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The L-type Ca 2+ channel (Ca V 1.2) is essential for cardiac excitation-contraction coupling. To contribute to the inward Ca 2+ flux that drives Ca 2+ -induced-Ca 2+ -release, Ca V 1.2 channels must be expressed on the sarcolemma; thus the regulatory mechanisms that tune Ca V 1.2 expression to meet contractile demand are an emerging area of research. A ubiquitously expressed protein called 14-3-3 has been proposed to affect Ca 2+ channel trafficking in non-myocytes, however whether 14-3-3 has similar effects on Ca V 1.2 in cardiomyocytes is unknown. 14-3-3 preferentially binds phospho-serine/threonine residues to affect many cellular processes and is known to regulate cardiac ion channels including Na V 1.5 and hERG. Altered 14-3-3 expression and function have been implicated in cardiac pathologies including hypertrophy. Accordingly, we tested the hypothesis that 14-3-3 interacts with Ca V 1.2 in a phosphorylation-dependent manner and regulates cardiac Ca V 1.2 trafficking and recycling. Confocal imaging, proximity ligation assays, super-resolution imaging, and co-immunoprecipitation revealed a population of 14-3-3 colocalized and closely associated with Ca V 1.2. The degree of 14-3-3/Ca V 1.2 colocalization increased upon stimulation of ß -adrenergic receptors with isoproterenol. Notably, only the 14-3-3-associated Ca V 1.2 population displayed increased cluster size with isoproterenol, revealing a role for 14-3-3 as a nucleation factor that directs Ca V 1.2 super-clustering. 14-3-3 overexpression increased basal Ca V 1.2 cluster size and Ca 2+ currents in ventricular myocytes, with maintained channel responsivity to isoproterenol. In contrast, isoproterenol-stimulated augmentation of sarcolemmal Ca V 1.2 expression and currents in ventricular myocytes were abrogated by 14-3-3 inhibition. These data support a model where 14-3-3 interacts with Ca V 1.2 in a phosphorylation-dependent manner to promote enhanced trafficking/recycling, clustering, and activity during ß -adrenergic stimulation. Significance Statement: The L-type Ca 2+ channel, Ca V 1.2, plays an essential role in excitation-contraction coupling in the heart and in part regulates the overall strength of contraction during basal and fight- or-flight ß -adrenergic signaling conditions. Proteins that modulate the trafficking and/or activity of Ca V 1.2 are interesting both from a physiological and pathological perspective, since alterations in Ca V 1.2 can impact action potential duration and cause arrythmias. A small protein called 14-3-3 regulates other ion channels in the heart and other Ca 2+ channels, but how it may interact with Ca V 1.2 in the heart has never been studied. Examining factors that affect Ca V 1.2 at rest and during ß -adrenergic stimulation is crucial for our ability to understand and treat disease and aging conditions where these pathways are altered.

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Voltage-gated ion channels (VGICs) are pivotal in regulating electrical activity in excitable cells and are critical pharmaceutical targets for treating many diseases including cardiac arrhythmia and neuropathic pain. Despite their significance, challenges such as achieving target selectivity persist in VGIC drug development. Recent progress in deep learning, particularly diffusion models, has enabled the computational design of protein binders for any clinically relevant protein based solely on its structure. These developments coincide with a surge in experimental structural data for VGICs, providing a rich foundation for computational design efforts. This review explores the recent advancements in computational protein design using deep learning and diffusion methods, focusing on their application in designing protein binders to modulate VGIC activity. We discuss the potential use of these methods to computationally design protein binders targeting different regions of VGICs, including the pore domain, voltage-sensing domains, and interface with auxiliary subunits. We provide a comprehensive overview of the different design scenarios, discuss key structural considerations, and address the practical challenges in developing VGIC-targeting protein binders. By exploring these innovative computational methods, we aim to provide a framework for developing novel strategies that could significantly advance VGIC pharmacology and lead to the discovery of effective and safe therapeutics.

