Genomes of the autonomous parvovirus minute virus of mice induce replication stress through RPA exhaustion.

The oncolytic autonomous parvovirus Minute Virus of Mice (MVM) establishes infection in the nuclear environment by usurping host DNA damage signaling proteins in the vicinity of cellular DNA break sites. MVM replication induces a global cellular DNA Damage Response (DDR) that is dependent on signaling by the ATM kinase and inactivates the cellular ATR-kinase pathway. However, the mechanism of how MVM generates cellular DNA breaks remains unknown. Using single molecule DNA Fiber Analysis, we have discovered that MVM infection leads to a shortening of host replication forks as infection progresses, as well as induction of replication stress prior to the initiation of virus replication. Ectopically expressed viral non-structural proteins NS1 and NS2 are sufficient to cause host-cell replication stress, as is the presence of UV-inactivated non-replicative MVM genomes. The host single-stranded DNA binding protein Replication Protein A (RPA) associates with the UV-inactivated MVM genomes, suggesting MVM genomes might serve as a sink for cellular stores of RPA. Overexpressing RPA in host cells prior to UV-MVM infection rescues DNA fiber lengths and increases MVM replication, confirming that MVM genomes deplete RPA stores to cause replication stress. Together, these results indicate that parvovirus genomes induce replication stress through RPA exhaustion, rendering the host genome vulnerable to additional DNA breaks.

Neonatal Enthesis Healing Involves Noninflammatory Acellular Scar Formation through Extracellular Matrix Secretion by Resident Cells.

Wound healing typically recruits the immune and vascular systems to restore tissue structure and function. However, injuries to the enthesis, a hypocellular and avascular tissue, often result in fibrotic scar formation and loss of mechanical properties, severely affecting musculoskeletal function and life quality. This raises questions about the healing capabilities of the enthesis. Herein, this study established an injury model to the Achilles entheses of neonatal mice to study the effectiveness of early-age enthesis healing. Histology and immunohistochemistry analyses revealed an atypical process that did not involve inflammation or angiogenesis. Instead, healing was mediated by secretion of collagen types I and II by resident cells, which formed a permanent hypocellular and avascular scar. Transmission electron microscopy showed that the cellular response to injury, including endoplasmic reticulum stress, autophagy, and cell death, varied between the tendon and cartilage ends of the enthesis. Single-molecule in situ hybridization, immunostaining, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays verified these differences. Finally, gait analysis showed that these processes effectively restored function of the injured leg. These findings reveal a novel healing mechanism in neonatal entheses, whereby local extracellular matrix secretion by resident cells forms an acellular extracellular matrix deposit without inflammation, allowing gait restoration. These insights into the healing mechanism of a complex transitional tissue may lead to new therapeutic strategies for adult enthesis injuries.

Modification of N-hydroxycytidine yields a novel lead compound exhibiting activity against the Venezuelan equine encephalitis virus.

Nucleoside and nucleobase analogs capable of interfering with nucleic acid synthesis have played essential roles in fighting infectious diseases. However, many of these agents are associated with important and potentially lethal off-target intracellular effects that limit their use. Based on the previous discovery of base-modified 2'-deoxyuridines, which showed high anticancer activity while exhibiting lower toxicity toward rapidly dividing normal human cells compared to antimetabolite chemotherapeutics, we hypothesized that a similar modification of the N4-hydroxycytidine (NHC) molecule would provide novel antiviral compounds with diminished side effects. This presumption is due to the substantial structural difference with natural cytidine leading to less recognizability by host cell enzymes. Among the 42 antimetabolite species that have been synthesized and screened against VEEV, one hit compound was identified. The structural features of the modifying moiety were similar to those of the anticancer lead 2'-deoxyuridine derivative reported previously, providing an opportunity to pursue further structure-activity relationship (SAR) studies directed to lead improvement, and obtain insight into the mechanism of action, which can lead to identifying drug candidates against a broad spectrum of RNA viral infections.

"As Long as I Got a Breath in My Body": Risk and Resistance in Black Maternal Embodiment.

