bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketogenic diet prevents methylglyoxal-evoked nociception by scavenging methylglyoxal
Authors: Enders Jonathan D. , Thomas Sarah , Swanson Matthew Taylor , Ryals Janelle M. , Wright Douglas E. 
Published: May 2022

Abstract
Methylglyoxal (MGO) is a reactive dicarbonyl byproduct of glycolysis implicated in a growing number of neuropathic pain conditions, including chemotherapy-induced peripheral neuropathy, diabetic peripheral neuropathy, and radiculopathy with lumbar disk herniation. Recent studies show success in preclinical models treating these disorders with an interventional ketogenic diet. Here, we tested the hypothesis that a ketogenic diet modifies pathological MGO signaling as a mechanism underlying neuropathy improvement. We found that mice injected with MGO displayed nocifensive behaviors, whereas mice prefed a ketogenic diet were resistant to mechanical allodynia elicited by MGO. In addition, levels of circulating MGO were reduced in ketogenic diet-fed mice and negatively correlated with levels of the ketone body β-hydroxybutyrate (β-HB). Methylglyoxal is normally scavenged by the glyoxalase system, and ketogenic diet-fed mice displayed increased glyoxalase 1 activity compared with chow-fed control mice. Recent studies also suggest that ketone bodies contribute to MGO detoxification, consistent with a negative correlation between β-HB and MGO. To assess whether ketone bodies modified MGO-evoked nociception through direct MGO detoxification, we coincubated either acetoacetate or β-HB with MGO before injection. Mice receiving intraplantar MGO injection exhibit increased nociceptive behavior (lifting, licking, biting, and scratching), which was significantly reduced by coincubation with either acetoacetate or β-HB. Methylglyoxal increased phospho-extracellular signal-regulated kinase–positive cells in the spinal dorsal horn, and this evoked spinal activation was ameliorated by preincubation with acetoacetate or β-HB. These results suggest that a ketogenic diet and ketone bodies ameliorate MGO-evoked nociception, partially through detoxification of MGO, and provide rationale for therapeutic intervention with a ketogenic diet in MGO-driven pathologies.
Pilot Study to Investigate the Effect of a 10-Week Aquatic Exercise Program on Individuals With High Levels of Disability Due to Multiple Sclerosis
Authors: Sames Carol , DeBlois Amy 
Published: May 2022

Background and Purpose:
Research has suggested that a properly designed and implemented aquatic exercise (AE) program can improve physiological function and quality-of-life (QOL) outcomes in individuals with minimal disability levels due to multiple sclerosis (MS). Minimal research has investigated AE in individuals with higher levels of disability. The purpose of this study was to investigate a 10-week AE program on walking speed and QOL outcomes, specifically the effect of fatigue, in individuals with higher levels of disability due to MS, at an Expanded Disability Status Scale (EDSS) score between 5.0 and 6.5.

Methods:
Fifteen females and 4 males with relapsing-remitting MS, mean age 46.4 years ± 10.0, EDSS score 5.9 ± 0.4, and disease duration 10.4 years ± 6.5. The AE group was individually modified and performed 3 times per week for 45 minutes at a rating of perceived exertion of 11 to 13 for 10 weeks. Prior to and upon completion of structured AE intervention, subjects performed the following tests: Multiple Sclerosis Functional Composite (MSFC), Multiple Sclerosis Quality of Life Inventory (MSQLI), and 25-ft Water Walk Test.

Results:
Improvement in the MSFC (P = .001) was noted in all 3 MSFC components: 25-ft Water Walk Test (P = .020), 9-Hole Peg Test (P = .006), and Paced Auditory Serial Addition Test (P = .005). Improvements in the following subtests of the MSQLI were noted: SF-36 (36-Item Short Form Health Survey) physical and mental component summary (PCS, P = .006) (MCS, P = .009); Modified Fatigue Impact Scale (P = .006); Pain Effects Scale (P = .006); Perceived Deficits Questionnaire (P = .003); and Mental Health Inventory (P = .040).