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Gray mold, caused by Botrytis sp., is a significant disease in Colombian rose crops and its control depends primarily on the intensive use of chemically synthesized fungicides. Despite the importance of this pathogen, there is limited information in Colombian floriculture about molecular taxonomy of species, fungicide resistance of populations and their genetic mechanism of resistance. In this study, we analyze 12 isolates of this fungus collected from rose-producing crops in the Department of Cundinamarca and conducted phylogenetic analysis using HSP60, G3PDH, and RPB2 gene sequences. Additionally, we realize phenotypic and genotypic characterization of resistance to the fungicides fenhexamid, carboxin, and prochloraz, evaluating the in vitro EC50 and presence of mutations of target genes of each isolate. All isolates were characterized as Botrytis cinerea in the phylogenetic analysis and presents different levels of resistance to each fungicide. These levels are related to mutations in target genes, with predominancy of L195F and L400F in the ERG27 gene to fenhexamid resistance, H272R/Y in the SDHB gene for carboxin resistance, and Y136F in the CYP51 gene for prochloraz resistance. Finally, these mutations were not related to morphological changes. Collectively, this knowledge, presented for the first time to the Colombian floriculture, contribute to a better understanding of the genetic diversity and population of B. cinerea from rose-producing crops in the department of Cundinamarca, and serve as a valuable tool for making informed decisions regarding disease management, future research, and improving crop management and sustainability in the Colombian floriculture industry.

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PURPOSE: At least thirty species of wild carnivores have been recorded harboring Bartonella, and one of the most common pathogenic species infecting them is Bartonella rochalimae, which can cause endocarditis in humans and dogs. This bacterium can infect various mammals including wild carnivores, as well as ectoparasitic vectors such as fleas and ticks. Here we report the presence of B. rochalimae, in a Pulex simulans flea collected from a Mephitis macroura skunk in the municipality of Santa Cruz in Sonora, Mexico. METHODS: Fleas were collected from a M. macroura in Sonora, Mexico, in October 2019. They were identified to species level and subsequently tested for the presence of Bartonella using molecular tools including conventional PCR, sequencing, and phylogenetic analysis. RESULTS: A total of 10 P. simulans fleas (one male, nine females) were collected from the M. macroura skunk. The PCR and phylogenetic analysis indicated a prevalence of 10% (1/10) and a sequence clustered with the clade of B. rochalimae. CONCLUSIONS: We confirmed the presence of B. rochalimae in a P. simulans flea collected from a M. macroura skunk in the area of Santa Cruz, Sonora, Mexico. Based on our results and previous studies in northern Mexico, which are consistent, it is necessary to continue monitoring Bartonella in M. macroura skunks and their fleas, since they could be important reservoirs of this bacterium in northern Mexico.

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Due to the multifactorial and complex nature of rest, we focus on phenotypes related to sleep. Sleep regulation is a multifactorial process. In this chapter, we focus on those phenotypes inherent to sleep that are highly prevalent in the population, and that can be modulated by lifestyle, such as sleep quality and duration, insomnia, restless leg syndrome and daytime sleepiness. We, therefore, leave in the background those phenotypes that constitute infrequent pathologies or for which the current level of scientific evidence does not favour the implementation of practical approaches of this type. Similarly, the regulation of sleep quality is intimately linked to the regulation of the circadian rhythm. Although this relationship is discussed in the sections that require it, the in-depth study of circadian rhythm regulation at the molecular level deserves a separate chapter, and this is how it is dealt with in this volume.

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This chapter aims to explore the usefulness of the latest advances in genetic studies in the field of the circadian system in the future development of individualised strategies for health improvement based on lifestyle intervention. Due to the multifactorial and complex nature of the circadian system, we focus on the highly prevalent phenotypes in the population that are key to understanding its biology from an evolutionary perspective and that can be modulated by lifestyle. Therefore, we leave in the background those phenotypes that constitute infrequent pathologies or in which the current level of scientific evidence does not favour the implementation of practical approaches of this type. Therefore, from an evolutionary paradigm, this chapter addresses phenotypes such as morning chronotypes, evening chronotypes, extreme chronotypes, and other key concepts such as circadian rhythm amplitude, resilience to changes in circadian rhythm, and their relationships with pathologies associated with circadian rhythm imbalances.

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Microbiota is a complex community of microorganisms living in a defined environment. Until the 20th century, knowledge of microbiota was partial, as the techniques available for their characterization were primarily based on bacteriological culture. In the last twenty years, the development of DNA sequencing technologies, multi-omics, and bioinformatics has expanded our understanding of microorganisms. We have moved from mainly considering them isolated disease-causing agents to recognizing the microbiota as an essential component of host biology. These techniques have shown that the microbiome plays essential roles in various host phenotypes, influencing development, physiology, reproduction, and evolution. This chapter provides researchers with a summary of the primary concepts, sample collection, experimental techniques, and bioinformatics analysis commonly used in microbiome research. The main features, applications in microbiome studies, and their advantages and limitations are included in each section.

