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Purpose: Our laboratory has developed and implanted a novel bioengineered internal anal sphincter (IAS) to treat anal incontinence. Fibroblast growth factor-2 (FGF-2) has been used in mice; however, the optimal growth factor for successful IAS implantation is unclear. This study compares several growth factors in order to optimize IAS viability and functionality.Methods: Bioengineered IAS rings were implanted subcutaneously into the dorsum of wildtype C57Bl/6 mice, with an osmotic pump dispensing FGF-2, vascular endothelial growth factor (VEGF), or platelet-derived growth factor (PDGF) (n = 4 per group). Control mice received IAS implants but no growth factor. The IAS was harvested approximately 25 days post-implantation. Tissue was subjected to physiologic testing, then histologically analyzed. Muscle phenotype was confirmed by immunofluorescence.Results: All implants supplemented with growth factors maintained smooth muscle phenotype. Histological scores, blood vessel density and muscle fiber thickness were all markedly better with growth factors. Neovascularization was comparable between the three growth factors. Basal tonic force of the constructs was highest with VEGF or PDGF.Conclusion: All growth factors demonstrated excellent performance. As our ultimate goal is clinical implantation, our strong results with PDGF, a drug approved for use in the United States and the European Union, pave the way for translating bioengineered IAS implantation to the clinical realm. [ABSTRACT FROM AUTHOR]

Enteral nutrient deprivation via total parenteral nutrition (TPN) administration leads to local mucosal inflammatory responses, but the underlying mechanisms are unknown. Wild-type (WT) and MyD88−/− mice underwent jugular vein cannulation. One group received TPN without chow, and controls received standard chow. After 7 d, we harvested intestinal mucosally associated bacteria and isolated small-bowel lamina propria (LP) cells. Bacterial populations were analyzed using 454 pyrosequencing. LP cells were analyzed using quantitative PCR and multicolor flow cytometry. WT, control mucosally associated microbiota were Firmicutes-dominant, whereas WT TPN mice were Proteobacteria-domiant. Similar changes were observed in MyD88−/− mice with TPN administration. UniFrac analysis showed divergent small bowel and colonic bacterial communities in controls, merging toward similar microbiota (but distinct from controls) with TPN. The percentage of LP T regulatory cells significantly decreased with TPN in WT mice. F4/80+CD11b+CD11cdull/− macrophage-derived proinflammatory cytokines significantly increased with TPN. These proinflammatory immunologic changes were significantly abrogated in MyD88−/− TPN mice. Thus, TPN administration is associated with significant expansion of Proteobacteria within the intestinal microbiota and increased proinflammatory LP cytokines. Additionally, MyD88 signaling blockade abrogated decline in epithelial cell proliferation and epithelial barrier function loss. [ABSTRACT FROM AUTHOR]

Background: We tested the coupling portion of a prototype intraluminal distraction enterogenesis device to allow flow-through of simulated enteric contents (SEC) in both pig and human jejunum. Materials and Methods: SEC was made using 80% corn syrup. Ten-cm pig and human intestinal segments had a spoke-shaped 2.2 cm coupling adaptor sutured in place, intraluminally. The adaptor had a flow-through area of 33.6 mm2. SEC was pumped into the proximal part of the intestinal segment at 0.083 mL/s. The times to first passage of SEC through the coupler (first drop), 10 mL, and 20mL of SEC eluted from the distal end were recorded. Results: Mean time to first drop elution was 155 ± 38 s with pig, and 149 ± 22 s with human bowel (P = 0.8). This corresponded to a hydrostatic pressure of 37.5 mmHg before the initial drop passed through. Mean flow rates were 0.094 mL/s in pig bowel and 0.084 mL/s in human bowel (P = 0.09). To account for occlusion from luminal debris, a 75% occlusion of coupler holes was studied in the smaller pig bowel to investigate if reductions in flow-through area could be tolerated. Mean time to first drop increased slightly to 171±15 s, but the elution rate stayed the same (P = 0.5). Conclusions: After a physiologic level of initial pressure buildup allowing the first drop of SEC to pass the coupling adaptor, our prototype intestinal coupling adaptor did not obstruct flow-through of SEC, even after a 75% decrease in flow-through area. This type of attachment represents a viable approach to placing a device in-continuity without obstructing flow of enteric contents. [Copyright &y& Elsevier]

