Characteristics of out-of-hospital births and perinatal outcomes: data from the Lazio Region, Italy, cross-sectional study from 2019 to 2021.

INTRODUCTION: In Italy, the primary place of birth is typically a hospital, with only a small number of women opting for an out-of-hospital setting. This study details the characteristics of midwifery care and perinatal and maternal outcomes of women who gave birth in an out-of-hospital setting in the Lazio Region, Italy, from 2019 to 2021. METHODS: A cross-sectional study was carried out. The study population included 542 healthy low-risk women who completed the process of planning an out-of-hospital birth, and excluding transfers, this resulted in a total sample of 478 women who gave birth out-of-hospital. Descriptive and inferential analyses and also a logistic regression model were performed. RESULTS: The main outcomes of the out-of-hospital deliveries were: intact perineum in 38.9% of cases, two cases of 3rd degree laceration (0.4%) and in one case (0.2%) episiotomy. Intrapartum emergencies occurred in 85 out of 478 women (17.8%) but only 10 women required a transfer to hospital after delivery. The one minute Apgar score was equal to or greater than 7 in 99.2% of cases. Exclusive breastfeeding of 96% one week after birth and 94.6% one month. Furthermore, having a previous vaginal hospital birth (adjOR 9.7; CI 95% 4.33-21.68 P<0.001) and a previous out-of-hospital birth (adjOR 24.2; CI 95% 3.23-181.48 P=0.002) was associated with the continuation of out-of-hospital birth. CONCLUSIONS: For low-risk pregnant women who have planned an out-of-hospital birth, it has been shown to be a safe, adequate, appropriate, and effective alternative.

Codesign and refinement of an optimised antenatal education session to better inform women and prepare them for labour and birth.

OBJECTIVE: Our objective was to codesign, implement, evaluate acceptability and refine an optimised antenatal education session to improve birth preparedness. DESIGN: There were four distinct phases: codesign (focus groups and codesign workshops with parents and staff); implementation of intervention; evaluation (interviews, questionnaires, structured feedback forms) and systematic refinement. SETTING: The study was set in a single maternity unit with approximately 5500 births annually. PARTICIPANTS: Postnatal and antenatal women/birthing people and birth partners were invited to participate in the intervention, and midwives were invited to deliver it. Both groups participated in feedback. OUTCOME MEASURES: We report on whether the optimised session is deliverable, acceptable, meets the needs of women/birthing people and partners, and explain how the intervention was refined with input from parents, clinicians and researchers. RESULTS: The codesign was undertaken by 35 women, partners and clinicians. Five midwives were trained and delivered 19 antenatal education (ACE) sessions to 142 women and 94 partners. 121 women and 33 birth partners completed the feedback questionnaire. Women/birthing people (79%) and birth partners (82%) felt more prepared after the class with most participants finding the content very helpful or helpful. Women/birthing people perceived classes were more useful and engaging than their partners. Interviews with 21 parents, a midwife focus group and a structured feedback form resulted in 38 recommended changes: 22 by parents, 5 by midwives and 11 by both. Suggested changes have been incorporated in the training resources to achieve an optimised intervention. CONCLUSIONS: Engaging stakeholders (women and staff) in codesigning an evidence-informed curriculum resulted in an antenatal class designed to improve preparedness for birth, including assisted birth, that is acceptable to women and their birthing partners, and has been refined to address feedback and is deliverable within National Health Service resource constraints. A nationally mandated antenatal education curriculum is needed to ensure parents receive high-quality antenatal education that targets birth preparedness.

Rac1 and Nectin3 are essential for PCP-directed axon guidance in the peripheral auditory system.

