Comorbidities are not associated with pain symptom or recurrence in patients with pilonidal disease.

BACKGROUND: Comorbidities can potentially impact the presentation or outcome of patients with pilonidal disease (PD) due to poor wound healing or increased inflammatory response. We hypothesized that certain comorbidities could lead to worse pain or higher recurrence rate. METHODS: A retrospective study was performed on all PD patients treated with standardized minimally invasive protocol at our clinic 2019-2022. Patients' demographics, comorbidities, initial/follow-up pain score, pain duration, and recurrence were recorded. Data were analyzed by t test and Chi-square test. RESULTS: Of 207 total PD patients (108 male, 99 female), 61 had comorbidities. Mean age was 18.2 years. The recurrence rate was 7%, and patients with recurrence were significantly younger. Associated comorbidities included mood/psychiatric disorders (31%), asthma/respiratory illness (30%), obesity-related illness (15%), gastrointestinal disorders (13%), diabetes (10%), thyroid disease (8%), cardiac disease (8%), musculoskeletal/connective tissue disorders (7%), immunologic disease (7%), inflammatory bowel disease (5%), and chest wall disorders (3%). The presence of comorbidities was not associated with PD recurrence. By dividing patients into adolescents (< 18 years) and adults (≥ 18 years), we found no association between comorbidity and recurrence in either group. 55% of patients had pain as an initial symptom. The initial pain score, pain duration, and pain score at follow-up were not associated with comorbidities. The comorbidities and recurrence were not associated with patient age or sex. CONCLUSIONS: Having comorbidities was not associated with pain symptoms or recurrence in PD patients. Even though patients with recurrence were younger, there was no association between comorbidity and recurrence in either adolescents or adults.

A standardized treatment protocol for pilonidal disease can influence the health mindset of adolescents.

PURPOSE: Pilonidal disease (PD) significantly impacts patients' quality of life and requires regular maintenance behaviors to achieve cure. Health mindset is a psychological construct which can influence health behaviors and outcomes, with a growth mindset being associated with better outcomes than a fixed. We propose that participation in a standardized treatment protocol can affect the health mindset for adolescents with pilonidal disease. METHODS: PD patients' demographics, recurrence, and comorbidities were prospectively collected from 2019 to 2022. We assessed patients' mindset score at initial presentation using the validated Three-Item Mindset Scale (1-6) then reassessed during follow-up. t-test was used to compare baseline and follow-up mindset scores and stratified by recurrence or comorbidities. p ≤ 0.05 was considered significant. RESULTS: A total of 207 PD patients (108 males, 99 females) with mean age 18.2 ± 3.7 years were followed for 351 ± 327 days. Mean baseline mindset score (4.76 ± 1.27) was significantly lower than mean follow-up mindset score (5.03 ± 1.18, p = 0.049). Baseline mindset score was significantly lower among patients with PD recurrence (4.00 ± 0.66) compared to those without recurrence (4.8 ± 1.29, p = 0.05). Among patients with PD recurrence, mean baseline mindset score (4.00 ± 0.66) was significantly lower than mean follow-up mindset score (5.27 ± 0.93, p = 0.0038). Patient comorbidity did not affect the baseline or follow-up mindset score. CONCLUSIONS: Participation in a standardized treatment protocol is associated with the development of a stronger growth mindset over time for patients with PD. Furthermore, a growth mindset was linked to lower recurrence rate than a fixed mindset. Further investigations into how treatment approaches can work in concert with health mindset are proposed.

Increasing Amount of Hair Reduction using Laser Correlates with Lower Probability of Recurrence in Patients with Pilonidal Disease.

