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Kristin Cornell,1 Alison De Souza,2 Mark Tacey,3 David M Long,4 Mayooran Veerasingham5 1Department of Obstetrics and Gynaecology, The Northern Hospital, Epping, VIC, 2Department of Urogynecology, Mercy Hospital for Women, Melbourne, VIC, 3Northern Clinical Research Centre, The Northern Hospital and Department of Medicine, University of Melbourne, Melbourne, VIC, 4Department of Emergency Medicine, The Austin Hospital, Melbourne, VIC, 5The Department of Obstetrics and Gynaecology, Ipswich General Hospital, Ipswich, QLD, Australia Background: Obstetric anal sphincter injury (OASI) is a serious complication of vaginal births, resulting in possible long-term consequences such as incontinence and pain. Adequate detection and management of these injuries is vital in minimizing the impact they have on women. Aim: To assess the rates of detection, management, and outcomes of OASI before and after the implementation of a new clinical practice guideline and operative pro forma. Materials and methods: A 12-month audit of the incidence, management, and outcomes of OASI was conducted in 2009. An operative pro forma and practice guideline were implemented in 2010 followed by a further audit undertaken between 2010 and 2012. Statistical analysis was performed to determine any significant change in practice. Results: The distribution of risk factors for OASI including primiparity, birthweight, and type of vaginal delivery was similar between the two audited groups. After implementation of the pro forma, the reported incidence of OASI increased from 1.62% to 3.1% (P=0.004). Significant changes in management included an increase in the use of recommended suture material (48% vs 80%, P=0.002), postoperative antibiotics (78% vs 99%, P=0.001), postoperative catheterization (52% vs 90%, P

Introduction: The diagnosis of female sexual arousal disorder (FSAD) requires that individuals experience clinically significant distress from their symptoms. Pre-trial content validity investigations were conducted by the sponsor to understand how women with FSAD best described their distress associated with this female sexual dysfunction (FSD) diagnosis. Objective: Responses to the Female Sexual Distress Scale – Desire, Arousal, Orgasm (FSDS-DAO) survey among healthy premenopausal women enrolled in a Phase 2b, exploratory, randomized, placebo-controlled, double-blind study of Sildenafil Cream, 3.6% for FSAD treatment (NCT04948151). Methods: After informed consent, enrollment diagnoses for each participant were established during a one-on-one clinical interview with independent experts. Baseline assessments were measured after a one-month, single-blind, placebo, run-in period. Participants were then randomized to Sildenafil Cream, 3.6% (n=101) versus Placebo (n=99) and used the investigational product (IP) as needed at home for 12 weeks, with monthly in-clinic assessments. The change from baseline at week 12 in question 14 (Q14) of the FSDS-DAO was a co-primary efficacy endpoint. All 15 FSDS-DAO questions begin with "How often did you feel, in the past 30 days" with a Likert score of 0 (Never) to 4 (Always). Results: Although changes from baseline at week 12 in FSDS-DAO Q14 responses were not different among active versus placebo users in the intent-to-treat population (p=0.84) or the future target population (women with FSAD only or primary FSAD with secondary hypoactive sexual desire disorder (HSDD)) (p=0.95), responses to several FSDS-DAO questions, showed reduced sexual distress among Sildenafil Cream, 3.6% users (Table 1). While Q14 asked specifically about concerns with sexual arousal, the other 5 questions asked about generalized sexual distress, using verbiage more congruent with pre-trial content validity investigations. Post-trial psychometric validation studies selected question 5 as the most appropriate for measuring sexual distress among this population. Conclusions: Data from this exploratory trial support that women with a diagnosis of FSAD only or primary FSAD with secondary HSDD experienced reduced sexual distress after receiving Sildenafil Cream, 3.6%. Disclosure: Yes, this is sponsored by industry/sponsor: Dare Bioscience and Strategic Science and Technologies. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Dare Bioscience and Strategic Science and Technologies. [ABSTRACT FROM AUTHOR]

