Structural models of the photointermediates in the rhodopsin photocascade, lumirhodopsin, metarhodopsin I, and metarhodopsin II.
Model building of the two photointermediates, lumirhodopsin and metarhodopsin I, and the activated form of rhodopsin, metarhodopsin II, is described. An outward swing of the C-terminal portion of transmembrane segment 3, pivoting on Cys110 at the N-terminal end of transmembrane segment 3, led to structural models of lumirhodopsin and metarhodopsin I. The conformation of the chromophore in the lumirhodopsin and metarhodopsin I models is controlled by the motion of transmembrane segment 3 and agreed closely with the hydrogen-bonding states of the protonated Schiff base in lumirhodopsin and metarhodopsin I as deduced from their FTIR and resonance Raman spectra and with the negative and positive CD bands of lumirhodopsin and metarhodopsin I, respectively. The structure of metarhodopsin II was constructed by an outward swing of transmembrane segment 3 and the rigid-body motion of transmembrane segment 6. The arrangement of the entire transmembrane segment of the metarhodopsin II model closely agreed with the electron paramagnetic resonance spectra of spin-labeled rhodopsin mutants and provided a structural basis for the protonation of Glu134, which is a key process in transducin activation.


α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies.
There is increasing interest in studying retinal biomarkers for various neurodegenerative diseases. Specific protein aggregates associated with neurodegenerative diseases are present in the retina and could be visualised in a non-invasive way. This study aims to assess the specificity and sensitivity of retinal α-synuclein aggregates in neuropathologically characterised α-synucleinopathies, other neurodegenerative diseases and non-neurological controls. Post-mortem eyes (N = 99) were collected prospectively through the Netherlands Brain Bank from donors with Parkinson's disease (and dementia), dementia with Lewy bodies, multiple system atrophy, Alzheimer's disease, other neurodegenerative diseases and non-neurological controls. Multiple retinal and optic nerve cross-sections were immunostained with anti-α-synuclein antibodies (LB509, KM51, and anti-pSer129) and assessed for aggregates and inclusions. α-Synuclein was observed as Lewy neurites in the retina and oligodendroglial cytoplasmic inclusions in the optic nerve and was highly associated with Lewy body disease (P < 0.001) and multiple system atrophy (P = 0.001). In all multiple system atrophy cases, the optic nerve showed oligodendroglial cytoplasmic inclusions, while retinal Lewy neurites were absent, despite coincidental brain Lewy pathology. With high specificity (97%) and sensitivity (82%), retinal/optic nerve α-synuclein differentiates primary α-synucleinopathies from other cases and controls. α-Synuclein pathology occurs specifically in the retina and optic nerve of primary α-synucleinopathies as opposed to other neurodegenerative diseases-with and without α-synuclein co-pathology-and controls. The absence of retinal Lewy neurites in multiple system atrophy could contribute to the development of an in vivo retinal biomarker that discriminates between Lewy body disease and multiple system atrophy.


Effects of pretraining and water temperature on female rats' performance in the Morris water maze.
The water maze is a complex spatial task that requires the coordination of multiple systems to perform efficiently. Various factors have been shown to influence performance in this task, including motivational state and prior experience. Although a consistent sex difference has been observed in acquiring the water maze in rats, the contribution of the various factors in female rat performance has not been fully assessed. Therefore, the current study tested the effects of motivation as manipulated by water temperature of the maze and prior experience in the maze on the performance of female rats. It was hypothesized that females pretrained in the maze would perform better than those without exposure to the water maze, regardless of water temperature, but in naïve rats, colder water would improve performance as shown previously in male rats. For pretraining, female rats were taught to find a visible platform in cold (19 °C, 4 trials on one day) and warm (25 °C, 4 trials on one day) water before acquisition trials, with the order of the water temperature randomly assigned. Control rats were not given any training and were naïve to the water maze procedure. Pretrained and control rats were then tested to locate a hidden platform in either cold or warm water for 5 consecutive days. Overall, pretraining had a significant effect on distance, latency, and directness of path to the platform. Water temperature did not show a significant effect on any measure or a significant interaction with pretraining. Thus, while our hypothesis that pretraining would improve performance was supported, the results did not support the prediction that water temperature would also significantly influence performance. These results show that non-spatial pretraining can critically improve the performance of females in acquiring a place strategy for the hidden platform, irrespective of water temperature.


Protein interaction predictions from diverse sources.
Protein-protein interactions play an important role in many cellular processes. The availability of a comprehensive and accurate list of protein interactions can facilitate drug target discovery. Recent advances in high-throughput experimental technologies have generated enormous amounts of data and provided valuable resources for studying protein interactions. However, these technologies suffer from high error rates because of their inherent limitations. Therefore, computational approaches capable of incorporating multiple data sources are needed to fully take advantage of the rapid accumulation of data. In this review, we focus on the computational methods that integrate multiple data sources by combining direct measurements on protein interactions from diverse organisms, and by integrating different types of indirect information from various genomic and proteomic approaches.


High-performance silica nanoparticle reinforced poly (vinyl alcohol) as templates for bioactive nanocomposites.
Silica nanoparticle reinforced poly (vinyl alcohol) cast sheets 40 μm thick were tested for mechanical and biological properties. The films were characterized using X-ray diffraction, scanning electron microscopy, and infrared spectroscopy. The crystallinity decreased with increased silica content. Changes in the morphology and structure upon the addition of silica suggest the formation of cross-linking. The modulus increased from 300 MPa for PVA to 7.2 GPa for 120 wt.% silica nanoparticle in the blend and the tensile strength increased from 3.5 MPa to 35 MPa. The modulus estimated using dynamic tests, tensile tests, and nanoindentation was comparable and was predicted well using the Halpin-Tsai's equation. The nanocomposites were an order of magnitude tougher than the pure polymer. Silica based nanocomposite was also found to be an excellent template for the deposition of calcium hydroxyapatite when immersed in simulated body fluid. The modulus and tensile strength of apatite coated silica nanoparticle (120 wt.%)-PVA composite increased to 11 GPa and 65 MPa respectively, close to that of cortical bone. The results represent one of the largest increases in mechanical properties of nanocomposite mimicking the properties of human bone. The addition of silica can also aid in osseointegration.


Oral cancer awareness and knowledge among dental patients in South India.
To assess the 1) levels of awareness and knowledge about risk factors and early signs of oral cancer among dental patients visiting dental hospital in Hyderabad city, South India 2) and to correlate the knowledge levels according to age, gender and education levels. The survey comprised of 16-item questionnaire which was distributed to patients attending Panineeya Institute of Dental Sciences, Hyderabad. Data was collected and statistically analysis was done using SPSS software (12.0 version). p<0.05 was considered statistically significant. 2045 participants completed the questionnaire (response rate - 97. 9%). The reliability of the questionnaire as calculated by Cronbach's alpha was 0.75. Mean age of the study population was 37.9 years. 60.2% of the respondents had heard about oral cancer. When knowledge towards risk factors of oral cancer was taken into consideration along with variables, significant differences were seen only in gender with female having better knowledge (p=0.02). No significant difference was noted among the age group and varying education levels. However, knowledge about early signs of oral cancer revealed a highly significant difference with the level of education (p=0.000). The awareness levels and knowledge about risk factors and early signs of oral cancer in this cross-section of Indian dental patients were satisfactory.


Increased expression of discoidin domain receptor 2 is linked to the degree of cartilage damage in human knee joints: a potential role in osteoarthritis pathogenesis.
To investigate the relationship between increased discoidin domain receptor 2 (DDR-2) expression and cartilage damage in osteoarthritis (OA). Full-thickness cartilage tissue samples from 16 human knee joints were obtained and the grade of cartilage damage was evaluated according to the Mankin scale. Expression of DDR-2, matrix metalloproteinase 13 (MMP-13), and MMP-derived type II collagen fragments was visualized immunohistochemically. Moreover, upon stimulation with either type II collagen or gelatin, levels of DDR-2 and MMP-13 messenger RNA (mRNA) in primary human articular chondrocytes were assessed by real-time polymerase chain reaction. Immunohistochemical analysis showed an increase in DDR-2 expression in human articular cartilage, which was correlated with the degree of tissue damage. In parallel, the extent of MMP-13 and type II collagen breakdown products was elevated as a function of increased DDR-2 expression and cartilage damage. Furthermore, in vitro experiments revealed an up-regulation of both DDR-2 and MMP-13 mRNA in human articular chondrocytes after stimulation with type II collagen. Our data indicate that 3 factors, DDR-2 expression, MMP-13 expression, and the degree of cartilage damage, are linked, such that DDR-2 promotes tissue catabolism, and tissue degradation promotes DDR-2 up-regulation and activation. Thus, the perpetuation of DDR-2 expression and activation can be seen as a vicious circle that ultimately leads to cartilage destruction in OA.


Hypothesis Testing and Statistical Analysis of Microbiome.
After the initiation of Human Microbiome Project in 2008, various biostatistic and bioinformatic tools for data analysis and computational methods have been developed and applied to microbiome studies. In this review and perspective, we discuss the research and statistical hypotheses in gut microbiome studies, focusing on mechanistic concepts that underlie the complex relationships among host, microbiome, and environment. We review the current available statistic tools and highlight recent progress of newly developed statistical methods and models. Given the current challenges and limitations in biostatistic approaches and tools, we discuss the future direction in developing statistical methods and models for the microbiome studies.