Background: Distraction enterogenesis is a novel method for increasing small bowel length by the application of linearly directed forces. However, the magnitude of distractive forces that human and animal small bowel can safely withstand is unknown. Methods: Acute ex vivo force-displacement curves for human (n = 5) and pig (n = 6) small intestine (with and without mesentery) were made by applying increasing amounts of distractive forces to bowel immersed in normal saline (39°C). Progressive load was applied until gross disruption of the tissue was detected, or the applied force reached 1000 gram-force (gf). Histology was used to detect evidence of load-induced damage. In vivo blood flow to pig bowel with distractive loads (30–200 gf) was measured by laser Doppler. Results: The relationship between the level of force and degree of displacement was linear. The presence of a mesentery increased stiffness of pig bowel, but did not affect human bowel. Gross tissue disruption in pig and human tissue was seen at forces between 235 and 295 gf, respectively. However, in grossly undamaged areas, histology was unchanged even after application of higher loads. With in vivo testing, mesenteric blood flow was present up to 200 gf; however, blood flow to the bowel wall was reduced to undetectable levels at loads exceeding 100 gf. Conclusions: While whole bowel tissue may tolerate greater applied loads, blood flow to the bowel wall was compromised at loads over 100 gf, suggesting that any higher forces place the bowel at risk for ischemia. These measurements will help guide the clinical application of distraction enterogenesis. [ABSTRACT FROM AUTHOR]

We have previously developed bioengineered three-dimensional internal anal sphincter (IAS) rings from circular smooth muscle cells isolated from rabbit and human IAS. We provide proof of concept that bioengineered mouse IAS rings are neovascularized upon implantation into mice of the same strain and maintain concentric smooth muscle alignment, phenotype, and IAS functionality. Rings were bioengineered by using smooth muscle cells from the IAS of C57BL/6J mice. Bioengineered mouse IAS rings were implanted subcutaneously on the dorsum of C57BL/6J mice along with a microosmotic pump delivering fibroblast growth factor-2. The mice remained healthy during the period of implantation, showing no external signs of rejection. Mice were killed 28 days postsurgery and implanted IAS rings were harvested. IAS rings showed muscle attachment, neovascularization, healthy color, and no external signs of infection or inflammation. Assessment of force generation on harvested IAS rings showed the following: 1) spontaneous basal tone was generated in the absence of external stimulation; 2) basal tone was relaxed by vasoactive intestinal peptide, nitric oxide donor, and nifedipine; 3) acetylcholine and phorbol dibutyrate elicited rapid-rising, dose-dependent, sustained contractions repeatedly over 30 min without signs of muscle fatigue; and 4) magnitudes of potassium chloride-induced contractions were 100% of peak maximal agonist-induced contractions. Our preliminary results confirm the proof of concept that bioengineered rings are neovascularized upon implantation. Harvested rings maintain smooth muscle alignment and phenotype. Our physiological studies confirm that implanted rings maintain 1) overall IAS physiology and develop basal tone, 2) integrity of membrane ionic characteristics, and 3) integrity of membrane associated intxacellular signaling transduction pathways for contraction and relaxation by responding to cholinergic, nitrergic, and VIP-ergic stimulation. IAS smooth muscle tissue could thus be bioengineered for the purpose of implantation to serve as a potential graft therapy for dysfunctional internal anal sphincter in fecal incontinence. [ABSTRACT FROM AUTHOR]

Postoperative (postop) management of pediatric perforated appendicitis varies significantly, and postop intra-abdominal abscesses (IAA) remain a significant issue. Between 2019 and 2020, our standardized protocol included routine postop labs after an appendectomy for perforated appendicitis. However, given the lack of predictive utility of these routine labs, we discontinued this practice in 2021. We hypothesize that discontinuing routine postop labs will not be associated with an increase in complication rates after an appendectomy for pediatric perforated appendicitis. A single-institution, retrospective review of all pediatric appendectomies for perforated appendicitis from January 2019 to December 2021 was conducted at University Hospitals Rainbow Babies and Children's Hospital in Cleveland, Ohio. Data were collected on rate of complications (IAA development, re-admissions, bowel obstructions, superficial surgical site infections, intensive care unit transfers, Clostridium difficile infections, allergic reactions, and transfusions), postop imaging, postop interventions, and length of stay. Statistical analysis was completed using Fisher's exact test and Mann–Whitney U -test. A total of 109 patients (2019-2020 n = 61, 2021 n = 48) were included in the study. All 61 patients from 2019 to 2020 had postop labs compared to only eight patients in 2021. There was no statistically significant difference between the two groups in overall complication rates, but there was a decrease in IAAs reported in 2021 (P = 0.03). There were no statistically significant differences in other complications, postop imaging usage, or postop interventions. The median length of stay was 4.5 d in 2021 compared to 6.0 d in 2019-2020 (P = 0.009). Discontinuing routine postop labs is not associated with an increase in overall complications rates. Further studies are needed to determine whether routine postop labs can be safely removed in pediatric patients with perforated appendicitis, which would reduce patient discomfort and care costs. [ABSTRACT FROM AUTHOR]