Introduction: There are no FDA-approved treatments for female sexual arousal disorder (FSAD). Women with FSAD also often have co-existing secondary female sexual dysfunction (FSD) diagnoses. Objective: Post-hoc subset analysis of the effect of enrollment FSD diagnoses on efficacy of Sildenafil Cream, 3.6% for treatment of FSAD. Methods: Phase 2b, exploratory, randomized, placebo-controlled, double-blind study of Sildenafil Cream, 3.6% among premenopausal women with FSAD (NCT04948151). The change from baseline at week 12 in the arousal sensation (AS) domain (questions 6-9) of the 28-question sexual function questionnaire (SFQ28) was a co-primary efficacy endpoint. Changes from baseline in the mean number of satisfactory sexual experiences (SSEs) was a secondary endpoint. Exploratory efficacy endpoints included the Desire and Orgasm domains of the SFQ28. Enrollment FSD diagnoses were established during a clinical interview with independent experts. A retrospective review was performed of the clinical interviews for the intent-to-treat (ITT) population who completed the study (n=174) and enrollment diagnoses were categorized. Results: Table 1 shows the breakdown of enrollment diagnoses by product group for the ITT population. Participants with FSAD and pain (n=6) were excluded. Although few women had FSAD as their sole diagnosis, when randomized to Sildenafil Cream, 3.6%, they had the largest mean increases in efficacy variables at week 12. Women with FSAD and secondary HSDD also experienced substantial benefit with Sildenafil Cream, 3.6% at week 12. Women with an enrollment diagnosis of FSAD with secondary FOD had the least benefit from Sildenafil Cream, 3.6% at week 12. Conclusions: Data from this exploratory trial support the future target populations, including women with FSAD or FSAD with HSDD, will likely benefit the most from Sildenafil Cream, 3.6% treatment. Disclosure: Yes, this is sponsored by industry/sponsor: Dare Bioscience and Strategic Science and Technologies LLC. Clarification: Industry initiated, executed and funded study. Any of the authors act as a consultant, employee or shareholder of an industry for: Dare Bioscience and Strategic Science and Technologies LLC. [ABSTRACT FROM AUTHOR]

Introduction: Quantifying the change in the mean number of satisfactory sexual experiences (SSEs) is an efficacy endpoint recommended by the US Food and Drug Administration in studies of treatments for female sexual dysfunctions (FSD), including female sexual arousal disorder (FSAD). Objective: Post-hoc analysis of sexual experiences in a study of Sildenafil Cream, 3.6% for treatment of FSAD Methods: Phase 2b, exploratory, randomized, placebo-controlled, double-blind study of Sildenafil Cream, 3.6% among premenopausal women with FSAD (NCT04948151). Following a baseline, single-blind, placebo, run-in period, participants were randomized and used investigational product (IP) at home for 12 weeks. Between monthly, in-clinic assessments, participants answered questions in an electronic diary (eDiary), within 24-hours of each sexual experience. Sexual experiences were categorized as "Partnered" versus "By Myself" and "Satisfactory" versus "Not Satisfactory". eDiary question 11 (Q11) asked "Were conditions appropriate for satisfactory sexual activity (enough time, no distractions, etc.)?". Changes from baseline in the mean number of SSEs was a secondary efficacy endpoint. The Orgasm domain (questions 22-24) of the Sexual Function Questionnaire (SFQ28) was an exploratory efficacy endpoint. Un-partnered women and women with sexual partners who did not sign informed consent were enrolled in the study, but in these cases (n=15), IP was only used in solo sexual experiences. Results: Sildenafil Cream users had more sexual experiences and more un-partnered sexual experiences during the double-blind treatment period compared to Placebo Cream users. Sildenafil Cream users were significantly more likely to engage in sexual experiences even when conditions were not appropriate for a satisfactory experience. Although, the change from baseline in the mean number of SSEs at week 12 decreased during solo, un-partnered sexual experiences for both product groups (-0.12±0.27 for Sildenafil versus -0.04±0.32 for Placebo, p=0.85), during the double-blind treatment period, Sildenafil Cream users reported significantly higher proportions of SSEs during un-partnered sexual experiences (197/261, 75.5%) compared to Placebo users (116/187, 62.0%) (p=0.002). Despite Sildenafil Cream users engaging in a sexual experience more frequently when conditions were not appropriate, the proportion of SSEs during these events when Q11="No" were not different between active (17/59, 28.8%) versus placebo (8/25, 32.0%) users (p=0.77). Finally, un-partnered women and women with un-enrolled sexual partners, who by definition had only solo sexual experiences, had an increase from baseline in their SFQ Orgasm at week 12 with Sildenafil use (2.58±1.13) versus Placebo users in this subset, who had decreases in this score (-0.34±1.13) (p=0.13). Conclusions: These data support that Sildenafil Cream 3.6% enhanced solo, un-partnered sexual experiences, which represented approximately 1 in 5 events in this FSAD treatment study. Disclosure: Yes, this is sponsored by industry/sponsor: Dare Bioscience and Strategic Science and Technologies LLC Clarification: Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Dare Bioscience and Strategic Science and Technologies LLC. [ABSTRACT FROM AUTHOR]