Electrophysiologic and electrocardiographic effects, efficacy and safety of encainide in malignant ventricular arrhythmias associated with coronary artery disease.
The electrophysiologic and electrocardiographic effects, efficacy and safety of encainide were evaluated in 48 patients with coronary artery disease undergoing programmed stimulation for ventricular tachyarrhythmias. The study group included 41 men and 7 women, aged 64 +/- 8 years (mean +/- standard deviation), who had presented with nonsustained ventricular tachycardia (VT) (4 patients), sustained VT (32), ventricular fibrillation (8) or unexplained syncope (4). The left ventricular ejection fraction averaged 34 +/- 13%. The arrhythmias induced at the baseline, drug-free electrophysiologic study included nonsustained VT in 8 patients, sustained VT in 35 and ventricular fibrillation in 5. All patients had failed greater than or equal to 1 class IA and a combination of class IA and IB agents (mean 2.2 +/- 1.1 drugs) before encainide. Oral encainide was given in a mean daily dose of 80 +/- 11 mg for greater than or equal to 3 days before repeat programmed stimulation. Encainide was discontinued before follow-up electrophysiologic testing in 5 patients due to spontaneous development of new sustained VT. Of the 43 patients undergoing electropharmacologic testing with encainide, 5 had no inducible arrhythmia. In 9 patients VT was inducible by fewer extrastimuli, in 2 patients a previously stable VT required cardioversion, whereas in 28 patients VT remained inducible by the same number of or more extrastimuli. Thus, encainide prevented the induction of VT or ventricular fibrillation in 5 of 48 patients (10%), while it had a possible proarrhythmic effect in 15 patients (31%). Of the 5 patients without inducible VT administered long-term encainide therapy, 1 returned within 4 weeks of hospital discharge with VT recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)


Biogenesis of multisubunit RNA polymerases.
Gene transcription in the nucleus of eukaryotic cells is carried out by three related multisubunit RNA polymerases, Pol I, Pol II and Pol III. Although the structure and function of the polymerases have been studied extensively, little is known about their biogenesis and their transport from the cytoplasm (where the subunits are synthesized) to the nucleus. Recent studies have revealed polymerase assembly intermediates and putative assembly factors, as well as factors required for Pol II nuclear import. In this review, we integrate the available data into a model of Pol II biogenesis that provides a framework for future analysis of the biogenesis of all RNA polymerases.


Synthetic peptides corresponding to keratin subunits elicit highly specific antibodies.
The presence of common antigenic determinants within all keratin proteins has made difficult the production of antisera which are monospecific for individual keratin subunits. Synthetic peptides corresponding to the carboxyl-terminal amino acid sequences of the mouse 59- and 67-kilodalton keratins were used to produce antibodies which were highly specific for these keratin subunits. This method of antibody production was chosen after examination of amino acid sequence data (which were deduced from the nucleotide sequence of cDNA clones for these and other mouse keratins) revealed that the carboxyl-terminal amino acid sequences of various keratins were unique. Indirect immunofluorescence staining of newborn-mouse skin with these antisera demonstrated that the 59- and 67-kilodalton keratins were only present within the differentiated cells of the epidermis (the suprabasal layers) and not in the undifferentiated cells (the basal layer). These results are consistent with our previous work concerning the expression of these keratin genes at the messenger RNA level (Roop, D. R., Hawley-Nelson, P., Cheng, C. K., and Yuspa, S. H. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 716-720). Data obtained with the antisera directed against the 67-kilodalton keratin also indicated that the carboxyl-terminal sequences of this subunit were not present in the nonliving layer (the stratum corneum) of the epidermis. This approach should be useful for the production of antisera specific for other keratin subunits as additional sequence information becomes available.


A label-free technique to quantify and visualize gold nanoparticle accumulation at the single-cell level.
Despite their wide bioapplications, potential health risks of gold nanoparticles (AuNPs) remain unclear. As a determinant of their risks, AuNP accumulation within a cell population is subject to cell-to-cell heterogeneity. Methods to simultaneously quantify and visualize intracellular AuNPs at the single-cell level are, however, lacking. Here we developed a novel label-free technique, based on hyperspectral imaging with enhanced darkfield microscopy (HSI-DFM), to visualize and quantify AuNP accumulation at the single-cell level. The identification ability of the hyperspectral libraries derived from extra- and intracellular AuNPs was compared. The spectral number in the libraries was optimized to maximize their identification ability while minimizing the identification time. In addition, a filtration method was established to merge spectral libraries from different cell lines based on their similarity. The intracellularly accumulated AuNPs as determined by HSI-DFM well correlated with those detected by inductively coupled plasma mass spectrometry. This validation allowed us to calculate the intracellular concentration of AuNPs at the single-cell level and to monitor the accumulation kinetics of AuNPs in living cells. The label-free method developed herein can be applied to other types of AuNPs differing in their physicochemical properties as well as other NPs, as long as they are detectable by HSI-DFM.


Depression, anxiety and stress symptoms in patients presenting with dyspepsia at a regional hospital in KwaZulu-Natal province.
Depression, anxiety and stress (DAS) have been shown to be co-morbid with dyspepsia. Local data on the factors associated with these co-morbidities could inform the role of psychiatric intervention in affected patients. The aim of this study was to describe the frequency of undiagnosed DAS and their associated protective and risk correlates in a sample of patients undergoing endoscopies for dyspepsia. The study was conducted at a regional hospital's gastro-intestinal unit in KwaZulu-Natal province. A cross-sectional survey was conducted on 201 in- and outpatients with symptoms of dyspepsia awaiting endoscopy. Information on DAS symptomatology (using the DASS-21 screening questionnaire, as well as socio-demographic and clinical data) were collected. Following a descriptive analysis of the participants' socio-demographic and clinical details, linear regression models were fitted to identify potential risk and protective correlates linked to DAS symptomatology. The mean age of participants (N = 201) was 48.89 years, of whom approximately two-thirds (n = 133; 66.17%) were women, 97% (n = 195) were African and 64.68% (n = 130) resided in rural areas. Anxiety was the most prevalent symptom category (n = 149; 74.13%) versus depression (n = 96; 47.76%) and stress (n = 68; 33.83%) in each category of symptom (mild to extremely) severity. In the severe and extremely severe range, anxiety existed without co-morbid depression or stress in 61.19% of anxious patients. Alcohol use was significantly associated with all three symptom categories (p < 0.01). Given high frequencies of depression and anxiety in patients undergoing endoscopies for dyspepsia, screening for common mental disorders is essential.


Muscle invasive schistosomal squamous cell carcinoma of the urinary bladder: frequency and prognostic significance of p53, BCL-2, HER2/neu, and proliferation (MIB-1).
Muscle invasion is the usual presentation of schistosomal squamous cell carcinoma of the urinary bladder. It is unclear whether this invasive behavior is secondary to the aggressive nature of the disease or to delay in diagnosis. Fixed paraffin-embedded hematoxylin and eosin-stained sections of 15 cystectomy specimens from 15 patients (14 males, 1 female) (age range, 40 to 67 years), histologically confirmed as schistosomal squamous cell carcinoma, were assessed for grade (G1, n = 3; G2, n = 7; G3, n = 5) and pathological stage (PT category: PT2, n = 4; PT3a, n = 9; PT3b, n = 2). Immunostaining was performed for mutant p53, bcl-2, HER2/neu, and MIB-1 (proliferation), using steam antigen retrieval and an avidin-biotin complex method. Frequency of strong immunoreactivity was high for mutant p53 (73%) and MIB-1 (87% intermediate or high) but low for bcl-2 (20%) and HER2/neu (27%). There was no significant correlation of any of the four markers with either grade or stage. Hence, schistosomal bladder squamous cell carcinoma is felt to be an aggressive carcinoma de novo. The high frequency of mutant p53 expression (73%) and an intermediate to high proliferation index (87%) suggests this. The lack of correlation between histological grade and all four markers studied suggests that grading is not of prognostic value.


Over-the-counter hearing aids: What will it mean for older Americans?
In October 2021 the Food and Drug Administration released draft rules creating a new class of hearing aids to be sold over the counter. Since Medicare does not cover hearing aids, the ready availability of low-cost aids is potentially good news for the millions of older Americans with hearing loss, a disorder that is associated with isolation, depression and poor health. However, better financial access to hearing aids will not necessarily translate into better hearing: many older people will need assistance in fitting, using and maintaining their aids. Policymakers, managers, and clinicians need to consider how to structure, fund and deliver these vital adjunctive services.


Role of wavelength in photocarrier absorption and plasma formation threshold under excitation of dielectrics by high-intensity laser field tunable from visible to mid-IR.
The development of high power mid-IR laser applications requires a study on laser induced damage threshold (LIDT) in the mid-IR. In this paper we have measured the wavelength dependence of the plasma formation threshold (PFT) that is a LIDT precursor. In order to interpret the observed trends numerically, a model describing the laser induced electron dynamics, based on multiple rate equations, has been developed. We show both theoretically and experimentally that PFT at mid-IR wavelengths is controlled by a transition from weak- to strong-field regime of free carrier absorption. In the case of MgF[Formula: see text] this transition occurs around 3-4 [Formula: see text]m corresponding to the region of the lowermost PFT. The region of the uppermost PFT is reached around 1 [Formula: see text]m and is governed by an interplay of photoionization and weak-field free carrier absorption which manifests itself in both MgF[Formula: see text] and SiO[Formula: see text]. The PFT observed in considered materials exhibits a universal dependence on the excitation wavelength in dielectrics. Thus, the presented results pave the route towards efficient and controllable laser-induced material modifications and should be of direct interest to laser researchers and application engineers for prevention of laser-induced damage of optical components in high-intensity mid-IR laser systems.


Peritoneal eosinophilia in patients on continuous ambulatory peritoneal dialysis: a prospective study.
A prospective study on peritoneal eosinophilia was conducted in 23 continuous ambulatory peritoneal dialysis (CAPD) patients for a mean period of 7.9 months. Peritoneal eosinophilia as defined by peritoneal eosinophil count exceeding 100/mm3 was found in 60.8% of patients. Most developed peritoneal eosinophilia within 3 months of the initiation of dialysis, although the phenomenon could occur as early as one day or as late as 6 months after dialysis. Fifty-seven percent of those with peritoneal eosinophilia also had peripheral blood eosinophilia. Although most peritoneal eosinophilic episodes subsided in a month, in one patient the process grumbled on for 150 days. The number of peritonitis episodes was not significantly different between patients with peritoneal eosinophilia and those without. The only distinction between the two groups of patients was that those who developed peritoneal eosinophilia had a significantly (P = .002) higher serum IgE concentration initially as well as throughout the period of observation.


