Prospective Solutions to Ovarian Reserve Damage during the Ovarian Tissue Cryopreservation and Transplantation (OTC/T) Procedure.

Birth rates continue to decline as more women experience fertility issues. Assisted reproductive technologies (ART) are available for patients seeking fertility treatment, including cryopreservation techniques. Cryopreservation can be performed on gametes, embryos, or gonadal tissue, and can be used for patients who desire to delay in vitro fertilization (IVF) treatment. This review focuses on ovarian tissue cryopreservation (OTC), the freezing of ovarian cortex containing immature follicles. OTC is the only available treatment for the restoration of ovarian function in patients who undergo gonadotoxic treatment(s) and its wide adoption has led to its recent designation as "no longer experimental" by the American Society for Reproductive Medicine (ASRM). OTC and subsequent transplantation (OTC/T) can restore native endocrine function and can support the possibility of pregnancy/live birth for the patient. Importantly, there are multiple steps in the procedure that put the ovarian reserve at risk of damage. The graft is highly susceptible to ischemic reperfusion injury and mass primordial follicle growth activation (PFGA), resulting in a "burnout," phenomenon. In this review, we summarize current efforts to combat the loss of primordial follicles (PF) in grafts through improvements in freeze/thaw protocols, transplantation techniques, and pharmacologic adjuvant treatments. We conducted a review of the literature, with emphasis on emergent research in the last 5 years. Regarding freeze/thaw protocols, we discuss the widely accepted slow freezing approach and newer vitrification protocols. Discussion of improved transplantation techniques includes consideration of the transplantation location of the ovarian tissue and the importance of graft sites in promoting neovascularization. Finally, we discuss pharmacologic treatments being studied to improve tissue performance post-graft. Of note, there is significant research into the efficacy of adjuvants used to reduce ischemic injury, improve neovascularization, and inhibit hyperactivation of PFGAs. While the "experimental" label has been removed from OTC/T, there is a significant need for further research to better understand sources of ovarian reserve damage in order to improve outcomes. Future research directions are provided as we consider how to reach the most hopeful results for women globally.

The Use of Telerehabilitation to Improve Movement-Related Outcomes and Quality of Life for Individuals With Parkinson Disease: Pilot Randomized Controlled Trial.

BACKGROUND: Individuals with Parkinson disease (PD) can improve their overall mobility and participation in daily activities as they engage in frequent exercise. Despite the need for individually tailored exercises, persons with PD often face barriers to accessing physical rehabilitation professionals who can provide them. Telerehabilitation (TR) may facilitate access to necessary and individually tailored rehabilitation for individuals with PD. OBJECTIVE: The purpose of this study was to assess the feasibility of TR for individuals with PD and explore clinical outcomes compared to in-person care. METHODS: This was a pilot randomized controlled trial conducted at 2 outpatient neurorehabilitation clinics with 3 study groups: clinic+TR, TR-only, and usual care (UC). TR was administered using a web-based application with a mobile app option. One-hour interventions were performed weekly for 4 weeks, in-person for the clinic+TR and UC groups and virtually for the TR-only group. Home exercises were provided on paper for the UC group and via the web-based platform for the clinic+TR and TR-only groups. Feasibility was assessed by recruitment and retention success and patient and therapist satisfaction, as rated in surveys. Clinical outcomes were explored using performance and patient-reported measures in between- and within-group analyses. RESULTS: Of 389 patients screened, 68 (17.5%) met eligibility criteria, and 20 (29.4% of those eligible) were enrolled (clinic+TR, n=6; TR-only, n=6; and UC, n=8). One patient (TR-only) was withdrawn due to a non-study-related injurious fall. Regardless of group allocation, both patients and therapists generally rated the mode of care delivery as "good" or "very good" across all constructs assessed, including overall satisfaction and safety. In the analysis of all groups, there were no differences in clinical outcomes at the discharge visit. Within-group differences (from baseline to discharge) were also generally not significant except in the UC group (faster 5-time sit-to-stand time and higher mini balance evaluation systems test balance score) and clinic+TR group (higher mini balance evaluation systems test balance score). CONCLUSIONS: High satisfaction amongst patients and clinicians regardless of group, combined with nonsignificant between-group differences in clinical outcomes, suggest that TR is feasible for individuals with PD in early-moderate stages. Future trials with a larger sample are necessary to test clinical effectiveness. As larger trials enroll patients with diverse characteristics (eg, in terms of age, disease progression, caregiver support, technology access and capacity, etc), they could begin to identify opportunities for matching patients to the optimal utilization of TR as part of the therapy episode. TRIAL REGISTRATION: ClinicalTrials.gov NCT06246747; https://clinicaltrials.gov/study/NCT06246747.

