Novel truncating variant of MN1 penultimate exon identified in a Chinese patient with newly recognized MN1 C-terminal truncation syndrome: Case report and literature review.
MN1 C-terminal truncation (MCTT) syndrome is a newly recognized neurodevelopmental disorder due to heterozygous gain-of-function C-terminal truncating mutations clustering in the last or penultimate exon of MN1 gene (MIM: 156100). Up to date, only 25 affected patients have been reported. Here, we report a 2-year-old Chinese girl with MCTT syndrome. The girl presented with the characteristic features of the syndrome, including global developmental delay (GDD), facial dysmorphism and hearing impairment. Notably, the patient did not have other frequently observed symptoms such as hypotonia, cranial or brain abnormalities, indicating variability of the phenotype of patients with MN1 C-terminal truncating mutations. Trio whole-exome sequencing revealed a novel de novo heterozygous nonsense variant in the extreme 3' region of penultimate exon of MN1 (NM_002430.3: c.3743G > A, p.Trp1248*). This rare truncating variant was classified as pathogenic due to its predicted gain-of-function effect, given that the gain-of-function MN1 truncating variants producing C-terminally truncated proteins have been confirmed to cause the recognizable syndrome. Additionally, a systematic review of previously reported MN1 variants including C-terminal truncating variants and N-terminal truncating variants shows that different location of MN1 truncating variants causes two distinct clinical subtypes. To our knowledge, this is the first reported case of MCTT syndrome caused by a novel MN1 C-terminal truncating variant in a Chinese population, which enriched the mutation spectrum of MN1 gene and further supporting the association of the novel MCTT syndrome with MN1 C-terminal truncating variants.


Competitive immobilization of Pb in an aqueous ternary-metals system by soluble phosphates with varying pH.
Chemical immobilization by phosphates has been widely and successfully applied to treat Pb in wastewater and contaminated soils. Pb in wastewaters and soils, however, always coexists with other heavy metals and their competitive reactions with phosphates have not been quantitatively and systematically studied. In this approach, immobilization of Pb, Zn, and Cd by mono-, di-, and tripotassium phosphate (KH2PO4, K2HPO4, and K3PO4) was observed in the single- and ternary-metals solutions. The immobilization rates of the three metals were determined by the residual concentration. The mineral composition and structure of the precipitates were characterized by powder X-ray diffraction (XRD) analysis and scanning electron microscopy (SEM). The results indicated that competitive reaction occurred in Pb-Zn-Cd ternary system, with immobilization rates decrease of <3.6%, <78%, and <89% for Pb, Zn and Cd (molar ratios of P: metal <1), respectively, compared to single metal system. The reaction of Pb with three phosphates exhibited intense competitiveness and the phosphates had a stronger affinity for Pb when Cl(-) was added. Pb-phosphate minerals formed by KH2PO4 with the better crystalline characteristics and largest size were very stable with a low dissolution rate (<0.02%) in the solution of pH 2.88, compared to K2HPO4 and K3PO4. This study demonstrated that Pb could be firstly and effectively immobilized by phosphates in multi-metal solutions containing Pb, Zn and Cd. Moreover, the research provided the insight of the importance of phosphate with low pH (e.g. KH2PO4) and the presence of Cl(-) for more efficient immobilization of Pb in the multi-metals pollution system.


Comparison of long occlusive femoropopliteal de novo versus previous endovascularly treated lesions managed with in situ saphenous bypass.
The aim of this study was to compare the 2-year outcomes of de novo versus postendovascular lesion treatment of femoropopliteal occlusions included in a national, multicenter, observational, prospective registry based on the treatment of critical Limb-threatening IschaeMia with infragenicular Bypass adopting in situ SAphenous VEin technique (LIMBSAVE) registry. From January 2018 to December 2019, 541 patients from 43 centers have been enrolled in the LIMBSAVE registry. Of these patients, 460 were included in the present study: 341 (74.1%) with de novo lesions (DN group) and 119 (25.9%) with postendovascular treatment lesions (PE group). Initial outcome measures were assessed at 30 days after treatment. Furthermore, at the 2-year follow-up, the estimated outcomes of primary patency, primary-assisted patency, secondary patency, and limb salvage were analyzed with Kaplan-Meier curves and compared between groups with the log-rank test. Both groups were homogeneous in terms of demographic data, preoperative risk factors, and clinical presentation. However, compared with DN group, more patients in PE group had a great saphenous vein diameter of less than 3 mm (11.1% vs 21%; P = .007). Intraoperatively, both groups showed similar distal anastomosis sites: below-the-knee popliteal artery (63% DN group, 66.4% PE group) and tibial vessel (37% DN group, 33.6% PE group) (P = .3). The overall mean duration of follow-up was 11.6 months (range, 1-24 months). At the 2-year follow-up, there were no differences between the two groups in terms of primary patency (66.3% DN group vs 74.1% PE group; P = .9), primary-assisted patency (78.2% DN group vs 79.5% PE group; P = .2), secondary patency (85.1% DN group vs 91.4% PE group; P = .2), and limb salvage (95.2% DN group vs 95.1% PE group; P = .9). The LIMBSAVE registry did not show a worsening of overall patency and limb salvages rates at the 2-year follow-up in patients undergoing in situ saphenous bypass after a failed endovascular approach for long femoropopliteal occlusive disease. This finding is in contrast with what has been published in literature.


Multicenter study of optical low-coherence interferometry and partial-coherence interferometry optical biometers with patients from the United States and China.
To evaluate the agreement between the measurements provided by a new optical biometer, the Aladdin, based on optical low-coherence interferometry (OLCI), and those provided by the most commonly used optical biometer (IOLMaster 500), based on partial-coherence interferometry (PCI). Multicenter clinical trial. Prospective evaluation of diagnostic test. In this study, 2 samples of adult patients were enrolled, 1 in the United States and the other in China. The U.S. group included a sample of consecutive patients scheduled for cataract surgery. The China group included a sample of healthy subjects with no cataracts. In both cases, only 1 eye of each patient was analyzed. Axial length (AL), corneal power (in diopters [D]) (K), anterior chamber depth (ACD) (corneal epithelium to lens), and corneal astigmatism were measured. All values were analyzed using a paired t test, the Pearson product-moment correlation coefficient (r), and Bland-Altman plots. In the U.S. and China groups, the OLCI mean AL values did not show a statistically significant difference from PCI values and showed excellent agreement and correlation. On the contrary, OLCI measured a lower mean K (-0.14 D) and a deeper ACD measurements (U.S. +0.16 mm and China +0.05 mm). These differences were statistically significant (P < .0001). Vector analysis did not show a statistically significant difference in astigmatism measurements. Agreement between OLCI and PCI was good. However, the small but statistically significant differences in K and ACD measurements make constant optimization necessary when calculating the intraocular lens power using theoretical formulas. Dr. Hoffer licenses the registered trademark name Hoffer to Carl Zeiss-Meditec (PCI), Haag-Streit (Lenstar), Movu (Argos), Oculus (Pentacam, AXL), Nidek (AL-Scan), Tomey (OA-2000), Topcon EU Visia Imaging (Aladdin), Ziemer (Galilei G6), and all A-scan biometer manufacturers. Dr. Shammas licenses his formulas to Carl Zeiss-Meditec (PCI), Haag-Streit (Lenstar), Nidek (AL-Scan), and Topcon EU (Visia Imaging) (Aladdin). None of the other authors has a financial or proprietary interest in any material or method mentioned.


Neuroprotective effect of cytoflavin during compression injury of the spinal cord.
Cytoflavin normalized energy metabolism, decreased the intensity of lipid peroxidation, and reactivated the antioxidant system in the spinal cord of rats with compression injury at the level of Th10-Th11. The neuroprotective effect of the test preparation manifested in normalization of hindlimb motor function and decrease in mortality rate of animals with spinal cord injury. Neuroprotective activity of cytoflavin was higher than that of Cerebrolysin.


Race-specific association of an IRGM risk allele with cytokine expression in human subjects.
Immunity-related GTPase family M (IRGM), located on human chromosome 5q33.1, encodes a protein that promotes autophagy and suppresses the innate immune response. The minor allele of rs13361189 (-4299T>C), a single nucleotide polymorphism in the IRGM promoter, has been associated with several diseases, including Crohn's disease and tuberculosis. Although patterns of linkage disequilibrium and minor allele frequency for this polymorphism differ dramatically between subjects of European and African descent, studies of rs13361189 have predominantly been conducted in Europeans and the mechanism of association is poorly understood. We recruited a cohort of 68 individuals (30 White, 34 African American, 4 other race) with varying rs13361189 genotypes and assessed a panel of immune response measures including whole blood cytokine induction following ex vivo stimulation with Toll-like Receptor ligands. Minor allele carriers were found to have increased serum immunoglobulin M, C-reactive protein, and circulating CD8+ T cells. No differences in whole blood cytokines were observed between minor allele carriers and non-carriers in the overall study population; however, minor allele status was associated with increased induction of a subset of cytokines among African American subjects, and decreased induction among White subjects. These findings underline the importance of broad racial inclusion in genetic studies of immunity.


Knee arthroplasty in rheumatoid arthritis. Four- to six-year follow-up study.
A consecutive series of total condylar knee arthroplasties in patients with rheumatoid or related arthritis, with a 4-6-year follow-up period, was studied. Eighty-seven percent had an excellent or good overall result (score of 70 or more on the HSS knee rating scale). The median total score increased from 45 points before operation to 83 after operation. Sixteen complications, mostly minor, occurred in 14 patients. There were no early infections. Two prostheses were removed for deep infection, after 3 and 5 years. One patient had patellectomy for avascular necrosis. The crude prosthesis survival rate was 97%. Tibial radiolucencies were noted in 76% of cases; in 29% they were significant (2 mm or more in one or more of three zones). Two tibial components (2%) were believed to be mechanically loose, but no revisions for mechanical loosening were done. The presence of radiolucencies did not signify an inferior clinical result.


Inter-gene correlation on oligonucleotide arrays: how much does normalization matter?
Normalization is a standard low-level preprocessing procedure in microarray data analysis to minimize the systematic technological variations and produce more reliable results. A variety of normalization approaches have been introduced and are widely applied. Normalization, however, remains controversial. The sensitivity of array results to normalization is an open question. No clear standard for comparing or judging normalization methods has yet emerged, and the effects of normalization on gene-to-gene co-expression are unclear. In this investigation, we applied 1-, 2-, and N-quantile normalization to several publicly available microarray datasets quantified with either MAS 5.0 or dCHIP and evaluated the effect on gene-to-gene co-expression. We introduced a graphical method to explore trends in gene correlation. We found clear differences in the distributions of gene dependencies by normalization method. Increasing the number of standardized quantiles in the normalization reduced trends in correlation by signal intensity in MAS 5.0 quantifications but not dCHIP. Increasing the number of standardized quantiles did not markedly reduce the correlation of known overlapping targets with MAS 5.0. Normalization plays a very important role in the estimation of inter-gene dependency. Caution should be used when making inferences concerning gene-wise dependencies with microarrays until this source of variation is better understood.


