Impact of Transfer of Maternal Care for Fetal Anomalies on Maternal Depression and Anxiety Screening: A Prospective Cohort at a Tertiary Care Center.

INTRODUCTION: Perinatal depression and anxiety are major causes of maternal morbidity, and are more common in high-risk pregnancies compared to low-risk pregnancies. This study used validated screening tools to assess the prevalence of depression and anxiety symptoms in pregnant patients who transferred their obstetric care to a specialized fetal center for fetal anomaly. METHODS: This is a prospective cohort of patients with a fetal anomaly prompting transfer of obstetric care to Texas Children's Hospital Fetal Center between January 2021 and February 2022. The primary outcome was a self-assessed Edinburgh Postnatal Depression Scale score of 13 or higher, either antepartum or postpartum ("ever-positive EPDS"). Secondary outcomes included self-assessed Perinatal Anxiety Screening Scale (PASS) scores of 21 or higher ("ever-positive PASS"), obstetric outcomes, and neonatal outcomes. A frequentist analysis was performed. RESULTS: Of 149 women who transferred to Texas Children's Hospital during the study period, 94 enrolled in this study. Twenty-six percent of women had an ever-positive EPDS; 20% of patients had an ever-positive PASS. Patients were more likely to have an ever-positive EPDS if they were single (46% compared to 20%, p = 0.025). Women who had an ever-positive EPDS were more likely to be referred to psychiatry (46% compared to 14%, p = 0.004) and psychotherapy (29% compared to 1%, p < 0.001). Surprisingly, patients were more likely to have an ever-positive PASS if they reported good social support (p = 0.03). Antepartum EPDS and PASS scores had no relationship with postpartum EPDS scores. CONCLUSION: Women who transfer care to a tertiary setting have positive EPDS scores at double the rate of the general population, but tend to experience this either antepartum or postpartum (not both). Fetal centers should be prepared to screen for mental health symptoms before and after delivery and provide appropriate referral or treatment.

Myositis ossificans: a rare neonatal presentation.

Myositis ossificans is a benign, ossifying, soft-tissue pseudotumor that most commonly occurs in men ages 30-40 years after trauma. Myositis ossificans may also occur in children, but it is extremely rare in those younger than 10 years of age. While myositis ossificans can often mimic malignant soft-tissue tumors, it has many unique findings that can aid in diagnostic differentiation. This differentiation is critical to avoid unnecessary risk with potentially harmful procedures. We present a very unusual presentation of myositis ossificans in the immediate post-birth perinatal period, as well as a review of key imaging findings.

Outcomes in pediatric patients with documented delays between ileocolic intussusception diagnosis and therapeutic enema attempt: evaluation of reduction efficacy and complication rate.

BACKGROUND: Ileocolic intussusception is considered a pediatric emergency, with concerns for risk of significant morbidity in children with a prolonged intussusception state. Emergent therapy is standard of care, as prior studies have shown poor outcomes in patients with long delays (> 24 h) before intervention. Various factors can result in shorter delays, and there are limited studies evaluating outcomes in these patients. This study aimed to determine if there were differences in reduction success rates associated with short in-hospital time delays. OBJECTIVE: This study is to determine enema success rate and morbidity in patients with documented time delays between intussusception diagnosis and therapeutic enema. MATERIALS AND METHODS: A retrospective evaluation of pediatric patients with intussusception at a single children's hospital between 2007 and 2019 was performed. Patient's records were reviewed for time of symptom onset, radiologic diagnosis, and attempted enema. Ultrasounds and radiographs were reviewed for bowel obstruction, free peritoneal fluid, trapped fluid around the intussusceptum, and absent bowel wall perfusion. Patients were evaluated for efficacy of reduction attempt, requirement for surgical reduction, and complications including bowel resection and bowel perforation. RESULTS: There were 175 cases of ileocolic intussusception requiring enema reduction. Successful reduction occurred in 72.2% (13/18) of cases performed within 1 h of diagnosis; 74.3% (78/105) between 1 and3 h; 73.2% (30/41) between 3 and 6 h; and 81.2% (9/11) with greater than 6 h. Need for bowel resection was not associated with short delays between diagnosis and reduction attempts (p = .07). CONCLUSIONS: There was no difference in intussusception reduction efficacy or complication rate in patients with increasing time between imaging diagnosis of ileocolic intussusception and reduction attempt, including delay intervals up to 8 h.

