Application of neural network and time series modeling to study the suitability of drain water quality for irrigation: a case study from Egypt.
Limited water resources are one of the major challenges facing Egypt during the current stage. The agricultural drainage water is an important water resource which can be reused for agriculture. Thus, the current study aims to assess the quality of drainage water for irrigation purpose through monitoring and predicting its suitability for irrigation. The chemical composition of Bahr El-Baqr water drain, especially salinity, as well as ions are mainly involved in calculating indicators of water suitability for irrigation, i.e., Ca2+, Mg2+, Na+, K+, HCO-3, Cl-, and SO42-. Further analysis was carried out to evaluate the irrigation water quality index (IWQI) through integrated approaches and artificial neural network (ANN) model. Further, ARIMA models were developed to forecast IWQI of Bahr El-Baqr drain in Egypt. The results indicated that the computed IWQI values ranged between 46 and 81. Around 11% of the samples were classified as excellent water, while 89% of the samples were categorized as good water. The results of IWQI showed a standard deviation of 8.59 with a mean of 62.25, indicating that IWQI varied by 13.79% from the average. ANN model showed much higher prediction accuracy in IWQI modeling with R2 value greater than 0.98 during training, testing and validation. A relatively good correlation was obtained, between the actual and forecasted IWQI based on the Akaike information criterion (AIC); the best fit models were ARIMA (1,0) (0,0) without seasonality. The determination coefficient (R2) of ARIMA models was 0.23. Accordingly, 23% of IWQI variability could be explained by different model parameters. These findings will support the water resources managers and decision-makers to manage the irrigation water resources that can be implemented in the future.


Pro-social cognition: helping, practical reasons, and 'theory of mind'.
There is converging evidence that over the course of the second year children become good at various fairly sophisticated forms of pro-social activities, such as helping, informing and comforting. Not only are toddlers able to do these things, they appear to do them routinely and almost reliably. A striking feature of these interventions, emphasized in the recent literature, is that they show precocious abilities in two different domains: they reflect complex 'theory of mind' abilities as well as 'altruistic motivation'. Our aim in this paper is to present a theoretical hypothesis that bears on both kinds of developments. The suggestion is that children's 'instrumental helping' reflects their budding understanding of practical reasons (in the standard sense of 'considerations that count in favour of' someone's acting in a certain way). We can put the basic idea in the familiar terminology of common coding: toddlers conceive of the goals of others' actions in the same format as the goals of their own actions: in terms of features of their situation that provide us with reasons to act.


Application of subproteomics in the characterization of Gram-positive bacteria.
Gram-positive bacteria cause a series of diseases in human, animals and plants. There has been increasing interest in efforts to investigate pathogenesis of bacteria using multiple "omic" strategies including proteomics. Proteins in different cell fractions of bacteria may play different vital roles in various physiological processes, such as adhesion, invasion, internalization, sensing, respiration, oxidative stress protection and pathogenicity. Subproteomics specifically focuses on the pre-fractionated cellular proteins and thus may be able to characterize more low-abundance molecules that are usually overlooked by the traditional whole-cell proteomics, providing comprehensive information for further investigations. This review intends to outline the current progress, challenges and future development of subproteomics in the characterization of Gram-positive bacteria. This article is part of a Special Issue entitled: Proteomics: The clinical link.


Cross-language use of pitch: an ethological view.
Certain signaling functions of the pitch of voice are remarkably similar across languages and cultures: (1) high or rising pitch to mark questions, low or falling pitch to mark nonquestions; (2) high pitch to signal politeness, low pitch to signal assertiveness; (3) in 'sound symbolic' vocabulary, high tone used with words connoting smallness or diminutive, low tone with words connoting largeness. These patterns can be explained by the assumption that human vocal communication exploits the 'frequency code', a cross-species association of high pitch vocalizations with smallness (of the vocalizer), lack of threat, and of low pitch vocalizations with the vocalizer's largeness and threatening intent.


Quality of life for the gynecologic oncology patient.
An attempt is made to define the quality of life in terms of the patient with gynecologic cancer. The effect of the diagnosis of cancer and its recurrence or its terminal state on the quality of life is considered. Possible methods of assessing the patient's individual feelings about the quality of her life are reviewed and suggestions made for incorporating these into plans of management at all stages of the disease.


How do previously inactive individuals restructure their time to 'fit in' morning or evening exercise: a randomized controlled trial.
The objective of this study was to investigate changes in sedentary and active behaviors when previously inactive adults start exercising in the morning or evening. One-hundred adults with overweight or obesity (BMI ≥ 25 kg/m2) were recruited for a 12-week intervention and randomized to one of three groups: (i) morning exercise (AMEx; 0600-0900); (ii) evening exercise (PMEx; 1600-1900); or (iii) waitlist control. AMEx and PMEx were prescribed self-paced aerobic exercise to achieve a weekly total of 250 min via a combination of supervised and unsupervised training. Sedentary and active behavior times were measured at baseline, mid- and post-intervention using the multimedia activity recall for children and adults. Time spent engaging in physical activity was significantly increased from baseline at both mid- (+ 14-22 min·day-1) and post-intervention (+ 12-19 min·day-1), for AMEx and PMEx. At 12-weeks, participants in both morning and evening exercise groups reported increased time spent Sleeping (+ 36 and + 20 min·day-1, respecitively), and reduced time spent watching TV/playing videogames (- 32 and - 25 min·day-1, respectively). In response to an exercise stimulus, previously inactive adults make encouraging modifications in how they use their time, and the patterns of change are similar with morning and evening exercise.


The estimation of fetal weight by computer-assisted analysis.
The need for a quick and easy method for estimating fetal weight in utero has been clearly established. Estimates by abdominal palpation and fetal hormone production have proved to be of limited value. Eight-five patients, ranging from 17 to 41 weeks' gestation, were ultrasonically scanned within 48 hours of delivery. Statistical analysis and multiple multivariant linear regressions were performed employing the BMD statistical packages. Our results show that birth weight is a logarithmic function of fetal body parameters and that the abdominal circumference has the single best correlation with the log10 birth weight. Our best linear regression with the use of two fetal dimensions (abdominal circumference and biparietal diameter) had a standard deviation of 106 grams per kilogram fetal weight. Since this derived formula is very cumbersome to manipulate, tables have been prepared with computer assistance to read the estimated fetal weight directly. Prospective estimates in 32 cases of both normal and pathologic gestations have proved to be within our expected accuracy.


Proteorhodopsin: characterisation of 2D crystals by electron microscopy and solid state NMR.
Proteorhodopsin (PR) a recent addition to retinal type 1 protein family, is a bacterial homologue of archaeal bacteriorhodopsin. It was found to high abundance in gamma-proteobacteria in the photic zone of the oceans and has been shown to act as a photoactive proton pump. It is therefore involved in the utilisation of light energy for energy production within the cell. Based on data from biodiversity screens, hundreds of variants were discovered worldwide, which are spectrally tuned to the available light at different locations in the sea. Here, we present a characterisation of 2D crystals of the green variant of proteorhodopsin by electron microscopy and solid state NMR. 2D crystal formation with hexagonal protein packing was observed under a very wide range of conditions indicating that PR might be also closely packed under native conditions. A low-resolution 2D projection map reveals a ring-shaped oligomeric assembly of PR. The protein state was analysed by 15N MAS NMR on lysine, tryptophan and methionine labelled samples. The chemical shift of the protonated Schiff base was almost identical to non-crystalline preparations. All residues could be cross-polarised in non-frozen samples. Lee-Goldberg cross-polarisation has been used to probe protein backbone mobility.


In situ evolutionary rate measurements show ecological success of recently emerged bacterial hybrids.
Few data are available on how quickly free-living microorganisms evolve. We analyzed biofilms collected from a well-defined acid mine drainage system over 9 years to investigate the processes and determine rates of bacterial evolution directly in the environment. Population metagenomic analyses of the dominant primary producer yielded the nucleotide substitution rate, which we used to show that proliferation of a series of recombinant bacterial strains occurred over the past few decades. The ecological success of hybrid bacterial types highlights the role of evolutionary processes in rapid adaptation within natural microbial communities.


In vivo expression of genes in the entomopathogenic fungus Beauveria bassiana during infection of lepidopteran larvae.
The entomopathogenic fungus Beauveria bassiana (Bals.) Vuillemin is commercially available as a bio insecticide. The expression of three genes previously identified to have a role in pathogenicity in in vitro studies was validated in vivo in three lepidopteran insects infected with B. bassiana. Expression of all three genes was observed in all the tested insects starting from 48 or 72h to 10d post infection corroborating their role in pathogenicity. We suggest that it is essential to test the expression of putative pathogenicity genes both in vitro and in vivo to understand their role in different insect species.


Systemic disturbance in Hodgkin's disease and its relation to histopathology and prognosis (BNLI report No. 30).
Systemic disturbances in Hodgkin's disease at presentation are not only manifested by 'B' symptoms (weight loss, fever, and night sweats), but are also mirrored in the peripheral blood as raised sedimentation rate, low haemoglobin, low albumin, and abnormal lymphocyte counts. Such systemic disturbance is more common than consideration of classical 'B' symptoms alone would suggest. In a series of 840 patients, 88% had some form of systemic disturbance on these criteria. Survival after treatment was found to be closely and inversely related to the degree of systemic disturbance present before treatment. Patients with no evidence of such disturbance had an almost 100% survival at 10 years. In the absence of 'B' symptoms the sedimentation rate was the most useful prognostic blood parameter, enabling about one third of the patients to be identified as having an excellent chance of survival, and identifying a further 12% as having a survival almost identical to that of patients with 'B' symptoms. The latter patients were those with a sedimentation rate of 60 mm/h or greater, and it is suggested that the term 'Systemic Symptoms' should be broadened to include a sedimentation rate of this magnitude. The degree of malignancy of the tumour, as reflected by histopathology, plays a dominant role in determining the amount of systemic disturbance in the host. However, the amount of disturbance varies amongst individual patients with the same histopathological subtype, reflecting either differences in the malignancy of the tumour within such subtypes, or differences in the constitution of the host.