"Mothering while black" in Cleveland, Ohio is a radical act. This highly segregated, highly unequal urban environment is replete with the chronic stressors that degrade well-being and diminish survival for Black mothers and their infants; specifically, a maternal mortality rate two and a half times that of their white counterparts and an infant mortality rate nearly three times that of infants born to white mothers. In the midst of such tragedy and disadvantage, Black mothers strive to love and care for their children in ways that mitigate the toxicity of structural racism. The seventeen pregnant and postpartum Black women in this ethnographic study describe transformational experiences with what we label "betterment:" whereby they center their children's perspective and needs, reconsider their social networks, and focus on the future with an unflinching understanding of the constraints of structural racism. Locating betterment alongside other examples of maternal embodiment and through the rich theoretical lens of Black feminist scholars these participant narratives suggest that the toxic effects of racism and the means to resist them are embodied by Black mothers. A nuanced understanding of Black motherhood disrupts public discourses of blame and responsibility that obscure our collective duty to dismantle structural racism.

Common cellular origin and diverging developmental programs for different sesamoid bones.

Sesamoid bones are small auxiliary bones that form near joints and contribute to their stability and function. Thus far, providing a comprehensive developmental model or classification system for this highly diverse group of bones has been challenging. Here, we compare our previously reported mechanisms of patella development in the mouse with those of two anatomically different sesamoids, namely lateral fabella and digit sesamoids. We show that all three types of sesamoid bones originate from Sox9+ /Scx+ progenitors under the regulation of TGFß and independently of mechanical stimuli from muscles. Whereas BMP2 regulates the growth of all examined sesamoids, the differentiation of lateral fabella or digit sesamoids is regulated redundantly by BMP4 and BMP2. Next, we show that whereas patella and digit sesamoids initially form in juxtaposition to long bones, lateral fabella forms independently and at a distance. Finally, our evidence suggests that, unlike the synovial joint that separates patella from femur, digit sesamoids detach from the phalanx by formation of a fibrocartilaginous joint. These findings highlight both common and divergent molecular and mechanical features of sesamoid bone development, which underscores their evolutionary plasticity.

Bone morphology is regulated modularly by global and regional genetic programs.

Bone protrusions provide stable anchoring sites for ligaments and tendons and define the unique morphology of each long bone. Despite their importance, the mechanism by which superstructures are patterned is unknown. Here, we identify components of the genetic program that control the patterning of Sox9+/Scx+ superstructure progenitors in mouse and show that this program includes both global and regional regulatory modules. Using light-sheet fluorescence microscopy combined with genetic lineage labeling, we mapped the broad contribution of the Sox9+/Scx+ progenitors to the formation of bone superstructures. Then, by combining literature-based evidence, comparative transcriptomic analysis and genetic mouse models, we identified Gli3 as a global regulator of superstructure patterning, whereas Pbx1, Pbx2, Hoxa11 and Hoxd11 act as proximal and distal regulators, respectively. Moreover, by demonstrating a dose-dependent pattern regulation in Gli3 and Pbx1 compound mutations, we show that the global and regional regulatory modules work in a coordinated manner. Collectively, our results provide strong evidence for genetic regulation of superstructure patterning, which further supports the notion that long bone development is a modular process.This article has an associated 'The people behind the papers' interview.

Epidemiology and Outcomes of Critically Ill Children at Risk for Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

OBJECTIVES: Interventional trials aimed at pediatric acute respiratory distress syndrome prevention require accurate identification of high-risk patients. In this study, we aimed to characterize the frequency and outcomes of children meeting "at risk for pediatric acute respiratory distress syndrome" criteria as defined by the Pediatric Acute Lung Injury Consensus Conference. DESIGN: Planned substudy of the prospective multicenter, international Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study conducted during 10 nonconsecutive weeks (May 2016-June 2017). SETTING: Thirty-seven international PICUs. PATIENTS: Three-hundred ten critically ill children meeting Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated the frequency of children at risk for pediatric acute respiratory distress syndrome and rate of subsequent pediatric acute respiratory distress syndrome diagnosis and used multivariable logistic regression to identify factors associated with subsequent pediatric acute respiratory distress syndrome. Frequency of at risk for pediatric acute respiratory distress syndrome was 3.8% (95% CI, 3.4-5.2%) among the 8,122 critically ill children who were screened and 5.8% (95% CI, 5.2-6.4%) among the 5,334 screened children on positive pressure ventilation or high-flow oxygen. Among the 310 at-risk children, median age was 2.1 years (interquartile range, 0.5-7.3 yr). Sixty-six children (21.3%) were subsequently diagnosed with pediatric acute respiratory distress syndrome, a median of 22.6 hours (interquartile range, 9.8-41.0 hr) later. Subsequent pediatric acute respiratory distress syndrome was associated with increased mortality (21.2% vs 3.3%; p < 0.001) and longer durations of invasive ventilation and PICU care. Subsequent pediatric acute respiratory distress syndrome rate did not differ by respiratory support modality at the time of meeting at risk criteria but was independently associated with lower initial saturation:Fio2 ratio, progressive tachycardia, and early diuretic administration. CONCLUSIONS: The Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria identify critically ill children at high risk of pediatric acute respiratory distress syndrome and poor outcomes. Interventional trials aimed at pediatric acute respiratory distress syndrome prevention should target patients early in their illness course and include patients on high-flow oxygen and positive pressure ventilation.