Early physical rehabilitation dosage in the intensive care unit associates with hospital outcomes after critical COVID-19.

OBJECTIVE: To examine the relationship between physical rehabilitation parameters including an approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. DESIGN: Retrospective practice analysis from March 5, 2020, to April 15, 2021. SETTING: Intensive care units (ICU) at four medical institutions. PATIENTS: n = 3780 adults with ICU admission and diagnosis of COVID-19. INTERVENTIONS: We measured the physical rehabilitation treatment delivered in ICU and patient outcomes: (1) mortality; (2) discharge disposition; and (3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) "6-Clicks" (6-24, 24 = greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital). MEASUREMENTS AND MAIN RESULTS: The cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m2 and 46% (n = 1739) required mechanical ventilation. For 2191 patients who received rehabilitation, the dosage and AM-PAC at discharge were moderately, positively associated (Spearman's rho [r] = 0.484, p < 0.001). Multivariate linear regression (model adjusted R2 = 0.68, p < 0.001) demonstrates mechanical ventilation (ß = - 0.86, p = 0.001), average mobility score in first three sessions (ß = 2.6, p < 0.001) and physical rehabilitation dosage (ß = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. CONCLUSIONS: Greater physical rehabilitation exposure early in the ICU is associated with better physical function at hospital discharge.

Inflammatory Cells in Control and Prolapsed Uterosacral Ligament Tissue.

Pelvic organ prolapse (POP), a downward descent of the vagina and/or uterus through the vaginal canal, is a prevalent condition affecting up to 40% of women. Several risk factors of POP have been identified, including childbirth, connective tissue defects, and chronic intra-abdominal pressure; however, the underlying etiologies of POP development are not fully understood, leading to a high burden on patients and the healthcare systems. The uterosacral ligaments are key support structures of the uterus and upper vagina. Our previous work describes observed histopathological changes in uterosacral ligament (USL) tissue and demonstrates the presence of neutrophils in a subgroup of POP individuals. This presence of neutrophils prompted an examination for the presence of a broader spectrum of inflammatory cell types in the USL. Immunohistochemical staining was performed to identify neutrophils, lymphocytes, macrophages, and mast cells outside of the vasculature. All 4 inflammatory cell types were increased in the POP-HQ system-defined POP-Inflammatory (POP-I) phenotype USL tissue relative to the USL tissues of control or other POP-HQ phenotypes. Focal T-lymphocyte and macrophage co-accumulations were observed in the arterial walls from some patients of the POP-vascular (POP-V) phenotype suggesting previous arterial injury. In addition, 1 control and 2 POP-V subjects' USLs contained arterial wall foamy macrophages, evidence of atherosclerosis. These findings further support a complex etiology for POP and indicate that personalized approaches to preventing and treating the condition may be warranted.

Use of the iPRISM webtool in a learning community to assess implementation context and fit of a novel clinical decision support tool for physical therapy triage in acute care hospitals.

BACKGROUND: The iPRISM webtool is an interactive tool designed to aid the process of applying the Practical, Robust Implementation and Sustainability Model (PRISM) for the assessment of and fit with context. A learning community (LC) is a multidisciplinary group of partners addressing a complex problem. Our LC coproduced the Physical TheraPy frEqueNcy Clinical decIsion support tooL (PT-PENCIL) to guide the use of physical therapist services in acute care hospitals. OBJECTIVE: To describe our LC's activities to co-produce the PT-PENCIL, use of the iPRISM webtool to assess its preimplementation context and fit, and develop a multicomponent implementation strategy for the PT-PENCIL. DESIGN: A descriptive research design. SETTING: Three tertiary care hospitals. PARTICIPANTS: Thirteen LC partners: six clinical physical therapists, three rehabilitation managers, three researchers, and a bioinformaticist. INTERVENTIONS: Not applicable. OUTCOME MEASURES: Using the iPRISM webtool, expected fit of the PT-PENCIL was rated 1 (not aligned) to 6 (well aligned) for each PRISM domain and expected reach, effectiveness, adoption, implementation, and maintenance were rated 1 (not likely at all) to 6 (very likely). Discrete implementation strategies were identified from the Expert Recommendations for Implementing Change. RESULTS: The process spanned 18 meetings over 8 months. Ten LC partners completed the iPRISM webtool. PRISM domains with the lowest expected alignment were the "implementation and sustainability infrastructure" (mean = 4.7 out of 6; range = 3-6) and the "external environment" (mean = 4.9 of 6; range = 4-6). Adoption was the outcome with the lowest expected likelihood (mean = 4.5 out of 6; range = 1-6). Six discrete implementation strategies were identified and combined into a multicomponent strategy. CONCLUSIONS: Within a LC, we used existing implementation science resources to co-produce a novel clinical decision support tool for acute care physical therapists and develop a strategy for its implementation. Our methodology can be replicated for similar projects given the public availability of each resource used.