LS/Ibg (LS) and SS/Ibg (SS) mice differ in ethanoHnduced duration of loss of righting response or sleep time, hypothermia, hyperglycemia, and blood ethanol concentrations at regaining righting response. These differences in response to ethanol are a result of differences in central nervous system sensitivity and are mediated by polygenic systems. Studies have indicated that catecholaminergic systems may be involved in the differential effects of ethanol in LS and SS lines of mice (Masserano JM, Werner N: Investigations into the neurochemical mechanisms mediating differences in ethanol sensitivity in two lines of mice. J Pharmacol Exp Ther 221:404-408, 1982). In this study the neurotoxin, 6-hydroxydopamine (6-OHDA), intracerebroventricular, was used to test this hypothesis. Administration of 6-OHDA markedly altered thermoregulation in LS mice but produced little effect in SS mice, and ethanoHnduced hyperglycemia was attenuated in both LS and SS mice by 6-OHDA. EthanoHnduced sleep time was increased in SS mice pretreated with 100 μg of 6-OHDA, intracerebroventricular, whereas this response in LS mice was unaffected by 6-OHDA administration. Changes in sleep time were not related to changes in blood ethanol concentrations, indicating that 6-OHDA alters ethanoHnduced sleep time by mechanisms other than brain sensitivity. Levels of norepinephrine and dopamine were determined in three brain regions, and the altered capacities for thermoregulation and glucoregulation were associated with changes in hypothalamic catecholamine levels. [ABSTRACT FROM AUTHOR]

Anti-idiotypic anti-DNA antibodies (anti-anti-DNA) have previously been described in both patients with systemic lupus erythematosus and healthy individuals. Jerne's hypothesis predicts that such antibodies would bear a paratope reactive with non-sequence specific DNA binding proteins. Here we have explored the notion of a molecular mimicry between anti-anti-DNA antibodies and antibodies to a previously described 28-29 kD cell surface DNA binding molecule. It was shown that affinity purified anti-anti-DNA antibodies inhibit the binding of DNA to cells and that MoAb to the 28 29 kD receptor react with anti-DNA antibodies. These findings indicate that a subset of anti-anti- DNA antibodies are idiotypically related to antibodies reactive with a cell surface DNA binding molecule. It is hypothesized that anti-DNA antibodies may arise when a convergence of genetic and environmental influences favours an unrestrained anti-idiotypic response to cell surface DNA binding molecule(s). [ABSTRACT FROM AUTHOR]

Previous experiments have established the presence of a 30-kD DNA binding protein on the surface of human leukocytes. Herein we report that selected sera from patients with systemic lupus erythematosus (SLE) and MCTD are reactive with a 28 30 kD protein on immunoblots of peripheral blood mononuclear cells (PBMC) cell membrane preparations; the reactivity is abolished by prior incubation of the blot with DNA. Antibodies eluted from the 28-30 kD strip inhibited the binding of 3H.DNA to human PBMC. An immunomatrix of 28-30 kD reactive immunoglobulins was able to extract a 29-kD DNA binding protein from a PBMC cell membrane preparation. Flow cytometry experiments confirmed the cell surface IgG reactivity of sera with T lymphocytes. Additional experiments indicated that cell surface IgG binding was not due to antibodies binding lo cell surface DNA, DNA anti-DNA immune complexes reacting with a DNA binding protein, anti-histone antibodies or anti-Sm antibodies. It is hypothesized that this autoimmune response could be one component of an idiotypic network involving anti-DNA antibodies. [ABSTRACT FROM AUTHOR]