Discussion and Conclusions:
Results suggest that a 10-week AE program for individuals with MS improved walking speed, arm function, memory, mental health, and generic QOL and reduced fatigue, pain, and perceived cognitive impairment in individuals with moderate to severe disability without adverse symptoms.
Association of Radiation Timing with Long-Term Satisfaction and Health-Related Quality of Life in Prosthetic Breast Reconstruction
Authors: Nelson Jonas A. , Cordeiro Peter G. , Polanco Thais , Shamsunder Meghana G. , Patel Aadit , Allen Robert J. , Matros Evan , Disa Joseph J. , Cuaron John J. , Morrow Monica , Mehrara Babak J. , Pusic Andrea L. , McCarthy Colleen M. 
Published: May 2022

Background:
Radiation therapy is increasingly used after breast cancer surgery, which may impact patients’ postoperative quality of life. This study assessed differences in long-term patient satisfaction and health-related quality of life after radiation therapy administered at different stages of implant-based breast reconstruction or with no radiation after surgery.

Methods:
In this observational study, long-term outcomes were evaluated for four cohorts of women who completed breast reconstruction and received (1) no radiation, (2) radiation before tissue expander placement, (3) radiation after tissue expander placement, or (4) radiation after permanent implant between 2010 and 2017 at Memorial Sloan Kettering. Satisfaction and health-related quality of life were assessed using the prospectively collected Satisfaction with Breasts and Physical Well-Being of Chest BREAST-Q subscales. Score distributions were examined by radiation exposure status for 3 years after surgery using nonparametric analyses and regression models.

Results:
Of 2932 patients who met the inclusion criteria, 25.8 percent received radiation during breast cancer treatment, including before tissue expander placement (n = 239; 8.2 percent), after tissue expander placement (n = 290; 9.9 percent), and after implant placement (n = 228; 7.8 percent). Radiotherapy patients had average scores 7 to 9 points lower at all postoperative time points for Satisfaction with Breasts and Physical Well-Being of Chest subscales (p < 0.001). Although patient-reported outcomes did not differ by radiation timing, there were higher rates of severe capsular contracture with postimplant radiotherapy (p < 0.001).

Conclusions:
Radiation therapy significantly affected patient satisfaction and health-related quality of life following implant breast reconstruction through 3 years postoperatively. Patient perception of outcome was unaffected by radiotherapy timing; however, capsular contracture was higher after postimplant radiotherapy, suggesting there may be an advantage to performing radiotherapy before placement of the final reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Nerve Blocks in Breast Plastic Surgery: Outcomes, Complications, and Comparative Efficacy
Authors: Abi-Rafeh Jad , Safran Tyler , Abi-Jaoude Joanne , Kazan Roy , Alabdulkarim Abdulaziz , Davison Peter G. 
Published: May 2022

Background:As plastic surgeons continue to evaluate the utility of nonopioid analgesic alternatives, nerve block use in breast plastic surgery remains limited and unstandardized, with no syntheses of the available evidence to guide consensus on optimal approach.Methods:A systematic review was performed to evaluate the role of pectoralis nerve blocks, paravertebral nerve blocks, transversus abdominus plane blocks, and intercostal nerve blocks in flap-based breast reconstruction, prosthetic-based reconstruction, and aesthetic breast plastic surgery, independently.Results:Thirty-one articles reporting on a total of 2820 patients were included in the final analysis; 1500 patients (53 percent) received nerve blocks, and 1320 (47 percent) served as controls. Outcomes and complications were stratified according to procedures performed, blocks employed, techniques of administration, and anesthetic agents used. Overall, statistically significant reductions in opioid consumption were reported in 91 percent of studies evaluated, postoperative pain in 68 percent, postanesthesia care unit stay in 67 percent, postoperative nausea and vomiting in 53 percent, and duration of hospitalization in 50 percent. Nerve blocks did not significantly alter surgery and/or anesthesia time in 83 percent of studies assessed, whereas the overall, pooled complication rate was 1.6 percent.Conclusions:Transversus abdominus plane blocks provided excellent outcomes in autologous breast reconstruction, whereas both paravertebral nerve blocks and pectoralis nerve blocks demonstrated notable efficacy and versatility in an array of reconstructive and aesthetic procedures. Ultrasound guidance may minimize block-related complications, whereas the efficacy of adjunctive postoperative infusions was proven to be limited. As newer anesthetic agents and adjuvants continue to emerge, nerve blocks are set to represent essential components of the multimodal analgesic approach in breast plastic surgery.
Beauty Is in the Eye of the Beholder: Factors Influencing Disparity in Perceptions of Breast Reconstruction Aesthetic Outcomes
Authors: Wu Shannon S. , Duraes Eliana F. R. , Scomacao Isis , Morisada Megan , Djohan Risal S. , Bernard Steven L. , Moreira Andrea , Schwarz Graham S. 
Published: May 2022

Background:
Patient-reported outcomes are the primary measurement of breast reconstruction success, but results may be affected by nontechnical factors such as socioemotional determinants. Third-party observers provide an independent assessment of aesthetic outcomes. Factors associated with disparity between patient and observer perceptions of outcomes are not well understood.