Association of Cumulative Paternal Early Life Stress With White Matter Maturation in Newborns.
Early life stress (ELS) has been shown to affect brain development and health outcomes. Recent animal studies have linked paternal early stress exposures with next-generation outcomes. Epigenetic inheritance through the male germline has been suggested to be one of the mechanisms. To test whether paternal ELS, as measured using the Trauma and Distress Scale, is associated with neonate brain development. This cohort study included data from participants from the prospective 2-generation FinnBrain Birth Cohort, which was collected from 2011 to 2015. Pregnant women and the fathers were consecutively recruited at gestational week 12 from maternity clinics in Finland. Magnetic resonance imaging data were analyzed in 2019. Participants in this study were 72 families (infant, father, mother). Paternal exposure to ELS. Fractional anisotropy (FA) values in the major white-matter tracts of the newborn brain. A total of 72 trios (infant, mother, and father) were analyzed. At the time of delivery, the mean (SD) age was 31.0 (4.4) years for fathers and 30.3 (4.5) years for mothers. Forty-one infants (57%) were boys; mean (SD) child age at inclusion was 26.9 (7.2) days from birth and 205 (8) days from estimated conception. Increasing levels of paternal ELS were associated with higher FA values in the newborn brain in the body of the corpus callosum, right superior corona radiata, and retrolenticular parts of the internal capsule. This association persisted after controlling for maternal ELS, maternal socioeconomic status (SES), maternal body mass index, maternal depressive symptoms during pregnancy, child sex, and child age from birth and gestation corrected age when imaged. In additional region-of-interest analyses, the association between FA values and paternal Trauma and Distress Scale sum scores remained statistically significant in the earliest maturing regions of the brain, eg, the genu of the corpus callosum (in the regression models, β = 0.00096; 95% CI, 0.00034-0.00158; P = .003) and the splenium (β = 0.00090; 95% CI, 0.00000-0.00180; P = .049). This cohort study found a statistically significant association between paternal ELS and offspring brain development. This finding may have far-reaching implications in pediatrics, as it suggests the possibility of a novel route of intergenerational inheritance of ELS on next-generation brain development.


Psychometric properties of the of the Persian version of the Coping Assessment for Bereavement and Loss Experiences (CABLE).
The loss of a loved one through death is practically an inevitable part of the human experience. However, not all grieving people cope with this blow in the same way. One of the factors that may differentiate the grieving reactions of mourners in the face of this lesion is the strategies that the person uses in this situation to adapt and manage the situation. A valid and reliable tool is also needed to measure and evaluate coping strategies. The aim of this study was to translate and determine the characteristics of psychological tools for measuring coping with experiences of grief and loss (28 items) in people living in Tehran. This is a methodological study with a descriptive cross-sectional design that after obtaining written permission from the original developer and according to the WHO protocol, the Persian version of the questionnaire was completed by 480 people who experienced mourn in Tehran in February 2021 to October 2021. Then, the Face validity, Content validity and Construct validity of questionnaire were assessed. Cronbach's alpha coefficient, McDonald's omega and Test-retest were used to determine the reliability. Cronbach's alpha for all items was 0.91 and intra-class correlation coefficient was 0.86, both of which indicate the reliability of the Persian version of the CABLE tool. Based on exploratory factor analysis, maximum likelihood (n = 260) and confirmatory factor analysis (n = 220) six factors were identified. Factors can explain 50% of the total variance observed. The model had an acceptable fit: GFI: 0.88, CFI: 0.96, IFI: 0.96, NFI: 0.92, PNFI: 0.82, RAMSEA: 0.058, CMIN / DF: 2.37 RMR: 0.056. Internal consistency and construct validity of the questionnaire were confirmed. The findings of the present study indicate that the Persian version of CABLE has the appropriate validity and reliability to assess the compliance with the experiences of grief and loss in Persian population.


Inhalable alginate nanoparticles as antitubercular drug carriers against experimental tuberculosis.
Pharmacokinetic and chemotherapeutic studies have been carried out with aerosolised alginate nanoparticles encapsulating isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA). The nanoparticles were prepared by cation-induced gelification of alginate and were 235.5 +/- 0 nm in size, with drug encapsulation efficiencies of 70-90% for INH and PZA and 80-90% for RIF. The majority of particles (80.5%) were in the respirable range, with mass median aerodynamic diameter of 1.1 +/- 0.4 microm and geometric standard deviation of 1.71 +/- 0.1 microm. The relative bioavailabilities of all drugs encapsulated in alginate nanoparticles were significantly higher compared with oral free drugs. All drugs were detected in organs (lungs, liver and spleen) above the minimum inhibitory concentration until 15 days post nebulisation, whilst free drugs stayed up to day 1. The chemotherapeutic efficacy of three doses of drug-loaded alginate nanoparticles nebulised 15 days apart was comparable with 45 daily doses of oral free drugs. Thus, inhalable alginate nanoparticles can serve as an ideal carrier for the controlled release of antitubercular drugs.


Treatment of hypertension and obstructive sleep apnea counteracts cognitive decline in common neurocognitive disorders in diagnosis-related patterns.
The aim of this study was to investigate the effect of arterial hypertension (AH) and of obstructive sleep apnea (OSA) on cognitive course in the neurocognitive disorder (NCD) cohort RIFADE which enrolled patients with NCD due to Alzheimer's disease (AD), vascular NCD (vNCD), and mixed NCD (AD + vNCD = mNCD). Multiple risk factors (RF), including AH and OSA, that contribute to the development of various kinds of dementia have been identified in previous studies. Studies that observed AH lacked investigation of long-term effects and did not isolate it from other RF. Studies involving OSA as a risk factor did not include participants with all stages of NCD. 126 subjects were screened for AH and OSA. Repeated cognitive measurements were performed with the DemTect as primary outcome and the clock drawing test as secondary outcome measure. 90 patients had AH (71.4%) and 40 patients had OSA (31.7%). RF-status had a significant effect on cognitive outcome in models with RF as single factors (AH p = 0.027, OSA p < 0.001), a 2-factor analysis with AH × OSA (AH as main factor p = 0.027) as well as a model including the 3 factors AH × OSA × diagnosis (p = 0.038). Similarly, a 3-factor model was significant for the clock-drawing test, whereas single factor-models remained insignificant. AH and OSA appear to be risk factors in common NCD and cognitive decline can be mitigated by treatment of these RF.


Molecular basis for pseudo vitamin D-deficiency rickets in the Hannover pig.
The molecular basis for pseudo vitamin D deficiency rickets (PDDR) in the Hannover pig model was determined in the current study. Consistent with the inability of Hannover PDDR pigs to maintain ambient levels of 1,25-dihydroxyvitamin D (i.e., 1,25D), the bioactivation enzyme cytochrome P450C1 (or CYP27B1) was determined to contain coding-region deletions that rendered the enzyme ineffective due to frame-shift mutations and expression of a premature termination codon. Expression levels of P450C1mRNA were up-regulated in response to the low-1,25D high-parathyroid hormone state of the PDDR animals. In a complementary manner, cytochrome P450C24 mRNA was not detectable in PDDR pigs. Two different deletions were detected within the Hannover pig strain in which the P450C1 coding region contained either 173 bp or 329 bp deletions that resulted in the expression of non-sense products beginning within the I-helix region and extending through the truncated C-terminal domains. The boundaries for the deletion segments aligned with derived mRNA processing sites. This observation was consistent with an mRNA processing error as the causative factor for the coding-region deletions. Based upon the expression of a non-functional P450C1 enzyme, the Hannover pig model for PDDR was determined to be identical to the human disease in which enzyme-inhibitory mutations are the molecular basis for the calcium disorder.


Molecular Pathogenesis of Cholangiocarcinoma.
Cholangiocarcinomas are a heterogeneous group of malignancies arising from a number of cells of origin along the biliary tree. Although most cases in Western countries are sporadic, large population-based studies have identified a number of risk factors. This review summarises the evidence behind reported risk factors and current understanding of the molecular pathogenesis of cholangiocarcinoma, with a focus on inflammation and cholestasis as the driving forces in cholangiocarcinoma development. Cholestatic liver diseases (e.g. primary sclerosing cholangitis and fibropolycystic liver diseases), liver cirrhosis, and biliary stone disease all increase the risk of cholangiocarcinoma. Certain bacterial, viral or parasitic infections such as hepatitis B and C and liver flukes also increase cholangiocarcinoma risk. Other risk factors include inflammatory disorders (such as inflammatory bowel disease and chronic pancreatitis), toxins (e.g. alcohol and tobacco), metabolic conditions (diabetes, obesity and non-alcoholic fatty liver disease) and a number of genetic disorders. Regardless of aetiology, most risk factors cause chronic inflammation or cholestasis. Chronic inflammation leads to increased exposure of cholangiocytes to the inflammatory mediators interleukin-6, Tumour Necrosis Factor-ɑ, Cyclo-oxygenase-2 and Wnt, resulting in progressive mutations in tumour suppressor genes, proto-oncogenes and DNA mismatch-repair genes. Accumulating bile acids from cholestasis lead to reduced pH, increased apoptosis and activation of ERK1/2, Akt and NF-κB pathways that encourage cell proliferation, migration and survival. Other mediators upregulated in cholangiocarcinoma include Transforming Growth Factor-β, Vascular Endothelial Growth Factor, Hepatocyte Growth Factor and several microRNAs. Increased expression of the cell surface receptor c-Met, the glucose transporter GLUT-1 and the sodium iodide symporter lead to tumour growth, angiogenesis and cell migration. Stromal changes are also observed, resulting in alterations to the extracellular matrix composition and recruitment of fibroblasts and macrophages that create a microenvironment promoting cell survival, invasion and metastasis. Regardless of aetiology, most risk factors for cholangiocarcinoma cause chronic inflammation and/or cholestasis, leading to the activation of common intracellular pathways that result in reactive cell proliferation, genetic/epigenetic mutations and cholangiocarcinogenesis. An understanding of the molecular pathogenesis of cholangiocarcinoma is vital when developing new diagnostic biomarkers and targeted therapies for this disease.


Enhancer RNAs Mediate Estrogen-Induced Decommissioning of Selective Enhancers by Recruiting ERα and Its Cofactor.
The function of enhancer RNAs (eRNAs) in transcriptional regulation remains obscure. By analyzing the genome-wide nascent transcript profiles in breast cancer cells, we identify a special group of eRNAs that are essential for estrogen-induced transcriptional repression. Using eRNAs of TM4SF1 and EFEMP1 as the paradigms, we find that these RNA molecules not only stabilize promoter-enhancer interactions but also recruit liganded estrogen receptor α (ERα) to particular enhancer regions, facilitate the formation of a functional transcriptional complex, and cause gene silencing. Interestingly, ERα is shown to directly bind with eRNAs by its DNA-binding domain. These eRNAs help with the formation of a specific ERα-centered transcriptional complex and promote the association of the histone demethylase KDM2A, which dismisses RNA polymerase II from designated enhancers and suppresses the transcription of target genes. Our work demonstrates a complete mechanism underlying the action of eRNAs in modulating and refining the locus-specific transcriptional program.