Development of migrating tendon-bone attachments involves replacement of progenitor populations.

Tendon-bone attachment sites, called entheses, are essential for musculoskeletal function. They are formed embryonically by Sox9+ progenitors and continue to develop postnatally, utilizing Gli1 lineage cells. Despite their importance, we lack information on the transition from embryonic to mature enthesis and on the relation between Sox9+ progenitors and the Gli1 lineage. Here, by performing a series of lineage tracing experiments in mice, we identify the onset of Gli1 lineage contribution to different entheses. We show that Gli1 expression is regulated embryonically by SHH signaling, whereas postnatally it is maintained by IHH signaling. During bone elongation, some entheses migrate along the bone shaft, whereas others remain stationary. Interestingly, in stationary entheses Sox9+ cells differentiate into the Gli1 lineage, but in migrating entheses this lineage is replaced by Gli1 lineage. These Gli1+ progenitors are defined embryonically to occupy the different domains of the mature enthesis. Overall, these findings demonstrate a developmental strategy whereby one progenitor population establishes a simple embryonic tissue, whereas another population contributes to its maturation. Moreover, they suggest that different cell populations may be considered for cell-based therapy of enthesis injuries.

Inhibitory control and negative affect in relation to food intake among youth.

Negative affect and poor inhibitory control are related to disinhibited eating behaviors in youth and may contribute to the development and/or maintenance of obesity. Although few studies have jointly examined these constructs in youth, it has been theorized that poor inhibitory control may be driven by negative affect. If supported, impaired inhibitory control, driven by negative affect, could represent a modifiable neurocognitive treatment target for disinhibited eating. The current study examined whether inhibitory control mediates the relationship between negative affect and eating among youth. Youth (8-17 years) participated in a Food Go/No-Go neurocognitive task to measure inhibitory control as the percentage of commission errors. A composite negative affect score was created from self-report measures of anxiety and depression. A laboratory buffet meal modeled to simulate disinhibited eating was used to measure total and snack food intake. Cross-sectional mediation models with bias-corrected bootstrap confidence intervals (CI) were conducted using negative affect as the independent variable, inhibitory control as the mediator, and intake patterns as dependent variables. One-hundred-eighty-one youths (13.2 ± 2.7y; 55% female; BMIz 0.6 ± 1.0) were studied. Total Go/No-Go commission errors mediated the relationship between negative affect and total intake (95%CI = [0.3, 31.6]), but not snack intake (95%CI = [-2.5, 7.3]). Commission errors for Food-Go blocks significantly mediated the relationship between negative affect and total intake (95%CI = [7.7, 44.4]), but not snack intake (95%CI = [-3.4, 9.5]). Commission errors on Neutral-Go blocks did not significantly mediate any of these relationships. Negative affect may lead to poorer inhibitory control as well as a stronger approach tendency toward food, increasing the likelihood of engaging in disinhibited eating. Future research should determine if, in combination with approaches to reduce negative affect, improved inhibitory control could help prevent overeating in youths with depressive or anxiety symptoms.

Assessment of loss-of-control eating in healthy youth by interview and questionnaire.

