Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Traditional healers' perception on scabies causation and management in Ghana.

INTRODUCTION: Scabies is an underdiagnosed skin infestation caused by the Sarcoptes scabiei mite. The infection causes severe itching and a skin rash but can be effectively treated using topical or systemic drugs. Scabies outbreaks are commonly reported in resource-poor countries, including Ghana. Traditional healers play an important role in primary care in rural areas. The role of these traditional healers in the management of scabies has so far not been explored. The aim of this study was therefore to investigate the perceptions of traditional healers regarding the causation and management of scabies. METHODS: A phenomenological qualitative approach was employed. Traditional healers in the Asante Akim North and Central districts in Ghana were approached with an interview request. Using a semi-structured interview protocol, 15 traditional healers were interviewed. The results were coded and analysed, after which seven themes were extrapolated. RESULTS: Scabies infections were frequently reported by traditional healers. Itching and skin rash were unanimously regarded as the major symptoms of scabies. The majority acknowledged the infectious nature of scabies, but no participant reported the causative organism. A dichotomous disease classification was noted, consisting of 'natural' and 'spiritual' variants each with a unique disease profile and management requirements, as reported by the traditional healers. All but two traditional healers reported to treat scabies using almost exclusively herbs and spiritual rituals. CONCLUSION: The majority of traditional healers were open to collaboration with allopathic healthcare providers. Collaboration could broaden the primary care network in rural areas, but mistrust and lack of transparency form potential barriers to collaboration. We, therefore, emphasise the need for additional efforts to investigate strategies for future collaboration.

What is Currently Known about Odontogenic Keratocysts?

PURPOSE: To present updated information on odontogenic keratocyst (OKC) classification, etiology, genetic and molecular alterations, epidemiology, clinical presentation, radiographic characteristics, histological and immune histochemical features, differential diagnosis, treatment, and controversies, as well as a literature review of case frequencies in different countries. MATERIALS AND METHODS: Studies were selected using the key words 'odontogenic keratocyst,' 'odontogenic cysts,' 'odontogenic keratocyst and clinical study'. Full-text papers were reviewed on the basis of the inclusion and exclusion criteria. The literature search aimed to find articles that would show the frequency of OKC, dentigerous cyst, radicular cyst, and other cysts. RESULTS: OKC presents local aggression and high recurrence; therefore, a better understanding of its clinical characteristics and the genetic and molecular factors involved in this peculiar and controversial lesion is required. It is always essential to discuss treatment alternatives. Although OKC is an entity with a high recurrence, aggressive treatment is not advisable in all cases because factors such as commitment to anatomical structures and possible complications should be considered. However, periodic radiographic controls are advised. CONCLUSION: To reduce the high number of present cases worldwide, it is important to improve knowledge on this pathology so that accurate diagnoses can be achieved and appropriate treatment can be provided. OKC presents local aggression and high recurrence; therefore, a better understanding is needed of the clinical characteristics and genetic and molecular factors involved in OKC. Furthermore, it is always essential to discuss treatment alternatives.

[Treatment and prognosis of 826 infants with critical congenital heart disease: a single center retrospective study].