Calcium and calmodulin in membrane fusion.
Regulated exocytosis was the first intracellular membrane fusion step that was suggested to involve both Ca(2+) and calmodulin. In recent years, it has become clear that calmodulin is not an essential Ca(2+) sensor for exocytosis but that it is likely to have a more regulatory role. A requirement for cytosolic Ca(2+) in other vesicle fusion events within cells has become apparent and in certain cases, such as homotypic fusion of early endosomes and yeast vacuoles, calmodulin may be the primary Ca(2+) sensor. A number of distinct targets for calmodulin have been identified including SNARE proteins and subunits of the vacuolar ATPase. The extent to which calmodulin regulates different intracellular fusion events through conserved SNARE-dependent or other mechanisms remains to be resolved.


PARP around the clock.
Cells possess internal ∼24 hr or circadian clocks that synchronize physiological processes with daily cycles of light and nutrient availability. In this issue, Asher et al. (2010) find that PARP-1 (poly(ADP-ribose) polymerase 1) modifies components of the clock machinery in response to feeding, providing a mechanism for how metabolic rhythms coordinate with circadian rhythms.


A simple apparatus for performing short-time (1--2 seconds) uptake measurements in small volumes; its application to D-glucose transport studies in brush border vesicles from rabbit jejunum and ileum.
An automated procedure allows uptake measurements with incubation times as short as 0.5 s and with volumes of 10--20 microliter. Using this technique the kinetic parameters Km and V of D-glucose transport in brush border vesicles from rabbit small intestine could be determined from unidirectional fluxes. A comparison of the data obtained from jejunum and from ileum shows that the Km for D-glucose is the same in both parts of the intestine, whereas the maximum flux is significantly larger in the jejunum.


Langmuir monolayers of cerebroside originated from Linckia laevigata: binary systems of cerebrosides and phospholipid.
The surface pressure (pi)-area (A), the surface potential (DeltaV)-A and the dipole moment (mu( perpendicular))-A isotherms were obtained for six cerebrosides of LLC-2, LLC-2-1, LLC-2-8, LLC-2-10, LLC-2-12, and LLC-2-15, which were isolated from Linckia laevigata, and two-component monolayers of two different cerebrosides (LLC-2 and LLC-2-8) with phospholipid of dipalmitoylphosphatidylcholine (DPPC) on a subphase of 0.15 M sodium chloride solution as a function of cerebroside compositions in the two-component systems by employing the Wilhelmy method, the ionizing electrode method, and the fluorescence microscopy. The new finding was that LLC-2 showed a stable and liquid expanded type film. Four of them (LLC-2-8, -10, -12, and -15) had the phase transition from the liquid-expanded (LE) to the liquid-condensed (LC) states at 298.2 K. The apparent molar quantity changes (Deltas(gamma), Deltah(gamma), and Deltau(gamma)) on their phase transition on 0.15M at 298.2 K were calculated. The miscibility of cerebroside and phospholipid in the two-component monolayers was examined by plotting the variation of the molecular area and the surface potential as a function of the cerebroside molar fraction (X(cerebroside)), using the additivity rule. From the A-X(cerebroside) and DeltaV(m)-X(phospholipid) plots, a partial molecular surface area (PMA) and an apparent partial molecular surface potential (APSP) were determined at the discrete surface pressure. The PMA and APSP with the mole fraction were extensively discussed for the miscible systems. Judging from the two-dimensional phase diagrams, these were found to be one type, a positive azeotropic type; all the cerebrosides were miscible with DPPC. Furthermore, assuming a regular surface mixture, the Joos equation for the analysis of the collapse pressure of two-component monolayers allowed calculation of the interaction parameter (xi) and the interaction energy (-Deltavarepsilon) between the cerebrosides and DPPC. The miscibility of cerebroside and phospholipid components in the monolayer state was also supported by fluorescence microscopy.


Cycling Stability of Lithium-Ion Batteries Based on Fe-Ti-Doped LiNi0.5 Mn1.5 O4 Cathodes, Graphite Anodes, and the Cathode-Additive Li3 PO4.
This study addresses the improved cycling stability of Li-ion batteries based on Fe-Ti-doped LiNi0.5 Mn1.5 O4 (LNMO) high-voltage cathode active material and graphite anodes. By using 1 wt% Li3 PO4 as cathode additive, over 90% capacity retention for 1000 charge-discharge cycles and remaining capacities of 109 mAh g-1 are reached in a cell with an areal capacity of 2.3 mAh cm- 2 (potential range: 3.5-4.9 V). Cells without the additive, in contrast, suffer from accelerated capacity loss and increase polarization, resulting in capacity retention of only 78% over 1000 cycles. An electrolyte consisting of ethylene carbonate, dimethyl carbonate, and LiPF6 is used without additional additives. The significantly improved cycling stability of the full cells is mainly due to two factors, namely, the low MnIII content of the Fe-Ti-doped LNMO active material and the use of the cathode-additive Li3 PO4 . Crystalline Li3 PO4 yields a drastic reduction of transition metal deposition on the graphite anode and prevents Li loss and the propagation of cell polarization. Li3 PO4 is added to the cathode slurry that makes it a very simple and scalable process, first reported herein. The positive effects of crystalline Li3 PO4 as electrode additive, however, should apply to other cell chemistries as well.


Apoptosis: a link between cancer genetics and chemotherapy.
Defects in apoptosis underpin both tumorigenesis and drug resistance, and because of these defects chemotherapy often fails. Understanding the molecular events that contribute to drug-induced apoptosis, and how tumors evade apoptotic death, provides a paradigm to explain the relationship between cancer genetics and treatment sensitivity and should enable a more rational approach to anticancer drug design and therapy.


Provisional model for propagation of electrical activity in upper urinary tract.
A theory on the function of the renal pelvis as a pacemaker for ureteral peristalsis is given. The bioengineering "black box" approach is used to describe peristaltic behavior monitored at the ureter and thr renal pelvis, by both peristaltic pressure and electromyographic methods. The model provides a stimulus to further thought on the nature and significance of electrical activity in the upper urinary tract.


Exosomal Proteins and Lipids as Potential Biomarkers for Lung Cancer Diagnosis, Prognosis, and Treatment.
Exosomes participate in cell-cell communication by transferring molecular components between cells. Previous studies have shown that exosomal molecules derived from cancer cells and liquid biopsies can serve as biomarkers for cancer diagnosis and prognosis. The exploration of the molecules transferred by lung cancer-derived exosomes can advance the understanding of exosome-mediated signaling pathways and mechanisms. However, the molecular characterization and functional indications of exosomal proteins and lipids have not been comprehensively organized. This review thoroughly collected data concerning exosomal proteins and lipids from various lung cancer samples, including cancer cell lines and cancer patients. As potential diagnostic and prognostic biomarkers, exosomal proteins and lipids are available for clinical use in lung cancer. Potential therapeutic targets are mentioned for the future development of lung cancer therapy. Molecular functions implying their possible roles in exosome-mediated signaling are also discussed. Finally, we emphasized the importance and value of lung cancer stem cell-derived exosomes in lung cancer therapy. In summary, this review presents a comprehensive description of the protein and lipid composition and function of lung cancer-derived exosomes for lung cancer diagnosis, prognosis, and treatment.


Rapid, sensitive and efficient HPLC assays for HIV-1 proteinase.
The proteinase encoded by human immunodeficiency virus type 1 (HIV-1) cleaves peptide substrates of sequences derived from processing sites in HIV-1 gag-pol polypeptide. Based on this cleavage, assays that utilize HPLC to measure activity of HIV-1 proteinase are reported herein. In the assay first described, a baseline separation of unlabeled substrate and products is achieved with a run time of 10 min and UV detection. Enzyme concentrations as low as 1 nM, which is the lowest reported for an assay employing underivatized peptide substrate, are attained. Even more powerful, versatile and sensitive, a second method that takes advantage of a peptide substrate labeled at its N-terminus with the fluorescein derivative is described as well. Because of the fluorescein label, this method offers several superior features, including very fast analysis of substrate and product in less than 3 min and fluorescence detection which provides essentially total freedom from interference. Synthesis of fluorescein-labeled peptide substrate is accomplished by solid-phase peptide synthesis.


Comparison of insulin-mediated and glucose-mediated glucose disposal in patients with insulin-dependent diabetes mellitus and in nondiabetic subjects.
To determine whether glucose-mediated as well as insulin-mediated regulation of glucose utilization and glucose production is impaired in patients with insulin-dependent diabetes mellitus (IDDM), six nonobese, diabetic patients and seven age-, sex-, and weight-matched nondiabetic subjects were studied. Despite slightly higher free insulin concentrations in the diabetic patients than in the nondiabetic subjects during 0.2 mU/kg X min (22 +/- 3 versus 15 +/- 2 microU/ml) and 1.0 mU/kg X min (98 +/- 10 versus 75 microU/ml) insulin infusions, glucose utilization at plasma glucose concentrations of 95, 135, and 175 mg/dl was lower in the diabetic patients than in the nondiabetic subjects. The increment in glucose utilization per increment in plasma glucose (i.e., slope) in the diabetic and nondiabetic subjects, respectively, did not differ significantly during either the 0.2 (1.7 +/- 1.3 versus 1.4 +/- 0.5 dl/kg X min) or 1.0 (4.4 +/- 1.1 versus 6.2 +/- 1.0 dl/kg X min) mU/kg X min insulin infusions, although they tended to be higher in the nondiabetic subjects during the latter infusion. Thus, although stimulation of glucose utilization by insulin is impaired in patients with IDDM, the ability of an increase in glucose concentration to increase glucose utilization does not appear to differ from that present in nondiabetic subjects, at insulin concentrations in the low physiologic range. Whether differences exist in the high physiologic range remains to be determined.


Protective Mechanisms for Depression among Racial/Ethnic Minority Youth: Empirical Findings, Issues, and Recommendations.
We (1) review empirical studies that report findings regarding putative protective mechanisms when exposed to risk of depression in African American and Hispanic adolescents; (2) identify key protective mechanisms for different risk contexts that garner empirical support; (3) synthesize the mechanisms identified as protective against depression among racial/ethnic minority adolescents; and (4) discuss improved methods for advancing understanding of resilience against depression in minority youth. The studies were selected from PsycINFO searches that met the following inclusion criteria: participants between 12 and 21 years of age, inclusions of racial/ethnic minority members, examining protection through an interaction with a risk factor, and outcome measures of depression, depressed mood, or depressive symptomatology. We found 39 eligible studies; 13 of which included multiple racial/ethnic groups. The following were supported as protective mechanisms, at least preliminarily, for at least one racial/ethnic group and in at least one risk context: employment, extracurricular activities, father-adolescent closeness, familism, maternal support, attending predominately minority schools, neighborhood composition, non-parent support, parental inductive reasoning, religiosity, self-esteem, social activities, and positive early teacher relationships. To investigate protective mechanisms more comprehensively and accurately across individual, social, and community levels of influence, we recommend incorporating multilevel modeling or multilevel growth curve analyses and large diverse samples.