Blood loss with use of the Shaw scalpel for the treatment of oral cancer.
The Shaw scalpel was used in seven radical operations for oral cancer. The amount of bleeding and postoperative exudate and the occurrence of postoperative complications were compared with that from 12 operations performed with the conventional steel scalpel. The blood loss during the radical neck dissection performed with the Shaw scalpel was 39% of the control value, and no blood transfusions were necessary. There was no increase in the amount of postoperative exudate in the Shaw scalpel group compared with the control group. Skin incision with the Shaw scalpel was accompanied by superficial wound dehiscences in three patients, which healed without any treatment.


A sensitive electrochemical DNA biosensor for antineoplastic drug 5-fluorouracil based on glassy carbon electrode modified with poly(bromocresol purple).
This paper describes an electrochemical sensor for the first time based on poly(bromocresol purple) (P(BCP)) developed to observe the interaction between 5-fluorouracil (5-FU) and fish sperm double strand DNA (dsDNA). The P(BCP) film was electrosynthesized by cyclic voltammetry method on the glassy carbon electrode (GCE). The dsDNA was electrochemically immobilized on the surface of P(BCP) modified GCE and the DNA biosensor was prepared. The interaction mechanism of dsDNA with 5-FU was investigated by differential pulse voltammetry using this biosensor. A decrease in the guanine oxidation peak current of the biosensor was observed after the interaction of dsDNA and 5-FU in 0.5 mol L(-1) acetate buffer (pH 4.8) containing 0.02 mol L(-1) NaCl. The accumulation time and dsDNA concentration were optimized to obtain the best peak current response. Under optimum conditions, the linear response on the guanine signal decreasing curve was observed in the 5-FU concentration range of 1.0-50 mg L(-1). The interaction mechanism between dsDNA and 5-FU was further investigated by UV-vis spectroscopy and viscometer. The results reveal that intercalation is the primary mode of interaction between 5-FU and dsDNA.


Retinal Nerve Fiber Layer Thickness in Healthy Eyes of Black, Chinese, and Latino Americans: A Population-Based Multiethnic Study.
To compare peripapillary retinal nerve fiber layer (RNFL) thickness among healthy adults by race and ethnicity and to identify determinants of RNFL thickness. Population-based cross-sectional study. Data from 6133 individuals (11 585 eyes) from 3 population-based studies in Los Angeles County, California, 50 years of age or older and of self-described African, Chinese, or Latin American ancestry. We measured RNFL thickness and optic nerve head parameters using the Cirrus HD-OCT 4000. Multivariate linear mixed regression was used to evaluate factors associated with RNFL thickness among participants without ocular diseases. Determinants and modifiers of RNFL thickness. The mean age of the participants was 60.1 years (standard deviation, 7.4 years). Black Americans showed the lowest RNFL thickness and smallest cup-to-disc ratio (CDR), and Chinese Americans showed the largest CDR and disc area after adjusting for age and gender (all P < 0.05). Per each 10-year older age group, the average RNFL thickness was 2.5 μm (95% confidence interval [CI], 1.8-3.1 μm), 2.8 μm (95% CI, 2.3-3.3 μm), and 3.5 μm (95% CI, 2.9-4.1 μm) thinner for Black, Chinese, and Latino Americans, respectively (age trend P < 0.05 and interaction P = 0.041). Black Americans compared with Chinese Americans, older age, male gender, hypertension, diabetes, greater axial length (AL), bigger disc area, and lower scan signal strength were associated with thinner average RNFL. Race, age, AL, disc area, and scan signal strength consistently were associated with RNFL thickness in all quadrants, whereas gender, hypertension, and diabetes were associated with RNFL thickness in select quadrants. Age and race explained the greatest proportion of variance of RNFL thickness. Clinically important differences in RNFL thickness are present in healthy adults 50 years of age or older from different racial and ethnic groups of the same age, with the thinnest measures observed in Black Americans. This difference remains after accounting for disc size and AL. Furthermore, age-related RNFL thinning differs by race and ethnicity. Longitudinal studies are needed to verify our findings and to assess the influence of race and ethnicity in the clinical application of RNFL thickness.


Effects of dexmedetomidine on glucose-related hormones and lactate in non-diabetic patients under general anesthesia: a randomized controlled trial.
The aim of this study was to explore the effects of dexmedetomidine on glucose-related hormones and lactate levels in non-diabetic patients undergoing malignant gastrointestinal tumor radical resection. Groups D<inf>1</inf> and D<inf>2</inf> received dexmedetomidine loading dose 1 µg/kg and maintenance dose 0.25 and 0.5 µg/kg/h, respectively. Group C received saline solution. Glucose, lactate, insulin, glucagon, cortisol, epinephrine, norepinephrine and dopamine levels were measured before dexmedetomidine infusion (T<inf>1</inf>), 1 h after surgery beginning (T<inf>2</inf>), at surgery ending (T<inf>3</inf>), and 1 h after transfer to the postanesthesia care unit (T<inf>4</inf>). Compared with group C, glucose levels increased in group D<inf>2</inf> at T<inf>2</inf> and reduced in groups D<inf>1</inf> and D<inf>2</inf> at T<inf>4</inf>. Lactate levels reduced in groups D<inf>1</inf> and D<inf>2</inf> at T<inf>4</inf>. A positive correlation between glucose and lactate levels was found in all groups. Compared with group C, insulin level reduced in group D<inf>2</inf> at T<inf>2</inf>; glucagon levels reduced in groups D<inf>1</inf> and D<inf>2</inf> at T<inf>4</inf>; cortisol levels reduced in group D<inf>1</inf> at T<inf>4</inf> and in group D<inf>2</inf> at T<inf>3</inf> and T<inf>4</inf>; epinephrine and norepinephrine levels reduced in group D<inf>1</inf> at T<inf>4</inf> and in group D<inf>2</inf> at T<inf>2</inf> and T<inf>4</inf>; and dopamine level reduced in group D<inf>2</inf> at T<inf>4</inf>. Dexmedetomidine loading dose 1 µg/kg and maintenance dose 0.25 µg/kg/h produces a stable insulin level and significant postoperative decreases in glucagon, cortisol, epinephrine and norepinephrine secretion with stable maintenance of intraoperative and postoperative blood glucose levels and decreased postoperative lactate levels in non-diabetic patients under general anesthesia.


Design and validation of the presenteeism scale in nursing.
The instruments used to measure presenteeism are all flawed and only incompletely measure the concept of presenteeism in employees of the general population. As a result, the concept of presenteeism is not measured, and in most of these instruments, the population for which the instrument has been developed differs from the nursing population. The present research was conducted to design and validate the instrument for evaluating presenteeism in nursing. The present study was part of an exploratory sequential mixed study. In this study, the instrument for measuring the level of presenteeism among nurses was developed and validated based on the results of the qualitative stage. To this end, the instrument's psychometric properties were investigated using face, content, and construct validity, as well as reliability through internal consistency and stability. In this study, an instrument containing 17 items and three dimensions (imperfect cognitive presence, imperfect emotional presence, and imperfect movement presence) with favorable validation characteristics was developed. Therefore, the instrument was able to explain 56.375% of the total variance. Furthermore, Cronbach's alpha and McDonald's omega coefficients were 0.881 and 0.815, respectively. The intra-cluster correlation coefficient (ICC) was also reported as 0.972 for the entire instrument, with a 95% confidence interval of 0.941 to 0.987. Based this study, it was possible to measure the level of nurses' presenteeism through an instrument with favorable psychometric properties. This study helps health managers lay the groundwork for designing a system for measuring presenteeism among Iranian nurses using the developed instrument.


Effects of colesevelam HC1 on sterol and bile acid excretion in patients with type IIa hypercholesterolemia.
Colesevelam HC1 is a potent bile acid-binding polymer. This study's aim was to determine effects of colesevelam HCl on sterol and bile acid excretion in patients with type IIa hypercholesterolemia. Twenty-four patients (low-density lipoprotein cholesterol, 130 to 220 mg/dL) enrolled in an open-label, parallel-design study, entered an American Heart Association/National Cholesterol Education Program diet for 6 weeks and were randomized to colesevelam HCl, 2.3 or 3.8 g/day for 4 weeks. In an apparent dose-related manner, respective mean serum concentrations HCl of low-density lipoprotein cholesterol decreased by 10% (P < 0.01) and 13% (P = 0.05), mean total cholesterol levels decreased by 4.9% (P = 0.05) and 6.1% (P = 0.09), and total fecal bile acid excretion showed median changes of +324% (P < 0.05) and +316% (P < 0.05). Colesevelam HCl did not affect fecal neutral sterol or fecal fatty acid excretion; however, 24-hr urinary mevalonic acid levels significantly increased in both treatment groups (P < 0.05). The cholesterol-lowering action of colesevelam HCl appears to be mediated through increased bile acid excretion.


Construction of carboxymethyl chitosan-based nanoparticles of hypoxia response for co-loading doxorubicin and tanshinone IIA.
As a first-line drug for breast cancer chemotherapy, the effectiveness of doxorubicin (DOX) is challenged by high doses and high toxicity. Studies showed the combination of Tanshinone IIA (TSIIA) and DOX could enhance the efficacy of DOX for cancer and reduce the toxic effects to normal tissues. Unfortunately, free drugs are easily metabolized in the systemic circulation, which are less prone to aggregation at the tumor site to exert anticancer efficacy. In present study, we prepared a carboxymethyl chitosan-based hypoxia-responsive nanoparticles loaded with DOX and TSIIA for the treatment of breast cancer. The results demonstrated that these hypoxia-responsive nanoparticles not only improved the delivery efficiency of the drugs but also enhanced the therapeutic efficacy of DOX. The average size of nanoparticles was about 200-220 nm, the optimal drug loading and encapsulation efficiency of TSIIA in DOX/TSIIA NPs were 9.06 % and 73.59 %, respectively. Hypoxia-responsive behavior were recorded in vitro, while the synergistic efficacy is significantly exhibited in vivo and the tumor inhibitory rate was 85.87 %. Notably, TUNEL assay and immunofluorescence staining verified that the combined nanoparticles exerted a synergistic anti-tumor effect by inhibiting tumor fibrosis, decreasing the expression of HIF-1α and inducing tumor cell apoptosis. Collectively, this carboxymethyl chitosan-based hypoxia-responsive nanoparticles could have promising application prospect for effective breast cancer therapy.


Growth and characterisation of human faecal astrovirus in a continuous cell line.
We report conditions for the growth of human faecal astrovirus in a continuous colonic carcinoma cell line (CaCo-2). Purified particles contained three polypeptides, one of which (24k) appeared loosely held on the exterior.


