The role of autologous chondrocyte implantation in the treatment of symptomatic chondromalacia patellae.
Chondromalacia patella is a distinct clinical entity of abnormal softening of the articular cartilage of the patella, which results in chronic retropatellar pain. Its aetiology is still unclear but the process is thought to be a due to trauma to superficial chondrocytes resulting in a proteolytic enzymic breakdown of the matrix. Our aim was to assess the effectiveness of autologous chondrocyte implantation on patients with a proven symptomatic retropatellar lesion who had at least one failed conventional marrow-stimulating therapy. We performed chondrocyte implantation on 48 patients: 25 received autologous chondrocyte implantation with a type I/III membrane (ACI-C) method (Geistlich Biomaterials, Wolhusen, Switzerland), and 23 received the Matrix-assisted Chondrocyte Implantation (MACI) technique (Genzyme, Kastrup, Denmark). Over a mean follow-up period of 40.3 months, there was a statistically significant improvement in subjective pain scoring using the visual analogue scale (VAS) and objective functional scores using the Modified Cincinnati Rating System (MCS) in both groups. Chondromalacia patellae lesions responded well to chondrocyte implantation. Better results occurred with MACI than with ACI-C. Excellent and good results were achieved in 40% of ACI-C patients and 57% of MACI patients, but success of chondrocyte implantation was greater with medial/odd-facet lesions. Given that the MACI procedure is technically easier and less time consuming, we consider it to be useful for treating patients with symptomatic chondral defects secondary to chondromalacia patellae.


Diagnostic value of cadmium-zinc-telluride myocardial perfusion imaging versus coronary angiography in coronary artery disease: A PRISMA-compliant meta-analysis.
Rapid progress has been made in research of cadmium-zinc-telluride (CZT) technology in the last few years, which might serve as a new method to diagnose coronary artery disease. However, compared with coronary angiography, the diagnostic value of CZT is still controversial. We aimed to evaluate diagnosis value of coronary angiography versus CZT in coronary artery disease. We searched the database for eligible researches associated with CZT- myocardial perfusion imaging (MPI) and invasive coronary angiography, extracted the relevant data, and rigorously screened it according to the inclusion and exclusion criteria. The accuracy indicators included sensitivity, specificity, accuracy, positive and negative likelihood ratios. According to the inclusion and exclusion criteria, we finally found 20 studies containing 2350 patients in this search. Pooled results showed that sensitivity of CZT-MPI was 0.84% and 95% confidence interval (95% CI): 0.78 to 0.89, specificity was 0.72, 95% CI (0.62-0.76), the specificity was lower apparently. The positive likelihood ratio was 3.0, 95% CI (2.4-3.8), the negative likelihood ratio was 0.22, 95% CI (0.16-0.31), diagnostic odds ratio was 14, 95% CI (7.84-17.42). This meta-analysis showed that CZT-MPI had satisfactory sensitivity and specificity for diagnosing coronary artery disease. Larger studies are required for further evaluation.


Screening of Cell Cycle-Related Genes of Pleurotus eryngii Using Yeast Mutant Strains.
Temperature-sensitive yeast mutants were used to screen for cell cycle-related genes from Pleurotus eryngii genomic DNA. A mushroom genomic DNA library was established and each gene was screened for the ability to rescue seven Saccharomyces cerevisiae temperature-sensitive strains. Hundreds of yeast transformants were selected at restrictive temperatures over 30℃. Plasmids from the transformants that survived were isolated and transformed back into their host strains. The temperature sensitivity of the resulting transformants was tested from 30℃ to 37℃. Ten DNA fragments from P. eryngii were able to rescue yeast temperature-sensitive strains, and their DNA sequences were determined.


New Sources of Adult Plant and Seedling Resistance to Puccinia coronata f. sp. avenae Identified among Avena sativa Accessions From the National Small Grains Collection.
Accessions of cultivated oat (Avena sativa L.) from the United States Department of Agriculture-Agricultural Research Service Small Grains Collection in Aberdeen, ID were characterized for adult plant resistance (APR) and seedling resistance to crown rust, caused by Puccinia coronata f. sp. avenae. Initially, 607 oat accessions with diverse geographic origins were evaluated in field tests in Baton Rouge, LA. Of those, 97 accessions were not fully susceptible and were tested in the field in St. Paul, MN against a diverse P. coronata f. sp. avenae population. Thirty-six accessions that had some level of resistance in both field tests and mean coefficients of infection of ≤20 were further evaluated for APR and seedling resistance. Among these, four accessions (PI 193040, PI 194201, PI 237090, and PI 247930) were resistant to eight P. coronata f. sp. avenae races as seedlings. Twenty-nine accessions had resistance to at least one of the P. coronata f. sp. avenae races. Three accessions (CIav 2272, CIav 3390, and PI 285583) were fully susceptible to all eight P. coronata f. sp. avenae races as seedlings. Further evaluation of the three seedling-susceptible accessions at the flag leaf stage in a growth chamber resulted in moderately susceptible to moderately resistant responses. The resistance sources presented here may contain genes not deployed in elite oat varieties, and may be useful for future crown rust resistance breeding. The adult and seedling resistance found in accessions of the cultivated oat species is especially valuable because it avoids problems associated with the transfer of genes from wild species to cultivated oat.


First isolation of blaIMP-7 in a Pseudomonas aeruginosa in Japan.
We report here the first isolation in Japan of a carbapenem-resistant Pseudomonas aeruginosa strain that carries the metallo-beta-lactamase gene bla(IMP-7). This isolate revealed high-level resistance to all of the tested antibiotics except for piperacillin, showing a multidrug-resistant phenotype.


Patterns of palliative radiotherapy fractionation for brain metastases patients in New South Wales, Australia.
There is a paucity of studies examining variation in the use of palliative radiation therapy (RT) fractionation for brain metastases. The aim of this study is to assess variation in palliative RT fractionation given for brain metastases in New South Wales (NSW), Australia, and identify factors associated with variation. This is a population-based cohort of patients who received whole brain RT (WBRT) for brain metastases (2009-2014), as captured in the NSW Central Cancer Registry. A logistic regression model was used to identify factors associated with fractionation type. Of the 2,698 patients that received WBRT, 1,389 courses (51%) were < 6 fractions, 1,050 courses (39%) were 6-10 fractions, and 259 courses (10%) were > 10 fractions. Older patients were more likely to be treated with shorter courses (P < 0.0001). Patients with primary lung cancers were more likely to receive shorter courses compared with other primary cancers (P < 0.0001). Patients without surgical excision were more likely to receive < 6 fractions compared to those who underwent surgical excision. Shorter courses were more likely to be delivered to patients with the most disadvantaged socioeconomic status (SES) compared with patients with the least disadvantaged SES (P < 0.0001). There were significant fluctuations in the proportion of courses using lower number of fractions over time from 2009 to 2014, but no apparent trend (P = 0.02). There was wide variation in the proportion of shorter courses across residence local health districts, ranging from 24% to 69% for < 6 fractions, 21% to 72% for 6-10 fractions, and 4% to 20% for > 10 fractions (P < 0.0001). This study has identified significant unwarranted variations in fractionation for WBRT in NSW. Accelerating the uptake of shorter fractionation regimens, if warranted through evidence, should be prioritised to enhance evidence-based care.


Short exposure to ethyl and methylmercury prompts similar toxic responses in Drosophila melanogaster.
Methylmercury (MeHg) and ethylmercury (EtHg) are important mercury organic forms in terms of human poisoning. Since the comparative effects of compounds are mainly in vitro, this study was designed to investigate the toxicities induced by MeHg and EtHg in an in vivo study using adult Drosophila melanogaster (D. melanogaster). Firstly, we performed a survival curve, where the flies were fed on a medium containing MeHg and EtHg at concentrations ranging from 2.5 to 200 μM, until the end of their lifespan. After that, the concentrations 25 and 200 μM of MeHg and EtHg were chosen to be tested in a short exposure for 5 days. The analysis of survival by Kaplan-Meier plot revealed that all concentrations of MeHg and EtHg reduced significantly the lifespan of the flies. Short exposure to both concentrations of MeHg and EtHg impaired the ability of flies in the climbing assay and induced lipid peroxidation. Only the flies exposed to the highest concentration had viability loss, thiol depletion, and increased reactive species (RS) and Hg levels in the whole body. Our findings indicate that MeHg and EtHg exhibit similar toxic effects in vivo, and that oxidative stress is a phenomenon behind the toxicity of both mercurials. The data obtained also reinforce the use of D. melanogaster as a useful organism for basic toxicological research.


The effects of Nod-like receptors on adaptive immune responses.
It has long been appreciated that cues from the innate immune system orchestrate downstream adaptive immune responses. Although previous work has focused on the roles of Toll-like receptors in this regard, relatively little is known about the ways in which Nod-like receptors instruct adaptive immunity. Here we review the functions of different members of the Nod-like receptor family in orchestrating effector and anamnestic adaptive immune responses. In particular, we address the ways in which inflammasome and non-inflammasome members of this family affect adaptive immunity under various infectious and environmental contexts. Furthermore, we identify several key mechanistic questions that studies in this field have left unaddressed. Our aim is to provide a framework through which immunologists in the adaptive immune field may view their questions through an innate-immune lens and vice-versa.


A cable-driven highly compact single port laparoscopic surgical robot with sequentially inserted arms.
The single port surgical robot causes only one incision and brings many benefits to patients. It is very challenging to design a single port surgical robot that causes a smaller incision than current products. This paper presents a highly compact single port laparoscopy surgical robot, which makes full use of the space of the port and only needs a 15 mm-diameter port. The robot is composed of a camera manipulator and two operating manipulators. The non-fully cylindrical manipulators enter the port sequentially, and the equivalent diameter of each operating manipulator is 12 mm. An additional 9 mm-diameter channel is left for other surgical tools to pass through after all manipulators entering the port. The kinematics model of the robot is established, including detailed forward kinematics model and inverse kinematics solution based on geometric iteration method. The teleoperation experiment shows that the manipulator can complete the object-grasping, object-transfer and weight-lifting tasks. The proposed single port surgical robot design concept can also be extended to the field of natural orifice transluminal endoscopic surgical robots.