NMR spectroscopy and chemical studies of an arabinan-rich system from the endosperm of the seed of Gleditsia triacanthos.
Exhaustive extraction of the endosperm from the seed of Gleditsia triacanthos using water at room temperature and 50 degrees C left a residue, which was further extracted at 95 degrees C. Precipitation of this extract with 2-propanol yielded major amounts of galactomannan components, while the supernatant was mainly composed of arabinose-rich constituents. Two fractions were obtained by anion-exchange chromatography. The fraction that eluted with water is an arabinan with (1-->5) alpha-L linkages and branching mainly on C-2, accompanied with equal amounts of a low-galactose galactomannan oligosaccharide, and a small proportion of a beta-(1-->4)-galactan. The fraction eluted with an increased ionic strength consists mainly of a similar arabinan, and lower proportions of a high-galactose galactomannan, galactan, and protein. The arabinan moiety in both fractions was characterized by chemical analysis and 1D and 2D NMR spectroscopic techniques.


Oligosaccharides of human milk. Structural studies of two new octasaccharides, difucosyl derivatives of para-lacto-N-hexaose and para-lacto-N-neohexaose.
Two new octasaccharides were isolated from human milk of a nonsecretor Lewis a+b- individual. Structural studies by sequential enzymic degradation and by quantitative methylation analysis revealed that their structures were as follows: Galbeta1 leads to 3 (Fucalpha1 leads to 4) GlcNAcbeta1 leads to 3Galbeta1 leads to 4 (Fucalpha1 leads to 3) GlcNAcbeta1 leads to 3Galbeta1 leads to 4Glc, Galbeta1 leads to 4 (Fucalpha1 leads to 3) GlcNAcbeta1 leads to 3Galbeta1 leads to 4 (Fucalpha1 leads to 3) GlcNAcbeta1 leads to 3Galbeta1 leads to 4Glc. The core portions of these sugars, which are newly found linear hexasaccharides, are named para-lacto-N-hexaose and para-lacto-N-neohexaose, respectively.


Amrinone and verapamil-propranolol induced cardiac depression during isoflurane anesthesia in dogs.
This study was designed to investigate the possibility of whether verapamil diminishes the effects of amrinone, whether amrinone can reverse verapamil-propranolol depression, and also to evaluate whether the order of administering the drugs would have any effect during 1.7-1.8% end-tidal isoflurane anesthesia in dogs. At 3-4-week intervals, each of six conditioned mongrel dogs (23 +/- 1 kg) received amrinone (A) (4 mg/kg plus 100 micrograms X kg-1 X min-1), verapamil (V) (200 micrograms/kg plus 7.5 micrograms X kg-1 X min-1) and propranolol (P) (150 micrograms/kg plus 0.8 microgram X kg-1 X min-1) in four different orders of administration: VAP, AVP, VPA, and PVA. Plasma levels achieved were 15 +/- 1 to 24 +/- 2 micrograms/ml for amrinone, 24 +/- 2 to 59 +/- 10 ng/ml for propranolol, and 81 +/- 10 to 163 +/- 17 ng/ml for verapamil, equivalent to high therapeutic (amrinone) and therapeutic (propranolol, verapamil) levels in humans. The results of this study show that amrinone is able to reverse many of the effects of verapamil (group VAP) and also many of the effects of verapamil-propranolol or propranolol-verapamil (groups VPA, PVA) combinations. Amrinone improved cardiac index, left ventricular dP/dtmax, pulmonary capillary wedge pressure, and central venous pressure without increasing catecholamines. However, mean arterial pressure remained decreased with decreased systemic vascular resistance, which necessitates careful consideration depending upon patient circumstances. The results also show that verapamil-propranolol can reverse the positive inotropic effects of amrinone (group AVP).(ABSTRACT TRUNCATED AT 250 WORDS)


Erythromycin Attenuates Hyperoxia Induced Lung Injury by Enhancing GSH Expression and Inhibiting Expression of Inflammatory Cytokines.
Introduction: Oxidative stress and inflammation have proven to be key factors contributing to the occurrence of BPD. Erythromycin has been shown to be effective in treating the redox imbalance seen in many non-bacterial infectious chronic inflammatory diseases. Methods: Ninety-six premature rats were randomly divided into air + saline chloride group, air + erythromycin group, hyperoxia + saline chloride group and hyperoxia + erythromycin group. Lung tissue specimens were collected from 8 premature rats in each group on days 1, 7 and 14, respectively. Results: Pulmonary pathological changes in premature rats after hyperoxia exposure were similar to those of BPD. Hyperoxia exposure induced high expression of GSH, TNF-α, and IL-1β. Erythromycin intervention caused a further increase in GSH expression and a decrease in TNF-α and IL-1β expression. Conclusion: GSH, TNF-α and IL-1β are all involved in the development of BPD. Erythromycin may alleviate BPD by enhancing the expression of GSH and inhibiting the release of inflammatory mediators.


Gadolinium dose optimisation in patients with multiple sclerosis: intra- and inter-individual comparisons.
To assess the efficacy of single, double and triple doses of 1M gadolinium in the magnetic resonance (MR) evaluation of multiple sclerosis (MS) lesions in order to establish the best trade-off in terms of dose and number of injections. Twenty-three patients with relapsing remitting or secondary progressive MS underwent MR scans of the brain, spine or both. Signal intensity, the number of enhancing lesions and the areas of MS plaque were measured in T1-weighted images before and after single, double or triple doses of contrast medium. Wilcoxon's two-sample test and the Mann-Whitney U-test were used to evaluate the differences between the groups, and between doses in the same patient. There was no significant difference in area signal intensity or the number of enhancing lesions between the group examined after a single injection of double-dose (DD) contrast medium and the group examined after multiple injections of a triple dose (TD). The difference in the areas of enhancement and signal intensity between a single dose (SD) and TD significantly increased after the second bolus. Gadolinium injections in MS patients can be optimised by giving a single DD bolus, which leads to the same results as a TD administered as two boli.


Rectal bismuth subsalicylate as therapy for ulcerative colitis.
In a prospective open study, 15 patients with ulcerative colitis which was unresponsive to conventional therapy were treated with enemas containing bismuth subsalicylate (700 or 800 mg b.d.). Nine out of the 15 patients showed a significant clinical response, and 6 had gone into complete clinical remission after 8 weeks treatment. Sigmoidoscopoic appearances of the rectal mucosa showed improvement in 9 out of 15 patients at 2 weeks, and 11 out of 15 at 8 weeks. The mucosa appeared sigmoidoscopically normal in 6 out of 15 at 8 weeks. It proved possible to reduce the oral prednisolone dosage from a median of 15 mg/day (range 10 to 35 mg/day) to 6 mg/day (range 0 to 18 mg/day) after 8 weeks of treatment; 5 patients were no longer taking oral steroids at this time. Rectal bismuth subsalicylate appears likely to be an effective therapy in ulcerative colitis and controlled trials are now required.


Impact of proprioception during the oral phase on initiating the swallowing reflex.
We hypothesized that proprioceptive signals during the oral phase play a pivotal role in the initiation of pharyngeal phase during volitional swallowing. Therefore, we tested if swallowing could be modified by changing the amount of proprioceptive feedback from a number of different receptors while holding a food bolus in the mouth and clenching. Basic research. Surface electromyography (sEMG) recordings of the masticatory muscles were obtained during volitional swallowing movements from seven healthy adults with no clinical history of swallowing difficulties. The swallowing procedure involved holding 5 ml of jelly on the tongue before swallowing it completely, according to visual cues on a computer display. Initiation of the swallowing reflex was detected by an anterior shift of the thyroid cartilage using a laser displacement sensor and by submental sEMG signals. To vary the proprioceptive input, the participants were instructed to occlude their teeth at various intensities (weak, intermediate, and strong) while holding the 5-ml jelly bolus on the tongue. Rectified and integrated sEMG (iEMG) signals obtained from the submental area showed two upward deflections. Contractile forces of the masseter muscles showed significant negative values for Pearson correlation coefficient against time intervals from the onset of the second submental iEMG deflection to the onset of the anterior shift of the thyroid cartilage in six of the seven participants (average -0.534, standard deviation 0.176). Contractile forces of the masseter muscles during occlusion tended to correlate negatively with electromechanical delays on suprahyoid muscle contraction. NA Laryngoscope, 126:1595-1599, 2016.


The value of Allen's test in harvesting a radial forearm flap: correlation of ex-vivo angiography and histopathological findings.
The radial forearm flap is one of the most commonly raised free flaps. In most cases an Allen's test is sufficient for preoperative assessment of the palmar arch, but an intact palmar arch does not imply that the radial artery is suitable for microvascular anastomosis. For a patient operated for oral squamous cell carcinoma, reconstruction was planned with a radial forearm flap. The flap had to be discarded because of advanced atherosclerosis in the presence of a negative Allen's test. The correlation of an ex-vivo angiography and the histopathologic findings was assessed. In cases of expected vascular disease, further examinations like color flow Doppler ultrasound are recommended to ensure sufficient perfusion of the radial artery.


The structure of the human thyroxine binding globulin (TBG) gene.
A portion of the human X-chromosome (> 5 kb) encoding the translated portion of the thyroxine-binding globulin (TBG) gene was sequenced. The primary templates for sequencing were isolated from a human X-chromosome library (two positive plaques from 400,000 screened initially with a TBG cDNA probe) or were produced by PCR amplification using leucocyte genomic DNA as the amplification template. Potential hormone response elements (HREs) were identified at either end of the gene. These HREs have sequences based on the consensus half-site of thyroid hormone response elements, although it is unclear whether the structures are functional HREs. Other potential regulatory elements also were identified towards the 3' end of the gene.