Additive effects of nicotine and high-fat diet on hepatocellular apoptosis in mice: involvement of caspase 2 and inducible nitric oxide synthase-mediated intrinsic pathway signaling.

Smoking is a major risk factor for diabetes and cardiovascular disease and may contribute to nonalcoholic fatty liver disease (NAFLD). The health risk associated with smoking is exaggerated by obesity and is the leading causes of morbidity and mortality worldwide. We recently demonstrated that combined treatment with nicotine and a high-fat diet (HFD) triggers greater oxidative stress, activates hepatocellular apoptosis, and exacerbates HFD-induced hepatic steatosis. Given that hepatocellular apoptosis plays a pivotal role in the pathogenesis of NAFLD, using this model of exacerbated hepatic steatosis, we elucidated the signal transduction pathways involved in HFD plus nicotine-induced liver cell death. Adult C57BL6 male mice were fed a normal chow diet or HFD with 60% of calories derived from fat and received twice daily IP injections of 0.75 mg/kg BW of nicotine or saline for 10 weeks. High-resolution light microscopy revealed markedly higher lipid accumulation in hepatocytes from mice received HFD plus nicotine, compared to mice on HFD alone. Addition of nicotine to HFD further resulted in an increase in the incidence of hepatocellular apoptosis and was associated with activation of caspase 2, induction of inducible nitric oxide synthase (iNOS), and perturbation of the BAX/BCL-2 ratio. Together, our data indicate the involvement of caspase 2 and iNOS-mediated apoptotic signaling in nicotine plus HFD-induced hepatocellular apoptosis. Targeting the caspase 2-mediated death pathway may have a protective role in development and progression of NAFLD.

Laparoscopy-assisted fetoscopy for laser surgery in twin-twin transfusion syndrome with anterior placentation.

OBJECTIVE: To compare a laparoscopy-assisted fetoscopic approach with an ultrasound-directed percutaneous approach for laser photocoagulation of placental anastomoses in cases of twin-twin transfusion syndrome (TTTS) with anterior placentation. METHOD: We performed a retrospective review of all cases that underwent laser ablation of placental anastomoses for TTTS with an anterior placenta at Texas Children's Fetal Center from November 2006 to November 2008. The two cohorts were identified by chart review based on the type of approach: laparoscopy-assisted vs. ultrasound-guided percutaneous uterine entry for fetoscopy. Operative and outcome data were extracted and the groups were compared using statistical methods, taking P < 0.05 as statistically significant. RESULTS: In the 100 cases of TTTS studied, 48 had an anterior placenta. Fifteen (31%) of these underwent laparoscopy-assisted fetoscopy (LAF) while a percutaneous approach was used in the remaining 33 (69%) cases. The total procedure time was longer in the LAF group than in the percutaneous group (96.1 +/- 25 vs. 67.9 +/- 28 min; P < 0.01). There was no difference in the rate of preterm premature rupture of membranes up to 2 weeks and 4 weeks after surgery (7 vs. 15% and 13 vs. 21%, for the LAF group vs. the percutaneous group, respectively; P = 0.7). The gestational ages at delivery were similar: 30.3 +/- 4.5 weeks in the LAF group and 29.2 +/- 4.6 weeks in the percutaneous group (P = 0.32). The overall survival rate at birth was tending towards better survival in the laparoscopic group than in the percutaneous group (80 vs. 61%, respectively; P = 0.06). The neonatal survival rate was better with the LAF approach than with the percutaneous approach (80 vs. 59%, respectively; P = 0.045). CONCLUSION: Laparoscopy-assisted entry of the uterus is associated with improved neonatal survival for laser photocoagulation in cases of TTTS with a complete anterior placentation.

Effects of retinoids on cancerous phenotype and apoptosis in organotypic cultures of ovarian carcinoma.