Early physical rehabilitation dosage in the IntensiveCare Unit predicts hospital outcomes after criticalCOVID-19.

Objective: to examine the relationship between physical rehabilitation parameters including a novel approach to quantifying dosage with hospital outcomes for patients with critical COVID-19. Design: Retrospective practice analysis from March 5, 2020, to April 15, 2021. Setting: Intensive care units (ICU) at four medical institutions. Patients: n = 3,780 adults with ICU admission and diagnosis of COVID-19. Interventions: We measured the physical rehabilitation treatment delivered in ICU and patient outcomes: 1) mortality; 2) discharge disposition; and 3) physical function at hospital discharge measured by the Activity Measure-Post Acute Care (AM-PAC) "6-Clicks" (6-24, 24=greater functional independence). Physical rehabilitation dosage was defined as the average mobility level scores in the first three sessions (a surrogate measure of intensity) multiplied by the rehabilitation frequency (PT + OT frequency in hospital). Measurements and Main Results: The cohort was a mean 64 ± 16 years old, 41% female, mean BMI of 32 ± 9 kg/m2 and 46% (n=1739) required mechanical ventilation. For 2191 patients with complete data, rehabilitation dosage and AM-PAC at discharge were moderately, positively associated (Spearman's rho [r] = 0.484, p < 0.001). Multivariate linear regression (model adjusted R2= 0.68, p <0.001) demonstrates mechanical ventilation (ß = -0.86, p = 0.001), average mobility score in first three sessions (ß = 2.6, p <0.001) and physical rehabilitation dosage (ß = 0.22, p = 0.001) were predictive of AM-PAC scores at discharge when controlling for age, sex, BMI, and ICU LOS. Conclusions: Greater physical rehabilitation exposure early in the ICU is associated with physical function at hospital discharge.

Medicare's Post-Acute Care Reimbursement Models as of 2023: Past, Present, and Future.

ABSTRACT: The Centers for Medicare & Medicaid Services is continually working to mitigate unnecessary expenditures, particularly in post-acute care (PAC). Medicare reimburses for orthopaedic surgeon services in varied models, including fee-for-service, bundled payments, and merit-based incentive payment systems. The goal of these models is to improve the quality of care, reduce health-care costs, and encourage providers to adopt innovative and efficient health-care practices.This article delves into the implications of each payment model for the field of orthopaedic surgery, highlighting their unique features, incentives, and potential impact in the PAC setting. By considering the historical, current, and future Medicare reimbursement models, we hope to provide an understanding of the optimal payment model based on the specific needs of patients and providers in the PAC setting.

An atlas of gross and histologic lesions and immunohistochemical immunoreactivity during the temporal progression of aerosolized Lassa virus induced hemorrhagic fever in cynomolgus macaques.

Lassa virus (LASV) causes an acute multisystemic hemorrhagic fever in humans known as Lassa fever, which is endemic in several African countries. This manuscript focuses on the progression of disease in cynomolgus macaques challenged with aerosolized LASV and serially sampled for the development and progression of gross and histopathologic lesions. Gross lesions were first noted in tissues on day 6 and persisted throughout day 12. Viremia and histologic lesions were first noted on day 6 commencing with the pulmonary system and hemolymphatic system and progressing at later time points to include all systems. Immunoreactivity to LASV antigen was first observed in the lungs of one macaque on day 3 and appeared localized to macrophages with an increase at later time points to include immunoreactivity in all organ systems. Additionally, this manuscript will serve as a detailed atlas of histopathologic lesions and disease progression for comparison to other animal models of aerosolized Arenaviral disease.