Studies on anabolic steroids. II--Gas chromatographic/mass spectrometric characterization of oxandrolone urinary metabolites in man.
The metabolism of 17 alpha-methyl-17 beta-hydroxy-2-oxa-5 alpha-androstan-3-one (oxandrolone) in man has been investigated by gas chromatography/mass spectrometry. After oral administration of a 10 mg dose to man, five metabolites were detected in the free fraction of the urinary samples. Oxandrolone, the major compound excreted in urine, was detected within 72 h after administration. During this period 35.8 and 8.4% of the administered dose was excreted as unchanged oxandrolone and 17-epioxandrolone, respectively. In addition, minute amounts of 16 alpha- and 16 beta-hydroxyoxandrolone and a delta-hydroxy acid resulting from the hydrolysis of the lactone group of oxandrolone were detected in the urine samples 8-60 h after administration. Furthermore, the susceptibility of oxandrolone to hydrolysis was investigated under several pH conditions. Extraction and fractionation of steroidal metabolites was achieved by using C18 and silica Sep Pak chromatography. The mass spectra of the metabolites are presented and major fragmentation pathways discussed.


Nanosecond laser-assisted cataract surgery: Endothelial cell study.
To evaluate corneal endothelial cell density (ECD) and morphology after cataract surgery using coaxial ultrasound (US) phacoemulsification or a recently introduced coaxial nanosecond laser technique. Department of Ophthalmology, Medical University of Sofia, Sofia, Bulgaria. Prospective cohort study. Coaxial US phacoemulsification was performed in 1 eye (US group) and coaxial nanosecond laser-assisted cataract surgery in the contralateral eye (laser group) of the same patient. Nuclear sclerosis was graded from nuclear opalescence (NO) 3, nuclear color (NC) 3 to NO4, NC4 using the Lens Opacities Classification System III. The central ECD, coefficient of variation (CoV) in cell size (objective measure of polymegethism), and percentage of hexagonal cells (an index of pleomorphism) were evaluated. Eighty-two eyes (41 patients) had uneventful surgery. The mean ECD was 2517 cells/mm(2) ± 137 (SD) preoperatively and 2287 ± 155 cells/mm(2) at 2 years in the US group and 2521 ± 233 cells/mm(2) and 2420 ± 292 cells/mm(2), respectively, in the laser group (both P < .001). The mean CoV was 0.27 ± 2.4 preoperatively and 0.30 ± 2.4 at 2 years in the US group and 0.27 ± 2.8 and 0.27 ± 2.0, respectively, in the laser group (both P < .001). The mean percentage of hexagonal cells was 42.3% ± 3.6% preoperatively and 37.74% ± 3.54% at 2 years in the US group and 42.8% ± 3.2% and 43.00% ± 2.68%, respectively, in the laser group (both P < .001). Nanosecond laser phacoemulsification had advantages over US phacoemulsification in terms of endothelial cell structure preservation. Dr. Kanellopoulos is consultant to Alcon Surgical, Inc., Allergan, Inc., Avedro, Inc., Keramed, Inc., Optovue, Inc., i-Optics Corp., and Carl Zeiss Meditec AG. Neither of the other authors has a financial or proprietary interest in any material or method mentioned.


Surgical treatments of infants with necrotizing enterocolitis.
With the improvements in neonatal intensive care, necrotizing enterocolitis (NEC) has become the most common gastrointestinal emergency amongst infants in neonatal intensive care units. The incidence of NEC varies between 1 and 8% of neonatal intensive care unit admissions and the disease has a mortality rate between 20 and 40%. There are a number of surgical options available to the paediatric surgeon depending on the clinical condition of the infant and the extent of the disease. However owing to a paucity of prospective data in this field and a lack of randomized controlled trials there is little consensus as to which is the most appropriate. Primary peritoneal drainage has become very popular in North America and Europe for the treatment of perforated NEC in very low-birthweight infants. It is a useful manoeuvre in the resuscitation of critically ill infants and in some of these infants, further operation may be avoided completely by inserting a peritoneal drain. Others however remain too unwell to undergo laparotomy and may die. Two randomized controlled trials are currently underway to determine the real benefit of peritoneal drainage. Laparotomy in very small neonates has become safer with improvements in anaesthesia and intensive care management. Resection and primary anastomosis has been proposed as a valid treatment modality in neonates with both focal and multifocal disease. The advantage of resection and primary anastomosis over stoma formation is still controversial. Different surgical techniques such as diverting jejunostomy or 'clip and drop' have been described to deal with extensive disease and avoid massive small bowel resection. Prospective studies and randomized controlled trials are needed to define the best operative treatment for neonates with severe NEC.


Iatrogenic endothelial damage during cataract extraction.
Morphological changes in the endothelium of rabbits' corneas after rinsing with Ringer's solution, chymytrase 0.05% or acetylcholine could not be demonstrated by vital staining with nitroblue tetrazolium. Local lesions caused by manipulations in the anterior chamber were conspicuous. Endothelial lesions due to manipulations with an intra-ocular lens were studied in the same way.


Effect of a computer-assisted general medicine diagnostic consultation service on housestaff diagnostic strategy.
Quick Medical Reference (QMR) is a microcomputer-based decision support system designed to provide diagnostic assistance in the field of internal medicine. In addition to providing plausible diagnostic hypotheses based upon patient specific findings, the program highlights history, physical and laboratory items which are potentially useful in discriminating among the diagnoses under consideration. We have evaluated the impact of a computer-assisted diagnostic consultation service on the diagnostic and management strategy of a housestaff in a university internal medicine training program. Differential diagnoses were obtained before and after the use of the program, and a questionnaire was used to assess the educational value of the service and the effect of the service on the diagnosis and planned management. Over an eight week period, 31 cases were identified which met inclusion criteria. The QMR consultation added a diagnosis to the original list in 14 out of 31 cases. The consultation reordered the diagnosis in an additional 7 cases, and in 8 cases a diagnosis was ruled out by the use of the program. After the use of the program the housestaff reported they would obtain an additional lab test in 10 cases, change the order of planned tests in two cases and eliminate a lab test in one case. The use of the program was rated as helpful educationally in 81% of the cases, and helpful with respect to management in also 81% of the cases.


Infectious barley stripe mosaic virus RNA transcribed in vitro from full-length genomic cDNA clones.
Full-length genomic cDNA clones of the Type and ND18 strains of barley stripe mosaic virus (BSMV) were transcribed in vitro using T7 RNA polymerase. The combination of RNAs alpha, beta, and gamma synthesized in the presence of 5' cap analogs was infectious after inoculation onto barley plants, conclusively demonstrating the tripartite nature of the BSMV genome. Transcripts synthesized in the absence of cap analogs were not infectious. A gamma-specific subgenomic RNA which is normally present in BSMV virions was not required to establish a systemic infection. In vitro transcripts of variant cDNA clones which were isolated from the ND18 strain, containing either a simple nucleotide substitution or a 372-nucleotide duplication similar to one found in the genome of the Type strain, were also found to be biologically active. Two dicotyledonous hosts which have a differential response to infection with the Type and ND18 strains of BSMV were identified and these phenotypes were shown to be faithfully reproduced by inoculation with in vitro transcripts derived from the appropriate full-length cDNA clones.


Effects of the 6 beta-7 beta-epoxide of 12-O-tetradecanoyl-phorbol-13-acetate on radiation transformation in vitro.
Experiments were performed to compare the abilities of 12-O-tetradecanoyl-phorbol-12-acetate (TPA), croton oil and TPA-6 beta-7 beta-epoxide to enhance radiation transformation in vitro. Both croton oil and TPA-6 beta-7 beta-epoxide were more powerful than TPA in the ability to promote radiation transformation in vitro.


AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa.
In the Royal College of Surgeons (RCS) rat, the retinal pigment epithelium (RPE) cannot phagocytose the outer segment discs that are continually shed from photoreceptors. The resulting accumulation of debris in the subretinal space leads to a progressive loss of photoreceptors. The defect results from a mutation in the Mertk gene, which is normally expressed in the RPE. Mertk is a receptor tyrosine kinase, involved in the binding of photoreceptor debris. Mutations in MERTK have also been described in patients with retinitis pigmentosa (RP). Here we demonstrate that subretinal injection of recombinant adeno-associated virus (AAV) expressing the murine Mertk gene can significantly prolong photoreceptor cell survival in the RCS rat. Electroretinographic analysis of treated eyes showed that functional photoreceptors were still present at 9 weeks, when there is virtually no activity in untreated control eyes. Histological analysis of treated eyes revealed a decrease in the amount of debris in the subretinal space, suggesting that RPE function was restored. Moreover, 9 weeks after treatment the number of photoreceptors was 2.5-fold higher in treated than in control eyes. This study provides strong support for the development of AAV-mediated gene therapy for RP caused by mutations in the MERTK gene.


Thyroid function in PMM2-CDG: diagnostic approach and proposed management.
Glycoproteins are essential in the production, transport, storage and regulation of thyroid hormones. Altered glycosylation has a potential impact on thyroid function. Abnormal thyroid function tests have been described in patients with congenital disorders of glycosylation. We evaluated the reliability of biochemical markers and investigated thyroid function in 18 PMM2-CDG patients. We propose an expectative therapeutic approach for neonates with thyroid abnormalities in CDG.


Basaloid squamous cell carcinoma of the larynx.
Basaloid squamous cell carcinoma (BSCC) is a rare tumor with distinct morphological and biological features that differentiate it from the common form of squamous cell carcinoma (SCC) in the head and neck region. It is mostly seen in the supraglottic larynx, hypopharynx and a base of the tongue. We present two cases of BSCC of the larynx; both being transglottic tumors. Both of the patients underwent primary surgery including bilateral neck dissections. None of the patients had cervical metastases at histopathological examination. Both patients received radiotherapy after surgery. They were alive and free of disease at 24 and 27 months, respectively.


The CОVID-19 pandemic became a catalyst for the transformation of the ideas of the existence of global ethics in favor of real moral pluralism, exposed the problem of abandoning the principles of personalized medicine in favor of public health ethics (collective ethics of civil society). The authors sequentially analyze the objective factors that influenced the change in the moral paradigm of the clinical medicine in Russia: the peculiarities of the course of infection, the lack of resources in the health-care sector, the inability to use advanced treatment methods in different groups of patients, the protection of medical workers, the provision of emergency and planned surgical interventions, and the prevention of further spread of infection. In addition, the moral consequences of the use of administrative measures to limit the spread of the pandemic are given: restriction of social contacts, the use of personal protective equipment, retraining of specialists, re-profiling of the bed fund, leveling problems of communication with colleagues, patients and students. Special attention is paid to the problem of "anti-vaxxers", representing a significant part of society and hindering the implementation of the vaccination program of the population. We believe that active and passive protest against vaccinations lie not in a rational plane, but in an emotional one, in an immanent distrust of the state and its institutions. Thus arises a secondary ethical problem of the state's responsibility for the life and health of every citizen, regardless of their beliefs. Contradictions in the moral principles of individual strata of the population (including groups like those who agree to get vaccinated, those who doubt, the indifferent ones, "active anti-vaccinators") currently seem irreconcilable due to the state's detachment from solving moral problems.Ethic divergence in the context of the pandemic has become real, stable and difficult to overcome, while the claims of a single, global, global bioethics are being questioned. The COVID-19 pandemic has formulated the ethical task of the 21st century, which will have to be the development of public policy and practice of clinical medicine in the context of serious moral contradictions and significant bioethical differences.


