Branched germline cysts and female-specific cyst fragmentation facilitate oocyte determination in mice.

During mouse gametogenesis, germ cells derived from the same progenitor are connected via intercellular bridges forming germline cysts, within which asymmetrical or symmetrical cell fate occurs in female and male germ cells, respectively. Here, we have identified branched cyst structures in mice, and investigated their formation and function in oocyte determination. In fetal female cysts, 16.8% of the germ cells are connected by three or four bridges, namely branching germ cells. These germ cells are preferentially protected from cell death and cyst fragmentation and accumulate cytoplasm and organelles from sister germ cells to become primary oocytes. Changes in cyst structure and differential cell volumes among cyst germ cells suggest that cytoplasmic transport in germline cysts is conducted in a directional manner, in which cellular content is first transported locally between peripheral germ cells and further enriched in branching germ cells, a process causing selective germ cell loss in cysts. Cyst fragmentation occurs extensively in female cysts, but not in male cysts. Male cysts in fetal and adult testes have branched cyst structures, without differential cell fates between germ cells. During fetal cyst formation, E-cadherin (E-cad) junctions between germ cells position intercellular bridges to form branched cysts. Disrupted junction formation in E-cad-depleted cysts led to an altered ratio in branched cysts. Germ cell-specific E-cad knockout resulted in reductions in primary oocyte number and oocyte size. These findings shed light on how oocyte fate is determined within mouse germline cysts.

Regional abundances of binder of sperm (BSP) proteins are negatively associated with the quality of frozen-thawed bovine spermatozoa.

In brief: The localization and abundance of the sperm BSP proteins correlate with in vitro fertility in domestic bulls used in artificial insemination service. Abstract: Binder of sperm (BSP) proteins, secreted mainly by the accessory sex glands, are the major protein family present in bovine seminal plasma and on the sperm surface after ejaculation. In vivo, BSP proteins facilitate sperm capacitation and sperm reservoir formation; however, their impact on sperm function within the in vitro systems is less clear. Therefore, this biomarker-based study aimed to characterize the localization and abundance of BSP proteins from in vitro processed frozen-thawed bovine spermatozoa. Using image-based flow cytometry and Western blotting, BSP protein localization, abundance, membrane and acrosomal integrity were investigated in the supernatant (nonmotile) and pellet (motile) fractions of gradient-separated bull spermatozoa. Spermatozoa from the supernatant fraction had high enrichment of all BSP proteins investigated (BSP1, BSP3, BSP5; P < 0.05) when compared to the pellet fraction. In the pellet fraction, BSP1 and BSP3 bound predominately to the acrosomal region, whereas BSP5 had a high affinity for the midpiece. However, in the supernatant fraction, BSP proteins predominately coated the entire sperm surface resulting in the loss of regional specificity. High BSP protein abundance in the spermatozoa also correlated with acrosome and membrane damage. Whereas a high abundance of BSP5 correlated with low embryo cleavage rates, high abundance of BSP1 on the sperm head coincided with a high blastocyst rate. Therefore, changes in the quantity and localization of specific BSP proteins could act as potential biomarkers of sperm quality and fertility.

Recurrent missense variant identified in two unrelated families with MPZL2-related hearing loss, expanding the variant spectrum associated with DFNB111.

MPZL2-related hearing loss is a rare form of autosomal recessive hearing loss characterized by progressive, mild sloping to severe sensorineural hearing loss. Thirty-five previously reported patients had biallelic truncating variants in MPZL2, with the exception of one patient with a missense variant of uncertain significance and a truncating variant. Here, we describe the clinical characteristics and genotypes of five patients from four families with confirmed MPZL2-related hearing loss. A rare missense likely pathogenic variant [NM_005797.4(MPZL2):c.280C>T,p.(Arg94Trp)] located in exon 3 was confirmed to be in trans with a recurrent pathogenic truncating variant that segregated with hearing loss in three of the patients from two unrelated families. This is the first recurrent likely pathogenic missense variant identified in MPZL2. Apparently milder or later-onset hearing loss associated with rare missense variants in MPZL2 indicates that some missense variants in this gene may cause a milder phenotype than that resulting from homozygous or compound heterozygous truncating variants. This study, along with the identification of truncating loss of function and missense MPZL2 variants in several diverse populations, suggests that MPZL2-related hearing loss may be more common than previously appreciated and demonstrates the need for MPZL2 inclusion in hearing loss testing panels.

