and suicide attempt facilitation were often underpinned by the relational interplay between acquired and practical contributors. For example, participants without a high pain tolerance seeking attempt methods that were perceived to be painless. The second element contained a novel finding relating to the agentic role of participants when deciding and attempting suicide. Agency was revealed within and across narratives emphasising the active role the individual plays in their movement from ideation-to-action. The role of individual agency in coming to a decision to take one's own life and then acting warrants further consideration within contemporary suicide theories.

Virtual Reality Facilitated Exercise Increases Sympathetic Activity and Reduces Pain Perception: A Randomized Crossover Study.

Both virtual reality (VR) and exercise reduce pain while avoiding the risks of traditional pharmacotherapy. The aim of this study was to assess how VR-facilitated exercise modulates sympathetic activity and pain perception. Healthy adult volunteers were randomized by hand dominance and then subjected to a standardized cold pressor test while experiencing a VR application. After a 5-minute washout, participants were crossed-over and repeated the test on their other hand while undergoing a VR-facilitated exercise application. Sympathetic activation, pain sensation, and pain tolerance data were collected identically during both conditions. 110 participants were analyzed. Sympathetic activity increased in both conditions but was higher in the VR-facilitated exercise condition (p < 0.0001). Pain sensation scores were initially higher with VR-facilitated exercise but dropped below the VR-only condition by the end of the intervention (p = 0.0175). There were no differences in pain tolerance between conditions (p = 0.18). The decrease in pain perception with VR-facilitated exercise condition compared to VR alone indicates VR-facilitated exercise can be a useful tool for managing pain. Though this effect did not translate into higher pain tolerance, VR-facilitated exercise may be a useful intervention in the setting of physical therapy or for patients with chronic pain.

Red-Haired People's Altered Responsiveness to Pain, Analgesics, and Hypnotics: Myth or Fact?-A Narrative Review.

Red hair has been linked to altered sensitivity to pain, analgesics, and hypnotics. This alteration may be impacted by variants in the melanocortin-1 receptor (MC1R) gene, which are mainly found in redheads. The aim of this narrative review was to explore and present the current state of knowledge on red hair and its plausible associations with altered responsiveness to pain, analgesics, and hypnotics. Structured searches in the PubMed, CINAHL Complete, and Scopus electronic databases were conducted. Evidence suggests that women with red hair have an increased sensitivity to pain. Conversely, data also indicate a higher pain tolerance in homozygous carriers of MC1R variant alleles. Varied responses to analgesia have been reported, with both increased analgesic responsiveness in homozygous carriers of MC1R variant alleles and less analgesia in redheads. Data indicate an increased need for hypnotics in redheads. However, failed attempts to find statistical associations between red hair and altered responsiveness to hypnotics are also evident. Even though there seems to be an association between red hair and an altered responsiveness to pain, analgesics, and/or hypnotics, the results of this narrative review are inconclusive. Further research studies with larger populations and MC1R testing are needed.

Pain tolerance as a ‘barrier’ to nonsuicidal self-injury: A longitudinal study

Theoretical perspectives underscore that low pain tolerance may be a relevant ‘barrier’ to non-suicidal self-injury (NSSI). However, there is limited longitudinal work on the link between pain tolerance and NSSI, which is needed to assess if pain tolerance precedes NSSI engagement, and/or if NSSI precedes altered pain tolerance. Further, assessing both NSSI frequency and versatility (or number of NSSI methods), in addition to engagement, can provide a more nuanced understanding of the influence of pain on NSSI severity. In the present study, 1125 undergraduate students at a large university (72 % female, Mage = 17.96) reported on their NSSI frequency, NSSI versatility, and perceived pain tolerance. Four individual regressions were run to examine the potential bidirectional nature of the association between NSSI frequency and pain tolerance, and NSSI versatility and pain tolerance. Pain tolerance predicted both NSSI frequency and versatility over time. Neither NSSI frequency nor versatility predicted pain tolerance. Results suggest that high pain tolerance may be a risk factor for severe NSSI engagement.

Pain sensitivity as a state marker and predictor for adolescent non-suicidal self-injury.