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Importance: Several clinical practice guidelines advise race- and ethnicity-based screening for youth-onset type 2 diabetes (T2D) due to a higher prevalence among American Indian and Alaska Native, Asian, Black, and Hispanic youths compared with White youths. However, rather than a biological risk, this disparity likely reflects the inequitable distribution of adverse social determinants of health (SDOH), a product of interpersonal and structural racism. Objective: To evaluate prediabetes prevalence by presence or absence of adverse SDOH in adolescents eligible for T2D screening based on weight status. Design, Setting, and Participants: This cross-sectional study and analysis used data from the 2011 to 2018 cycles of the National Health and Nutrition Examination Survey. Data were analyzed from June 1, 2023, to April 5, 2024. Participants included youths aged 12 to 18 years with body mass index (BMI) at or above the 85th percentile without known diabetes. Main Outcomes and Measures: The main outcome consisted of an elevated hemoglobin A1c (HbA1c) level greater than or equal to 5.7% (prediabetes or undiagnosed presumed T2D). Independent variables included race, ethnicity, and adverse SDOH (food insecurity, nonprivate health insurance, and household income <130% of federal poverty level). Survey-weighted logistic regression was used to adjust for confounders of age, sex, and BMI z score and to determine adjusted marginal prediabetes prevalence by race, ethnicity, and adverse SDOH. Results: The sample included 1563 individuals representing 10 178 400 US youths aged 12 to 18 years (mean age, 15.5 [95% CI, 15.3-15.6] years; 50.5% [95% CI, 47.1%-53.9%] female; Asian, 3.0% [95% CI, 2.2%-3.9%]; Black, 14.9% [95% CI, 11.6%-19.1%]; Mexican American, 18.8% [95% CI, 15.4%-22.9%]; Other Hispanic, 8.1% [95% CI, 6.5%-10.1%]; White, 49.1% [95% CI, 43.2%-55.0%]; and >1 or other race, 6.1% [95% CI, 4.6%-8.0%]). Food insecurity (4.1% [95% CI, 0.7%-7.5%]), public insurance (5.3% [95% CI, 1.6%-9.1%]), and low income (5.7% [95% CI, 3.0%-8.3%]) were each independently associated with higher prediabetes prevalence after adjustment for race, ethnicity, and BMI z score. While Asian, Black, and Hispanic youths had higher prediabetes prevalence overall, increasing number of adverse SDOH was associated with higher prevalence among White youths (8.3% [95% CI, 4.9%-11.8%] for 3 vs 0.6% [95% CI, -0.7% to 2.0%] for 0 adverse SDOH). Conclusions and Relevance: Adverse SDOH were associated with higher prediabetes prevalence, across and within racial and ethnic categories. Consideration of adverse SDOH may offer a more actionable alternative to race- and ethnicity-based screening to evaluate T2D risk in youth.

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Microorganisms have been used in nutrition and medicine for thousands of years worldwide, long before humanity knew of their existence. It is now known that the gut microbiota plays a key role in regulating inflammatory, metabolic, immune and neurobiological processes. This text discusses the importance of microbiota-based precision nutrition in gut permeability, as well as the main advances and current limitations of traditional probiotics, new-generation probiotics, psychobiotic probiotics with an effect on emotional health, probiotic foods, prebiotics, and postbiotics such as short-chain fatty acids, neurotransmitters and vitamins. The aim is to provide a theoretical context built on current scientific evidence for the practical application of microbiota-based precision nutrition in specific health fields and in improving health, quality of life and physiological performance.

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This chapter analyses the interaction between microbiota and humans from an evolutionary point of view. Long-term interactions between gut microbiota and host have been generated as a result of dietary choices through coevolutionary processes, where mutuality of advantage is essential. Likewise, the characteristics of the intestinal environment have made it possible to describe different intrahost evolutionary mechanisms affecting microbiota. For its part, the intestinal microbiota has been of great importance in the evolution of mammals, allowing the diversification of dietary niches, phenotypic plasticity and the selection of host phenotypes. Although the origin of the human intestinal microbial community is still not known with certainty, mother-offspring transmission plays a key role, and it seems that transmissibility between individuals in adulthood also has important implications. Finally, it should be noted that certain aspects inherent to modern lifestyle, including refined diets, antibiotic intake, exposure to air pollutants, microplastics, and stress, could negatively affect the diversity and composition of our gut microbiota. This chapter aims to combine current knowledge to provide a comprehensive view of the interaction between microbiota and humans throughout evolution.