Comprehensive Gene Panel Testing for Hearing Loss in Children: Understanding Factors Influencing Diagnostic Yield.

OBJECTIVE: To evaluate factors influencing the diagnostic yield of comprehensive gene panel testing (CGPT) for hearing loss (HL) in children and to understand the characteristics of undiagnosed probands. STUDY DESIGN: This was a retrospective cohort study of 474 probands with childhood-onset HL who underwent CGPT between 2016 and 2020 at a single center. Main outcomes and measures included the association between clinical variables and diagnostic yield and the genetic and clinical characteristics of undiagnosed probands. RESULTS: The overall diagnostic yield was 44% (209/474) with causative variants involving 41 genes. While the diagnostic yield was high in the probands with congenital, bilateral, and severe HL, it was low in those with unilateral, noncongenital, or mild HL; cochlear nerve deficiency; preterm birth; neonatal intensive care unit admittance; certain ancestry; and developmental delay. Follow-up studies on 49 probands with initially inconclusive CGPT results changed the diagnostic status to likely positive or negative outcomes in 39 of them (80%). Reflex to exome sequencing on 128 undiagnosed probands by CGPT revealed diagnostic findings in 8 individuals, 5 of whom had developmental delays. The remaining 255 probands were undiagnosed, with 173 (173/255) having only a single variant in the gene(s) associated with autosomal recessive HL and 28% (48/173) having a matched phenotype. CONCLUSION: CGPT efficiently identifies the genetic etiologies of HL in children. CGPT-undiagnosed probands may benefit from follow-up studies or expanded testing.

Calving date as a potential predictor for the probability of approval in the first breeding soundness evaluation of Nellore bulls.

Beef production systems primarily use natural service (NS) for breeding. However, a significant number of bulls used for NS are subfertile, limiting the profitability of the cow-calf operations. Therefore, producers should select bulls based on breeding soundness evolutions (BSE) to ensure higher pregnancy rates. Several factors can affect the bull ability to pass a BSE. We hypothesize that calving date would be a factor that affects the bull probability of approval at the first BSE. For this purpose, a multivariate logistic regression in a dataset of 14,737 BSEs from young Nellore bulls was used. Correlations between calving date, biometrics, and semen traits were evaluated using Pearson's correlation coefficient. Our results demonstrated that the calving date affected the probability of approval at the first BSE (p < .05). Indeed, the variable that added more information to our model was the calving date, far more than the age group of the bulls according to Akaike's information criterion. Hence, bulls born on day 0 of the calving season have 1.26 more chances to be approved at the first BSE than bulls born 21 days later. This result highlights the importance of getting the dams of future bulls pregnant as soon as possible in the breeding season. In addition, the calving season should be no longer than 47 days to achieve 80% BSE approval in 20-22 months old Nellore bulls. The strongest correlation was with SC, which decreased as the calving date increased. Therefore, the calving date may be used as a predictor of the outcome of the first BSE in young bulls. In that way, the calving date can help seedstock producers to maximize efficiency in making crucial management decisions during the breeding and calving season including nutrition, reproductive, and culling.

Characterization of a possible founder synonymous variant in TECTA in multiple individuals with autosomal recessive hearing loss.

Synonymous variants have been shown to alter the correct splicing of pre-mRNAs and generate disease-causing transcripts. These variants are not an uncommon etiology of genetic disease; however, they are frequently overlooked during genetic testing in the absence of functional and clinical data. Here, we describe the occurrence of a synonymous variant [NM_005422.4 (TECTA):c.327C>T, p.(Gly109=)] in seven individuals with hearing loss from six unrelated families. The variant is not located near exonic/intronic boundaries but is predicted to impact splicing by activating a cryptic splicing donor site in exon 4 of TECTA. In vitro minigene assays show that the variant disrupts the reading frame of the canonical transcript, which is predicted to cause a premature termination codon 48 amino acids downstream of the variant, leading to nonsense-mediated decay. The variant is present in population databases, predominantly in Latinos of African ancestry, but is rare in other ethnic groups. Our findings suggest that this synonymous variant is likely pathogenic for TECTA-associated autosomal recessive hearing loss and seems to have arisen as a founder variant in this specific Latino subpopulation. This study demonstrates that synonymous variants need careful splicing assessment and support from additional testing methodologies to determine their clinical impact.

