Biochemical characterization of an esterase from Thermobifida fusca YX with acetyl xylan esterase activity.

BACKGROUND: Esterases (EC 3.1.1.X) are enzymes that catalyze the hydrolysis ester bonds. These enzymes have large potential for diverse applications in fine industries, particularly in pharmaceuticals, cosmetics, and bioethanol production. METHODS AND RESULTS: In this study, a gene encoding an esterase from Thermobifida fusca YX (TfEst) was successfully cloned, and its product was overexpressed in Escherichia coli and purified using affinity chromatography. The TfEst kinetic assay revealed catalytic efficiencies of 0.58 s-1 mM-1, 1.09 s-1 mM-1, and 0.062 s-1 mM-1 against p-Nitrophenyl acetate, p-Nitrophenyl butyrate, and 1-naphthyl acetate substrates, respectively. Furthermore, TfEst also exhibited activity in a pH range from 6.0 to 10.0, with maximum activity at pH 8.0. The enzyme demonstrated a half-life of 20 min at 70 °C. Notably, TfEst displayed acetyl xylan esterase activity as evidenced by the acetylated xylan assay. The structural prediction of TfEst using AlphaFold indicated that has an α/ß-hydrolase fold, which is consistent with other esterases. CONCLUSIONS: The enzyme stability over a broad pH range and its activity at elevated temperatures make it an appealing candidate for industrial processes. Overall, TfEst emerges as a promising enzymatic tool with significant implications for the advancement of biotechnology and biofuels industries.

Population Pharmacokinetic of the Diterpenes ent-Polyalthic Acid and Dihydro-ent-Agathic Acid from Copaifera Duckei Oil Resin in Rats.

Copaifera duckei oleoresin is a plant product extensively used by the Brazilian population for multiple purposes, such as medicinal and cosmetic. Despite its ethnopharmacological relevance, there is no pharmacokinetic data on this important medicinal plant. Due to this, we determined the pharmacokinetic profile of the major nonvolatile compounds of C. duckei oleoresin. The diterpenes ent-polyalthic acid and dihydro-ent-agathic acid correspond to approximately 40% of the total oleoresin. Quantification was performed using LC-MS/MS, and the validated analytical method showed to be precise, accurate, robust, reliable, and linear between 0.57 and 114.74 µg/mL plasma and 0.09 to 18.85 µg/mL plasma, respectively, for ent-polyalthic acid and dihydro-ent-agathic acid, making it suitable for application in preclinical pharmacokinetic studies. Wistar rats received a single 200 mg/kg oral dose (gavage) of C. duckei oleoresin, and blood was collected from their caudal vein through 48 h. Population pharmacokinetics analysis of ent-polyalthic and dihydro-ent-agathic acids in rats was evaluated using nonlinear mixed-effects modeling conducted in NONMEN software. The pharmacokinetic parameters of ent-polyalthic acid were absorption constant rate = 0.47 h-1, central and peripheral apparent volume of distribution = 0.04 L and 2.48 L, respectively, apparent clearance = 0.15 L/h, and elimination half-life = 11.60 h. For dihydro-ent-agathic acid, absorption constant rate = 0.28 h-1, central and peripheral apparent volume of distribution = 0.01 L and 0.18 L, respectively, apparent clearance = 0.04 L/h, and elimination half-life = 3.49 h. The apparent clearance, central apparent volume of distribution, and peripheral apparent volume of distribution of ent-polyalthic acid were approximately 3.75, 4.00-, and 13.78-folds higher than those of dihydro-ent-agathic.

Suppression of multiple anti-apoptotic BCL2 family proteins recapitulates the effects of JAK2 inhibitors in JAK2V617F driven myeloproliferative neoplasms.