How to have more things by forgetting how to count them†.
Cohen's first model is a model of Zermelo-Fraenkel set theory in which there is a Dedekind-finite set of real numbers, and it is perhaps the most famous model where the Axiom of Choice fails. We force over this model to add a function from this Dedekind-finite set to some infinite ordinal κ. In the case that we force the function to be injective, it turns out that the resulting model is the same as adding κ Cohen reals to the ground model, and that we have just added an enumeration of the canonical Dedekind-finite set. In the case where the function is merely surjective it turns out that we do not add any reals, sets of ordinals, or collapse any Dedekind-finite sets. This motivates the question if there is any combinatorial condition on a Dedekind-finite set A which characterises when a forcing will preserve its Dedekind-finiteness or not add new sets of ordinals. We answer this question in the case of 'Adding a Cohen subset' by presenting a varied list of conditions each equivalent to the preservation of Dedekind-finiteness. For example, 2 A is extremally disconnected, or [A]<ω is Dedekind-finite.


Evaluation of epiglottoplasty as treatment for severe laryngomalacia.
Six patients with severe laryngomalacia underwent epiglottoplasty. Four of these patients had life-threatening episodes of airway obstruction before surgery; of these, two had required tracheal intubation and one had required cardiopulmonary resuscitation. Two patients had failure to thrive and two had cor pulmonale. Patients had required a mean of two hospitalizations related to upper airway obstruction. We performed polysomnography during a daytime nap, both before and after epiglottoplasty, in all patients. Respiratory effort, arterial oxygen saturation, and end-tidal carbon dioxide pressure were monitored with continuous electrocardiograms and electrooculograms. All patients had abnormal polysomnograms preoperatively. Six patients had obstructive apnea, four had hypoxemia (arterial oxygen saturation less than 90% while breathing room air), and four had hypoventilation (end-tidal carbon dioxide pressure greater than 45 mm Hg) before epiglottoplasty. Mean age (+/- SEM) at epiglottoplasty was 10.3 +/- 5.3 months. No patients had surgical complications. An endotracheal tube was in place for 25 +/- 7 hours postoperatively, and patients were discharged 4 +/- 1 days postoperatively. Polysomnography performed 2.8 +/- 1.0 months after surgery showed that all patients had improved. Two patients had residual, mild episodes of obstructive apnea, and one patient had mild hypoventilation and desaturation. No patient had further life-threatening events or required further hospitalizations after epiglottoplasty. We conclude that epiglottoplasty is an effective and safe treatment for a selected group of patients with severe laryngomalacia.


Kinesin-5: cross-bridging mechanism to targeted clinical therapy.
Kinesin motor proteins comprise an ATPase superfamily that works hand in hand with microtubules in every eukaryote. The mitotic kinesins, by virtue of their potential therapeutic role in cancerous cells, have been a major focus of research for the past 28 years since the discovery of the canonical Kinesin-1 heavy chain. Perhaps the simplest player in mitotic spindle assembly, Kinesin-5 (also known as Kif11, Eg5, or kinesin spindle protein, KSP) is a plus-end-directed motor localized to interpolar spindle microtubules and to the spindle poles. Comprised of a homotetramer complex, its function primarily is to slide anti-parallel microtubules apart from one another. Based on multi-faceted analyses of this motor from numerous laboratories over the years, we have learned a great deal about the function of this motor at the atomic level for catalysis and as an integrated element of the cytoskeleton. These data have, in turn, informed the function of motile kinesins on the whole, as well as spearheaded integrative models of the mitotic apparatus in particular and regulation of the microtubule cytoskeleton in general. We review what is known about how this nanomotor works, its place inside the cytoskeleton of cells, and its small-molecule inhibitors that provide a toolbox for understanding motor function and for anticancer treatment in the clinic.


Gut-derived lipopolysaccharide remodels tumoral microenvironment and synergizes with PD-L1 checkpoint blockade via TLR4/MyD88/AKT/NF-κB pathway in pancreatic cancer.
Lipopolysaccharide (LPS) as an important inflammatory mediator activates the innate/adaptive immune system. The existence of LPS in pancreatic ductal adenocarcinoma (PDAC) has been reported, however, its biological function in PDAC remains unclear. Here, we demonstrated that circulating and tumoral LPS was significantly increased by intestinal leakage in the orthotopic murine PDAC model, and LPS administration promoted T cell infiltration but exhaustion paradoxically in the subcutaneous murine PDAC model. By bioinformatic analysis, Toll-like receptor 4 (TLR4), LPS receptor, was further found to enrich in immune tolerance signaling in PDAC tissues. Then, a significant positive correlation was found between TLR4 and programmed death ligand-1 (PD-L1) in clinical PDAC tissues, as well as serum LPS and tumoral PD-L1. Meanwhile, LPS stimulation in vitro and in vivo obviously upregulated tumor PD-L1 expression, and effectively promoted cancer cells resistance to T cell cytotoxicity. Mechanistically, the activation of TLR4/MyD88/AKT/NF-κB cascade was found to participate in LPS mediated PD-L1 transcription via binding to its promoter regions, which was enhanced by crosstalk between NF-κB and AKT pathways. Finally, PD-L1 blockade could significantly reverse LPS-induced immune escape, and synergized with LPS treatment. Taken together, LPS can remodel tumor microenvironment, and synergize with PD-L1 blockade to suppress tumor growth, which may be a promising comprehensive strategy for PDAC.


Short- and medium-chain chlorinated paraffins in T-shirts and socks.
The short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) are complex mixtures of persistent compounds used mainly as plastic additives. They can have a negative impact on human health as they are suspected of disrupting the endocrine system and being carcinogenic, which is why monitoring their presence in the human environment is desirable. Clothing was selected for this study because they are produced in large quantities worldwide and the final products are worn for long periods throughout the day, in direct contact with human skin. The concentrations of CPs in this type of sample have not been sufficiently reported. We determined SCCPs and MCCPs in 28 samples of T-shirts and socks by gas chromatography coupled with high-resolution mass spectrometry in negative chemical ionisation mode (GC-NCI-HRMS). CPs were found above the limits of quantification in all samples, with concentrations ranging from 33.9 to 5940 ng/g (mean 1260 ng/g, median 417 ng/g). The samples with a substantial proportion of synthetic fibres contained higher CP concentrations (22 times higher mean for SCCPs and 7 times higher mean for MCCPs) than garments composed exclusively of cotton. Finally, the effect of washing in the washing machine was investigated. The individual samples behaved differently: (i) excessively emitting CPs; (ii) being contaminated; (iii) retaining the original CP levels. The CP profiles also changed for some samples (with a substantial proportion of synthetic fibres and samples composed exclusively of cotton).


Functions of triacylglycerols during plant development and stress.
Plant oil in the form of triacylglycerols (TAGs) is a major storage compound used as food, feed and sustainable feedstock for biofuel production. Recent findings suggest that TAGs are more than a carbon and energy reserve in seeds and other storage tissues. In vegetative tissues, TAG metabolism is involved in cell division and expansion, stomatal opening, and membrane lipid remodeling. Moreover, in reproductive tissues, TAGs are important for both organ formation and successful pollination. Here we provide a brief overview of the physiological function and contribution of TAGs during plant development under optimal and varying environmental conditions. These roles of TAGs need to be considered during engineering attempts to further improve TAG content in different tissues.


[Is APRI score a suitable tool for prediction of fibrosis in Tunisian patients with genotype 1 chronic viral hepatitis C?].
Therapeutic indications in chronic genotype 1 hepatitis C are based on severity of fibrosis. APRI score is a simple, cheap and reproducible biochemical test. Performances of APRI score in Tunisian population with chronic hepatitis C were not previously prospectively studied. To evaluate the performances of APRI score in prediction of severity of fibrosis in chronic genotype 1 hepatitis C based on a prospective study. We prospectively include patients with chronic genotype 1 hepatitis C and positive viral load. Hepatic biopsy was performed in all included patients and abnormalities were classified according to METAVIR classification. In all patients, APRI score was calculated based on biochemical data collected within the 15 days before hepatic biopsy. We studied 140 patients (46 men, mean age 48.4 years (20 - 65 years)). Mean APRI score was 0.89 (0.18 - 3.72). Statistically significant correlation was observed between APRI score and fibrosis severity (r = 0.31 p < 0.0001). APRI score was higher in patients with severe fibrosis (F2, F3 or F4) compared to patients with moderate fibrosis (F0 or F1) (0.97 + 0.68 vs 0.62 + 0.44; p 0.009). Threshold value of APRI score of 0.72 was associated with area under the curve of 0.65 + 0.05 (0.57 - 0.73), sensitivity of 56.3% and specificity of 75.8% in prediction of severe fibrosis. APRI score was also higher in patients with cirrhosis (1.24 + 0.79 vs 0.85 + 0.61; p = 0.01). Threshold value of 0.86 was associated with area under the curve of 0.69 + 0.07 (0.61 - 0.77), sensitivity of 76.4% and specificity of 65.8% in prediction of cirrhosis. APRI score is not a good alternative to hepatic biopsy although a strong correlation with fibrosis severity, because of relatively low area under the curve, sensitivity and specificity in prediction of severe fibrosis and cirrhosis.


Biosynthesis of silver nanoparticle from leaf extract of Desmodium gangeticum (L.) DC. and its biomedical potential.
An aqueous leaf extract of Desmodium gangeticum was employed to synthesize silver nano particles. Rapid formation of stable silver nanoparticles were observed on exposure of the aqueous leaf extract with solution of silver nitrate. The silver nanoparticles were characterized by UV-visible spectroscopy, scanning electron microscopy, energy dispersive X-ray analysis and transmission electron microscopy (TEM), and Fourier Transform Infra-Red spectroscopy (FTIR) UV-visible spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDAX), transmission electron microscopy (TEM), and Fourier Transform Infra-Red spectroscopy (FTIR). UV-visible spectrum of the aqueous medium peaked at 450 nm corresponding to the plasmon absorbance of silver nanoparticles. SEM analysis revealed the spherical shape of the particles with sizes ranging from 18 to 39 nm and the EDAX spectrum confirmed the presence of silver along with other elements in the plant metabolite. Further, these biologically synthesized nanoparticles were found to be highly toxic against pathogenic bacteria Escherichia coli, thus implying significance of the present study in production of biomedical products.


