Ponseti method of treating clubfoot - Is there difference if treatment is started before or after one month of age?

INTRODUCTION: Most of the authors currently agree that congenital talipes equinovarus (CTEV) or idiopathic clubfoot can be effectively treated with the Ponseti method instead of extensive soft tissue surgery. This study was conducted to investigate whether there is a difference in the outcome between starting treatment before one month of age or after that age. METHODS: This is a retrospective study on babies with CTEV treated in University Malaya Medical Centre from 2013 to 2017. The 54 babies (35 boys and 19 girls) were divided into two cohorts, Group 1 that had treatment before the age of one month, and Group 2 that had treatment after one month old. The number of cast changes, rate of full correction, and rate of relapse after treatment were compared between the two groups. RESULTS: Of the 54 babies, with 77 CTEV treated during the period, our outcome showed that the mean number of cast change was 5.9 for Group 1 and 5.7 for Group 2. The difference was not statistically significant. All the affected feet (100%) achieved full correction. One foot in the Group 1 relapsed, while three feet in Group 2 relapsed, but the difference was also not statistically significant. All of the relapsed feet were successfully treated with repeated Ponseti method. CONCLUSIONS: Treating CTEV using Ponseti method starting after one month was not associated with more casting change of higher rate of relapse.

Isolation and characterization of novel microsatellites for Abies koreana and A. nephrolepis (Pinaceae).

Abies koreana is an endemic and rare species from Korea and is classified as endangered by the International Union for Conservation of Nature. Although the genetic diversity assessment for current population of A. koreana needs to be performed urgently, no microsatellite markers have been developed for this species. In the present study, we developed 22 novel polymorphic microsatellite loci and the characteristics of these loci were determined in A. koreana as well as in Abies nephrolepis, the most closely related species, and these loci were compared with previously reported microsatellite markers developed for the Abies genus. Genomic sequence (161 Mbp; 325,776 reads) was obtained from one individual of A. koreana using Roche 454 GS-FLX Titanium sequencing and 19,258 repeat motifs were identified from it. A total of 288 primer pairs with high copy numbers of di-repeat motifs were evaluated for amplification in A. koreana and A. nephrolepis. A total of 71 primer pairs successfully amplified fragments, of which 22 showed polymorphisms in A. koreana and A. nephrolepis. The average expected diversity was 0.767 and 0.717 in A. koreana and A. nephrolepis, respectively; these heterozygosity levels were moderate compared to the previously reported microsatellite loci from Abies species. This is the first set of microsatellite markers developed for A. koreana as well as A. nephrolepis and further population genetic studies of both species and genetic delimitation can be carried out for the species conservation and management.

Conservation of Hox gene clusters in the self-fertilizing fish Kryptolebias marmoratus (Cyprinodontiformes; Rivulidae).

In this study, whole Hox gene clusters in the self-fertilizing mangrove killifish Kryptolebias marmoratus (Cyprinodontiformes; Rivulidae), a unique hermaphroditic vertebrate in which both sex organs are functional at the same time, were identified from whole genome and transcriptome sequences. The aim was to increase the understanding of the evolutionary status of conservation of this Hox gene cluster across fish species.

Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer.

BACKGROUND: Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, ∼50% of patients are chemoresistant. This study examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort. METHODS: PC3 cells or their docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. The circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel from 55 men with CRPC, and compared with prostate-specific antigen (PSA) response. RESULTS: PC3Rx-U937 co-culture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared with PC3-U937 co-culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co-culture, while reducing cytokine levels in PC3-U937. In patients, changes in the levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1), interleukin (IL)-1ra, IL-1ß, IL-4, IL-6, IL-12 and IFNγ) after cycle 1 of docetaxel were associated with progressive disease (all P<0.05). The combination of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002). CONCLUSIONS: In vitro studies suggest docetaxel resistance is mediated, at least in part, by cytokines induced by the interaction between the docetaxel-resistant tumour cells and macrophages. Early changes in circulating cytokine levels were associated with docetaxel resistance in CRPC patients. When considered together, these data suggest a significant role for the inflammatory response and macrophages in the development of docetaxel resistance in CRPC.