Our sense of hearing is critically dependent on the spiral ganglion neurons (SGNs) that connect the sound receptors in the organ of Corti (OC) to the cochlear nuclei of the hindbrain. Type I SGNs innervate inner hair cells (IHCs) to transmit sound signals, while type II SGNs (SGNIIs) innervate outer hair cells (OHCs) to detect moderate-to-intense sound. During development, SGNII afferents make a characteristic 90-degree turn toward the base of the cochlea and innervate multiple OHCs. It has been shown that the Planar Cell Polarity (PCP) pathway acts non-autonomously to mediate environmental cues in the cochlear epithelium for SGNII afferent turning towards the base. However, the underlying mechanisms are unknown. Here, we present evidence that PCP signaling regulates multiple downstream effectors to influence cell adhesion and the cytoskeleton in cochlear supporting cells (SCs), which serve as intermediate targets of SGNII afferents. We show that the core PCP gene Vangl2 regulates the localization of the small GTPase Rac1 and the cell adhesion molecule Nectin3 at SC-SC junctions through which SGNII afferents travel. Through in vivo genetic analysis, we also show that loss of Rac1 or Nectin3 partially phenocopied SGNII peripheral afferent turning defects in Vangl2 mutants, and that Rac1 plays a non-autonomous role in this process in part by regulating PCP protein localization at the SC-SC junctions. Additionally, epistasis analysis indicates that Nectin3 and Rac1 likely act in the same genetic pathway to control SGNII afferent turning. Together, these experiments identify Nectin3 and Rac1 as novel regulators of PCP-directed SGNII axon guidance in the cochlea.

The Feasibility and Efficacy of a Virtual Reality Tandem Cycling Program for Persons with Parkinson's Disease and Their Care Partners.

INTRODUCTION: Persons with Parkinson's disease (PwPD) suffer from motor and non-motor symptoms which significantly affect their quality of life (QoL), and the QoL of their care partners (CP). Tandem cycling reduces PwPD motor symptoms; however, no studies have examined other benefits or included PwPD CP. We conducted an 8-week community virtual reality (VR) tandem cycling intervention to assess the feasibility and efficacy for PwPD and their CP (i.e., PD dyads). We hypothesized that dyadic tandem cycling would improve (1) PwPD motor and non-motor symptoms and (2) dimensions of PD dyads' QoL and physiologic health. METHODS: Ten PD dyads were recruited to complete 8 weeks of progressive intensity, bi-weekly tandem cycling. At pre- and post-testing, PwPD were assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III (MDS-UPDRS-III), functional gait assessment (FGA), and 10-m gait speed test. PD dyads also completed emotional and cognitive status questionnaires [e.g., Geriatric Depression Scale-Short Form (GDS-SF)], and wore BodyGuard 2 heart rate (HR) monitors for 48 h to assess surrogate measures of heart rate variability. Statistical analyses were conducted using Student's t tests with significance set at p ≤ 0.05. RESULTS: Eight PD dyads and one PwPD completed the intervention. Retention of PwPD (90%) and CP (80%) was adequate, and PD dyad adherence ranged from 91.67 to 97.91%. PwPD demonstrated significant clinical improvements in MDS-UPDRS-III scores (- 7.38, p < 0.01), FGA scores (+ 3.50, p < 0.01), and 10-m gait speed times (+ 0.27 m/s, p < 0.01), in addition to significant self-reported improvements in mobility (- 13.61, p = 0.02), fatigue (- 5.99, p = 0.02), and social participation (+ 4.69, p < 0.01). CP depressive symptoms significantly decreased (- 0.88, p = 0.02), and PD dyads shared a significant increase in root mean square of the successive differences (RMSSD; p = 0.04). CONCLUSION: Our pilot study demonstrated feasibility and multiple areas of efficacy supporting further investigation of community VR tandem cycling as a therapeutic intervention for PD dyads.

Missed Opportunities for HIV Prevention in a Large County Safety Net Health System.

INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) is effective at reducing HIV transmission. However, PrEP uptake is low for racial and ethnic minorities and women, especially in the Southern US Health care clinicians should be prepared to identify all patients eligible for PrEP, provide counseling, and prescribe PrEP. METHODS: Retrospective analysis of persons newly diagnosed with HIV was conducted at a large public health system from January 2015 to June 2021. Interactions with the health system in the 5 years preceding HIV diagnosis were analyzed, and missed opportunities for HIV prevention interventions, including PrEP and condom use counseling, were identified. RESULTS: We identified 454 patients with a new HIV diagnosis with previous health system interactions. 166(36.6%) had at least 1 identifiable indication for PrEP: 42(9.3%) bacterial STI, 63(13.9%) inconsistent condom use, or 82(18%) injection drug use before HIV diagnosis. Only 7(1.5%) of patients were counseled on PrEP. Most patients (308; 67.8%) had no documented condom use history in the EHR before diagnosis, a surrogate marker for obtaining a sexual history. Patients who exclusively interacted with the emergency care setting did not receive PrEP education and were less likely to receive condom use counseling. CONCLUSION: Missed opportunities to offer HIV prevention before diagnosis were common among patients newly diagnosed with HIV. Most patients did not have sexual history documented in the chart before their HIV diagnosis. Educational interventions are needed to ensure that clinicians are prepared to identify those eligible and discuss the benefits of PrEP.

Real-world application of Wound, Ischemia, and foot Infection scores in peripheral arterial disease patients.

OBJECTIVE: The Society for Vascular Surgery (SVS) Wound, Ischemia, and foot Infection (WIfI) classification system aims to risk stratify patients with chronic limb-threatening ischemia (CLTI), predicting both amputation rates and the need for revascularization. However, real-world use of the system and whether it predicts outcomes accurately after open revascularization and peripheral interventions is unclear. Therefore, we sought to determine the adoption of the WIfI classification system within a contemporary statewide collaborative as well as the impact of patient factor, and WIfI risk assessment on short- and long-term outcomes. METHODS: Using data from a large statewide collaborative, we identified patients with CLTI undergoing open surgical revascularization or peripheral vascular intervention (PVI) between 2016 and 2022. The primary exposure was preoperative clinical WIfI stage. Patients were categorized according to the SVS Lower Extremity Threatened Limb Classification System into clinical WIfI stages 1, 2, 3, or 4. The primary outcomes were 30-day and 1-year amputation and mortality rates. Multivariable logistic regression was performed to estimate the association of WIfI stage on postrevascularization outcomes. RESULTS: In the cohort of 17,417 patients, 83.4% (n = 14,529) had WIfI stage documented. PVIs were performed on 57.6% of patients, and 42.4% underwent an open surgical revascularization. Of the patients, 49.5% were classified as stage 1, 19.3% stage 2, 12.8% stage 3, and 18.3% of patients met stage 4 criteria. Stage 3 and 4 patients had higher rates of diabetes, congestive heart failure, and renal failure, and were less likely to be current or former smokers. One-half of stage 3 patients underwent open surgical revascularization, whereas stage 1 patients were most likely to have received a PVI (64%). As WIfI stage increased from 1 to 4, 1-year mortality increased from 12% to 21% (P < .001), 30-day amputation rates increased from 5% to 38% (P < .001), and 1-year amputation rates increased from 15% to 55% (P < .001). Finally, patients who did not have WIfI scores classified had significantly higher 30-day and 1-year mortality rates, as well as higher 30-day and 1-year amputation rates. CONCLUSIONS: The SVS WIfI clinical stage is significantly associated with 1-year amputation rates in patients with CLTI after lower extremity revascularization. Because nearly 55% of stage 4 patients require a major amputation within 1 year of intervention, this finding study supports use of the WIfI classification system in clinical decision-making for patients with CLTI.

Regulation of Microprocessor assembly and localization via Pasha's WW domain in C. elegans.

Primary microRNA (pri-miRNA) transcripts are processed by the Microprocessor, a protein complex that includes the ribonuclease Drosha and its RNA binding partner DGCR8/Pasha. We developed a live, whole animal, fluorescence-based sensor that reliably monitors pri-miRNA processing with high sensitivity in C. elegans. Through a forward genetic selection for alleles that desilence the sensor, we identified a mutation in the conserved G residue adjacent to the namesake W residue of Pasha's WW domain. Using genome editing we also mutated the W residue and reveal that both the G and W residue are required for dimerization of Pasha and proper assembly of the Microprocessor. Surprisingly, we find that the WW domain also facilitates nuclear localization of Pasha, which in turn promotes nuclear import or retention of Drosha. Furthermore, depletion of Pasha or Drosha causes both components of the Microprocessor to mislocalize to the cytoplasm. Thus, Pasha and Drosha mutually regulate each other's spatial expression in C. elegans.