BACKGROUND: Retinoic acid analogues, called retinoids, have shown promise in clinical trials in preventing breast and ovarian cancers. Classic retinoids bind to retinoic acid receptors, which regulate cell growth. Some novel retinoids, such as fenretinide, i.e., N-(4-hydroxyphenyl)retinamide (4-HPR), induce apoptosis through retinoic acid receptor-independent mechanisms; however, they appear to do so only at concentrations above those achieved in clinical chemoprevention trials. At lower concentrations (< or =1 microM), 4-HPR acts like classic retinoids, by inducing differentiation through a receptor-dependent mechanism. Our goal was to compare the effects of novel receptor-independent (apoptotic) retinoids with those of classic growth-inhibitory retinoids at clinically achievable doses on growth, differentiation, and apoptosis in ovarian tissue. METHODS: Four receptor-independent (apoptotic) and seven growth-inhibitory retinoids, including synthetic, low-toxicity compounds called heteroarotinoids, were administered at concentrations of 1 microM to organotypic cultures of ovarian primary and cancer cell lines: OVCAR-3, Caov-3, and SK-OV-3. After fixation, embedding, and sectioning, the growth fraction was quantified by measuring expression of the proliferation marker Ki-67/myb, differentiation was assessed by expression of mucin, and apoptosis was evaluated by the TUNEL assay. Spearman correlation analysis was performed on the data, and all P values were two-sided. RESULTS: All 11 retinoids reversed characteristics associated with the cancerous phenotype in all neoplastic cultures. Glandular structures were observed consistently in retinoid-treated, but not in untreated, OVCAR-3 and Caov-3 cultures. All retinoids decreased growth fractions, and some increased mucin expression. All receptor-independent retinoids and two receptor-dependent retinoids induced apoptosis, and the induction correlated significantly with increased expression of the mucin MUC1 (r =.83; P =.03). Retinoids with ester-linking groups did not induce apoptosis but decreased the growth fraction in correlation with MUC1 induction (r = -.93; P =.02). CONCLUSIONS: At clinically achievable concentrations, all retinoids tested decrease the growth fraction, induce differentiation and apoptosis. Induction of MUC1 expression is implicated in the mechanisms of action.

Synthesis, structure-activity relationships, and RARgamma-ligand interactions of nitrogen heteroarotinoids.

Three heteroarotinoids containing a nitrogen atom in the first ring and a C-O linking group between the two aryl rings were synthesized and evaluated for RAR and RXR retinoid receptor transactivation, tumor cell growth inhibition, and transglutaminase (TGase) induction. Ethyl 4-(N,4,4-trimethyl-1,2,3,4-tetrahydroquinolinyl)benzoate (1) contained an N-CH(3) group and activated all retinoid receptors except for RARgamma. Inceasing the hydrophobicity around the rings with analogues ethyl 4-(N,4,4,7-tetramethyl-1,2,3, 4-tetrahydroquinolin-6-oyloxy)benzoate (2) [7-methyl group added] and ethyl 4-(4,4-dimethyl-N-isopropyl-1,2,3, 4-tetrahydroquinolin-6-oyloxy)benzoate (3) [NCH(CH(3))(2) group at C-4] increased the potency and specificity for RARalpha, RARbeta, and RXRalpha, compared to 1, but had little effect on RXRbeta and RXRgamma activation. Although 1 and 3 were unable to activate RARgamma, 2 did activate this receptor with efficacy and high potency equal to that of 9-cis-retinoic acid (9-c-RA). All three heteroarotinoids exhibited 5-8-fold greater specificities for RARbeta over RARalpha. In addition, esters 1-3 inhibited the growth of two cell lines each derived from cervix, vulvar, ovarian, and head/neck tumors with similar efficiencies to that of 9-c-RA through a mechanism independent of apoptosis. The vulvar cell lines were the most sensitive, and the ovarian lines were the least sensitive. Ester 2 was similar to 1 and 3 except that 2 was a much more potent growth inhibitor of the two vulvar cell lines, which is consistent with strong RARgamma activation by 2 (but not by 1 and 3) and the high levels of RARgamma expression in skin. All three heteroarotinoids induced production of TGase, a marker of retinoid activity in human erythroleukemic cells. Esters 2 and 3 were the more potent TGase activators than 1, in agreement with the stronger activation of the RAR receptors by 2 and 3. The biological activities of these agents, and the RARgamma potency of 2 in particular, demonstrate the promise of these compounds as pharmaceutics for cancer and skin disorders.