Polygenic hazard score modified the relationship between hippocampal subfield atrophy and episodic memory in older adults.
Understanding genetic influences on Alzheimer's disease (AD) may improve early identification. Polygenic hazard score (PHS) is associated with the age of AD onset and cognitive decline. It interacts with other risk factors, but the nature of such combined effects remains poorly understood. We examined the effect of genetic risk and hippocampal atrophy pattern on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD using structural MRI. Participants included 51 memory unimpaired normal control (NC), 69 mild cognitive impairment (MCI), and 43 AD adults enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Hierarchical linear regression analyses examined the main and interaction effects of hippocampal subfield volumes and PHS, indicating genetic risk for AD, on a validated episodic memory composite score. Diagnosis-stratified models further assessed the role of PHS. Polygenic hazard score moderated the relationship between right fimbria/hippocampus volume ratio and episodic memory, such that patients with high PHS and lower volume ratio had lower episodic memory composite scores [ΔF = 6.730, p = 0.011, ΔR 2 = 0.059]. This effect was also found among individuals with MCI [ΔF = 4.519, p = 0.038, ΔR 2 = 0.050]. In contrast, no interaction effects were present for those NC or AD individuals. A follow-up mediation analysis also indicated that the right fimbria/hippocampus volume ratio might mediate the link between PHS and episodic memory performance in the MCI group, whereas no mediation effects were present for those NC or AD individuals. These findings suggest that the interaction between AD genetic risk and hippocampal subfield volume ratio increases memory impairment among older adults. Also, the results highlighted a potential pathway in which genetic risk affects memory by degrading hippocampal subfield volume ratio in cognitive decline subjects.


Management of asymptomatic severe hypertriglyceridemia.
Severe hypertriglyceridemia is an urgent presentation that requires acute treatment. We present a rare case that could not be controlled by medical management and required plasmapheresis.


Non-bladder conditions in female Taiwanese patients with interstitial cystitis/hypersensitive bladder syndrome.
To detect non-bladder conditions in patients with interstitial cystitis/hypersensitive bladder syndrome. A total of 122 female interstitial cystitis/hypersensitive bladder syndrome patients and a control group of 122 age-matched female patients with stress urinary incontinence completed screening questionnaires for irritable bowel syndrome, temporomandibular disorder, multiple chemical sensitivities, tension and migraine headache, localized myofascial pain disorder, and fibromyalgia. Interstitial cystitis/hypersensitive bladder syndrome patients also completed questionnaires on interstitial cystitis/hypersensitive bladder syndrome symptom severity, including the O'Leary-Sant symptom index, and the visual analog scale for pain and urgency. Interstitial cystitis/hypersensitive bladder syndrome patients were more likely to meet diagnostic criteria for irritable bowel syndrome than controls (37.5% vs 11.5%), and tension/migraine headache (38.7% vs 15.7%; all P < 0.001). The prevalence of temporomandibular disorder, multiple chemical sensitivities, localized myofascial pain disorders and fibromyalgia did not reach a statistical significant difference between the two groups. In the multivariate model, associations were also observed for irritable bowel syndrome (odds ratio 2.546; 95% confidence interval 1.136-5.704) and tension/migraine headache (odds ratio 2.684; 95% confidence interval 1.233-5.842). Patients with more comorbid conditions had more severe and bothersome interstitial cystitis/hypersensitive bladder syndrome symptoms as measured by the visual analog scale of pain (P = 0.008) and O'Leary-Sant bother index (P = 0.035). Interstitial cystitis/hypersensitive bladder syndrome patients are more likely to have multiple non-bladder conditions. These conditions correlate with the severity of interstitial cystitis/hypersensitive bladder syndrome symptoms.


Inadequate intravenous feeding in sick neonates: a retrospective study.
It is a common experience that during intravenous feeding (IVF) in neonates the administered amounts do not always meet the recommendations. In an attempt to quantify these deficits and to determine the causes we studied the data of 2 comparable groups of neonates admitted to a neonatal intensive care unit (NICU). In Group 1 (N = 107; gestational age 25-42 weeks; birth weight 690-5920 g) the minimum recommended intake of energy (70 kCal/kg/d) and of aminoacids (2.5g/kg/d) was not met in 17% and in 71% respectively. The main causes of inadequate intake were believed to be the nearly exclusive use of peripheral venous access, and the restriction in glucose and/or lipid administration because of extreme prematurity and/or severe illness. In Group 2 (N = 99; gestational age 24-42 weeks; birth weight 670-4300 g), where these causes were corrected, 11% and 54% of the patients still received an insufficient amount of energy and amino acids respectively. It can be concluded that in the daily practice in a NICU, even in optimal conditions and following the recent recommendations for IVF, a considerable proportion of preterm neonates do not receive the minimal recommended amount of energy and aminoacids.


Industrial medicine and acute musculoskeletal rehabilitation. 1. Diagnosing and managing the injured worker with low back pain.
This self-directed learning module highlights the evaluation and management of the injured worker with low back pain (LBP). This chapter reviews the importance of recognizing the physiologic implications of a lifting injury and evaluating its structural etiology in a worker with LBP. A review of the steps required to make an accurate diagnosis is included. Justifying restrictions and prescribing therapeutic intervention is summarized. To be able to provide a step-by-step plan for evaluating, treating, and safely returning to work the injured worker with LBP.


Recent progress in direct production of furfural from lignocellulosic residues and hemicellulose.
Furfural is a vital biomass-derived platform molecule, which can be used to synthesize a wide range of value-added chemicals. Furfural and its derivatives are promising alternatives to conventional petroleum chemicals. However, recent industrial production of furfural existed some thorny problems, including low efficiency, energy waste, and environmental pollution. Therefore, tremendous and continuous efforts have been made by researchers to develop novel furfural production processes with high economic viability, production efficiency, and sustainability. This review summarized the merits and shortcomings of disparate catalytic systems for the synthesis of furfural from biomass and biomass pretreatment hydrolysate on the basis of recently published literature. Furthermore, the suggestions for furfural production research were put forward.


Postoperative radiotherapy in thymic carcinoma: treatment results and prognostic factors.
To analyze the treatment results and prognostic factors of patients with primary thymic carcinoma treated by total or subtotal tumor resection followed by radiotherapy alone. Between October 1987 and October 1997, 26 patients with thymic carcinoma were treated with complete or incomplete surgical resection and postoperative adjuvant irradiation without chemotherapy. The radiation was delivered with 10-MV X-ray given 5 days per week at 1.8 to 2 Gy per fraction. Total doses ranged from 40 to 70 Gy. All patients had at least 40 months of follow-up. The 5-year overall survival rate, local control rate, and distant metastasis-free rate were 77%, 91%, and 57%, respectively. Several prognostic factors, including sex, age, extent of resection (total resection vs. subtotal resection), Masaoka staging (early Stage I + II vs. advanced Stage III + IV), pathology (low-grade vs. high-grade), and postoperative radiation dose (> or =60 Gy vs. <60 Gy), were evaluated in univariate analysis. The Masaoka staging system was the only statistically significant predictor in overall survival rate (p = 0.0482) and distant metastasis-free rate (p = 0.0193). The Masaoka staging system is the most important prognostic factor in primary thymic carcinoma patients receiving postoperative radiotherapy alone. For resectable tumors, surgery and postoperative radiotherapy can achieve good local control, but the distant metastatic rate is still high. Further investigation of more effective chemotherapy is needed.


Novel vaccines against influenza viruses.
Killed and live attenuated influenza virus vaccines are effective in preventing and curbing the spread of influenza epidemics when the strains present in the vaccines are closely matched with the predicted epidemic strains. These vaccines are primarily targeted to induce immunity to the variable major target antigen, hemagglutinin (HA) of influenza virus. However, current vaccines are not effective in preventing the emergence of new pandemic or highly virulent viruses. New approaches are being investigated to develop universal influenza virus vaccines as well as to apply more effective vaccine delivery methods. Conserved vaccine targets including the influenza M2 ion channel protein and HA stalk domains are being developed using recombinant technologies to improve the level of cross protection. In addition, recent studies provide evidence that vaccine supplements can provide avenues to further improve current vaccies.


Aspects influencing clinical reasoning and decision-making when matching treatment to patients with low back pain in primary healthcare.
It is unclear how physiotherapists match treatment to patients with low-back pain (LBP) in primary healthcare. A further exploration of physiotherapists' perspective of matching treatments to the individual patient in this setting is needed. The aim of this study was to explore and describe aspects influencing physiotherapists' clinical reasoning in the decision-making on individualized treatment of LBP in primary healthcare. This was an explorative study using qualitative content analysis. Fifteen semi-structured individual interviews were conducted with physiotherapists, men and women, experienced and novice, working in primary healthcare settings in one sparsely populated region and in one larger city in Sweden. Two overarching themes were identified influencing decision-making for individualized treatment of LBP: 1) Matching requires differentiation and adaptation, with categories describing specific patient characteristics, assessment findings and treatment adaptations (classification of pain and bodily findings; patient physical capacity and emotions; patient awareness and motivation; treatment combinations and atypical treatment rationales): and 2) The tension between trust and barriers; with categories describing aspects of physiotherapists' convictions, constraints and working environment (confidence in treatments and oneself; physiotherapists' terms overrule patients' preferences; personal constraints and workplace approach and priorities). This study describes aspects of the patients, the physiotherapists and their workplaces that influence decisions for individualized treatment of LBP. The findings underpin the need for clinician self-reflection, initiatives for skilled clinical competence and the weight clinician observations carry on the complex treatment selection process which need to be appreciated when implementing evidence-based recommendations in clinical practice.


Antagonist of sphingosine 1-phosphate receptor 3 reduces cold injury of rat donor hearts for transplantation.
Cold storage is widely used to preserve an organ for transplantation; however, a long duration of cold storage negatively impacts graft function. Unfortunately, the mechanisms underlying cold exposure remain unclear. Based on the sphingosine-1-phosphate (S1P) signal involved in cold tolerance in hibernating mammals, we hypothesized that S1P signal blockage reduces damage from cold storage. We used an in vitro cold storage and rewarming model to evaluate cold injury and investigated the relationship between cold injury and S1P signal. Compounds affecting S1P receptors (S1PR) were screened for their protective effect in this model and its inhibitory effect on S1PRs was measured using the NanoLuc Binary Technology (NanoBiT)-β-arrestin recruitment assays. The effects of a potent antagonist were examined via heterotopic abdominal rat heart transplantation. The heart grafts were transplanted after 24-hour preservation and evaluated on day 7 after transplantation. Cold injury increased depending on the cold storage time and was induced by S1P. The most potent antagonist strongly suppressed cold injury consistent with the effect of S1P deprivation in vitro. In vivo, this antagonist enabled 24-hour preservation, and drastically improved the beating score, cardiac size, and serological markers. Pathological analysis revealed that it suppressed the interstitial edema, inflammatory cell infiltration, myocyte lesion, TUNEL-positive cell death, and fibrosis. In conclusion, S1PR3 antagonist reduced cold injury, extended the cold preservation time, and improved graft viability. Cold preservation strategies via S1P signaling may have clinical applications in organ preservation for transplantation and contribute to an increase in the donor pool.