Methods:
One hundred forty-seven patients underwent breast reconstruction at the authors’ institution between 2009 and 2011, completed the BREAST-Q, and had photographs graded by a diverse panel using the Validated Breast Aesthetic Scale. Patient satisfaction with breasts scores that aligned with observer scores were categorized as group 2; patient satisfaction that exceeded observer scores were group 1; and those lower than observer scores were group 3. Statistical analysis was performed using SPSS, with values of p < 0.05 considered statistically significant.

Results:
Twenty-eight patients (19 percent) were categorized as group 1, 93 (63 percent) in group 2, and 26 (18 percent) in group 3. Median overall appearance was highest in group 3 (median, 4.0; interquartile range, 4 to 4) and lowest in group 1 (median, 3.0; interquartile range, 2 to 3) (p < 0.001). Psychosocial, sexual, and physical well-being were significantly associated with disparity (group 1 or 3 status) (p < 0.01). Satisfaction with outcomes, nipples, abdomen, and breasts were significantly associated with disparity. Factors not significantly associated with disparity include age, body mass index, autologous or implant-based, adjuvant therapies, and timing of reconstruction.

Conclusions:
Incongruously high patient satisfaction with breast reconstruction aesthetics relative to third-party perception of aesthetic outcomes is associated with high quality-of-life scores. Incongruously low patient satisfaction with breast cosmesis compared with higher third-party perceptions was associated with low quality-of-life scores.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, II.
Brief Report: Pediatric Saliva-Based HIV Testing: Health care Worker and Caregiver Acceptability
Authors: Neary Jillian , Bulterys Michelle A. , Ogutu Emily A. , O'Malley Gabrielle , Otieno Anita A. , Omondi Vincent O. , Wang Yu , Zhai Xinyi , Katz David A. , Oyiengo Laura , Wamalwa Dalton C. , Slyker Jennifer A. , John-Stewart Grace C. , Njuguna Irene N. , Wagner Anjuli D. 
Published: May 2022

Background:
Pediatric HIV testing remains suboptimal. The OraQuick test [saliva-based test (SBT)] is validated in pediatric populations ≥18 months. Understanding caregiver and health care worker (HCW) acceptability of pediatric SBT is critical for implementation.

Methods:
A trained qualitative interviewer conducted 8 focus group discussions (FGDs): 4 with HCWs and 4 with caregivers of children seeking health services in western Kenya. FGDs explored acceptability of pediatric SBT and home- and facility-based SBT use. Two reviewers conducted consensus coding and thematic analyses of transcripts using Dedoose.

Results:
Most HCWs but few caregivers had heard of SBT. Before seeing SBT instructions, both had concerns about potential HIV transmission through saliva, which were mostly alleviated after kit demonstration. Noted benefits of SBT included usability and avoiding finger pricks. Benefits of facility-based pediatric SBT included shorter client waiting and service time, higher testing coverage, and access to HCWs, while noted challenges included ensuring confidentiality. Benefits of caregivers using home-based SBT included convenience, privacy, decreased travel costs, increased testing, easier administration, and child comfort. Perceived challenges included not receiving counseling, disagreements with partners, child neglect, and negative emotional response to a positive test result. Overall, HCWs felt that SBT could be used for pediatric HIV testing but saw limited utility for caregivers performing SBT without an HCW present. Caregivers saw utility in home-based SBT but wanted easy access to counseling in case of a positive test result.

Conclusions:
SBT was generally acceptable to HCWs and caregivers and is a promising strategy to expand testing coverage.
A Demedicalized Model to Provide PrEP in a Sexual Health Clinic
Authors: Ramchandani Meena S. , Berzkalns Anna , Cannon Chase A. , Dombrowski Julia C. , Ocbamichael Negusse , Khosropour Christine M. , Barbee Lindley A. , Golden Matthew R. 
Published: May 2022

Background:
Sexual health clinics (SHCs) serve large numbers of patients who might benefit from preexposure prophylaxis (PrEP). Integrating longitudinal PrEP care into SHCs can overburden clinics. We implemented an SHC PrEP program that task shifted most PrEP operations to nonmedical staff, disease intervention specialists (DIS).

