Factors influencing the development of Multicystic Dysplastic Kidney (MCDK) following urinary tract obstruction in the fetal lamb.

BACKGROUND: Creating obstructive uropathy (OU) during glomerulogenesis in the fetal lamb results in multicystic dysplastic kidney (MCDK) at term. We explored this using immunohistochemical techniques. METHOD: OU was created in fetal lambs at 60-day gestation, ligating the urethra and urachus. The kidneys of MCDK lambs, 60-day gestation fetal lambs, full-term lamb (145 days), term sham-operated lambs, and adult ewes were evaluated by HE staining, and immunohistochemistry with paired box genes 2 (PAX2) and CD10. RESULTS: Multiple cysts were found in the MCDK model. CD10 was expressed in proximal tubular epithelial cells, glomerular epithelial cells, and medullary stromal cells in the kidneys of 60-day gestation fetal lambs and full-term lambs and adult ewes. PAX2 expression was found in ureteric buds, C- and S-shaped bodies, epithelial cells of collecting ducts, and Bowman's capsule of fetal kidneys at 60-day gestation, but only in the collecting ducts of full-term fetal lambs and adult ewes. Both CD10 and PAX2 were expressed in the cystic epithelial cells of the MCDK model. DISCUSSION: PAX2 expression in cystic epithelial cells suggests that cyst formation is associated with disturbed down-regulation of PAX2 in the nephrogenic zone epithelial cells during the renal development in the OU model.

Muscle imbalance as a cause of scoliosis: a study in a fetal lamb abdominal wall defect model.

BACKGROUND: We created abdominal wall defects (AWD) in fetal lambs to investigate possible causes of scoliosis. METHODS: We incised the upper abdominal wall (including Rectus) in 60-day gestation fetal lambs, from the midline to either the right (Group A) or left (Group B) costal margin, in 14 lambs carried by 7 ewes. They were delivered by cesarean section at term (about 145 days). Scoliosis was evaluated by anterio-posterior X-rays, determining the Cobb angle. RESULTS: Four fetuses in Group A and 3 in Group B survived. There were 3 successful AWD lambs Group A and 2 in Group B. One lamb in each group survived with the AWD covered with a thick capsule. The convexity of spinal curve was the direction of scoliosis. Right scoliosis was only seen in the 4 Group A lambs. Left scoliosis was only seen in Group B lambs (2/3, 67%). The mean Cobb angle was 41.7 ± 11.5° in Group A and in Group B the Cobb angles were 59.6o and 60.6°. Overall, 4/5 lambs with organ prolapse (80%) and both lambs without organ prolapse had scoliosis. CONCLUSION: Muscle imbalance may contribute to the development of scoliosis in a fetal lamb AWD model.

The Expression of Transcription Factors in Fetal Lamb Kidney.

(1) Background: Renal development involves frequent expression and loss of transcription factors, resulting in the activation of genes. Wilms' tumor 1 (WT1), hepatocyte nuclear factor-1-beta (HNF1ß), and paired box genes 2 and 8 (Pax2 and Pax8) play an important role in renal development. With this in vivo study, we examined the period and location of expression of these factors in renal development. (2) Methods: Fetal lamb kidneys (50 days from gestation to term) and adult ewe kidneys were evaluated by hematoxylin and eosin staining. Serial sections were subjected to immunohistochemistry for WT1, HNF1ß, Pax2, and Pax8. (3) Results: Pax2, Pax8, and HNF1ß expression was observed in the ureteric bud and collecting duct epithelial cells. We observed expression of WT1 alone in metanephric mesenchymal cells, glomerular epithelial cells, and interstitial cells in the medullary rays and Pax8 and HNF1ß expression in tubular epithelial cells. WT1 was highly expressed in cells more proximal to the medulla in renal vesicles and in C- and S-shaped bodies. Pax2 was expressed in the middle and peripheral regions, and HNF1ß in cells in the region in the middle of these. (4) Conclusions: WT1 is involved in nephron development. Pax2, Pax8, and HNF1ß are involved in nephron maturation and the formation of peripheral collecting ducts from the Wolffian duct.

Inclusive dissonance-based body image interventions for college students: Two randomized-controlled trials of the EVERYbody Project.