Objective: To analyze the current status of clinical treatment and factors influencing postoperative mortality in infants with critical congenital heart disease (CCHD) in China, optimize the perioperative management of CCHD, and provide a new scientific basis for clinical decision-making for the optimal management of these patients. Methods: This is a retrospective single-center study. Infants diagnosed with CCHD in Guangdong Provincial People's Hospital from January 2017 to December 2019 (aged 0-1 years at admission) were enrolled. General clinical information, inpatient treatment information, prognosis and complications were collected and analyzed. Multivariate logistic regression analysis was used to explore the independent risk factors of postoperative death in infants with CCHD. Results: A total of 826 infants with CCHD were included, including 556 males (67.3%) and the age at first admission was 51.0 (5.0,178.3) days. 264 (32.0%) cases were tetralogy of Fallot and 137 (16.6%) cases were total anomalous pulmonary venous return. 195 cases (23.6%) were diagnosed prenatally. 196 cases (23.7%) were treated with prostaglandin. The preoperative invasive ventilation time was 0 (0, 0) hour, and the postoperative invasive ventilation time was 95.0 (26.0, 151.8) hours. A total of 668 cases (80.9%) underwent surgical treatment. The age was 100.5 (20.0, 218.0) days during operation and the operation time was 190.0 (155.0, 240.0) hours. Sixty-two cases (7.5%) received medical treatment, and 96 cases (11.6%) gave up treatment. A total of 675 cases (81.7%) were discharged with improvement, 96 cases (11.6%) were discharged after giving up treatment, 55 cases (6.7%) died and 109 cases (13.2%) were readmitted within one year. Complications occurred in 565 (68.6%) cases, including pneumonia in 334 cases (40.4%) and cardiac arrhythmias in 182 cases (22.0%). Multifactorial analysis showed that delayed chest closure (OR=49.775, 95%CI 3.291-752.922, P=0.005), prolonged post-operative invasive ventilator ventilation (OR=1.003, 95%CI 1.000-1.005, P=0.038) and cardiac hypoplasia syndrome (OR=272.658, 95%CI 37.861-1 963.589, P<0.001) were the independent risk factors for mortality in CCHD infants post-operation. Conclusions: Tetralogy of Fallot and total anomalous pulmonary venous return account for the majority of infants with CCHD. The proportion of infants diagnosed prenatally was less than 1/4. The majority CCHD infants received surgical treatment. The main complications are pneumonia and arrhythmia. Delayed chest closure, prolonged postoperative invasive ventilator ventilation and low cardiac output syndrome are the independent risk factors for postoperative death in infants with CCHD.

Utility of radiomic zones for risk classification and clinical outcome predictions using supervised machine learning during simultaneous 11 C-choline PET/MRI acquisition in prostate cancer patients.

PURPOSE: In most radiomic studies related to cancer research, the traditional tumor-centric view has predominated. In this retrospective study, we go beyond the single-tumor region and investigate the utility of proposed radiomic zones for risk classification and clinical outcome predictions using radiomic features extracted from 11 C-choline positron emission tomography (PET) imaging and supervised machine learning in prostate tumors. MATERIALS AND METHODS: Seventy-seven prostate tumors were selected and delineated. The prostate organ was divided into three radiomic zones, with zone-1 being the metabolic tumor zone, zone-2 the proximal peripheral tumor zone, and zone-3 the extended peripheral tumor zone. LIFEx was used for PET-radiomic feature extraction. Risk groups were created using Gleason scores (GS), prostate-specific antigen (PSA) levels, clinical TNM staging, and progression-free survival (PFS). Random forest (RF) and AdaBoost advanced machine learning algorithms were used for supervised machine learning. Accuracy, positive predictive value, area under the receiver operating characteristic curve (AreaROC), and other metrics were calculated for comparisons of predictive performance between zones. RESULTS: For the GS risk classification group, the accuracies of risk classification predictions were 71%, 71%, and 67% using RF and 65%, 64%, and 63% using AdaBoost for zones -1, -2, and -3, respectively. For the PSA group, the accuracies of risk classification predictions were 74%, 65%, and 64% using RF and 76%, 66%, and 67% using AdaBoost for zones -1, -2, and -3, respectively. For the TNM group, the accuracies of risk classification predictions were 68%, 76%, and 78% using RF and 66%, 75%, and 80% using AdaBoost for zones -1, -2, and -3, respectively. For the PFS group, the accuracies of clinical outcome predictions were 77%, 75%, and 83% using RF and 77%, 74%, and 83% using AdaBoost in zones -1, -2, and -3, respectively. CONCLUSIONS: We proposed three radiomic zones with different standard uptake value characteristics and created four risk groups of prostate cancer patients for testing this idea. We showed that these radiomic zones have different predicting strengths in classifying risk groups and might allow us to identify a radiomic zone with higher accuracy for patient outcome prediction.

[An outbreak of acute gastroenteritis caused by Sapovirus in a community of Guangdong province].