OBJECTIVE: The aim of this study is to evaluate two questionnaires, an updated youth version of the questionnaire on eating and weight patterns (Questionnaire on Eating and Weight Patterns-5 Children/Adolescent [QEWP-C-5]) and the Loss-of-Control (LOC) Eating Disorder Questionnaire (LOC-ED-Q), against the Eating Disorder Examination (EDE) interview to assess the presence of LOC-eating among youth. METHOD: Two-hundred and eighteen youths (12.8 ± 2.7 years) completed the QEWP-C-5, LOC-ED-Q, and EDE, depressive and anxiety questionnaires, and adiposity assessment. Sensitivity, specificity, positive-predictive value, negative-predictive value, and diagnostic accuracy were calculated; Cochran's Q and McNemar's tests were used to compare measures. Receiver operating characteristic area under the curve (AUC) analyses were performed. Mood and adiposity based on LOC-eating presence and absence based on each measure were examined. RESULTS: The QEWP-C-5 and LOC-ED-Q demonstrated poor sensitivity (33%; 30%) and high specificity (95%; 96%) compared with the EDE. The AUCs suggested neither the QEWP-C-5 (0.64) nor the LOC-ED-Q (0.62) demonstrated acceptable diagnostic accuracy. Comparing distributions of LOC-eating presence between assessments, the QEWP-C-5 and EDE did not differ significantly (p = .10), while the LOC-ED-Q and EDE had significantly different distributions (p = .03). LOC-eating presence was associated with higher depressive and anxiety symptoms across all measures (ps < .02). Greater adiposity (ps < .02) was associated with LOC-eating presence on the EDE and LOC-ED-Q, and higher BMI z-score (p = .02) on the LOC-ED-Q. DISCUSSION: Neither the QEWP-C-5 nor the LOC-ED-Q was sensitive for identifying LOC-eating presence as determined by the EDE, although both were associated with greater mood symptoms. Research is needed to improve self-report questionnaires to better screen for LOC-eating presence among pediatric populations.

The association between alexithymia and eating behavior in children and adolescents.

OBJECTIVE: Alexithymia, or the difficulty identifying or describing one's own emotions, may be a risk factor for dysregulated eating and excess weight gain. However, the relationships between alexithymia and eating behaviors in community samples of non-clinical youth have not been well-characterized. We hypothesized that alexithymia would be positively associated with disordered and disinhibited eating in a community-based sample of boys and girls without an eating disorder. METHOD: Two hundred children (8-17 years old) across the weight spectrum completed an interview to assess loss of control (LOC) eating and eating-related psychopathology, a laboratory test meal designed to induce disinhibited eating, and questionnaires to assess alexithymia, eating in the absence of hunger, and emotional eating. Linear and logistic regressions were conducted to examine the relationship between alexithymia and eating variables, with age, sex, race, and fat mass as covariates. Test meal analyses also adjusted for lean mass. Given the overlap between alexithymia and depression, all models were repeated with depressive symptoms as an additional covariate. RESULTS: Alexithymia was associated with an increased likelihood of reporting LOC eating (p < .05). Moreover, alexithymia was positively associated with disordered eating attitudes, emotional eating, and eating in the absence of hunger (ps < .05). Greater alexithymia was associated with more carbohydrate and less fat intake at the test meal (ps < .05). After adjusting for depressive symptoms, alexithymia remained associated with eating in the absence of hunger and carbohydrate and fat intake (ps < .05). DISCUSSION: In healthy children, alexithymia is associated with some facets of eating behavior and food intake. If supported prospectively, these preliminary findings suggest alexithymia may be a modifiable risk factor to reduce disordered eating and excess weight gain in youth.

Effort of breathing in children receiving high-flow nasal cannula.

OBJECTIVE: High-flow humidified nasal cannula is often used to provide noninvasive respiratory support in children. The effect of high-flow humidified nasal cannula on effort of breathing in children has not been objectively studied, and the mechanism by which respiratory support is provided remains unclear. This study uses an objective measure of effort of breathing (Pressure. Rate Product) to evaluate high-flow humidified nasal cannula in critically ill children. DESIGN: Prospective cohort study. SETTING: Quaternary care free-standing academic children's hospital. PATIENTS: ICU patients younger than 18 years receiving high-flow humidified nasal cannula or whom the medical team planned to extubate to high-flow humidified nasal cannula within 72 hours of enrollment. INTERVENTIONS: An esophageal pressure monitoring catheter was placed to measure pleural pressures via a Bicore CP-100 pulmonary mechanics monitor. Change in pleural pressure (ΔPes) and respiratory rate were measured on high-flow humidified nasal cannula at 2, 5, and 8 L/min. ΔPes and respiratory rate were multiplied to generate the Pressure.Rate Product, a well-established objective measure of effort of breathing. Baseline Pes, defined as pleural pressure at end exhalation during tidal breathing, reflected the positive pressure generated on each level of respiratory support. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients had measurements on high-flow humidified nasal cannula. Median age was 6.5 months (interquartile range, 1.3-15.5 mo). Median Pressure,Rate Product was lower on high-flow humidified nasal cannula 8 L/min (median, 329 cm H2O·min; interquartile range, 195-402) compared with high-flow humidified nasal cannula 5 L/min (median, 341; interquartile range, 232-475; p = 0.007) or high-flow humidified nasal cannula 2 L/min (median, 421; interquartile range, 233-621; p < 0.0001) and was lower on high-flow humidified nasal cannula 5 L/min compared with high-flow humidified nasal cannula 2 L/min (p = 0.01). Baseline Pes was higher on high-flow humidified nasal cannula 8 L/min than on high-flow humidified nasal cannula 2 L/min (p = 0.03). CONCLUSIONS: Increasing flow rates of high-flow humidified nasal cannula decreased effort of breathing in children, with the most significant impact seen from high-flow humidified nasal cannula 2 to 8 L/min. There are likely multiple mechanisms for this clinical effect, including generation of positive pressure and washout of airway dead space.