Angiotensin receptor blockers: novel role in high-risk patients.
The identification of patients at high risk for cardiovascular events is imperative in the reduction of cardiovascular mortality and morbidity. Although coronary artery disease, peripheral arterial disease, cerebrovascular disease, hypertension, and diabetes mellitus contribute to the risk of developing cardiovascular events, we are now faced with emerging fronts because of an increase in life expectancy and the epidemic of hypertension, obesity, metabolic syndrome, and diabetes. Recent data emphasize the beneficial role of renin-angiotensin-aldosterone system (RAAS) blockers. This article addresses the role of RAAS activation in the high-risk metabolic milieu and the role of angiotensin receptor blockers in targeting and inhibiting the RAAS for cardiovascular protection.


Anatomy of motion.
Review of muscle function during the walking gait cycle suggests that once the body is put in motion, its own kinetic force tends to keep it moving. This progression, however, must be controlled and stabilized by muscles acting on the limb segments during weight bearing. Primary, accelerating muscle action is most important during swing phase when the iliopsoas and quadriceps femoris bring the limb forward to maintain continuity of the gait cycle. Once the limb is in stance phase, most muscles exert controlling forces on the limb by decelerating movement of the limb segments and stabilizing the joints.


Ocular Vascular Changes: Choroidal Thickness as an Early Biomarker for Alzheimer's Disease?
Alzheimer's disease (AD) is an age-related neurodegenerative and progressive disorder representing the most common form of dementia among the elderly [...].


Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins.
Recent years have seen a growing interest in Berberine, a phytochemical with multispectrum therapeutic activities, as anti-tumoral agent for photodynamic therapy (PDT). In this context, low density lipoproteins (LDL) play a key role in the delivery of the photosensitizer in tumor cells. We correlate the physicochemical parameters of the berberine association to LDL with the influence of LDL-delivery on its accumulation in a glioma cell line and on its photo-induced activity in view of antitumor PDT. Our results evidence an important binding of 400 berberine molecules per LDL. Changes in berberine and apoprotein fluorescence suggest different fixation types, involving various LDL compartments including the vicinity of the apoprotein. The berberine association to LDL does not affect their recognition by the specific B/E receptors, of which over-expression increases the cellular uptake of LDL-preloaded berberine. Fluorescence microscopy evidences the mitochondrial labeling of the glioma model cells, with no significant modification upon LDL-delivery. Moreover, the cellular delivery of berberine by LDL increases its photocytotoxic effects on such cells. So, this research illustrates the potential of berberine as a photosensitizing agent for PDT, in particular due to their behavior towards LDL as plasma vehicles, and gives insights into its mechanisms of cell uptake.


Computational implementation of the conditional logistic regression model in the analysis of epidemiologic matched studies.
Adaptation of a BMDP packaged program for the proportional hazards survival models to the analysis of an epidemiologic matched study is discussed and illustrated with numerical examples.


The synthesis of bacterial cellulose-chitosan zwitterionic hydrogels with pH responsiveness for drug release mechanism of the naproxen.
The human digestive and absorption system has a specific pH environment, which makes it difficult to for accurate drug-release. Zwitterionic hydrogel, as a kind of drug carrier, is a feasible response strategy. In this work, a facile method was employed to prepare a series zwitterionic hydrogels composed of BC and chitosan. The composite gels could in-situ formed via Schiff's base reaction between partially oxidated bacterial cellulose and chitosan which exhibited relatively well mechanical properties. Besides, the rich amino and carboxyl groups endowed the hydrogels with excellent pH responsive performance. The minimum swelling rate of the hydrogels appeared at pH 3.5-pH 5.0. In lower or higher pH solutions, the swelling rate was greatly increased. The drug (naproxen) loading of the hydrogels was above 110 mg/g. The release amount of naproxen in the simulated gastric juice was less than intestinal fluid with the sustained release time exceeded 24 h. Through kinetic simulation analysis, the drug release behavior is in accordance with zero-order release model. Such kind of composite hydrogel is suggested to be a potential drug carrier for clinical therapy.


An analysis of distribution and abundance of populations of the high-shore limpet, Notoacmea petterdi (tenison-woods).
Notoacmea petterdi occurs only on vertical surfaces at the highest levels on the shore. On a given surface, density of limpets decreases with increasing height. Mean and maximum sizes of limpets increase with increasing height, due to faster rates of growth at higher levels where densities are lower. Rates of mortality are also negatively correlated with height on the shore, and are therefore generally less at higher levels. Both adult and juvenile limpets exhibit well-developed homing behaviour. There is no evidence of seasonal migrations, density-dependent migrations, nor gradual upward migrations as limpets grow older.Hypotheses are formed on the basis of these preliminary observations and measurements. Results of subsequent experimental manipulations of densities support the hypothesis that density-dependent mortality, due to intraspecific competition, plays a major role in regulating population densities of this limpet. It is also suggested that the pattern of settlement of juvenile limpets is the major factor that determines the limits to the vertical distribution of this species.


Optimization of Verapamil drug analysis by excitation-emission fluorescence in combination with second-order multivariate calibration.
Excitation emission fluorescence matrices (EEMs) of Verapamil drug were obtained by direct and by derivatization fluorescence spectroscopy. The fluorescence excitation and emission wavelengths were displaced to longer wavelengths and the fluorescence intensity was enhanced upon derivation with respect to the native fluorescence of the drug. The complete EEM of the native fluorescence of the drug and of the derivatization product were rapidly acquired by using a charged-coupled device detector (CCD), which is advantageous in terms of speed in the analysis, with respect to the use of a conventional photomultiplier detector. The EEMs were analyzed by several second-order multivariate calibration methods exploiting the second order advantage. The three-dimensional decomposition methods used, based in different assumptions about the trilinearity of the three way data structure under analysis, were parallel factor analysis (PARAFAC), bilinear least squares (BLLS), parallel factor analysis 2 (PARAFAC2) and multivariate curve resolution-alternating least squares (MCR-ALS). The determination was performed by using the standard addition approach. The figures of merit of the PARAFAC and BLLS methods were calculated, obtaining a lower limit of detection with the derivatization procedure, when compared with the direct measurement of the fluorescence of the drug. In Verapamil drug the best estimations were found with the BLLS and the MCR-ALS models. In the quantification of Verapamil in a pharmaceutical formulation the best estimation, when compared with the result obtained by the US Pharmacopeia high performance liquid chromatography approach, was obtained by direct fluorescence spectroscopy with MCR-ALS and by derivatization fluorescence spectroscopy with the PARAFAC2 model.


Sexual function following pelvic floor surgery.
To prospectively evaluate sexual function in women who underwent surgery for incontinence and/or prolapse using the Pelvic Organ Prolapse-Urinary Incontinence Sexual Questionnaire (PISQ), and to provide a preliminary evaluation of the PISQ's psychometric properties for a population of women in the United Kingdom. Women who underwent surgery for pelvic organ prolapse and/or urinary incontinence completed the PISQ, the Sheffield Prolapse Symptoms Questionnaire, and the King's Health Questionnaire preoperatively and 4 months postoperatively. Rates of item completion were assessed to evaluate the performance of the PISQ, and Cronbach alpha values and item-total correlations were calculated for the full scale and each of the 3 domains (behavioral-emotive, physical, and partner-related). Thirty-five women responded to the questionnaire. Postoperatively an improvement was demonstrated for overall score (P=0.002), and for physical (P<0.001) and partner-related domains (P=0.004). Women reported a significant improvement in sexual function 4 months after surgery for incontinence and prolapse.


3-Hydroxy-3-methylglutaryl coenzyme A synthase. Evidence for an acetyl-S-enzyme intermediate and identification of a cysteinyl sulfhydryl as the site of acetylation.
Homogeneous liver 3-hydroxy-3-methylglutaryl coenzyme A synthase, which catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA, also carries out: (a) a rapid transacetylation from acetyl-CoA to 31-dephospho-CoA and (b) a slow hydrolysis of acetyl-CoA to acetate and CoA. Transacetylation and hydrolysis occur at 50 and 1 percent, respectively, the rate of the synthasecatalyzed condensation reaction. It appears that an acetyl-enzyme intermediate is involved in the transacetylase and hydrolase reactions of 3-hydroxy-3-methylglutaryl-CoA synthase, as well as in the over-all condensation process. Covalent binding to the enzyme of a [14C]acetyl group contributed by [1(-14)C]acetyl-CoA is indicated by migration of the [14C]acetyl group with the dissociated synthase upon electrophoresis in dodecyl sulfate-urea and by precipitation of [14C]acetyl-enzyme with trichloroacetic acid. At 0 degrees and a saturating level of acetyl-CoA, the synthase is rapidly (less than 20 s) acetylated yielding 0.6 acetyl group/enzyme dimer. Performic acid oxidation completely deacetylates the enzyme, suggesting the site of acetylation to be a cysteinyl sulfhydryl group. Proteolytic digestion of [14C]acetyl-S-enzyme under conditions favorable for intramolecular S to N acetyl group transfer quantitatively liberates a labeled derivative with a [14C]acetyl group stable to performic acid oxidation. The labeled oxidation product is identified as N-[14C]acetylcysteic acid, thus demonstrating a cysteinyl sulfhydryl group as the original site of acetylation. The ability of the acetylated enzyme, upon addition of acetoacetyl-CoA, to form 3-hydroxy-3-methylglutaryl-CoA indicates that the acetylated cysteine residue is at the catalytic site.


Differences of blink-reflex abnormalities in patients suffering from idiopathic and symptomatic trigeminal neuralgia.
We investigated the brainstem blink reflex in patients suffering from idiopathic and symptomatic trigeminal neuralgia to establish possible dysfunction in the reflex cycle and determine eventual differences between the two disease types. The study included 35 patients with idiopathic disease and seven patients with symptomatic disease, their results compared with those of 50 normal controls. We stimulated the forehead afferents of the supraorbital nerve and recorded the response from both orbicularis oculi muscles. We tested latencies of bilateral late components (R2, R2'), irritative R3 component and the incidence of R3 component. The patients with idiopathic trigeminal neuralgia showed normal parameters of blink reflex, except for the greater incidence of R3 component. Patients with symptomatic trigeminal neuralgia showed prolonged latencies of R2, R2' and R3 components when stimulating the afflicted side, but no significant difference in incidence of R3 component compared with the control group. The results indicate that abnormalities of blink reflex are significantly different in the two groups of patients. The high incidence of R3 component seems to be typical of idiopathic disease, whereas the prolonged latencies of late reflex components after stimulation of the afflicted side seem to be typical for symptomatic disease. These results suggest that testing the blink reflex may prove a significant aid in distinguishing the idiopathic and symptomatic disease types.