Objective: To investigate the epidemiological characteristics and clinic symptoms of an outbreak of infectious diarrhea caused by Sapovirus, in CT community, Zhaoqing, Guangdong province. Methods: Retrospective study of field epidemiology investigation was carried out and Chi-square test was used enteroviruses were detected by RT-PCR in swab, fecal specimens and water samples. Results: A total of 422 cases were identified in this outbreak, with the prevalence as 11.95%. Cases mainly concentrated between 21 and 24, December, with curves noticed by point- source and peaked on the 22(nd). Symptoms mainly appeared as vomiting, with watery stool. Patients were founded in every village, with the highest prevalence appeared in the elderly (25.20%) but involved in every age group. Sapovirus infection was most frequently seen in the population under 25 years of age, with overall prevalence as 16.41%. People older than 50 years of age took the second place (12.05%), and the lowest was seen between 25 to 49 years age group (8.42%). Sapovirus was detected in both swab and fecal specimens, with the positive rate as 38.78%. Both general and heat- resistant coliformed-bacteria were detected in the 24 monitored water samples, with the qualification rates as 95.83%, 45.83% and 50.00%, respectively. However, Sapovirus was not detected in any of the water samples. Conclusions: Our findings confirmed that an outbreak, caused by sapovirus infection in CT community was most likely related to the central water supply. The surveillance system for infectious diarrheal diseases should be improved and both public health awareness and surveillance programs on drinking water should be strengthened.

Generation of a novel mouse strain with conditional, cell-type specific, expression of DND1.

Dead-End 1 (DND1) encodes an RNA binding protein critical for viable primordial germ cells in vertebrates. When introduced into cancer cell lines, DND1 suppresses cell proliferation and enhances apoptosis. However, the molecular function of mammalian wild-type DND1 has mostly been studied in cell lines and not verified in the organism. To facilitate study of wild-type DND1 function in mammalian systems, we generated a novel transgenic mouse line, LSL-FM-DND1 flox/+ , which conditionally expresses genetically engineered, FLAG-tagged and myc-tagged DND1 in a cell type-specific manner. We report that FLAG-myc-DND1 is indeed expressed in specific tissues of the mouse when LSL-FM-DND1 flox/+ is combined with mouse strains expressing Cre-recombinase. LSL-FM-DND1 flox/+ mice are fertile with no overt health effects. We expressed FLAG-myc-DND1 in the pancreas and found that chronic, ectopic expression of FLAG-myc-DND1 led to increase in fasting glucose levels in older mice. Thus, this novel LSL-FM-DND1 flox/+ mouse strain will facilitate studies on the biological and molecular function of wild-type DND1.

Multicentre study evaluating matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of clinically isolated Elizabethkingia species and analysis of antimicrobial susceptibility.

OBJECTIVES: Rapid identification of Elizabethkingia species is essential because these species show variations in antibiotic susceptibility and clinical outcomes. Many recent inaccuracies in Elizabethkingia identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) have been noted. Accordingly, in this study, we evaluated the use of MALDI-TOF MS with an amended database to identify isolates of Elizabethkingia anophelis, E. miricola and E. meningoseptica. We then investigated the antimicrobial susceptibility of Elizabethkingia. METHODS: MALDI-TOF MS spectra were acquired from formic acid extracts overlaid with α-cyano-4-hydroxycinnamic acid matrix on target slides in linear positive ion mode for m/z 2000 to 20 000 Da. Spectra were analysed and SuperSpectra were created with SARAMIS premium software. 16S rRNA gene sequencing was used as the reference standard for species identification. Antibiotic susceptibility was assessed by broth microdilution. RESULTS: A total of 103 E. anophelis, 21 E. miricola and 11 E. meningoseptica isolates were used to calculate the average spectra and exclude common peaks. SuperSpectra were added to the SARAMIS taxonomy database; all validation results were correct, even for isolates not included in SuperSpectra. Confirmation by direct colony formation was also performed. Overall, the positive predictive value of SuperSpectra was 100% for all isolates. E. miricola (77%, 17/22) was more susceptible to levofloxacin than E. anophelis (16%, 17/105). Doxycycline and minocycline were effective against all Elizabethkingia species. CONCLUSIONS: Spectral analysis software identified significant species-specific peaks to create reference masses for efficient and accurate identification of Elizabethkingia species, providing accurate information for clinical treatment of Elizabethkingia infections.

Tumor suppressor miR-145-5p sensitizes prolactinoma to bromocriptine by downregulating TPT1.