The pain analgesia hypothesis suggests that reduced pain sensitivity (PS) is a specific risk factor for the engagement in non-suicidal self-injury (NSSI). Consistent with this, several studies found reduced PS in adults as well as adolescents with NSSI. Cross-sectional studies in adults with borderline personality disorder (BPD) suggest that PS may (partially) normalize after remission or reduction of BPD symptoms. The objective of the present study was to investigate the development of PS over 1 year in a sample of adolescents with NSSI and to investigate whether PS at baseline predicts longitudinal change in NSSI. N = 66 adolescents who underwent specialized treatment for NSSI disorder participated in baseline and 1-year follow-up assessments, including heat pain stimulation for the measurement of pain threshold and tolerance. Associations between PS and NSSI as well as BPD and depressive symptoms were examined using negative binomial, logistic, and linear regression analyses. We found that a decrease in pain threshold over time was associated with reduced NSSI (incident rate ratio = 2.04, p = 0.047) and that higher pain tolerance at baseline predicted lower probability for NSSI (odds ratio = 0.42, p = 0.016) 1 year later. However, the latter effect did not survive Holm correction (p = 0.059). No associations between PS and BPD or depressive symptoms were observed. Our findings suggest that pain threshold might normalize with a decrease in NSSI frequency and could thus serve as a state marker for NSSI.

Individual Factors Modifying Postoperative Pain Management in Elective Total Hip and Total Knee Replacement Surgery.

Total hip and knee replacements are the most common orthopedic procedures performed due to osteoarthritis. Pain is an intrinsic symptom accompanying osteoarthritis, persisting long before surgery, and continuing during the preoperative and postoperative periods. Appropriate pain management after surgery determines the comfort, duration, and cost of hospitalization, as well as the effectiveness of postoperative rehabilitation. Individual differences in pain perception and tolerance in orthopedic patients remain an important research topic. Therefore, the aim of this study was to investigate the predictors of analgesic requirements (morphine, acetaminophen, and ketoprofen), including individual pain threshold and tolerance, body mass index (BMI), diabetes, and beliefs about pain control in patients undergoing elective hip or knee arthroplasty using a multilevel regression model (N = 147, 85 women, 62 men, 107 after hip replacement, and 40 after knee replacement). Results: Higher pain tolerance was associated with a lower dose of morphine per kg after surgery. Patients undergoing hip surgery received a lower dose of ketoprofen than patients undergoing knee surgery. The more the patient believed in personal pain control, the stronger the negative relationship between pain tolerance and morphine requirement. The lowest doses were given to patients with the highest pain tolerance and the greatest belief in personal control. Factors such as belief in pain control and pain tolerance should be considered in comprehensive postoperative pain management in orthopedic patients to reduce opioid doses and, thus, side effects.

Changes in pain perception during pregnancy after one-time maximal physical exertion and an 8-week high-intensity interval training.

Background: Pain, a subjective sensation, poses a great challenge to the human body as a stressor. There is empirical evidence that moderate to intense physical activity increases pain tolerance and this may be critical during pregnancy for optimal pregnancy, fetal development, and delivery. To the best of our knowledge, it is the first study examining the changes in pain perception in pregnant women after a maximal progressive exercise test and after 8weeks of high-intensity interval training (HIIT). Methods: Thirty-five women with uncomplicated singleton pregnancies between 13 and 28weeks of gestation participated in the study. The HIIT intervention was developed in accordance with the recommendations and available data on HIIT during pregnancy. The maximal progressive cardiopulmonary exercise test was performed on a cycle ergometer with an electronically controlled load. Pressure pain threshold and pressure pain tolerance were measured with an algometer. Results: We found significant effects of the maximal exercise test and high-intensity interval training, such that the pregnant women had higher pain tolerance after the maximal exercise test than before and after the high-intensity interval training than the baseline. Conclusion: Our results suggest that post-exercise analgesia may be important in pregnant women and that high-intensity interval training appears to be beneficial for pregnant women to improve their pain tolerance while being obstetrically safe. Increased pain tolerance before labor could lead to better management of pain during labor and in the postpartum and lactation periods. Increasing pregnant women's awareness of this issue can improve their wellbeing and provide more comfort during labor.