Pharmacokinetic modeling and Monte Carlo simulation of ondansetron following oral administration in dogs.

Ondansetron is a potent antiemetic drug that has been commonly used to treat acute and chemotherapy-induced nausea and vomiting (CINV) in dogs. The aim of this study was to perform a pharmacokinetic analysis of ondansetron in dogs following oral administration of a single dose. A single 8-mg oral dose of ondansetron (Zofran(®) ) was administered to beagles (n = 18), and the plasma concentrations of ondansetron were measured by liquid chromatography-tandem mass spectrometry. The data were analyzed by modeling approaches using ADAPT5, and model discrimination was determined by the likelihood-ratio test. The peak plasma concentration (Cmax ) was 11.5 ± 10.0 ng/mL at 1.1 ± 0.8 h. The area under the plasma concentration vs. time curve from time zero to the last measurable concentration was 15.9 ± 14.7 ng·h/mL, and the half-life calculated from the terminal phase was 1.3 ± 0.7 h. The interindividual variability of the pharmacokinetic parameters was high (coefficient of variation > 44.1%), and the one-compartment model described the pharmacokinetics of ondansetron well. The estimated plasma concentration range of the usual empirical dose from the Monte Carlo simulation was 0.1-13.2 ng/mL. These findings will facilitate determination of the optimal dose regimen for dogs with CINV.

Circulating microRNAs are associated with docetaxel chemotherapy outcome in castration-resistant prostate cancer.

BACKGROUND: Docetaxel is the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, response rates are ∼50% and determined quite late in the treatment schedule, thus non-responders are subjected to unnecessary toxicity. The potential of circulating microRNAs as early biomarkers of docetaxel response in CRPC patients was investigated in this study. METHODS: Global microRNA profiling was performed on docetaxel-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards were used to measure the levels of 46 candidate microRNAs in plasma/serum samples, collected before and after docetaxel treatment, from 97 CRPC patients. RESULTS: Fourteen microRNAs were associated with serum prostate-specific antigen (PSA) response or overall survival, according to Mann-Whitney U or log-rank tests. Non-responders to docetaxel and patients with shorter survival generally had high pre-docetaxel levels of miR-200 family members or decreased/unchanged post-docetaxel levels of miR-17 family members. Multivariate Cox regression with bootstrapping validation showed that pre-docetaxel miR-200b levels, post-docetaxel change in miR-20a levels, pre-docetaxel haemoglobin levels and visceral metastasis were independent predictors of overall survival when modelled together. CONCLUSIONS: Our study suggests that circulating microRNAs are potential early predictors of docetaxel chemotherapy outcome, and warrant further investigation in clinical trials.

Unusual maternal uniparental isodisomic x chromosome mosaicism with asymmetric y chromosomal rearrangement.

Infertile men with azoospermia commonly have associated microdeletions in the azoospermia factor (AZF) region of the Y chromosome, sex chromosome mosaicism, or sex chromosome rearrangements. In this study, we describe an unusual 46,XX and 45,X mosaicism with a rare Y chromosome rearrangement in a phenotypically normal male patient. The patient's karyotype was 46,XX[50]/45,X[25]/46,X,der(Y)(pter→q11.222::p11.2→pter)[25]. The derivative Y chromosome had a deletion at Yq11.222 and was duplicated at Yp11.2. Two copies of the SRY gene were confirmed by fluorescence in situ hybridization analysis, and complete deletion of the AZFb and AZFc regions was shown by multiplex-PCR for microdeletion analysis. Both X chromosomes of the predominant mosaic cell line (46,XX) were isodisomic and derived from the maternal gamete, as determined by examination of short tandem repeat markers. We postulate that the derivative Y chromosome might have been generated during paternal meiosis or early embryogenesis. Also, we suggest that the very rare mosaicism of isodisomic X chromosomes might be formed during maternal meiosis II or during postzygotic division derived from the 46,X,der(Y)/ 45,X lineage because of the instability of the derivative Y chromosome. To our knowledge, this is the first confirmatory study to verify the origin of a sex chromosome mosaicism with a Y chromosome rearrangement.

