The discovery of multiple active mys-related LTR-retroelements within the Neotominae subfamily of cricetid rodents.

Retrotransposon families in the rodent family Cricetidae have been understudied in contrast to Muridae, both taxa classified within the superfamily Muroidea. Therefore, we carried out a study to advance our knowledge of the unique mys LTR-retroelement identified in Peromyscus leucopus, by incorporating intra-ORF PCR, quantitative dot blots, DNA and protein library screens, the generation of molecular phylogenies, and analyses of orthologous LTR-retroelement loci. These analyses led to the discovery of three additional related families of LTR-retroelements, which include a 2900 bp full-length element of mys-related sequences (mysRS), an 8000 bp element containing the mys ORF1 sequence (mORF1) with ERV-related sequences downstream in the reverse orientation, as well as an 1800 bp element primarily consisting of mys ORF2 (mORF2) related sequences flanked by LTRs. Our data revealed only a few full-length mys elements among genera of the Neotominae subfamily of cricetid rodents, most existing as partial copies. The mysRS and mORF1 elements are also limited to the genomes of the Neotominae subfamily, whereas mORF2 appears to be restricted to the Peromyscus genus. Molecular phylogenies demonstrating concerted evolution along with an assessment of orthologous loci in Peromyscus for the presence or absence of elements are consistent with activity of these novel LTR-retroelement families within this genus. Together with known activity of various families of non-LTR retroelements in Peromyscus species, we propose that retrotransposons have been continually contributing to the dynamics of Peromyscus genomes promoting genomic diversity and may be correlated with the evolution of more than 50 identified Peromyscus species.

Barriers and enablers faced by regional and rural schools in supporting student mental health: A mixed-methods systematic review.

BACKGROUND: Australian policy reports recommended schools to be leveraged to better support student mental health, with a focus on regional and rural areas where students have poorer mental health outcomes. In designing solutions to address this systemic gap, decision-makers require an understanding of the barriers and facilitators experienced by regional and rural schools. However, current literature has focused on metropolitan schools and neglected to explore facilitators. OBJECTIVE: To review the evidence on barriers and facilitators in delivering student mental health support experienced by regional and rural schools in Organisation for Economic Co-operation and Development nations. DESIGN: A mixed-methods systematic review of peer-reviewed and grey literature. FINDINGS: The search identified 4819 studies. A full-text review by 2 reviewers resulted in 5 papers, which met the inclusion criteria and were assessed using methodological appraisal. One study used qualitative data, 2 studies used quantitative data, and 2 studies were a mixed-methods design. DISCUSSION: While there was a paucity of studies, this review draws together the most up-to-date research. The barriers and facilitators were categorised into 3 themes: access to services and resources; mental health literacy of staff and parents; and communication and collaboration between stakeholders. CONCLUSION: This review presents a comprehensive synthesis of the literature and highlights opportunities to leverage rural and regional schools to support student mental health, focusing on the quality of communication and collaboration, and increasing access to services and resources, and mental health literacy. Research should explore the unique advantages of rural and regional areas to inform policy, including a focus on strengths.

Precise quantification of translation inhibition by mRNA structures that overlap with the ribosomal footprint in N-terminal coding sequences.

A mRNA's translation rate is controlled by several sequence determinants, including the presence of RNA structures within the N-terminal regions of its coding sequences. However, the physical rules that govern when such mRNA structures will inhibit translation remain unclear. Here, we introduced systematically designed RNA hairpins into the N-terminal coding region of a reporter protein with steadily increasing distances from the start codon, followed by characterization of their mRNA and expression levels in Escherichia coli. We found that the mRNAs' translation rates were repressed, by up to 530-fold, when mRNA structures overlapped with the ribosome's footprint. In contrast, when the mRNA structure was located outside the ribosome's footprint, translation was repressed by <2-fold. By combining our measurements with biophysical modeling, we determined that the ribosomal footprint extends 13 nucleotides into the N-terminal coding region and, when a mRNA structure overlaps or partially overlaps with the ribosomal footprint, the free energy to unfold only the overlapping structure controlled the extent of translation repression. Overall, our results provide precise quantification of the rules governing translation initiation at N-terminal coding regions, improving the predictive design of post-transcriptional regulatory elements that regulate translation rate.