The Predictive Value of Cold Pack Test for Pain After Third Molar Surgery

Early identification of patients who are prone to postoperative pain may provide individualization of postoperative analgesia strategies. The aim of the study was to investigate whether the cold pack test is associated with postoperative pain levels after mandibular third molar surgery. This prospective cohort study included healthy male patients admitted to Department of Oral and Maxillofacial Surgery of a tertiary health-care center between June 2022 and December 2022 and scheduled for lower third molar extraction. Those who had used any analgesic within the past 10days or had a history of intolerance/allergy to analgesics were excluded. The primary predictor variable was pain tolerance, measured using the endurance test score. Subjects were grouped into two categories, low tolerance test score (withdrew the hand from the cold pack in <240seconds) and high tolerance test score (maintained the hand on the cold pack for 240seconds). The primary outcome variable was pain measured by the patients from 0 to 10 with the visual analog scale, and the secondary outcome variables were the amount of ibuprofen and paracetamol consumed in the postoperative period. Pain measurements and ibuprofen consumption were recorded at 0-2, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, and 96hours (0-2 interval of the first 2hours immediately after surgery). Age, classification and position of mandibular third molar were utilized as covariates. The relationship between pain tolerance and postoperative pain was analyzed using the Mann-Whitney U test and the Fisher exact test. Statistical analysis was performed using the SPSS version 28.0 software. A total of 30 male patients with a mean age of 22.5±4.8years were included in our study. In the group with low pain tolerance, the pain scores at the first 2hours, 32, and 48hours after the operation (4.55±3.59, 2.91±2.59, 2.91±2.43, respectively) were found to be significantly higher than the group with high pain tolerance (2.00±2.67, 0.95±1.68, 0.95±1.39, respectively) (P<.05). In the first 2hours after the operation, the amount of ibuprofen consumed was also significantly higher in the group with low pain tolerance compared to the other group, and 81.8% of this group felt the need to consume ibuprofen (P<.05). The cold pack test, a more practical version of quantitative sensory testing, is useful in identifying male patients at risk of developing greater pain after third molar surgery. It can be helpful to provide effective analgesia in male patients with different pain tolerance thresholds.

Alterations of Cerebral Metabolites Are Associated with Frequency of Vasoocclusive Crises and Pain Sensitivity in Patients with Sickle Cell Disease

Purpose Sickle cell disease (SCD) is an inherited hemolytic disorder complicated by acute and chronic pain. Acute vasoocclusive crises (VOCs) associated with SCD are extremely painful episodes that are recurrent, unpredictable, and frequently require hospitalization and opioids for pain control. Changes in brain metabolites were identified in other chronic pain populations but haven't been well studied in SCD. Our ongoing trial (ClinicalTrials.gov Identifier: NCT05045820) aims to evaluate the characteristics of brain metabolites in SCD and understand the relationship between the altered cerebral metabolite(s) and clinical pain in patients with SCD. Materials and Methods Metabolite measurements from a single voxel (size: 2×3×3 cm 3) located within the posterior insula cortex (PIC) were acquired from 26 patients with SCD (31.9 ± 13.9 years, 14-73; 14 females) and 19 healthy controls (HCs) (37.9 ± 16.4 years, 17-62; 10 females) with PRESS (TR/TE = 3000/25 ms, Averages =128) and MEGA-PRESS (TR/TE = 3000/68 ms, Averages =256) sequences using a Siemens Prisma 3T scanner. Written consent was obtained from each participant before scanning. LCModel was used for PRESS analysis to obtain concentration values of glutamine + glutamate (Glx), total creatine (tCr), N-acetylaspartate (NAA), total choline (tCho), and myoinositol (MI). Gannet was used for processing MEGA-PRESS data to estimate GABA+. Ratios of each metabolite to tCr were also quantified. Tissue correction for cerebrospinal fluid was performed for each voxel using the tissue composition estimated from SPM12. The Cramer-Rao Lower Bounds of each metabolite analyzed with LCModel was less than 20%. The frequency of VOCs in the preceding 12 months was recorded for each participant. A moderate pressure pain stimuli (using a 0-100 scale with “0” representing “no pain” and “100” representing “most intense pain imaginable”, pain rating at 40-60 abbreviated as P40 is considered as moderate pain) was delivered via a pressure cuff to the gastrocnemius area of the non-dominant leg using a validated MR-compatible air compressor to induce a tonic pressure pain for 8 min right before MRS scan. Higher pressure intensity (mmHg) of P40 indicated higher pain tolerance and lower pain sensitivity. Correlation between the brain metabolites and pain-related outcomes was studied. Results Due to the large range of age in the SCD group, the brain metabolite profile was compared between 17 SCD patients and 17 ethnicity-, age- and gender-matched HCs. The concentration of Glx (p =0.012) and ratio of Glx to tCr (p =0.034) in PIC were significantly higher in patients with SCD compared to HCs (Figure 1). Within the SCD patient group, there was a significant positive correlation between frequency of VOCs in the preceding 12 months and Glx/tCr (r= 0.39, p=0.047, Spearman's), a significant negative correlation between P40 and Glx (r= -0.46, p=0.019, Spearman's). There were no group differences in any other metabolites. Conclusion We find increased Glx in the PIC in patients with SCD. Previous studies have also found increased Glx and/ or Glx/tCr in the PIC as well as other brain regions including the amygdala, the posterior cingulate, the ventral lateral prefrontal cortex and the anterior insula in fibromyolgia. The PIC is thought to be involved in discriminative activities of sensory pain, which suggests that Glx in PIC is related to pain processing in patients with SCD. Glx/tCr was correlated with frequency of VOCs in patients with SCD, indicating that the SCD patients with higher level of Glx/tCr had more VOCs in the preceding 12 months. In addition, the SCD patients with higher level of Glx had lower pressure intensity of P40, suggesting that elevated Glx in the PIC was related to higher pain sensitivity. Our preliminary data provide the first evidence of a link between alterations in excitatory neurotransmitter levels in the PIC in patients with SCD and indicates new information of potential brain markers for pain in SCD, which may guide treatment. Clinical Relevance Statement: Treatment of pain in SCD remains very challenging in part due to a lack of understanding of the underlying mechanisms and pathophysiology of pain. Brain excitatory neurotransmitters and their relationship with pain have been largely unexplored in SCD. These findings indicate that the relationship between clinical outcomes and excitatory brain neurotransmitters may be a potential objective outcome measure in SCD.