PURPOSE: Prolactinoma is the most commonly seen secretory tumor of pituitary glands, which accounts for approximately up to 40% of total pituitary adenomas. Due to its high drug resistance, dopamine agonist, such as bromocriptine, has limited effect on the treatment of patients with prolactinoma. Recent discoveries have revealed that multiple miRNAs were involved in regulating drug resistance. In this research, we explored the relationship between miR-145-5p expression as well as bromocriptine sensitivity both in vitro and in vivo. METHODS: To study the role of miR-145-5p in drug resistance of prolactinoma, the expression levels of miR-145-5p in bromocriptine-resistant prolactinoma cell line MMQ/BRC and its parental cell line MMQ cells, 24 bromocriptine-resistant as well as eight sensitive clinical samples were measured by qRT-PCR. Moreover, CCK8, flow cytometry and immunofluorescence were performed to identify the biological characteristics of MMQ/BRC and MMQ. TPT1 was predicted as a direct target gene of miR-145-5p by bioinformatic methods. In addition, qRT-PCR, western blot and immunohistochemistry were used to detect the expression level of TPT1 in clinical specimens and cell lines. Xenograft mouse model was constructed to analyze whether miR-145-5p could reverse bromocriptine resistance in prolactinoma in vivo. RESULTS: In our study, bromocriptine-resistant prolactinoma clinical samples and cell line had decreased miR-145-5p levels and expressed high levels of TPT1 compared with their sensitive counterparts. Bioinformatic methods and our preliminary dual luciferase reporter assay were utilized to elucidate that TPT1 was a direct target gene of miR-145-5p. Furthermore, introducing miR-145-5p mimic into MMQ cells led to a decrease of IC50 along with upregulation of TPT1; nevertheless, transfecting the corresponding inhibitor into MMQ cells resulted in an upregulation of IC50 as well as reduction of TPT1. CONCLUSIONS: Collectively, our findings elucidated the role of miR-145-5p as an important regulator of drug resistance in prolactinoma by controlling TPT1, and implicated the potential application of miR-145-5p in cancer therapy as well.

MBD2 regulates differentiation and function of Th17 cells in neutrophils- dominant asthma via HIF-1α.

BACKGROUND: T helper 17 (Th17) cells have proven to be crucial in the pathogenesis of neutrophils-dominant asthma. Hypoxia inducible factor-1α (HIF-1α) is involved in allergic responses in asthma. Our previous studies indicated that Methtyl-CpG binding domain protein 2 (MBD2) expression was increased in asthma patients. The aim of the present study is to understand how MBD2 interacts with HIF-1α to regulate Th17 cell differentiation and IL-17 expression in neutrophils-dominant asthma. METHODS: A neutrophils-dominant asthma mouse model was established using female C57BL/6 mice to investigate Th17 cell differentiation and MBD2 and HIF-1α expression regulation using flow cytometry, western blot or qRT-PCR. MBD2 and HIF-1α genes were silenced or overexpressed through lentiviral transduction to explore the roles of MBD2 in Th17 cell differentiation and IL-17 release in neutrophils-dominant asthma. RESULTS: A neutrophilic inflammatory asthma phenotype model was established successfully. This was characterized by airway hyperresponsiveness (AHR), increased BALF neutrophil granulocytes, activated Th17 cell differentiation, and high IL-17 levels. MBD2 and HIF-1α expression were significantly increased in the lung and spleen cells of mice with neutrophils-dominant asthma. Through overexpression or silencing of MBD2 and HIF-1α genes, we have concluded that MBD2 and HIF-1α regulate Th17 cell differentiation and IL-17 secretion. Moreover, MBD2 was also found to regulate HIF-1α expression. CONCLUSIONS: Our findings have uncovered new roles for MBD2 and HIF-1α, and provide novel insights into the epigenetic regulation of neutrophils-dominant asthma.

Inhibition of RhoA reduces propofol-mediated growth cone collapse, axonal transport impairment, loss of synaptic connectivity, and behavioural deficits.