Processes for engaging and retaining women who are experiencing adversity in longitudinal health services research.

BACKGROUND: Women and families experiencing socioeconomic and psychosocial adversity are the least likely to access health care but most likely to benefit. For health services to effectively meet the needs of individuals experiencing adversity, research involving the health services must be truly representative. However, individuals experiencing adversity are typically excluded from or underrepresented in health services research. This paper reports on the implementation of a quality improvement approach designed to support recruitment and retention of pregnant women experiencing adversity in a longitudinal, health services randomized controlled trial ("right@home"). METHODS: right@home recruited Australian women from 10 public maternity hospitals across the states of Victoria and Tasmania who were experiencing adversity (≥2 risk factors on screening survey). Regular follow-up assessments were conducted by phone or face-to-face to child age 2 years. Research processes were designed taking heed of previous research demonstrating effective strategies for recruiting and retaining minority groups (e.g. piloting the recruitment process; recruiting via the health service providing care to the subgroup; remunerating participants); however, we were concerned that important information was missing. Therefore, once recruitment began, we conducted a continuous evaluation of the research processes, testing and implementing changes to processes or new strategies to maximize recruitment and retention (e.g. using a suite of strategies to maintain contact with families, using flexible data collection methods, obtaining consent for data linkage for future health and education data). RESULTS: right@home enrolled a large cohort of women (N = 722) experiencing high levels of adversity according to socioeconomic status and psychosocial risk factors, and achieved excellent retention (83% completion at 2 years). Most strategies appeared to increase recruitment and retention. All required additional time from the research team to develop and test, and some required extra funding, which ranged from minor (e.g. printing) to substantial (e.g. salaries, remuneration). CONCLUSIONS: By taking a quality improvement approach, supported by sufficient resourcing and flexible research processes, it is possible to recruit and retain a large cohort of women experiencing adversity who are typically missed or lost from longitudinal research.

Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants.

PurposeThe clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility.MethodsWhole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient-participants and their clinicians. We queried patient-participants' electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient-participants of eligible age who had begun risk management.ResultsThirty-seven MyCode patient-participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer-including a stage 1C fallopian tube cancer-via these procedures.ConclusionScreening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility.

The effect of groin treatment modality and sequence on clinically significant chronic lymphedema in patients with vulvar carcinoma.

OBJECTIVE: Chronic lymphedema (CL) after inguinal lymph node dissection (ILND) or radiotherapy (RT) is a significant problem for vulvar cancer survivors. The treatment modality or combination of therapies that poses the greatest risk is not known. The objective of this study was to describe rates of clinically significant CL conferred by different groin treatment modalities. METHODS: Medical records of vulvar cancer patients who had groin treatment with ILND, RT, or both were retrospectively reviewed. Each treated groin was considered individually, and divided into 4 treatment groups: ILND alone, ILND with adjuvant RT, neoadjuvant chemoradiation therapy (NCRT), or NCRT followed by ILND. Clinically significant CL was defined as that which required treatment and was recorded by laterality. Differences among groups were evaluated with χ(2) and Fisher exact test. RESULTS: Between 2000 and 2010, 146 patients with vulvar cancer who underwent therapy to 1 or both groins were identified for a total of 266 treated groins. The rates of CL for single-modality treatment, ILND or NCRT, were 10.9% and 6.7%, respectively. Multimodal treatment resulted in higher rates of CL, 13.5% for ILND followed by RT and 17.2% for NCRT followed by ILND, although differences were not significant (P = 0.37). CONCLUSIONS: Clinically significant CL was not different between treatment modalities in this study, but is underpowered. The results provide valuable information about treatment complications that will be useful for patient-centered counseling. Prospective evaluation of CL and its impact on quality of life is warranted.

The risk of subsequent malignancies in women with uterine papillary serous or clear cell endometrial cancers.