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Optimal nutrition is essential for health and physiological performance. Nutrition-related diseases such as obesity and diabetes are major causes of death and reduced quality of life in modern Western societies. Thanks to combining nutrigenetics and nutrigenomics, genomic nutrition allows the study of the interaction between nutrition, genetics and physiology. Currently, interrelated multi-genetic and multifactorial phenotypes are studied from a multiethnic and multi-omics approach, step by step identifying the important role of pathways, in addition to those directly related to metabolism. It allows the progressive identification of genetic profiles associated with specific susceptibilities to diet-related phenotypes, which may facilitate individualised dietary recommendations to improve health and quality of life.

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Colorectal cancer (CRC) is the second most deadly and the third most diagnosed cancer in both sexes worldwide. CRC pathogenesis is associated with risk factors such as genetics, alcohol, smoking, sedentariness, obesity, unbalanced diets, and gut microbiota dysbiosis. The gut microbiota is the microbial community living in symbiosis in the intestine, in a dynamic balance vital for health. Increasing evidence underscores the influence of specific gut microbiota bacterial species on CRC incidence and pathogenesis. In this regard, conjugated linoleic acid (CLA) metabolites produced by certain gut microbiota have demonstrated an anticarcinogenic effect in CRC, influencing pathways for inflammation, proliferation, and apoptosis. CLA production occurs naturally in the rumen, and human bioavailability is through the consumption of food derived from ruminants. In recent years, biotechnological attempts to increase CLA bioavailability in humans have been unfruitful. Therefore, the conversion of essential dietary linoleic acid to CLA metabolite by specific intestinal bacteria has become a promising process. This article reviews the evidence regarding CLA and CLA-producing bacteria as therapeutic agents against CRC and investigates the best strategy for increasing the yield and bioavailability of CLA. Given the potential and limitations of the present strategies, a new microbiome-based precision nutrition approach based on endogenous CLA production by human gut bacteria is proposed. A literature search in the PubMed and PubMed Central databases identified 794 papers on human gut bacteria associated with CLA production. Of these, 51 studies exploring association consistency were selected. After excluding 19 papers, due to health concerns or discrepancies between studies, 32 papers were selected for analysis, encompassing data for 38 CLA-producing bacteria, such as Bifidobacterium and Lactobacillus species. The information was analyzed by a bioinformatics food recommendation system patented by our research group, Phymofood (EP22382095). This paper presents a new microbiome-based precision nutrition approach targeting CLA-producing gut bacterial species to maximize the anticarcinogenic effect of CLA in CRC.

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BACKGROUND: Much evidence-based physical activity (PA) interventions have been tested and implemented in urban contexts. However, studies that adapt, implement, and evaluate the effectiveness of these interventions in micropolitan rural contexts are needed. The study aimed to evaluate the effectiveness of the Active Ottumwa intervention to promote PA in a micropolitan community. METHODS: Between 2013 - 2019, we implemented Active Ottumwa in a micropolitan setting, and subsequently implemented and evaluated its effectiveness using a Hybrid Type I design. In this paper, we describe the intervention's effectiveness in promoting PA. We collected PA data over 24 months from a cohort of community residents using accelerometers and PA data from two cross-sectional community surveys administered in 2013 and 2018, using the Global Physical Activity Questionnaire. RESULTS: From the cohort, we found significant change in PA over 24 months (P = 0.03) corresponding to a 45-min daily decrease in sedentary activity, a daily increase of 35-min in light PA and 9 min in moderate-to-vigorous PA. There was a statistically significant (P = 0.01) increasing trend at the population-level in the moderate-to-vigorous composition of 7 min between the two cross-sectional assessments (95% CI: 0.1%-1.34%). CONCLUSIONS: The study demonstrates that the adapted evidence-based PA interventions in a micropolitan context is effective.