OBJECTIVES: Two randomized-controlled studies explored the feasibility, acceptability, and efficacy of the EVERYbody Project, a gender-inclusive, diversity-focused, dissonance-based body image intervention for college students. METHOD: Trial 1 (N = 98; 80% female, 14% male, and 6% gender-expansive) piloted the two-session intervention delivered by an expert (faculty or staff) and peer cofacilitators compared to a waitlist control. Trial 2 (N = 141; 79% female, 15% male, and 6% gender-expansive) utilized peer leaders, comparing the EVERYbody Project to a video and expressive writing intervention. Around half of the participants in both trials self-identified in one or more specific marginalized identity category. Changes in eating disorder symptoms and risk factors were assessed through 1-month follow-up. Trial 1 also assessed the intervention's impact on students with marginalized identities through qualitative interviews. RESULTS: In Trial 1, the EVERYbody Project produced greater reductions in eating disorder symptoms, internalized appearance norms, body dissatisfaction, and negative affect compared to the waitlist control through 1-month follow-up, with medium effect sizes. The impact was similar in students with marginalized and majority identities, and qualitative interviews suggested specific positives of the intervention. In Trial 2, there were significant changes in two of four outcomes for participants in the EVERYbody Project compared to the video and expressive writing intervention, but overall, the intervention impact was modest. CONCLUSIONS: The EVERYbody Project is a feasible and acceptable inclusive dissonance-based body image program. It appears to be beneficial when delivered via experts, but research is needed to establish whether the program can be delivered using peer leaders with greater impact. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A new approach using image analysis to assess pulmonary hypoplasia in the fetal lamb diaphragmatic hernia model.

BACKGROUND: In congenital diaphragmatic hernia (CDH), there is pulmonary hypoplasia (PH) and also pulmonary vascular and bronchial abnormalities. Few studies have investigated bronchial maldevelopment in CDH. We evaluated bronchial area (BA) by bronchography in a fetal lamb DH model to develop a measure of PH. METHODS: We created DH in fetal lambs at 75 days gestation, delivering by cesarean section and killing them at term (DH, n = 12). Normal term fetuses provided controls (C, n = 5). We measured total lung volume (TLV) and performed barium bronchography. Using image analysis, BA, total lung area (TLA) and bronchial area/lung area ratio (B/L ratio) were calculated. Student's T test (p < 0.05; significant) and Spearman's correlation coefficient were performed. RESULTS: TLV (ml) was 133.3 ± 41.2 in DH and 326 ± 22.5 in C (p = 0.0000001). TLA (cm2) was 78.8 ± 17.4 in DH and 107.1 ± 10.3 in C (p = 0.006). BA (cm2) was 39.6 ± 11.9 in DH and 52.2 ± 7.7 in C (p = 0.019). The B/L ratio was 0.45 ± 0.06 in DH and 0.49 ± 0.05 in C (p = 0.28). There are correlations in DH between TLV and TLA (r = 0.79), TLV and BA (r = 0.73) and in C between TLV and TLA (r = 0.97) and TLV and BA (r = 0.67). CONCLUSION: It may be possible to assess PH on fetal MRI, given the correlation between TLV and TLA, and TLV and BA.

The role of the ureteric bud in the development of the ovine fetal kidney.

BACKGROUND: The kidney develops from an intimate interaction between the ureteric bud and the metanephric mass. We attempted to differentially stain the derivatives of the ureteric bud and the metanephric mass in ovine fetuses. METHODS: After appropriate approval, 47 fetal lambs' kidneys at 50 (4), 60 (6), 70 (5), 80 (4), 100 (10), 110 (8), 145 (10) days' gestation (term is 140-145 days) were obtained. After confirming the pregnancy, the sheep were anesthetized, and the fetuses sacrificed. The fetal kidneys were prepared for histological examination, using immunostaining for ß-catenin, Laminin, CK34ßE12, CK7, E-cadherin, and EMA. RESULTS: In the nephrogenic zone, positive staining was only seen for ß-catenin and Laminin. Areas with linear ß-catenin expression increased with increasing gestational age, whereas cytoplasmic granular expression in the nephrogenic zone diminished. At 50 days, Laminin-positive cells appeared in the ureteric bud epithelial cells, but not in the proximal tubule epithelium. They were found only in the immature collecting duct at 60 days. CONCLUSION: We have shown that the distribution of ß-catenin and Laminin positive-stained cells initially appearing in the ureteric bud changes with gestational age. Further studies may help inform the optimal timing of fetal shunt insertion in obstructive uropathy.