Sublingual microcirculatory flow is impaired by the vasopressin-analogue terlipressin in a patient with catecholamine-resistant septic shock.
For many decades arterial blood pressure regulation has been an important issue in the treatment of septic shock. The pathogenesis of this persistent hypotension is complex and multifactorial, but inability of vascular smooth muscle to contract in the presence of vasoconstrictive agents seems to be a key factor. Many mechanisms have been proposed to account for this failure, including nitric oxide (NO) overproduction and vasopressin deficiency (1). However, improvement of outcome due to intervention in these mechanisms fails to be reported despite the restoration of blood pressure. Recent studies of the microcirculation in humans by means of orthogonal polarization spectral (OPS) imaging have opened challenging new perspectives to study the microcirculation (2, 3). We report a case in which sublingual OPS imaging was performed upon administration of terlipressin in a patient with catecholamine-resistant septic shock. It indicates that much caution should be taken when considering such potent vasoconstrictor when correcting blood pressure during shock.


Multicommutated flow analysis system based on fluorescence microdetectors for simultaneous determination of phosphate and calcium ions in human serum.
A bianalyte multicommutated flow analysis (MCFA) system allowing simultaneous determination of calcium and phosphate ions is developed. The detection of ions is based on measurements of fluorescence of calcein and rhodamine B, respectively. For such measurements performed under flow analysis conditions two dedicated detectors made of three integrated light emitting diodes each and operating according to fluorometric paired emitter detector diode (FPEDD) principle, have been used. The developed 2FPEDD-MCFA system has been applied for serum analysis. The system provides low detection limits (16 µM and 3.6 µM for calcium and phosphate ions, respectively) and therefore small consumption of sample (8 µL) for analysis. The throughput of the system allows about 20 bianalyte determinations per hour. The presented system was validated using human serum samples. The analysis results show good correlation with those from the clinical laboratory obtained using reference photometric methods. The results of real samples analysis show that it is necessary to determine both calcium and phosphate ions simultaneously because their levels is serum are rather weakly correlated.


Cisternographic imaging patterns: effects of partial extra-arachnoid radiopharmaceutical injection and postinjection CSF leakage.
A cisternographic pattern of subarachnoid block with transient or no ventricular radiopharmaceutical reflux was observed in 52% of 105 patients with partial extra-arachnoid injections or postinjection leakage of CSF or both at the lumbar puncture site. In several patients, adequate repeat studies demonstrated considerably different CSF flow patterns. This block pattern was seen in only 11% of 217 patients with adequate intrathecal injections. Lumbar CSF leakage may alter the pattern seen on a cisternographic study and, if present, the study should be interpreted with caution.


[Screening for mitochondrial DNA mutation in two pedigrees with nonsyndromic inherited sensorineural hearing loss].
To investigate the genetic mechanism of maternal nonsyndromic inherited sensorineural hearing loss(SNHL), to identify the incidence of the 7445(G) mutation in such pedigrees and sporadic patients with SNHL, and to provide the theoretical evidence for the diagnosis of this disease. Blood samples were obtained from 2 pedigrees and 14 sporadic patients with SNHL. DNA was extracted from the isolated leukocytes. The mitochondrial DNA (mtDNA) fragments were amplified by PCR. The 1555(G), 3243(G) and 7445(G) mutation was detected by Alw 26 I, Apa I and Xba I restriction endonuclease digestion respectively. The sequence of 12S rRNA, tRNA(Leu(UUR)) and tRNA(Ser(UCN)) was examined. Restriction endonuclease digestion analysis showed that 12 individuals from 2 pedigrees carried homoplasmic 7445(G) mutation, which was of maternal inheritance. Six individuals from 2 pedigrees and 14 sporadic patients did not have 7445(G) mutation. All individuals did not have 1555(G) and 3243(G) mutation. The sequence analysis further showed that none of them carried homoplasmic 1555(G) and 3243(G) mutation, 12 individuals had (nt)7445 A--> G substitution in tRNA(Ser(UCN)) gene. The incidence of 7445(G) mutation in such pedigrees is higher than that in sporadic patients. Screening for mtDNA 7445(G) mutation combined with 1555(G) examination is of much value to clinical use.


Cytoarchitectonic correlates of the vibrissae in the medullary trigeminal complex of the mouse.
Cytoarchitectonic patterns in the medullary trigeminal complex of the mouse corresponding to mystacial vibrissae are described. These patterns are found within trigeminal sub-nuclei principalis, interpolaris and caudalis. The patterns are due to differential cell packing and are homeomorphic to the arrangement of the mystacial vibrissae on the face. The cytoarchitecture is similar, but complementary, to patterns of trigeminal afferents previously described using histochemical staining methods. Neonatal cautery of groups of vibrissae produces appropriate, specific and localized cytoarchitectural changes within all 3 trigeminal sub-nuclei.


Evaluation of the neurofilament light chain as a biomarker in children with spinal muscular atrophy treated with nusinersen.
This study aimed to evaluate the neurofilament light chain (NfL) as a biomarker for treatment responses in children with a broad spectrum of spinal muscular atrophy (SMA) under nusinersen treatment. We measured NfL levels in serum (sNfL) and cerebrospinal fluid (cNfL) in nusinersen-treated patients with SMA and children without neurologic disorders. Correlations between cNfL and sNfL levels and motor function scores were analyzed. sNfL and cNfL levels were measured in eight patients with SMA (SMA type 1, n = 3; SMA type 2, n = 5). sNfL levels were strongly correlated with cNfL levels regardless of the SMA subtype (r = 0.97, P < 0.001). Patients with SMA type 1 had higher baseline cNfL and sNfL levels before treatment initiation than those with SMA type 2 and neurologically healthy children. In patients with acute stage of SMA type 1 and 2, the NfL level rapidly decreased during the nusinersen treatment loading phase followed by stabilization at a lower plateau level. In contrast, in a patient with a chronic stage of SMA type 2, the NfL level remained within the normal range with no apparent downward trend. Motor function scores showed a tendency toward an inverse correlation with NfL levels in patients with acute stage although not in patients with chronic stage. cNfL and sNfL levels can be promising biomarkers for monitoring treatment response in patients within their acute stage, particularly in SMA type 1, although not in patients with a chronic stage of SMA type 2.


Family, educational and peer influences on the alcohol use of female and male adolescents.
This research provides estimates of how strongly family bonds, family drug use, age, educational commitment and peer drug use are associated with the frequency and amount of alcohol consumption among adolescents, and compares females and males. Using questionnaire data from a random sample of 27,000 adolescents, structural equation modeling is used to evaluate the strength of several risk factors. The influence of family bonds is moderately strong but operates primarily through peers; adolescents with higher family bonds are less likely to have close friends who are involved with drugs. Family bonds have a relatively strong, positive association with educational commitment, and adolescents with a higher educational commitment tend to drink less frequently; and when they drink, they tend to consume smaller amounts. Living in a family where other family members have a problem with alcohol or other drugs increases the chance that an adolescent has friends who drink or use other drugs. Family bonding has small but significant direct effects and moderate indirect effects on both the frequency and amount of alcohol use. Family and peer influences are similar for both females and males. Living in a family where other family members have a drug problem increases the chance that an adolescent has friends who use drugs. Family bonding appears to be an important social control mechanism that may decrease the risk of alcohol abuse among adolescents.


In situ deprotection and dynamic covalent assembly using a dual role catalyst.
Utilization of constituent molecular precursors bearing covalently coreactive functional groups for self-assembly risks premature reaction, impeding synthetic and purification efforts. To prevent premature amine-aldehyde condensation for oligomers bearing both groups, we employ a dual-role Lewis acid catalyst for both in situ acetal deprotection and subsequent imine exchange, effecting oligomer assembly.


Inhaled albuterol powder for the treatment of asthma--a dose-response study.
Many patients are unable to obtain optimal benefit from inhaled bronchodilators as delivered by metered-dose aerosol spray because of difficulty in synchronizing release of medication with the start of inspiration. The Rotahaler is a flow-activated device that avoids this problem since the act of inspiration itself delivers medication to the lungs. In this randomized, double-blind, crossover study, each of 20 male patients with moderate to severe asthma, ages 12 to 23 yr, received a single treatment with 100, 200, or 400 mcg of albuterol powder or placebo by Rotahaler on 4 study days separated by 2 to 10 days. All patients stopped theophylline and inhaled beta-agonists as needed 24 and 12 hr, respectively, before study days. All patients emptied the Rotahaler with a single inhalation. Pulmonary functions were followed for 8 hr after medication. Statistical analyses of FEV1, FEF25-75, and FVC revealed that all doses of albuterol powder were superior to placebo within 5 min with a log dose-response trend for both degree and duration of bronchodilation.


Do Corticosteroids Still Have a Role in the Management of Third Molar Surgery?
The use of corticosteroids to reduce the post-operative sequelae of lower third molar surgery, namely pain, swelling and trismus, has been well studied by many researchers over the past 6 decades. This study reviewed the reported outcome of corticosteroids used in controlling the above sequalae after third molar surgery. A PubMed, Medline, EMBASE and Google search was undertaken of all controlled clinical trials on the effects of corticosteroids on pain, swelling and trismus after lower third molar surgery. The review was limited to studies published over the last 10 years (2006-2015). Of the 46 initially retrieved articles, 34 were finally included. Eleven studies compared the effect of 2 similar (but different dose) or different group of corticosteroids. Thirty-one studies reported the effects of corticosteroids on all sequale, 2 reported the outcome on swelling and trismus and another 1 on swelling and pain only. In 16 of the studies, corticosteroid use resulted in significant reductions in pain after third molar removal. Twenty-two out of 29 studies reported reduced swelling against negative control while 18 out of 25 studies reported improved mouth opening. Fourteen studies reported the benefit of corticosteroids on all 3 sequelae, with 71.4% resulted from the use of methylprednisolone. Although there are some conflicting effects, the results of this analysis shows in general the benefits derived from short-term use of corticosteroids in relation to pain, swelling and trismus following third molar surgical extraction, with no side effects observed. This work was supported by the University of Malaya's High Impact Research grant UM.C/625/1/HIR/MOHE/05.