Fewer anchors achieves successful arthroscopic shoulder stabilization surgery: 114 patients with 4 years of follow-up.

BACKGROUND: The shoulder is the most frequently dislocated joint, with an incidence of 10 to 20 per 100,000 each year. The optimum number of anchors to use in arthroscopic stabilization is a topic of growing interest; most surgeons use 3. Our stabilization technique is to commonly use only a single suture anchor to purse-string the capsulolabral tissue up and toward the glenoid. This study aimed to ascertain whether successful stabilization can be achieved with fewer than 3 anchors. METHODS: Our study comprised 114 consecutive patients with anterior instability and a Bankart lesion undergoing arthroscopic stabilization with 4 years of follow-up. Outcome was measured by Oxford Instability Score (OIS) and recurrence of instability or dislocation. Patient demographics were 86.8% male, 13.2% female, mean age of 31 years, 76.3% Hill-Sachs lesions, 13.2% bony Bankart lesions, 13.2% glenoid defects, and 9.6% SLAP lesions. The majority of patients, 71 patients (62.3%), received only 1 anchor; 40 patients (35.1%) received 2 anchors, and 3 patients (2.6%) had 3 anchors. RESULTS: The mean OIS was 44.3 preoperatively and 17.3 postoperatively (P < .0001). There was no difference in OIS improvement between the patients who received a single anchor and those who received 2 or 3 anchors (P > .05). Even with minor bony Bankart lesions and glenoid defects, a single suture anchor can be sufficient. Our failure rate of 6.1% is comparable with that of other published series. CONCLUSION: Successful shoulder stabilization can be achieved with fewer than 3 anchors, and a single anchor is usually sufficient.

Fluoroscopic-guided hysteroscopic tubal cannulation results in high technical success and pregnancy rates comparable with the more traditional laparoscopically guided hysteroscopic tubal cannulation.

Objective: To compare women with proximal tubal obstruction (PTO) undergoing hysteroscopic tubal cannulation with fluoroscopic guidance vs. laparoscopic guidance. Design: Retrospective cohort study. Setting: All fluoroscopically-guided hysteroscopic tubal cannulations were performed in an ambulatory suite. All laparoscopically-guided hysteroscopic tubal cannulations were performed in a hospital operating room. Patients: Infertile women with unilateral or bilateral PTO on hysterosalpingography who failed selective salpingography in the radiology suite and had a planned laparoscopy or hysteroscopy in the operating room for defects seen on sonohysterography were studied. Intervention: All women had a Novy catheter system positioned hysteroscopically to cannulate the occluded fallopian tube(s). Women undergoing fluoroscopically guided hysteroscopic tubal cannulation (FHTC), which used contrast and C-arm pelvic imaging at an ambulatory center, were compared with those undergoing hospital-based laparoscopically guided hysteroscopic tubal cannulation (LHTC) with laparoscopic visualization. Main Outcome Measurements: Tubal cannulation success; bilateral cannulation success; tubal perforations; post-FHTC non-in vitro fertilization (non-IVF) intrauterine pregnancies; days from procedure to pregnancy for non-IVF intrauterine pregnancies; and time to non-IVF pregnancy hazards ratio. Results: A total of 76 infertile women undergoing either FHTC (34 women) or LHTC (42 women) between 2015 and 2019 were included. Demographic variables were similar among the 2 groups. A total of 31 (92%) of 34 of patients undergoing FHTC and 36 (86%) of 42 of patients undergoing LHTC had at least one tube successfully cannulated. In total, 30 (78%) of 34 of patients undergoing FHTC and 32 (79%) of 42 patients undergoing LHTC had all occluded tubes successfully cannulated. Tubal perforation occurred in 1 (3%) of 34 FHTC cases and 3 (7%) of 42 LHTC cases. A similar percentage of non-IVF treatment-induced intrauterine pregnancies were achieved in the FHTC and LHTC groups (10/34 [29%] vs. 12/42 [29%]). Among patients who conceived without IVF, time from procedure to pregnancy was lower in the FHTC group (101 ± 124.6 days) compared with the LHTC group (228 ± 216 days). There was a significant difference in time to pregnancy when only those who conceived were considered (hazard ratio, 9.39; 95% confidence interval, 2.42-36.51); however, there was no significant difference when all subjects regardless of pregnancy outcome were analyzed (hazard ratio, 1.48; 95% confidence interval, 0.64-3.446). Conclusion: Fluoroscopically guided hysteroscopic tubal cannulation is a safe, effective, incision free procedure that results in comparable rates of tubal patency and intrauterine pregnancies as LHTC. This technique should be considered in women undergoing treatment of PTO when operative laparoscopy is not otherwise indicated.