Pursuing one's life calling can be personally fulfilling and professionally rewarding, but it also requires sacrifice. We provide evidence of a strong vocational drive using veterinary students as a case study and find that they willingly contribute higher monetary donations for helping animals relative to students in other fields. We also find a significant reduction in the cognitive performance of veterinarian students when exposed to an animal-in-need manipulation. The performance of non-veterinary students in the cognitive task is unaffected by the manipulation. Our results highlight the need for programs to address the economic, financial, and mental health well-being of students and professionals to promote sustainable vocational career commitment. "You owe it to all of us to get on with what you're good at." W.H. Auden., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Palma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Clostridioides difficile remains a problematic pathogen resulting in significant morbidity and mortality, especially for high-risk groups that include immunocompromised patients. Both the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA), as well as the American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recently provided guideline updates for C. difficile infection (CDI). In this narrative review, the authors reviewed available literature regarding the prevention or treatment of CDI in adults and focused on disagreements between the IDSA/SHEA and ACG guidelines, as well as articles that have been published since the updates. Several options for primary prophylaxis are available, including probiotics and antibiotics (vancomycin, fidaxomicin). The literature supporting fidaxomicin is currently quite limited. While there are more studies evaluating probiotics and vancomycin, the optimal patient populations and regimens for their use have yet to be defined. While the IDSA/SHEA guidelines discourage metronidazole use for mild CDI episodes, evidence exists that it may remain a reasonable option for these patients. Fidaxomicin has an advantage over vancomycin in reducing recurrences, but its use is limited by cost. Despite this, recent studies suggest fidaxomicin's cost-effectiveness as a first-line therapy, though this is highly dependent on institutional contracts and payment structures. Secondary prophylaxis should focus on non-antimicrobial options to lessen the impact on the microbiome. The oral option of fecal microbiota transplantation (FMT), SER109, and the now FDA-approved RBX2660 represent exciting new options to correct dysbiosis. Bezlotoxumab is another attractive option to prevent recurrences. Further head-to-head studies of newer agents will be needed to guide selection of the optimal therapies for CDI primary and secondary prophylaxis.

Importance: The US arrival of the Omicron variant led to a rapid increase in SARS-CoV-2 infections. While numerous studies report characteristics of Omicron infections among vaccinated individuals or persons with previous infection, comprehensive data describing infections among adults who are immunologically naive are lacking., Objectives: To examine COVID-19 acute and postacute clinical outcomes among a well-characterized cohort of unvaccinated and previously uninfected adults who contracted SARS-CoV-2 during the Omicron (BA.1/BA.2) surge, and to compare outcomes with infections that occurred during the Delta wave., Design, Setting, and Participants: This prospective multisite cohort study included community-dwelling adults undergoing high-resolution symptom and virologic monitoring in 8 US states between June 2021 and September 2022. Unvaccinated adults aged 30 to less than 65 years without an immunological history of SARS-CoV-2 who were at high risk of infection were recruited. Participants were followed for up to 48 weeks, submitting regular COVID-19 symptom surveys and nasal swabs for SARS-CoV-2 polymerase chain reaction (PCR) testing. Data were analyzed from May to October 2022., Exposures: Omicron (BA.1/BA.2 lineages) vs Delta SARS-CoV-2 infection, defined as a positive PCR test result that occurred during a period when the variant represented at least 50% of circulating SARS-CoV-2 variants in the participant's geographic region., Main Outcomes and Measure(s): The main outcomes examined were the prevalence and severity of acute (≤28 days after onset) and postacute (≥5 weeks after onset) symptoms., Results: Among 274 participants who were immunologically naive (mean [SD] age, 49 [9.7] years; 186 [68%] female; 19 [7%] Hispanic participants; 242 [88%] White participants), 166 (61%) contracted SARS-CoV-2. Of these, 137 infections (83%) occurred during the Omicron-predominant period and 29 infections (17%) occurred during the Delta-predominant period. Asymptomatic infections occurred among 7% (95% CI, 3%-12%) of Omicron-wave infections and 0% (95% CI, 0%-12%) of Delta-wave infections. Health care use among individuals with Omicron-wave infections was 79% (95% CI, 43%-92%) lower relative to individuals with Delta-wave infections (P = .001). Compared with individuals infected during the Delta wave, individuals infected during the Omicron wave also experienced a 56% (95% CI, 26%-74%, P = .004) relative reduction in the risk of postacute symptoms and a 79% (95% CI, 54%-91%, P < .001) relative reduction in the rate of postacute symptoms., Conclusions and Relevance: These findings suggest that among adults who were previously immunologically naive, few Omicron-wave (BA.1/BA.2) and Delta-wave infections were asymptomatic. Compared with individuals with Delta-wave infections, individuals with Omicron-wave infections were less likely to seek health care and experience postacute symptoms.