Cross Sectional Survey of Antenatal Educators' Views About Current Antenatal Education Provision.

OBJECTIVES: Antenatal education (ANE) is part of National Health Service (NHS) care and is recommended by The National Institute for Health and Care Excellence (NICE) to increase birth preparedness and help pregnant women/birthing people develop coping strategies for labour and birth. We aimed to understand antenatal educator views about how current ANE supports preparedness for childbirth, including coping strategy development with the aim of identifying targets for improvement. METHODS: A United Kingdom wide, cross-sectional online survey was conducted between October 2019 and May 2020. Antenatal educators including NHS midwives and private providers were purposively sampled. Counts and percentages were calculated for closed responses and thematic analysis used for open text responses. RESULTS: Ninety-nine participants responded, 62% of these did not believe that ANE prepared women for labour and birth. They identified practical barriers to accessing ANE, particularly for marginalised groups, including financial and language barriers. Educators believe class content is medically focused, and teaching is of variable quality with some midwives being ill-prepared to deliver antenatal education. 55% of antenatal educators believe the opportunity to develop coping strategies varies between location and educators and only those women who can pay for non-NHS classes are able to access all the coping strategies that can support them with labour and birth. CONCLUSIONS FOR PRACTICE: Antenatal educators believe current NHS ANE does not adequately prepare women for labour and birth, leading to disparities in birth preparedness for those who cannot access non-NHS classes. To reduce this healthcare inequality, NHS classes need to be standardised, with training for midwives in delivering ANE enhanced.

Why surveys are 'very hard': exploring challenges and insights for collection of authentic patient experience information with speakers of Australian First Nations languages.

INTRODUCTION: Health services collect patient experience data to monitor, evaluate and improve services and subsequently health outcomes. Obtaining authentic patient experience information to inform improvements relies on the quality of data collection processes and the responsiveness of these processes to the cultural and linguistic needs of diverse populations. This study explores the challenges and considerations in collecting authentic patient experience information through survey methods with Australians who primarily speak First Nations languages. METHODS: First Nations language experts, interpreters, health staff and researchers with expertise in intercultural communication engaged in an iterative process of critical review of two survey tools using qualitative methods. These included a collaborative process of repeated translation and back translation of survey items and collaborative analysis of video-recorded trial administration of surveys with languages experts (who were also receiving dialysis treatment) and survey administrators. All research activities were audio- or video-recorded, and data from all sources were translated, transcribed and inductively analysed to identify key elements influencing acceptability and relevance of both survey process and items as well as translatability. RESULTS: Serious challenges in achieving equivalence of meaning between English and translated versions of survey items were pervasive. Translatability of original survey items was extensively compromised by the use of metaphors specific to the cultural context within which surveys were developed, English words that are familiar but used with different meaning, English terms with no equivalent in First Nations languages and grammatical discordance between languages. Discordance between survey methods and First Nations cultural protocols and preferences for seeking and sharing information was also important: the lack of opportunity to share the 'full story', discomfort with direct questions and communication protocols that preclude negative or critical responses constrained the authenticity of the information obtained through survey methods. These limitations have serious implications for the quality of information collected and result in frustration and distress for those engaging with the survey. CONCLUSION: Profound implications for the acceptability of a survey tool as well as data quality arise from differences between First Nations cultural and communication contexts and the cultural context within which survey methods have evolved. When data collection processes are not linguistically and culturally congruent there is a risk that patient experience data are inaccurate, miss what is important to First Nations patients and have limited utility for informing relevant healthcare improvement. Engagement of First Nations cultural and language experts is essential in all stages of development, implementation and evaluation of culturally safe and effective approaches to support speakers of First Nations languages to share their experiences of health care and influence change.

Comparative evaluation of transcutaneous oxygen tension and ankle-brachial index as predictors of reoperation following below-knee amputation.