Parenteral nutrition associated cholestasis (PNAC) is a common morbidity in neonates requiring total parenteral nutrition (TPN). Previous studies in infants with intestinal failure have shown a benefit of mixed lipid emulsion (MLE) in reducing PNAC. It is not known whether this benefit extends to a general neonatal intensive care unit (NICU) population, where MLE is used on a selective basis. The objective of this study is to examine associations between MLE use and PNAC rate in the general NICU setting. This is a retrospective review of NICU patients who received TPN for 7 or more days. We compared patients born between 1/1/2014 and 12/31/2015 (pre-MLE) to patients born between 7/1/2017 and 12/31/2018 (post-MLE). Fisher's exact test and two-sample t -test were used to compare the two groups. There were 353 patients in 2014-2015 and 271 patients in 2017-2018. Demographics were similar between the two groups, but there were more patients with congenital heart disease in the MLE era (P < 0.001). Mortality was similar (6.2% pre-MLE versus 6.3% post-MLE). There was no significant difference in PNAC rate between the pre-MLE (11.5%) and post-MLE (14.1%) patient cohorts (P = 0.342). Among patients receiving MLE (n = 38), 58% developed PNAC, while only 6.4% of the post-MLE cohort not receiving MLE developed PNAC. Of the patients coded with a surgical diagnosis, there was no significant difference in PNAC rates between pre-MLE and post-MLE groups. Discharge rates of PNAC did differ between pre-MLE surgical patients (13.0%) and post-MLE surgical patients (8.2%). In the subgroup of post-MLE surgical patients, PNAC rate differed significantly between those receiving MLE (43.5%) and not receiving MLE (15.4%). However, this difference was resolved by discharge (8.7% versus 7.7%). There were no significant differences in PNAC rates between the pre-MLE and post-MLE cohorts. However, in surgical patients, MLE was associated with reduced PNAC at discharge, with levels equivalent to those seen in neonates receiving TPN for 7 or more days, despite having a higher starting rate of PNAC. Further studies are needed to determine whether the general NICU population may benefit from MLE or certain selective subpopulations like surgical patients. [ABSTRACT FROM AUTHOR]

We aim to evaluate the utility of postoperative labs in predicting the development of an intra-abdominal abscess (IAA) in pediatric patients with perforated appendicitis. We hypothesize that postoperative labs are not predictive of IAA development. This was a single-institution retrospective cohort study that included pediatric patients (n = 61) who underwent surgery for perforated appendicitis from January 1, 2019 to December 1, 2020. Patients were stratified into those who developed a postoperative IAA (n = 22) and those who did not (n = 39). Postoperative labs (white blood cell [WBC] count, absolute neutrophil count, platelet count, C-reactive protein) were examined. Mann–Whitney U tests and chi-square tests were used to assess for differences between groups. There was extensive heterogeneity and overlap in postoperative lab values between patients who developed an IAA and those who did not. Almost all patients who developed an IAA had clinical signs that were indicative of abscess formation regardless of their postoperative WBC count or change in WBC count. While patients who developed an IAA had a higher postoperative median WBC count (10.8 versus 8.4, P = 0.003) and a smaller WBC count decrease (−4.9 versus −7.4, P = 0.01), no cutoff value for any of the examined lab values specifically predicted abscess formation. Postoperative median absolute neutrophil count (7.4 versus 4.0, P = 0.15), platelet count (360 versus 353, P = 0.98), and C-reactive protein (8.20 versus 5.32, P = 0.06) did not differ significantly. We conclude that postoperative labs have limited clinical utility in evaluating IAA development in children with perforated appendicitis. [ABSTRACT FROM AUTHOR]

Bladder agenesis is a rare congenital anomaly infrequently reported in the literature, with an incidence of 1/600,000 patients.1 Commonly associated with other fatal malformations, the condition is often incompatible with life.2 Prior reports estimate that over 90% of living children born with this malformation are female, owing to renal preservation resulting from low pressure drainage of urine into the vagina, uterus, and vestibule.3,4 Herein we report a rare case of an infant male born with penoscrotal transposition and end stage renal disease secondary to bilateral cystic renal dysplasia found to have concurrent bladder agenesis and bilateral ureteral ectopia. [ABSTRACT FROM AUTHOR]