Several lines of research suggest that Bcl-xL-mediated anti-apoptotic effects may contribute to the pathogenesis of myeloproliferative neoplasms driven by JAK2V617F and serve as therapeutic target. Here, we used a knock-in JAK2V617F mouse model and confirmed that Bcl-xL was overexpressed in erythroid progenitors. The myeloproliferative neoplasm (MPN)-induced phenotype in the peripheral blood by conditional knock-in of JAK2V617F was abrogated by conditional knockout of Bcl2l1, which presented anemia and thrombocytopenia independently of JAK2 mutation status. Mx1-Cre Jak2V617W/VF /Bcl2l1f/f mice presented persistent splenomegaly as a result of extramedullary hematopoiesis and pro-apoptotic stimuli in terminally differentiated erythroid progenitors. The pan-BH3 mimetic inhibitor obatoclax showed superior cytotoxicity in JAK2V617F cell models, and reduced clonogenic capacity in ex vivo assay using Vav-Cre Jak2V617F bone marrow cells. Both ruxolitinib and obatoclax significantly reduced spleen weights in a murine Jak2V617F MPN model but did not show additive effect. The tumor burden reduction was observed with either ruxolitinib or obatoclax in terminal differentiation stage neoplastic cells but not in myeloid-erythroid precursors. Therefore, disrupting the BCL2 balance is not sufficient to treat MPN at the stem cell level, but it is certainly an additional option for controlling the critical myeloid expansion of the disease.

Clinical treatment for hepatitis C reverses CYP2C19 inhibition.

AIMS: Infection by the hepatitis C virus (HCV) generates inflammatory response selectively modulating cytochrome P450 protein (CYP) activities. This study assessed the effect of chronic hepatitis C on CYP2C19 activity in patients with HCV. METHODS: Patients with HCV infection (n = 23) at different fibrosis stages were allocated into groups 1 (F0/F1 and F2, mild to moderate fibrosis) and 2 (F3 and F4, advanced fibrosis stages). Phase 1 was conducted before the treatment with direct-acting antivirals (DAAs) and phase 2 after the sustained virological response. Participants were administered 2 mg of a single oral dose of omeprazole (OME) as probe drug in both phases. Metabolic ratios (MRs) (plasma samples collected at 4 h after OME administration) were calculated by dividing plasma concentrations of 5-hydroxyomeprazole by OME. RESULTS: The MRs for group 1 were 0.45 (0.34-0.60, 90% confidence interval) and 0.69 (0.50-0.96) for phases 1 and 2, respectively, while the MRs for group 2 were 0.25 (0.21-0.31) and 0.41 (0.30-0.56) for phases 1 and 2, respectively. MRs were different (P < .05) between phases 1 and 2 for both groups, as well as between groups 1 and 2 in phase 1, but not in phase 2 (P > .05). CONCLUSIONS: Both groups presented different MRs before and after treatment with DAAs, evidencing that CYP2C19 inhibition during inflammation was at least partially reversed after DAA treatment. Groups 1 and 2 were also found to be different in phase 1 but not phase 2, showing that CYP2C19 metabolic activity does not differ between groups after DAA treatment.

New insights on the relation between zooplankton and humic substances in tropical freshwater ecosystems.

Aquatic humic substances (HS) represent about 60-95% of the dissolved organic carbon (DOC) present in coastal environments of northern Rio de Janeiro state, Brazil. Although they are important regulators of processes involving aquatic communities, the response of the zooplankton community to their presence remains poorly understood, especially in natural tropical environments. Therefore, our objective was to elucidate zooplankton community responses along a natural gradient of HS. Such natural humic gradient was obtained in coastal freshwater environments with distinct DOC concentrations (20-200 mg L-1). Results show a decrease in zooplankton density and biomass along the HS gradient. However, microphages organisms (e.g. non-predatory rotifers and smaller testate amoeba, such as Difflugia) were most present in environments with higher concentration of HS, probably due to a stronger importance of the microbial-loop in these environments. Some species - such as Scapholeberis armata (Cladocera) and Lecane boettgeri (Rotifera) were only accounted for environments with high HS concentration, illustrating their potential as bioindicators for HS presence. Nevertheless, we were able to observe the effects of HS on the structure and composition of primary consumers and how these substances might indirectly affect species dynamics. We point out to new findings in highly humic tropical environments, which are still poorly studied and understood.

Therapeutic Doses of Eltrombopag do not Inhibit Hepatic BCRP in Healthy Volunteers: Intravenous Ceftriaxone as a Model.