Detection of thyroid tumours using radio-labelled anti-thyroglobulin.
IgG antibody to human thyroglobulin was labelled with 131Iodine (131I) and used to locate deposits of thyroid follicular and papillary tumours with a gamma camera. Of twelve patients studied a total of 40 tumour 'areas' were detected by a variety of clinical and radiological techniques. Sixteen of these were detected using conventional 131I uptake scans whereas 34 were positive on the antibody scans. The difficulty of assessing diffuse pulmonary lesions (3 areas) and the possibility that free 131I from labelled antibody may have contributed to the antibody scan results in six areas left 31 definite areas for scan comparison. Twenty seven (87%) areas were positive on the antibody scan, nine (29%) were positive on conventional 131I scans whilst 24 (77%) areas were detected by a combination of clinical and other radiological criteria. Five areas were positive on the antibody scan alone but there was evidence, albeit indefinite, that these areas contained tumour. Four of the 31 areas were not detected by the antibody scans. The results indicate that anti-thyroglobulin scanning is more sensitive than conventional 131I-iodide scans and may contribute to the staging and management of thyroid cancer.


Operative challenges in management of concurrent interrupted aortic arch and descending thoracic aortic aneurysm.
Interrupted aortic arch is a rare finding in the adult patient. This condition in combination with a descending thoracic aortic aneurysm is an even more exceptional occurrence. Surgical management includes open, endovascular, and hybrid options. We present the case of a 57-year-old man with interrupted aortic arch and concomitant descending thoracic aortic aneurysm, review characterization of this entity, and discuss management options with consideration to associated risks.


Needs Assessment for Behavioral Health Workforce: a State-Level Analysis.
This study describes trends in the supply and the need for behavioral health professionals in Nebraska. A state-level health workforce database was used to estimate the behavioral health workforce supply and need. Compared with national estimates, Nebraska has a lower proportion of all categories of behavioral health professionals. The majority of Nebraska counties have unusually high needs for mental health professionals, with rural areas experiencing a decline in the supply of psychiatrists over the last decade. Availability of robust state-level health workforce data can assist in crafting effective policy for successful systems change, particularly for behavioral health.


Are persistent delusions in schizophrenia associated with aberrant salience?
It has been suggested that positive psychotic symptoms reflect 'aberrant salience'. Previously we provided support for this hypothesis in first-episode schizophrenia patients, demonstrating that delusional symptoms were associated with aberrant reward processing, indexed by the Salience Attribution Test (SAT). Here we tested whether salience processing is abnormal in schizophrenia patients with long-standing treatment-refractory persistent delusions (TRS). Eighteen medicated TRS patients and 31 healthy volunteers completed the SAT, on which participants made a speeded response to earn money in the presence of cues. Each cue comprised two visual dimensions, colour and form. Reinforcement probability varied over one of these dimensions (task-relevant), but not the other (task-irrelevant). Participants responded significantly faster on high-probability relative to low-probability trials, representing implicit adaptive salience; this effect was intact in TRS patients. By contrast, TRS patients were impaired on the explicit adaptive salience measure, rating high-probability stimuli less likely to be associated with reward than controls. There was little evidence for elevated aberrant salience in the TRS group. These findings do not support the hypothesis that persistent delusions are related to aberrant motivational salience processing in TRS patients. However, they do support the view that patients with schizophrenia have impaired reward learning.


Misconceptions - vitamin D insufficiency causes malabsorption of calcium.
The negative effect of vitamin D insufficiency on bone is commonly attributed to a decrease in calcium absorption although little evidence has been produced to support this assumption. Using two previously published series of elderly patients we refute this common assumption and present evidence that low circulating levels of 25 hydroxyvitamin D have a direct and deleterious effect on bone.


Photocatalytic surface patterning of cellulose using diazonium salts and visible light.
Coumarin-functionalized cellulose sheets were chemically modified using a visible light catalyzed "Photo-Meerwein" arylation. Use of a photomask to pattern the surface resulted in directly visible images.


Pandangolide 1a, a metabolite of the sponge-associated fungus Cladosporiumsp., and the absolute stereochemistry of pandangolide 1 and iso-cladospolide B.
Fractionation of the ethyl acetate extract of a Cladosporium sp., isolated from the Red Sea sponge Niphates rowi, yielded a new hexaketide, pandangolide 1a (1), together with its known diastereomer pandangolide 1 (2) and the known iso-cladospolide B (3). The structures of the compounds were determined by 1D and 2D NMR techniques and mass spectrometric data. The absolute configurations of the stereocenters in these compounds were determined by Riguera's method and circular dichroism.


[Urological surgery with analogosedation and local anesthesia. What makes sense?].
Analogosedation and local anesthesia, including regional nerve blocks are used for endoscopic diagnostic or radiological and ultrasound-guided procedures in which the patient should not move or has to be free of pain. We retrospectively analyzed patient satisfaction, complications and the risk of urological interventions with analgosedation and/or local anesthesia between 2008 and 2012. In total 21,690 urological patients underwent surgical treatment at the Department of Urology of the University Hospital of Essen between 2008 and 2012 and 3,327 of these cases were performed by urologists with the patient under analogosedation (n=1484) and local anesthesia (n=1843). In total 13 surgical and endoscopic procedures were separately analyzed and evaluated for safety and practicability. In five cases (0.15%) the procedures with analgosedation or local anesthesia were interrupted because of agitation (n=3) and in one case the transurethal resection was stopped due to a large bladder tumor. One patient suffered anaphylactic shock after preoperative intravenous application of cefuroxim 1.5 g. After cardiopulmonary resuscitation and a short stay on the intensive care unit the patient was discharged after 2 days.Conclusions. Local anesthesia and analgosedation should be performed by urologists for minor surgery, endoscopic procedures and radiological or ultrasound-guided treatment. For safety reasons there should always be a second medical doctor present for assistance. Analgesia with deep sedation or loss of defensive reflexes should be administered by anesthesiologists.


This is a case report of an observation of bradycardia and inverted T-waves anteroseptally on the electrocardiogram along with cardiac symptoms, in a previously healthy 35-year-old woman with post-partum pre-eclampsia. Initially, she had no hypertension or proteinuria, which delayed the time of diagnosis. A possible explanation of bradycardia is a baroreceptor-mediated response to hypertension and hypervolaemia. The changes on the electrocardiogram can be explained by pectus excavatum, an enlarged uterus and endothelial dysfunction. One should always consider peri-partum as well as post-partum pre-eclampsia.


Hypertension.
This article seeks to inform the reader about the global burden of hypertension and highlight the need for therapies to reduce societal costs and mortality associated with hypertension. Hypertension is a worldwide health concern for which international and European evidence and guidelines should be incorporated with the high-quality evidence that has been generated and synthesized in the United States. Together the guidelines broaden our understanding of hypertension and how best to manage the disease based upon realistic resources available across countries and regions where resources are more limited in availability.


O-GlcNAc Transferase (OGT) Protects Cerebral Neurons from Death During Ischemia/Reperfusion (I/R) Injury by Modulating Drp1 in Mice.
Previous studies have demonstrated that increased O-linked N-acetylglucosamine (O-GlcNAc) level could promote cell survival following environmental stresses. This study aimed to explore the role of O-GlcNAc transferase (OGT) during cerebral ischemia/reperfusion (I/R) injury. The mouse model with cerebral I/R injury was induced by middle cerebral artery occlusion/reperfusion (MCAO/R). The expression of ogt in brain tissues was detected by qRT-PCR, Western blot, and immunohistochemistry (IHC) staining assay. Neurological deficit was evaluated using a modified scoring system. The infarct volume was assessed by TTC staining assay. Neuronal apoptosis in brain tissues was evaluated by TUNEL staining assay. The level of cleaved caspase-3 in brain tissues was detected by Western blot and IHC staining assay. The expression of critical proteins involved in mitochondrial fission, including OPA1, Mfn1, and Mfn2, as well as Mff and Drp1 was detected by Western blot and IHC, respectively. The expression of ogt during cerebral I/R injury was significantly upregulated. Ogt knockdown significantly increased neurological score and infarct volume in I/R-induced mice. Meanwhile, ogt knockdown significantly enhanced neuronal apoptosis and cleaved caspase-3 level in brain tissues of I/R-induced mice. In addition, ogt knockdown markedly decreased serine 637 phosphorylation level of mitochondrial fission protein dynamin-related protein 1 (Drp1) and promoted Drp1 translocation from the cytosol to the mitochondria. Moreover, the specific Drp1 inhibitor mdivi-1 effectively attenuated ogt knockdown-induced brain injury of I/R-stimulated mice in vivo. Our study revealed that OGT protects against cerebral I/R injury by inhibiting the function of Drp1 in mice, suggesting that ogt may be a potential therapeutic target for cerebral I/R injury.


Sphenoid Sinus Pneumatization Types and Correlation with Adjacent Neurovascular Structures Using Cone-Beam Computed Tomography.
Aims: This study aimed to assess the sphenoid sinus pneumatization types and their correlation with adjacent neurovascular structures using cone-beam computed tomography (CBCT). Materials and methods: This cross-sectional study was conducted on 97 CBCT scans of patients over 18 years of age that were retrieved from the archives of the Oral & Maxillofacial Radiology Department of School of Dentistry. Type of sphenoid sinus pneumatization based on its relationship with sella turcica (conchal, presellar, sellar, and postsellar), the correlation of internal carotid artery (ICA) and optic nerve (ON) with the sinus cavity in the axial and coronal planes (smooth or prolonged type), and presence of Onodi cells and their correlation with the sphenoid sinus (lateral, superior, and superolateral) were all evaluated on CBCT sections. Data were analyzed by the Chi-square and Fisher's exact tests (alpha = 0.05). Results: Postsellar type was the most common sphenoid sinus pneumatization type (82.5%). The Smooth type was the most common form of correlation of ON and ICA with the sphenoid sinus. Onodi cells were noted in 28.9% of the cases; among which, the lateral type had the highest prevalence. Conclusion: Considering the high prevalence of sphenoid sinus pneumatization, Onodi cells, and ON and ICA protrusion in our study population, CBCT should be requested prior to trans-sphenoidal surgical procedures to prevent perioperative and postoperative complications. The online version contains supplementary material available at 10.1007/s12070-023-03796-0.