Pain-related fear among adult patients undergoing open-heart surgery: an interpretative phenomenological analysis

Background One of the sources of anxiety and fear among patients undergoing open-heart surgery is the possibility of experiencing pain, such as sternotomy-related chest pain. Giving them the chance to express their feelings about the potential pain may be effective in reducing their anxiety and may support their coping strategies. Objectives To examine pain-related fear among patients undergoing open-heart surgery and to understand the underlying reasons of their fears. Methods A qualitative interview based on Heidegger’s interpretative phenomenological approach was conducted adhering to the COREQ guidelines. Sixteen patients who were undergoing open-heart surgery in the following day were interviewed at the cardiovascular surgery ward of a university hospital. The organization and mapping of the qualitative data was done by using ATLAS.ti 8.0. Results The patients who were afraid of experiencing pain after surgery seemed to be more concerned about open-heart surgery itself (such as pain from sternotomy and chest tubes) and the possibility of prolongation of postoperative pain. To cope with these fears, the patients employed a variety of social and self-coping strategies. Trusting the healthcare team, having a high pain tolerance, and having personal thoughts that take precedence over pain-related fear were the key factors explaining not being afraid of experiencing pain. Conclusions This study provides a deeper understanding of the underlying reasons and the needs of patients in controlling their pain-related fears before open-heart surgery. Trusting the healthcare professionals is one of the main factors for patients to control their pain-related fears. To develop a supportive sense of trust and to help patients in controlling their pain-related fears, surgical nurses must dedicate enough time for understanding patients’ concerns while planning their nursing care plans. Future studies may focus on exploring the role of nursing interventions and multidisciplinary team approaches on the management of preoperative pain-related fear.

Five Reasons Why Some Herniated Intervertebral Discs are Painless.

Herniated intervertebral discs (HIVDs) can cause lower back pain and leg pain, but not all cases are painful. We suggest five potential reasons for painless HIVDs. First, when inflammation resolves or is insufficient, pain may not occur. Second, rare cases exhibit motor or sensory deficits without pain, suggesting a mechanical rather than inflammatory component. Third, changes in gene expression within the dorsal root ganglia may prevent persistent inflammation and pain. Fourth, reorganization of neural circuits in the spinal dorsal horn can reduce nociceptive signals and lead to painlessness. Fifth, effective pain coping strategies and higher pain tolerance may mask any discomfort. Understanding these factors can improve clinicians' knowledge and aid in pain management.