PURPOSE: Ceftriaxone elimination occurs through breast cancer resistance transporter (BCRP) and multidrug resistance-associated protein 2 (MRP-2) which are expressed on the canalicular membrane of hepatocytes. Eltrombopag, a thrombopoetin receptor agonist used in the treatment of immune thrombocytopenic purpura, is reported in in vitro studies as an inhibitor of intestinal BCRP but not an inhibitor of hepatic BCRP. Thus, the present study evaluates the effect of therapeutic doses of eltrombopag on the clinical pharmacokinetics of intravenous ceftriaxone. METHODS: Healthy adult (n=12) were treated with oral doses of eltrombopag (0, 25 or 50 mg) 28 and 4 h prior to intravenous ceftriaxone administration (1g). Serial blood samples were collected up to 48 h after ceftriaxone administration and plasma samples were analysed by LC-MS/MS using 50 µL aliquots (total concentration) and 100 µL (unbound concentration). RESULTS: A method to analyze total and unbound ceftriaxone in plasma using LC-MS/MS was developed and validated with linearity from 1 to 200 µg/mL. Both methods are sensitive, precise and accurate with coefficients of variation less than 15% in the study of inter- and intra-assay precision and accuracy. Ceftriaxone pharmacokinetics in healthy adults were described using a bicompartmental model, with a mean clearance of 0.96 L/h (CI95% 0.71-1.20) and AUC0-∞of 1106 mg.h/mL (CI95% 811-1400) for volunteers that received only ceftriaxone; clearance of 0.95 L/h (CI95% 0.77-1.13) and AUC0-∞ of 1083 mg.h/mL (CI95% 876-1290) for volunteers that received ceftriaxone plus 25 mg of eltrombopag and clearance of 0.96 L/h (CI95% 0.74-1.19) and AUC0-∞ of 1072 mg.h/mL (CI95% 872-1273) for volunteers that received ceftriaxone plus 50 mg of eltrombopag. CONCLUSIONS: The results do not support the existence of a clinical pharmacokinetic drug interaction involving hepatic BCRP in human subjects receiving intravenous ceftriaxone and oral eltrombopag. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Pelvic floor muscle function and quality of life in postmenopausal women with and without pelvic floor dysfunction.

INTRODUCTION: This study aims to compare pelvic floor muscle (PFM) function in postmenopausal women with and without pelvic floor dysfunction (PFD) and the relation between PFM function and quality of life. MATERIAL AND METHODS: A case-control study with 216 postmenopausal women with (n = 126) and without (n = 90) PFD. PFM function was assessed by digital vaginal palpation using the PERFECT scale. Specific quality of life was evaluated using the King's Health Questionnaire for women with urinary incontinence and the Prolapse Quality-of-Life Questionnaire for women with pelvic organ prolapse. We analyzed women with PFD into two categories: Oxford's grade ≤2 or ≥3 using a chi-squared test. RESULTS: Out of 126 womem with PFD 44 (34.9%) presented stress urinary incontinence, 21 (16.6%) had pelvic organ prolapse and 61 (48.4%) had urinary incontinence + pelvic organ prolapse. Strength had a median value 2 (0-5) in all women studied and most of them had insufficient strength, reduced endurance and repetition without statistical difference between groups. Incontinent women with strength ≤2 had worse perception of general health domain of King's Health Questionnaire (p = 0.007). No association was found between PFM function and Prolapse Quality-of-Life Questionnaire. CONCLUSIONS: PFM function assessed by bidigital palpation in postmenopausal women was not sufficiently sensitive to differentiate between women with vs. women without PFM dysfunction and was not related with specific quality of life in women with urinary incontinence and pelvic organ prolapse, respectively. These data should be used to reinforce the widespread recommendation that PFM training is essencial in PFD treatment.

A New Radiographic Classification System for Developmental Hip Dysplasia is Reliable and Predictive of Successful Closed Reduction and Late Pelvic Osteotomy.

BACKGROUND: The Tonnis radiographic classification of developmental dysplasia of the hip (DDH) has been used as a prognostic indicator for patients with walking-age DDH. The International Hip Dysplasia Institute (IHDI) classification, a new radiographic classification system, has been proposed to be more reliable by its creators. We sought to validate its reliability using independent observers, to compare it to the Tonnis method, and to assess its prognostic significance in a large cohort of patients. METHODS: A consecutive series of walking-age DDH patients were examined radiographically and classified by the Tonnis and IHDI schemes by 3 independent observers. Interobserver agreement was determined using the Kappa method. Clinical data were collected on patients with regard to success of closed reduction, need for later pelvic osteotomy, and presence of subsequent radiographic avascular necrosis (AVN). The prognostic value of the Tonnis and IHDI classifications to predict these clinical outcomes was determined. RESULTS: A total of 287 hips were available for analysis of the classification schemes. In total, 235 hips underwent attempted closed reduction and were eligible for analysis of successful closed reduction, and 131 hips had >4-year follow-up and were utilized for analysis of late pelvic osteotomy and AVN. Both classifications showed excellent interobserver reliability and in general, there was nonstatistically significant better reliability for the IHDI versus the Tonnis classification. In multivariate analysis, both IHDI and Tonnis classifications were found to be predictive of successful closed reduction and need for late pelvic osteotomy. Both methods showed trends toward being predictive of AVN rate, without statistical significance. CONCLUSIONS: The IHDI classification is subjectively more facile to use and has excellent interrelater agreement for classifying the radiographic severity of DDH. It is also reliable in predicting success of closed reduction and need for late pelvic osteotomy. SIGNIFICANCE: practitioners and researchers should consider the IHDI classification as a useful classification scheme and prognosticator when considering treatment options for late-presenting DDH. SIGNIFICANCE: Practitioners and researchers should consider the IHDI classification as a useful classification scheme and prognosticator when considering treatment options for late-presenting DDH. LEVEL OF EVIDENCE: Level III.