OBJECTIVE: Type II endometrial cancers include uterine papillary serous carcinoma (UPSC) and clear cell endometrial cancer (CC). Given their relative rarity, aggressive nature, and poor prognosis, little is known about the risk of subsequent malignancies at other sites. Our objective was to determine if women with UPSC or CC are at increased risk of subsequent malignancies.Type II endometrial cancers include uterine papillary serous carcinoma (UPSC) and clear cell endometrial cancer (CC). Given their relative rarity, aggressive nature, and poor prognosis, little is known about the risk of subsequent malignancies at other sites. Our objective was to determine if women with UPSC or CC are at increased risk of subsequent malignancies. METHODS: Women diagnosed with UPSC or CC were identified from the SEER (Surveillance Epidemiology and End Results) Program from 1973 to 2005. Cases with a second gynecologic malignancy were excluded. Using SEER*Stat software, standardized incidence ratios (SIRs) of subsequent malignancies were calculated. RESULTS: A total of 8045 and 1740 patients were diagnosed with UPSC and CC, respectively. Four hundred sixty-one (5.7%) of the UPSC cases were diagnosed with at least 1 additional nongynecologic malignancy. Significant associations were found with the following malignancies: the renal pelvis, soft-tissue sarcomas, acute myeloid leukemia, the bladder, and colon. Seventy-eight CC cases (4.5%) were diagnosed with at least 1 additional malignancy. In comparison with the baseline population risk, there was no statistically significant increased risk of any subsequent malignancy with a primary diagnosis of CC. CONCLUSIONS: This is the first large population-based analysis of second primary malignancies after type II endometrial cancers. Uterine papillary serous carcinoma is associated with increased risks of certain subsequent malignancies, and providers should be aware of these when following up patients with this diagnosis, especially those with stage I disease. In contrast, no such associations were found with CC in this cohort.

Intraplacental choriocarcinoma in a term pregnancy: Is serial postpartum hCG assessment necessary?

Intraplacental choriocarcinoma (IC), or choriocarcinoma in situ, is a rare disease on the gestational trophoblastic disease (GTD) spectrum, with <100 case reports available in the literature. We propose that many patients with IC are likely to be missed as the majority of patients do not present with metastases. Currently, there are no standardized protocols in existence for postpartum monitoring of these patients. We present a case of IC identified in the term placenta of a 21-year-old who delivered by primary cesarean due to concern for fetal intolerance of labor. Subsequently, we review the recommendations available on postpartum monitoring of this likely under-diagnosed condition.

Mothers' experiences of emotional abuse from an intimate partner and its associations with children's developmental outcomes at 5 years.

BACKGROUND: Intimate partner violence (IPV) is associated with an increased risk of poorer child development. Existing research has focused on physical abuse with less known about the associations with emotional IPV. OBJECTIVE: To describe the period prevalence of mother's experiences of emotional IPV during children's preschool years and associations with child mental, physical, social, and cognitive development. METHODS: Secondary analysis of control group data (n = 194) from an Australian randomised trial (right@home), which recruited pregnant women experiencing social adversity from antenatal clinics in 2013-14. Women reported emotional abuse (Composite Abuse Scale) at child ages 3-5 years. Measures of child development at 5 years included: Strengths and Difficulties Questionnaire, Social Skills Improvement System, Pediatric Quality of Life Inventory, Clinical Evaluation of Language Fundamentals, School Entry Alphabetic and Phonological Awareness Readiness Test, NIH executive function subtests, sleep and health. The prevalence of emotional IPV from 3 to 5 years was estimated. Regression models compared developmental outcomes according to emotional IPV exposure, adjusted for child age, child gender, and maternal education. Missing data were accounted for using multiple imputation. RESULTS: From 3-5 years, emotional IPV was experienced by 57% of women. Emotional IPV exposure was consistently associated with poorer child developmental outcomes. Differences were most apparent for SDQ internalising (mean difference 1.2, 95% CI 0.2 to 2.1) and externalising difficulties (1.2, 95% CI -0.1 to 2.4). CONCLUSIONS: Emotional IPV was highly prevalent amongst families experiencing social adversity. Developing acceptable and effective identification processes and interventions that prioritise families experiencing co-occurring social adversities should be a public health priority.