OBJECTIVE: Decision-making regarding level of lower extremity amputation is sometimes challenging. Selecting an appropriate anatomic level for major amputation requires consideration of tradeoffs between postoperative function and risk of wound complications that may require additional operations, including debridement and/or conversion to above-knee amputation (AKA). We evaluated the utility of common, non-invasive diagnostic tests used in clinical practice to predict the need for reoperations among patients undergoing primary, elective, below knee-amputations (BKAs) by vascular surgeons. METHODS: Patients undergoing elective BKA over a 5-year period were identified using Current Procedural Terminology codes. Medical records were reviewed to characterize demographics, pre-amputation testing transcutaneous oxygen tension (TcPO2), and ankle-brachial index (ABI). The need for ipsilateral post-BKA reoperation (including BKA revision and/or conversion to AKA) regardless of indication was the primary outcome. Associations were evaluated using univariable and multivariable logistic regression models. Cutpoints for TcPO2 values associated with amputation reoperation were evaluated using receiver operating characteristic curves. RESULTS: We identified 175 BKAs, of which 46 (26.3%) required ipsilateral reoperation (18.9% BKA revisions and 14.3% conversions to AKA). The mean age was 63.3 ± 14.8 years. Most patients were male (65.1%) and White (72.0%). Mean pre-amputation calf TcPO2 was 40.0 ± 20.5 mmHg, and mean ABI was 0.64 ± 0.45. In univariable models, post-BKA reoperation was associated with calf TcPO2 (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.94-0.99; P = .013) but not ABI (OR, 0.53; 95% CI, 0.19-1.46; P = .217). Univariable associations with reoperation were also identified for age (OR, 0.97; 95% CI, 0.94-0.990; P = .003) and diabetes (OR, 0.43; 95% CI, 0.21-0.87; P = .019). No associations with amputation revision were identified for gender, race, end-stage renal disease, or preoperative antibiotics. Calf TcPO2 remained associated with post-BKA reoperation in a multivariable model (OR, 0.97; 95% CI, 0.94-0.99; P = .022) adjusted for age (OR, 0.98; 95% CI, 0.94-1.01; P = .222) and diabetes (OR, 0.98; 95% CI, 0.94-1.01; P = .559). Receiver operating characteristic analysis suggested a TcPO2 ≥38 mmHg as an appropriate cut-point for assessing risk for BKA revision (area under the curve = 0.682; negative predictive value, 0.91). CONCLUSIONS: Reoperation after BKA is common, and reoperation risk was associated with pre-amputation TcPO2. For patients undergoing elective BKA, higher risk of reoperation should be discussed with patients with an ipsilateral TcPO2 <38 mmHg.

Artificial Intelligence-Generated Draft Replies to Patient Inbox Messages.

Importance: The emergence and promise of generative artificial intelligence (AI) represent a turning point for health care. Rigorous evaluation of generative AI deployment in clinical practice is needed to inform strategic decision-making. Objective: To evaluate the implementation of a large language model used to draft responses to patient messages in the electronic inbox. Design, Setting, and Participants: A 5-week, prospective, single-group quality improvement study was conducted from July 10 through August 13, 2023, at a single academic medical center (Stanford Health Care). All attending physicians, advanced practice practitioners, clinic nurses, and clinical pharmacists from the Divisions of Primary Care and Gastroenterology and Hepatology were enrolled in the pilot. Intervention: Draft replies to patient portal messages generated by a Health Insurance Portability and Accountability Act-compliant electronic health record-integrated large language model. Main Outcomes and Measures: The primary outcome was AI-generated draft reply utilization as a percentage of total patient message replies. Secondary outcomes included changes in time measures and clinician experience as assessed by survey. Results: A total of 197 clinicians were enrolled in the pilot; 35 clinicians who were prepilot beta users, out of office, or not tied to a specific ambulatory clinic were excluded, leaving 162 clinicians included in the analysis. The survey analysis cohort consisted of 73 participants (45.1%) who completed both the presurvey and postsurvey. In gastroenterology and hepatology, there were 58 physicians and APPs and 10 nurses. In primary care, there were 83 physicians and APPs, 4 nurses, and 8 clinical pharmacists. The mean AI-generated draft response utilization rate across clinicians was 20%. There was no change in reply action time, write time, or read time between the prepilot and pilot periods. There were statistically significant reductions in the 4-item physician task load score derivative (mean [SD], 61.31 [17.23] presurvey vs 47.26 [17.11] postsurvey; paired difference, -13.87; 95% CI, -17.38 to -9.50; P < .001) and work exhaustion scores (mean [SD], 1.95 [0.79] presurvey vs 1.62 [0.68] postsurvey; paired difference, -0.33; 95% CI, -0.50 to -0.17; P < .001). Conclusions and Relevance: In this quality improvement study of an early implementation of generative AI, there was notable adoption, usability, and improvement in assessments of burden and burnout. There was no improvement in time. Further code-to-bedside testing is needed to guide future development and organizational strategy.