Evaluation of self-esteem and depression symptoms in depressed and nondepressed subjects treated with onabotulinumtoxinA for glabellar lines.
Botulinum toxin type A (BoNT-A) injection has become the most popular cosmetic nonsurgical procedure, and it has been suggested that BoNT-A injections may improve emotional states when frown lines are treated. To evaluate symptoms of depression and self-esteem before and after onabotulinumtoxinA (ONA) injections in the glabella in subjects with and without depression. Twenty-five subjects with depression were allocated into one group and 25 subjects without depression were matched to those according to demographic characteristics. The Beck Depression Inventory (BDI) and Rosenberg Self-Esteem Scale (RSES) were used to assess depression symptoms and self-esteem, respectively. Patients were assessed up to 12 weeks after the intervention. Patients with depression had significant improvement in depression symptoms after ONA injections. The maximum effect occurred within the first 8 weeks after treatment. A significant reduction from baseline in BDI score and significant improvement in self-esteem were also observed in patients with depression. This research presents new data regarding BoNT-A as a potential treatment to improve depression symptoms in patients with Major Depressive Disorder. Self-esteem scores alone cannot explain the improvement in depression symptoms.


Perturbation Analysis of Quantum Reset Models.
This paper is devoted to the analysis of Lindblad operators of Quantum Reset Models, describing the effective dynamics of tri-partite quantum systems subject to stochastic resets. We consider a chain of three independent subsystems, coupled by a Hamiltonian term. The two subsystems at each end of the chain are driven, independently from each other, by a reset Lindbladian, while the center system is driven by a Hamiltonian. Under generic assumptions on the coupling term, we prove the existence of a unique steady state for the perturbed reset Lindbladian, analytic in the coupling constant. We further analyze the large times dynamics of the corresponding CPTP Markov semigroup that describes the approach to the steady state. We illustrate these results with concrete examples corresponding to realistic open quantum systems.


Evaluating Intensity-Modulated Radiation Therapy in Locally Advanced Non-Small-Cell Lung Cancer: Results From the National Cancer Data Base.
Reports have suggested improvements in dosimetry, toxicity, and quality of life with intensity-modulated radiation therapy (IMRT) in locally advanced non-small-cell lung cancer (NSCLC). The selection criteria for those patients who may benefit is unclear. This study sought to identify subgroups of patients who may derive survival benefit from intensity modulated radiation therapy (IMRT) compared with 3D conformal radiation therapy (3DCRT). The National Cancer Data Base was queried for stage III NSCLC treated with radiation and chemotherapy alone with curative intent. All received ≥ 58 Gy. Kaplan-Meier and log-rank test were performed to compare overall survival (OS) by treatment modality. A multivariable Cox proportional hazards model was used to assess association with OS. Propensity score matching was also implemented. A total of 2543 patients treated between 2003 and 2006 were eligible; 422 (16.6%) received IMRT, 2121 (83.4%) received 3DCRT. In patients with T3 and T4 disease, IMRT was associated with an improvement in median OS and 5-year survival rate (17.2 vs. 14.6 months; 19.9% vs. 13.4%, P = .021.) In multivariable analysis, there was an interaction between treatment type and T stage that was found to be significant (P = .03). In the propensity matched cohort of T3 and T4 patients, the use of IMRT remained associated with improved OS (hazard ratio, 0.80; 95% confidence interval, 0.64-1.00; P = .048). Use of IMRT in patients with T3 and T4 tumors was associated with improved overall survival in this large population-based analysis. This is a novel finding that is in concordance with the well-described dosimetric benefits of IMRT in NSCLC.


High-quality antidepressant discovery by understanding stress hormone physiology.
Compensating the consequences of impaired corticosteroid receptor signaling is a novel strategy to discover better antidepressants. The prevailing drugs gradually improve stress hormone regulation along with ameliorating psychopathology. The current understanding of how neuropeptides, such as corticotropin-releasing hormone (CRH) and vasopressin (AVP), drive cortisol secretion via corticotrophin has paved the way for CRH- and AVP-receptor antagonists. As alternative strategies, the blockade of corticosteroid receptors or inhibition of cortisol synthesis has emerged. All these strategies are not yet fully clinically developed, but preliminary data from basic and clinical research strongly underscore that such strategies may lead to innovative treatment modalities.


Effect of sphenopalatine ganglion block on intracranial pressure and cerebral venous outflow oxygenation during craniotomy for supratentorial brain tumours.
Intraoperative intracranial pressure (ICP) control continues to be a challenge for anaesthetists during craniotomies. Although many standard brain-dehydrating protocols are available, they may be ineffective in certain surgical situations and may result in harm either to the systemic or cerebral circulation. Sphenopalatine ganglion block (SPGB) can reverse the vasodilatory effects of anaesthesia during craniotomy. This prospective randomised study was carried from June 2020 to February 2021. Fifty-two patients were randomly allocated into two groups, the block group (B) and the non-block control group (Non). Twenty-six patients were enrolled in the (B) group and received a bilateral transnasal SPG block with 2% lidocaine using a hallow culture swab prior to anaesthesia induction. Intraoperative monitoring was performed using standard American Society of Anesthesiologists (ASA) monitors in addition to invasive monitoring using intra-arterial cannulas and jugular venous bulb catheters. Subdural ICP monitors were also employed. The arterio-jugular oxygen difference in mmol/l (AjvDO2) was then calculated. Mean flow velocity cm/s (MFV) and pulsatility index (PI) were monitored in both groups using Transcranial Doppler. Haemodynamic data were recorded every 30 min from induction of anaesthesia until the closure of the dura. There was a significant difference in ICP prior to the dural opening between the block group (B), mean ± sd 7.58 ± 1.47, and the non-block group (Non), mean ± sd (11.69 ± 1.72), p-value < 0.001. There was no significant difference in MFV between (B) group, mean ± sd 72.65 ± 2.28 and (Non) group, mean ± sd 71.19 ± 3.09 before intubation (baseline values). While there was a significant difference after intubation between block group, mean ± sd 72.12 ± 1.77 and non-block group, mean ± sd 74.62 ± 5.07, p-value = 0.02. There was an insignificant difference between (B) and (Non) groups before intubation regarding PI values, while PI was significantly higher in (B) group than the (Non) group after intubation where mean ± sd was 1.17 ± 0.05 versus 0.96 ± 0.09, respectively, p-value = 0.001. There was no significant difference regarding cerebral oxygenation between the groups. SPGB can control factors that increase CBF during anaesthesia by the block of parasympathetic vasodilatory fibres to the arterial system in the anterior cerebral circulation, while neither hindering cerebral venous drainage nor impairing cerebral oxygenation, as it gives no supply to cerebral veins and does not affect basal CBF. Additionally, it does not affect systemic circulation.


Correlation between serum IGF-1 and EGF levels and neuropsychiatric and cognitive in Parkinson's disease patients.
Insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF) exert neuroprotective effects in Parkinson's disease (PD). To date, studies on the relationships between serum IGF-1 and EGF levels and nonmotor symptoms in PD patients have been rare. A Siemens automatic chemical analyzer was used to determine serum IGF-1 levels, and enzyme-linked immunosorbent assay was used to detect serum EGF levels in 100 healthy controls and 100 PD patients, including those in the early (n = 49) and middle-late (n = 51) stage of the disease. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Serum IGF-1 and EGF levels were higher in PD patients than in healthy controls, and serum IGF-1 and EGF levels were higher in early stage PD patients than in middle-late stage PD patients. Serum IGF-1 levels were significantly negatively correlated with anxiety, depression, and cognitive dysfunction; serum EGF levels were significantly negatively correlated with cognitive dysfunction. Combining IGF-1 and EGF in the diagnosis of PD was more valuable than using a single factor in the diagnosis. This study shows that serum IGF-1 levels were correlated with the nonmotor symptoms of anxiety, depression, and cognitive dysfunction and that EGF levels were correlated with cognitive dysfunction. The combination of IGF-1 and EGF increased the value for a PD diagnosis. This is the first report of the simultaneous detection of IGF-1 and EGF levels to explore the correlation with nonmotor symptoms of PD.


Association between p53 gene variants and oral cancer susceptibility in population from Gujarat, West India.
p53 gene variants i.e. 16 bp duplication in intron 3, Arg72Pro in exon 4 and G>A in intron 6 have been reported to modulate susceptibility to various malignancies. Therefore, the present study evaluated the role of these p53 polymorphisms in oral cancer susceptibility in a population from Gujarat, West India. Genotype frequencies at the three p53 loci in 110 controls and 79 oral cancer cases were determined by the PCR-RFLP method. Heterozygous individuals at exon 4 showed protection from developing oral cancer. Homozygous wild and heterozygous individuals at intron 3 and those heterozygous at exon 4 in combination appeared to be at lowered risk. Furthermore, carriers of the 16 bp duplication allele at intron 3, proline allele at exon 4 and G allele at intron 6 were protected from oral cancer development. p53 polymorphisms, especially Arg72Pro in exon 4 could significantly modify the risk of oral cancer development in Gujarat, West Indian population.


A pūrākau analysis of institutional barriers facing Māori occupational therapy students.
Across Aotearoa (New Zealand), there are chronic shortages of qualified Māori (Indigenous peoples of Aotearoa) health practitioners and systemic ethnic health inequities. This study, focussing on the discipline of occupational therapy, explores Māori graduates' recollections of the institutional barriers that impacted on their study in this field over a 25-year period. This qualitative study interviewed seven Māori occupational therapy graduates using pūrākau-an innovative Māori narrative inquiry method. Pūrākau (stories) were collected in 2018 via kanohi ki te kanohi (face to face) semi-structured interviews. They were analysed using the kaupapa Māori (Māori philosophical) framework of Pū-Rā-Ka-Ū which draws on traditional Māori mātauranga (knowledge). The institutional barriers identified were (1) cultural dissonance, (2) cultural (in)competency and (3) the limitations of (Western) pastoral care. This study highlighted how racism is embedded within the Western tertiary education system. To create a safe learning environment for Māori students, tertiary education institutions require a planned approach to address racism within policy, procedures, the curriculum, teaching and professional staff.