Metastatic melanoma posing as a pelvic mass.

Pelvic metastasis of melanoma is extremely rare and may pose a diagnostic challenge. We present a case report of a female with a history of colon cancer who underwent exploratory surgery for a pelvic mass that was suspicious for ovarian malignancy. Pathology was consistent with both recurrent colon cancer as well as synchronous newly diagnosed metastatic melanoma.

Luteoma of pregnancy masquerading as a granulosa cell tumor.

Pregnancy luteomas are rare, nonmalignant lesions thought to be caused by hormonal changes during pregnancy. Granulosa cell tumor is a rare type of ovarian cancer; 10% occur during pregnancy and typically present with elevated inhibin levels. Herein, we present a case of a pregnant female with a pelvic mass and elevated inhibin B suggestive of a granulosa cell tumor, yet with final pathology consistent with a pregnancy luteoma.

Dual-console robotic surgery compared to laparoscopic surgery with respect to surgical outcomes in a gynecologic oncology fellowship program.

OBJECTIVE: Minimally invasive surgical techniques decrease surgical morbidity and recovery time. Studies demonstrate similar surgical outcomes comparing robotic to laparoscopic surgery. These studies have not accounted for the incorporation of fellow education. With the dual-console da Vinci Si Surgical System®, a two surgeon approach could be performed. We sought to compare surgical outcomes at a gynecologic oncology fellowship program of traditional laparoscopic to robotic surgeries using the dual-console system. METHODS: We identified patients who underwent laparoscopic or robotic surgery performed by a gynecologic oncologist from November 2009-November 2010. Robotic surgeries were conducted using the dual-console, utilizing a two surgeon approach. Surgeries involved a staff physician with a gynecologic oncology fellow. Statistical analysis was performed using student t-test and chi-squared analysis. RESULTS: A total of 222 cases were identified. Cases were analyzed in groups: all cases identified, all cancer cases, and endometrial cancer cases only. When analyzing all cases, no statistical difference was noted in total operating room time (172 vs. 175 min; p=0.6), pelvic lymph nodes removed (10.1 vs. 9.6; p=0.69), para-aortic lymph nodes dissected (3.7 vs. 3.8; p=0.91), or length of stay (1.5 vs. 1.3 days; p=0.3). There was a significant difference in total surgical time (131 vs.110 min; p<0.0001) and EBL (157 vs.94 ml; p<0.0001), favoring robotic surgery. When analyzing all cancer cases, the advantage in total surgical time for robotic surgery was lost. Complications were similar between cohorts. CONCLUSION: Incorporating fellow education into robotic surgery does not adversely affect outcomes when compared to traditional laparoscopic surgery.

Outcomes of robotic surgery in morbidly obese patients with endometrial cancer: a retrospective study.

With advances in minimal invasive surgery, robotic surgery has become the widespread approach for surgical staging of endometrial cancer in the obese population. This study aimed to evaluate safety and surgical outcomes of robotic surgery in the morbidly obese and extremely morbidly obese patients with endometrial cancer. Retrospective cohort study. A total of 391 obese women undergoing robotic-assisted surgical staging were identified and included in the study. Surgical outcomes for obese patients (BMI > 30 kg/m2) who underwent surgical staging between 2011 and 2019 were retrospectively collected. Preoperative characteristics, perioperative outcomes and postoperative complications were analyzed among the categories of obesity (BMI ≥ 30-34.9 kg/m2, ≥ 35-39.9 kg/m2, ≥ 40-49.9 kg/m2) including the extremely morbid obese (BMI > 50 kg/m2). Comparative analysis revealed a higher percentage of postoperative complications with increasing BMI, although the results were not statistically significant. Postoperative complications are observed at higher rates among women with increasing BMI.

No evidence for increased fitness of offspring from multigenerational effects of parental size or natal carcass size in the burying beetle Nicrophorus marginatus.