A computer simulation model of the cost-effectiveness of routine Staphylococcus aureus screening and decolonization among lung and heart-lung transplant recipients.

Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations.

Stormwater runoff quality in correlation to land use and land cover development in Yongin, South Korea.

Stormwater runoff quality is sensitive to land use and land cover (LULC) change. It is difficult to understand their relationship in predicting the pollution potential and developing watershed management practices to eliminate or reduce the pollution risk. In this study, the relationship between LULC change and stormwater runoff quality in two separate monitoring sites comprising a construction area (Site 1) and mixed land use (Site 2) was analyzed using geographic information system (GIS), event mean concentration (EMC), and correlation analysis. It was detected that bare land area increased, while other land use areas such as agriculture, commercial, forest, grassland, parking lot, residential, and road reduced. Based on the analyses performed, high maximum range and average EMCs were found in Site 2 for most of the water pollutants. Also, urban areas and increased conversion of LULC into bare land corresponded to degradation of stormwater quality. Correlation analysis between LULC and stormwater quality showed the influence of different factors such as farming practices, geographical location, and amount of precipitation, vegetation loss, and anthropogenic activities in monitoring sites. This research found that GIS application was an efficient tool for monthly monitoring, validation and statistical analysis of LULC change in the study area.

The leucosiid crabs described by Thomas Bell in 1855: original description and dates of publication (Crustacea: Decapoda: Brachyura).

Thomas Bell proposed 37 species- and 5 genus-group names for the Leucosiidae in four publications that appeared in 1855. The version appearing in the Proceedings of the Linnean Society of London is the earliest of these publications and the first available description of these taxa.

On the identity of Clistocoeloma balansae A. Milne-Edwards, 1873, and C. tectum (Rathbun, 1914), with description of a new species from the West Pacific (Crustacea: Decapoda: Sesarmidae).

The identity of the mangrove sesarmid crab Clistocoeloma balansae A. Milne-Edwards, 1873, is clarified on the basis of the types from New Caledonia, and fresh material from Vanuatu and the Philippines. Sesarma (Sesarma) tectum Rathbun, 1914, is shown to be a junior subjective synonym of C. balansae A. Milne-Edwards, 1873. A new species, C. melanesicum, superficially similar to C. balansae, is described from Vanuatu, New Caledonia, and, Solomon Islands.

Parametric study of lotus-type pore shape in solid subject to Henry's laws at interfaces.

Mechanisms of the length and maximum radius of lotus-type or single pores in ice or nonmetals satisfied by Henry's law at gas-liquid interfaces dissolved by a gas during unidirectional solidification are rigorously investigated and supported by a Table from algebraic predictions involving different dimensionless working parameters. Lotus-type porous materials characterized by directional properties have been often used as functional materials in food, biomedical, and micro- and nano-technologies. Following previous work taking into account solute amount and transport within the pore, and concentration boundary layers on the advancing solid-liquid interface and bubble cap, and the Young-Laplace equation and Henry's law at liquid-gas interfaces, the algebraic study further provides a Table for a quantitative and extensive understanding of different mechanisms of length and maximum radius. Dimensionless parameters include solute transport parameters of Henry's law constant, mass transfer coefficient, partition coefficient, solute gas amount in imposed ambient, and solute transport parameter, and fluid and thermal parameters of solidification rate, imposed gas pressure, hydrostatic pressure, and geometrical parameter of inter-pore spacing. The controlling of the shapes of lotus-type pores is achieved by a good comparison between predicted maximum diameter and inter-pore spacing during freezing of water dissolved by oxygen gas.

Molecular and clinical characteristics of 26 cases with structural Y chromosome aberrations.