Long-term Outcomes of Operative and Nonoperative Treatment of Congenital Coxa Vara.

BACKGROUND: Congenital coxa vara (CCV) is a rare hip condition with few long-term studies. The purpose of this study was to assess clinical, radiographic, and functional outcomes after operative and nonoperative treatment of CCV, assess reliability of radiographic parameters, and investigate risk factors for recurrence after surgery. METHODS: Retrospective review was performed of all CCV patients treated at 1 institution from 1980 to 2010. In addition, patients were recalled for additional follow-up x-rays, modified Harris Hip Score (mHHS), and gait analysis. Radiographic measurements [neck-shaft angle (NSA), head-shaft angle (HSA), Hilgenreiner-epiphyseal angle (HEA), and femoral neck length (FNL)] were assessed for reliability using intraclass correlation coefficients. Multivariate analysis was performed to identify risk factors for recurrence after surgery. RESULTS: Forty-six hips in 32 patients were reviewed. Mean age at presentation was 5.4±4.9 years. Mean follow-up was 11.8±5.8 years. Valgus proximal femoral osteotomy was performed in 27 hips (20 patients). Initial deformity was greater in the operative group (NSA 90±17 degrees, HEA 68±19 degrees) versus nonoperative patients (NSA 122±19 degrees, HEA 34±14 degrees) (P<0.0001), but radiographic outcomes were similar at follow-up. Most nonoperative hips had normal FNL growth rates (80%), but resolution of varus NSA occurred in only 21%. In contrast, 56% of operative hips showed decreased FNL growth rates. Interobserver reliability was excellent for HEA (0.98), NSA (0.90), and FNL (0.89), and good for HSA (0.79). Repeat osteotomy was performed in 6 cases (22%). No significant predictors for recurrence were identified. At long-term follow-up for recalled patients, 72% had significantly abnormal gait, and 50% had fair-poor functional outcomes (mHHS<79). CONCLUSIONS: Valgus osteotomy corrects severe deformity in CCV with improved clinical and radiographic outcomes. HEA and NSA are the most reliable radiographic measurements of proximal femoral deformity in CCV. Recurrence is not uncommon, but no predictors were identified. Many patients have persistent gait abnormalities and functional impairment at long-term follow-up, regardless of prior treatment. LEVEL OF EVIDENCE: Level III-retrospective cohort.

Perioperative Interdisciplinary Intervention Contributes to Improved Outcomes of Adolescents Treated With Hip Preservation Surgery.