A high-performance method for pitch extraction is proposed for the purposes of real-time sequential speech processing that can be used in such applications as speech rate conversion systems. According to this method, autocorrelation functions of the input speech waveforms are calculated for one analyzed point in time using multiple lengths of the analysis windows, and the largest peaks of each autocorrelation function are detected within the appropriate ranges, after which the optimum pitch period is selected by weighting the candidates of the pitch period obtained by the number of windows. Such selection processing is carried out independently for each analyzed point without using such characteristics as the continuity of the fundamental frequencies of the entire speech segment. This method was applied to analysis of a large number of speech materials, including recordings made by different speakers and speech samples mixed with noise. The tests have demonstrated that the proposed method features pitch extraction potentials superior to those of the cepstrum pitch determination method and the LPC residual autocorrelation method within a wide range of fundamental frequencies and power levels. © 1999 Scripta Technica, Electron Comm Jpn Pt 3, 83(2): 67–79, 2000 [ABSTRACT FROM AUTHOR]

Total parenteral nutrition (TPN) administration in a mouse model leads to a local mucosal inflammatory response, resulting in a loss of epithelial barrier function (EBF). Although, the underlying mechanisms are unknown, a major contributing factor is a loss of growth factors and subsequent critical downstream signaling. An important component of these is the p-Akt pathway. An additional contributing factor to the loss of EBF with TPN is an increase in proinflammatory cytokine abundance within the mucosal epithelium, including TNF-α and IFN-γ. Loss of critical nutrients, including glutamine and glutamate, may affect EBF, contributing to the loss of tight junction proteins. Finding protective modalities for the small intestine during TPN administration may have important clinical applications. Supplemental glutamine and glutamate may be examples of such agents. [ABSTRACT FROM AUTHOR]

In speech recognition systems where the speaker and utterance environment cannot be designated, the drop in recognition precision due to the incompatibility of the input speech and acoustic model's training data is a problem. Although this problem is normally solved by speaker adaptation, sufficient precision cannot be achieved for speaker adaptation unless good-quality adaptation data can be obtained. In this paper, the authors propose a method of efficiently clustering large-scale data using the likelihoods of a cluster model that was created from small-scale data as the criteria to obtain a high-precision adapted acoustic model. They also propose a method of using the cluster model to automatically determine the adapted acoustic model during recognition from only the beginning of the sentences of the input speech. The results of applying the proposed technique to news speech recognition experiments show that the adapted acoustic model selection precision can be ensured by using only 0.5 second of data of the beginnings of sentences of the input speech and that the proposed technique achieves a reduction rate for invalid recognitions of 20% and a reduction in the time required for recognition of 23% compared with when the adapted acoustic model for each cluster is not used. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 88(2): 41–51, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20157 [ABSTRACT FROM AUTHOR]

This paper proposes a now method of high-quality pitch modification by complex cepstrum analysis-synthesis algorithm (hereafter referred to as the CCAS algorithm). The algorithm of the new conversion method presented here is as follows: the complex cepstra obtained within each pitch-synchronized frame are divided into pitch components and other spectral components by using comb filters. The pitch pulses obtained by inverse transformation of the pitch components are equalized adaptively to zero-phase, while the spectral complements also are transformed inversely into unit responses in time-domain. This equalization makes the pitch components more impulsive, resulting in clear separation of the voice source from the vocal tract characteristics. Speech synthesis is performed by convoluting the phase-adjusted pitch pulses with the nit responses. The results of listening tests showed that the pitch-modified speech by the CCAS method subjectively retains as high quality as the original speech. [ABSTRACT FROM AUTHOR]

This paper proposes a new method of high-quality pitch modification by complex cepstrum analysis-synthesis algorithm (hereafter referred to as the CCAS algorithm). The algorithm of the new conversion method presented here is as follows: the complex cepstra obtained within each pitch-synchronized frame are divided into pitch components and other spectral components by using comb filters. The pitch pulses obtained by inverse transformation of the pitch components are equalized adaptively to zero-phase, while the spectral components also are transformed inversely into unit responses in time-domain. This equalization makes the pitch components more impulsive, resulting in clear separation of the voice source from the vocal tract characteristics. Speech synthesis is performed by convoluting the phase-adjusted pitch pulses with the nit responses. The results of listening tests showed that the pitch-modified speech by the CCAS method subjectively retains as high quality as the original speech. [ABSTRACT FROM AUTHOR]