Structural abnormalities include various types of translocations, inversions, deletions, duplications and isochromosomes. Structural abnormalities of the Y chromosome are estimated to affect less than 1% of the newborn male population and are particularly hazardous for male reproductive function. The objective of this study was to characterize a group of patients with structural abnormalities of the Y chromosome. All patients who visited our laboratory between 2007 and 2010 underwent cytogenetic investigations. Among these, we detected 26 patients with structural abnormalities of the Y chromosome. To confirm the structural Y chromosome alterations, we used special bandings, FISH and multiplex PCR to detect Y chromosome microdeletions. Of the 26 patients presented here, 11 had an isodicentric Y chromosome, 7 had an inversion, 3 had a translocation, 2 had a derivative, 2 had a Yqs and 1 had a deletion. Sixteen were diagnosed with azoospermia, 8 as normal fertile males and 1 as a man who was unable to donate semen due to mental retardation. One of the patients having 45,X/46,X,idic(Y) was reported to be phenotypically female with primary amenorrhea and without uterus. Deletions of the AZFbc region were correlated with the sperm concentration (p < 0.05), but no correlation with the levels of FSH, LH, testosterone, prolactin and estradiol were found. The present report shows that the precise identification of structural Y chromosome aberrations may be clinically important for genetic counseling and assisted reproductive technology treatment.

The potential economic value of screening hospital admissions for Clostridium difficile.

Asymptomatic Clostridium difficile carriage has a prevalence reported as high as 51-85 %; with up to 84 % of incident hospital-acquired infections linked to carriers. Accurately identifying carriers may limit the spread of Clostridium difficile. Since new technology adoption depends heavily on its economic value, we developed an analytic simulation model to determine the cost-effectiveness screening hospital admissions for Clostridium difficile from the hospital and third party payer perspectives. Isolation precautions were applied to patients testing positive, preventing transmission. Sensitivity analyses varied Clostridium difficile colonization rate, infection probability among secondary cases, contact isolation compliance, and screening cost. Screening was cost-effective (i.e., incremental cost-effectiveness ratio [ICER] ≤ $50,000/QALY) for every scenario tested; all ICER values were ≤ $256/QALY. Screening was economically dominant (i.e., saved costs and provided health benefits) with a ≥10.3 % colonization rate and ≥5.88 % infection probability when contact isolation compliance was ≥25 % (hospital perspective). Under some conditions screening led to cost savings per case averted (range, $53-272). Clostridium difficile screening, coupled with isolation precautions, may be a cost-effective intervention to hospitals and third party payers, based on prevalence. Limiting Clostridium difficile transmission can reduce the number of infections, thereby reducing its economic burden to the healthcare system.

Hypoxia inducible factor-1α gene polymorphisms in Korean patients with pre-eclampsia.

BACKGROUND: Placental hypoxia has been implicated in the pathogenesis of pre-eclampsia. Hypoxia inducible factor-1α (HIF-1α) is activated by low oxygen tension and is a key regulator of genes involved in the cellular responses to hypoxia. AIM: We determined whether maternal blood c.1722C>T (Pro582Ser) and c.1790G>A (Ala588Thr) polymorphisms in exon 12 of the HIF-1α gene are associated with pre-eclampsia. SUBJECTS AND METHODS: Subjects included 163 pre-eclamptic patients (48 mild and 115 severe preeclampsia) and 194 healthy pregnant women. Polymorphisms were genotyped by PCR and direct DNA sequencing. RESULTS: There were no significant differences in genotype or allele frequencies of the c.1772C>T and c.1790G>A polymorphisms of the HIF-1α gene among the study groups. Moreover, subgroup analysis according to pre-eclampsia severity revealed no significant differences in genotype or allele frequencies of the HIF-1α c.1772C>T and c.1790G>A polymorphism in mild pre-eclamptic compared to severe pre-eclamptic group. In addition, there were no significant differences in the frequencies of 3 haplotypes (C-G,-G, T-G, and C-A) between the control and pre-eclamptic groups. CONCLUSIONS: Our results suggest that the HIF-1α gene polymorphisms are not associated with the development of pre-eclampsia in the studied Korean women population.

Comparative protein binding of taxotere and SID530, a new docetaxel formulation with hydroxypropyl-beta-cyclodextrin, in human plasma in vitro.