Hemospan improves outcome in a model of perioperative hemodilution and blood loss in the rat: comparison with hydroxyethyl starch.
Hemospan (Sangart Inc, San Diego, CA) (MP4) is a hemoglobin-based oxygen carrier consisting of human hemoglobin modified with polyethylene glycol. This study evaluated the effects of MP4 on blood volume, hemodynamics, and metabolic stability in a rat model of hemodilution and hemorrhage. MP4 was compared with hydroxyethyl starch solutions of differing concentrations (ie, HES 260/0.45 and HES 130/0.4). An open-label, randomized comparison of treatments. Pharmaceutical industry. Sprague Dawley rats. Rats underwent 50% hemodilution with one of the solutions. Control rats were not hemodiluted. Blood volume was determined at baseline and 0, 60, and 120 minutes after exchange. In separate groups, hemodilution and subsequent 60% hemorrhage were examined to determine effectiveness of hemodilution. Endpoints were blood volume after hemodilution and survival, hemodynamics, and acid-base status during hemorrhage. Volume expansion was similar with MP4 (159% of infused volume) and HES 260/0.45 (145%) and less with HES 130/0.4 (104%). The duration of expansion was longest with MP4 (1-2 hours). In the hemorrhage studies, 2-hour survival was 90% with MP4, 50% with controls, and 10% and 0% with HES 260/0.45 and HES 130/0.4, respectively. The severity of hemodynamic and acid-base changes paralleled the survival, with the least disturbance observed in MP4-treated animals. Hemodilution with MP4 was more effective in maintaining hemodynamic and metabolic stability than starch solutions or no hemodilution before simulated intraoperative hemorrhage. The benefit of MP4 is not ascribed solely to volume expansion. The results suggest that perioperative administration of MP4 may improve outcomes in surgical settings.


[Preoperative evaluation of arteriosclerotic symptoms in the lower extremities by means of intravenous digital subtraction angiography].
Intravenous DSA was performed in 106 patients with symptoms of arterial insufficiency in the lower extremities, requiring treatment according to preceding clinical examination. The examinations were carried out using a 36.5 cm (14 in.) intensifier and a 5.5 F pigtail catheter located centrally. 71% of the examinations were carried out on out-patients. No complications were observed. In 96% of the cases, the intravenous DSA provided sufficient information to make decisions about treatment.


Optic disc cupping and prematurity. Large cups as a possible low birth weight sequel.
In a previous ophthalmic study of ex-prematures around the age of 10 years it was accidentally found that cupping of the optic disc was significantly more pronounced in children of a low birth weight (less than 2000 g) than in full-term controls (Fledelius 1976). This was true for cup size (cup/disc diameter ratio) as well as depth (as indicated by a visible cribriform plate). The present analyses make up an extension of the above study, with additional calculations based on some of its data. Within the ex-prematures (n = 268) the cup size did not seem to be related to birth weight, sex, or visual acuity. Eyes with myopia of prematurity were not especially 'loaded' with large cups. For the whole sample (including the 187 full-term control there was a weak association between cup size and refraction (and axial eye length). Larger cups occurred relatively more often in myopic eyes. Possible mechanisms behind early changes in disc are discussed (astroglial hypothesis--distension of disc--loss of retinal nerve fibers). It is felt that this new observation--large disc cupping as a possible low birth weight sequel--has to be substantiated by further clinical evidence, as statistical type 1 error (mass significance) cannot be ruled out.


Studies of nicotinic acetylcholine receptor protein from rat brain. II. Partial purification.
The pharmacological specificity of the binding of 125I-labeled alpha-bungarotoxin to a 1% Emulphogene BC-720 extract of a rat brain particulate fraction has been investigated. The extract contains a component which possesses the binding characteristics of a nicotinic acetylcholine receptor protein. The crude soluble acetylcholine receptor protein was purified by affinity chromatography utilizing the alpha-neurotoxin of Naja naja siamensis as ligand and 1.0 M carbamylcholine chloride as eluant. A single, batch-wise, affinity chromatography procedure yields an average purification of 510-fold. When this purified material is treated a second time by affinity chromatography, purification as high as 12600-fold has been obtained. Binding of 125I-labeled alpha-bungarotoxin to this purified acetylcholine receptor protein is saturable with a Kd of 1 - 10(-8) M. Nicotine and acetylcholine iodide at concentrations of 10(-5) M inhibit 125I-labeled toxin-acetylcholine receptor protein complex formation by 41 and 61% respectively. At 10(-4) M, carbamylcholine chloride and (+)-tubocurarine chloride give respectively 52 and 82% inhibition. Eserine sulfate and atropine sulfate have no effect on complex formation at a concentration of 10(-4) M. These data support the isolation of a partially purified nicotinic acetylcholine receptor protein.


Woman wins claim for tax deductability of complementary/alternative medical expenses.
On 30 April 2001, the Tax Court of Canada granted judgment in favour of a Victoria woman who claimed that she should be entitled to deduct from her taxable income, as legitimate "medical expenses," her expenses for vitamin supplements and for rehabilitative therapies such as massage and therapeutic touch.


Acute bacterial meningitis among children, in Manhiça, a rural area in Southern Mozambique.
Acute bacterial meningitis (ABM) is one of the most severe diseases in Sub-Saharan Africa. Although data for the continent is very limited, more than one million cases are estimated per year, with mortality and life-long sequelae occurring in 50% of these cases. As part of the clinical management of children admitted to the Manhiça District Hospital, information on cases of ABM was recorded. We analysed data from June 1998 to November 2003. During the study period, 475 cerebrospinal-fluid (CSF) samples were collected from 20,173 children <15 years of age admitted to hospital. Culture results confirmed 71 (15%) cases of ABM. The most prevalent bacterial aetiologies were Streptotoccus pneumoniae (pneumococcus, n=31), Haemophilus influenzae (n=13) and Neisseria meningitis (n=8). Other important bacteria were Streptococcus sp. (n=7), Salmonella sp. (n=4) and Staphylococcus aureus (n=3). Crude incidence rates of ABM and pneumococcal meningitis were 20/100,000 and 10/100,000 children-year-at-risk, respectively. Incidences were more than three times higher in the <1 year age group. Overall case fatality rate was 36%, and was highest for H. influenzae and pneumococcal meningitis (55% and 45%, respectively, p=0.044). Pneumococcal susceptibility was 81% for oxacillin and 93% for chloramphenicol. For H. influenzae isolates, susceptibility was 54% for ampicillin and 62% for chloramphenicol. S. pneumoniae and H. influenzae are the main aetiologies responsible for the high burden of morbidity and mortality associated with ABM in rural Mozambique. These findings are important to evaluate treatment guidelines and potential impact of control measures.


Energetics of enzyme catalysis. I. Isotopic experiments, enzyme interconversion, and oversaturation.
An enzyme-catalyzed interconversion of one substrate, S, and one product P, by an enzyme that exists in two forms E1 and E2 where E1 binds S and E2 binds P, is considered S + E1 in equilibrium E1S in equilibrium E2P in equilibrium E2 + P. Under reversible conditions (where the concentrations of S and P are not far removed from their equilibrium values) it is shown that, in addition to the usual unsaturated and saturated behaviour there exists a third regime at high substrate concentration: the oversaturated region. In this region, the rate-limiting transition state is the interconversion of the unliganded forms of the enzyme: E1 and E2. Expressions for six different experiments involving deuterium, tritium and 14C labels are presented. By considering the results from these experiments, the nature and importance of the enzyme interconversion steps can be elucidated.


A new petunia flower colour generated by transformation of a mutant with a maize gene.
Petunia hybrida is one of the classical subjects of investigation in plants in which the pathway of anthocyanin biosynthesis has been analysed genetically and biochemically. In petunia cyanidin- and delphinidin-derivatives, but no pelargonidin-derivatives are produced as pigments. This is due to the substrate specificity of the dihydroflavonol 4-reductase of petunia, which cannot reduce dihydrokaempferol. The petunia mutant RL01, which accumulates dihydrokaempferol, shows no flower pigmentation. RL01 served as a recipient for the transfer of the A1 gene of Zea mays encoding dihydroquercetin 4-reductase, which can reduce dihydrokaempferol and thereby provided the intermediate for pelargonidin biosynthesis. Transformation of RL01 with a vector p35A1, containing the A1-complementary DNA behind the 35S promotor leads to red flowers of the pelargonidin-type. Thus a new flower pigmentation pathway has been established in these plants.


Return to theatre--experience at the Mercy Maternity Hospital, Melbourne 1971-1982.
This paper summarizes the problems which necessitated return to theatre at the Mercy Maternity Hospital, 1971-1982. There were 154 of 29,488 patients (0.5%) having obstetrical or gynaecological treatment in theatre who made this journey. They all survived, some after heroic resuscitative measures. Haemorrhage necessitated the patient's return to theatre following 0.2% of Caesarean sections and 0.2% of gynaecological operations. Many obstetric patients who return to theatre are potential maternal deaths. The assistance of an experienced colleague is essential in their management. When massive or continuing haemorrhage occurs at Caesarean section, hysterectomy should be considered, especially if the placenta appears to be morbidly adherent, these being the very patients at risk of a return to theatre if hysterectomy is not performed. With the increasing Caesarean section rate, placenta praevia accreta has become more common, to the extent that ultrasonographic localization of the placenta is recommended in all patients who have had a previous Caesarean section. Curettage is not indicated in the treatment of primary postpartum haemorrhage after Caesarean section; moreover, its performance in the management of secondary postpartum haemorrhage when the patient was delivered by Caesarean section should be regarded as a formidable procedure. When a patient who was delivered vaginally returns to theatre because of continuing haemorrhage after curettage performed for secondary postpartum haemorrhage hysterectomy is likely to be required. Safe methods of suturing the lower uterine segment incision at Caesarean section, and the lateral angles of the vaginal vault after abdominal hysterectomy are described.