Promoting Functional Recovery in Critically Ill Children.

Over two-thirds of pediatric critical illness survivors will experience functional impairments that persist after discharge, that is, post-intensive care syndrome in pediatrics (PICS-p). Risk factors include child and family characteristics, invasive procedures, and social determinants of health. Approaches to remediate PICS-p include early rehabilitation, minimizing sedation, psychosocial resources for caregivers, delivery of family-centered care, and longitudinal screening for PICS-p. Challenges include feasible and validated approaches to screening, and resources and coordination for multidisciplinary care. Next steps should include resources to identify and address adverse social determinants of health and examination of treatment efficacy and implementation equity.

Review of Endometrial Receptivity Array: A Personalized Approach to Embryo Transfer and Its Clinical Applications.

Successful outcomes of in vitro fertilization (IVF) rely on both the formation of a chromosomally normal embryo and its implantation in a receptive endometrium. Pre-implantation genetic testing for aneuploidy (PGT-A) has been widely accepted as a tool to assess the viability of an embryo. In 2011, the endometrial receptivity array (ERA) was first published as a tool to determine when the endometrium is most receptive to an embryo, commonly referred to as the "window of implantation" (WOI). The ERA uses molecular arrays to assess proliferation and differentiation in the endometrium and screens for inflammatory markers. Unlike PGT-A, there has been dissent within the field concerning the efficacy of the ERA. Many studies that contest the success of the ERA found that it did not improve pregnancy outcomes in patients with an already-good prognosis. Alternatively, studies that utilized the ERA in patients with repeated implantation failure (RIF) and transfer of known euploid embryos demonstrated improved outcomes. This review aims to describe the ERA as a novel technique, review the various settings that the ERA may be used in, such as natural frozen embryo transfer (nFET) and hormone replacement therapy frozen embryo transfer (HRT-FET), and provide a summary of the recent clinical data for embryo transfers in patients with RIF utilizing the ERA.

Pediatric rheumatic disease in the intensive care unit: lessons learned from 15 years of experience in a tertiary care pediatric hospital.

OBJECTIVE: This study describes the 15-yr experience of a large urban tertiary care children's hospital in treating critically ill patients with pediatric rheumatic diseases. DESIGN: Retrospective case series. SETTING: Children's Hospital Los Angeles, a large urban tertiary care children's hospital. PATIENTS: All patients with pediatric rheumatic diseases admitted to the Children's Hospital Los Angeles pediatric intensive care unit from January 1995 to July 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An internal database and medical records were reviewed for demographics, diagnoses, treatments, organ dysfunction, interventions, infections, and outcomes. Standardized mortality ratio was calculated based on Pediatric Risk of Mortality III estimated mortality. Factors associated with mortality were identified by univariate analyses.Ninety patients with 122 total admissions were identified. The majority of patients were Hispanic (63%), female (73%), and had systemic lupus erythematosus (62%). Pediatric rheumatic disease-related complications (50%) were the most common reason for admission; 32% of admissions involved multiorgan dysfunction. Eighteen admissions (15%) resulted in mortality. Deaths were most commonly attributed to combined infection and active rheumatic disease (50%), infection only (22%), rheumatic disease only (11%), or other causes (17%). In 30 (25%) admissions, a new rheumatologic diagnosis was established. Standardized mortality ratio was 0.72 (95% confidence interval 0.38-1.25) for pediatric rheumatic disease patients compared to 0.87 (95% confidence interval 0.79-0.96) for all pediatric intensive care unit patients. Factors associated with mortality included use of mechanical ventilation, vasopressors, and renal replacement (continuous venovenous hemodialysis) (all p < .05). CONCLUSIONS: Pediatric rheumatic disease-related complications were the principal cause of pediatric intensive care unit admission. Deaths occurred most often from severe infections in patients with active rheumatic disease. Pediatric rheumatology patients admitted to the pediatric intensive care unit had outcomes similar to the global pediatric intensive care unit population when adjusted for severity of illness.