The Importance of Personality Traits, Optimism and Quality of Life for Pain Threshold and Pain Tolerance in the Elderly

With increasing age, the frequency of chronic pain increases compared to acute pain. This is due to structural and functional changes caused by ageing of the nervous system. The aim of this study was to investigate relationships between personality traits, optimism, quality of life, and subjective assessment of pain measured experimentally with an algometer and clinically with the Visual Analoque Scale (VAS). In the group of 133 seniors (61-86 years; 78% women), we used an algometer to measure pain threshold and tolerance, the VAS scale to assess subjective intensity, and standardized questionnaires (EPQ-R(s), LOTR, SWLS) to measure psychological variables. Extraversion was found to promote both higher pain threshold and higher pain tolerance, whereas pain tolerance was negatively correlated with neuroticism. Higher severity of the psychotic trait was associated with more intense subjective pain experience. Optimism and overall quality of life were not associated with any pain measures. A better understanding of the personality correlates of pain perception could support a more accurate tailoring of pain management in elderly patients.

1253. Acceptability and feasibility of long-acting injectable antiretroviral therapy for persons who inject drugs in Vietnam: using the Consolidated Framework on Implementation Research to identify determinants and inform implementation strategies

Abstract Background Long-acting injectable antiretroviral therapy (LAI) is an exciting alternative to daily oral ART. Less frequent dosing afforded by LAI may be especially pertinent for persons who inject drugs (PWID), who experience more HIV-related mortality largely driven by inadequate ART adherence. We used the Consolidated Framework on Implementation Research (CFIR) to characterize determinants of LAI implementation, focusing on use among PWID, in Hanoi, Vietnam. Methods We conducted in-depth interviews with HIV-infected PWID, ART providers, and policymakers using purposive sampling, recruiting respondents with diverse ART experience from public HIV/ART clinics and national regulatory agencies. Participants were briefed regarding LAI ART, including administration, effectiveness, side effects, and dosing frequency. Data were coded and analyzed using thematic analysis. Results We interviewed 19 PWID, 14 providers, and five policymakers (February-November, 2021). We identified recurrent themes in CFIR domains. Intervention: All informants were excited about LAI, citing convenience and discrete dosing as major facilitators. Surprisingly, provider concerns, including more frequent clinic visits and injection reactions, were rarely voiced by PWID who described monthly injections as similar to current visit frequency and cited “high pain tolerance.” Outer: Providers and policymakers were eager to offer patients ART choice but were divided as to if LAI distribution should proceed with sub-population prioritization. Inner: Providers described personnel and clinic logistic concerns but were confident these could be addressed. Individual: Providers were motivated and confident in their ability to deliver LAI. Process: Transitions to new ART and provision of COVID-19 vaccines were frequently invoked by providers and policymakers as interventions informing LAI implementation. FigureDeterminants of LAI ART implementation in Vietnam using the domains of the Consolidated Framework on Implementation Research Conclusion Using CFIR, we identified multiple determinants of LAI implementation in Vietnam. Stakeholders agreed that LAI was feasible and acceptable. Medication tolerance and efficacy concerns highlight the importance of patient and provider education. Areas where stakeholders diverge should be considered in designing LAI implementation strategies. Disclosures Joseph J. Eron, MD, Adagio Therapeutics: data safety monitoring committee|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Glaxo Smith Kline: Advisor/Consultant|Merck: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support.

Are Prayer-Based Interventions Effective Pain Management Options? A Systematic Review and Meta-analysis of Randomized Controlled Trials.

This review examined the effects of private and communal participatory prayer on pain. Nine databases were searched. Six randomized controlled trials were included. For private prayer, medium to large effects emerged for 67% to 69% of between-group comparisons; participants in the prayer condition reported lower pain intensity (0.59 < d < 26.17; 4 studies) and higher pain tolerance (0.70 < d < 1.05; 1 study). Pre- to post-intervention comparisons yielded medium to large effects (0.76 < d < 1.67; 2 studies); pain intensity decreased. Although firm conclusions cannot be made because meta-analysis was based on only two studies, the analysis suggested prayer might reduce pain intensity (SMD = - 2.63, 95% CI [- 3.11, - 2.14], I = 0%). (PROSPERO: CRD42020221733).

Myoclonic-Atonic Epilepsy Caused by a Novel de Novo Heterozygous Missense Variant in the SLC6A1 Gene: Brief Discussion of the Literature and Detailed Case Description of a Severely Intellectually Disabled Adult Male Patient.