Should body image programs be inclusive? A focus group study of college students.

OBJECTIVE: Most evidence-based body image programs for college students (e.g., the Body Project) are designed for female-only audiences, although body dissatisfaction is not limited to female-identified individuals. Furthermore, programs do not explicitly discuss diversity, although individuals with marginalized gender, racial, and sexual identities may be particularly vulnerable to body image disturbances. Making programs more inclusive may increase their disseminability. METHOD: This qualitative study examined the feasibility of adapting the Body Project for universal and inclusive use with college students. Participants (N = 36; M age = 21.66 years; 73% female-identified; 20% sexual minority; 23% racial minority) attended one of five semi-structured focus groups to explore the inclusivity of appearance-based cultural norms using adapted Body Project activities and discuss the feasibility of universal and inclusive interventions. Inductive qualitative content analysis with three-rater consensus identified focus group themes. RESULTS: There was consensus that inclusive interventions could have a positive impact (broadening perspectives, normalizing body image concerns, increasing awareness) despite potential barriers (poor diversity representation, vulnerability). There was strong consensus regarding advice for facilitating inclusive interventions (e.g., skilled facilitation, education, increasing diversity). DISCUSSION: Results suggest that inclusive body image programs are desirable and provide a framework for creating the EVERYbody Project, a program for more universal audiences.

Evaluation of alveolar epithelial cells in the sheep model of congenital diaphragmatic hernia: Type 1 alveolar epithelial cells and histopathological image analysis.

BACKGROUND: There are few reports comparing type 1 alveolar epithelial cell development with histopathological image analysis. We investigated these as indicators of maturity in fetal lambs' lungs in a congenital diaphragmatic hernia (CDH) model. METHODS: We created left CDH in 4 fetal lambs at 75 or 76days' gestation (Group A). Controls were 5 sham-operated lambs (Group B); both groups delivered at term. The right lower lung lobe (RLL) and left lower lobe (LLL) were sampled. Using histopathological image analysis, alveoli/air sacs count (AC), alveoli/air sacs area percentage (AP), average area (AA), total area (TA), and perimeter (PM) were determined. We also evaluated total lung volumes, radial alveolar count (RAC), and Type 1 alveolar epithelial cells ratio (AT1 ratio), which we previously reported. Regression analysis was performed, with p<0.05 considered significant. RESULTS: RLL and LLL AT1 ratio and LLL RAC in Group A were lower than in Group B. There are no significant differences demonstrated by histopathological image analysis. In Group A, the AT1 ratio in the LLL was lower than in the RLL. There were no differences between LLL and RLL in Group B. CONCLUSION: AT1 ratio was superior to the other indicators evaluating lung maturity.

Does a large abdominal wall defect affect lung growth?

BACKGROUND/PURPOSE: Respiratory distress in babies with large abdominal wall defects suggests a relationship to decreased diaphragmatic movement. We evaluated pulmonary development in a fetal lamb gastroschisis model. METHODS: We created gastroschisis in 25 fetal lambs at 60days gestation (group A). Controls were 14 nonoperated lambs. (Group B) were all delivered at term. Lung volume, histology, and type 1 (AT1)/type 2 (AT2) cell ratios (AT1 ratio) were determined. We subdivided group A, comparing lambs with a large defect and scoliosis [group A (S)] with the remainder [group A (NS)]. RESULTS: Twenty-five lambs survived (11 fetuses in group A and 14 fetuses in group B). Lung volume in group A (S) was less than in group A (NS) (p<0.05). The AT1 ratio in group A was lower than in group B (p<0.01), without any difference in radial alveolar counts (RACs) or alveolar growth, and no association between scoliosis and alveolar differentiation. CONCLUSION: Gastroschisis in a sheep model reduces the AT1 ratio but not the RAC. Severe scoliosis affects lung volume but not the AT1 ratio, suggesting reduced diaphragmatic movement in fetuses with large abdominal defects.

Childhood cholecystectomy in New Zealand: A multicenter national 10year perspective.