Randomised controlled trial of video clips and interactive games to improve vision in children with amblyopia using the I-BiT system.
Traditional treatment of amblyopia involves either wearing a patch or atropine penalisation of the better eye. A new treatment is being developed on the basis of virtual reality technology allowing either DVD footage or computer games which present a common background to both eyes and the foreground, containing the imagery of interest, only to the amblyopic eye. A randomised control trial was performed on patients with amblyopia aged 4-8 years with three arms. All three arms had dichoptic stimulation using shutter glass technology. One arm had DVD footage shown to the amblyopic eye and common background to both, the second used a modified shooter game, Nux, with sprite and targets presented to the amblyopic eye (and background to both) while the third arm had both background and foreground presented to both eyes (non-interactive binocular treatment (non-I-BiT) games). Seventy-five patients were randomised; 67 were residual amblyopes and 70 had an associated strabismus. The visual acuity improved in all three arms by approximately 0.07 logMAR in the amblyopic eye at 6 weeks. There was no difference between I-BiT DVD and non-I-BiT games compared with I-BiT games (stated primary outcome) in terms of gain in vision. There was a modest vision improvement in all three arms. Treatment was well tolerated and safe. There was no difference between the three treatments in terms of primary stated outcomes but treatment duration was short and the high proportion of previously treated amblyopia and strabismic amblyopia disadvantaged dichoptic stimulation treatment. NCT01702727, results.


Relationship between Negative Running Addiction and Eating Disorder Patterns in Runners.
Current studies show an increase in the risk of eating disorders in runners. Since it is known that abusive exercise can be both a cause and a consequence of such developments, the main objective of the present study was to examine the risk and possible relationships between negative running addiction (NRA), as measured by the reduced and validated SAS-40 scale, and the tendency to be a compulsive eater (measured by YFAS 2.0), anorexia nervosa (AN), and/or bulimia nervosa (BN) (measured by EAT-40). This study highlights the novelty of researching the level of influence of NRA on each defined eating disorder. A total of 167 Spanish-speaking federated runners in cross-country and track running (42% women and 58% men), with an average age of 24 years and an average BMI of 21 kg/m2, responded to an online questionnaire that asked about sociodemographic data and the Spanish versions of the SAS-40, YFAS 2, YFAS 3, and YFAS 4. Through a quantitative methodology using logistic regressions-the coefficient of determination and Pearson's correlation coefficient-we created a sample analysis that related the significant items of the DSM-V to the results of the questionnaires administered, as well as their relationship with the practice of the sport in question and various variables of the environment. The rates of CE, AN, and BN were 65, 11.4, and 16.2%, respectively. The tendency towards CE increased with a lower weight (r = 0.156, p < 0.05), not having been overweight in childhood (r = 0.151, p < 0.05), and being a long-distance runner (r = 0.123 p < 0.05). The risk of AN increased with the absence of menstruation for more than 3 months (r = 0.271 p < 0.01), having suffered from childhood obesity (r = 0.213 p < 0.05), and being underweight (r = 0.064 p < 0.05). The risk of BN increased with having suffered from childhood obesity (r = 0.194 p < 0.05), having a higher weight (r = 0.140, p < 0.05), and practicing athletics, especially the relay modality (r = 0.044 p < 0.05). A considerable number of runners are at risk of suffering from some type of eating disorder. A significant relationship was observed between long-distance runners and the risk of eating disorders (AN, BN, and CE), and the association is stronger for CE than for AN and BN. Lastly, childhood experiences (such as being obese/a healthy weight) were notorious for increasing the risk of eating disorders. Further studies are needed to research each particular parameter and the relationships between the possible levels of dependence on exercise. Level III, cohort analytic study.


Urokinase and plasminogen activator inhibitor type 1 in pulmonary adenocarcinoma.
The urokinase pathway of plasminogen activation is involved in proteolytic degradation of various tissues, including dissolution of the extracellular matrix and basement membranes during the process of cancer cell invasion. We have studied the prognostic value of urokinase-type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAI-1) in tumor extracts from 106 patients with adenocarcinoma of the lung. uPA and PAI-1 levels were determined by sandwich enzyme-linked immunosorbent assays. No correlation was found between uPA and PAI-1 (r = 0.23). High PAI-1 levels were significantly associated with short-duration overall survival (P = 0.017), while uPA levels showed no significant association with overall survival. Relating the levels of PAI-1 to other prognostic factors such as stage and age, no significant correlations were found. The prognostic impact of uPA and PAI-1 were investigated together with other prognostic factors in Cox multivariate analysis. PAI-1 was found to be an independent prognostic variable for survival, the relative risks being 1.5 (low versus medium PAI-1 values (95% confidence interval, 1.2-1.8) and 2.2 (low versus high (95% confidence interval, 1.8-2.6)). In patients with stage I disease (69 patients) high levels of PAI-1 were significantly associated with poor prognosis compared to low levels (P = 0.037). These data indicate that PAI-1 is a potentially important prognostic factor in pulmonary adenocarcinoma and may as such be used to select patients with low stage and poor prognosis for adjuvant therapy subsequent to complete surgical resection.


Molecular markers in pituitary tumors.
This review summarizes our current understanding of the mechanisms and factors involved in pituitary tumorigenesis. It provides a comprehensive review on the role of genetic mutations, epigenetics, oncogenes, tumor suppressor genes, cell cycle deregulation, and highlights recent findings of altered micro-RNA and long noncoding RNA expression in pituitary tumors. This article provides a concise summary of our knowledge regarding oncogenes, tumor suppressor genes, and cell cycle deregulation in pituitary tumors. Additionally, it highlights new findings in epigenetics and altered micro-RNA and long noncoding RNA expression in pituitary tumors. Improved understanding of the mechanism(s) and candidates implicated in pituitary tumorigenesis may result in the identification of new therapeutic targets in pituitary tumors.


Acute circulatory actions of intravenous amiodarone loading in cardiac surgical patients.
The duration, severity, and cause of hypotension after intravenous amiodarone has not been well characterized in anesthetized cardiac surgical patients. Because amiodarone is tolerated in patients with advanced cardiac disease, we hypothesized that left ventricular systolic performance is preserved despite hypotension during amiodarone loading. In a prospective double-blind trial, 30 patients undergoing coronary artery bypass graft (CABG) surgery were randomly assigned to receive intravenous amiodarone (n = 15) or placebo (n = 15). Cardiac output (CO), mixed venous oxygen saturation (SVO), arterial blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP]), pulmonary artery pressure, and central venous pressure (CVP) were recorded. Transesophageal echocardiographic left ventricular end-diastolic area (EDA), end-systolic area (ESA), fractional area change (FAC), and end-systolic wall stress (ESWS) were measured every 5 minutes. Mean arterial pressure, SBP, and DBP decreased over time after drug administration in both groups (p < 0.05). At 6 minutes, amiodarone decreased the MAP by 14 mm Hg (p = 0.004) and placebo decreased the MAP by 4 mm Hg. The change in MAP, SBP, and DBP between groups was statistically different for the first 15 minutes after drug administration. Hypotension requiring intervention occurred in 3 of 15 after amiodarone and 0 of 15 after placebo (p = 0.22). The mean heart rate was 11.5 beats per minute less after amiodarone (p < 0.02), but pulmonary artery pressure, CVP, SVO, and FAC were not different between groups. Intravenous amiodarone decreased heart rate and caused a significant, but transient decrease in arterial pressure in the first 15 minutes after administration. Left ventricular performance was maintained suggesting that selective arterial vasodilation was the primary cause of drug-induced hypotension.


Effect of Concomitant Radiochemotherapy on Invasion Potential of Glioblastoma.
Glioblastoma (GBM) is the most common primary brain tumor in adults with inevitable recurrence after oncotherapy. The insufficient effect of "gold standard" temozolomide-based concomitant radiochemotherapy may be due to the inability to prevent tumor cell invasion. Peritumoral infiltration depends mainly on the interaction between extracellular matrix (ECM) components and cell membrane receptors. Changes in invasive behaviour after oncotherapy can be evaluated at the molecular level by determining the RNA expression and protein levels of the invasion-related ECM components. The expression of nineteen ECM molecules was determined at both RNA and protein levels in thirty-one GBM samples. Fifteen GBM samples originated from the first surgical procedure on patients before oncotherapy, and sixteen GBM samples were collected at the second surgery due to local recurrence after concomitant chemoirradiation. RNA expressions were measured with qRT-PCR, and protein levels were determined by quantitative analysis of Western blots. Only MMP-9 RNA transcript level was reduced (p < 0.05) whereas at protein level, eight molecules showed changes concordant with RNA expression with significant decrease in brevican only. The results suggest that concomitant radiochemotherapy does not have sufficient impact on the expression of invasion-related ECM components of glioblastoma, oncotherapy does not significantly affect its invasive behavior. To avoid the spread of tumors into the brain parenchyma, supplementation of antiproliferative treatment with anti-invasive agents may be worth consideration in oncotherapy for glioblastoma.


Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice.
To facilitate a functional analysis of neuronal connectivity in a mammalian nervous system that is tightly packed with billions of cells, we developed a new technique that uses inducible genetic manipulations in fluorescently labeled single neurons in mice. Our technique, single-neuron labeling with inducible Cre-mediated knockout (SLICK), is achieved by coexpressing a drug-inducible form of Cre recombinase and a fluorescent protein in a small subsets of neurons, thus combining the powerful Cre recombinase system for conditional genetic manipulation with fluorescent labeling of single neurons for imaging. Here, we demonstrate efficient inducible genetic manipulation in several types of neurons using SLICK. Furthermore, we applied SLICK to eliminate synaptic transmission in a small subset of neuromuscular junctions. Our results provide evidence for the long-term stability of inactive neuromuscular synapses in adult animals and demonstrate a Cre-loxP compatible system for dissecting gene functions in single identifiable neurons.


Mouse brain c-fos mRNA distribution following a single electroconvulsive shock.
The regional distribution of c-fos mRNA in the mouse brain has been investigated by in situ hybridization autoradiography after seizures induced by an acute electroconvulsive shock (ECS). ECS led to a widespread induction of the proto-oncogene c-fos in the brain, with highest concentrations in discrete areas within the limbic system and also in the hypothalamus and cerebellum. The mild stress of sham treatment in earclipped animals induced a weaker and qualitatively different pattern of c-fos mRNA expression involving the cortex, hippocampus, and cerebellum. These data suggest the usefulness of c-fos in situ hybridization as a marker of neuronal stimulation and in mapping a range of effects from a mild stress to the robust changes of an electroconvulsive seizure.


Recurrent Mycobacterium chelonae Skin Infection Unmasked as Factitious Disorder Using Bacterial Whole Genome Sequence Analysis.
Mycobacterium chelonae infections usually resolve with adequate therapy. We report the case of an adolescent with a chronic and progressive M chelonae infection refractory to combined antimicrobial and surgical therapy. Whole genome sequence analysis of consecutive isolates distinguished reinfection from recurrence and contributed to the diagnosis of a factitious disorder.