Multigenerational effects (often called maternal effects) are components of the offspring phenotype that result from the parental phenotype and the parental environment as opposed to heritable genetic effects. Multigenerational effects are widespread in nature and are often studied because of their potentially important effects on offspring traits. Although multigenerational effects are commonly observed, few studies have addressed whether they affect offspring fitness. In this study we assess the effect of potential multigenerational effects of parental body size and natal carcass size on lifetime fitness in the burying beetle, Nicrophorus marginatus (Coleoptera; Silphidae). Lifespan, total number of offspring, and number of offspring in the first reproductive bout were not significantly related to parental body size or natal carcass size. However, current carcass size used for reproduction was a significant predictor for lifetime number of offspring and number of offspring in the first brood. We find no evidence that multigenerational effects from larger parents or larger natal carcasses contribute to increased fitness of offspring.

A pediatric high-flow nasal cannula protocol standardizes initial flow and expedites weaning.

OBJECTIVE: Respiratory illnesses compose the most common diagnoses of patients admitted to pediatric intensive care units. In pediatrics, high-flow nasal cannula (HFNC) therapy is an intermediate level of respiratory support with variability in practice. We conducted a pre-post intervention study of patients placed on HFNC therapy before and after the implementation of an HFNC protocol. METHODS: This was a quality improvement/pre-post intervention study of pediatric patients who received HFNC therapy in our teaching, tertiary care children's hospital between January 2015 and April 2019. Patients were evaluated before and after the implementation of a protocol that promoted initiation of higher flow and rapid weaning. Our primary outcomes were initial flow and rate of weaning pre- and post-protocol; our secondary outcomes were HFNC failure rate (defined as escalation to noninvasive ventilation or mechanical ventilation) and length of hospital stay. Propensity matching was used to account for differences in age and weight pre- and post-protocol. RESULTS: In total, 584 patients were included, 292 pre-protocol, and 292 post-protocol. The median age was 20 months, and the indication for HFNC therapy was bronchiolitis in 29% of patients. Post-protocol patients compared to pre-protocol patients had significantly a higher initial flow (median 14.5 L/min vs. 10 L/min, p < .001) and a higher weaning rate of flow (median 4.1 L/min/h vs. 2.4 L/min/h, p < .001). Post-protocol patients also had a lower HFNC failure rate (10% vs. 17%, p = .015) and a shorter length of stay (5.97 days vs. 6.80 days, p = .006). CONCLUSION: Among pediatric patients, the implementation of an HFNC protocol increases initial flow, allows for more rapid weaning, and may decrease the incidence of escalation to noninvasive ventilation or mechanical ventilation.

Conservative surgery in early-stage cervical cancer: what percentage of patients may be eligible for conization and lymphadenectomy?

OBJECTIVE: To determine the proportion of young patients with early-stage invasive cervical cancer treated with radical hysterectomy who may have been eligible for fertility-sparing surgery consisting of cervical conization with pelvic lymph node dissection. METHODS: We retrospectively identified all patients with early-stage cervical cancer (stages IA1-IB1) who underwent a radical hysterectomy at The University of Texas M. D. Anderson Cancer Center between 1990 and 2009. We reviewed these patients' records to identify patients who were <40 years who had not previously undergone tubal ligation and who would have been considered candidates for cold-knife conization with pelvic lymph node dissection-i.e., women with tumors smaller than 2 cm, low-risk histology (squamous, adenocarcinoma, or adenosquamous), and no lymphovascular space invasion (LVSI). RESULTS: A total of 507 patients with early-stage cervical cancer were identified who underwent radical hysterectomy during the review period. Of these women, 277 (55%) were 40 years or younger. Of these 277 patients, 75 (27%) had had a previous tubal ligation and 202 (73%) had not. Of these 202 patients potentially interested in fertility preserving surgery, 53 (26%) had favorable pathologic characteristics including low-risk histology, tumors ≤2 cm in size and no LVSI present. Of these 53 patients, none had parametrial involvement or positive lymph nodes. CONCLUSION: Among 202 women with age younger than 40 years and no previous tubal ligation who underwent radical hysterectomy, 53 (26%) may have been eligible for fertility-sparing surgery such as cold-knife conization with pelvic lymph node dissection.