The purpose of this study was to evaluate the plasma-protein binding of docetaxel in two different formulations, Taxotere and SID530, a new docetaxel formulation with hydroxypropyl-beta-cyclodextrin (HP-beta-CD), in human plasma in vitro, using equilibrium dialysis. Unbound docetaxel concentration in the human plasma was determined by LC-MS/MS analysis. SID530 showed a plasma-protein binding profile comparable to that of Taxotere in the clinically relevant concentration range of docetaxel. In both formulations, the unbound fraction of docetaxel increased in a concentration-dependent biphasic manner. The resulting data indicate that the excipient used in SID530, HP-beta-CD, generates similar effects as polysorbate 80 of Taxotere in terms of plasma-protein binding of docetaxel.

Uterine müllerian adenosarcoma with sarcomatous overgrowth and lung metastasis in a 25-year-old woman.

Uterine müllerian adenosarcoma with sarcomatous overgrowth (MASO), uncommon in premenopausal women, is a rare variant of uterine adenosarcomas characterized by a sarcomatous portion constituting >25% of the tumor. Uterine MASO often appears as a benign, protruding cervical polyp. However, in contrast to typical müllerian adenosarcomas (MAs), MASO is a highly aggressive tumor, frequently associated with a fatal outcome. Though very rare in premenopausal women, because of the high aggressiveness and malignant potential, uterine MASO should be considered, even in women of a young age with benign-appearing polypoid masses, and treated aggressively at the time of initial diagnosis without delay. We present herein a case of uterine MASO in a 25-year-old woman with lung metastasis who was lost to follow-up for one month after the initial diagnosis had been established.

Scaffold printing using biodegradable poly(1,4-butylene carbonate) ink: printability, in vivo physicochemical properties, and biocompatibility.

This study is the first to assess the applicability of biodegradable poly(1,4-butylene carbonate) (PBC) as a printing ink for fused deposition modeling (FDM). Here, PBC was successfully prepared via the bulk polycondensation of 1,4-butanediol and dimethyl carbonate. PBC was melted above 150°C in the heating chamber of an FDM printer, after which it flowed from the printing nozzle upon applying pressure and solidified at room temperature to create a three-dimensional (3D) scaffold structure. A 3D scaffold exactly matching the program design was obtained by controlling the temperature and pressure of the FDM printer. The compressive moduli of the printed PBC scaffold decreased as a function of implantation time. The printed PBC scaffold exhibited good in vitro biocompatibility, as well as in vivo neotissue formation and little host tissue response, which was proportional to the gradual biodegradation. Collectively, our findings demonstrated the feasibility of PBC as a suitable printing ink candidate for the creation of scaffolds via FDM printing.

Modelling seasonality and viral mutation to predict the course of an influenza pandemic.

As the 2009 H1N1 influenza pandemic (H1N1) has shown, public health decision-makers may have to predict the subsequent course and severity of a pandemic. We developed an agent-based simulation model and used data from the state of Georgia to explore the influence of viral mutation and seasonal effects on the course of an influenza pandemic. We showed that when a pandemic begins in April certain conditions can lead to a second wave in autumn (e.g. the degree of seasonality exceeding 0.30, or the daily rate of immunity loss exceeding 1% per day). Moreover, certain combinations of seasonality and mutation variables reproduced three-wave epidemic curves. Our results may offer insights to public health officials on how to predict the subsequent course of an epidemic or pandemic based on early and emerging viral and epidemic characteristics and what data may be important to gather.

Pharmacokinetics of mirodenafil and its two metabolites, SK3541 and SK3544, after intravenous and oral administration of mirodenafil to streptozotocin-induced diabetes mellitus rats.

The area under the curve (AUC) of mirodenafil after intravenous administration in diabetes mellitus induced by streptozotocin (DMIS) rats was significantly smaller (by 28.0 %) than the control value, and the AUC(SK3541)/AUC(mirodenafil) ratio was significantly greater (by 130 %) in DMIS rats. This may be explained by the significantly faster hepatic CL(int) of mirodenafil, owing to increased hepatic CYP1A, CYP2B1/2, CYP2D, and CYP3A expression, and a faster hepatic blood flow rate, compared with control values. The AUC of mirodenafil after oral administration was comparable between DMIS and control rats, possibly because of the comparable intestinal CL(int), which may be attributable to increased CYP1A2 expression and decreased CYP2D expression in the intestines of DMIS rats.