Association of the interleukin-4Rα rs1801275 and rs1805015 polymorphisms with glioma risk.
Potential single-nucleotide polymorphisms (SNPs) of interleukin-4 receptor alpha (IL-4Rα) rs1801275 and rs1805015 have been implicated in glioma risk; however, the findings of previous published case-control studies are conflicting and inconclusive. We performed the updated meta-analysis with the aim to provide a more precise estimate for the role of interleukin-4Rα SNPs in glioma risk. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the gene association. Overall, the pooled analysis showed that the IL-4Rα rs1801275 polymorphism was associated with a decreased risk of glioma in the comparison of G vs. A (OR = 0.87, 95% CI = 0.76-0.99, P OR = 0.041). Subgroup analysis by ethnicity revealed that the IL-4Rα rs1801275 variant G and GG + AG exerted a decreased risk effect on the development of glioma among Asians, but not Caucasians (G vs. A, OR = 0.81, 95% CI = 0.69-0.95, P OR = 0.011; GG + AG vs. AA, OR = 0.80, 95% CI = 0.66-0.96, P OR = 0.018). However, the IL-4Rα rs1805015 polymorphism did not modify the risk of glioma. Sensitivity analysis confirmed the reliability for all of the results. Our meta-analysis suggests that the polymorphism of IL-4Rα rs1801275 but not IL-4Rα rs1805015 plays a protective role in the glioma pathogenesis, particularly among Asians.


Effects of low vs. moderate dose of recreational football on cardiovascular risk factors.
This study aimed to compare the effectiveness of recreational football performed once (LOW) vs. twice (MOD) a week on cardiovascular risk factors in healthy, sedentary men. Body composition, resting blood pressure, blood lipid profile and maximal oxygen consumption (VO2max) were measured at baseline, after a 12-week control and training period, using an interrupted time-series study (study 1, n = 18: n = 8, LOW and n = 10, MOD) nested in a randomized parallel trial (study 2, n = 34: n = 18 LOW and n = 16 MOD). After the intervention in study 1, LDL-cholesterol (-12.3 mg·dL-1 [-22.7 to -2.0]) and VO2max (4.5 ml·kg-1·min-1 [1.2-7.8 ]) changed in LOW whereas differences were found in weight (-2.1 kg [-3.7 to -0.4]), BMI (-0.7 kg·m-2 [-1.2 to -0.1]), total cholesterol (-22.2 mg·dL-1 [-36.0 to -8.4]), no-HDL-cholesterol (-17.5 mg·dL-1 [-30.5 to -4.5]), LDL-cholesterol (-14.9 mg·dL-1 [-23.6 to -6.2]) and VO2max (5.7 ml·kg-1·min-1 [2.8-8.6]) in MOD. Study 2 showed no evidence of differences between groups. Our results therefore suggest positive health effects of recreational football even when performed at low frequency as it can happen in real context.Highlights Moderate and high amount of recreational football practice (i.e. 2 or 3 h a week) have been shown to be effective to improve health-related factors in both healthy and unhealthy people.Scarce data are present regarding the effect of a low frequency of recreational football practice (i.e. 1 h a week) that is often usual in a real context.Our results showed the practice of recreational football, once a week, is effective for improving some cardiovascular risk factors (maximal oxygen consumption and LDL-cholesterol) in sedentary, healthy middle-aged men.Moreover, practising recreational football once or twice a week seems to lead to similar positive health adaptations.


Enteral nutrition and the function of the intestinal microflora in healthy adults.
An oral feeding formula was given to 5 healthy volunteers for 8 days. Faecal samples were collected before, during and after the feeding period. The effect of enteral nutrition (EN) on the following seven intestinal microflora-associated characteristics (MACs) was studied: formation of urobilinogen, coprostanol and deoxycholic acid, degradation of mucin and beta-aspartylglycine, faecal tryptic activity, and production of short-chain fatty acids (SCFAs). None of the microbial functions studied were lost during the study. The urobilinogen level increased during EN (P < 0.05) but it seems reasonable to assume that this was a concentration effect due to a decrease in stool mass. The concentration of SCFAs decreased during EN (P < 0.05) and this reflects the absence of dietary fibre in the feed used.


Observation of random-phase gap solitons in photonic lattices.
We report what is to our knowledge the first experimental observation of gap random-phase lattice solitons: self-trapped spatially incoherent entities whose modal constituents lie within a photonic bandgap.


Acute adrenal insufficiency following unilateral radical nephrectomy: a case report.
Adrenal insufficiency following unilateral radical nephrectomy has not been previously described in medical literature. We present a 78-year-old male patient who experienced a difficult postoperative course with vague findings, and was ultimately diagnosed with acute adrenal insufficiency. Treatment with glucocorticoids and mineralocorticoids resulted in prompt control of the disease.


Urachal signet-ring cell carcinoma, a rare variant of vesical adenocarcinoma: incidence and pathological criteria.
Of 715 cases of vesical tumors reviewed 18 adenocarcinomas were selected for further study, 5 of which fulfilled all criteria of urachal origin. Herein is reported 1 rare case of such a carcinoma of the signet-ring cell type and the morphological criteria of this variant are discussed briefly. After undergoing radical cystectomy and ureterosigmoidostomy the patient has been free of recurrent tumor or metastasis for 6 years.


[Technical notes about radiculosaccography (author's transl)].
We insist about the following notions: contra-indications: epilepsy, papillary stasis, important ethylism, folliculitis in the lumbar punction area; preparation by intra-venous hydrocortisone and Primperan in two different syringes (to prevent lipothymia and vomiting); localisation by TV of the space L2-L3; cytology and albumin in the cerebrospinal fluid; localised X-rays on the suspected intervertebral disk.


[Human genome project: a federator program of genomic medicine].
The Human Genome Project improves our understanding of the molecular genetics basis of the inherited and complex diseases such as diabetes, schizophrenia, and cancer. Information from the human genome sequence is essential for several antenatal and neonatal screening programmes. The new genomic tools emerging from this project have revolutionized biology and medicine and have transformed our understanding of health and the provision of healthcare. Its implications pervade all areas of medicine, from disease prediction and prevention to the diagnosis and treatment of all forms of disease. Increasingly, it will be possible to drive predisposition testing into clinical practice, to develop new treatments or to adapt available treatments more specifically to an individual's genetic make-up. This genomic information should transform the traditional medications that are effective for every members of the population to personalized medicine and personalized therapy. The pharmacogenomics could give rise to a new generation of highly effective drugs that treat causes, not just symptoms.


Honey Bee Queen Replacement: An Analysis of Changes in the Preferences of Polish Beekeepers through Decades.
We conducted a survey on honey bee (Apis mellifera) queen management. Data were collected every year from 1980 to 2018. In total, 2964 questionnaires were collected from all over Poland. We examined the trends by decade timeslot, apiary size, and geographical location. Regardless of the decade and the size of the apiary, on average, above 90% of Polish beekeepers replace old queens with new ones in their colonies. In general, during the observed period, beekeepers replaced almost 52% of their queens, 21% of which were purchased. In the last decade, there was an upward trend in the percentage of beekeepers replacing queens throughout the country. The involvement of purchased queens in colony management is associated with the size of the apiary, and it significantly grows with the number of colonies in the apiary. The percentage of purchased queens went up in all the voivodeships over time. Research and education in this area are needed in order to track the trends and further improve Polish beekeepers' practices.


Association of preoperative muscle composition of the lower extremity with gait function after total knee arthroplasty.
Limitations of gait function persist in some patients with knee osteoarthritis after total knee arthroplasty. This study aimed to identify preoperative muscle composition variables of the operated limb associated with postoperative gait function. Longitudinal data from 45 patients who underwent unilateral primary total knee arthroplasty were retrospectively analyzed. Timed Up-and-Go test and gait speed were measured preoperatively and at 3 and 6 months postoperatively. Preoperative muscle composition in the glutei medius and minimus, the quadriceps, the hamstrings, and combination of the hamstrings and quadriceps were evaluated by computed tomography. The area ratio of the individual muscle composition to the total muscle was calculated. The factors associated with Timed Up-and-Go test and gait speed were identified using stepwise regression analysis. Shorter Timed Up-and-Go test and faster gait speed at each time point correlated with higher lean muscle mass area of the total hamstrings, higher area ratio of lean muscle mass to the total hamstrings or to combination of the hamstrings and quadriceps, and lower area ratio of low density lean tissue or intramuscular adipose tissue to the total hamstrings. Shorter Timed Up-and-Go test at each time point also correlated with higher combined area of lean muscle mass of the hamstrings and quadriceps. Faster gait speed at each time point additionally correlated with lower area ratio of intramuscular fat to the total hamstrings and lower area ratio of lean tissue mass or intramuscular adipose tissue to combination of the hamstrings and quadriceps. Regression analysis using the significant muscle composition variables revealed that the area ratio of lean muscle mass to the total hamstrings was the only predictor of Timed Up-and-Go test and gait speed after operation. Preoperative area ratio of ipsilateral lean muscle mass to the total hamstrings could predict gait function after total knee arthroplasty.


Comparative evaluation of supplemental hepatitis C virus antibody test systems.
Implementation of routine blood donor screening using anti-hepatitis C virus (HCV) enzyme immunoassay (EIA) has resulted in an urgent need for well-characterized supplemental assays to confirm the presence of HCV antibodies. A comparative study of four commercially available supplemental assays is reported here: first- and second-generation versions of a strip recombinant immunoblot assay (RIBA-1 and RIBA-2), an HCV neutralization EIA, and HCV neutralization plus synthetic peptide EIA. Three hundred sixty-seven blood donor specimens that were repeatedly reactive on HCV EIA were studied. Most specimens (93%) were also evaluated by radioimmunoassay (RIA) with a six-antigen panel, and 60 selected specimens were tested for HCV RNA by the polymerase chain reaction (PCR). RIBA-1 and RIBA-2 gave concordant results with 86 percent of specimens, while an additional 13 percent were correctly classified by RIBA-2 but not RIBA-1. Neutralization EIA alone correctly identified 94 percent of the study group, while the remaining 6 percent required the peptide EIA or the combined neutralization-peptide assay system for correct classification. The RIBA-2 and neutralization-peptide assay system for correct classification. The RIBA-2 and neutralization-peptide assay systems yielded identical results for 86 percent of specimens, and these results were supported by RIA and selected PCR testing. Only 2 specimens (0.5%) were frankly discrepant, while 51 specimens were indeterminate on either (47) or both (4) assays. When either the RIBA-2 or neutralization-peptide assay yielded an indeterminate interpretation, the other system correctly classified the specimen (based on concordance with RIA and PCR data) in a high proportion (92%) of cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Payback arising from research funding: evaluation of the Arthritis Research Campaign.
Using a structured evaluation framework to systematically review and document the outputs and outcomes of research funded by the Arthritis Research Campaign in the early 1990s. To illustrate the strengths and weaknesses of different modes of research funding. The payback framework was applied to 16 case studies of research grants funded in the early 1990s. Case study methodology included bibliometric analysis, literature and archival document review and key informant interviews. A range of research paybacks was identified from the 16 research grants. The payback included 302 peer-reviewed papers, postgraduate training and career development, including 28 PhD/MDs, research informing recommendations in clinical guidelines, improved quality of life for people with RA and the reduction of the likelihood of recurrent miscarriage for women with antiphospholipid syndrome. The payback arising from project grants appeared to be similar to that arising from other modes of funding that were better resourced. There is a wide diversity of research payback. Short focused project grants seem to provide value for money.