BACKGROUND: Exposure of the developing brain to propofol results in cognitive deficits. Recent data suggest that inhibition of neuronal apoptosis does not prevent cognitive defects, suggesting mechanisms other than neuronal apoptosis play a role in anaesthetic neurotoxicity. Proper neuronal growth during development is dependent upon growth cone morphology and axonal transport. Propofol modulates actin dynamics in developing neurones, causes RhoA-dependent depolymerisation of actin, and reduces dendritic spines and synapses. We hypothesised that RhoA inhibition prevents synaptic loss and subsequent cognitive deficits. The present study tested whether RhoA inhibition with the botulinum toxin C3 (TAT-C3) prevents propofol-induced synapse and neurite loss, and preserves cognitive function. METHODS: RhoA activation, growth cone morphology, and axonal transport were measured in neonatal rat neurones (5-7 days in vitro) exposed to propofol. Synapse counts (electron microscopy), dendritic arborisation (Golgi-Cox), and network connectivity were measured in mice (age 28 days) previously exposed to propofol at postnatal day 5-7. Memory was assessed in adult mice (age 3 months) previously exposed to propofol at postnatal day 5-7. RESULTS: Propofol increased RhoA activation, collapsed growth cones, and impaired retrograde axonal transport of quantum dot-labelled brain-derived neurotrophic factor, all of which were prevented with TAT-C3. Adult mice previously treated with propofol had decreased numbers of total hippocampal synapses and presynaptic vesicles, reduced hippocampal dendritic arborisation, and infrapyramidal mossy fibres. These mice also exhibited decreased hippocampal-dependent contextual fear memory recall. All anatomical and behavioural changes were prevented with TAT-C3 pre-treatment. CONCLUSION: Inhibition of RhoA prevents propofol-mediated hippocampal neurotoxicity and associated cognitive deficits.

[Prevalence and clinical characteristics of blood eosinophilia in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To investigate the prevalence and clinical characteristics of peripheral blood eosinophilia (EOS) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: From July 2014 to June 2016, AECOPD patients in the Department of Respiratory Medicine of Affiliated Hospital of Chengdu University, were retrospectively stratified into two groups according to two standards of eosinophilic exacerbations (the peripheral blood eosinophil count ≥2% or ≥3% on admission). Demography, clinical symptoms, laboratory results, length of stay, total hospitalization expenses, and defined daily expenses were compared between groups. Results: A total of 559 cases with AECOPD were finally recorded, the prevalence of eosinophilia was 43.1% (241 cases by EOS≥2%) and 27.2% (152 cases by EOS≥3%), respectively. According to either standard, there were no significant differences in sexes, age, course of disease (P>0.05), and there were no significant differences in global initiative for chronic obstructive lung disease (GOLD) grades, parameters of pulmonary function, modified british medical research council (mMRC) scores, rate of antibiotic use, systemic glucocorticoids administration, and average daily expenses (P>0.05). According to 2% standard, leucocytes, neutrophils, monocytes, hs-CRP were lower than non-eosinophilic patients [(5.9±2.0)×10(9)/L vs (8.2±4.0)×10(9)/L, (3.9±1.6)×10(9)/L vs (6.5±3.8)×10(9)/L, (0.446±0.169)×10(9)/L vs (0.501±0.276)×10(9)/L, (25.8±35.9) vs (46.2±55.6) mg/L, all P<0.01]; basophils, lymphocytes were higher than non-eosinophilic patients [(0.043±0.025)×10(9)/L vs (0.029±0.021) ×10(9)/L, (1.3±0.6) ×10(9)/L vs (1.1±0.6) ×10(9)/L, both P<0.01]; length of stay, total hospital expense were shorter (or lower) than non-eosinophilic patients [(10.6±5.0) vs (11.6±5.8) d, (11 851±7 491) vs (14 254±10 751) RMB, both P<0.05]. According to 3% standard, leucocytes, neutrophils, monocytes, hs-CRP were lower than non-eosinophilic patients (all P<0.05), and basophil were higher than non-eosinophilic patients (P<0.01), but no significant differences were observed in lymphocytes, length of stay and total hospital expense (all P>0.05). Conclusion: Eosinophilia is of relative high prevalence in AECOPD patients, and basophil in eosinophilic patients is higher than non-eosinophilic patients.