Influence of sidewall retention and interference fit in total ankle replacement on implant-bone micromotion: A finite element study.

The success of uncemented total ankle replacement (TAR) is linked to initial stability because bony ingrowth depends upon limited early micromotion. Tibial implant design fixation features resist micromotion aided by bony sidewall retention and interference fit. Our goal was to investigate factors influencing implant-bone micromotion in TAR. Two TAR tibial components were virtually inserted into CT-derived computer models of two distal tibias from patients with end-stage ankle arthritis. Density-based inhomogeneous material assignment was used to model bone compaction during press-fit. Finite element analysis (FEA) was used to simulate three fixation cases: (1) no sidewalls + line-to-line fit, (2) sidewalls + line-to-line fit, and (3) sidewalls + 50, 100, or 200 µm interference fit. Kinetic profiles from the stance phase of gait were simulated and micromotions computed from FEA output. Without sidewalls or interference fit, micromotions were largest in early and late stance, with largest micromotions (averaging ~150-250 µm) observed near heel strike. Micromotions decreased 39%-62% when sidewalls were retained. When interference fit was also modeled, micromotions decreased another 37%-61% to ~10 µm. Micromotion differences between patients persisted with sidewall retention but largely disappeared with interference fit. This study presents new insights into the effects of TAR fixation features on implant-bone micromotion. Stability appeared to be influenced by surrounding bone quality, but this influence was greatly diminished when interference fit was introduced. More complete understanding of TAR implant features and performance is needed, but our results show the importance of bone quality and interference fit in the stability of uncemented TAR.

A Single-shot ChAd3 Vaccine Provides Protection from Intramuscular and Aerosol Sudan Virus Exposure.

Infection with Sudan virus (SUDV) is characterized by an aggressive disease course with case fatality rates between 40-100% and no approved vaccines or therapeutics. SUDV causes sporadic outbreaks in sub-Saharan Africa, including a recent outbreak in Uganda which has resulted in over 100 confirmed cases in one month. Prior vaccine and therapeutic efforts have historically prioritized Ebola virus (EBOV), leading to a significant gap in available treatments. Two vaccines, Erbevo ® and Zabdeno ® /Mvabea ® , are licensed for use against EBOV but are ineffective against SUDV. Recombinant adenovirus vector vaccines have been shown to be safe and effective against filoviruses, but efficacy depends on having low seroprevalence to the vector in the target human population. For this reason, and because of an excellent safety and immunogenicity profile, ChAd3 was selected as a superior vaccine vector. Here, a ChAd3 vaccine expressing the SUDV glycoprotein (GP) was evaluated for immunogenicity and efficacy in nonhuman primates. We demonstrate that a single dose of ChAd3-SUDV confers acute and durable protection against lethal SUDV challenge with a strong correlation between the SUDV GP-specific antibody titers and survival outcome. Additionally, we show that a bivalent ChAd3 vaccine encoding the GP from both EBOV and SUDV protects against both parenteral and aerosol lethal SUDV challenge. Our data indicate that the ChAd3-SUDV vaccine is a suitable candidate for a prophylactic vaccination strategy in regions at high risk of filovirus outbreaks. One Sentence Summary: A single-dose of ChAd3 vaccine protected macaques from lethal challenge with Sudan virus (SUDV) by parenteral and aerosol routes of exposure.

High Risk of Readmission After THA Regardless of Functional Status in Patients Discharged to Skilled Nursing Facility.