BACKGROUND: Adolescent hip preservation surgery (HPS) candidates typically present with chronic pain, which can negatively affect psychological function and surgical outcomes. A previous study demonstrated high rates of psychological symptoms and maladaptive behaviors in this population. This study quantified psychological and functional improvements in these patients from preoperative presentation to postoperative follow-up. An integrated interdisciplinary approach is also described. METHODS: A total of 67 patients undergoing HPS were evaluated preoperatively and postoperatively at 1 year by staff psychologists. Perioperative psychological intervention consisted of education, counseling, and administration of self-report measures. Self-report measure scores were compared preoperatively and postoperatively, grouped by orthopaedic diagnoses. Frequency analysis, correlational analysis, and analysis of variance were conducted. RESULTS: Psychological function improved significantly at follow-up: decreased emotional symptomatology (46.1 to 43.6, P=0.013), anxiety (49.6 to 45.8, P<0.001), school problems (46.6 to 44.7, P=0.035), internalizing problems (46.3 to 44.1, P=0.015), social stress (44.5 to 42.3, P=0.024), sense of inadequacy (49.0 to 46.0, P=0.004), and increased self-concept (51.1 to 54.1, P=0.003). Resiliency factors also significantly improved: increased mastery (50.3 to 52.9, P=0.001) and resourcefulness (49.7 to 52.0, P=0.046), decreased emotional reactivity (46.3 to 42.9, P=0.001), and vulnerability (47.7 to 44.7, P=0.011). Physical function and return to activity also significantly improved (University of California-Los Angeles: 7.1 to 8.7, P=0.017; modified Harris Hip Score: 67.3 to 83.8, P<0.001). Return to activity positively correlated with optimism and self-efficacy (P=0.041). Femoroacetabular impingement and hip dysplasia patients consistently reported feeling less depressed (P=0.036), having fewer somatic complaints (P=0.023), fewer internalized problems (P=0.037), and exhibiting fewer atypical behaviors (P=0.036) at follow-up. Slipped capital femoral epiphysis patients did not demonstrate improvements in psychological functioning postoperatively. CONCLUSIONS: Perioperative psychological education and counseling, in combination with HPS, improved postoperative psychological and physical function. Patients reported reduced anxiety, school problems, and social stress, with marked increase in resilience. Increased mobility and return to activity significantly correlated with improved optimism and self-efficacy. LEVEL OF EVIDENCE: Level II-therapeutic studies-investigating the results of treatment.

mTOR Pathway in Papillary Thyroid Carcinoma: Different Contributions of mTORC1 and mTORC2 Complexes for Tumor Behavior and SLC5A5 mRNA Expression.

The mammalian target of rapamycin (mTOR) pathway is overactivated in thyroid cancer (TC). We previously demonstrated that phospho-mTOR expression is associated with tumor aggressiveness, therapy resistance, and lower mRNA expression of SLC5A5 in papillary thyroid carcinoma (PTC), while phospho-S6 (mTORC1 effector) expression was associated with less aggressive clinicopathological features. The distinct behavior of the two markers led us to hypothesize that mTOR activation may be contributing to a preferential activation of the mTORC2 complex. To approach this question, we performed immunohistochemistry for phospho-AKT Ser473 (mTORC2 effector) in a series of 182 PTCs previously characterized for phospho-mTOR and phospho-S6 expression. We evaluated the impact of each mTOR complex on SLC5A5 mRNA expression by treating cell lines with RAD001 (mTORC1 blocker) and Torin2 (mTORC1 and mTORC2 blocker). Phospho-AKT Ser473 expression was positively correlated with phospho-mTOR expression. Nuclear expression of phospho-AKT Ser473 was significantly associated with the presence of distant metastases. Treatment of cell lines with RAD001 did not increase SLC5A5 mRNA levels, whereas Torin2 caused a ~6 fold increase in SLC5A5 mRNA expression in the TPC1 cell line. In PTC, phospho-mTOR activation may lead to the activation of the mTORC2 complex. Its downstream effector, phospho-AKT Ser473, may be implicated in distant metastization, therapy resistance, and downregulation of SLC5A5 mRNA expression.

Microbial Food-Web Drivers in Tropical Reservoirs.

Element cycling in aquatic systems is driven chiefly by planktonic processes, and the structure of the planktonic food web determines the efficiency of carbon transfer through trophic levels. However, few studies have comprehensively evaluated all planktonic food-web components in tropical regions. The aim of this study was to unravel the top-down controls (metazooplankton community structure), bottom-up controls (resource availability), and hydrologic (water residence time) and physical (temperature) variables that affect different components of the microbial food web (MFW) carbon stock in tropical reservoirs, through structural equation models (SEM). We conducted a field study in four deep Brazilian reservoirs (Balbina, Tucuruí, Três Marias, and Funil) with different trophic states (oligo-, meso-, and eutrophic). We found evidence of a high contribution of the MFW (up to 50% of total planktonic carbon), especially in the less-eutrophic reservoirs (Balbina and Tucuruí). Bottom-up and top-down effects assessed through SEM indicated negative interactions between soluble reactive phosphorus and phototrophic picoplankton (PPP), dissolved inorganic nitrogen, and heterotrophic nanoflagellates (HNF). Copepods positively affected ciliates, and cladocerans positively affected heterotrophic bacteria (HB) and PPP. Higher copepod/cladoceran ratios and an indirect positive effect of copepods on HB might strengthen HB-HNF coupling. We also found low values for the degree of uncoupling (D) and a low HNF/HB ratio compared with literature data (mostly from temperate regions). This study demonstrates the importance of evaluating the whole size spectrum (including microbial compartments) of the different planktonic compartments, in order to capture the complex carbon dynamics of tropical aquatic ecosystems.