Effectiveness of an Artificial Intelligence-Enabled Intervention for Detecting Clinical Deterioration.

Importance: Inpatient clinical deterioration is associated with substantial morbidity and mortality but may be easily missed by clinicians. Early warning scores have been developed to alert clinicians to patients at high risk of clinical deterioration, but there is limited evidence for their effectiveness. Objective: To evaluate the effectiveness of an artificial intelligence deterioration model-enabled intervention to reduce the risk of escalations in care among hospitalized patients using a study design that facilitates stronger causal inference. Design, Setting, and Participants: This cohort study used a regression discontinuity design that controlled for confounding and was based on Epic Deterioration Index (EDI; Epic Systems Corporation) prediction model scores. Compared with other observational research, the regression discontinuity design facilitates causal analysis. Hospitalized adults were included from 4 general internal medicine units in 1 academic hospital from January 17, 2021, through November 16, 2022. Exposure: An artificial intelligence deterioration model-enabled intervention, consisting of alerts based on an EDI score threshold with an associated collaborative workflow among nurses and physicians. Main Outcomes and Measures: The primary outcome was escalations in care, including rapid response team activation, transfer to the intensive care unit, or cardiopulmonary arrest during hospitalization. Results: During the study, 9938 patients were admitted to 1 of the 4 units, with 963 patients (median [IQR] age, 76.1 [64.2-86.2] years; 498 males [52.3%]) included within the primary regression discontinuity analysis. The median (IQR) Elixhauser Comorbidity Index score in the primary analysis cohort was 10 (0-24). The intervention was associated with a -10.4-percentage point (95% CI, -20.1 to -0.8 percentage points; P = .03) absolute risk reduction in the primary outcome for patients at the EDI score threshold. There was no evidence of a discontinuity in measured confounders at the EDI score threshold. Conclusions and Relevance: Using a regression discontinuity design, this cohort study found that the implementation of an artificial intelligence deterioration model-enabled intervention was associated with a significantly decreased risk of escalations in care among inpatients. These results provide evidence for the effectiveness of this intervention and support its further expansion and testing in other care settings.

Mid-Term Follow Up of the Nexel Total Elbow Arthroplasty.