BACKGROUND: Hair at the gluteal cleft plays a key role in the development and recurrence of pilonidal disease (PD). We hypothesized that more hair reduction achieved using laser could correlate with lower chance of PD recurrence. METHODS: PD patients who underwent laser epilation (LE) were categorized by Fitzpatrick skin type, hair color, and hair thickness. Photos taken at LE sessions were compared to determine hair reduction amount. LE sessions completed prior to the recurrences were recorded. Groups were compared using multivariate T-test. RESULTS: 198 PD patients had mean age 18.1 ± 3.6 years. 21, 156, and 21 patients had skin types 1/2, 3/4, and 5/6, respectively. 47 patients had light- and 151 had dark-colored hair. 29 patients had fine hair, 129 medium, and 40 thick. Median follow-up was 217 days. 95%, 70%, 40%, and 19% of patients reached 20%, 50%, 75%, and 90% hair reduction after mean LE sessions of 2.6, 4.3, 6.6, 7.8 sessions, respectively. To reach 75% hair reduction, patients require a mean of 4.8-6.8 LE sessions, depending on different skin/hair characteristics. PD recurrence rate was 6%. Probability of recurrence after 20%, 50%, 75% hair reduction was decreased by 50%, 78%, 100%, respectively. Dark hair and skin type 5/6 were associated with higher recurrence rates. CONCLUSION: Patients with dark-color and thick hair require more LE sessions to achieve certain degree of hair reduction. Patients with dark hair and skin type 5/6 were more likely to recur; more hair reduction correlated with lower chance of recurrence. LEVEL OF EVIDENCE: Level IV.

Burden of pilonidal disease and improvement in quality of life after treatment in adolescents.

PURPOSE: Pilonidal Disease (PD) affects adolescents in different aspects. We hypothesized that patients with different gender, ethnicity, and age have different quality of life (QOL) measurements which could improve with minimally invasive treatment (MIT). METHODS: 131 PD patients underwent MIT (laser epilation ± trephination) from 2019 to 2021. Patients' demographics were recorded. Before and after MIT, patients received QOL questionnaire consisting of four categories: daily activities, sports participation, school/work attendance, and socializing. Data were analyzed using Student and multivariate t test. P < 0.05 was considered statistically significant. RESULTS: 101 (51 male, 50 female) patients were included. 30 patients with incomplete data were excluded. 54% of patients were < 18 years old. 47.5% were Hispanic. Median symptom duration prior to presentation was 5.4 (1.3-15) months. Prior to MIT, patients' ability to perform daily activities, participate in sports, attend school/work, and socialize was moderately or severely impacted in 66%, 57%, 45%, and 23% of respondents, respectively; after MIT, only 7%, 8%, 2%, and 4% were affected (p < 0.01). Recurrence rate was 6%. Pre-MIT, older patients and non-Hispanics reported worse impact on their QOL. Symptom duration or PD recurrence did not correlate with patient's pre- or post-MIT QOL. CONCLUSION: Patients' ethnicity and age impacted QOL in PD. All patients' QOL significantly improved with MIT. Considering the importance of socializing, playing sports, and school/work attendance in adolescents, our study highlights importance of early treatment of PD.

Assessment of the Components of the Electrostatic Potential of Proteins in Solution: Comparing Experiment and Theory.

In this work, the components of the protein electrostatic potentials in solution are analyzed with NMR paramagnetic relaxation enhancement experiments and compared with continuum solution theory, and multiscale simulations. To determine the contributions of the solution components, we analyze them at different ionic strengths from 0 to 745 mM. A theoretical approximation allows the determination of the electrostatic potential at a given proton without reference to the protein structure given the ratio of paramagnetic relaxation enhancements rates between a cationic and an anionic probe. The results derived from simulations show good agreement with experiment and simple continuum solvent theory for many of the residues. A discrepancy including a switch of sign of the electrostatic potential was observed for particular residues. By considering the components of the potential, we found the discrepancy is mainly caused by angular correlations of the probe molecules with these residues. The correction for the correlations allows a more accurate analysis of the experiments determining the electrostatic potential of proteins in solution.

Contributions of higher-order proximal distribution functions to solvent structure around proteins.