A systematic review of research using the diagnostic criteria for cancer-related fatigue.
Prevalence rates for cancer-related fatigue vary widely depending on how fatigue is defined and assessed. In 1998, formal diagnostic criteria were proposed for a syndrome of cancer-related fatigue. These criteria were intended to facilitate the study of cancer-related fatigue and the development of appropriate interventions to ameliorate fatigue. Although the criteria have been widely cited, to date, there has been no systematic review of research using the criteria that might inform their continued use or revision. We conducted a systematic review of the literature reporting results based on use of the diagnostic criteria. Data were analyzed to characterize the reliability and validity of the criteria and to describe the prevalence of cancer-related fatigue. We identified nine eligible studies. The purpose of the majority of the studies was to estimate the prevalence of cancer-related fatigue; there was considerable variability with respect to design and nature of the samples included. Although few studies examined reliability of the criteria, findings reported support their reliability. The validity of the criteria judged relative to established measures of fatigue and related constructs appears to be strong. Prevalence rates for cancer-related fatigue based on the diagnostic criteria vary widely, reflecting a lack of consistency in how the criteria have been applied. As a comprehensive approach to diagnosing cancer-related fatigue, the diagnostic criteria have received relatively scant attention by the clinical research community. Our findings suggest the need for research aimed at revising the criteria, enhancing their usefulness, and promoting their more widespread use.


An Efficient Detection and Classification of Acute Leukemia Using Transfer Learning and Orthogonal Softmax Layer-Based Model.
For the early diagnosis of hematological disorders like blood cancer, microscopic analysis of blood cells is very important. Traditional deep CNNs lead to overfitting when it receives small medical image datasets such as ALLIDB1, ALLIDB2, and ASH. This paper proposes a new and effective model for classifying and detecting Acute Lymphoblastic Leukemia (ALL) or Acute Myelogenous Leukemia (AML) that delivers excellent performance in small medical datasets. Here, we have proposed a novel Orthogonal SoftMax Layer (OSL)-based Acute Leukemia detection model that consists of ResNet 18-based deep feature extraction followed by efficient OSL-based classification. Here, OSL is integrated with the ResNet18 to improve the classification performance by making the weight vectors orthogonal to each other. Hence, it integrates ResNet benefits (residual learning and identity mapping) with the benefits of OSL-based classification (improvement of feature discrimination capability and computational efficiency). Furthermore, we have introduced extra dropout and ReLu layers in the architecture to achieve a faster network with enhanced performance. The performance verification is performed on standard ALLIDB1, ALLIDB2, and C_NMC_2019 datasets for efficient ALL detection and ASH dataset for effective AML detection. The experimental performance demonstrates the superiority of the proposed model over other compairing models.


Endometrial compaction is associated with the outcome of artificial frozen-thawed embryo transfer cycles: a retrospective cohort study.
The relationships between the outcome of frozen-thaw embryo transfer (FET) cycle and endometrial compaction were not quite consistent. To analyze the relationship between the outcome of FET cycle and endometrial compaction. A total of 1420 women using FET were researched. The change in endometrial thickness on ET day and those on the day of progesterone (P) administration start is the basis for grouping. Group 1 was endometrial compaction group, and group 2 was the endometrial non-compaction group. Outcome measure was clinical pregnancy, estradiol (E2) levels, progesterone (P) levels, endometrial morphology, and thickness in each period of FET cycle. A significantly lower clinical pregnancy rate was observed in group 2 in comparison with group 1 (43.4% vs. 55.1%, P < 0.01). In addition, P levels on the day of P administration start were lower in group 2 (0.73 ± 0.93 ng/ml vs. 0.90 ± 1.85 ng/ml, P = 0.006), while E2 levels on ET day were higher in group 2 (316.42 ± 304.95 pg/ml vs. 257.88 ± 219.15 pg/ml, P = 0.001) than in group 1. The binary logistic regression analysis showed a lower rate of clinical pregnancy in group 2 (aOR = 0.617, 95% CI 0.488-0.779, P = 0.001). Clinical pregnancy rates were significantly higher in women with endometrial compaction on ET day compared to women with no changes or thickening. Therefore, we recommend paying closer attention to endometrial compaction in women undergoing FET as a method to estimate endometrial receptivity.


The use of radionuclide retinal scintigraphy for the assessment of retinopathy in diabetes mellitus.
A computerized radiotracer technique for the detection of loss of retinal vascular integrity secondary to diabetes is presented. Radionuclide retinal scintigraphy with Technetium-99m DTPA was performed on 40 insulin-dependent diabetics and 10 nondiabetics. A ratio of eye to brain activity was used to eliminate errors associated with absolute counting. Ratios were found to be significantly higher in diabetics, especially those with active neovascularization. This technique may prove useful in the assessment and staging of eyes prone to retinopathy.


Preservative activity in diluted corticosteroid creams.
The preservative efficacy of both 'Betnovate' and 'Synalar' creams diluted 1:1 with 'Unguentum Merck' was investigated. Each formulation was challenged with Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa at an initial inoculum level of approximately 1 X 10(6) viable organisms per gram of cream. All formulations tested were found to be effectively preserved against the organisms used and no viable bacteria were detected 7 days after inoculation.


Unveiling the impact and mechanisms of Cd-driven ecological assembly and coexistence of bacterial communities in coastal sediments of Yellow Sea.
The microbial community assembly processes and underlying mechanisms in response to heavy metal accumulation in coastal sediments remain underexplored. In this study, the heavy metal concentration in samples were found below the marine sediment quality standards. Through partial Mantel tests and linear regression analysis, Cd was identified as the major influencing factor, displaying strongest correlation with the bacterial community in the sediments. The class Desulfuromonadia was identified as a biomarker which showed enrichment in the sediments with high Cd content. Additionally, the results of null model and the neutral community model demonstrated the prominent role of stochastic processes in the assembly of bacterial community. However, with the increase in Cd concentration, the influence of selection processes intensified, resulting in a decline in species migration rate and subsequent reduction in ecological niche width. Furthermore, the intensified competition and an increase in keystone species among bacterial populations further enhanced the stability of the microbial co-occurrence network in response to high Cd concentration. This study offers an insight into the effects of heavy metal on microbial assembly and coexistence, which are conducive to marine ecosystem management and conservation.


Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli.
The transcription factor NF-kappaB modulates apoptotic responses induced by genotoxic stress. We show that NF-kappaB essential modulator (NEMO), the regulatory subunit of IkappaB kinase (IKK) (which phosphorylates the NF-kappaB inhibitor IkappaB), associates with activated ataxia telangiectasia mutated (ATM) after the induction of DNA double-strand breaks. ATM phosphorylates serine-85 of NEMO to promote its ubiquitin-dependent nuclear export. ATM is also exported in a NEMO-dependent manner to the cytoplasm, where it associates with and causes the activation of IKK in a manner dependent on another IKK regulator, a protein rich in glutamate, leucine, lysine, and serine (ELKS). Thus, regulated nuclear shuttling of NEMO links two signaling kinases, ATM and IKK, to activate NF-kappaB by genotoxic signals.


Late onset malnutrition from esophageal and phrenic dysfunction after radiotherapy for Hodgkin's lymphoma: a case report.
Radiotherapy may lead to late-onset, rare, but sometimes life-threatening complications that need to be recognized for timely management. We report the case of a 39-year-old man who presented with a 20-kg weight loss with severe dysphagia and respiratory failure. His medical history was noticeable for Hodgkin's lymphoma that was treated 20 y previously. The physical examination and electroneuromyography indicated vagal and phrenic neuropathies. We concluded that the patient had late-onset esophageal motor disorder and bilateral phrenic paralysis secondary to the radiotherapy received 20 y previously for the lymphoma. The patient's management included long-term nutritional support. Although late-onset vagal and phrenic nerve injuries have been described separately after radiotherapy, we report the first case of paralysis at both sites. Another striking feature of this observation is the subsequent severe malnutrition that accompanied these paralyses.


Left atrial systolic force and cardiac markers of preclinical disease in hypertensive patients: the Hypertension Genetic Epidemiology Network (HyperGEN) Study.
Left atrial systolic force (LASF) has been recently reported to be associated with prolonged left ventricular (LV) relaxation and concentric LV geometry in a clinical setting. This study analyzes the association of increased LASF to LV geometry and function in hypertensive patients from a population study. Doppler echocardiographic findings were examined in 684 subjects with treated hypertension and without prevalent cardiovascular disease from the Hypertension Genetic Epidemiology Network (HyperGEN) Study (426 African American, 448 female, 125 diabetic, 174 obese; age 53.8+/-10.8 years). The LASF was assessed from the mitral orifice area and pulse-wave Doppler peak A flow velocity. The LASF was defined as being high if >14.33 kdynes (90th percentile of the normal distribution in 246 normal adults). The LASF was high in 269 participants (39.3% of study population), who were older and had higher mean body mass index (all P<.01). Participants with high LASF had higher systolic BP and heart rate (both P<.01) but similar diastolic BP. After controlling for covariates, participants with high LASF exhibited higher LV dimensions and mass than those with normal LASF (all P<.01). The prevalence of LV hypertrophy was also higher (P<.001). Participants with high LASF exhibited normal ejection fraction, higher stroke volume, cardiac output, E and A velocities, slower E deceleration, and lower E/A ratio than those with normal LASF (all P<.01). Enhanced LASF is associated with LV hypertrophy, normal LV chamber function, increased cardiac output, and prolonged relaxation. The LASF is a preload-dependent measure.