Advanced approach for comprehensive mtDNA genome testing in mitochondrial disease.

Mitochondrial disease diagnosis requires interrogation of both nuclear and mitochondrial (mtDNA) genomes for single-nucleotide variants (SNVs) and copy number alterations, both in the proband and often maternal relatives, together with careful phenotype correlation. We developed a comprehensive mtDNA sequencing test ('MitoGenome') using long-range PCR (LR-PCR) to amplify the full length of the mtDNA genome followed by next generation sequencing (NGS) to accurately detect SNVs and large-scale mtDNA deletions (LSMD), combined with droplet digital PCR (ddPCR) for LSMD heteroplasmy quantification. Overall, MitoGenome tests were performed on 428 samples from 394 patients with suspected or confirmed mitochondrial disease. The positive yield was 11% (43/394), including 34 patients with pathogenic or likely pathogenic SNVs (the most common being m.3243A > G in 8/34 (24%) patients), 8 patients with single LSMD, and 3 patients with multiple LSMD exceeding 10% heteroplasmy levels. Two patients with both LSMD and pathogenic SNV were detected. Overall, this LR-PCR/NGS assay provides a highly accurate and comprehensive diagnostic method for simultaneous mtDNA SNV detection at heteroplasmy levels as low as 1% and LSMD detection at heteroplasmy levels below 10%. Inclusion of maternal samples for variant classification and ddPCR to quantify LSMD heteroplasmy levels further enables accurate pathogenicity assessment and clinical correlation interpretation of mtDNA genome sequence variants and copy number alterations.

[Efforts towards the consolidation of public policies for the prevention of HPV-associated cancers in Puerto RicoEsforços realizados em Porto Rico para a consolidação de políticas públicas de prevenção de cânceres associados ao HPV]. / Esfuerzos realizados en Puerto Rico hacia la consolidación de políticas públicas para la prevención de cánceres asociados al VPH.

The purpose of this special report is to describe chronologically the events that contributed to the development and approval of legislation and subsequent implementation of a school vaccination mandate in order to prevent HPV and HPV-associated cancers in Puerto Rico (PR). Starting in 2010, PR initiated public-policy approvals aimed at improving cancer registries and HPV vaccine coverage through health insurance for adolescents aged 11 to 18 years. In 2014, scientific and community efforts succeeded in documenting the magnitude of morbidity caused by HPV and jointly developing HPV vaccine prevention and promotion strategies. In August 2018, PR became one of the first four territories of the United States of America to implement the HPV vaccine school entry requirement to decrease the incidence of HPV-associated cancers on the island. In 2019, it was enshrined in law that every immunization provider must submit immunization data to the Puerto Rico Immunization Registry. The case of PR demonstrates that public policy-making alongside collaboration between academic, scientific, and community coalitions can achieve population change and measurable outcomes aimed at HPV prevention. Countries with a similar public health problem could adopt efforts similar to those presented herein and align them with the World Health Organization goal of eradicating cervical cancer by 2030.

O propósito deste relatório especial é descrever cronologicamente os eventos que contribuíram para o desenvolvimento e a aprovação de legislação, e a implementação da exigência escolar de vacinação em Porto Rico (PR), a fim de prevenir o HPV e os cânceres associados a ele. A partir de 2010, PR iniciou as aprovações de políticas públicas com o objetivo de aprimorar o registro dos casos de câncer e a cobertura vacinal contra o HPV, por meio de planos de saúde, em adolescentes de 11 a 18 anos. Em 2014, esforços científicos e comunitários permitiram documentar a magnitude das doenças causadas pelo HPV e elaborar conjuntamente estratégias de prevenção e promoção da vacina contra o HPV. Em agosto de 2018, PR foi um dos primeiros quatro territórios dos Estados Unidos da América a implementar a vacina contra o HPV como exigência escolar, a fim de diminuir a incidência de cânceres associados ao HPV na ilha. Em 2019 ficou garantido por lei que todos os vacinadores devem enviar informações ao Registro de Imunização. O caso de PR demonstra que o desenvolvimento de políticas públicas, em conjunto com parcerias entre coalizões acadêmicas, científicas e comunitárias, alcança mudanças populacionais e resultados mensuráveis dirigidos à prevenção do HPV. Países com uma problemática de saúde pública similar poderiam adotar esforços semelhantes aos apresentados e alinhá-los ao objetivo da Organização Mundial da Saúde: a erradicação do câncer cervical até 2030.