Pair-correlation properties and momentum distribution of finite number of interacting trapped bosons in three dimensions.
We study the ground state pair-correlation properties of a weakly interacting trapped Bose gas in three dimensions by using a correlated many-body method. The use of the van der Waals interaction potential and an external trapping potential shows realistic features. We also test the validity of shape-independent approximation in the calculation of correlation properties.


The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1.
YAP and TAZ are transcriptional co-activators and function as the major effectors of the Hippo tumor suppressor pathway, which controls cell growth, tissue homeostasis, and organ size. Here we show that YAP/TAZ play an essential role in amino acid-induced mTORC1 activation, particularly under nutrient-limiting conditions. Mechanistically, YAP/TAZ act via the TEAD transcription factors to induce expression of the high-affinity leucine transporter LAT1, which is a heterodimeric complex of SLC7A5 and SLC3A2. Deletion of YAP/TAZ abolishes expression of LAT1 and reduces leucine uptake. Re-expression of SLC7A5 in YAP/TAZ knockout cells restores leucine uptake and mTORC1 activation. Moreover, SLC7A5 knockout cells phenocopies YAP/TAZ knockout cells which exhibit defective mTORC1 activation in response to amino acids. We further demonstrate that YAP/TAZ act through SLC7A5 to provide cells with a competitive growth advantage. Our study provides molecular insight into the mechanism of YAP/TAZ target genes in cell growth regulation.


Tactually-related cognitive impairments: sharing of neural substrates across associative tactile agnosia, agraphesthesia, and kinesthetic reading difficulty.
A precise understanding of the neural substrates underlying tactually-related cognitive impairments such as bilateral tactile agnosia, bilateral agraphesthesia, kinesthetic alexia and kinesthetic reading difficulty is currently incomplete. In particular, recent data have implicated a role for the lateral occipital tactile visual region, or LOtv, in tactile object naming (Amedi et al. Cerebral Cortex 2002). Thus, this study set out to examine the degree to which the LOtv may be involved in tactually-related cognitive impairments by examining two unique cases. To assess whether LOtv or the visual word form area (VWFA) is involved in tactually-related cognitive impairments, the average activation point of LOtv and that of VWFA were placed on the single-photon emission computed tomography (SPECT) cerebral blood flow images of two patients: one with bilateral associative tactile agnosia, bilateral agraphesthesia, and ineffective kinesthetic reading, and the other with kinesthetic reading difficulty. The average LOtv coordinate was involved in the area of hypoperfusion in both patients, whereas that of VWFA was not included in any of the hypoperfused areas. The results support the view that interruption of LOtv or disconnection to LOtv and to VWFA may cause these tactually-related cognitive impairments. Further, bilateral associative tactile agnosia and bilateral agraphesthesia are attributable toward the damage of the occipital lobe, whereas unilateral or predominantly one-sided associative tactile agnosia and agraphesthesia are attributable toward the damage of the parietal lobe.


Ultrastructure of a primary fibrosarcoma of the human thyroid gland.
A primary fibrosarcoma of the thyroid occurring in a patient with a nodular goiter is described. Light microscopy showed interwoven bundles of spindle cells admixed with plump ovoid cells, and foci of multinucleated giant cells. Remnants of distorted thyroid follicles were found only at the periphery of the tumor. "Transitional" epithelial elements were not discernible but the tumor resembled an anaplastic giant cell carcinoma. Multiple blocks studied by electron microscopy, however, revealed that the tumor cells, including the giant cells, have the ultrastructure features of a fibroblast.


The persuasive appeal of alternative medicine.
Alternative medicine has a major presence and persuasive attraction in the industrialized western world. The extent to which these practices have clinical efficacy according to biomedical criteria is a matter of ongoing research and debate. It may be that independent of any such efficacy, the attraction of alternative medicine is related to the power of its underlying shared beliefs and cultural assumptions. The fundamental premises are an advocacy of nature, vitalism, "science," and spirituality. These themes offer patients a participatory experience of empowerment, authenticity, and enlarged self-identity when illness threatens their sense of intactness and connection to the world. A discussion of these themes may enable conventionally trained clinicians to better understand their patients' attraction to and acceptance of alternative medical therapies.


Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization.
Mast cells accumulate in tissues undergoing angiogenesis during tumor growth, wound healing, and tissue repair. Mast cells can secrete angiogenic factors such as vascular endothelial growth factor (VEGF). Ionizing irradiation has also been shown to have angiogenic potential in malignant and nonmalignant diseases. We observed that low-dose irradiation fosters mast cell-dependent vascular regeneration in a limb ischemia model. Irradiation promoted VEGF production by mast cells in a matrix metalloproteinase-9 (MMP-9)-dependent manner. Irradiation, through MMP-9 up-regulated by VEGF in stromal and endothelial cells, induced the release of Kit-ligand (KitL). Irradiation-induced VEGF promoted migration of mast cells from the bone marrow to the ischemic site. Irradiation-mediated release of KitL and VEGF was impaired in MMP-9-deficient mice, resulting in a reduced number of tissue mast cells and delayed vessel formation in the ischemic limb. Irradiation-induced vasculogenesis was abrogated in mice deficient in mast cells (steel mutant, Sl/Sl(d) mice) and in mice in which the VEGF pathway was blocked. Irradiation did not induce progenitor mobilization in Sl/Sl(d) mice. We conclude that increased recruitment and activation of mast cells following irradiation alters the ischemic microenvironment and promotes vascular regeneration in an ischemia model. These data show a novel mechanism of neovascularization and suggest that low-dose irradiation may be used for therapeutic angiogenesis to augment vasculogenesis in ischemic tissues.


Density-dependent tumor cell death and reversible cell cycle arrest: mutually exclusive modes of monocyte-mediated growth control.
The population development of five human tumor cell lines is examined under the influence of elutriator-prepared human monocytes in a serum-free hormone- and growth factor-supplemented medium. Analysis was performed by electronic counting and sizing of tumor cell nuclei and flow cytometric detection of cell cycle phases. Tumor cell death is triggered at rather low monocyte:tumor cell ratios (1:2 to 1:4) whereas it is strongly reduced at high monocyte densities. Furthermore, it is shown that confluence of the target cell population is a necessary prerequisite for lysis. The data suggest that in monocyte/tumor cell cocultures the decision on target cell lysis is not made by the effector cell, but rather by the target cell and that the criterion for this decision is the target cell's ability or inability to respond to a monocyte challenge by arresting the cell cycle in G1. Interactions between target cells play an important role in determining the result of this decision process. A common basis is suggested for this kind of density-dependent monocyte-triggered lysis and density-dependent cell death in 3T3 cell cultures as described previously.


Pacific white shrimp (Litopenaeus vannamei) vitelline membrane outer layer protein 1 (VMO1) is produced in the hepatopancreas and transported into ovarian oocytes during vitellogenesis.
In birds, vitelline membrane outer layer protein 1 (VMO1) is an exogenous protein that can be absorbed by eggs as a barrier to prevent the mixing of yolk and egg white. However, researches on VMO1 are limited in birds but not other non-avian species until now. In this study, we first identified a novel Vmo1 cDNA (Lv-Vmo1) in Pacific white shrimp (Litopenaeus vannamei), the most important cultured shrimp in the world. We further analyzed its gene organization, phylogenetic relationship and protein structure. The Lv-Vmo1 transcript was specifically expressed in the hepatopancreas without sexual dimorphism. During ovarian development in female, the hepatopancreatic Lv-Vmo1 mRNA levels showed a significant increase. By in situ hybridization, Lv-Vmo1 mRNA was present in three cell types of the hepatopancreas but neither oocytes nor follicle cells of the ovary. In contrast, immunofluorescence revealed that Lv-VMO1 protein was distributed in the cytoplasms of both hepatopancreatic cells and ovarian oocytes. Western blot showed that Lv-VMO1 protein was produced in the hepatopancreas and transported to the ovary via hemolymph circulation. Identification of a species-specific egg-entry guide protein is the key to the receptor-mediated ovarian transduction of cargo, a novel gene editing approach in oviparous animals. This study lays the mechanism for exogenous transport into penaeid shrimp eggs by VMO1, as a foundation for achieving exogenous protein-mediated incorporation into oocytes.


A long-term experience with Mutars tumor megaprostheses: analysis of 187 cases.
Modular megaprostheses have widely replaced allografts, as a reconstructive option; however, failures of these devices remain high. Aim of this study was to analyze outcomes, survival of the implants, incidence and types of complications with Mutars modular endoprostheses at long term. Between 2000 and 2019, 187 Mutars prostheses were implanted in two dedicated centers: 72 upper limbs and 115 lower limbs reconstructions. Diagnoses included 107 primary malignant bone or soft tissue tumors, 65 metastases, 8 benign bone tumors and 7 non-oncologic cases. Silver-coated prostheses were used in 118/187 (63%) cases. At last follow-up, 76.5% of patients had retained their implant. The overall failure rate was 23.5% at a mean of 1.7 years. There were 22 mechanical failures and 22 non-mechanical failures. The overall implant survival to all types of failure was 68% and 52% at 5 and 10 years, respectively. Infection was the most common mode of failure with an incidence of 6.9%. Implant survival to infection was better for silver-coated implants than for standard implants even if with no significant difference (p = 0.56). Functional results were satisfactory in 97% of patients. The overall implant survival at long term was satisfactory with Mutars prostheses. The incidence of complications with Mutars prosthesis is in line with the incidence reported in the literature with other types of tumor prosthesis. The most frequent cause of failure was infection with a lower incidence in silver-coated prostheses; silver coating seems to prevent infection in distal femur and proximal tibia. The silver coating seems to be particularly useful in two-stage revisions with a lower incidence of secondary amputation. In higher risk patients, silver-coated prostheses are the preferable choice for the reduction of the reinfection rate. The functional results of Mutars prostheses were excellent or good in most of cases. The current paper is design to enhance the literature on megaprosthesis in tumor surgery, proven that this system is one of the most used all over the word and one of the best performing.