Three-dimensional digitalized virtual planning for saphenous artery flap: a pilot study.

OBJECTIVE: Since the 1970s, research and applications on flap and muscle flap had solved many problems in microsurgical reconstruction. However, the traditional flap design is completely dependent on two-dimensional (2D) images. The purpose of this study was to discuss the methods in the visualization of saphenous artery flap by digitalized technique and its applications by digitalized technique. METHODS: Two adult fresh cadaver specimens, one male and one female, were subject to radiographic computerized tomography (CT) scanning before and after perfused with lead oxide-gelatine mixture, whose collimation are 0.625 mm (120 kV, 110 mA, 512 × 512 matrix). Through Amira 5.4.1 software, the 2D images in DICOM format were transformed into the 3D models of the entire region. The structures of saphenous artery were observed and the digitized visible models of saphenous artery flap were established through three-dimensional (3D) computerized reconstructions methods from these data using Amira 5.4.1 software. Next six cases of soft-tissue defects of the tibia region, involving the exposure bones underwent contrast-enhanced CT angiography of lower limbs utilizing a 64-row multi-slice spiral CT after median cubital vein injection with Ultravist (3.5 ml/s). 2D images from these data in DICOM format were transformed into computer. The structures of saphenous artery flap were observed and measured using Amira 5.4.1 software. Then, all cases were treated by saphenous artery flap. RESULTS: The 3D reconstructed visible models established from these datasets perfectly displayed the saphenous artery flap anatomy. In six cases, the main trunk and branched of the blood vessels in the designed flap were consistent with the surgical findings. The starting point of the saphenous artery to the average distance of the knee clearance were 119.2 ± 9.6 mm, the average diameter of the saphenous artery from the starting point were 1.5 ± 0.3 mm. The range of flap was 8.0 × 5.0 cm to 20.0 × 8.0 cm. All flaps survived well. After 8-24 months' follow-up the knee flexion was 120-140°, the straight 0-10°. There was no case appeared incision infection. CONCLUSIONS: The preoperative use of 3D digitalized virtual planning for the saphenous artery flap improves the surgical accuracy, decreases the operation time and increases the survival rate of the flap.

Alignment of the lower extremity mechanical axis by computer-aided design and application in total knee arthroplasty.

PURPOSE: The success of total knee arthroplasty (TKA) depends on many factors. The position of a prosthesis is vitally important. The purpose of the present study was to evaluate the value of a computer-aided establishing lower extremity mechanical axis in TKA using digital technology. METHODS: A total of 36 cases of patients with TKA were randomly divided into the computer-aided design of navigation template group (NT) and conventional intramedullary positioning group (CIP). Three-dimensional (3D) CT scanning images of the hip, knee, and ankle were obtained in NT group. X-ray images and CT scans were transferred into the 3D reconstruction software. A 3D bone model of the hip, knee, ankle, as well as the modified loading, was reconstructed and saved in a stereolithographic format. In the 3D reconstruction model, the mechanical axis of the lower limb was determined, and the navigational templates produced an accurate model using a rapid prototyping technique. The THA in CIP group was performed according to a routine operation. CT scans were performed postoperatively to evaluate the accuracy of the two TKA methods. RESULTS: The averaged operative time of the NT group procedures was [Formula: see text] min shorter than those of the conventional procedures ([Formula: see text]  min). The coronal femoral angle, coronal tibial angle, posterior tibial slope were [Formula: see text], [Formula: see text], [Formula: see text] in NT group and [Formula: see text], [Formula: see text], [Formula: see text] in CIP group, respectively. Statistically significant group differences were found. CONCLUSIONS: The navigation template produced through mechanical axis of lower extremity may provide a relative accurate and simple method for TKA.

Urine phyto-oestrogen metabolites are not significantly associated with risk of type 2 diabetes: the Singapore Chinese health study.