Atomic/molecular layer deposition: a direct gas-phase route to crystalline metal-organic framework thin films.
Atomic/molecular layer deposition offers us an elegant way of fabricating crystalline copper(ii)terephthalate metal-organic framework (MOF) thin films on various substrate surfaces. The films are grown from two gaseous precursors with a digital atomic/molecular level control for the film thickness under relatively mild conditions in a simple and fast one-step process.


Ultrastructural and cytophotometric studies of lectin binding by human pulmonary macrophages from asthmatic and normal subjects.
Pulmonary macrophages from normal subjects and asthmatic patients were examined for the presence of sugar residues on their surface. The technique of bronchoalveolar lavage was employed to obtain cell samples. Ultrastructural and cytophotometric methods were used for studying the patterns of lectin binding by these two groups of macrophages. Three lectins, Concanavalin A (Con A), Wheat germ agglutinin (WGA) and Ricinus communis agglutinin (RCA), were used in this investigation. Pulmonary macrophages from both normal and asthmatic persons revealed a high level of Con A, WGA and RCA binding. The distribution of the electron dense reaction product on the macrophage surfaces was relatively uniform. Quantitative cytophotometric studies showed that the level of binding of Con A by macrophages from both groups was approximately the same. Similar results were obtained with WGA--the difference between macrophages from normal and asthmatic persons was not statistically significant. In the case of RCA, macrophages from asthmatic patients showed a higher level of lectin binding than macrophages from normal persons. The conclusion is made that macrophages from asthmatic persons have more D-galactose residues on their surface.


γ-Glutamyltranspeptidase from Bacillus amyloliquefaciens: transpeptidation activity enhancement and L-theanine production.
L-theanine, a unique amino acid in green tea with health benefits, can be enzymatically synthesized by γ-glutamyltranspeptidase (γ-GT; EC 184.108.40.206). Here, a salt-tolerant γ-glutamyltranspeptidase from a marine bacterium Bacillus amyloliquefaciens was expressed in Escherichia. coli BL21 (DE3) and was shown to be optimally active at 55 °C, pH 8.5 and alkali stable. A mutant, with higher transpeptidation activity, was obtained following two rounds of directed evolution using error-prone PCR and site-saturation mutagenesis. The mutation increased the ratio of transpeptidation to hydrolysis from 1.6 to 35.6. Additionally, Kinetic analysis exhibited 17.5% decrease of Km, 13.0-fold increase of Kcat, and 16.3-fold increase of Kcat/Km in mutant V319A/S437 G versus the wild-type. The 3-D modelling analysis revealed a tighter binding pocket in mutant V319A/S437 G. The frequency of hydrogen bond between donor substrate and two residues in the catalytic pocket (Gly437 and Thr375) was enhanced, which stabilized the ligand binding and thus improved the catalytic efficiency. The optimal conditions for the biocatalytic synthesis were determined as pH 10.0, 20 μg mL-1BaGT, 200 mM L-glutamine, 2 M ethylamine, and a reaction time of 5 h. The V319A/S437 G mutant was shown to increase the percentage yield of L-theanine from 58% to 83%. These results indicate the great potential of V319A/S437 G in L-theanine production after further study.


COVID-19 AdenoviralVector Vaccine and Central Retinal Vein Occlusion.
The purpose of this article is to report a case of sudden onset ischemic retinal central vein occlusion after a second dose of COVID-19 adenoviral vector vaccine. A 54-year-old woman with systemic arterial hypertension developed ischemic central retinal vein occlusion in her right eye on day 2 after the second dose of COVID-19 adenoviral vector vaccine ChAdOx1 nCoV-19/ AZD1222, Oxford-AstraZeneca. Adenoviral vector vaccine promotes both cellular and humoral immune responses, increasing the level of inflammatory cytokines. These cytokines are the same implied in the possible pathogenesis of central retinal vein occlusion. Subsequently, we recommend informing patients at risk of possible ocular adverse events, which require urgent evaluation.


Investigating the role of glycans in Omicron sub-lineages XBB.1.5 and XBB.1.16 binding to host receptor using molecular dynamics and binding free energy calculations.
Omicron derived lineages viz. BA.2, BA.3, BA.4 BA.5, BF.7 and XBBs show prominence with improved immune escape, transmissibility, infectivity, and pathogenicity in general. Sub-variants, XBB.1.5 and XBB.1.16 have shown rapid spread, with mutations embedded throughout the viral genome, including the spike protein. Changing atomic landscapes in spike contributes significantly to modulate host pathogen interactions and infections thereof. In the present work, we computationally analyzed the binding affinities of spike receptor binding domains (RBDs) of XBB.1.5 and XBB.1.16 towards human angiotensin-converting enzyme 2 (hACE2) compared to Omicron. We have employed simulations and binding energy estimation of molecular complexes of spike-hACE2 to assess the interplay of interaction pattern and effect of mutations if any in the binding mode of the RBDs of these novel mutants. We calculated the binding free energy (BFE) of the RBD of the Omicron, XBB.1.5 and XBB.1.16 spike protein to hACE2. We showed that XBB.1.5 and XBB.1.16 can bind to human cells more strongly than Omicron due to the increased charge of the RBD, which enhances the electrostatic interactions with negatively charged hACE2. The per-residue decompositions further show that the Asp339His, Asp405Asn and Asn460Lys mutations in the XBBs RBD play a crucial role in enhancing the electrostatic interactions, by acquiring positively charged residues, thereby influencing the formation/loss of interfacial bonds and thus strongly affecting the spike RBD-hACE2 binding affinity. Simulation results also indicate less interference of heterogeneous glycans of XBB.1.5 spike RBD towards binding to hACE2. Moreover, despite having less interaction at the three interfacial contacts between XBB S RBD and hACE2 compared to Omicron, variants XBB.1.5 and XBB.1.16 had higher total binding free energies (ΔGbind) than Omicron due to the contribution of non-interfacial residues to the free energy, providing insight into the increased binding affinity of XBB1.5 and XBB.1.16. Furthermore, the presence of large positively charged surface patches in the XBBs act as drivers of electrostatic interactions, thus support the possibility of a higher binding affinity to hACE2.


Denitrification and phenol degradation in a contaminated aquifer.
A natural groundwater system modified by pollutant phenols and agricultural nitrate has been modelled in the laboratory by a series of sacrificial microcosm experiments. Samples of aquifer sediment and groundwater from the margin of the phenol plume were used to inoculate anaerobic microcosms enriched in nitrate and pollutant phenols. Rapid degradation of phenol and p-cresol was observed over a 35-day period leading to the generation of inorganic carbon and a number of transient intermediates. O-cresol proved to be recalcitrant on the experimental time-scale. A mass balance calculation shows that, during degradation, carbon was conserved in the aqueous phase. Groundwater-sediment interactions were monitored using carbon stable isotope data. A mass balance for solution TIC indicates thatp-cresol degradation stimulated the dissolution of sedimentary carbonate phases due to the formation of carbonic acid. Compound-specific carbon isotope analysis (GC-IRMS) was used to search for 13C enrichment in residual p-cresol. A slight enrichment trend (epsilon = -2.5/1000) was tentatively identified. The potential of this fractionation effect for obtaining in situ degradation rates is discussed. Results from the microcosm experiments help to explain the observed distribution of nitrate and phenols within the polluted aquifer.


Monitoring and risk assessment of exposure to organochlorine pesticides through the water supply system, case of Karkheh River in southwest Iran.
In this investigation, the concentration of some organochlorine pesticides (OCPs) was monitored in the Karkheh River and the risk assessment of exposure to these pesticides residue through the water supply system was calculated. The mean concentrations of Lindane, Heptachlor, Chlordane, Dieldrin, Endrin, DDT were 0.135, 0.123, 0.077, 0.081, 0.076, 0.01 µg/L, respectively. The average risk of Lindane, Heptachlor, Chlordane, Dieldrin, DDT, and Endrin for adults was 1.2 E-6, 1.1E-6, 7E-7, 7.6E-7, 9E-8, 7E-7 or non-carcinogenic risks to adults decreased in Dieldrin > Chlordane > Heptachlor > Endrine > DDT > lindane. The hazard index for all organochlorine pesticides was less than 1. These results did not raise concerns about the health of people exposed to studied pesticides. Total concentrations of all OCPs in the Karkheh River were below guidelines for individual pesticides. The hazard quotient showed that the consumption of treated water from the Susangard drinking water treatment plant has no non-cancerous effects. The HI was less than 1 that indicating the risk of exposure to a mixture of OCPs was not significant. Developing policies to reduce the use of pesticides and the use of suitable management practices could be implemented to lower the pesticide levels in the Karkheh River.


Role of hypoxia in tumor angiogenesis-molecular and cellular angiogenic crosstalk.
The mechanisms by which tumors recruit their vasculature has been subject to intense investigations. The acquisition of a functional blood supply seems to be rate-limiting for the ability of a tumor to grow beyond a certain size and to metastasize to other sites. Accumulating evidence indicates that hypoxia and the key transcriptional system, HIF (hypoxia-inducible factor), are the major triggers for new blood vessel growth in malignant tumors. Although vessel growth and maturation are complex and highly coordinated processes requiring the sequential activation of a multitude of factors, there is a consensus that vascular endothelial growth factor and angiopoietin signaling represent crucial steps in tumor angiogenesis. Recent insights into cellular and molecular crosstalk suggest a model in which hypoxia, HIF, and several HIF target genes participate in the coordinated collaboration between tumor, endothelial, inflammatory/hematopoietic, and circulating endothelial precursor cells to enhance and promote tumor vascularization. A well-integrated understanding of this intricate microenvironment may offer new opportunities for therapeutic intervention.


Pavlovian conditioning-induced hallucinations reduce MMN amplitudes for duration but not frequency deviants.
The mismatch negativity (MMN) is an evoked potential that indexes auditory regularity violations. Since the 90's, a reduced amplitude of this brain activity in patients with schizophrenia has been consistently reported. Recently, this alteration has been related to the presence of auditory hallucinations (AHs) rather than the schizophrenia diagnostic per se. However, making this attribution is rather problematic due to the high heterogeneity of symptoms in schizophrenia. In an attempt to isolate the AHs influence on the MMN amplitude from other cofounding variables, we artificially induced AHs in a non-clinical population by Pavlovian conditioning. Before and after conditioning, volunteers (N = 31) participated in an oddball paradigm that elicited an MMN. Two different types of deviants were presented: a frequency and a duration deviant, as the MMN alteration seems to be especially present in schizophrenia with the latter type of deviant. Hence, this pre-post design allowed us to compare whether experiencing conditioning-induced AHs exert any influence on MMN amplitudes. Our results show that duration-deviant related MMN reductions significantly correlate with the number of AHs experienced. Moreover, we found a significant correlation between AHs proneness (measured with the Launay-Slade Hallucination Extended Scale) and the number of AHs experienced during the paradigm. In sum, our study shows that AHs can be conditioned and exert similar effects on MMN modulation in healthy participants as has been reported for patients with schizophrenia. Thus, conditioning paradigms offer the possibility to study the association between hallucinations and MMN reductions without the confounding variables present in schizophrenia patients.