A brief note on the resemblance between relatives in the presence of population stratification.
Population stratification occurs when a study population is comprised of several sub-populations, and can result in increased false positive findings in genomewide-association studies. Recently published work shows that sub-population-specific positive assortative mating at the genotypic level results in population stratification. We show that if the allele frequency of a single nucleotide polymorphism responsible for a trait varies between sub-populations and there is no dominance variance, then the heritability of the trait increases, primarily due to an increase in the additive genetic variance of the trait.


Novel mutations of SOX10 gene in Chinese patients with type II Waardenburg syndrome.
Waardenburg Syndrome (WS) is a condition characterized by sensorineural deafness and pigment disturbances of the skin, hair and iris. By using the latest genomics technology, the WS-related gene mutations and corresponding mechanisms have been widely studied and reported. and the high genetic heterogeneity of the disease has also been explained. However, the SOX10 gene transcription and expression has still be unclear. In this study, we determined the phenotypic gene expression of WS patients in two Chinese WS families. More importantly, we identified two novel SOX10 mutations, c.482-487del (p.R161-M162del)and c.52G > T (p.E18X) in WSII for the first time in the Chinese population.


Detection of Candida proteinase by enzyme immunoassay and interaction of the enzyme with alpha-2-macroglobulin.
Double antibody immunoassay of secretory aspartic proteinases from 2 strains of the yeast Candida albicans was performed in microtest plates with rabbit antibody and peroxidase conjugated rabbit antibody. The test detects approximately 0.1 ng of proteinase and is 2 orders of magnitude more sensitive than direct measurement of enzymic activity with hemoglobin as a substrate. The immunoassay was affected both by alkaline denaturation, which is a common feature of aspartic proteinases, and by the presence of the proteinase scavenger alpha-2-macroglobulin. Conditions are described that allow for comparison of proteinases from different strains of yeast and minimize the interference of macroglobulin.


Quantitative urine collection in renal clearance studies in the dog.
A double-walled urinary catheter is described which allows rapid and quantitative urine collection at short time intervals. The catheter consists of a polyurethane outer cannula in which a small Teflon cannula is inserted. The essential of the catheter is that at the end of a collection period, residual urine in the bladder can be collected completely via the outer cannula by flushing the bladder with physiological salt through the inner cannula. In this manner urine can be collected in a very reproducible way at intervals down to 5 min. The use of the catheter was illustrated in a study on the renal clearance of hippuric acid in the dog. Plasma concentration and renal excretion rate were followed after i.v. injection of 0.9 g sodium hippurate. In accordance with previous studies, it was found that the renal excretion of hippuric acid consisted of glomerular filtration and active tubular secretion. A large variability was observed in the tubular transport maximum (3,800-11,600 micrograms/min) and the Michaelis-Menten constant (22-190 micrograms/ml), which were used to characterize the secretory system. The interpretation and value of these transport parameters is discussed briefly.


Concomitant T- and Tk-activation associated with acquired-B antigens.
Three patients with acquired-B antigens are reported whose red blood cells also manifested T- and Tk-activation. The results of tests using purified Arachis hypogaea and Bandeiraea simplicifolia (BS II) lectins, and red blood cells either T, Tk or both T and Tk-activated by bacterial enzymes in vitro, suggest that the acquired-B phenomenon, T-activation and Tk-activation result from the action of different bacterial enzymes.


A new method for asperphenamate synthesis and its antimicrobial activity evaluation.
Asperphenamate is a natural phenylalanine derivative. This compound was produced through a new, two-step synthetic route. It was also evaluated by the antimicrobial activity of the pure substance against Escherichia coli, Staphylococcus aureus and Cladosporium herbarum.


[Minimally invasive stabilization of sacral fractures].
Sacral fractures can be of traumatic origin and can also occur as insufficiency fractures. While the therapeutic target of mechanically stable insufficiency fractures is mainly pain relief, mechanically unstable insufficiency fractures and traumatic sacral fractures following high-energy trauma require biomechanical stabilization. Various surgical strategies are available for this, whereby minimally invasive techniques are now preferred whenever possible. This article presents the clinical challenges and options for minimally invasive treatment of sacral fractures. Selected important study data are discussed and our own treatment approach is presented. The most important minimally invasive techniques for operative treatment of sacral fractures are presented: sacroiliac screw osteosynthesis, lumbopelvic stabilization and sacroplasty. The selection of the surgical technique should be made on an individual basis. While sacroiliac screw osteosynthesis is the international gold standard, diverse authors have also published minimally invasive techniques for lumbopelvic stabilization. The latter enables a higher mechanical stability. In contrast, sacroplasty should only be used as an alternative treatment in insufficiency fractures. Comparative studies of the described techniques are still missing. All surgical options have their indications. Nevertheless, the biomechanical stability which can be achieved differs widely. Therefore, an exact analysis should be carried out of what is necessary with respect to reduction and retention and what should be achieved when treating sacral fractures.


Pulse signal analysis of patients with coronary heart diseases using Hilbert-Huang transformation and time-domain method.
To explore characteristic of pulse signal to distinguish patients with coronary heart diseases (CHD) from patients without CHD and healthy adults, and accordingly evaluate the potential role of pulse signal to diagnosis CHD. Totally 407 patients enrolled from 4 collaborating medical centers were assigned to a CHD group (205 patients) and a non-CHD group (202 patients). The healthy control group (62 adults) enrolled from Shanghai University of Traditional Chinese Medicine. Pulse signals were collected using the synchronous multiplex pulse signal acquisition system. The pulse signals were analyzed and extracted using Hilbert-Huang transformation (HHT) and time-domain, respectively. The time-domain parameters of pulse signal were processed by the analysis of variance (SNK test). Special patterns in the CHD group pulse signal were found in this study: (1) time-domain parameters of pulse signal, h1, h3, h4, h3/h1, ts, t4/t were increased and w was wider; (2) 44% of C2 waves in HHT were chaotic and disordered and 72% of C waves were exhibited irregularly with average amplitude over 10 g-forces, which were all significantly different from controls. Characteristic wave and time-domain parameters of pulse signal were extracted using HHT and time-domain which could be served as a non-invasive approach for assessing patients with CHD.


Long-circulating sterically stabilized liposomes as carriers of agents for treatment of infection or for imaging infectious foci.
Liposomes are considered as potential carriers for biologically active compounds. One evident drawback of 'classical' liposomes is their fast elimination by cells of the mononuclear phagocyte system (MPS), primarily by liver and spleen. An important breakthrough in this respect is the development of long-circulating liposomes among which liposomes coated with polyethyleneglycol (PEG), the so-called 'sterically stabilized' liposomes (SSL). An important characteristic of SSL is that their prolonged blood residence time and infectious target localization is relatively independent of the lipid dose, particle size or lipid composition of the bilayer. SSL are applied as carriers of antimicrobial agents to achieve infectious target localization, to reduce side effects, or to serve as a micro-reservoir in the circulation. In addition, radiolabelled SSL are used to image infectious and inflammatory foci.


Relationships between hemodynamic alterations and Child-Pugh Score in patients with cirrhosis.
In this study, central and nonsplanchnic hemodynamic alterations in liver cirrhosis and correlation between Child-Pugh Score and these hemodynamic alterations were evaluated. With this aim, angiotensin-I, aldosterone, femoral blood flow, cardiac index, free water clearance and renal blood flow index were evaluated in 30 cirrhotic patients and 10 healthy control subjects. Child-Pugh score was found to be directly related with serum levels of angiotensin-I and aldosterone, cardiac and renal blood flow index (r = 0.60 - p < 0.001, r = 0.57 - p < 0.01, r = 0.55 - p < 0.01 and r = 0.65 - p < 0.001 respectively), and indirectly related with free water clearance and femoral blood flow (r = 0 .72 -p < 0 .001, r = 0.71 -p < 0 .001 respectively). We concluded that, in patients with cirrhosis, as the Child-Pugh score becomes greater angiotensin-I and aldosterone, cardiac output and non-splanchnic vasoconstriction progressively increase, on the other hand free water clearance and renal perfusion progressively decrease. Alterations in cardiac index and femoral artery blood flow begin before ascites formation. And the hyperdynamic circulation is a primary event independent of the central blood volume.


Community variation: disparities in health care quality between Asian and white medicare beneficiaries.
Few studies have focused on Asian-white disparities. This study examines the use of selected cancer screening and diabetes services under the traditional Medicare program of whites and Asians by socioeconomic status and among U.S. metropolitan statistical areas in which elderly Asians reside. It demonstrates that existing data, with enrichment, can be used to examine Asian-white disparities. It finds that Asians often receive poorer quality of care than whites, but disparities differ among metropolitan areas. This research enables policymakers to better understand and target resources to address Asian-white disparities at the national and local community levels.


The leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) does not activate transcription in mammalian mitochondria.
Regulation of mtDNA expression is critical for controlling oxidative phosphorylation capacity and has been reported to occur at several different levels in mammalian mitochondria. LRPPRC (leucine-rich pentatricopeptide repeat-containing protein) has a key role in this regulation and acts at the post-transcriptional level to stabilize mitochondrial mRNAs, to promote mitochondrial mRNA polyadenylation, and to coordinate mitochondrial translation. However, recent studies have suggested that LRPPRC may have an additional intramitochondrial role by directly interacting with the mitochondrial RNA polymerase POLRMT to stimulate mtDNA transcription. In this study, we have further examined the intramitochondrial roles for LRPPRC by creating bacterial artificial chromosome transgenic mice with moderately increased LRPPRC expression and heterozygous Lrpprc knock-out mice with moderately decreased LRPPRC expression. Variation of LRPPRC levels in mice in vivo, occurring within a predicted normal physiological range, strongly affected the levels of an unprocessed mitochondrial precursor transcript (ND5-cytochrome b) but had no effect on steady-state levels of mitochondrial transcripts or de novo transcription of mtDNA. We further assessed the role of LRPPRC in mitochondrial transcription by performing size exclusion chromatography and immunoprecipitation experiments in human cell lines and mice, but we found no interaction between LRPPRC and POLRMT. Furthermore, addition of purified LRPPRC to a recombinant human in vitro transcription system did not activate mtDNA transcription. On the basis of these data, we conclude that LRPPRC does not directly regulate mtDNA transcription but rather acts as a post-transcriptional regulator of mammalian mtDNA expression.