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The infection process of the hemibiotrophic fungus Colletotrichum lindemuthianum has been independently studied at the microscopic and genomic levels. However, the relationship between the morphological changes and the pathogenicity mechanisms of the fungus at the early stages of the infection remains uncharacterized. Therefore, this study attempts to bridge this gap by integrating microscopic and transcriptional approaches to understand the infection process of C. lindemuthianum. Fungal structures were followed by fluorescence microscopy for 120 hours. Simultaneously, the transcriptomic profile was made using RNAseq. Morphological characterization shows that appressoria, infective vesicles, and secondary hypha formation occur before 72 hours. Additionally, we assembled 38,206 transcripts with lengths between 201 and 3,548 bp. The secretome annotation revealed the expression of 1,204 CAZymes, of which 17 exhibited secretion domains and were identified as chitinases and ß-1,3-glucanases, 27 were effector candidates, and 30 were transport proteins mostly associated with ABC-type. Finally, we confirmed the presence and expression of CAC1 role during the appressoria formation of Clr7. This result represents the first report of adenylate cyclase expression evaluated under three different approaches. In conclusion, C. lindemuthianum colonizes the host through different infection structures complemented with the expression of multiple enzymes, where CAC1 favors disease development.

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Lopezia racemosa is known as a "mosquito flower or perlilla." It is commonly found in corn crops. In traditional Mexican medicine, this plant is used to treat stomach cancer and urinary tract infections. Likewise, compounds and extracts isolated from plants have shown cytotoxic and anti-inflammatory effects. The objective of this study was to evaluate the photochemoprotective effect of topical treatment with the methanolic extract of L. racemosa (MELR) as a photochemoprotective agent against the harmful effects of UV irradiation (UVR) on a bacterial model and hairless mice. The MELR components were separated and analyzed via HPLC-UV-ESI-MS. Antioxidant activity was evaluated by the ability of MERL to scavenge DPPH and ABTS free radicals and by its FRAP capacity. The toxicity of MELR was evaluated in keratinocyte cultures. The photoprotective capacity of MELR was assessed through challenge experiments using models with bacteria and hairless CD1 et/et mice; cytokines related to the damage caused by UVR were also measured. In the methanolic extract of L. racemosa, five metabolites were detected and identified: two isomers of quercetin 6-C glycoside, orientin, quercetin 3-(6″-acetylglycoside) and quercetin 3-(6″-galloylglycoside) 7-(2,3-dihydroxytetrahydro-2H-pyran-4-yl acetate). MELR exhibited DPPH and ABTS radical scavenging properties, in addition to Fe ion reducing activity. MELR showed a photoprotective effect against UVB radiation-induced death in Escherichia coli bacteria. At the histological level, topical treatment of CD-1 et/et mice with MERL reduced the damage caused by UVR. Quantification of interleukins in the blood of mice revealed that the expression of IL-12 was greater in the control group treated with ultraviolet radiation than in the group protected with MELR. The methanolic extract of L. racemosa has photochemoprotective properties.

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Ion channels play key roles in human physiology and are important targets in drug discovery. The atomic-scale structures of ion channels provide invaluable insights into a fundamental understanding of the molecular mechanisms of channel gating and modulation. Recent breakthroughs in deep learning-based computational methods, such as AlphaFold, RoseTTAFold, and ESMFold have transformed research in protein structure prediction and design. We review the application of AlphaFold, RoseTTAFold, and ESMFold to structural modeling of ion channels using representative voltage-gated ion channels, including human voltage-gated sodium (NaV) channel - NaV1.8, human voltage-gated calcium (CaV) channel - CaV1.1, and human voltage-gated potassium (KV) channel - KV1.3. We compared AlphaFold, RoseTTAFold, and ESMFold structural models of NaV1.8, CaV1.1, and KV1.3 with corresponding cryo-EM structures to assess details of their similarities and differences. Our findings shed light on the strengths and limitations of the current state-of-the-art deep learning-based computational methods for modeling ion channel structures, offering valuable insights to guide their future applications for ion channel research.

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BACKGROUND AND AIMS: Despite high rates of relapse after treatment for drug use, to our knowledge there is no systematic literature identifying psychological factors that predict risk of relapse to drug use (excluding alcohol or tobacco). Our aim was to identify psychological factors that predict risk of relapse to drug use after enrollment in drug use treatment. The identification of such factors can support treatment planning and relapse prevention. METHODS: We searched for peer-reviewed articles published between 2000 and 2023 in PsycINFO, PsycArticles, Web of Science, and PubMed. The inclusion criteria were: peer-reviewed publications, quantitative studies, in English, adult samples, with a prospective design, and analyses of minimum one psychological factor as predictor of relapse to drug use. All authors were involved in abstract and full-text screening, and in assessing risk of bias. The findings are presented in a narrative synthesis and tables are organized by type of drug. RESULTS: Of 2226 publications initially identified, 45 were eligible. Twenty-three focused on predicting relapse to stimulants, 15 to opioids, and 7 to unspecified drugs. Substance use at baseline was an important factor predicting risk of relapse to opioids, and possibly stimulants. There was an indication that craving and attention problems potentially predict relapse to use of some drugs. Mental health factors (e.g., psychiatric diagnosis) did not predict relapse. Several psychological factors (e.g., cognition, emotion, personality, motivation) were scarcely examined. Over half of the studies had moderate to high risk of bias. CONCLUSIONS: Based on the 45 studies, few psychological factors predicted risk of relapse to drug use. Higher comparability between studies and more rigorous methodology are necessary in order to derive more precise recommendations that inform and improve clinical practice. PRE-REGISTRATION: PROSPERO, CRD42020182839.