We evaluated the relationship between urine concentrations of phyto-oestrogens (isoflavones and lignans) and risk of incident type 2 diabetes in middle-aged and elderly Chinese residing in Singapore. Urine metabolites of isoflavones and lignans were assayed by HPLC among 564 diabetes cases and 564 matched controls in a case-control study nested within the Singapore Chinese Health Study cohort. Participants were free of diagnosed diabetes, CVD and cancer at morning urine collections during 1999-2004. Cases were participants who reported to have physician-diagnosed diabetes at follow-up visits during 2006-2010, whereas controls were randomly selected among those who remained free of diabetes and were matched to the index cases by age, sex, dialect group and date of urine collection. Conditional logistic regression models were used to calculate OR and 95 % CI with adjustment for potential confounders. The mean age of the participants at the time of urine collection was 59·8 years, and the average interval between urine collection and diabetes diagnosis was 4·0 years. The multivariate-adjusted OR for diabetes were 1·00 (reference), 0·76 (95 % CI 0·52, 1·11), 0·78 (95 % CI 0·53, 1·14) and 0·79 (95 % CI 0·54, 1·15) across quartiles of urine isoflavones (P for trend=0·54), and were 1·00 (reference), 0·87 (95 % CI 0·60, 1·27), 1·10 (95 % CI 0·77, 1·56) and 0·93 (95 % CI 0·63, 1·37) for lignans (P for trend=0·93). The results were similar in men and women, as well as for individual metabolites of isoflavones (genistein, daidzein, glycitin and equol) or lignans (enterodiol and enterolactone). The present study did not find a significant association between urine phyto-oestrogen metabolites and risk of type 2 diabetes in Chinese adults.

Essential role of proteasomes in maintaining self-renewal in neural progenitor cells.

Protein turnover and homeostasis are regulated by the proteasomal system, which is critical for cell function and viability. Pluripotency of stem cells also relies on normal proteasomal activity that mitigates senescent phenotypes induced by intensive cell replications, as previously demonstrated in human bone marrow stromal cells. In this study, we investigated the role of proteasomes in self-renewal of neural progenitor cells (NPCs). Through both in vivo and in vitro analyses, we found that the expression of proteasomes was progressively decreased during aging. Likewise, proliferation and self-renewal of NPCs were also impaired in aged mice, suggesting that the down-regulation of proteasomes might be responsible for this senescent phenotype. Lowering proteasomal activity by loss-of-function manipulations mimicked the senescence of NPCs both in vitro and in vivo; conversely, enhancing proteasomal activity restored and improved self-renewal in aged NPCs. These results collectively indicate that proteasomes work as a key regulator in promoting self-renewal of NPCs. This potentially provides a promising therapeutic target for age-dependent neurodegenerative diseases.

HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer.

BACKGROUND: In the Trastuzumab for GAstric cancer (ToGA) study, trastuzumab plus chemotherapy improved median overall survival by 2.7 months in patients with human epidermal growth factor receptor 2 (HER2)-positive [immunohistochemistry (IHC) 3+/fluorescence in situ hybridization-positive] gastric/gastroesophageal junction cancer compared with chemotherapy alone (hazard ratio 0.74). Post hoc exploratory analyses in patients expressing higher HER2 levels (IHC 2+/fluorescence in situ hybridization-positive or IHC 3+) demonstrated a 4.2-month improvement in median overall survival with trastuzumab (hazard ratio 0.65). The ToGA study provides the largest screening dataset available on HER2 overexpression/amplification in this indication. We further analyzed correlation(s) of HER2 overexpression/amplification with clinical and epidemiological factors. METHODS: HER2-positivity was analyzed by histological subtype, tumor location, geographic region, and specimen type. Exploratory efficacy analyses were performed. RESULTS: The HER2-positivity rate was 22.1 % across analyzed tumor samples. Rates were similar between European and Asian patients (23.6 % vs. 23.9 %), but higher in intestinal- vs. diffuse-type (31.8 % vs. 6.1 %), and gastroesophageal junction cancer versus gastric tumors (32.2 % vs. 21.4 %). Across all IHC scores, variability in HER2 staining (≤30 % stained cells) was observed in almost 50 % of cases, with increasing rates in lower IHC categories, and did not affect treatment outcome. The polysomy rate was 4 %. CONCLUSIONS: HER2 expression varies by tumor location and type. All patients with advanced gastric or gastroesophageal junction cancer should be tested for HER2 status, preferably using IHC initially. Due to the unique characteristics of gastric cancer, specific testing/scoring guidelines should be adhered to.