Over the past decade, the field of education has seen stark changes in the way that data are collected and leveraged to support high-stakes decision-making. Utilizing big data as a meaningful lens to inform teaching and learning can increase academic success. Data-driven research has been conducted to understand student learning performance, such as predicting at-risk students at an early stage and recommending tailored interventions to support services. However, few studies in veterinary education have adopted Learning Analytics. This article examines the adoption of Learning Analytics by using the retrospective data from the first-year professional Doctor of Veterinary Medicine program. The article gives detailed examples of predicting six courses from week 0 (i.e., before the classes started) to week 14 in the semester of Spring 2018. The weekly models for each course showed the change of prediction results as well as the comparison between the prediction results and students' actual performance. From the prediction models, at-risk students were successfully identified at the early stage, which would help inform instructors to pay more attention to them at this point.

Objective: The goal of this study was to evaluate and report details of a remotely taught surgical laboratory., Study Design: Observational., Sample Population: Second-year veterinary students (n = 143) enrolled in a surgical laboratory; 9 weeks were taught traditionally, and 6 weeks were taught remotely., Methods: Because of the global pandemic, remote laboratories were developed and delivered. Students performed surgical procedures in model organs remotely while being observed by and receiving feedback from instructors on an internet-based video platform. Methods for remote surgical teaching were explored, and successes and challenges were detailed. Surveys were administered to the students and faculty to gather perspectives on their experience and subsequent confidence., Results: Surveys were completed by 81 of 143 (57%) students and seven of seven (100%) instructors. The mean overall student satisfaction score (1 not at all satisfied, 10 very satisfied) for in-person instruction was 8.2, and the mean score for remote instruction was 6.2 (P < .001). Overall, the instructors had a mean satisfaction score of 8 for in-person laboratories and a mean satisfaction score of 6 for remotely taught laboratories. Most students had a perception of greater one-on-one instructor attention in remote laboratories. Students reported similar confidence levels for three surgical procedures., Conclusion: The described remote teaching method resulted in the perception of greater instructor attention given to students. Student and instructor satisfaction was lower with remote teaching than with in-person teaching., Impact: The described method of remote teaching may be applied to teaching surgical students in settings when face-to-face instruction cannot be achieved and may be developed further to create an experience equivalent to face-to-face instruction., (© 2021 The American College of Veterinary Surgeons.)

Nutritional status is a well-recognized prognostic indicator in chronic obstructive pulmonary disease (COPD); however, very little is known about the relationship between lung function and saturated fat intake. We used data from the cross-sectional National Health and Nutrition Examination Surveys (NHANES) to assess the relationship between saturated fatty acid (SFA) intake and lung function in the general US adult population. Adults in NHANES (2007⁻2012) with pre-bronchodilator spirometry measurements and dietary SFA intake were included. Primary outcomes were lung function including forced expiratory volume in one second (FEV₁) , FEV₁, forced vital capacity (FVC), FEV₁/FVC ratio, percent predicted FEV₁ and percent predicted FVC. Multivariable regression models in the general population as well as those with spirometry-defined airflow obstruction were used to assess the relationship between lung function measurements and dietary SFA intake after adjustment for confounders. 11,180 eligible participants were included in this study. Univariate analysis revealed a statistically significant positive association between total SFA intake and lung function outcomes; however, these relationships were attenuated after adjustment for covariates. A secondary analysis of individuals with spirometry-defined airflow obstruction (FEV₁/FVC < 0.7) revealed that a lower intake of SFA was associated with reduced FEV 1 (β = -126.4, p = 0.04 for quartile 1 vs. quartile 4), FVC (β = -165.8. p = 0.01 for quartile 1 vs. quartile 4), and percent predicted FVC (β = -3.3. p = 0.04 for quartile 1 vs. quartile 4), after adjustment for relevant confounders. No associations were observed for the FEV₁/FVC ratio and percent predicted FEV₁. It is possible that characteristics such as food source and fatty acid chain length may influence associations between saturated fatty acid intake and health outcomes., Competing Interests: The authors declare no conflict of interest.