BACKGROUND: The postoperative period and subsequent discharge planning are critical in our continued efforts to decrease the risk of complications after THA. Patients discharged to skilled nursing facilities (SNFs) have consistently exhibited higher readmission rates compared with those discharged to home healthcare. This elevated risk has been attributed to several factors but whether readmission is associated with patient functional status is not known. QUESTIONS/PURPOSES: After controlling for relevant confounding variables (functional status, age, gender, caregiver support available at home, diagnosis [osteoarthritis (OA) versus non-OA], Charlson comorbidity index [CCI], the Area Deprivation Index [ADI], and insurance), are the odds of 30- and 90-day hospital readmission greater among patients initially discharged to SNFs than among those treated with home healthcare after THA? METHODS: This was a retrospective, comparative study of patients undergoing THA at any of 11 hospitals in a single, large, academic healthcare system between 2017 and 2022 who were discharged to an SNF or home healthcare. During this period, 13,262 patients were included. Patients discharged to SNFs were older (73 ± 11 years versus 65 ± 11 years; p < 0.001), less independent at hospital discharge (6-click score: 16 ± 3.2 versus 22 ± 2.3; p < 0.001), more were women (71% [1279 of 1796] versus 56% [6447 of 11,466]; p < 0.001), insured by Medicare (83% [1497 of 1796] versus 52% [5974 of 11,466]; p < 0.001), living in areas with greater deprivation (30% [533 of 1796] versus 19% [2229 of 11,466]; p < 0.001), and had less assistance available from at-home caregivers (29% [527 of 1796] versus 57% [6484 of 11,466]; p < 0.001). The primary outcomes assessed in this study were 30- and 90-day hospital readmissions. Although the system automatically flags readmissions occurring within 90 days at the various facilities in the overall healthcare system, readmissions occurring outside the system would not be captured. Therefore, we were not able to account for potential differential rates of readmission to external healthcare systems between the groups. However, given the large size and broad geographic coverage of the healthcare system analyzed, we expect the readmissions data captured to be representative of the study population. The focus on a single healthcare system also ensures consistency in readmission identification and reporting across subjects. We evaluated the association between discharge disposition (home healthcare versus SNF) and readmission. Covariates evaluated included age, gender, primary payer, primary diagnosis, CCI, ADI, the availability of at-home caregivers for the patient, and the Activity Measure for Post-Acute Care (AM-PAC) 6-clicks basic mobility score in the hospital. The adjusted relative risk (ARR) of readmission within 30 and 90 days of discharge to SNF (versus home healthcare) was estimated using modified Poisson regression models. RESULTS: After adjusting for the 6-clicks mobility score, age, gender, ADI, OA versus non-OA, living environment, CCI, and insurance, patients discharged to an SNF were more likely to be readmitted within 30 and 90 days compared with home healthcare after THA (ARR 1.46 [95% CI 1.01 to 2.13]; p= 0.046 and ARR 1.57 [95% CI 1.23 to 2.01]; p < 0.001, respectively). CONCLUSION: Patients discharged to SNFs after THA had a slightly higher likelihood of hospital readmission within 30 and 90 days compared with those discharged with home healthcare. This difference persisted even after adjusting for relevant factors like functional status, home support, and social determinants of health. These results indicate that for suitable patients, direct home discharge may be a safer and more cost-effective option than SNFs. Clinicians should carefully consider these risks and benefits when making postoperative discharge plans. Policymakers could consider incentives and reforms to improve care transitions and coordination across settings. Further research using robust methods is needed to clarify the reasons for higher SNF readmission rates. Detailed analysis of patient complexity, care processes, and causes of readmission in SNFs versus home health could identify areas for quality improvement. Prospective cohorts or randomized trials would allow stronger conclusions about cause-and-effect. Importantly, no patients should be unfairly "cherry-picked" or "lemon-dropped" based only on readmission risk scores. With proper support and care coordination, even complex patients can have good outcomes. The goal should be providing excellent rehabilitation for all, while continuously improving quality, safety, and value across settings. LEVEL OF EVIDENCE: Level III, therapeutic study.

Modeling delay of age at natural menopause with planned tissue cryopreservation and autologous transplantation.

BACKGROUND: Ovarian tissue cryopreservation has been proven to preserve fertility against gonadotoxic treatments. It has not been clear how this procedure would perform if planned for slowing ovarian aging. OBJECTIVE: This study aimed to determine the feasibility of cryopreserving ovarian tissue to extend reproductive life span and delay menopause by autotransplantation near menopause. STUDY DESIGN: Based on the existing biological data on follicle loss rates, a stochastic model of primordial follicle wastage was developed to determine the years of delay in menopause (denoted by D) by ovarian tissue cryopreservation and transplantation near menopause. Our model accounted for (1) age at ovarian tissue harvest (21-40 years), (2) the amount of ovarian cortex harvested, (3) transplantation of harvested tissues in single vs multiple procedures (fractionation), and (4) posttransplant follicle survival (40% [conservative] vs 80% [improved] vs 100% [ideal or hypothetical]). RESULTS: Our model predicted that, for most women aged <40 years, ovarian tissue cryopreservation and transplantation would result in a significant delay in menopause. The advantage is greater if the follicle loss after transplant can be minimized. As an example, the delay in menopause (D) for a woman with a median ovarian reserve who cryopreserves 25% of her ovarian cortex at the age of 25 years and for whom 40% of follicles survive after transplantation would be approximately 11.8 years, but this extends to 15.5 years if the survival is 80%. As another novel finding, spreading the same amount of tissue to repetitive transplants significantly extends the benefit. For example, for the same 25-year-old woman with a median ovarian reserve, 25% cortex removal, and 40% follicle survival, fractionating the transplants to 3 or 6 procedures would result in the corresponding delay in menopause (D) of 23 or 31 years. The same conditions (3 or 6 procedures) would delay menopause as much as 47 years if posttransplant follicle survival is improved to 80% with modern approaches. An interactive Web tool was created to test all variables and the feasibility of ovarian tissue freezing and transplantation to delay ovarian aging (here). CONCLUSION: Our model predicts that with harvesting at earlier adult ages and better transplant techniques, a significant menopause postponement and, potentially, fertile life span extension can be achieved by ovarian tissue cryopreservation and transplantation in healthy women.