Methods:
We conducted a retrospective cohort analysis of PrEP patients in an SHC in Seattle, WA, from 2014 to 2020 to assess the number of patients served and factors associated with PrEP discontinuation. Clinicians provide same-day PrEP prescriptions, whereas DIS coordinate the program, act as navigators, and provide most follow-up care.

Results:
Between 2014 and 2019, 1387 patients attended an initial PrEP visit, 93% of whom were men who have sex with men. The number of patients initiating PrEP per quarter year increased from 20 to 81. The number of PrEP starts doubled when the clinic shifted from PrEP initiation at scheduled visits to initiation integrated into routine walk-in visits. The percentage of visits performed by DIS increased from 3% in 2014 to 45% in 2019. Median duration on PrEP use was 11 months. PrEP discontinuation was associated with non-Hispanic black race/ethnicity [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.02 to 1.76], age <20 years (HR 2.17, 95% CI: 1.26 to 3.75), age between 20 and 29 years (HR 1.55, 95% CI: 1.06 to 2.28), and methamphetamine use (HR 1.98, 95% CI: 1.57 to 2.49). The clinic had 750 patients on PrEP in the final quarter of 2019.

Conclusions:
A demedicalized SHC PrEP model that task shifts most operations to DIS can provide PrEP at scale to high priority populations.
Sexual Relationship Power Equity Is Associated With Consistent Condom Use and Fewer Experiences of Recent Violence Among Women Living With HIV in Canada
Authors: Closson Kalysha , Lee Melanie , Gibbs Andrew , Nicholson Valerie , Gormley Rebecca , Parry Rebeccah , Ding Erin , Li Jenny , Carter Allison , Pick Neora , Loutfy Mona , de Pokomandy Alexandra , Greene Saara , Logie Carmen H. , Kaida Angela 
Published: May 2022

Background:
Sexual relationship power (SRP) inequities, including having a controlling partner, have not been widely examined among women living with HIV (WLWH). We measured the prevalence and key outcomes of relationship control among WLWH in Canada.

Methods:
Baseline data from WLWH (≥16 years), reporting consensual sex in the last month enrolled in a Canadian community-collaborative cohort study in British Columbia, Ontario, and Quebec, included the relationship control SRP subscale by Pulerwitz (2000). Scale scores were dichotomized into medium/low (score = 1–2.82) vs. high relationship control (score = 2.82–4), and high scores indicate greater SRP equity. Cronbach's alpha assessed scale reliability. Bivariate analyses compared women with high vs. medium/low relationship control. Crude and adjusted multinomial regression examined associations between relationship control and condom use [consistent (ref), inconsistent, or never]; any sexual, physical, and/or emotional violence; and physical and/or sexual violence [never (ref), recent (≤3 months ago), and previous (>3 months ago)].

Results:
Overall, 473 sexually active WLWH (33% of cohort), median age = 39 (IQR = 33–46) years, 81% on antiretroviral therapy, and 78% with viral loads <50 copies/mL were included. The subscale demonstrated good reliability (Cronbach's alpha = 0.92). WLWH with high relationship control (80%) were more likely (P < 0.05) to be in a relationship, have no children, have greater resilience, and report less sociostructural inequities. In adjusted models, high relationship control was associated with lower odds of inconsistent vs. consistent condom use [adjusted odds ratio (aOR): 0.39 (95% confidence interval: 0.18 to 0.85)], any recent violence [aOR: 0.14 (0.04–0.47)] as well as recent physical and/or sexual [aOR : 0.05 (0.02–0.17)] but not previous violence (vs. never).

Discussion:
Prioritizing relationship equity and support for WLWH is critical for addressing violence and promoting positive health outcomes.
Improved antiproliferative activity of doxorubicin-loaded calcium phosphate nanoparticles against melanoma cells
Authors: Lima Igor Barbosa , Alvarenga Betania Mara , Tótaro Priscila Izabel Santos de , Boratto Fernanda , Leite Elaine Amaral , Guimaraes Pedro Pires Goulart 
Published: May 2022