Electrolyte concentrations in sheep cerebrospinal fluid.
Cerebrospinal fluid (csf) of sheep was obtained by acute lumbar puncture and from chronic cannulations of the lateral cerebral ventricle. The concentrations of ions in the csf including chloride which had previously been reported to be very high, were found to be similar to those of other mammals and were not greatly affected by changes in plasma electrolyte composition associated with adrenalectomy.


[Change in the treatment of tibial plateau fractures].
The treatment of tibial plateau fractures has experienced a number of very different conceptual developments in recent years, not only with respect to technical innovations but also against the background of changing fracture patterns and the growing requirements of patients. What developments in recent years have had a significant impact on current treatment strategies for tibial plateau fractures? Narrative review of publications listed in PubMed on the topic of treatment of complex tibial plateau fractures. While the two-dimensional classifications are becoming less important, computed tomography (CT)-based three-dimensional assessment of fracture progression and an access strategy based on it are coming to the fore. Direct dorsal approaches have been shown to be superior, particularly in the case of relevant posteromedial and/or posterolateral fracture involvement. The step-by-step approach extension via specific osteotomies of ligamentous attachments also enables a needs-dependent and fracture-dependent complete joint visualization and reduction control. In the treatment of geriatric tibial plateau fractures, primary treatment with endoprostheses is becoming increasingly more important to enable early mobilization under full load bearing with significantly shorter rehabilitation times. Modern developments in the context of fracture treatment around the tibial plateau have led to a relevant reduction of infections and improved surgical outcomes; however, the high demands and the improved understanding of fractures still underline the great challenge in the treatment of complex fracture patterns.


Small particle reagents: development of fluorescent variants.
Small particle reagent (SPR) is a widely used method to develop latent fingerprints on non-porous and wet surfaces. Conventionally, molybdenum disulfide based SPR has been used for the development of latent fingerprints while some SPR based on other materials such as charcoal powder, zinc carbonate and titanium dioxide have been reported. Fluorescent preparations of molybdenum disulfide based SPR have also been reported. In the present work, a number of SPR based on zinc carbonate have been developed in combination with various fluorescent dyes to develop latent fingerprints on a number of non-porous surfaces. The quality of the developed fingerprints have been evaluated and found to be reproducible. The shelf life of the reagents developed is found to be acceptable for case work purposes. The relationship between the immersion period of the substrate bearing the latent fingerprints and reagent has also been examined.


Gastrocystoplasty and colocystoplasty in canines: the metabolic consequences of acute saline and acid loading.
An experimental canine model was developed to quantitate the net transmural ion flux of colon and gastric segments used for augmentation cystoplasty. Gastrocystoplasty (4) or colocystoplasty (4) was constructed in 8 female mongrels. Acute intravenous saline and acid loading experiments were performed 2 to 4 weeks after cystoplasty. The mean solute excretion rates for sodium, chloride, phosphorus and ammonia exhibited opposite trends during acute saline and acid loading in this experimental model. The net flux of chloride, ammonia, phosphorus and sodium ions in the colocystoplasty animals was from the mucosa/urine surface to the serum (reabsorption). The opposite trend was true for the gastrocystoplasty. By not reabsorbing ammonium chloride, the gastrocystoplasty preserved an important renal mechanism for systemic acid elimination. This may help to prevent the hyperchloremic metabolic acidosis that can develop when urine comes in contact with small or large bowel segments.


Novel bi-allelic variants in ACTL7A are associated with male infertility and total fertilization failure.
What are the genetic causes of total fertilization failure (TFF) in a proband suffering from male infertility? Novel compound heterozygous variants (c.[463C>T];[1084G>A], p.[(Arg155Ter)];[(Gly362Arg)]) in actin-like protein 7A (ACTL7A) were identified as a causative genetic factor for human TFF. ACTL7A, an actin-related protein, is essential for spermatogenesis. ACTL7A variants have been reported to cause early embryonic arrest in humans but have not been studied in human TFF. We recruited a non-consanguineous family whose son was affected by infertility characterized by TFF after ICSI. Whole-exome sequencing was used to identify the potential pathogenic variants. Artificial oocyte activation (AOA) after ICSI was performed to overcome TFF and any resulting pregnancy was followed up. Sanger sequencing was performed to validate the variants. Pathogenicity of the identified variants was predicted by in silico tools. The ultrastructure of spermatozoa was studied by transmission electron microscopy (TEM). Immunofluorescence staining and western blotting were used to investigate the mechanism of the variants on the affected spermatozoa. Novel compound heterozygous variants in ACTL7A (c.[463C>T];[1084G>A], p.[(Arg155Ter)];[(Gly362Arg)]) were identified in a family with TFF after ICSI. In silico analysis predicted that the variants lead to a disease-causing protein. TEM showed that the ACTL7A variants caused ultrastructural defects in the acrosome and perinuclear theca. Protein expression of ACTL7A and phospholipase C zeta, a key sperm-borne oocyte activation factor, was significantly reduced in the affected sperm compared to healthy controls, suggesting that the ACLT7A variants lead to an oocyte activation deficiency and TFF. AOA by calcium ionophore (A23187) after ICSI successfully rescued the TFF and achieved a live birth for the patient with ACTL7A variants. Given the rarity of sperm-associated TFF, only one family with an only child carrying the ACTL7A variants was found. In addition, the TFF phenotype was not assessed in two or more ICSI cycles, due to the intervention in ICSI with AOA after one failed ICSI cycle. Further studies should validate the ACTL7A variants and its effect on male infertility in larger independent cohorts. : Our findings revealed a critical role of ACTL7A in male fertility and identified bi-allelic variants in ACTL7A associated with human TFF, which expands the genetic spectrum of TFF and supports the genetic diagnosis of TFF patients. We also rescued TFF by AOA and obtained a healthy live birth, which provides a potentially effective intervention for patients with ACTL7A pathogenic variants. This work was supported by the National Natural Science Foundation of China (81971374 and 81401267). No conflicts of interest were declared. N/A.


Single-rooted maxillary first molar with a single canal: endodontic retreatment.
This case report presents an unusual root canal system in a maxillary first molar tooth: a single canal in a single root. The endodontic access cavity displayed only 1 canal orifice. This case demonstrated that: 1) clinicians must have adequate knowledge about root canal morphology and its variations; 2) the location and morphology of root canals should be identified radiologically before the root canal treatment; and 3) careful examination of radiographs and the internal anatomy of teeth is essential.


SEM surface morphology of the contractile cells in the rat seminiferous tubules.
The SEM observation of the basal surface of the contractile cells in the boundary tissue of the seminiferous tubule of the rat revealed that the contractile cells are extremely flat, vary in shape from rectangular to hexagonal, and are arranged close to each other, in the fashion of a tiled floor, around the seminiferous epithelium.


Determination of the Monoclonal Antibody Tocilizumab by a Validated Micellar Electrokinetic Chromatography Method.
Tocilizumab is a monoclonal antibody used in the treatment of several inflammatory and autoimmune diseases as well as cancers. Tocilizumab improves clinical outcomes and reduce mortality rates in patients with COVID-19 disease. A novel, simple and reliable method was developed to determine tocilizumab using micellar electrokinetic chromatography (MEKC). Separation of tocilizumab and the internal standard, methotrexate, was achieved with a background electrolyte consisting of phosphoric acid buffer and sodium dodecyl sulfate (SDS) with UV detection at 195 nm. The method was linear in the concentration range from 10 to 250 µg/mL with correlation coefficient greater than 0.995. The method was successfully applied to the analysis of human and rat plasma samples with good recoveries. Sample preparation involved protein precipitation followed by dilution of the supernatant. The intra- and inter-day precisions were less than 5%, the accuracy varied from - 2.71 to 3.84%. The proposed method has acceptable analytical performance and could be applied in future clinical and pharmacokinetic studies including anticancer therapy. The online version contains supplementary material available at 10.1007/s10337-022-04148-w.


Ependymoma: a heterogeneous tumor of uncertain origin and limited therapeutic options.
Ependymomas are tumors that typically occur with an age-based site preference, with adults harboring supratentorial and spinal tumors and pediatric tumors being mainly in the posterior fossa. Despite their similar histologic appearance, the prognosis varies significantly by age and tumor location, with a better prognosis in increasing age. The mainstay of treatment remains surgical excision with or without radiation therapy as the tumor biology is poorly understood and chemotherapy is generally considered to be ineffective. More recently, molecular biology data have increased our understanding of the genetic and epigenetic changes that drive these tumors, but still it will take a lot of effort to find effective chemotherapeutic regimens. Currently, we are trying to define a subset of tumors, for which radiation therapy can be avoided.


Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice.
A murine model for acute lethal graft vs. host disease (GVHD) was used to study the role that a number of cytokines play in the development of lethal GVHD. In this study we focused on the role of IL-1, IL-2, IL-4, IL-6, IFN-gamma and TNF-alpha. Lethally irradiated (C57BL x CBA)F1 mice were reconstituted either with 10(7) allogeneic BALB/c spleen cells or with a similar number of syngeneic cells, as a control. A significant rise in serum levels of IL-6, TNF-alpha and IFN-gamma levels was found in allogeneically reconstituted mice. This is in contrast to the syngeneic control group in which no rise was seen. Serum IL-2 and IL-4 levels were below the detection limit. In the supernatant of Con A stimulated spleen cells from allogeneically reconstituted mice IL-6, IFN-gamma and TNF-alpha concentrations were increased. The expression of mRNA for cytokines as detected by reverse transcription PCR was studied in spleen cells. In the allogeneic reconstituted mice the mRNA expression of IL-1alpha, IL-2, IL-6, IFN-gamma and TNF-alpha displayed faster kinetics compared with that in syngeneic reconstituted mice. The effect of treatment with recombinant cytokines, antibodies to cytokines and to cytokine receptors on the development of GVHD was investigated. Administration of recombinant IL-2 to allogeneically reconstituted mice strongly increased the morbidity and mortality whereas injection of IL-1alpha and TNF-alpha did not influence survival. Administration of antibodies against IL-2 or the IL-2 receptor decreased the morbidity and mortality. Anti-IL-6, anti-IFN-gamma, and anti-TNF-alpha mAB, on the other hand, did not affect the morbidity and mortality of GVHD. The results of this study suggest successive waves of cytokine-secreting cell populations consistent with the induction of an inflammatory response in the development of acute GVH disease.