An analytical approach for the non-invasive selection of consolidants in rubber artworks.
The effectiveness of five polymeric materials for the long-term conservation and restoration of rubber artworks was evaluated by accelerated photo-oxidative degradation studies. Two different ethylene vinyl-acetate resins, generally used in industry and uncommon in conservation field, a new water-based polyurethane, and two ethylene butyl-acrylate resins were assessed for the consolidation of rubber. By monitoring their degradation along time with LED imaging coupled to statistics and Fourier transform infrared spectroscopy (FTIR), the polymeric materials with the best properties that ensure the protection and security of the artwork were identified. The degradation was performed in solar box simulating the light exposure in a museum, under controlled temperature at no more than 35 °C in order to exclude the thermal effects that could influence the ageing of polymers. The mechanical stress of the treated samples was also investigated. The spectroscopic analyses, the chromatic changes study, and the mechanical degradation were used as indicators of the consolidant stability, allowing the evaluation of the materials selected for the consolidation and conservation of rubber. The ethylene-vinyl acetate copolymers resulted the most stable and suitable for the conservation of rubber artworks. Lastly, the conservation treatment identified in this research was employed for the restoration of the contemporary artwork "Presagi di Birnam" made with bicycle inner tubes by the artist Carol Rama.


A perspective on mammalian upstream open reading frame function.
Post-transcriptional control makes a major contribution to the overall regulation of gene expression pathway. Within the cytoplasm this is mediated by a combination of regulatory RNA motifs within the 5' and 3' untranslated regions of mRNAs and their interacting protein/RNA partners. One of the most common regulatory RNA elements in mammalian transcripts (present in approximately 40% of all mRNAs) are upstream open reading frames (uORFs). However, despite the prevalence of these RNA elements how they function is not well understood. In general, they act to repress translation of the physiological ORF under control conditions, and under certain pathophysiological stresses this repression can be alleviated. It is known that re-initiation following the translation of an uORF is utilised in some situations however there are numerous alternative mechanisms that control the synthesis of a protein whose mRNA contains uORFs. Moreover, the trans-acting factors that are also involved in this process are not well defined. In this review we summarise our current understanding of this area and highlight some common features of these RNA motifs that have been discovered to date.


Preoperative neuroimage findings as a predictor of postoperative neurological deficit in intracranial meningiomas.
The present study aimed to find radiological parameters that can provide indirect information on the invasive growth of meningioma relevant enough to predict the likely risk of postoperative neurological deficit. The cohort consisted of 40 consecutive adult patients (from January 2004 till May 2005) with comparable general condition parameters (age 18-75 years, KRS 70-100, ASA 1-2) with meningiomas solely attacking brain tissue with the whole of their volume. The Pearson chi-square test was used for statistical evaluation. Radical resection of the meningioma was attained in 33 (82.5%) patients and subtotal resection in 7 (17.5%). Ten (25%) patients at 7 days after the operation had neurological findings which were worse than before. Seven were found to have a new neurological deficit and there were three cases of progression of the existing neurological symptoms. Three patients (7.5%) were worse off neurologically than before the operation as long as 3 months after surgery, while seven had their neurological condition restored ad integrum. All of the ten patients with postoperatively worsened neurological findings had their meningiomas localised in the eloquent area. A correlation was found between the eloquent area and neurological deficits, and also between the presence of peritumoral oedema (small, medium, large) and neurological deficits. Interdependence was detected between a discernible tumour-brain interface and the absence of oedema, between a discernible tumour-brain interface and a dural type of vascular supply, and between the dural type of vascularisation and an absence of oedema. As follows from the outcomes, meningioma growth in the eloquent area and the presence of peritumoral oedema are the two adverse parameters predicting the development of postoperative neurological deficits. In contrast, dural types of vascularisation, a visible tumour-brain interface, meningioma growing in a non-eloquent area, and the absence of peritumoral oedema are favourable predictive parameters. To go by the results, in the presence of the last two parameters the patient need not be exposed to the risks of invasive selective angiography.


Does ultrasound equally improve the quality of beef? An insight into longissimus lumborum, infraspinatus and cleidooccipitalis.
Quality of bovine longissimus lumborum, infraspinatus and cleidooccipitalis muscles after high-intensity ultrasound (HIU; 40 kHz and a power of 11 W/cm2 for 0, 40, 60, and 80 min) and aging (0, 7 and 14 d) was evaluated. The effects of HIU on pH and color of meat were not considered negative. HIU improved water holding capacity (WHC) of l.lumborum and infraspinatus only after aging. Whereas, the WHC of cleidooccipitalis increased immediately after sonication. The total collagen of HIU treated samples was significantly lower compared to the untreated samples. Ultrasonication for 80 min was the most effective for infraspinatus and cleidooccipitalis. Toughness decreased with HIU, iii nfraspinatus and l.lumborum tenderized more than cleidooccipitalis. HIU application and 7 d aging is an excellent combined treatment to improve tenderness of the three muscles. Infraspinatus was the most tender meat. HIU could help industry to improve the quality of beef as it helps in tenderization and accelerates maduration particularly of l.lumborum.


Hematopathology of Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Coronavirus Disease-19.
Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 and is associated with pronounced hematopathologic findings. Peripheral blood features are heterogeneous and very often include neutrophilia, lymphopenia, myeloid left shift, abnormally segmented neutrophils, atypical lymphocytes/plasmacytoid lymphocytes, and atypical monocytes. Bone marrow biopsies and aspirates are often notable for histiocytosis and hemophagocytosis, whereas secondary lymphoid organs may exhibit lymphocyte depletion, pronounced plasmacytoid infiltrates, and hemophagocytosis. These changes are reflective of profound innate and adaptive immune dysregulation, and ongoing research efforts continue to identify clinically applicable biomarkers of disease severity and outcome.


Proteome analysis of rat polymorphonuclear leukocytes: a two-dimensional electrophoresis/mass spectrometry approach.
The development of a two-dimensional (2-D) map of rat polymorphonuclear (PMN) leukocytes is here reported for the first time. The map is built up by utilizing a wide immobilized pH gradient (IPG), pH 3-10, in the first dimension and also a narrower IPG pH 4.5-8.5 gradient. In addition, the map is constructed by adopting the most recent protocols in 2-D mapping, which call for reduction and alkylation of the sample prior to the start of any electrophoretic step, including the IPG dimension. Fifty-two major protein spots have been so far identified by utilizing both matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) and electrospray quadrupole (Q)-TOF mass spectrometry. A large number of house-keeping and cytoskeleton proteins were detected, together with proteins which are specific to PMN organelles or related to PMN functions such as phagocytosis and chemotaxis. The results obtained demonstrate the possibility of obtaining a single 2-D gel based proteomic map of PMN with representative proteins from different cellular compartments, also including membrane components, allowing the study of PMN protein expression on a proteome-wide scale. The aim of this project is to build an extensive database of such proteins, to be utilized for future studies where the expression of PMN proteins is used as a disease- or drug treatment marker.


Bilateral massive renal angiomyolipoma concurrent with oncocytoma in tuberous sclerosis complex associated with pulmonary lymphangioleiomyomatosis.
We describe a patient with tuberous sclerosis complex and massive bilateral renal angiomyolipomas (AMLs) in association with pulmonary lymphangioleiomatosis, who experienced hemorrhagic shock because of rupture of the left renal AML. She was treated with transarterial embolization, followed by bilateral nephrectomy. The total tumor burden weighed 5800 g, making it the largest AML by weight in published reports. The histopathologic examination revealed concurrent oncocytomas with AMLs in the right kidney, indicating a possible shared mechanism in the pathogenesis of these two disorders. This case also represents a rare, but significant, overlap between renal AML, pulmonary lymphangioleiomatosis, and tuberous sclerosis complex.


Genomic analyses and expression evaluation of thaumatin-like gene family in the cacao fungal pathogen Moniliophthora perniciosa.
Thaumatin-like proteins (TLPs) are found in diverse eukaryotes. Plant TLPs, known as Pathogenicity Related Protein (PR-5), are considered fungal inhibitors. However, genes encoding TLPs are frequently found in fungal genomes. In this work, we have identified that Moniliophthora perniciosa, a basidiomycete pathogen that causes the Witches' Broom Disease (WBD) of cacao, presents thirteen putative TLPs from which four are expressed during WBD progression. One of them is similar to small TLPs, which are present in phytopathogenic basidiomycete, such as wheat stem rust fungus Puccinia graminis. Fungi genomes annotation and phylogenetic data revealed a larger number of TLPs in basidiomycetes when comparing with ascomycetes, suggesting that these proteins could be involved in specific traits of mushroom-forming species. Based on the present data, we discuss the contribution of TLPs in the combat against fungal competitors and hypothesize a role of these proteins in M. perniciosa pathogenicity.


Influence of structural modifications on the phase behavior of semi-synthetic cerebroside sulfate.
Cerebroside sulfate (galactosylceramide I3-sulfate) containing alpha-hydroxy lignoceric acid (C24:0h-CBS), nervonic acid (C24:1-CBS), or hexacosanoic acid (C26:0-CBS) was prepared by a semi-synthetic procedure and studied by differential scanning calorimetry. The phase behavior of these species in 2 M KCl was compared to that of shorter chain length hydroxy and non-hydroxy fatty acid species reported earlier. All three of the new lipids undergo metastable phase behavior similar but not identical to the other species. In addition, the metastable phase behavior of all of the non-hydroxy fatty acid species was found to be more complex than previously thought, with several phases of high transition temperatures and enthalpies possible. Fatty acid hydroxylation inhibits the transition from the metastable to some of the more stable phases. It also significantly increases the phase transition temperatures of both the metastable and stable phases indicating that it contributes to the hydrogen bonding network formed between the lipid molecules and helps overcome the lateral repulsive effect of the negatively charged sulfate. The C-15 cis double bond significantly lowers the temperature and enthalpy of the phase transition indicating that it increases the lateral separation of the lipid molecules and decreases the intermolecular hydrogen bonding interactions. However, it does not prevent formation of a more stable phase. By comparing the effect of various structural modifications reported here and earlier it could be concluded that fatty acid chain length has little effect on the phase transition temperature and enthalpy. This suggests that the forces between the lipid molecules may be dominated by head group interactions rather than interactions between the lipid chains. However, fatty acid chain length has a significant effect on the tendency of the hydroxy fatty acid species to form the more stable phase. The ease of formation of the stable phase increases with increase in chain length. Thus an increase in chain length helps overcome the kinetic barrier to stable phase formation presented by hydroxylation of the fatty acid.


Spin-labelling of sialic acid in soluble and cell-surface glycoproteins.
A new, mild method is described for spin-labelling sialic acid residues in situ. The procedure involves the formation of C-1 sialamides and has been applied to a serum glycoprotein, a mucin, tissue sections from human colon, and erythrocyte membrane components. The selectivity of the method and its possible applicability to other types of labelling are discussed.