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The use of bioluminescence as a reporter for physiology in neuroscience is as old as the discovery of the calcium-dependent photon emission of aequorin. Over the years, luciferases have been largely replaced by fluorescent reporters, but recently, the field has seen a renaissance of bioluminescent probes, catalyzed by unique developments in imaging technology, bioengineering, and biochemistry to produce luciferases with previously unseen colors and intensity. This is not surprising as the advantages of bioluminescence make luciferases very attractive for noninvasive, longitudinal in vivo observations without the need of an excitation light source. Here, we review how the development of dedicated and specific sensor-luciferases afforded, among others, transcranial imaging of calcium and neurotransmitters, or cellular metabolites and physical quantities such as forces and membrane voltage. Further, the increased versatility and light output of luciferases have paved the way for a new field of functional bioluminescence optogenetics, in which the photon emission of the luciferase is coupled to the gating of a photosensor, e.g., a channelrhodopsin and we review how they have been successfully used to engineer synthetic neuronal connections. Finally, we provide a primer to consider important factors in setting up functional bioluminescence experiments, with a particular focus on the genetic model Caenorhabditis elegans, and discuss the leading challenges that the field needs to overcome to regain a competitive advantage over fluorescence modalities. Together, our paper caters to experienced users of bioluminescence as well as novices who would like to experience the advantages of luciferases in their own hand.

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OBJECTIVE: No consensus currently exists regarding patient-reported outcome measure (PROM) instruments. This structured review was conducted to identify the PROMs used by randomized controlled trials (RCTs) that evaluated surgical treatment in patients with endometriosis. DATA SOURCES: Two parallel searches were conducted by a medical librarian using Ovid MEDLINE, Ovid Embase, and Cochrane Library for RCTs published from 2000 to July 2022. One search focused on studies reporting quality of life (QoL), and the second search focused on studies reporting pain and sexual, bowel, and bladder function. METHOD OF STUDY SELECTION: During the title and abstract screening and reference check, 600 results were identified on PROMs relating to QoL and 465 studies on PROMs relating to pain and sexual, bowel, and/or bladder function and an evaluation of 17 and 12 studies conducted, respectively. The inclusion criteria involved selecting RCTs that focused on surgical intervention and assessing QoL, pain, and sexual, bowel, and/or bladder function using PROMs. TABULATION, INTEGRATION, AND RESULTS: Covidence software was used to organize and identify duplicate articles through screening. We developed a data extraction form to collect key information about each included study, as well as the pertinent PROMs used in the study. Assessment of the risk of bias of each study was also performed. A total of 19 studies were identified involving 2089 participants and a total of 16 PROMs used across the studies; 9 of 19 studies (47%) were rated as having a low risk of bias. There were no high-risk studies identified in this review. CONCLUSION: This study identified a large number of RCTs in surgical treatment of endometriosis that used various PROMs to assess QoL, pain, and bladder, bowel, and sexual function. The PROMs used by high-quality RCTs for QoL include Endometriosis Health Profile-30, Endometriosis Health Profile-5, Short-Form 36, Short-Form 12, and EQ-5D; for bowel-related symptoms Knowles-Eccersley-Scott-Symptom Questionnaire, Gastrointestinal Quality of Life Index, and Cleveland Clinic Fecal Incontinence Severity Scoring System/Wexner; for bladder-related function Bristol Female Lower Urinary Tract Symptoms, International Prostate Symptom Score, Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire, and Urinary Symptom Profile; and finally for sexual function Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire and Sexual Activity Questionnaire. Unlike other domains, only one tool (visual analog scale) was the dominant PROM used for the assessment of pain. In addition, the use of more than one PROM in each study to assess different aspects of patient's health and pain symptoms did not become prevalent until after 2015.

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