A Quantitative Risk Estimation Platform for Indoor Aerosol Transmission of COVID-19.
Aerosol transmission has played a significant role in the transmission of COVID-19 disease worldwide. We developed a COVID-19 aerosol transmission risk estimation model to better understand how key parameters associated with indoor spaces and infector emissions affect inhaled deposited dose of aerosol particles that convey the SARS-CoV-2 virus. The model calculates the concentration of size-resolved, virus-laden aerosol particles in well-mixed indoor air challenged by emissions from an index case(s). The model uses a mechanistic approach, accounting for particle emission dynamics, particle deposition to indoor surfaces, ventilation rate, and single-zone filtration. The novelty of this model relates to the concept of "inhaled & deposited dose" in the respiratory system of receptors linked to a dose-response curve for human coronavirus HCoV-229E. We estimated the volume of inhaled & deposited dose of particles in the 0.5-4 μm range expressed in picoliters (pL) in a well-documented COVID-19 outbreak in restaurant X in Guangzhou China. We anchored the attack rate with the dose-response curve of HCoV-229E which provides a preliminary estimate of the average SARS-CoV-2 dose per person, expressed in plaque forming units (PFUs). For a reasonable emission scenario, we estimate approximately three PFU per pL deposited, yielding roughly 10 PFUs deposited in the respiratory system of those infected in restaurant X. To explore the model's utility, we tested it with four COVID-19 outbreaks. The risk estimates from the model fit reasonably well with the reported number of confirmed cases given available metadata from the outbreaks and uncertainties associated with model assumptions.


Mesenchymal stem cell-derived extracellular vesicles: emerging concepts in the treatment of spinal cord injury.
Spinal cord injury (SCI) is a prevalent central nervous system disease with a high disability rate, leading to the loss of motor and sensory nerve function. Due to the complex pathophysiology of SCI, more effective clinical treatment strategies are needed. Research has indicated the considerable potential of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC-EVs) as a cell-free therapy in SCI repair and regeneration due to their ability to regulate immune cell activity and stimulate damaged neuron regeneration. Moreover, applying MSCs and engineered EVs can fully exploit the potential of MSC-EVs in spinal cord repair. Here, we outline the pathological process of SCI and its current clinical treatment status, summarize the latest MSC-EVs research and its pretreatment and engineering strategies in SCI treatment, and explore MSC-EVs application prospects.


Prevention of endophthalmitis by collagen shields presoaked in fourth-generation fluoroquinolones versus by topical prophylaxis.
To compare the prophylaxis of collagen shields presoaked in antibiotics versus antibiotic drops after bacterial anterior chamber challenge. John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Forty rabbits received bilateral 0.03 mL intracameral injections of Staphylococcus epidermidis (5 x 10(8) colony-forming units). Four groups of 10 rabbits had their eyes randomized to receive (1) 3 mg/mL gatifloxacin (Zymar) drops or shield in Zymar, (2) Zymar drops or shield in 10 mg/mL gatifloxacin (Tequin), (3) 5 mg/mL moxifloxacin (Vigamox) drops or shield in Vigamox, or (4) balanced salt solution (BSS) drops or shield in BSS. Each eye received Zymar, Vigamox, or BSS 4 times 1 hour before injection. The antibiotic-BSS was administered every 2 hours (5 doses total). One day later, signs of endophthalmitis were scored under the slitlamp. Groups 1 and 2 had significantly lower endophthalmitis incidences (total score > or = 8) than the BSS controls. Shield scores were not significantly different from those of the counterpart drops. The comparison between drops was not significant (P = .0513); the difference between shields (P = .0232) and the post-comparison Zymar versus BSS shields (P = .0021) were significant. Topical therapy with gatifloxacin before and after intraocular bacteria challenge led to lower incidences of endophthalmitis in rabbits. Prophylaxis with presoaked collagen shields was not statistically different than that with topical drops.


Correction to: Analysis of the quinoa genome reveals conservation and divergence of the flowering pathways.
The above article was published online with incorrect Fig. 5 legend. The legend for Fig. 4 was repeated in Fig. 5.


Management of iatrogenic lower limb ischaemia in children.
An acutely ischaemic lower limb following femoral artery cannulation in children is a problem infrequently encountered by plastic surgeons in the UK. When such a case presented to us, we performed a search of published literature to guide us to the optimum treatment. This included methods for extraperitoneal exposure of the common iliac artery and vein. We describe the surgical technique that we used to salvage an acutely ischaemic lower limb following femoral puncture and a review of the literature.


A gene for DNA invertase and an invertible DNA in Escherichia coli K-12.
An assay system for the pin gene function, which suppresses the vh2 mutation of Salmonella, was developed and used to show that most strains of Escherichia coli K-12 are Pin+, whereas all the strains of E. coli C examined are Pin-. An E. coli host strain was constructed and used for detection of DNA fragments carrying the E. coli K-12 pin gene cloned in the plasmid vector pBR322. Restriction analysis of the cloned fragments showed that the invertible DNA (designated P region) is adjacent to the pin gene and that its inversion is mediated by the pin gene product. The pin gene was found to be functionally homologous to the gin gene of Mu phage and the cin gene of P1 phage. The P region most probably resides within the cryptic prophage e14, and the Pin- phenotype is likely to be associated with the loss of e14.


Analysis of the surgical approach in prostate cancer staging: results from the surveillance, epidemiology and end results program.
Surgery is not used as a criterion for staging prostate cancer, although there is evidence that the number of analyzed and affected lymph nodes have prognosis value. The aim of this study was to determine whether there are significant differences in staging criteria in patients who underwent prostatectomy compared to those who did not, and whether the number of affected and analyzed lymph nodes (LN) plays a prognostic role. In this retrospective study, a test cohort consisting of 404,210 newly diagnosed men with prostate cancer, between 2004 and 2010, was obtained from the 17 registries (Nov 2021 submission); a validation consisting of 147,719 newly diagnosed men with prostate cancer between 2004 and 2019 was obtained from the 8 registries (Nov 2021 submission). Prostate cancer-specific survival was analyzed by Kaplan-Meier curves, survival tables and Cox regression; overall survival was analyzed only to compare Harrell's C-index between different staging criteria. In initial analyses, it was observed that the prognostic value of lymph node metastasis changes according to the type of staging (clinical or pathological), which is linked to the surgical approach (prostatectomy). Compared with T4/N0/M0 patients, which are also classified as stage IVA, N1/M0 patients had a shorter [adjusted HR: 1.767 (1429-2184), p < 0.0005] and a longer [adjusted HR: 0.832 (0.740-0.935), p = 0.002] specific survival when submitted to prostatectomy or not, respectively. Analyzing separately the patients who were submitted to prostatectomy and those who were not, it was possible to obtain new LN metastasis classifications (N1: 1 + LN; N2: 2 + LNs; N3: > 2 + LNs). This new (pathological) classification of N allowed the reclassification of patients based on T and Gleason grade groups, mainly those with T3 and T4 disease. In the validation group, this new staging criterion was proven to be superior [specific survival C-index: 0.908 (0.906-0.911); overall survival C-index: 0.788 (0.786-0.791)] compared to that currently used by the AJCC [8th edition; specific survival C-index: 0.892 (0.889-0.895); overall survival C-index: 0.744 (0.741-0.747)]. In addition, an adequate number of dissected lymph nodes results in a 39% reduction in death risk [adjusted HR: 0.610 (0.498-0.747), p < 0.0005]. As main conclusion, the surgery has a major impact on prostate cancer staging, mainly modifying the effect of N on survival, and enabling the stratification of pathological N according to the number of affected LN. Such a factor, when considered as staging criteria, improves the prognosis classification.


Proteomics of red and white corolla limbs in petunia reveals a novel function of the anthocyanin regulator ANTHOCYANIN1 in determining flower longevity.
The Petunia hybrida ANTHOCYANIN1 (AN1) gene encodes a transcription factor that regulates both the expression of genes involved in anthocyanin synthesis and the acidification of the vacuolar lumen in corolla epidermal cells. In this work, the comparison between the red flowers of the R27 line with the white flowers of the isogenic an1 mutant line W225 showed that the AN1 gene has further pleiotropic effects on flavonoid biosynthesis as well as on distant physiological traits. The proteomic profiling showed that the an1 mutation was associated to changes in accumulation of several proteins, affecting both anthocyanin synthesis and primary metabolism. The flavonoid composition study confirmed that the an1 mutation provoked a broad attenuation of the entire flavonoid pathway, probably by indirect biochemical events. Moreover, proteomic changes and variation of biochemical parameters revealed that the an1 mutation induced a delay in the onset of flower senescence in W225, as supported by the enhanced longevity of the W225 flowers in planta and the loss of sensitivity of cut flowers to sugar. This study suggests that AN1 is possibly involved in the perception and/or transduction of ethylene signal during flower senescence.


[Intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length in 16 887 neonates with a gestational age of 27-42 weeks in Shenzhen, China].
To establish the intrauterine growth curves of neonates in Shenzhen, China and to investigate the intrauterine growth of neonates in Shenzhen. Cross-sectional cluster sampling was performed for an on-the-spot investigation of 16 887 neonates (9 418 males and 7 469 females) with a gestational age of 27-42 weeks who were born in two hospitals in Shenzhen from April 2013 to September 2015. The Lambda Mu Sigma (LMS) method was used for the curve fitting of body weight, body length, head circumference, chest circumference, and crown-rump length. The 3rd-97th percentile intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length were plotted for the neonates with a gestational age of 27-42 weeks who were divided into three groups (male, female, and mixed). The male neonates had significantly higher curves for the five indices than the female counterparts. The pattern and changing trend of body weight curves of these neonates were basically consistent with those in China Neonatal Network. The percentile intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length in neonates with a gestational age of 27-42 weeks in Shenzhen which has been established can provide a reference for clinical practice in the department of neonatology.