Overhead Bryant's Traction Does Not Improve the Success of Closed Reduction or Limit AVN in Developmental Dysplasia of the Hip.

BACKGROUND: Preoperative Bryant's overhead traction before closed reduction (CR) in developmental dysplasia of the hip (DDH) remains controversial and its success in increasing CR rates and reducing avascular necrosis (AVN) rates has not been specifically reported in a large cohort. METHODS: IRB-approved retrospective study of patients (below 3 y)who were treated with attempted CR for idiopathic DDH from 1980 to 2009. Successful CR was defined as a hip that remained reduced and did not require repeat CR or open reduction. Patients were grouped by age, hip instability [Ortolani positive (reducible) vs. fixed dislocation], and Tonnis classification and rates of successful CR were compared between groups with P<0.05. RESULTS: A total of 342 hips were included with a mean age of 0.9 years (0.2 to 2.8 y) and a mean follow-up of 10.4 years (2.0 to 27.7 y). There were 269 hips with fixed dislocations and 73 Ortolani-positive hips. Traction was used in 276 hips. There was no difference in traction utilization in the 3 age groups (below 1, below 1.5, and below 2 y) for either Ortolani-positive hips (P=0.947) or fixed dislocations (P=0.943). There was no difference in achieving a successful CR comparing traction (60.9%) and no-traction groups (60.6%) (P=1.00). For Ortolani-positive hips, traction did not improve the incidence of a successful CR for any age group: below 1 year: P=0.19; below 1.5 years: P=0.23; and below 2 years: P=0.25. Similarly, fixed dislocation patients had no benefit from traction: below 1 year: P=0.76; below 1.5 years: P=0.82; and below 2 years: P=0.85. Tonnis classification did predict success of CR but had no influence on traction success. There was no difference in the rate of AVN between the traction (18%) and no-traction (8%) groups for all patients (P=0.15). CONCLUSIONS: In this retrospective series, preoperative Bryant's traction does not improve the rate of a successful CR for patients with DDH and has no protective effect on the development of AVN of the femoral head. These results suggest that Bryant's overhead traction may not be warranted for patients below 3 years of age with DDH. LEVEL OF EVIDENCE: Level III.

Surgical Hip Dislocation is Safe and Effective Following Acute Traumatic Hip Instability in the Adolescent.

BACKGROUND: A traumatic hip dislocation in the pediatric patient is a rare but potentially catastrophic injury. The purpose of this study was to review our early clinical results and radiographic morphology of hips treated with a surgical hip dislocation (SHD) approach for intra-articular hip pathology resulting from traumatic instability in pediatric and adolescent patients. METHODS: This is a retrospective analysis of a consecutive series of patients presenting with nonconcentric reduction after traumatic hip instability. All patients were treated with a transtrochanteric SHD with concomitant procedures based on intra-articular findings. Radiographic evaluations and Harris Hip Scores were completed at final follow-up. RESULTS: Eleven male patients, mean age of 12.3 years (range, 9.3 to 16.1 y) and mean body mass index 19.6 kg/m (range, 15.4 to 28.0 kg/m). Intraoperative findings included: labral tear (8), femoral cartilage injury (5), acetabular rim fracture (4), acetabular cartilage delamination (3), loose body (2), and femoral head osteochondral fracture (1). Postoperatively, 1 patient developed a transient peroneal nerve palsy. At a mean 24.5 months (range, 12.0 to 48.1 mo) postoperatively, no hips have radiographic evidence of osteonecrosis. The mean lateral center edge angle was 20 degrees (range, 9 to 38 degrees) with 6 hips of <20 degrees; mean acetabular index 9 degrees (range, -2 to 23 degrees) with 5 hips of >10 degrees; mean α-angle 56 degrees (range, 48 to 62 degrees) with 6 hips of >55 degrees; mean acetabular version 12 degrees (range, 8 to 16 degrees) with 8 hips of <15 degrees. At 1-year follow-up, the mean Harris Hip Score was 95.8 (range, 84.7 to 100). CONCLUSIONS: Early results suggest that SHD is a safe approach to treat an incomplete reduction following posterior hip instability and is effective for identification and treatment of acute intra-articular pathology. Acetabular dysplasia, relative acetabular retroversion, and/or decreased femoral offset may be risk factors for posterior hip instability in adolescents. LEVEL OF EVIDENCE: Level IV.