Obstetric Violence in Their Own Words: How Women in Mexico and South Africa Expect, Experience, and Respond to Violence.

This article, based on ethnographic research in Mexico and South Africa, presents two central arguments about obstetric violence: (a) structural inequalities across diverse global sites are primarily linked to gender and lead to similar patterns of obstetric violence, and (b) ethnography is a powerful method to give voice to women's stories. Connecting these two arguments is a temporal model to understand how women across the world come to expect, experience, and respond to obstetric violence-that is, before, during, and after the encounter. This temporal approach is a core feature of ethnography, which requires long-term immersion and attention to context.

Factors associated with men's opinion about female genital mutilation in Ethiopia.

BACKGROUND: Female genital mutilation (FGM) is considered a human rights violation against women and girls causing serious short and long-term health complications. Despite being a criminal offence in Ethiopia since 2004, the practice continues. Minimal research has been published on factors associated with men's opinion about FGM in Ethiopia. OBJECTIVE AND AIMS: The present cross-sectional study used secondary data to identify factors associated with men's opinions about the practice of FGM. METHODS: Secondary data analysis was conducted using data from 8,718 men who responded to the 2016 Ethiopian Demographic and Health Surveys (EDHS). The dependent variable was men's opinion about FGM. Demographic, socioeconomic, and other characteristics were examined. RESULTS: Variables associated with men's support for FGM were lack of education (AOR = 2.91; 95% CI: 1.93, 4.40, p = <0.001), poor wealth index (AOR, 1.76; 95% CI 1.32, 2.35, p = 0.001), ethnically Afar (AOR = 2.50, 95% CI: 1.27, 4.95, p = 0.009) and Somali (AOR = 2.02, 95% CI: 1.15, 3.54, p = 0.015), Muslim religion (AOR = 1.58, 95% CI 1.13, 2.50, p = 0.007), and support for wife beating with at least one justification (AOR = 2.04, 95% CI: 1.66, 2.50, p = <0.001). CONCLUSION: Lack of education, poor household wealth index, being Muslim and being a member of the Afar or Somali ethnicity and having a tendency that it is appropriate for a husband to beat his wife, were positively associated support for FGM. These findings suggest that context-specific interventions are needed to eradicate the practice.

The petrous bone contains high concentrations of osteocytes: One possible reason why ancient DNA is better preserved in this bone.

The characterization of ancient DNA in fossil bones is providing invaluable information on the genetics of past human and other animal populations. These studies have been aided enormously by the discovery that ancient DNA is relatively well preserved in the petrous bone compared to most other bones. The reasons for this better preservation are however not well understood. Here we examine the hypothesis that one reason for better DNA preservation in the petrous bone is that fresh petrous bone contains more DNA than other bones. We therefore determined the concentrations of osteocyte cells occluded inside lacunae within the petrous bone and compared these concentrations to other bones from the domestic pig using high resolution microCT. We show that the concentrations of osteocyte lacunae in the inner layer of the pig petrous bone adjacent to the otic chamber are about three times higher (around 95,000 lacunae per mm3) than in the mastoid of the temporal bone (around 28,000 lacunae per mm3), as well as the cortical bone of the femur (around 27,000 lacunae per mm3). The sizes and shapes of the lacuna in the inner layer of the petrous bone are similar to those in the femur. We also show that the pig petrous bone lacunae do contain osteocytes using a histological stain for DNA. We therefore confirm and significantly expand upon previous observations of osteocytic lacuna concentrations in the petrous bone, supporting the notion that one possible reason for better preservation of ancient DNA in the petrous bone is that this bone initially contains at least three times more DNA than other bones. Thus during diagenesis more DNA is likely to be preserved in the petrous bone compared to other bones.