AIM: International studies show increasing incidence of cholelithiasis in childhood and an increasing caseload for the pediatric surgeon. We reviewed pediatric cholecystectomy in all four centers in New Zealand, examining changes in incidence and the demographics of the patient population. METHOD: Coding data were used to retrieve case notes and extract demographic data, diagnosis, comorbidities, length of stay, and complications for patients less than 16years old undergoing cholecystectomy from January 1st, 2004-December 31st, 2013. Patients with congenital biliary malformations were excluded. Statistical analysis was performed using SPSS. RESULTS: 170 children required cholecystectomy. On average, 15 procedures were performed annually (IQR 8-24). There was a slight upward trend, with a gradient of 0.34 (P=0.63). Median age was 14 (range 2-15)years, male:female 2:3. While 72% of children were Caucasian, Maori were significantly overrepresented (20%). Numbers of Pacific Islander increased significantly over time (P=0.05), in line with population increases. Of 114 patients with complete dataset, 31% were overweight or obese. Complication rates were 8.8% overall, but 27% of complications occurred in Maori children. 40% of those suffering a complication were obese. Three complications were major, requiring return to theater. Mean length of stay was 5days. CONCLUSIONS: New Zealand has not seen the rapid increase in pediatric cholecystectomy experienced elsewhere in the OECD. However, the problem of adolescent biliary disease is prevalent. The average recipient of a cholecystectomy is 14years old, overweight, and Caucasian; though Maori have a high relative risk of both biliary disease and complicated postoperative course. The reasons for this remain unclear and require further study.

Intestinal perforation in premature neonates: The need for subsequent laparotomy after placement of peritoneal drains.

AIM: In view of recent studies questioning the usefulness of peritoneal drainage (PD) in premature neonates with pneumoperitoneum, suggesting approximately 75% of those treated with PD needed delayed laparotomy, we reviewed the requirement for laparotomy after initial PD at our institution. METHODS: Retrospective cohort of all premature infants with a diagnosis of intestinal perforation (ICD Code P78.0) from 1995 to 2012. Inclusion criteria were pneumoperitoneum on x-ray (isolated perforation or necrotising enterocolitis), birthweight <1800 g and gestational age <33 weeks. RESULTS: Fifty patients met the criteria (38 PD, 12 primary laparotomy). Thirty-two per cent (95% CI 18-49%) received secondary laparotomy after initial PD. There was no significant difference when stratified according to isolated perforation (24%) versus necrotising enterocolitis (56%, P = 0.11). There was no significant difference between PD and primary laparotomy for time to full enteral nutrition, hazard ratio (HR) 0.99 (95% CI 0.48-2.04) or mortality, HR 2.15 (95% CI 0.48-9.63). The HR for mortality was partly confounded by birthweight, birthweight-adjusted HR 1.52 (95% CI 0.32-7.23). CONCLUSIONS: Thirty-two per cent of neonates treated with primary PD received secondary laparotomy, with no significant difference in key outcomes. Primary PD still appears to be of benefit for those without features of necrotising enterocolitis.

Pressure limited vesico-amniotic shunt allows normal lung growth in a fetal lamb model of obstructive uropathy.

BACKGROUND: In our fetal lamb model of lower urinary tract obstruction, a pressure limited shunt preserves bladder function and renal development. This study investigates the effects on pulmonary histology. METHODS: We created obstructive uropathy (OU) in 60-day gestation fetal lambs, ligating the urethra and urachus, and delivering them at term (130-145days). We compared pulmonary histology in 4 groups: group A, OU without shunt; group B, pressure limited shunt; group C, non-valved shunt. Shunts were inserted 3weeks post-obstruction. Group D were normal controls. RESULTS: We compared 27 fetuses: 7 fetuses in group A, 4 fetuses in group B, 2 fetuses in group C, and 14 fetuses in group D. There was no significant difference in lung volume in any group. In group A, there were some areas of atelectasis and incomplete alveolar formation histologically. The alveoli in group A lambs lungs had a predominance of type II cells, whereas group B lambs lungs were lined by type I epithelial cells and were essentially indistinguishable from controls. CONCLUSIONS: This study suggests that using a pressure-limited vesico-amniotic shunt in OU may preserve the renal tract and the lungs.

Can a pressure-limited V-A shunt for obstructive uropathy really protect the kidney?