The cross-table lateral radiograph results in a significantly increased effective radiation dose compared with the Dunn and single frog lateral radiographs.

BACKGROUND: A lateral radiograph of the proximal femur is critical in the evaluation of patients with suspected femoroacetabular impingement. Positioning patients for a cross-table lateral (XTL) image is difficult, which may result in repeat exposures and increased cumulative radiation. Alternatively, the 45-degree Dunn (Dunn) and single frog lateral (SFL) views have been shown to accurately reveal proximal femoral abnormalities in femoroacetabular impingement. The purpose of this study was to compare the effective radiation doses (ERD) for 3 lateral hip projections that provide similar diagnostic information. METHODS: Patients presenting to the adolescent hip clinic with indicated examinations were evaluated with a standard anteroposterior (AP) pelvic radiograph and one of 3 lateral hip radiographs: XTL (n=16), Dunn (n=17), or SFL (n=27). Technical exposure parameters and published reference data for an AP pelvic radiograph were used to extrapolate the ERD. A simple Pearson r correlation test determined the relationships between body mass index, age, and ERD. The rate of repeat exposures per study was calculated. RESULTS: Body mass index positively correlated (r=0.34) and age and negatively correlated (r=-0.27) with ERD. ERD was increased for the XTL (0.83±0.98 mSv) over the Dunn (0.37±0.15 mSv) and SFL (0.22±0.11 mSv; P<0.05). Repeat exposures were performed in 10.4%, 4%, and 6% of XTL, Dunn, and SFL studies, respectively. CONCLUSIONS: The ERD for a single projection is highest for the XTL, and the examination is more likely to be repeated. The XTL radiograph should be avoided whenever possible and substituted with alternative images providing similar diagnostic information, such as the Dunn or SFL, to minimize lifetime cumulative radiation exposure to the patient. LEVEL OF EVIDENCE: Level II.

Preoperative psychological findings in adolescents undergoing hip preservation surgery.

BACKGROUND: Chronic pain is associated with increased anxiety, depression, and maladaptive behaviors, especially in adolescents. We hypothesized that adolescents with chronic hip pain selected for hip preservation surgery (HPS) would demonstrate increased anxiety and depression compared with same-age peers. We designed a study to assess the psychological state of adolescents before HPS. METHODS: We prospectively evaluated 58 patients (23 males, 35 females), average age 16.5 years (range, 11 to 19 y) before HPS. Their diagnoses included: femoroacetabular impingement (n=25), acetabular dysplasia (16), Perthes disease (11), and slipped capital femoral epiphysis (6). Psychological questionnaires included patient-completed and parent-completed Behavioral Assessment System for Children, Second Edition (BASC-2), Beck Youth Inventory, Second Edition (BYI-II), and Resiliency Scales. Self-reported functional questionnaires included the modified Harris hip score (mHHS, max 100) and the UCLA activity score. Psychological scores were compared between diagnoses, procedures performed, and self-reported functional scores with a Student t test and ANOVA. RESULTS: All patients reported pain, 52 (90%) reported pain >6 months with 28 (54%) >1 year. A total of 44 patients (76%) reported moderate or severe pain. All reported decreased function: average UCLA 7.25 (range, 2 to 10), average HHS 65.5 (range, 27.5 to 97.9). At presentation, 10 patients (17.2%) were receiving psychological intervention and 30% had a family history of mental illness. On the basis of the BYI-II scales, 10% and 31% of patients reported at-risk or clinically significant symptoms of anxiety and depression, respectively. Similarly, using the BASC-2 measure, 28% and 14% reported at-risk or clinically significant anxiety and depression, respectively. Resiliency scales demonstrated that 21% to 36% of patients report maladaptive behavior. There were no significant correlations between any psychological score and diagnosis, procedure, or preoperative functional score. CONCLUSIONS: Preoperative evaluation identified patients who reported at-risk or clinically significant symptoms of anxiety and/or depression, with up to one third of patients reporting maladaptive behavior that may significantly influence their postoperative outcomes. Preoperative psychological evaluation, with appropriate intervention and follow-up, if needed, should be considered before surgery selection as mental health conditions may be undiagnosed and will likely influence functional outcomes.