INTRODUCTION: Aseptic loosening is one of the most common complications of total elbow arthroplasty (TEA). Modern implants, such as the Nexel, have been designed in an attempt to decrease loosening. The present study aims to report implant survivorship, radiographic assessment of loosening and lucency, and patient-reported outcome measures (PROMs) in patients treated with the Nexel TEA at mid-term follow-up. METHODS: Consecutive series of adult patients underwent TEA using the Nexel by a single surgeon via standardized technique. Patients with minimum 3 year follow-up with radiographic and PROM data were included. Survivorship was defined by the absence of revision. Loosening was assessed via Wrightington method by three independent fellowship-trained shoulder and elbow surgeons. Lucency was analyzed across individual radiographic zones on orthogonal radiographs. PROMs included the Quick Dash (QDASH), Patient Rated Elbow Evaluation (PREE), and EuroQoL (EQ5D). RESULTS: 38 consecutive patients (22 female, 16 male) with mean age of 67 underwent TEA via triceps-sparing isolated medial window approach. Mean follow-up was 5.5 years (range 3-9). Primary diagnoses were: 19 osteoarthritis (OA), 9 rheumatoid arthritis (RA), 9 post-traumatic arthritis (PA), 1 conversion of elbow arthrodesis. Overall survivorship was 97.4%, with one patient undergoing revision for infection. Loosening was found in 5.3% of elbows, averaged across three observers. Lucency was most pronounced at the level of the humeral condyles. PROMs demonstrated significant and clinically meaningful improvements in 76%, 92%, and 73% of patients for QDASH, PREE, and EQ5D, respectively. No significant correlations were found between patient age, gender, loosening, lucency, and PROMs. CONCLUSION: At mid-term follow-up, the Nexel TEA demonstrated excellent overall survivorship and low rate of implant loosening. The single failure requiring revision for infection was conversion of a prior elbow arthrodesis. PROMs overall exhibited marked and consistent improvement from preop to final postop follow-up. Although promising, these results should be interpreted with some caution as long term data regarding this prosthesis are still lacking.

Lumican, a Multifunctional Cell Instructive Biomarker Proteoglycan Has Novel Roles as a Marker of the Hypercoagulative State of Long Covid Disease.

This study has reviewed the many roles of lumican as a biomarker of tissue pathology in health and disease. Lumican is a structure regulatory proteoglycan of collagen-rich tissues, with cell instructive properties through interactions with a number of cell surface receptors in tissue repair, thereby regulating cell proliferation, differentiation, inflammation and the innate and humoral immune systems to combat infection. The exponential increase in publications in the last decade dealing with lumican testify to its role as a pleiotropic biomarker regulatory protein. Recent findings show lumican has novel roles as a biomarker of the hypercoagulative state that occurs in SARS CoV-2 infections; thus, it may also prove useful in the delineation of the complex tissue changes that characterize COVID-19 disease. Lumican may be useful as a prognostic and diagnostic biomarker of long COVID disease and its sequelae.

Accidental Gunshot Wound Fatalities Related to Dropped Firearms.

ABSTRACT: A death resulting from the accidental discharge of a firearm represents a rare but oftentimes preventable tragedy. Such deaths may occur in a variety of settings. One such setting involves the discharge of a loaded firearm, which occurs when it is accidentally dropped, thrown, or falls to the ground. We report on 3 cases in which a loaded firearm discharged when it was dropped, resulting in the deaths of 3 individuals. In 2 cases, the person carrying the dropped firearm was killed, whereas in the third case, a child standing near the person who dropped the weapon was killed. We discuss the risk factors involved in these tragic incidents and present preventive strategies.

Mediational pathways exploring the link between adverse childhood experiences and physical health in a transgender population.

BACKGROUND: Adverse childhood experiences (ACEs) consist of instances of abuse, neglect, or household dysfunction occurring before adulthood. Prevalence rates of ACEs are higher among specific populations, including gender minorities. In addition to ACEs, transgender individuals (TG) face many personal, social, and structural factors that have the potential to negatively impact their physical health. OBJECTIVE: This study examines exploratory mediational pathways between ACEs and two health outcomes (i.e., general health and days physically ill) in TG. Mediators include everyday discrimination, social support, gender non-affirmation, and mental distress. METHODS: Cross-sectional data from the U.S. Transgender Population Health Survey (TransPop) was used to conduct a serial/parallel mediation analysis. The TransPop survey included a total of 274 TG. RESULTS: For both outcome variables, the same three indirect pathways were significant. First, ACEs were associated with increased mental distress, which was associated with a decrease in general health and an increase in days physically ill. Second, ACEs were associated with increased discrimination, which was associated with increased mental distress, and this was associated with a decrease in general health and an increase in days physically ill. Finally, ACEs were associated with discrimination, which was associated with increased gender non-affirmation which was associated with increased mental distress, and this was associated with a decrease in general health and an increase in days physically ill. CONCLUSION: Interventions focused on reducing discrimination, gender non-affirmation, and poor mental health may be vital to improving the health of TG and to mitigating the indirect role of ACEs on TG health.