Priority setting for horizon scanning of new health technologies in Denmark: views of health care stakeholders and health economists.
In the context of the establishment of a Danish Horizon Scanning System (HSS) the views of health care stakeholders and health economists were solicited by means of postal surveys on the need for adaptation of a priority setting instrument for health technology assessment (HTA). The aim was to investigate if the instrument needed adaptation for priority setting in the context of a Danish HSS and, if so, how the instrument should be changed. A literature study served to enhance interpretation of the findings of the surveys and to formulate changes in the instrument that synthesize or bridge any differing views between the two groups. The results show that the instrument should apply a health care perspective, and that technologies should be prioritised on the basis of the criteria: marginal benefits, marginal costs, budget impact, impact on access to care, and additional criteria with an impact on health policy, such as the educational needs and organisational changes associated with the new technology. The proposed changes are regarded as an intermediate step in the process of producing a fully adapted instrument that can serve as a formal support for priority setting of new health technologies for assessment in the Danish HSS.


Immune genes outside immune cells for multiple sclerosis.
In this issue of Neuron, Meijer and Agirre et al. (2022) demonstrate that immune genes exhibit a primed chromatin state in healthy oligodendroglia and are transcriptionally activated in MS through a series of epigenetic activations including histone modification deposition, transcription factor binding, and chromatin reconfiguration.


A qualitative study on the impact of COVID-19 on the behavior and attitudes of smokers and non-smokers in South Korea.
The COVID-19 pandemic has affected all aspects of human society, including education, culture, and the economy, and has also introduced changes in people's health behaviors such as drinking alcohol, nutrition intake, and practicing healthy living. This study conducted qualitative research in the Korean context to examine the changes in the smoking behavior of smokers and secondhand smoke exposure of non-smokers during the COVID-19 pandemic. Focus group interviews were conducted with 36 Korean participants (18 men and 18 women). The groups were composed of cigarette smokers, e-cigarette users, heated tobacco product users, and non-smokers. During the pandemic, it was found that there was an increase in the frequency of use, irrespective of the tobacco product, in users who refrained from social interaction and worked or studied from home. Users who continued to be socially active increased the amount used with each usage. Smokers showed a tendency to avoid smoking rooms and to smoke alone in places unoccupied by people. In addition, non-smokers' exposure to secondhand smoke did not decrease, but since non-smokers used masks, they reported more relief from the risk of exposure to secondhand smoke than before. Despite smokers being a high-risk group for COVID-19, the risk did not result in smoking cessation among smokers. Therefore, policies and educational campaigns to raise awareness about the dangers of smoking and to encourage smoking cessation are needed in the future.


P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation.
p53 immunohistochemistry (IHC) has been proposed as a surrogate for TP53 mutations in penile squamous cell carcinomas (PSCC). We aimed to evaluate the performance of a pattern-based evaluation of p53 IHC in PSCC. Human papilloma virus (HPV) DNA testing, p16 and p53 IHC, and whole exome sequencing were performed in a series of 40 PSCC. p53 IHC was evaluated following a pattern-based framework and conventional p53 IHC evaluation. Out of 40 PSCC, 12 (30.0%) were HPV-associated, and 28 (70.0%) were HPV-independent. The agreement between the p53 IHC pattern-based evaluation and TP53 mutational status was almost perfect (k = 0.85). The sensitivity and accuracy of the pattern-based framework for identifying TP53 mutations were 95.5% and 92.5%, respectively, which were higher than the values of conventional p53 IHC interpretation (54.5% and 70.0%, respectively), whereas the specificity was the same (88.9%). In conclusions, the pattern-based framework improves the accuracy of detecting TP53 mutations in PSCC compared to the classical p53 IHC evaluation.


[Age discrimination. Point of view of the professionals].
It is generally believed that legislation is an essential resource in the prevention of discriminatory behaviour against older people. This study first examines the Spanish legislation for potential age discrimination and then uses the C-EVE-D questionnaire to ask professionals in social work and health care settings the extent to what certain ageist behaviours described in the questionnaire are observed in practice. The field study was carried out with professionals in geriatrics and gerontology, who are members of Spanish Society for Geriatrics and Gerontology (SEGG). The EVE discrimination questionnaire consists of 28 items which investigate the existence of age discrimination in medical and social care contexts. A total of 174 people (63% women; mean age: 45.6 years) took part in the study, with a mean professional experience of 17.2 years. Doctors made up 59% of the sample, psychologists 19%, with the rest coming from other professions. The first 20 discrimination items of the EVE-D questionnaire were significantly positively reported by more than 60% of the sample. Although Spanish legislation, from the constitution down to the rules that govern social and health care settings, clearly prohibits any kind of discrimination with regard to age, our results show that Spanish professionals most closely involved in the care of older people perceive both direct and indirect age discrimination. Furthermore, evidence was found of prejudice in the treatment of older people as a phenomenon in day-to-day health and social services care, both when analysing medical cases and, to a greater extent, cases of a more general nature and/or relating to co-existence.


Characterization of an estuarine environment by means of an index based on intertidal macrofauna.
Macrobenthic intertidal assemblages from five Atlantic Iberian estuaries were analyzed to develop an estuarine index. An R-mode analysis revealed a close association between the isopod Cyathura carinata, the polychaete Hediste diversicolor and the bivalve Scrobicularia plana. Although these species are abundant in all the estuaries considered, they tend to be absent from sites at the marine and freshwater ends of the environmental gradient. Three different ways of calculating the estuarine index are proposed. The index is comprised in the interval [0,1] and was constructed using relative abundances rather than absolute abundances. Transformation of the raw data helped improve the performance of the index. A non-parametric statistical test is proposed for application to the estuarine index to find sites with the same values after a significant omnibus test. The index appears to be a good proxy for recognizing estuarine limits by use of indicator species.


Daily ingestion of Akkermansia mucciniphila for one month promotes healthy aging and increases lifespan in old female mice.
The ingestion of certain probiotics has been suggested as a promising nutritional strategy to improve aging. The objective of this work was to evaluate the effects of the daily intake, for a month, of a new probiotic Akkermansia muciniphila (AKK) (2 × 108 cfu/100µL PBS) on behavior, as well as function and redox state of immune cells of old female ICR-CD1 mice (OA group). For this, several behavioral tests were performed, and function and oxidative-inflammatory stress parameters of peritoneal leukocytes were analyzed in OA group, in a group of the same age that did not take AKK (old control, OC group) and in another adult control (AC) group. The results showed, in OA group, a significant improvement of several behavioral responses (coordination, balance, neuromuscular vigor, exploratory ability and anxiety like-behaviors), as well as in immune functions (chemotaxis, phagocytosis, NK activity and lymphoproliferation) and in oxidative stress parameters (glutathione peroxidase and reductase activities, oxidized glutathione and lipid oxidation concentrations) of the peritoneal leukocytes in comparison to those observed in OC group. In addition, peritoneal immune cells from the OA group released lower basal concentrations of pro-inflammatory cytokines (IL-2, IL-6 and TNF-α) compared to those from the OC group. The values of parameters in OA were similar to those in AC group. These improvements in the old mice receiving the probiotic were reflected in an increase in their lifespan. In conclusion, our data indicate that AKK supplementation for a short period could be a good nutritional strategy to promote healthy longevity.


Harvest location has a minimal impact on differences in cross-sectional area of quadriceps tendon in anterior cruciate ligament reconstruction.
Anterior cruciate ligament (ACL) reconstruction with quadriceps tendon (QT) has been gaining popularity. However, it is unknown how differences in harvest location of the QT affect its thickness and cross-sectional area (CSA). The present study aimed to clarify the differences in thickness and CSA of the QT based on location of tendon harvesting. Patients scheduled for, or who underwent, ACL reconstruction were prospectively included in the study. The short-axis images on ultrasound were used to assess the CSA of the QT at 30 and 60 mm proximal to the superior pole of the patella. QT autografts with CSAs greater than or equal to 10 mm of width were included and measured at three different locations, namely the center, medial one-third, and lateral one-third at the widest diameter of the QT. Patients with less than 10-mm width of the QT at 60 mm proximal to the superior pole of the patella were excluded. The thickness and CSA were compared based on the location of tendon harvest. Thirty-seven patients were recruited for the study. The mean thickness and CSA were larger in the center of the QT compared to the lateral one-third at 30 mm proximal to the superior pole of the patella (thickness, 6.7 ± 1.3 mm vs. 5.9 ± 1.3 mm; P = 0.009; CSA, 65.6 ± 11.4 mm2 vs. 58.8 ± 11.9 mm2; P = 0.036). There were no significant differences in thickness and CSA of the QT among the three assessment locations at 60 mm proximal to the superior pole of the patella (n.s.). The thickness and CSA of QT was greater in the center compared to the lateral one-third at 30 mm proximal to the QT insertion point. However, the difference in value was clinically non-significant, and therefore, harvest location of the QT autograft may not meaningfully impact intraoperative graft diameter. As a result, surgeons may choose the harvest location without concern for resultant graft diameter as long as the enough length of QT is secured. III.


Estimation of Doppler shift frequency using selected phase information for high frame rate color flow mapping.
We describe a new approach to processing signals used to estimate the Doppler shift frequency in high frame-rate color flow mapping with fewer pulse transmissions. When an ultrasound pulse is transmitted to a large number of scatterers, the echoes from the scatterers overlap and interfere with one another. This interference causes the phase of the received echo signal to fluctuate, thus disturbing the estimated shift in Doppler frequency. The technique proposed here eliminates this disturbed phase information, leaving the remaining information for use in estimating the shift in Doppler frequency. The instantaneous frequency of the echo signal can serve as an index of the influence of interference. To test this technique in vivo we used radio-frequency echo signals from the carotid artery for simulation and evaluated the error of the estimated Doppler shift frequency in several cases. Performance was enhanced when the number of pulses transmitted was limited and this technique was used.


A review of the toxic effects of ammonia on invertebrates in aquatic environments.
Aquatic invertebrates are the organisms most susceptible to ammonia toxicity. However, the toxic effects of ammonia on invertebrates are still poorly understood. This study reviews the research progress in ammonia toxicology for the period from 1986 to 2023, focusing on the effects on invertebrates. Through examining the toxic effects of ammonia at different levels of organization (community, individual, tissue and physiology, and molecular) as well as the results from omics studies, we determined that the most significant effects were on the reproductive capacity of invertebrates and the growth of offspring, although different populations show variation in their tolerance to ammonia, and tissues have varied potential to respond to ammonia stress. A multicomponent analysis is an in-depth technique employed in toxicological studies, as it can be used to explore the enrichment pathways and functional genes expressed under ammonia stress. This study comprehensively discusses ammonia toxicity from multiple aspects in order to provide new insights into the toxic effects of ammonia on aquatic invertebrates.