Prevalence of unreported bowel symptoms in women with pelvic floor dysfunction and the impact on their quality of life.

INTRODUCTION AND HYPOTHESIS: Little information is available on the recurrent coexistence of pelvic organ prolapse (POP), urinary (UI) and/or anal (AI) incontinence and defecatory dysfunctions and the relationship between these disorders. The purpose of this study is to report the prevalence, bother, and impact on quality of life (QoL) of unreported bowel symptoms in women presenting to a Brazilian tertiary urogynecology clinic. METHODS: The study was a cross-section survey of 172 patients with symptoms of pelvic floor disorders (PFD). Patients who reported any defecatory and/or continence disorders were included in the study group, and the others were included in the control group. Patients with UI were also compared with those with double incontinence (DI): AI and UI. Univariate analysis was conducted using the Mann-Whitney U test for continuous nonparametric data. RESULTS: After the interview, 54.6 % (n = 94) of patients presented AI and/or defecatory disorders: 67.0 % constipation, 41.4 % AI, and 34.0 % fecal urgency. Women from the study group scored worse in the QoL questionnaires compared with women from the control group. Among women with UI, 23.21 % had associated AI. Women with DI scored worse in the QoL questionnaires. CONCLUSION: Anal and urinary dysfunctions are usually associated and have a great impact on a woman's QoL. An integrated approach across specialties should lead to improved patient care. Therefore, our study is relevant because it emphasizes the importance of urogynecologists routinely investigating such symptoms. To do so, standardized questionnaires should be included in the evaluation of all these patients.

High-grade SCFE: the role of surgical hip dislocation and reduction.

The patient with an unstable slipped capital femoral epiphysis poses a challenging problem to the treating physician to improve the position of the displaced epiphysis to avoid femoroacetabular impingement without developing avascular necrosis (AVN)-a potentially devastating complication. Although the standard operative procedure of in situ pinning following an incidental reduction while positioning the patient on the table, has been the mainstay of treatment in North America, other viable options are available including a surgical dislocation approach to the hip followed by a modified Dunn osteotomy with control of the retinacular vessels, reduction of the epiphysis, and internal fixation with pins or screws. Although technically demanding, this approach offers an opportunity to reduce the epiphysis to avoid femoroacetabular impingement, and limit the possibility for the development of AVN. The early results for this procedure are promising with all studies demonstrating excellent reduction of the epiphysis and an overall lower incidence of AVN when compared with in situ pinning.

Intestinal P-gp activity is reduced in postmenopausal women under breast cancer therapy.

Intestinal P-glycoprotein (P-gp) activity plays a crucial role in modulating the oral bioavailability of its substrates. Fexofenadine has commonly been used as a P-gp probe, although it is important to note the involvement of other drug transporters like, OATP1B1, OATP1B3, and OATP2B1. In vitro studies demonstrated an upregulation of P-gp protein in response to exposure to pregnancy-related hormones. The objective of this study was to investigate how intestinal P-gp activity is impacted by menopausal status. This study sampled fexofenadine plasma concentrations over 0-12 h after probe drug administration from two groups of patients with breast cancer: premenopausal (n = 20) and postmenopausal (n = 20). Fexofenadine plasma concentrations were quantified using liquid-chromatography tandem mass spectrometry. Area under the plasma concentration-time curve from zero to infinity (AUCinf ) was calculated through limited sampling strategies equation. Multiple linear regression was applied on AUCinf , maximum plasma concentration (Cmax ), and time to Cmax . Postmenopausal patients showed a significant increase in Cmax (geometric mean and 95% confidence interval [CI] 143.54, 110.95-176.13 vs. 223.54 ng/mL, 161.02-286.06 and in AUCinf 685.55, 534.98-878.50 vs. 933.54 ng·h/mL 735.45-1184.99) compared to premenopausal patients. The carriers of the ABCB1 3435 allele T displayed higher Cmax values of 166.59 (95% CI: 129.44-214.39) compared to the wild type at 147.47 ng/mL (95% CI: 111.91-194.34, p = 0.02). In postmenopausal individuals, the decrease in P-gp activity of ~40% may lead to an increased plasma exposure of orally administered P-gp substrates.