A brief survey to identify pregnant women experiencing increased psychosocial and socioeconomic risk.

PROBLEM: Identifying pregnant women whose children are at risk of poorer development in a rapid, acceptable and feasible way. BACKGROUND: A range of antenatal psychosocial and socioeconomic risk factors adversely impact children's health, behaviour and cognition. AIM: Investigate whether a brief, waiting room survey of risk factors identifies women experiencing increased antenatal psychosocial and socioeconomic risk when asked in a private, in-home interview. METHODS: Brief 10-item survey (including age, social support, health, smoking, stress/anxious mood, education, household income, employment) collected from pregnant women attending 10 Australian public birthing hospitals, used to determine eligibility (at least 2 adverse items) for the "right@home" trial. 735 eligible women completed a private, in-home interview (including mental health, wellbeing, substance use, domestic violence, housing problems). Regression models tested for dose-response trends between the survey risk factor count and interview measures. FINDINGS: 38%, 31%, 15% and 16% of women reported a survey count of 2, 3, 4 and 5 or more adverse risk factors, respectively. Dose-response relationships were evident between the survey count and interview measures, e.g. of women with a survey count of 2, 8% reported ever having a drug problem, 4% experienced domestic violence in the last year and 10% experienced housing problems, contrasting with 31%, 31% and 26%, respectively, for women reporting a survey count of 5 or more. DISCUSSION/CONCLUSIONS: A brief, waiting room survey of psychosocial and socioeconomic risk factors concurs with a private antenatal risk factor interview, and could help health professionals quickly identify which women would benefit from more support.

Nurse Home Visiting for Families Experiencing Adversity: A Randomized Trial.

OBJECTIVES: Nurse home visiting (NHV) may redress inequities in children's health and development evident by school entry. We tested the effectiveness of an Australian NHV program (right@home), offered to pregnant women experiencing adversity, hypothesizing improvements in (1) parent care, (2) responsivity, and (3) the home learning environment at child age 2 years. METHODS: A randomized controlled trial of NHV delivered via universal child and family health services was conducted. Pregnant women experiencing adversity (≥2 of 10 risk factors) with sufficient English proficiency were recruited from antenatal clinics at 10 hospitals across 2 states. The intervention comprised 25 nurse visits to child age 2 years. Researchers blinded to randomization assessed 13 primary outcomes, including Home Observation of the Environment (HOME) Inventory (6 subscales) and 25 secondary outcomes. REULTS: Of 1427 eligible women, 722 (50.6%) were randomly assigned; 306 of 363 (84%) women in the intervention and 290 of 359 (81%) women in the control group provided 2-year data. Compared with women in the control group, those in the intervention reported more regular child bedtimes (adjusted odds ratio 1.76; 95% confidence interval [CI] 1.25 to 2.48), increased safety (adjusted mean difference [AMD] 0.22; 95% CI 0.07 to 0.37), increased warm parenting (AMD 0.09; 95% CI 0.02 to 0.16), less hostile parenting (reverse scored; AMD 0.29; 95% CI 0.16 to 0.41), increased HOME parental involvement (AMD 0.26; 95% CI 0.14 to 0.38), and increased HOME variety in experience (AMD 0.20; 95% CI 0.07 to 0.34). CONCLUSIONS: The right@home program improved parenting and home environment determinants of children's health and development. With replicability possible at scale, it could be integrated into Australian child and family health services or trialed in countries with similar child health services.

Malignant Brenner tumor: Two case reports.

Malignant Brenner tumor (MBT) is a rare ovarian tumor that, given the infrequency of the disease, has not been well documented in the literature. Diagnosing MBT both radiographically and histologically remains a challenge. We report two cases of ovarian MBT, detailing the clinical presentation, radiographic characteristics, and histologic findings with supplementary imaging. Our cases demonstrate the pathologic challenge of histologically diagnosing MBT versus other Brenner tumors and transitional cell carcinoma (TCC) of the ovary.