An extended clinical EEG dataset with 15,300 automatically labelled recordings for pathology decoding.
Automated clinical EEG analysis using machine learning (ML) methods is a growing EEG research area. Previous studies on binary EEG pathology decoding have mainly used the Temple University Hospital (TUH) Abnormal EEG Corpus (TUAB) which contains approximately 3,000 manually labelled EEG recordings. To evaluate and eventually even improve the generalisation performance of machine learning methods for EEG pathology, decoding larger, publicly available datasets is required. A number of studies addressed the automatic labelling of large open-source datasets as an approach to create new datasets for EEG pathology decoding, but little is known about the extent to which training on larger, automatically labelled dataset affects decoding performances of established deep neural networks. In this study, we automatically created additional pathology labels for the Temple University Hospital (TUH) EEG Corpus (TUEG) based on the medical reports using a rule-based text classifier. We generated a dataset of 15,300 newly labelled recordings, which we call the TUH Abnormal Expansion EEG Corpus (TUABEX), and which is five times larger than the TUAB. Since the TUABEX contains more pathological (75%) than non-pathological (25%) recordings, we then selected a balanced subset of 8,879 recordings, the TUH Abnormal Expansion Balanced EEG Corpus (TUABEXB). To investigate how training on a larger, automatically labelled dataset affects the decoding performance of deep neural networks, we applied four established deep convolutional neural networks (ConvNets) to the task of pathological versus non-pathological classification and compared the performance of each architecture after training on different datasets. The results show that training on the automatically labelled TUABEXB dataset rather than training on the manually labelled TUAB dataset increases accuracies on TUABEXB and even for TUAB itself for some architectures. We argue that automatically labelling of large open-source datasets can be used to efficiently utilise the massive amount of EEG data stored in clinical archives. We make the proposed TUABEXB available open source and thus offer a new dataset for EEG machine learning research.


Differential myocardial fibrosis of the systemic right ventricle and subpulmonary left ventricle after atrial switch operation for complete transposition of the great arteries.
This study aimed to assess diffuse myocardial fibrosis of the systemic right ventricle and subpulmonary left ventricle in patients after Senning or Mustard operation for complete transposition of the great artery (TGA) using cardiac magnetic resonance (CMR) T1 mapping. Thirty-one adult TGA patients after Senning (n = 24) or Mustard (n = 7) operation were studied at the age of 33.3 ± 4.0 years. Systemic right ventricular (RV) and subpulmonary left ventricular (LV) volumes, ejection fraction, and myocardial T1 values and extracellular volume fraction (ECV) were determined using CMR. The RV and LV ejection fractions were 47.0 ± 10.9% and 61.3 ± 7.4%, respectively. Compared to published normative values, patients had significantly greater RV and LV native T1 and ECV values (all p < 0.001). For each of the basal, mid, and apical segments, the LV native T1 and ECV values were significantly greater in the left than the right ventricle (all p < 0.05). There is a significant trend on progressive increase in ECV value from the basal towards the apical segments in both the right (p = 0.002) and the left (p < 0.001) ventricle. Modestly strong correlations were found between RV and LV native T1 (r = 0.60, p < 0.001) and ECV (r = 0.49, p = 0.005) values but not with ejection fractions of the respective ventricles. Differential myocardial fibrosis, with greater involvement of the subpulmonary left ventricle than the systemic right ventricle, is present in patients with TGA after atrial switch operation. Associations between the magnitude of RV and LV fibrosis suggests adverse ventricular-ventricular interaction at the cardiac extracellular matrix level.


Systematic review and meta-analysis of complications and outcomes of obese patients with burns.
Obesity has been described as a factor that contributes to poorer outcomes and more severe complications in burned patients. We thus aimed to meta-analyse the literature present regarding the extent to which obesity contributes to the prevalence of various complications in burns. We searched MEDLINE, Science Direct and Web of Science for 363 articles. Eventually, we selected only 7 articles for our analysis based on our selection criteria. Data was analysed via Review Manager 5.3, using Mantel-Haenszel statistics and random effect models. Length of stay and mortality rates were significantly different for obese patients compared to non-obese patients at a Mean Difference (MD) of 2.16 (95% CI=0.42-3.87; I2=0; p=0.01) and Odds Ratio (OR)=1.97 (95% CI=1.07-3.46; I2=65%; p=0.03) respectively. Number of wound infections, number of burn operations and length of ICU stay were not found to be statistically different. We postulate that our significant findings are due to the proinflammatory state and poorer glycemic control in obese patients. As our review was limited by the few articles currently available in the literature, it is suggested that more studies of high quality be performed to better understand the implications of obesity in burns.


Femoral nerve block using lower concentration ropivacaine preserves quadriceps strength while providing similar analgesic effects after knee arthroscopy.
Femoral nerve block (FNB) is widely used in patients undergoing knee arthroscopy. However, the most commonly used concentration of ropivacaine (0.2% or above) may cause an unexpected decrease in the muscle strength of the quadriceps. Therefore, a lower concentration of ropivacaine (0.1%) for FNB was administered to investigate the effect on quadriceps strength and postoperative pain after knee arthroscopy. This was a double-blind, randomized, controlled trial (ChiCTR2000041404). A total of 83 patients scheduled for elective knee arthroscopy were randomized to receive 0.1% or 0.2% ropivacaine for FNB under ultrasound guidance. The primary outcomes were quadriceps strength and numerical rating scale (NRS) pain score. Quadriceps strength was measured before surgery and 6 h and 24 h after surgery, while NRS score was recorded before surgery, at the postanaesthesia care unit (PACU), and 6 h and 24 h after surgery. Multiple linear regression tests were used to compare the differences in quadriceps strength and NRS score between the two groups. Two-factor analysis of variance, using the factors group and time of measurement, was used for repeated NRS scores. Secondary outcomes included knee mobility, side effects, patient satisfaction, and length of hospital stay. The mean (SD) quadriceps strength at 6 h after surgery was 7.5 (5.7) kg for the 0.1% ropivacaine group and 3.0 (4.4) kg for the 0.2% ropivacaine group. The mean difference adjusted for baseline characteristics was - 5.2 (95% CI - 7.2 to - 3.1) kg (P < 0.001). There was no significant difference between the two groups in quadriceps strength at 24 h after surgery. The mean differences in the average NRS score and maximum NRS score in the PACU were - 0.6 (P = 0.008) and - 1.0 (P < 0.001), respectively. There was no significant difference in NRS score at 6 h or 24 h after surgery. Two-factor analysis of variance showed no significant difference in the interaction factors of time and group for average NRS score and maximum NRS score. Compared with 0.2% ropivacaine, 0.1% ropivacaine for FNB preserved quadriceps strength at 6 h after knee arthroscopy while providing similar analgesic effects. I.


Multidisciplinary management of a large pheochromocytoma presenting with cardiogenic shock: a case report.
Pheochromocytoma is well-known for sudden initial presentations, particularly in younger patients. Hemodynamic instability may cause serious complications and delay a patient's ability to undergo surgical resection. Larger tumors present a further challenge because of the risk of catecholamine release during manipulations. In the case we present, increases in systemic vascular resistance caused cardiogenic shock, and the size of the lesion prompted surgeons to veer off from their usual approach. A 38-year-old female patient was admitted to our intensive care unit with hypertension and later cardiogenic shock. Profound systolic dysfunction (left ventricular ejection fraction of 0.12) was noted together with severely increased systemic vascular resistance, and gradually responded to vasodilator infusion. A left-sided 11-cm adrenal mass was found with computed tomography and confirmed a pheochromocytoma with a meta-iodo-benzyl-guanidine scintigraphy. Surgical treatment was carefully planned by the endocrinologist, anesthesiologist and surgeon, and was ultimately successful. After prolonged hemodynamic stabilization, open adrenalectomy and nephrectomy were deemed safer because of lesion size and the apparent invasion of the kidney. Surgery was successful and the patient was discharged home 5 days after surgery. She is free from disease at almost 2 years from the initial event. Large, invasive pheochromocytoma can be safely and effectively managed with open resection in experienced hands, provided all efforts are made to achieve hemodynamic stabilization and to minimize. Catecholamine release before and during surgery.


An antibiotic depleted microbiome drives severe Campylobacter jejuni-mediated Type 1/17 colitis, Type 2 autoimmunity and neurologic sequelae in a mouse model.
The peripheral neuropathy Guillain-Barré Syndrome can follow Campylobacter jejuni infection when outer core lipooligosaccharides induce production of neurotoxic anti-ganglioside antibodies. We hypothesized that gut microbiota depletion with an antibiotic would increase C. jejuni colonization, severity of gastroenteritis, and GBS. Microbiota depletion increased C. jejuni colonization, invasion, and colitis with Type 1/17 T cells in gut lamina propria. It also stimulated Type 1/17 anti-C. jejuni and -antiganglioside-antibodies, Type 2 anti-C. jejuni and -antiganglioside antibodies, and neurologic phenotypes. Results indicate that both C. jejuni strain and gut microbiota affect development of inflammation and GBS and suggest that probiotics following C. jejuni infection may ameliorate inflammation and autoimmune disease.


A Perspective of Clinical Behaviour and Management of Deep Neck Space Infections (DNSI): The Clinical Conundrum.
The diagnosis and management of deep neck space infections remain a challenging task for otolaryngologists. A retrospective observational analysis of 137 cases of deep neck infections at a tertiary care centre was reviewed. We present 137 treated cases of DNSIs in a retrospective 5 years clinical study conducted in the department of otolaryngology at a tertiary care center from January 2012 to December 2016. Demographic information, Socio-economic data, etiopathogenesis, clinical presentation, spaces involved, diagnosis, and treatment strategies, associated morbidities, course and complications were analysed and compared with past experiences. Odontogenic and salivary gland infections causes were the most common source of DNIs. Major complication observed was skin defect. In this study, submandibular space infection was found to be the most common space involved in DNSI. Pain (100%) was the most common clinical complaint followed by neck swelling (65.69%). Staphylococcus aureus (38 cases) was the most common micro-organism isolated. Surgical intervention was the main modality of treatment and there was one mortality. DNSIs are fairly common challenging and potentially lethal entities which can lead to severe complications in a very short time, should there be delay in its prompt diagnosis and management. Computerized Tomography Scan (CT scan) with contrast is the investigation of choice in diagnosing DNSIs. Assessment of airway control must take precedence.