The proximal distribution function (pDF) quantifies the probability of finding a solvent molecule in the vicinity of solutes. The approach constitutes a hierarchically organized theory for constructing approximate solvation structures around solutes. Given the assumption of universality of atom cluster-specific solvation, reconstruction of the solvent distribution around arbitrary molecules provides a computationally convenient route to solvation thermodynamics. Previously, such solvent reconstructions usually considered the contribution of the nearest-neighbor distribution only. We extend the pDF reconstruction algorithm to terms including next-nearest-neighbor contribution. As a test, small molecules (alanine and butane) are examined. The analysis is then extended to include the protein myoglobin in the P6 crystal unit cell. Molecular dynamics simulations are performed, and solvent density distributions around the solute molecules are compared with the results from different pDF reconstruction models. It is shown that the next-nearest-neighbor modification significantly improves the reconstruction of the solvent number density distribution in concave regions and between solute molecules. The probability densities are then used to calculate the solute-solvent non-bonded interaction energies including van der Waals and electrostatic, which are found to be in good agreement with the simulated values.

Stochasticity of replication forks' speeds plays a key role in the dynamics of DNA replication.

Eukaryotic DNA replication is elaborately orchestrated to duplicate the genome timely and faithfully. Replication initiates at multiple origins from which replication forks emanate and travel bi-directionally. The complex spatio-temporal regulation of DNA replication remains incompletely understood. To study it, computational models of DNA replication have been developed in S. cerevisiae. However, in spite of the experimental evidence of forks' speed stochasticity, all models assumed that forks' speeds are the same. Here, we present the first model of DNA replication assuming that speeds vary stochastically between forks. Utilizing data from both wild-type and hydroxyurea-treated yeast cells, we show that our model is more accurate than models assuming constant forks' speed and reconstructs dynamics of DNA replication faithfully starting both from population-wide data and data reflecting fork movement in individual cells. Completion of replication in a timely manner is a challenge due to its stochasticity; we propose an empirically derived modification to replication speed based on the distance to the approaching fork, which promotes timely completion of replication. In summary, our work discovers a key role that stochasticity of the forks' speed plays in the dynamics of DNA replication. We show that without including stochasticity of forks' speed it is not possible to accurately reconstruct movement of individual replication forks, measured by DNA combing.

Another look at matrix correlations.

MOTIVATION: High throughput technologies are widely employed in modern biomedical research. They yield measurements of a large number of biomolecules in a single experiment. The number of experiments usually is much smaller than the number of measurements in each experiment. The simultaneous measurements of biomolecules provide a basis for a comprehensive, systems view for describing relevant biological processes. Often it is necessary to determine correlations between the data matrices under different conditions or pathways. However, the techniques for analyzing the data with a low number of samples for possible correlations within or between conditions are still in development. Earlier developed correlative measures, such as the RV coefficient, use the trace of the product of data matrices as the most relevant characteristic. However, a recent study has shown that the RV coefficient consistently overestimates the correlations in the case of low sample numbers. To correct for this bias, it was suggested to discard the diagonal elements of the outer products of each data matrix. In this work, a principled approach based on the matrix decomposition generates three trace-independent parts for every matrix. These components are unique, and they are used to determine different aspects of correlations between the original datasets. RESULTS: Simulations show that the decomposition results in the removal of high correlation bias and the dependence on the sample number intrinsic to the RV coefficient. We then use the correlations to analyze a real proteomics dataset. AVAILABILITY AND IMPLEMENTATION: The python code can be downloaded from http://dynamic-proteome.utmb.edu/MatrixCorrelations.aspx. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

qDSB-Seq is a general method for genome-wide quantification of DNA double-strand breaks using sequencing.

DNA double-strand breaks (DSBs) are among the most lethal types of DNA damage and frequently cause genome instability. Sequencing-based methods for mapping DSBs have been developed but they allow measurement only of relative frequencies of DSBs between loci, which limits our understanding of the physiological relevance of detected DSBs. Here we propose quantitative DSB sequencing (qDSB-Seq), a method providing both DSB frequencies per cell and their precise genomic coordinates. We induce spike-in DSBs by a site-specific endonuclease and use them to quantify detected DSBs (labeled, e.g., using i-BLESS). Utilizing qDSB-Seq, we determine numbers of DSBs induced by a radiomimetic drug and replication stress, and reveal two orders of magnitude differences in DSB frequencies. We also measure absolute frequencies of Top1-dependent DSBs at natural replication fork barriers. qDSB-Seq is compatible with various DSB labeling methods in different organisms and allows accurate comparisons of absolute DSB frequencies across samples.