The role of physical forces in the management of bone and cartilage diseases and bone consolidation.
The international literature shows how the good results expected by the orthopaedic community and by patients themselves can only be achieved through a complete knowledge of the mechanism of action of physical forces in the management of bone tissue and cartilage, and through knowledge of the clinical indications and modality of treatment.


Tissue specific differentially methylated regions (TDMR): Changes in DNA methylation during development.
Tissue specific differentially methylated regions (TDMRs) were identified and localized in the mouse genome using second generation virtual RLGS (vRLGS). Sequenom MassARRAY quantitative methylation analysis was used to confirm and determine the fine structure of tissue specific differences in DNA methylation. TDMRs have a broad distribution of locations to intragenic and intergenic regions including both CpG islands, and non-CpG islands regions. Somewhat surprising, there is a strong bias for TDMR location in non-promoter intragenic regions. Although some TDMRs are within or close to repeat sequences, overall they are less frequently associated with repetitive elements than expected from a random distribution. Many TDMRs are methylated at early developmental stages, but unmethylated later, suggesting active or passive demethylation, or expansions of populations of cells with unmethylated TDMRs. This is notable during postnatal testis differentiation where many testis specific TDMRs become progressively "demethylated". These results suggest that methylation changes during development are dynamic, involve demethylation and methylation, and may occur at late stages of embryonic development or even postnatally.


Does geographic location matter for transportation risk behaviors among U.S. public high school students?
Teen motor vehicle crash fatality rates differ by geographic location. Studies assessing teen transportation risk behaviors by location are inconclusive. Therefore, we explored the role of census region and metropolitan status for driving prevalence and four transportation risk behaviors among U.S. public high school students. Data from 2015 and 2017 national Youth Risk Behavior Surveys were combined and analyzed. Multivariable models controlled for sex, age, race/ethnicity, grades in school, and school socioeconomic status. Overall, 41% of students did not always wear a seat belt. Students attending schools in the Northeast were 40% more likely than those in the Midwest to not always wear a seat belt. Among the 75% of students aged ≥16 years who had driven during the past 30 days, 47% texted/e-mailed while driving. Students in the Northeast were 20% less likely than those in the Midwest to text/e-mail while driving, and students attending suburban or town schools were more likely to text/e-mail while driving (20% and 30%, respectively) than students attending urban schools. Nineteen percent of students rode with a driver who had been drinking alcohol, and 7% of drivers aged ≥16 years drove when they had been drinking alcohol, with no significant differences by location for either alcohol-related behavior. We found few differences in teen transportation risk behaviors by census region or metropolitan status. Age at licensure, time since licensure, driving experience, and the policy and physical driving environment might contribute more to variation in teen fatal crashes by location than differences in transportation risk behaviors. Regardless of location, teen transportation risk behaviors remain high. Future research could address developing effective strategies to reduce teen cell phone use while driving and enhancing community implementation of existing, effective strategies to improve seat belt use and reduce alcohol consumption and driving after drinking alcohol.


External monitoring of a data coordinating center: experience of the National Cooperative Gallstone Study.
A Biostatistical Monitoring Committee was established to review periodically the procedures and performance of the data coordinating center of the National Cooperative Gallstone Study. The functions of this committee, the types of data coordinating center activities reviewed, the manner in which monitoring of these activities was carried out, and an assessment of the value of this committee to the study are discussed in this article.


Distinct activities of the alpha-catenin family, alpha-catulin and alpha-catenin, on beta-catenin-mediated signaling.
Alpha-catenin, an integral part of cadherin-catenin adhesion complexes, is a major binding partner of beta-catenin, a key component of the Wnt pathway, which activates T-cell factor (TCF)/lymphoid enhancer factor (LEF) transcription and is often upregulated in cancers. Recently, we identified an alpha-catenin-related protein, alpha-catulin, whose function is poorly understood, as part of a Rho GTPase signaling complex. Here, based on evidence suggesting that alpha-catulin may associate with a beta-catenin fraction, we investigated the role of alpha-catenin family members in beta-catenin-mediated signals. Expression of the full length or a 103-residue region of alpha-catenin strongly inhibits the induction of the TCF/LEF-responsive TOPFLASH reporter in HEK293T cells expressing activated beta-catenin or in cancer cells with constitutively upregulated Wnt signaling, whereas alpha-catulin expression had no effect. Interestingly, alpha-catulin expression attenuates the activation of the cyclin D1 promoter, a target of Wnt pathway signals. Alpha-catulin appears to inhibit Ras-mediated signals to the cyclin D1 promoter, rather than beta-catenin signals, and the synergy between Ras and beta-catenin required to fully activate this promoter. Data suggesting the involvement of Rho in this response are presented and discussed. These results suggest a novel function for alpha-catulin and imply that alpha-catenin and alpha-catulin have distinct activities that downregulate, respectively, beta-catenin and Ras signals converging on the cyclin D1 promoter.


Implication of peritubular capillary loss and altered expression of vascular endothelial growth factor in IgA nephropathy.
To determine the roles of peritubular capillary (PTC) loss and expression of vascular endothelial growth factor (VEGF) and its transcription factor, hypoxia-inducible factor-1 (HIF-1), in the progression of IgA nephropathy (IgAN), we analyzed the expression of VEGF and HIF-1, and the number of PTCs in patients with variable severity of IgAN. Renal biopsy specimens from patients with IgAN (n = 23) were classified according to interstitial injury score: grade 0 (0%), grade 1 (1-25%), grade 2 (25-50%) and grade 3 (50-100%). We examined the immunohistochemical expression of CD34, VEGF and HIF-1alpha. VEGF was expressed in the cytoplasm of tubular epithelia, and VEGF-positive area significantly expanded in grades 1 (35.5 +/- 5.9%, mean +/- SD) and 2 (32.5 +/- 5.9%) compared with grade 0 (23.4 +/- 4.5%). The numbers of PTCs were significantly lower in grades 2 (559 +/- 49/mm2) and 3 (510 +/- 56/mm2) than grade 0 (708 +/- 49/mm2). HIF-1alpha was weakly expressed in tubular epithelia in grade 0, increased with progression to grade 2, and markedly decreased in grade 3. It was also increased in pericapsular interstitial area in grade 1. The expression pattern of HIF-1alpha did not parallel that of VEGF. In renal biopsies of 5 control patients with minor glomerular abnormality, glomerular expression levels of VEGF and HIF-1alpha were similar to those of IgAN grade 0 kidneys. VEGF production was accelerated in the early stage of IgAN but it did not protect against PTC injury/loss. The lack of correlation between VEGF and HIF-1alpha expression suggests HIF-independent VEGF production in IgAN.


Polypropylene mesh combined with electrospun poly (L-lactic acid) membrane in situ releasing sirolimus and its anti-adhesion efficiency in rat hernia repair.
This study developed, a novel polypropylene (PP) mesh combined with poly (L-lactic acid) (PLA) electrospun nanofibers loaded sirolimus (SRL). The PP mesh was combined with PLA/SRL (1/0, 1/0.01, 1/0.02; mass ratios) composed electrospun membrane characterized by FTIR spectroscopy, XPS and SEM, and evaluated for cytocompatibility in vitro. In an in vivo study, a total of 84 Sprague-Dawley rats were employed to evaluate the efficacy of the novel composite PP mesh anti-adhesion, mechanical properties and inflammation. As a results, the PLA/SRL membrane could compound with PP mesh stably and load SRL. Although tensile testing showed that the mechanical properties of composite mesh decreased in vivo, the integration strength between the tissue and mesh was still able to counteract intra-abdominal pressure. Compared with the native PP mesh group, the novel PP mesh group showed a lower score for abdominal adhesion and inflammation. More importantly, the novel PP mesh completely integrated with the abdominal wall and had sufficient mechanical strength to repair abdominal wall defects.


[Caudal regression syndrome and diastematomyelia. What is contained in Hohl's first publication of sacral dysgenesis? (author's transl)].
Hypoplasias and defective development of the caudal end of the spine are called caudal regression-syndrome. Occasionally such patients also show diastematomyelia. This combination, clinically important and of developmental interest is described on the basis of the first description and an observation of the author. The means of diagnosis are discussed.


A genome-wide association study for loin depth and muscle pH in pigs from intensely selected purebred lines.
Genome-wide association studies (GWAS) aim at identifying genomic regions involved in phenotype expression, but identifying causative variants is difficult. Pig Combined Annotation Dependent Depletion (pCADD) scores provide a measure of the predicted consequences of genetic variants. Incorporating pCADD into the GWAS pipeline may help their identification. Our objective was to identify genomic regions associated with loin depth and muscle pH, and identify regions of interest for fine-mapping and further experimental work. Genotypes for ~ 40,000 single nucleotide morphisms (SNPs) were used to perform GWAS for these two traits, using de-regressed breeding values (dEBV) for 329,964 pigs from four commercial lines. Imputed sequence data was used to identify SNPs in strong ([Formula: see text] 0.80) linkage disequilibrium with lead GWAS SNPs with the highest pCADD scores. Fifteen distinct regions were associated with loin depth and one with loin pH at genome-wide significance. Regions on chromosomes 1, 2, 5, 7, and 16, explained between 0.06 and 3.55% of the additive genetic variance and were strongly associated with loin depth. Only a small part of the additive genetic variance in muscle pH was attributed to SNPs. The results of our pCADD analysis suggests that high-scoring pCADD variants are enriched for missense mutations. Two close but distinct regions on SSC1 were associated with loin depth, and pCADD identified the previously identified missense variant within the MC4R gene for one of the lines. For loin pH, pCADD identified a synonymous variant in the RNF25 gene (SSC15) as the most likely candidate for the muscle pH association. The missense mutation in the PRKAG3 gene known to affect glycogen content was not prioritised by pCADD for loin pH. For loin depth, we identified several strong candidate regions for further statistical fine-mapping that are supported in the literature, and two novel regions. For loin muscle pH, we identified one previously identified associated region. We found mixed evidence for the utility of pCADD as an extension of heuristic fine-mapping. The next step is to perform more sophisticated fine-mapping and expression quantitative trait loci (eQTL) analysis, and then interrogate candidate variants in vitro by perturbation-CRISPR assays.