In vivo and in vitro interaction of DnaK and a chloroplast transit peptide.

Chloroplast transit peptides have been proposed to function as substrates for Hsp70 molecular chaperones. Many models of chloroplast protein import depict Hsp70s as the translocation motors that drive protein import into the organelle, but to our knowledge, no direct evidence has demonstrated that transit peptides function either in vivo or in vitro as substrates for the chaperone. In this report, we demonstrate that DnaK binds SStp (the full-length transit peptide for the precursor to the small subunit of Rubisco) in vivo when fused to either glutathione-S-transferase (GST) or to an His6-S-peptide tag (His-S) via an ATP-dependent mechanism. Three independent biophysical and biochemical assays confirm the ability of DnaK and SStp to interact in vitro. The cochaperones, DnaJ and GrpE, were also associated with the DnaK/SStp complex. Therefore, both GST-SStp and His-S-SStp can be used as affinity-tagged substrates to study prokaryotic chaperone/transit peptide interactions as well as to provide a novel functional probe to study the dynamics of DnaK/DnaJ/GrpE interactions in vivo. The combination of these results provides the first experimental support for a transit peptide-dependent interaction between a chloroplast precursor and Hsp70. These results are discussed in light of a general mechanism for protein translocation into chloroplasts and mitochondria.

Antigenic peptides complexed to phylogenically diverse Hsp70s induce differential immune responses.

The Hsp70 class of heat shock proteins (Hsps) has been implicated at multiple points in the immune response, including initiation of proinflammatory cytokine production, antigen recognition and processing, and phenotypic maturation of antigen-presenting cells (APCs). This class of chaperones is highly conserved in both sequence and structure, from prokaryotes to higher eukaryotes. In all cases, these chaperones function to bind short segments of either peptides or proteins through an adenosine triphosphate-dependent process. In addition to a possible role in antigen presentation, these chaperones have also been proposed to function as a potent adjuvant. We compared 4 evolutionary diverse Hsp70s, E. coli DnaK, wheat cytosolic Hsc70, plant chloroplastic CCS1, and human Hsp70, for their ability to prime and augment a primary immune response against herpes simplex virus-1 (HSV1). We discovered that all 4 Hsp70s were highly effective as adjuvants displaying similar ability to lipopolysaccharides in upregulating cytokine gene expression. In addition, they were all capable of inducing phenotypic maturation of APCs, as measured by the display of various costimulatory molecules. However, only the human Hsp70 was able to mediate sufficient cross-priming activity to afford a protective immune response to HSV1, as judged by protection from a lethal viral challenge, in vitro proliferation, cytotoxicity, and intracellular interferon-gamma production. The difference in immune response generated by the various Hsp70s could possibly be due to their differential ability to interact productively with other coreceptors and different regulatory cochaperones.

Peritoneal fluid lactic acid and diagnostic dilemmas in acute abdominal disease.

Our previous canine research suggested that the determination of peritoneal fluid lactic acid levels may be helpful in the evaluation of potential acute abdomen cases. To investigate the clinical significance of those findings, we obtained simultaneous peritoneal and plasma lactic acid values from patients undergoing emergency celiotomy or in whom surgical consultation was sought to rule out an acute abdomen. The lactic acid value was significantly higher in peritoneal fluid than in plasma in patients who were found to have hollow viscus perforation, gangrenous intestine, peritonitis, or intra-abdominal abscess. In contrast, the values were similar in patients who did not have those conditions. Our findings suggest that the calculated difference between simultaneous peritoneal and plasma lactic acid values is a helpful diagnostic index for patients in whom the diagnosis of acute abdomen is not otherwise obvious.

Comparison of adhesion formation in transperitoneal laparoscopic herniorrhaphy techniques.