AbstractThe high incidence of melanoma has received significant attention. Despite advances in early detection and standard treatment options, new strategies that improve therapy with reduced side effects are highly desirable. Several studies have demonstrated the efficiency of doxorubicin (Dox) to treat melanoma, however, side effects limit its clinical use. Drug delivery systems, especially nanostructured ones, are a useful approach to enhance antitumor activity and reduce the toxicity of drugs. Here, we report the use of calcium phosphate nanoparticles functionalized with Dox and hyaluronic acid (N-Dox) to enhance Dox antiproliferative activity. The effects were accessed in A-375 melanoma cells, in which N-Dox significantly decreased IC50 over 48 hours (0.142 ± 0.07) compared to the free drug (0.44 ± 0.25). Treatment triggered DNA damage, increased nuclear area, and senescent phenotype. Furthermore, it did not form colonies after 14 days of incubation preceded by short exposure treatment. These preliminary results indicate that N-Dox hold promise for melanoma treatment, reducing the minimum effective dose and perhaps a reduction in the cost of treatment.
Direct Visualization of Translesion DNA Synthesis Polymerase IV at the Replisome
Authors: Tuan Pham Minh , Gilhooly Neville , Marians Kenneth J. , Kowalczykowski Stephen C. 
Published: May 2022

AbstractIn bacterial cells, DNA damage tolerance is manifested by the action of translesion DNA polymerases that can synthesize DNA across template lesions that typically block the replicative DNA polymerase III. It has been suggested that one of these TLS DNA polymerases, DNA polymerase IV, can either act in concert with the replisome, switching places on the β sliding clamp with DNA polymerase III to bypass the template damage, or act subsequent to the replisome skipping over the template lesion in the gap in nascent DNA left behind as the replisome continues downstream. Evidence exists in support of both mechanisms. Using single-molecule analyses we show that DNA polymerase IV associates with the replisome in a concentration-dependent manner and remains associated over long stretches of replication fork progression under unstressed conditions. This association slows the replisome, requires DNA polymerase IV binding to the β clamp but not its catalytic activity, and is reinforced by the presence of the γ subunit of the β clamp-loading DnaX complex in the DNA polymerase III holoenzyme. Thus, DNA damage is not required for association of DNA polymerase IV with the replisome. We suggest that under stress conditions such as induction of the SOS response, the association of DNA polymerase IV with the replisome provides both a surveillance/bypass mechanism and a means to slow replication fork progression, thereby reducing the frequency of collisions with template damage and the overall mutagenic potential.SignificanceDamage to the nucleotide bases that make up the DNA in chromosomes creates a problem for their subsequent accurate duplication each time a cell divides. Typically, the cellular enzymatic machinery that replicates the DNA cannot copy a damaged base and specialized trans-lesion DNA polymerases, which are prone to making errors that result in mutations, are required to copy the damaged base, allowing replication to proceed. We demonstrate that the bacterial replisome, which is comprised of the enzymes required to replicate the chromosome, can associate with one of these specialized trans-lesion polymerases over long distances of replicated DNA. This association slows the speed of replication, thereby reducing the chance of mutations arising in the cell under conditions of stress.
Detection of M. tuberculosis in the environment as a tool for identifying high-risk locations for tuberculosis transmission
Authors: Verma Renu , Moreira Flora Martinez Figueira , Morais Agne Oliveira do Prado , Walter Katharine S. , Santos Paulo César Pereira dos , Kim Eugene , Soares Thiego Ramon , Araujo Rafaele Carla Pivetta de , Silva Bruna Oliveira da , Santos Andrea da Silva , Croda Julio , Andrews Jason R. 
Published: May 2022

ABSTRACTTuberculosis (TB) remains a leading cause of infectious mortality globally, yet most cases cannot be epidemiologically linked even with extensive contact investigations and whole genome sequencing. Consequently, there remain major gaps in our understanding of where and when M. tuberculosis (Mtb) exposures occur. We aimed to investigate whether Mtb can be detected in environments where TB patients were recently present, which could serve as a tool for characterizing exposure risk. We collected 389 environment surface (ES) swabs from two high TB burden prisons in Brazil, sampling 41 (n=340) cells occupied by individuals with active TB and 7 (n=49) cells from individuals without TB. In a subset of pooled swabs (n=6) and a swab from a cigarette lighter from the cell with active TB patients, we enriched Mtb DNA using RNA-bait hybrid capture assays and performed whole genome sequencing. In prison cells, Mtb DNA was detected in 55/340 (16%) of ES swabs from cells occupied by active TB patients and none (0/49) from cells in which no active TB patients were present. Mtb was detected in 13/16 (81%) prison cells occupied by the individuals with high/medium sputum Xpert Mtb load and 8/25 (32%) with low/very low sputum Mtb load (p=0.003). Seven hybrid capture samples had a median genomic coverage of 140X. rpoB mutations conferring high-level rifampin resistance were detected in 3/7 ES swabs. Mtb was frequently detectable in environments recently occupied by individuals with active TB. This approach could be applied in congregate environments to identify and characterize high-risk settings for Mtb exposure.