Second allogeneic transplantation for relapsed acute leukemia after initial allogeneic hematopoietic stem cell transplantation.
We retrospectively reviewed the medical records of 45 patients with relapsed acute leukemia after initial allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among 45 patients, a total of 11 patients eventually underwent second allo-HSCT (HSCT-2). Median survival after relapse was 294 days (range, 135-942 days) for HSCT-2. Multivariate analysis showed significantly better survival for recipients of second allo-HSCT than for other patients (hazard ratio, 4.38; 95 % confidence interval, 1.45-13.2; P = 0.009). Although outcomes for patients with relapsed leukemia were generally poor, our results suggest that second HSCT could offer a survival advantage over other conventional salvage strategies.


Systematic Review and Meta-Analysis of the Relationship between EPHX1 Polymorphisms and the Risk of Head and Neck Cancer.
To evaluate the association between the EPHX1 Tyr113His and His139Arg polymorphisms in the EPHX1 gene and the risk of head and neck cancer. Studies on the association of EPHX1 Tyr113His and His139Arg polymorphisms with HNC performed up until June 1st, 2014, were identified using a predefined search strategy. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of these associations. In this meta-analysis, 10 case-control studies, which included 9 studies of Tyr113His (1890 cases and 1894 controls) and 10 studies of His139Arg polymorphisms (1982 cases and 2024 controls), were considered eligible for inclusion. Overall, the pooled results indicated that the EPHX1 Tyr113His polymorphism was significantly associated with increased HNC risk (Tyr/His vs. Tyr/Tyr, OR = 1.26, 95%1.02-1.57;His/His+ Tyr/His vs. Tyr/Tyr, OR = 1.29, 95% I = 1.03-1.61). However, no significant association was found between the His139Arg polymorphism and HNC risk. In the subgroup analysis, a statistically significant association between the EPHX1 Tyr113His polymorphism and HNC was observed in population-based case-control studies (PCC), which involved less than 500 participants and genotype frequencies in HWE. This association showed minimal heterogeneity after excluding studies that were determined to contribute to heterogeneity. After categorizing the studies by publication time, a sensitivity analysis and cumulative meta-analysis of the two associations were conducted, and the results of the two analyses were consistent. Our meta-analysis suggests that EPHX1 Tyr113His polymorphism may be a risk factor for HNC, while the EPHX1 His139Arg polymorphism has no association with HNC risk.


[Nursing care in reconstructive surgery in cases of head and neck cancer].
The treatment of cancers of the upper aerodigestive tract favours an organ- and function- preserving surgical approach. The nursing care draws on multiple skills, on both a technical and educational level, in order to assure global patient management.


Spectral composition of NREM sleep in healthy subjects with moderately increased daytime sleepiness.
This study addressed the relationship between daytime sleepiness and spectral composition of the preceding NREM sleep. Nineteen healthy volunteers (mean age: 36.5 years; SD: 10.1) underwent polysomnography during two consecutive nights and the multiple sleep latency test (MSLT) on the following day. Daytime sleepiness was also assessed by the Epworth sleepiness scale (ESS). The sleep recordings were visually scored according to standard criteria. The quantitative sleep EEG analysis was performed using a fast Fourier transform routine. The sleep parameters were compared between subjects with short and long MSLT sleep latencies (cut-off=10 min) and between subjects with low and high ESS scores (cut-off=6 points). Subjects with short MSLT sleep latencies showed a reduced theta EEG activity. There was no evidence of reduced synchronization of sleep EEG in subjects with high ESS scores. Moderately increased daytime sleepiness as indicated by MSLT sleep latency less than 10 min is accompanied by decreased power of theta activity during NREM sleep indicating a deficit of sleep EEG synchronization.


Results of radiation therapy for unresected soft-tissue sarcomas.
Definitive radiotherapy is uncommonly used in the management of soft-tissue sarcoma (STS). The purpose of the study was to evaluate the results of radiotherapy for unresected STSs treated in a single institution. Between 1970 and 2001, 112 patients with STSs underwent radiotherapy for gross disease. Locations of the tumor were 43% in the extremities, 26% retroperitoneal, 24% in the head and neck, and 7% in the truncal wall. Histologic grades were 11% G1 and 89% G2 to G3. Median size of tumor at radiotherapy was 8 cm (range, 1-30 cm). Median radiation dose was 64 Gy (range, 25-87.5 Gy). Twenty percent of patients received chemotherapy. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated in univariate (log-rank) and then multivariate (Cox model) analysis to determine prognostic factors for STS. Median follow-up for patients is 139 months (range, 30-365 months). The 5-year actuarial LC, DFS, and OS were 45%, 24%, and 35%, respectively. Tumor size at radiotherapy and radiation dose influenced LC, DFS, and OS in univariate analysis. LC at 5 years was 51%, 45%, and 9% for tumors less than 5 cm, 5 to 10 cm, and greater than 10 cm, respectively. Patients who received doses of less than 63 Gy had 5-year LC, DFS, and OS rates of 22%, 10%, and 14%, respectively, compared with 5-year LC, DFS, and OS rates of 60%, 36%, and 52%, respectively, for patients who received doses of 63 Gy or more. AJCC stage was related to the OS and DFS without statistically significant influence on LC. Use of chemotherapy, histologic grade, age, and location did not influence results. In multivariate analysis, LC was related to total dose (p = 0.02), T size at radiotherapy (p = 0.003), and AJCC stage (p = 0.04); DFS was related to total dose (p = 0.007), T size at radiotherapy (p = 0.01), and AJCC stage (p < 0.0001); and OS was related to AJCC stage (p = 0.0001) and total dose (p = 0.002), but not to T size, at radiotherapy. Major radiotherapy complications were noted in 14% of patients; 27% of patients who received doses of 68 Gy or more had these complications compared with 8% of patients treated with doses of less than 68 Gy. Definitive radiotherapy for STS should be considered in clinical situations where no acceptable surgical option is available. Higher radiation doses yield superior tumor control and survival. A rise in complications occurs in patients who receive doses of 68 Gy or more, which provides a therapeutic window for benefit in these patients.


Compensation of postural effects of hemilabyrinthectomy in the cat. A sensory substitution process?
A photographic technique was used to study the evolution of lateral head-tilt following hemilabyrinthectomy in adult cats. Animals were maintained post-operatively in normally lit conditions (LM cats), in total darkness (DM cats), or in stroboscopic light. In LM casts, the head tilt peaked at 45 degrees (with the lesionned side down) on the second post-operative day, and decreased to about 0 degree within about 10 days. This evolution was followed by rebounds of head-tilt to large angles before a stable compensated head postion could be maintained (approximately at the end of the third post-operative month). In DM cats the head remained tilted by a large angle throughout the duration of the dark period. Re-exposure to light was followed by a rapid decrease of head-tilt. In stroboscopic light, the evolution of head-tilt was found to be closely similar to that in the normally lit condition. Finally, when put back in the dark at a late post-operative stage, already compensated animals were found to loose their symmetrical head position, and to re-acquire a strong head tilt. This effect resumed on re-exposure to light. It is inferred that static visual input is a necessary condition for compensation of the postural deficits of hemi-labyrinthctomy in the cat. Maintenance of a stable head posture also depends upon continuous availability of visual input.


Quantitative imaging of Candida utilis and its organelles by soft X-ray Nano-CT.
Soft X-ray microscopy has excellent characteristics for imaging cells and subcellular structures. In this paper, the yeast strain, Candida utilis, was imaged by soft X-ray microscopy and three-dimensional volumes were reconstructed with the SART-TV method. We performed segmentation on the reconstruction in three dimensions and identified several types of subcellular architecture within the specimen cells based on their linear absorption coefficient (LAC) values. Organelles can be identified by the correlation between the soft X-ray LAC values and the subcellular architectures. Quantitative analyses of the volume ratio of organelles to whole cell in different phases were also carried out according to the three-dimensional datasets. With such excellent features, soft X-ray imaging has a great influence in the field of biological cellular and subcellular research.


Single-dose systemic methotrexate for the treatment of persistent ectopic pregnancy after conservative surgery.
To determine whether a single outpatient methotrexate injection successfully treats persistent ectopic pregnancy. Nineteen consecutive patients with increasing beta-hCG titers after conservative surgery for ectopic pregnancy were treated with a single intramuscular methotrexate (50 mg/m2) injection. All 19 patients had resolution of their beta-hCG titers without subsequent surgery. Beta-hCG levels commonly increased during the first 3 days after treatment, but subsequently declined. Two patients required hospital admission for observation and analgesia. One of these two patients had probable self-limited intra-abdominal bleeding and required a blood transfusion. A single methotrexate injection is a safe and successful treatment for persistent ectopic pregnancy. Delayed hemorrhage may be a rare complication, and close surveillance is necessary.


Comparative analysis of Staphylococcus epidermidis strains utilizing quantitative and cell surface shaving proteomics.
Staphylococcus epidermidis is an opportunistic pathogen that is an emerging risk factor in hospitals worldwide and is often difficult to eradicate as virulent strains produce a protective biofilm matrix. We utilized cell shaving proteomics to profile surface-exposed proteins from two fully genome sequenced S. epidermidis strains: the avirulent, non-biofilm forming ATCC12228 and the virulent, strongly adherent biofilm forming ATCC35984 (RP62A). A false positive control strategy was employed to calculate the probabilities of proteins being truly surface-exposed. A total of 78 surface-exposed proteins were identified, of which only 19 proteins were common to ATCC12228 and RP62A, and which thus represents the core surfaceome. S. epidermidis RP62A displayed additional proteins involved in biofilm formation (cell wall-associated Bhp and intercellular adhesion protein IcaB), surface antigenicity, peptidoglycan biosynthesis and antibiotic resistance. We concurrently profiled whole cell proteomes of the two strains using iTRAQ quantitation and LC-MS/MS. A total of 1610 proteins were confidently identified (representing 64% of the theoretical S. epidermidis proteome). One hundred and ninety one proteins were differentially abundant between strains. Proteins associated with RP62A were clustered into functions including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-mediated defense, sulfate assimilation, antibiotic resistance and biofilm formation. Validation of the sulfate assimilation and cysteine/methionine biosynthesis pathways showed RP62A contained elevated levels (~25% increase) of methionine that are likely linked to biofilm formation. Cell shaving and quantitative proteomics identified proteins associated with a biofilm-forming, virulent strain of S. epidermidis (RP62A). These proteins show RP62A maintains an active CRISPR-mediated defense, as well as heightened antibiotic resistance in comparison to a non-virulent, non-biofilm forming strain. Increased abundances of sulfate assimilation proteins lead to elevated intracellular methionine. Proteins and their exposed peptides identified on the surface of S. epidermidis RP62A may be useful vaccine antigens in clinical settings if administered in at-risk patients prior to surgical implantations.