Two techniques of transperitoneal laparoscopic inguinal hernia repair were studied to evaluate the incidence of short term adhesion formation. Two methods were evaluated in thirty pigs with induced bilateral inguinal hernia defects. Half of the defects were repaired by incising the peritoneum, placing the mesh over the muscle defect, securing the mesh with staples, and reapproximating the peritoneum over the defect with staples. The other hernias were repaired by positioning the mesh over the defect and securing the mesh with staples, with no reapproximation of the peritoneum. The animals were allowed to recover and were killed at the end of two weeks. At autopsy, the animals were examined for the presence of adhesions to bowel. A statistically greater number of adhesions were formed with peritoneal reapproximation, 43 per cent (13/30), compared with 10 per cent (3/30) when the peritoneum was not reapproximated. The simpler method of repair, with no reapproximation, resulted in a statistically lower incidence of adhesions.

P300 response: habituation.

This study used the "oddball" counting paradigm to examine the possible habituation of the auditory P300 response. Twenty subjects kept a mental record of the number of rarely occurring tone pips presented in a series of more frequently occurring tone pips. Data were collected continuously until responses to 150 rare tone pips were obtained. Findings indicated that the P300 complex decreased in amplitude as a result of repeated stimulation. The decline was logarithmic, not linear, which suggests a stabilization of the amplitude over time. We suggest that the attenuation of amplitude was habituation and not a result of a recovery cycle.

EXIT-to-resection for fetuses with large lung masses and persistent mediastinal compression near birth.

PURPOSE: To identify prenatal diagnostic features that will help select fetuses with lung masses (LM) who may benefit from ex-utero intrapartum treatment (EXIT procedure) as the preferred mode of delivery. METHODS: The CCAM-volume ratio (CVR), fetal treatment, and outcomes of all fetuses with LM evaluated between 2001 and 2011 were reviewed retrospectively. Fetuses with hydrops or CVR>1.6 were classified as high risk. Indications for fetal interventions included hydrops and heart failure, and indication for EXIT-to-resection was the finding of persistent mediastinal compression (PMC) near birth. RESULTS: Of 110 fetuses evaluated for LM, 78 were classified as low-risk. No fetus in this group had PMC near birth and none required perinatal treatment. Of 32 high-risk fetuses, 8 developed heart failure of which 4 survived (3 following fetal surgery). Nine high-risk fetuses with no PMC near birth were asymptomatic postnatally and treated electively. Sixteen high-risk fetuses had PMC near birth. All 9 babies with PMC treated with EXIT-to-resection did well with discharge at a median of 10 days post-operatively. All 7 fetuses treated without an EXIT developed respiratory distress following birth requiring an urgent operation; 2 died. CONCLUSION: The EXIT-to-resection procedure is a favorable delivery approach for those fetuses with large LM and PMC near birth.

Ex-utero intrapartum treatment procedure for giant neck masses--fetal and maternal outcomes.

BACKGROUND/PURPOSE: For fetuses with giant neck masses and tracheal obstruction, an ex-utero intrapartum treatment (EXIT) procedure allows for safe nonemergent airway management while on placental support. Our objective was to examine fetal and maternal outcomes after EXIT procedure specifically for giant neck masses. METHODS: The medical records of all patients referred to a comprehensive fetal center for a giant neck mass between 2001 and 2010 were reviewed retrospectively. RESULTS: Among 24 patients referred, an EXIT procedure was performed in 12 with evidence of tracheal compression. An EXIT procedure was not performed because of minimal tracheal involvement (n = 8), elective abortion (n = 2), fetal demise (n = 1), or obstetric complication (n = 1). In all fetuses, the airway was successfully secured; tracheal intubation was achieved with rigid bronchoscopy (n = 10), direct laryngoscopy (n = 1), and tracheostomy (n = 1). Eleven patients survived to discharge, whereas 1 patient with significant pulmonary hypoplasia died 8 days after emergency EXIT procedure. Of 11 surviving infants, 10 are neurodevelopmentally intact. All mothers who desired future pregnancies have subsequently had uncomplicated deliveries (n = 6). CONCLUSIONS: Ex-utero intrapartum treatment procedure for giant neck mass can be performed safely for both mother and child. Most fetuses can be orotracheally intubated with minimal long-term morbidity. The potential for future pregnancies is preserved.