Understanding parents' views toward the newly enacted HPV vaccine school entry policy in Puerto Rico: a qualitative study.

BACKGROUND: The Human papillomavirus vaccine (HPV) is an essential tool for the prevention of HPV-related cancers. In Puerto Rico, the Secretary of Health established a school entry requirement of at least one dose of HPV vaccination in girls and boys aged 11 and 12 years, taking effect in August 2018. Our study aimed to examine parents' and guardians' views of unvaccinated children about the process of implementation of the new HPV vaccination school entry policy in Puerto Rico and identify potential barriers and facilitators related to the implementation of this requirement. METHODS: During April through November 2019, we conducted three focus groups (n = 12) and eight in-depth semi-structured interviews with parents of children aged 11 and 12 who had not yet initiated the HPV vaccine series. The interview topics addressed were: perception of vaccination, HPV vaccine and it is inclusion as new school entry requirement practice, procedure of the sources of information, influencers, and willingness to change. The interviews were recorded and transcribed by our staff members. We identified emergent themes through thematic analysis. RESULTS: The participants' perspective on the HPV vaccine school requirement was mixed. Lack of information of the HPV vaccines and lack of communication about the school-entry requirement were the themes most mentioned in the interviews. Moreover, previous negative experiences from friends or family members and adverse effects deterred some participants from vaccinating their kids. We discussed barriers in the process of soliciting an exemption. CONCLUSION: Most barriers mentioned by study participants are modifiable. Information about the HPV vaccine mandate's implementation and educational materials regarding HPV vaccine safety need to be provided to address parents' concerns related to the vaccine's side effects. Schools (teachers, principal directors, and administrative staff), the government, and parent organizations need to be part of these efforts. This multilevel approach will help to improve disseminating information about HPV vaccination to clarify doubts and misinformation among parents.

Content analysis of digital media coverage of the human papillomavirus vaccine school-entry requirement policy in Puerto Rico.

BACKGROUND: In August 2018, Puerto Rico (PR) became the 4th state or territory in the United States to adopt a human papillomavirus (HPV) vaccine school-entry requirement, for students 11-12 years old. Evidence suggests that the content of media coverage may impact people's perception of HPV vaccine and their willingness to vaccinate. This study aimed to analyze the content of digital news coverage related to the implementation of the policy in PR. METHODS: A content review was conducted of digital media published from January 2017 through December 2018. The content reviewed was carried out in two steps: 1) creating a matrix to summarize each article's content about the policy and 2) qualitative analysis using a grounded theory approach. RESULTS: The search resulted in 34 articles obtained from 17 online local and international news outlets that reported the policy's implementation. Analyses showed that 61% of the news articles did not mention the number of required doses, and 79% discussed the new policy concerning cancer prevention. In 2017, news coverage focused mostly on describing the policy, while 2018 coverage focused on controversies surrounding the implementation. Neutral emergent codes included: 1) Description of the policy; 2) Information about HPV related cancers; and 3) General information about HPV vaccine. Negative emergent codes included: 1) infringement to patient and parental autonomy; 2) Hesitancy from the political sector, and 3) Hesitancy from groups and coalitions. Positive content included: 1) knowledge and acceptance of HPV vaccine for cancer prevention; 2) importance of education and protective sexual behaviors; and 3) new vaccination law proposal. CONCLUSIONS: Most of the media coverage in PR was neutral and included limited information related to the vaccine, HPV, and HPV-related cancers. Neutral and negative themes could influence public concerns regarding the new policy, as well as HPV vaccination rates in PR.

In vitro evaluation of cryopreserved bovine sperm and its relation to field fertility in fixed-time artificial insemination.