The effect of post-acute rehabilitation setting on 90-day mobility after stroke: A difference-in-difference analysis.

Background: After discharged from the hospital for acute stroke, individuals typically receive rehabilitation in one of three settings: inpatient rehabilitation facilities (IRFs), skilled nursing facilities (SNFs), or home with community services (i.e., home health or outpatient clinics). The initial setting of post-acute care (i.e., discharge location) is related to mortality and hospital readmission; however, the impact of this setting on the change in functional mobility at 90-days after discharge is still poorly understood. The purpose of this work was to examine the impact of discharge location on the change in functional mobility between hospital discharge and 90-days post-discharge. Methods: In this retrospective cohort study, we used the electronic health record to identify individuals admitted to Johns Hopkins Medicine with an acute stroke and who had measurements of mobility [Activity Measure for Post Acute Care Basic Mobility (AM-PAC BM)] at discharge from the acute hospital and 90-days post-discharge. Individuals were grouped by discharge location (IRF=190 [40%], SNF=103 [22%], Home with community services=182 [(38%]). We compared the change in mobility from time of discharge to 90-days post-discharge in each group using a difference-in-differences analysis and controlling for demographics, clinical characteristics, and social determinants of health. Results: We included 475 individuals (age 64.4 [14.8] years; female: 248 [52.2%]). After adjusting for covariates, individuals who were discharged to an IRF had a significantly greater improvement in AM-PAC BM from time of discharge to 90-days post-discharge compared to individuals discharged to a SNF or home with community services (ß=-3.5 (1.4), p=0.01 and ß=-8.2 (1.3), p=<0.001, respectively). Conclusions: These findings suggest that the initial post-acute rehabilitation setting impacts the magnitude of functional recovery at 90-days after discharge from the acute hospital. These findings support the need for high-intensity rehabilitation and for policies that facilitate the delivery of high-intensity rehabilitation after stroke.

Mathematical recapitulation of the end stages of human ovarian aging.

Ovarian aging in women can be described as highly unpredictable within individuals but predictable across large populations. We showed previously that modeling an individual woman's ovarian reserve of primordial follicles using mathematical random walks replicates the natural pattern of growing follicles exiting the reserve. Compiling many simulations yields the observed population distribution of the age at natural menopause (ANM). Here, we have probed how stochastic control of primordial follicle loss might relate to the distribution of the preceding menopausal transition (MT), when women begin to experience menstrual cycle irregularity. We show that identical random walk model conditions produce both the reported MT distribution and the ANM distribution when thresholds are set for growing follicle availability. The MT and ANM are shown to correspond to gaps when primordial follicles fail to grow for 7 and 12 days, respectively. Modeling growing follicle supply is shown to precisely recapitulate epidemiological data and provides quantitative criteria for the MT and ANM in humans.

Development of a hybrid point-of-care ultrasound curriculum for first year medical students in a rural medical education program: a pilot study.