Bacterial chromosome origins of replication.
Bacteria regulate chromosomal replication from one specific origin. We compare the regulatory requirements, DNA structures, and biochemical properties of the prototypic Escherichia coli origin with those of evolutionarily distant Bacillus subtilis and Caulobacter crescentus origins. The ubiquitous DnaA protein is a major regulator of all three bacterial origins. Unique features of these origins, however, may reflect specific regulatory requirements placed on them.


Antigenic determinant recognized by a monoclonal antibody to human myelin basic protein.
From an examination of electroimmunoblots and peptide maps, a mouse monoclonal antibody to human myelin basic protein MBP was shown to react with the amino acid sequence Ala-Ser-Asp-Tyr-Lys-Ser which is located in the C-terminal half of MBP. Although a completely different immunization schedule was used by Sires et al. (1981) they obtained a monoclonal antibody reacting with the same determinant. In contrast to results with other monoclonal antibodies to globular proteins (Todd et al. 1982) this monoclonal antibody seems to react with a sequential rather than a topographical determinant.


Melianone inhibits Secreted Aspartic Proteases (SAP), a Virulence Factor During Hyphal Formation in Candida albicans.
Candida albicans (C.-P. Robin) Berkhout, the pathogenic yeasts' ability to transform from yeast to hyphal forms in the bloodstream is essential during systemic infections. Among the several virulence factors studied, secreted aspartic proteinases (SAPs) involved in hyphal penetration are targets of putative hyphal inhibitors. Upregulation of SAP6 gene, (two-to 31- fold high) during budded to hyphal transition and lack of studies on its inhibition, prompted us to investigate this particular protein using in silico tools. Hyphal inhibition of germinating yeast cells by melianone, a triterpenoid, from Swietenia mahagoni (L.) Jacq. (Meliaceae) was observed at 0.1 μM (IC50). One of the targets of putative hyphal inhibitors, SAP, was assayed and for the first time, 50 % of the biological SAP activity was found to be inhibited by melianone at 0.125 μM. This data on SAP inhibition led us to analyse the 3-dimensional structure for SAP6 protein that was constructed through a combination of homology modelling and ab-initio method (Phyre2) and validated before performing Induced Fit Docking (IFD). Melianone formed H-bond and hydrophobic interactions with the crucial residues (ASP108, TYR160, ALA161, ASP162, ASP294, THR297, ASP379) in the catalytic site of SAP6 with a glide energy (-)54.9327 kcal/mol upon Induced Fit Docking (IFD). We report here for the first time on the SAP inhibitory ability of melianone at 0.125 uM. Being a small molecular mass inhibitor, binding with high affinity to the S3 pocket sites of SAP proteins provides evidence for pre-clinical testing of such compounds against fungal pathogens. The study is a valuable insight for further research on novel and effective inhibitors targeting SAP.


Determination of adenosine and deoxyadenosine in urine by high-performance liquid chromatography with column switching.
The means of measurement of adenosine and deoxyadenosine in urine was developed by separating adenosine and deoxyadenosine from other compounds using high-performance liquid chromatography with column switchings. This method is simple and convenient since no pretreatment of the urine is needed. Using this method, it could be demonstrated that urinary adenosine was higher in an adenosine deaminase (ADA) deficient patient who had a bone marrow transplant treatment (1.97 micromol/mmol creatinine) and in a heterozygote who had a markedly low erythrocyte ADA activity (1% of control ADA activity) (1.33 micromol/mmol creatinine) as compared to normal subjects (0.22+/-0.09 micromol/mmol creatinine, n=11). It was also noted that urinary deoxyadenosine was below the detection limits in the ADA-deficient bone marrow transplant patient, but it was detected in the heterozygote (3.7 micromol/mmol creatinine). Furthermore, it was also demonstrated that a fructose infusion increased the urinary concentration of adenosine from 0.21+/-0.03 to 2.66+/-1.21 micromol/mmol creatinine in five normal subjects.


Effects of nutrient limitation on cell growth, exopolysaccharide secretion and TEP production of Phaeocystis globosa.
Phaeocystis globosa (P. globosa) often colonizes and produces mucus, which may cause massive blooms in coastal areas. To understand mechanism of the growth and the impact factors for better control of the bloom, we conducted a laboratory experiment on the effect of nitrogen (N) or phosphorus (P) limitation on the cell growth, production of exopolysaccharide (EPS), and transparent exopolymeric particles (TEP) of P. globosa. Results show no obvious differences in the N- and/or P-limitation in TEP production, polysaccharide secretion, and colony growth of P. globosa. Particularly in the death phase of the algae growth, the TEP production level in the experiment differed significantly, and was higher in the P-limitation group than that in the N-limitation group; additionally, the P-limitation group produced a relatively higher amount of EPS than N-limitation group, with greater cellular chlorophyll-a content, and in greater photosynthetic reaction rate of P. globosa cells, than those of the N-limitation group. However, under N-limited conditions, the algae colony survived longer. Under P-limited condition, P. globosa cells spend the photosynthesis-produced substances and energy for the secretion of extracellular substances but for cell reproduction, which was indicated by P. globosa cell growth and carbon content ratio between TEP and biomass.


Preventive Effects of Long-Term Caloric Restriction on Aging Related In Vivo Bladder Dysfunction and Molecular Biological Changes in the Bladder and Dorsal Root Ganglia in Rats.
We evaluated aging related bladder dysfunctions and biological changes in the bladder and dorsal root ganglia in rats. We also investigated whether long-term caloric restriction may have preventive effects on these changes. Male Fischer 344 rats were divided into a young group (age 6 months) and an old group (age 25 to 28 months), each with free access to normal food, and an old group (age 25 to 28 months) with food restricted to 3 days per week. Conscious cystometry, cDNA microarray analysis, immunohistochemistry and oxidative stress measurements of the bladder and dorsal root ganglia were performed. The old group with free access to normal food showed higher threshold pressure, more nonvoiding contractions and lower bladder compliance than the young group with free access to food. Old rats with free access showed greater post-void residual volume and lower voiding efficiency than old rats with caloric restriction and young rats. In the old group with free access 83 genes in the bladder and 48 in the L6 dorsal root ganglia were up-regulated compared with old rats with caloric restriction and young rats. These genes were mostly related to immune and inflammatory responses. Immunohistochemistry showed stronger expression of the immune response protease Gzm (granzyme) B and the collagenase Mmp13 (matrix metalloproteinase-13) in the bladder of old rats with free access vs old rats with caloric restriction and young rats. The level of malondialdehyde, an oxidative stress marker, was higher in the bladder of old rats with free access than in young rats but there was no difference between old rats with caloric restriction and young rats with free access to food. In rats aging leads to storage and voiding dysfunctions associated with immune and inflammatory related responses in the bladder and dorsal root ganglia, and with increased oxidative stress in the bladder. Caloric restriction reduced these aging related changes.


The neutrophil-to-lymphocyte ratio as a prognostic biomarker in Guillain-Barre syndrome: a systematic review with meta-analysis.
Guillain-Barre syndrome (GBS) is an immune-mediated neuropathy. This has raised the possibility that the neutrophil-lymphocyte ratio (NLR) may be a biomarker of its activity. We conducted a systematic review and meta-analysis to summarize the evidence of NLR as a potential biomarker for GBS. We systematically searched databases (PubMed, Ovid-Medline, Embase, Scopus, Web of Science, SciELO Citation Index, LILACS, and Google Scholar) until October 2021 for studies evaluating pre-treatment NLR values in GBS patients. A meta-analysis using a random-effects model to estimate pooled effects was realized for each outcome and a narrative synthesis when this was not possible. Subgroup and sensitivity analysis were realized. GRADE criteria were used to identify the certainty of evidence for each result. Ten studies from 745 originally included were selected. Regarding GBS patients versus healthy controls, a meta-analysis of six studies (968 patients) demonstrated a significant increase in NLR values in GBS patients (MD: 1.76; 95% CI: 1.29, 2.24; I2 = 86%) with moderate certainty due to heterogeneity of GBS diagnosis criteria used. Regarding GBS prognosis, assessed by Hughes Score ≥ 3, NLR had a sensitivity between 67.3 and 81.5 and a specificity between 67.3 and 87.5 with low certainty due to imprecision, and heterogeneity. In relation to respiratory failure, NLR had a sensitivity of 86.5 and specificity of 68.2 with high and moderate certainty, respectively. With moderate certainty, mean NLR is higher in GBS patients compared to healthy controls. Furthermore, we found that NLR could be a prognostic factor for disability and respiratory failure with low and moderate certainty, respectively. These results may prove useful for NLR in GBS patients; however, further research is needed. https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021285212.


Current and future therapeutical approaches for COVID-19.
We review the evolution of our clinical understanding of COVID-19, possible therapeutic targets, and prospects for COVID-19 management.


[Release of DNA from the nuclei of hepatocytes of rats following their treatment with heparin].
The influence of heparin on the protein fractions and DNA of the isolated nuclei of hepatocytes was studied by biochemical and cytospectrophotometrical methods on Wistar rats. It was found that 0.05% sodium heparinate solution blocked 95% of the histones, not influencing the non-histone proteins of the cell nucleus. Histone blocking was connected with the DNA release into the incubation medium in the amounts proportional to the incubation period.