This study aimed to assess characteristics of bovine cryopreserved sperm and evaluate its relation to field fertility in fixed-time artificial insemination (FTAI). Semen samples of 16 bulls were used to inseminate 811 Nellore cows, and four of these bulls were also used to inseminate 101 Nellore heifers. Samples of the same ejaculate used for FTAI from each bull were analysed in the laboratory after thawing. Sperm motility and vigour were subjectively assessed by light microscope, and integrity of the plasma and acrosome membranes, and H2 O2 production were evaluated by flow cytometer. Relation among sperm characteristics and pregnancy rate of cows and heifers were evaluated by univariate and multivariate logistic regression. Subjective sperm motility and vigour did not affect the probability of pregnancy in cows or heifers. In univariate analysis for pregnancy in cows, sperm traits related to acrosome injury positively affected probability of pregnancy mainly when associated with plasma membrane integrity; H2 O2 production seems to be less important than plasma membrane integrity in affecting probability of pregnancy. In multivariate analysis, sperm traits related to injured acrosome positively affected probability of cow and heifer pregnancies while intact acrosome was negatively related to cow pregnancy. Intact plasma membrane and high H2 O2 production were positively related to cow pregnancy but negatively related to heifer pregnancy. Results suggest that a capacitation-like status of the acrosome may benefit probability of pregnancy in cows.

Recognizing and treating anal cancer: training medical students and physicians in Puerto Rico.

OBJECTIVE: This training activity aimed at increasing the knowledge of anal cancer screening, diagnostic and treatment options in medical students and physicians, to determine the interest of these individuals in receiving training in the diagnosis and treatment of anal cancer, and to explore any previous training and/or experience with both anal cancer and clinical trials that these individuals might have. METHODS: An educational activity (1.5 contact hours) was attended by a group of medical students, residents and several faculty members, all from the Medical Sciences Campus of the University of Puerto Rico (n = 50). A demographic survey and a 6-item pre- and post-test on anal cancer were given to assess knowledge change. RESULTS: Thirty-four participants (68%) answered the survey. Mean age was 29.6 +/- 6.6 years; 78.8% had not received training in anal cancer screening, 93.9% reported being interested in receiving anal cancer training, and 75.8% expressed an interest in leading or conducting a clinical trial. A significant increase in the test scores was observed after the educational activity (pre-test: 3.4 +/- 1.2; post-test: 4.7 +/- 0.71). Three of the items showed an increase in knowledge by the time the post-test was taken. The first of these items assessed the participants' knowledge regarding the existence of any guidelines for the screening/treatment of patients with human papillomavirus (HPV)-related anal disease. The second of these items attempted to determine whether the participants recognized that anal intraepithelial neoplasia (AIN) 2 is considered to be a high-grade neoplasia. The last of the 3 items was aimed at ascertaining whether or not the participants were aware that warty growths in the anus are not necessarily a manifestation of high-grade AIN. CONCLUSION: This educational activity increased the participants' knowledge of anal cancer and revealed, as well, that most of the participants were interested in future training and in collaborating in a clinical trial. Training physicians from Puerto Rico on anal cancer clinical trials is essential to encourage recruitment of Hispanic patients in these studies now that the guidelines in anal cancer screening and treatment are on their way to be defined.

Infusible Extracellular Matrix Biomaterial Promotes Vascular Integrity and Modulates the Inflammatory Response in Acute Traumatic Brain Injury.

Traumatic brain injury (TBI) affects millions of people each year and, in many cases, results in long-term disabilities. Once a TBI has occurred, there is a significant breakdown of the blood-brain barrier resulting in increased vascular permeability and progression of the injury. In this study, the use of an infusible extracellular matrix-derived biomaterial (iECM) for its ability to reduce vascular permeability and modulate gene expression in the injured brain is investigated. First, the pharmacokinetics of iECM administration in a mouse model of TBI is characterized, and the robust accumulation of iECM at the site of injury is demonstrated. Next, it is shown that iECM administration after injury can reduce the extravasation of molecules into the brain, and in vitro, iECM increases trans-endothelial electrical resistance across a monolayer of TNFα-stimulated endothelial cells. In gene expression analysis of brain tissue, iECM induces changes that are indicative of downregulation of the proinflammatory response 1-day post-injury/treatment and neuroprotection at 5 days post-injury/treatment. Therefore, iECM shows potential as a treatment for TBI.

Attitudes towards HPV and COVID school-entry policies among adults living in Puerto Rico.