Objective: To investigate the frequency, source, and risk factors of intraoperative (IO) surgeon and patient bacterial contamination during clean orthopedic surgeries, and to investigate the relationship between IO contamination and surgical site infection (SSI) in dogs., Study Design: Prospective clinical study., Sample Population: Client-owned dogs undergoing stifle surgery (n = 100)., Methods: IO cultures were taken in each case from surgical foot wrap, peri-incisional skin, surgical gloves, and the surgical team's hands. The environment (operating room [OR] lights, computers, scrub sink faucet, anesthesia gurney, and radiology table) was sampled every 5 months. Bacteria were identified and the contamination of each case was categorized. All gloves from the surgical team were collected and tested for perforations using a water infusion test. Cases were followed for at least 8 weeks to determine the presence or absence of SSI. Perioperative variables were evaluated for association with IO contamination and SSI., Results: Bacterial isolates were yielded from 81% of procedures from 1 or more sources; 58% had positive hand cultures, 46% had positive glove cultures, 23% had positive patient skin cultures, and 12% had positive foot wrap cultures. Staphylococcus spp. was the most commonly recovered bacteria. There was no apparent association between IO contamination and SSI. The highest level of environmental contamination was associated with the scrub sink faucet, followed by the radiology table, anesthesia gurney, and OR computers. The IO glove perforation rate was 18%., Conclusion: Clean orthopedic procedures commonly had clinically insignificant bacterial contamination. In our study, bacteria responsible for SSI did not appear to colonize the patient in the OR., (© Copyright 2016 by The American College of Veterinary Surgeons.)

Background: Prescribing opioids for chronic non-cancer pain (CNCP) is a challenge due to associated risks from abuse, addiction and adverse effects. We surveyed resident physicians on their knowledge, attitude and practices in opioid prescription practices in the ambulatory setting and conducted an educational module to address their knowledge gaps., Methods: A phase 1 survey assessed knowledge, attitudes and practices of residents in the out-patient management of CNCP with opioids. Demographics, numbers of patients seen, those with concerns for risky behaviors, adverse effects and the reasons for concern were also recorded. In Phase 2, an educational module in the form of didactics and case based discussions addressed the perceived deficiencies noted from results of phase 1 survey. Pre and post module surveys assessed the effectiveness of the educational module., Results: In the phase 1 study (45/49, 92% response rate, M:F = 30:15) 33.3% (15/45) were in Post-Graduate Year (PGY) 1, 35.6% (16/45) PGY2s and 31.1% (14/45) PGY3s; 80% (36/45) saw more than one patient with CNCP in the previous 3 months; 62.2% (28/45) had at least one patient with concerns for misuse and addiction; 77.8% (35/45) and 86.7% (39/45) reported a lack of training and consistent documentation respectively, and 82.2% (37/45) were uncomfortable to refill for other provider's patients. All (100%, 45/45) consulted the clinical pharmacist; 86.7% (39/45) believed that either focused education would be beneficial. In the phase 2 study (44/49, 89.7% response rate, M: F = 29: 15), the pre- and post-module responses showed that > 90% of the residents perceived improvement in knowledge and confidence in management of CNCP with opioids after the educational module., Conclusions: Internal medicine residents perceived deficits in their ability to manage CNCP. Following a focused educational training, residents' knowledge and confidence in prescription of opioids improved, demonstrating the need to include management of CNCP with opioids into their curriculum.