NAT1 genotypes do not predict response to mesalamine in patients with ulcerative colitis.
5- Aminosalicylic acid (5-ASA) is metabolised in colonic mucosa by N-acetyltransferase 1 (NAT1). Common genetic polymorphisms in this enzyme result in rapid or slow acetylation. 5-ASA treatment causes side effects in up to 10 % of patients with ulcerative colitis (UC). We therefore determined genetic variations of NAT1 in patients with UC and looked for a possible association with the clinical response to 5-ASA. DNA was obtained from 78 patients with UC. 77 % of the patients were in remission during 5-ASA treatment, whereas 23 % suffered from active disease. NAT1 genotyping was performed for 23 known alleles using RFLP and sequence analysis. Clinical response to 5-ASA was determined by medical record review and associated with NAT1 genotypes. Utilising PCR we amplified a 570-bp coding region of the human NAT1 gene in addition to 240 bp in the 3'-untranslated region (UTR). 4 NAT1 alleles previously known as NAT1*3, *4, *10 and *11 were recovered. 31 % of the patients were heterozygous and 4 % homozygous for the NAT1*10 allele. 6 % were heterozygous for the NAT1*3 allele. 6 % were heterozygous for the NAT1*11 allele. No association was found between NAT1 genotype and clinical response as well as side effects to 5-ASA in patients with UC. NAT1 genotypes do not predict response or side effects to mesalamine in patients with UC. Variations caused by non-genomic effects may be associated with the clinical response to 5-ASA.


The Change in Winter Wheat Response to Deoxynivalenol and Fusarium Head Blight Through Technological and Agronomic Progress.
Fusarium head blight (FHB) in wheat causes yield loss, quality reduction, and mycotoxin contamination in temperate wheat production areas worldwide. The objective of this study was to quantify the progress of agronomic and FHB management strategies over the past two decades in FHB suppression and agronomic performance of winter wheat in environments favorable for FHB. Field experiments were conducted in environments typical of FHB epidemics to compare common agronomic and FHB management practices used in the 1996 era compared with those used in 2016. The experiments included a comparison of three different nitrogen (N) fertilizer application rates and six old (1996-era) and new (modern-era) winter wheat cultivars representing combinations of susceptibility and era to FHB, with and without a fungicide applied at flowering (pydiflumetofen + propiconazole). To mimic environments favorable for infection (similar to 1996 in Ontario, Canada), plots were challenged at 50% anthesis with F. graminearum macroconidia suspension followed by mist irrigation. The modern management strategy of using moderately resistant cultivars, a fungicide applied at flowering, and a high rate of N fertilizer reduced total deoxynivalenol by 67%, reduced Fusarium-damaged kernels by 49%, reduced FHB index by 86%, increased grain test weight by 11%, and increased grain yield by 31% compared with the standard management practice of seeding highly susceptible cultivars with no fungicide and a lower rate of N fertilizer recommended in the 1996 era. This study enabled a published economic assessment of the return on investment for the improvements in cultivars, fungicide, and N fertilizer applications since 1996.


Beyond style guides: suggestions for better scientific English.
The benefit of publishing research in English is obvious, but so is the problem: authors with a limited knowledge of English find it difficult to compete with their proficient colleagues. In this note, we offer suggestions for improving the English of papers in the biological sciences. The suggestions aim to help authors enhance writing skills, are based on our experiences as language correctors and do not appear in major guides to scientific writing. We also argue for the need for regular publication of language tips in the pages of science journals.


Monitoring Caco-2 to enterocyte-like cells differentiation by means of electric impedance analysis on printed sensors.
Colorectal adenocarcinoma cells (Caco-2) are a widely used model of intestinal barrier to study cancer development, toxicological assessments, absorption and metabolism in food science or drug discovery. Caco-2 spontaneously differentiate into a monolayer expressing several specific characteristics, typically showed by mature enterocytes. For in vitro experiments, it is crucial to identify non-invasive and non-destructive techniques able to evaluate the integrity and differentiation of the cells monolayer. Thus, we aimed to assess these properties by analyzing electrical impedance measurements. Caco-2 cells were differentiated for 21 days. The monolayer integrity and differentiation were primarily evaluated by means of morphological, biochemical and molecular data. Impedance measurements in a range of frequencies from 400 Hz to 50 kHz were performed using a dedicated set up, including customized Aerosol Jet Printed carbon-based sensors. The trends of RI observed at three different frequencies were able to describe cell growth and differentiation. In order to evaluate which frequencies better correlate with cell differentiation, Principal Component Analysis have been employed and the concordance analysis between RI magnitude and morphological, biochemical and molecular data, highlighted 40 kHz as the optimal frequency to assess Caco-2 cells differentiation process. We demonstrated the feasibility and reliability of applying impedance-based measurements not only to provide information about the monolayer status, but also for cell differentiation monitoring. This study underlined the possibility to use a dedicated sensor to assess the integrity and differentiation of Caco-2 monolayer, as a reliable non-destructive alternative to conventional approaches.


The effect of operative position on lumbar lordosis. A radiographic study of patients under anesthesia in the prone and 90-90 positions.
The effect of intraoperative positioning on lumbar lordosis was retrospectively studied by radiographic analysis of 40 patients under general anesthesia. The aim of this study was to document changes in segmental and total lumbar lordosis between preoperative standing and intraoperative radiographs taken in the "90-90" and prone positions. Preservation of physiologic lordosis was an important consideration in reconstructive lumbar spine surgery. To avoid iatrogenic loss of lordosis when using spinal instrumentation and to facilitate decompressive procedures, it was necessary to understand how segmental alignments were affected by intraoperative positioning. Although many positioning techniques were used, the effect on lumbar lordosis was not well established. Preoperative (standing 36" lateral spine) and intraoperative radiographs (lateral lumbar spine L1 to the sacrum) in either the "90-90" position on a Hastings frame (n = 20) or the prone position on a Jackson table (n = 20) were measured twice by two independent observers using Cobb methodology for total and segmental lordosis between L1 and S1. Data were analyzed for intra- and interobserver reliability and changes in segmental and total lordosis between standing and intraoperative radiographs. Analysis of intra- and interobserver reliability revealed measurements were accurate and reproducible. The "90-90" position produced significant loss (P < or = 0.01) of total and segmental lordosis at all levels except L1-L2, which showed no change. Segmental lordosis was reduced nearly 60% at L2-L3, L3-L4, and L4-L5, and total lordosis was reduced by more than 35%. The prone position on the Jackson table increased segmental lordosis at L5-S1 by 22% (P < or = 0.01) and preserved total and segmental standing lordosis at all other levels. The "90-90" position on the Hastings frame was associated with significant reduction of total and segmental lordosis in the middle and lower lumbar spine. Positioning prone on a Jackson table maintained standing lumbar lordosis and increased lumbosacral lordosis.


Motor and extra-motor gray matter atrophy in amyotrophic lateral sclerosis: quantitative meta-analyses of voxel-based morphometry studies.
Considerable evidence from previous voxel-based morphometry studies indicates widespread but heterogeneous gray matter (GM) deficits in amyotrophic lateral sclerosis (ALS). Here, we aimed to investigate the concurrence across voxel-based morphometry studies to help clarify the spatial pattern of GM abnormalities that underlie this condition. Comprehensive meta-analyses to assess regional GM anomalies in ALS were conducted with the Anisotropic Effect Size version of Signed Differential Mapping software package. Twenty studies, which reported 22 comparisons and were composed of 454 ALS patients and 426 healthy controls, were included in the meta-analyses. Regional GM atrophy in ALS was consistently found in the frontal, temporal, and somatosensory areas. Meta-regression demonstrated that the disease duration, disease severity, and age were significantly related to GM deficits in ALS patients. The present meta-analysis provides convergent evidence that ALS is a multisystem degenerative disorder that is accompanied by a unique and widespread pattern of robust cortical GM atrophy. Future studies should investigate whether this atrophy pattern is a diagnostic and prognostic marker.


Clinical nutrition in internal medicine: An Italian survey by the scientific societies FADOI and SINPE.
Patients hospitalized in internal medicine are frequently malnourished or at risk for malnutrition. The aim of this study, conducted by the Federation of Associations of Hospital Internists (FADOI) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) was to assess the nutritional management of internal medicine inpatients in Italy, to identify critical issues and formulate practical proposals to improve nutritional treatment. From February to April 2021, FADOI and SINPE conducted a national web-based survey, including a 13 multiple-choice item questionnaire related to three key areas: screening and assessment of malnutrition and associated/overlapping sarcopenia and dysphagia; specialist consultations; and management of nutritional support. Responding to the questionnaire were 266 physicians among FADOI members (10.76%). Screening for malnutrition is performed with validated tests, within standardized care pathways, or routinely, only by 22% of participants. Global Leadership Initiative on Malnutrition criteria for diagnosis of malnutrition are little used (20%). Screening for sarcopenia was insufficient as the systematic use of assessment tools (handgrip/chair test) was minimal (3%). Screening for dysphagia is not a routine procedure for at-risk patients according to 33% of participants. Systematic involvement of clinical nutrition services/units in the management of malnourished/sarcopenic patients was reported by only 17% of internists. To overcome the critical issues that emerged from the present study, FADOI and SINPE experts proposed practical solutions to promote the application of the most recent guidelines and to improve awareness and sensitivity to nutritional management in internal medicine real-life settings.


Horse heart cytochrome c entrapped into the hydrated liquid-crystalline phases of phytantriol: X-ray diffraction and Raman spectroscopic characterization.
Small angle X-ray diffraction (SAXD), resonance Raman (RR) spectroscopy with 413 nm excitation, and non-resonance Raman technique with 785 nm excitation were used to probe the influence of entrapped cytochrome c (Cyt c) on the structure of hydrated phytantriol (Phyt) liquid-crystalline phases as well as conformational changes of heme group and secondary structure of the protein. SAXD measurements indicated that incorporation of Cyt c affects both nanostructure dimensions and type of liquid-crystalline phases of hydrated Phyt. The unit cell dimensions decrease with increasing Cyt c concentration for all phases. In addition, protein perturbs the nanostructure of Q(230) and Q(224) liquid-crystalline phases of hydrated Phyt to such an extent that they transform into the Q(229) phase with the Im3m space group. RR data revealed that entrapment of oxidized Cyt c into the Q(230) phase at 1 wt.% content results in near complete reduction of central iron ion of the heme group, while its low-spin state and six-ligand coordination configuration are preserved. Based on the analysis of heme out-of-plane folding vibration near 568 cm(-1) (γ(21)) and ν(48) mode at 633 cm(-1), it was demonstrated that the protein matrix tension on the heme group is relaxed upon incorporation of protein into Q(230) phase. Non-resonant Raman bands of difference spectra showed the preservation of α-helix secondary structure of Cyt c in the liquid-crystalline phase at relatively high (5 wt.%) content. The Cyt c induced spectroscopic changes of Phyt bands were found to be similar as decrease in temperature.