Personalized dietary management of advanced prostate cancer using nutrigenomics: a case report.

While there are emerging reports in the scientific literature on potential associations between cholesterol/lipids and prostate cancer, information on the dietary management of these cancer patients is currently lacking. We report on a 57-year-old white Australian male diagnosed with advanced prostate cancer who had personalized dietary management in preparation for and following his medical treatment: radiation and radical prostatectomy. Dietary recommendations were based on his blood results and nutrigenomic tests which showed a history of and genetic predisposition to dyslipidemia. Nutritional analysis also confirmed the need for dietary modification of his fat intake. Eighteen months post medical and dietary intervention his PSA level was reported at 0.1 ug/L and all blood lipid levels were within reference ranges. At two years there was no detectable disease recurrence and androgen deprivation therapy (ADT) was not required. Personalized dietary recommendations could be a clinically beneficial addition to the multidisciplinary management of prostate cancer patients.

A recombinant signalling-selective activated protein C that lacks anticoagulant activity is efficacious and safe in cutaneous wound preclinical models.

Various preclinical and clinical studies have demonstrated the robust wound healing capacity of the natural anticoagulant activated protein C (APC). A bioengineered APC variant designated 3K3A-APC retains APC's cytoprotective cell signalling actions with <10% anticoagulant activity. This study was aimed to provide preclinical evidence that 3K3A-APC is efficacious and safe as a wound healing agent. 3K3A-APC, like wild-type APC, demonstrated positive effects on proliferation of human skin cells (keratinocytes, endothelial cells and fibroblasts). Similarly it also increased matrix metollaproteinase-2 activation in keratinocytes and fibroblasts. Topical 3K3A-APC treatment at 10 or 30 µg both accelerated mouse wound healing when culled on Day 11. And at 10 µg, it was superior to APC and had half the dermal wound gape compared to control. Further testing was conducted in excisional porcine wounds due to their congruence to human skin. Here, 3K3A-APC advanced macroscopic healing in a dose-dependent manner (100, 250 and 500 µg) when culled on Day 21. This was histologically corroborated by greater collagen maturity, suggesting more advanced remodelling. A non-interference arm of this study found no evidence that topical 3K3A-APC caused either any significant systemic side-effects or any significant leakage into the circulation. However the female pigs exhibited transient and mild local reactions after treatments in week three, which did not impact healing. Overall these preclinical studies support the hypothesis that 3K3A-APC merits future human wound studies.

Treatment of Oral Disease in Eight Pet Pot-Bellied Pigs (Sus scrofa domesticus): A Case Series.

Evidence of porcine oral pathology in client-owned domestic pigs has been reported in recent literature. The most common abnormalities are missing teeth and periodontal disease. This case series reviews the diagnosis and treatment of dental disease in 8 pet Vietnamese Pot-Bellied Pigs (Sus scrofa domesticus) over a 6-year period (2015-2021). Inclusion criteria included pigs over 1 year of age that had at least 2 sequential visits involving photographs, full-mouth intraoral radiographs, and dental charting. Eight pigs were identified for study inclusion. The study population included 4 castrated males, 3 spayed females, and 1 intact female. The 8 subjects had a total of 28 visits. Fifty-five intraoral dental extractions were performed and complete healing of 44 extraction sites was observed (11 sites were lost to follow up). Canine tooth reduction was performed on 52 tusks in 7 pigs with exposure of 1 pulp that was treated by partial pulpectomy and direct pulp capping. Restoration of carious lesions was performed on 4 teeth. The most commonly extracted teeth were the right and left maxillary first molars (10 of 47 teeth). Reasons for tooth extraction included: periodontal disease, complicated crown fracture, nonvital +/- periapical pathology, and persistent deciduous teeth. Additional treatments ranged from type 1 crown lengthening with restoration of carious lesions, tusk trimming, closed and open root planing, dental extractions, ultrasonic scaling, and polishing. This article stresses the importance of routine dental healthcare and early intervention for periodontal disease in pigs.