Hurricane Katrina: medical response at the Houston Astrodome/Reliant Center Complex.

On September 1, 2005, with only 12 hours notice, various collaborators established a medical facility--the Katrina Clinic--at the Astrodome/Reliant Center Complex in Houston. By the time the facility closed roughly two weeks later, the Katrina Clinic medical staff had seen over 11,000 of the estimated 27,000 Hurricane Katrina evacuees who sought shelter in the Complex. Herein, we describe the scope of this medical response, citing our major challenges, successes, and recommendations for conducting similar efforts in the future.

Tympanometric curves and otosclerosis.

Patients with clinical otosclerosis (28 ears) were examined audiometrically and with an electroacoustic impedance bridge. The results were compared to corresponding findings for normal ears. The tympanometric curves of surgically proven otosclerosis were found to differ characteristically from those of normal ears. A curve typical of footplate fixation shows a rapid increase in acoustic impedance as external auditory canal pressure is reduced from ambient air pressure.

Middle-component AERs during backward masking.

This study examined the middle-component averaged electroencephalic response (AER) to tonal stimuli presented in a backward-masking paradigm. Ss were 4 normal-hearing young adults. Tone-Only (TO), Masker-Only (MO), and Tone-Masker (TM) responses were collected. The visual impression was that the TO response was not significantly different from the extracted response to the tone (T) from the TM response. This result obtained when the tone in the TM condition was presented either slightly above (+5 db) or slightly below (-5 db) perceptual threshold. Backward masking was discussed in terms of two contrasting views of the auditory system: the classical auditory nervous system alone and a parallel system combining the classical auditory and the reticular sensory systems. Speculations were made for each system regarding the type of AER expected for a stimulus submerged in backward masking. The mechanism responsible for backward masking was seen as a preperceptual device that allows discrete samples of the auditory environment to be processed. This mechanism was discussed in terms of its possible relation to forward masking and to loudness enhancement.

Effect of paracetamol on gastric mucosa.

The effect of paracetamol on the gastric mucosa was examined in seven healthy volunteers. The dose used (2 g instilled in 100 ml isotonic saline) was equivalent to about six tablets taken with water. Biopsy specimens were taken before and 10 and 60 minutes after instillation. The mean incidence of damaged surface cells in the control period was 1.7%. Ten minutes after instillation 3.5% of the surface cells were damaged. This increase was not significant. Light microscopy showed focal cell disruption and infiltration of red blood cells. Scanning electronmicroscopy showed minimal loss of normal cell apices. No erosions were seen on microscopy. Biopsy specimens taken 60 minutes after paracetamol showed similar changes. These findings differ appreciably from the extensive cell damage and microscopic erosions caused by therapeutic doses of 600 mg (two tablets) of aspirin. We conclude that large "analgesic" doses of paracetamol cause minimal ultrastructural changes in normal human gastric mucosa. The continued use of paracetamol in place of aspirin appears to be justified when there is a possibility of gastric mucosal injury.

Repetitive DNA insertion in a protein kinase ORF of a latent FSV (Feldmannia sp. virus) genome.

We describe the structure of a Feldmannia sp. virus (FsV) genome integrated in the brown alga, Feldmannia. This integrated FsV genome appears to be permanently inactivated and lost its ability to excise and replicate. Unlike the replicated form of FsV, this integrated FsV genome contains a large (>50 kb) repeat region inserted in a protein kinase open reading frame. While related to the 173-bp repeats previously characterized in the FsV genome (Lee et al., 1995), Southern blot analysis indicates that the repeats in the inactive, integrated FsV genome are distinct from those previously characterized. Fine structural analysis of the repeat-insertion sites in the protein kinase gene indicates that there are 8- and 10-bp palindromic sequences present in multiple locations located near the repeat-insertion site. The translated protein kinase contains all of the catalytic motifs conserved in most serine/threonine protein kinases and a potential autophosphorylation site. This protein kinase gene is expressed as RNA in sporophyte plants where virus production is active but not in gametophyte plants where the virus genome is latent. The structure of the integrated virus genome is discussed.