Prior to the COVID pandemic, Puerto Rico (PR) had one of the highest Human Papillomavirus (HPV) vaccine rates in the United States. The COVID pandemic and administration of COVID vaccines might have impacted attitudes toward HPV vaccination. This study compared attitudes toward HPV and COVID vaccines with respect to school-entry policies among adults living in PR. A convenience sample of 222 adults (≥21 years old) completed an online survey from November 2021 to January 2022. Participants answered questions about HPV and COVID vaccines, attitudes toward vaccination policies for school-entry, and perceptions of sources of information. We assessed the magnitude of association between the agreement of school-entry policies for COVID and HPV vaccination by estimating the prevalence ratio (PRadjusted) with 95% Confidence Intervals (95% CI). The most trusted source of information for HPV and COVID vaccines were healthcare providers (42% and 17%, respectively) and the CDC (35% and 55%, respectively), while the least trusted were social media (40% and 39%, respectively), and friends and family (23% n = 47, and 17% n = 33, respectively). Most participants agreed that HPV (76% n = 156) and COVID vaccines (69% n = 136) should be a school-entry requirement. Agreement with school policy requiring COVID vaccination was significantly associated with agreement of school policy requiring HPV vaccination (PRadjusted:1.96; 95% CI:1.48-2.61) after controlling for potential confounders. Adults living in PR have an overall positive attitude about mandatory HPV and COVID vaccination school-entry policies, which are interrelated. Further research should elucidate the implications of the COVID pandemic on HPV vaccine attitudes and adherence rates.

The development of new biomarkers of spermatozoa quality in cattle.

There is a current need for new biomarkers of spermatozoa quality, that consistently and correctly identify spermatozoa that will successfully contribute to subsequent embryo development. This could improve the standardization of semen analysis, decrease early embryo mortality, and use these biomarkers as a selection tool before servicing females. This study utilized imaging techniques to identify potential biomarkers of sperm quality, using sires previously classified as high (n = 4) or low (n = 4) performing at producing blastocysts in vitro. Spermatozoa were assessed before and following a gradient purification protocol, to understand how populations of cells are impacted by such protocols and may differ between in vivo and in vitro use. Pre-gradient samples from low-performing sires had an increased incidence of DNA damage, although post-gradient samples from high-performing sires were found to have an increased incidence of DNA damage. When evaluating morphology via fluorescent microscopy, the most prevalent defects in pre-gradient samples from high-performing sires were tail defects, which are successfully removed during purification processing. The most prevalent defects in pre-gradient samples from low-performing sires were aggresome defects located in the head, which would be brought into an oocyte upon fertilization and may impair embryo development. Image-based flow cytometry (IBFC) was employed to quantify defect prevalence to evaluate a greater sample size decreasing the variability that exists in manual assessments. Using IBFC, aggresome defects were again identified in the heads of spermatozoa from low-performing sires. Post-gradient samples from low-performing sires had a significantly greater (p < 0.05) incidence of aggresome defects than post-gradient samples from high-performing sires. Additionally, IBFC was used to evaluate spermatozoa viability following gradient purification. Distinct populations of sperm cells were identified. High-performing sires had more spermatozoa in the population deemed most viable than low-performing sires. This study demonstrated that spermatozoa defects vary in populations before and following gradient purification, indicating that it may be beneficial to separately evaluate semen for in vivo and in vitro use. Furthermore, a prevalent defect in low-performing sires that could explain a discrepancy between successful fertilization and embryo development was identified. Therefore, elucidating a malfunction regulated by sire, that could potentially affect early embryo development.

Temporal and spatial staging of lung alveolar regeneration is determined by the grainyhead transcription factor Tfcp2l1.

Alveolar epithelial type 2 (AT2) cells harbor the facultative progenitor capacity in the lung alveolus to drive regeneration after lung injury. Using single-cell transcriptomics, software-guided segmentation of tissue damage, and in vivo mouse lineage tracing, we identified the grainyhead transcription factor cellular promoter 2-like 1 (Tfcp2l1) as a regulator of this regenerative process. Tfcp2l1 loss in adult AT2 cells inhibits self-renewal and enhances AT2-AT1 differentiation during tissue regeneration. Conversely, Tfcp2l1 blunts the proliferative response to inflammatory signaling during the early acute injury phase. Tfcp2l1 temporally regulates AT2 self-renewal and differentiation in alveolar regions undergoing active regeneration. Single-cell transcriptomics and lineage tracing reveal that Tfcp2l1 regulates cell fate dynamics across the AT2-AT1 differentiation and restricts the inflammatory program in murine AT2 cells. Organoid modeling shows that Tfcp2l1 regulation of interleukin-1 (IL-1) receptor expression controlled these cell fate dynamics. These findings highlight the critical role Tfcp2l1 plays in balancing epithelial cell self-renewal and differentiation during alveolar regeneration.

Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues.

Decellularized extracellular matrix in the form of patches and locally injected hydrogels has long been used as therapies in animal models of disease. Here we report the safety and feasibility of an intravascularly infused extracellular matrix as a biomaterial for the repair of tissue in animal models of acute myocardial infarction, traumatic brain injury and pulmonary arterial hypertension. The biomaterial consists of decellularized, enzymatically digested and fractionated ventricular myocardium, localizes to injured tissues by binding to leaky microvasculature, and is largely degraded in about 3 d. In rats and pigs with induced acute myocardial infarction followed by intracoronary infusion of the biomaterial, we observed substantially reduced left ventricular volumes and improved wall-motion scores, as well as differential expression of genes associated with tissue repair and inflammation. Delivering pro-healing extracellular matrix by intravascular infusion post injury may provide translational advantages for the healing of inflamed tissues 'from the inside out'.

Providing Contraceptive Health Services to Adolescents and Young Adults by Telemedicine: A Scoping Review of Patient and Provider Perspectives.

OBJECTIVE: The objective of this scoping review is to synthesize and identify gaps in existing research on accessibility of telemedicine-delivered contraceptive health services to female adolescents and young adults (AYAs) and acceptability of these services to AYA patients and their medical providers. METHODS: We searched the PubMed, Scopus, Embase, and CINAHL databases to extract relevant studies on telemedicine and provision of contraceptive services among non-institutionalized, non-chronically ill female AYAs, ages 10 through 24 years. RESULTS: We screened 154 articles, and 6 articles representing 5 studies met the full inclusion criteria. Three studies assessed telemedicine acceptability and accessibility from the perspective of providers, and 3 described patients' perceived accessibility and acceptability of a theoretical telemedicine visit. No studies directly assessed AYA patients' satisfaction with actual telemedicine visits for contraceptive services. Providers viewed telemedicine-delivered sexual and reproductive health (SRH) services as acceptable to themselves and AYA patients. Most AYAs reported that they would use telemedicine for SRH services, although they would prefer in-person care. All articles identified concerns about privacy and confidentiality as a barrier to SRH telemedicine care. CONCLUSIONS: Telemedicine-delivered contraceptive health services for AYAs were perceived as acceptable and accessible by providers and by most AYA patients, although patients reported a preference for in-person care. However, none of these findings are based on patients' actual experiences with SRH telemedicine. Further research is needed to directly assess the accessibility and acceptability of telemedicine-delivered contraceptive health services for female AYA patients.

Human papillomavirus vaccine initiation and up-to-date vaccine coverage for adolescents after the implementation of school-entry policy in Puerto Rico.

The human papillomavirus (HPV) vaccine has been proven effective in the prevention of infection with high-risk HPV types, which can lead to the development of six HPV-related cancers. Puerto Rico (PR) adopted a mandatory HPV vaccination school-entry policy that took effect in August 2018. While school-entry requirements are generally accepted as an effective approach for increasing vaccination rates, there are few studies that have documented their impact on improving HPV vaccination rates. The objective of this study was to evaluate the impact of the HPV school-entry policy in PR on HPV vaccine coverage. We used a pre-post natural experiment. The study population included adolescents registered in the PR Immunization Registry during 2008-2019. We calculated HPV vaccine initiation and up-to-date (UTD) vaccine coverage rates. We estimated age-standardized rates (ASR) and standardized rate ratio with 95%CI. Vaccine data corresponding to a total of 495,327 adolescents were included for analysis; 50.9% were male and 49.1% were females. After policy implementation, a marked increase in raw HPV vaccine initiation among 11- to 12-year-old adolescents was observed across years 2017 (a pre-policy year), 2018, and 2019 (58.3%, 76.3%, and 89.8%, respectively). UTD coverage also showed a moderate increase after policy implementation among 11- to 12-year-old adolescents. The gap between sexes in vaccine initiation and UTD coverage narrowed over time; the ASRs in 2019 showed an increase of 19% in initiation and 7% increase in UTD relative to 2017 for males and females combined (both significant at p<0.05). This study demonstrated evidence of improvement in HPV vaccination rates following implementation of the school-entry policy and a narrowed sex gap in vaccine rates over time in PR. Future analyses should assess how the policy continues to affect vaccine coverage in subsequent years and how the COVID-19 pandemic has impacted HPV vaccination uptake.