BACKGROUND: The field of point-of-care ultrasound (POCUS) has advanced in recent decades due to the benefits it holds for medical providers. However, aspiring POCUS practitioners require adequate training. Unfortunately, there remains a paucity of resources to deliver this training, particularly in rural and underserved areas. Despite these barriers, calls for POCUS training in undergraduate medical education are growing, and many medical schools now deliver some form of POCUS education. Our program lacked POCUS training; therefore, we developed and implemented a POCUS curriculum for our first-year medical students. METHODS: We developed a POCUS curriculum for first year medical students in a rural medically underserved region of the United States. To evaluate our course, we measured learning outcomes, self-reported confidence in a variety of POCUS domains, and gathered feedback on the course with a multi-modal approach: an original written pre- and post-test, survey tool, and semi-structured interview protocol, respectively. RESULTS: Student (n=24) knowledge of POCUS significantly increased (pre-test average score = 55%, post-test average score = 79%, P<0.0001), and the course was well received based on student survey and interview feedback. In addition, students reported increased confidence toward a variety of knowledge and proficiency domains in POCUS use and their future clinical education and practice. CONCLUSIONS: Despite a lack of consensus in POCUS education, existing literature describes many curricular designs across institutions. We leveraged a combination of student initiatives, online resources, remote collaborations, local volunteers, and faculty development to bring POCUS to our institution in a rural and medically underserved region. Moreover, we demonstrate positive learning and experiential outcomes that may translate to improved outcomes in students' clinical education and practice. Further research is needed to evaluate the psychomotor skills, broader learning outcomes, and clinical performance of students who take part in our POCUS course.

Reducing Physical Therapy Consults for Patients With High Functional Mobility in the Acute Medical Inpatient Setting: A Difference-in-Difference Analysis.

OBJECTIVE: To evaluate the effectiveness of clinical decision support for reducing misallocation of physical therapy (PT) consults. DESIGN: A prospective quasi-experimental study. Between October 2018 and November 2021, routinely documented data on functional status and physical therapy referrals were collected from electronic medical records. SETTING: Hospital Medicine and General Internal Medicine service lines at a large quaternary academic medical center. PARTICIPANTS: 20,810 adult patients hospitalized on any of the included treatment (hospital medicine) or control (general internal medicine) service lines. MAIN OUTCOME MEASURE: The primary outcome was "change in proportion of misallocated PT consults" measured as likelihood of PT consults for patients admitted with high functional mobility scores. Changes in the primary outcome from the pre-intervention to post-intervention period were compared in the control and treatment groups using propensity score-weighted difference-in-differences multivariable logit regression adjusting for clinically relevant covariates. INTERVENTION: The intervention period was measured for 20 months and consisted of a clinical decision support tool embedded in the daily note templates for hospital medicine providers. The tool provided education on patient mobility scores and their relation to need for PT consult. The tool was rolled out without any further announcements or education. RESULTS: Our cohort included 20,810 unique admissions (mean age 58.9, 55% women, 83% Black). Post-intervention, the likelihood of PT referrals for patients with high baseline mobility (AM-PAC >18) decreased by 7.3% (P<.001) for the treatment group compared with control, adjusted for age, sex, race, ethnicity, length-of-stay, and mobility change. CONCLUSION: Mobility score-based clinical decision support can decrease unneeded PT consults in the inpatient setting. This could help allocate therapy time for at-risk patients while also having a positive effect on health care systems.

AefR, a TetR Family Transcriptional Repressor, Regulates Several Auxin Responses in Pseudomonas syringae Strain PtoDC3000.

The plant hormone indole-3-acetic acid (IAA), also known as auxin, plays important roles in plant growth and development, as well as in several plant-microbe interactions. IAA also acts as a microbial signal and in many bacteria regulates metabolism, stress responses, and virulence. In the bacterial plant pathogen Pseudomonas syringae pv. tomato strain DC3000 (PtoDC3000), exposure to IAA results in large-scale transcriptional reprogramming, including the differential expression of several known virulence genes. However, how PtoDC3000 senses and responds to IAA and what aspects of its biology are regulated by IAA is not understood. To investigate the mechanisms involved in perceiving and responding to IAA, we carried out a genetic screen for mutants with altered responses to IAA. One group of mutants of particular interest carried disruptions in the aefR gene encoding a TetR family transcriptional regulator. Gene expression analysis confirmed that the aefR mutants have altered responses to IAA. Thus, AefR is the first demonstrated auxin response regulator in PtoDC3000. We also investigated several aspects of PtoDC3000 biology that are regulated by both AefR and IAA, including antibiotic resistance, motility, and virulence. The observation that the aefR mutant has altered virulence on Arabidopsis, suggests that the sector of the IAA response regulated by aefR is important during pathogenesis. Our findings also provide evidence that AefR plays a role in coordinating changes in gene expression during the transition from early to late stages of infection. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.