Diagnostic exome sequencing has yielded over the past decades a great number of molecular diagnoses for genetic disorders in which both intellectual disability and epilepsy are present. One of these syndromes is myoclonic-atonic epilepsy (MAE) that is caused by pathogenic variants in the SLC6A1 gene located at 3p25.3. The most relevant clinical characteristics are intellectual disability, several forms of mostly treatment-resistant epilepsy starting at young age, serious disinhibitory behavioural problems, language impairment, higher pain tolerance, and symptoms from the autism spectrum, all in the absence of any consistent dysmorphism or malformation. After an overview of the literature, here, the developmental trajectory of a 55-year-old severely intellectually disabled male with therapy-resistant epilepsy and aggressive outburst is reported in detail, in whom no etiological diagnosis had been performed. Next to genetic, neurological, and neuropsychiatric examination, psychological assessment with validated instruments was performed. Exome sequencing and targeted analysis of the patient and both his parents demonstrated a de novo missense variant in the SLC6A1 gene which was never before described in the literature nor in control databases. The phenotypical presentation of the patient with treatment-resistant epilepsy, especially absences and myoclonic seizures, as well as sleep disturbances and autism, corresponds with a diagnosis of MAE. This case stresses that exome sequencing should be the first-tier diagnostic test for patients with unexplained neurodevelopmental disorders, regardless of their age, and that as yet the most suitable approach is the formation of an interdisciplinary team for treatment design and clinical management.

Expansion and mechanistic insights into de novo DEAF1 variants in DEAF1-associated neurodevelopmental disorders.

De novo deleterious and heritable biallelic mutations in the DNA binding domain (DBD) of the transcription factor deformed epidermal autoregulatory factor 1 (DEAF1) result in a phenotypic spectrum of disorders termed DEAF1-associated neurodevelopmental disorders (DAND). RNA-sequencing using hippocampal RNA from mice with conditional deletion of Deaf1 in the central nervous system indicate that loss of Deaf1 activity results in the altered expression of genes involved in neuronal function, dendritic spine maintenance, development, and activity, with reduced dendritic spines in hippocampal regions. Since DEAF1 is not a dosage-sensitive gene, we assessed the dominant negative activity of previously identified de novo variants and a heritable recessive DEAF1 variant on selected DEAF1-regulated genes in 2 different cell models. While no altered gene expression was observed in cells over-expressing the recessive heritable variant, the gene expression profiles of cells over-expressing de novo variants resulted in similar gene expression changes as observed in CRISPR-Cas9-mediated DEAF1-deleted cells. Altered expression of DEAF1-regulated genes was rescued by exogenous expression of WT-DEAF1 but not by de novo variants in cells lacking endogenous DEAF1. De novo heterozygous variants within the DBD of DEAF1 were identified in 10 individuals with a phenotypic spectrum including autism spectrum disorder, developmental delays, sleep disturbance, high pain tolerance, and mild dysmorphic features. Functional assays demonstrate these variants alter DEAF1 transcriptional activity. Taken together, this study expands the clinical phenotypic spectrum of individuals with DAND, furthers our understanding of potential roles of DEAF1 on neuronal function, and demonstrates dominant negative activity of identified de novo variants.

A case report: ovarian apoplexy and ectopic pregnancy at once

Introduction: Ovarian Apoplexy is the sudden rupture of the ovarium that commonly occurs at the site of the corpus luteum cyst, followed by hemoperitoneum. Extremely uncommon but potentially fatal presentation, hemoperitoneum owing to cyst rupture has just a few cases documented in the literature. We report a woman 6 weeks delaying menstrual period, the pregnancy test was positive (second pregnancy). In this article, we aimed to report a rare case of ectopic pregnancy and ovarian apoplexy. Case Presentation: A 26 Years old woman with a history of abortion in her first pregnancy came to the emergency room with 3 days history of vaginal spotting and mild (2/10) continous right lower abdominal pain. She was suspected of incomplete abortion from primary health care. She was in 6 weeks delaying her menstrual period which is an uncommon case for incomplete abortion. The pregnancy test was positive (second pregnancy). Surgery was performed after completing the consent. Upon exploration of the abdomen, approximately 500 MLS of intraabdominal blood was identified. The right ovary's ruptured corpus luteum cyst was discovered to be the cause of the intra-abdominal bleeding. The hemorrhage was simply stopped by electrocauterization. Conclusion: Ovarian Apoplexy concomitantly occurs with an ectopic pregnancy and has not been reported before. Clinical signs and symptoms, especially pain perception of acute abdomen in a person with high pain tolerance, may bias the diagnosis.