BACKGROUND: In our fetal lamb model of lower urinary tract obstruction, a valved shunt preserves bladder function. This study investigates the effects on renal histology. METHODS: We created obstructive uropathy (OU) in 60-day gestation fetal lambs, ligating the urethra and urachus, and delivering them at term (130-145days). We compared renal histology in 4 groups: group A-OU without shunt, group B-low-pressure shunt (15-54mmH2O), group C-high-pressure shunt (95-150mmH2O). Shunts were inserted 3weeks post-obstruction. Group D were normal controls. RESULTS: We delivered 32 fetuses from 23 ewes: 13 fetuses in group A (9 survived), 6 fetuses in group B (5 survived), 7 fetuses in group C (5 survived), and 6 fetuses in group D. Histologically, we found renal tubular distention, vacuolated degeneration of tubular epithelial cells in 7 lambs, and cyst formation in 4 lambs in group A. There was renal tubular distention in two lambs, and cyst formation in one lamb in both groups B and C, with vacuolated degeneration of tubular epithelial cells observed in all but 1 lamb in each group. CONCLUSIONS: V-A shunting prevents multicystic dysplastic kidney (MCDK). Some lambs have renal tubular distention and vacuolated degeneration of renal tubular epithelial cells.

Position statement on fetal myelomeningocele repair.

Following the promising multicenter randomized trial results of in utero fetal myelomeningocele repair; we anticipate that an increasing number of tertiary care centers may want to offer this therapy. It is essential to establish minimum criteria for centers providing open fetal myelomeningocele repair to ensure optimal maternal and fetal/pediatric outcomes, as well as patient safety both short- and long-term; and to advance our knowledge of the role and benefit of fetal surgery in the management of fetal myelomeningocele. The fetal myelomeningocele Maternal-Fetal Management Task Force was initially convened by the Eunice Kennedy Shriver National Institute of Child Health and Human Development to discuss the implementation of maternal fetal surgery for myelomeningocele. The decision was made to develop the optimal practice criteria presented in this document for the purpose of medical and surgical leadership. These criteria are not intended to be used for legal or regulatory purposes.

Valved shunt as a treatment for obstructive uropathy: does pressure make a difference?

PURPOSE: A valved ventriculo-peritoneal shunt (V-P shunt) as a vesico-amniotic shunt (V-A shunt) preserves the filling/emptying cycle and normal bladder development in fetal lambs with bladder outlet obstruction. The optimal pressure for such shunts is unknown. MATERIALS AND METHODS: We created obstructive uropathy in 60-day gestation fetal lambs. A V-A shunt was placed 3 weeks later, using a low-pressure (Group L: 15-54 mmH2O) or a high-pressure (Group H: 95-150 mmH2O) V-P shunt. We included non-shunted (obstructive uropathy, Group O) and control lambs (Group C). All were delivered at 130 days. Bladder volumes, bladder thickness, renal and bladder histology were compared. RESULTS: Seventeen lambs had an obstructive uropathy created. Five Group L (four survived), four Group H (three survived) and five Group O survived. Body weight and crown-to-rump lengths of the three groups were not significantly different. Group H lambs had a dilated urachus, urinary ascites and severe ureteral dilatation similar to Group O lambs. There were four Group C lambs. Bladder volume was 10, 15 and 1,150 ml in Group H, 115 ± 67.9 ml in Group L, 128 ± 99.8 ml in Group O and 24.5 ± 3.84 ml in Group C. Unlike Group O lambs, Group L did not have urinary ascites, urinomas or renal dysplasia. CONCLUSION: Low-pressure shunts preserved both bladder volume and renal development. High-pressure shunts did neither.

Bladder development following bladder outlet obstruction in fetal lambs: optimal timing of fetal therapy.

BACKGROUND: Lower urinary tract obstruction causes both renal failure and bladder dysfunction after birth. This study examined the early bladder wall changes after creating an obstructive uropathy focusing on bladder wall thickness and muscle integrity. METHODS: We created obstructive uropathy in fetal lambs at 60 days' gestation, ligating the urethra and urachus. The fetuses (n = 28) were delivered at 48 hours and 3, 4, 5, 7, and 14 days after obstruction and at term (145 days' gestation). Sham-operated lambs were used as controls (n = 20). Histology samples were stained using α-smooth muscle actin) immunohistochemistry and also hematoxylin-eosin, Masson trichrome, and colloidal Fe stain. RESULTS: The bladder wall initially expanded and stretched. By day 4, the bladder wall became thicker. Histologically, the bladder in obstructed lambs demonstrated a prominent submucosal fibrotic change by 7 days. The mean bladder wall thickness at 14 days after obstruction was thicker than controls, and fibrosis was prominent. CONCLUSION: The initial changes in the bladder wall were expansion of the muscle component followed by fibrosis. The bladder wall thickness dramatically increased 4 to 7 days after obstruction. We conclude that shunting operations to preserve bladder function may be needed earlier than expected.

Rising incidence of gastroschisis and exomphalos in New Zealand.

BACKGROUND: An apparent increase in the incidence of gastroschisis and exomphalos has been reported from several parts of the world. The exact mechanism of this trend is unknown. The aim of this study was to determine the regional and national trends in the incidence of gastroschisis and exomphalos in New Zealand. MATERIAL AND METHODS: This retrospective multicenter study involved collection of data from all 4 tertiary care pediatric surgical centers in New Zealand. The incidence was calculated per 10,000 live births. Data were analyzed to determine the regional and national trends. The statistical analysis was done using linear regression model and Poisson distribution. RESULTS: The incidence of gastroschisis has increased from 2.96 per 10,000 live births to 5.16 per 10,000 live births between 1996 and 2004. During the same period, the incidence of exomphalos has increased from 0.69 per 10,000 live births to 3.27 per 10,000 live births. Gastroschisis was observed more in younger mothers, whereas exomphalos was associated with older mothers. CONCLUSION: The incidence of gastroschisis and exomphalos is increasing in New Zealand, which is consistent with worldwide trends in showing the increasing incidence of anterior abdominal wall defects.

Placenta accreta in the first trimester of pregnancy: sonographic findings.

In a case of histologically confirmed placenta increta, decidual protrusion into the myometrium was observed sonographically at 6 weeks' gestation, corresponding to placental protrusion from a disrupted placental-uterine wall interface seen in the later part of the first and second trimester. It is hypothesized that the histologic finding of decidual scarcity in placenta accreta is not a cause but rather an end result of the recruitment of trophoblasts across the decidual-placental interface in a maternal attempt at healing and/or repair in the presence of uterine injury, disease, or malformation that accounts for the associated factors and course of the condition.

Can a pressure-limited vesico-amniotic shunt tube preserve normal bladder function?

INTRODUCTION: We have previously shown that a vesico-amniotic shunt (V-A shunt) produces fibrotic bladders with poor compliance in normal fetal lambs. We hypothesized that using a ventriculo-peritoneal shunt (V-P shunt) as a V-A shunt in normal bladders may preserve the filling/emptying cycle and normal bladder development. MATERIALS AND METHODS: The V-A shunting in normal fetal lambs was performed at 74 days of gestation using a V-P shunt (group A) and a free-draining shunt tube (group B). Sham-operated lambs were used as controls (group C). They were all delivered at term (145 days), and the pressure-volume curve, bladder volume, and histologic features of the bladder wall were compared. RESULT: The mean bladder volume in group B (n = 5), 5 +/- 2.4 mL, was significantly smaller (P < .01) than that in group A (n = 6), 53 +/- 14 mL, and group C (n = 10), 57.3 +/- 12 mL. The bladder wall thickness in group A was 338 + 94.2 microm; group B, 741 +/- 128 microm; and group C, 374 +/- 120 microm. Group B bladders had very poor compliance with thick bladder wall (P < .01). Histologically, group B bladders showed prominent submucosal fibrotic change, but group A bladders were similar to controls. CONCLUSION: This study shows that a pressure-limited shunt tube for V-A shunting preserves the normal fetal bladder development.

Antenatal topographical assessment of placenta accreta with ultrasound.

The major risk of placenta accreta is severe haemorrhage when the placenta is separated at delivery. A case series of placenta accreta with antenatal sonographic topographical assessment of myometrial involvement is presented. The extent of myometrial involvement and the vascularity could be assessed by the observation of the extent of placental-uterine wall interface disruption and the vessels crossing the interface disruption sites. Such assessment results in strategic planning of management of the placenta at delivery with favourable pregnancy outcomes.