The negative impact of vitamin D on antipsychotic drug exposure may counteract its potential benefits in schizophrenia.
Patients with schizophrenia frequently show insufficient vitamin D levels, which are associated with somatic comorbidity and may contribute to psychopathology. For many reasons, vitamin D supplementation may be indicated for this patient cohort. However, there is growing evidence for a vitamin D-mediated increase of drug metabolism by induction of cytochrome P450 (CYP) 3A4. Hence, this study aimed to assess vitamin D's impact on both antipsychotic drug concentrations and psychopathology in a non-interventional manner. Totals of 107 serum concentrations of different antipsychotic drugs (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine and risperidone), 80 serum concentrations of vitamin D and psychopathological assessments were obtained from 80 patients with schizophrenia. The impact of Vitamin D on antipsychotic drug concentrations and symptomatology was assessed using a generalized linear model, path and correlation analyses. We observed a negative relationship between vitamin D and dose-adjusted antipsychotic drug concentrations, which was particularly pronounced for drugs which are predominantly metabolized via CYP3A4 (i.e., aripiprazole and quetiapine). A path analysis suggested a relieving effect of vitamin D on symptomatology which was, however, counteracted by its negative impact on antipsychotic drug levels. Finally, patients with vitamin D levels above the median exhibited a significantly higher proportion of therapeutically insufficient dose-normalized drug concentrations of aripiprazole and quetiapine. Despite vitamin D's potential benefits on physical and mental health, clinicians should be aware of its negative impact on blood concentrations of antipsychotics metabolized by CYP3A4 in patients with schizophrenia. Therefore, when considering its supplementation, therapeutic drug monitoring should be applied to guide dose adjustment.


Rapid screening for plasmid DNA.
A procedure is described for demonstrating plasmid DNA and its molecular weight, based on rate zonal centrifugation of unlabelled DNA in neutral sucrose gradients containing a low concentration of ethidium bromide. Each DNA species is then visualized as a discrete fluorescent band when the centrifuge tube is illuminated with ultra-violet light. Plasmids exist as closed circular and as relaxed circular molecules, which sediment separately, but during preparation of lysates, closed circular molecules are nicked so that each plasmid forms only a single band of relaxed circles within the gradient.


Impact of renal-replacement therapy strategies on outcomes for patients with chronic kidney disease: a secondary analysis of the STARRT-AKI trial.
To assess whether pre-existing chronic kidney disease (CKD) modified the relationship between the strategy for renal-replacement theraphy (RRT) initiation and clinical outcomes in the STARRT-AKI trial. This was a secondary analysis of a multi-national randomized trial. We included patients who had documented pre-existing estimated glomerular filtration rate (eGFR) data prior to hospitalization, and we defined CKD as an eGFR ≤ 59 mL/min/1.73 m2. The primary outcome was all-cause mortality at 90 days. Secondary outcomes included RRT dependence and RRT-free days at 90 days. We used logistic and linear regression and interaction testing to explore the effect of RRT initiation strategy on outcomes by CKD status. We studied 1121 patients who had pre-hospital measures of kidney function. Of these, 432 patients (38.5%) had CKD. The median (IQR) baseline serum creatinine was 130 (114-160) and 76 (64-90) µmol/L for those with and without CKD, respectively. Patients with CKD were older and more likely to have cardiovascular comorbidities and diabetes mellitus. Patients with CKD had higher 90-day mortality (47% vs. 40%, p < 0.001) compared to those without CKD, though this was not significant after covariate adjustment (adjusted odds ratio [aOR], 1.05; 95% CI, 0.79-1.41). Patients with CKD were more likely to remain RRT dependent at 90 days (14% vs. 8%; aOR, 1.89; 95% CI, 1.05-3.43). CKD status did not modify the effect of RRT initiation strategy on 90-day mortality. Among patients with CKD, allocation to the accelerated strategy conferred more than threefold greater odds of RRT dependence at 90 days (aOR 3.18; 95% CI, 1.41-7.91) compared with the standard strategy, whereas RRT initiation strategy had no effect on this outcome among those without CKD (aOR 0.71; 95% CI, 0.34-1.47, p value for interaction, 0.009). In this secondary analysis of the STARRT-AKI trial, an accelerated strategy of RRT initiation conferred a higher risk of 90-day RRT dependence among patients with pre-existing CKD; however, no effect was observed in the absence of CKD.


Therapeutic approaches of uncomplicated arterial hypertension in patients with COPD.
The concomitant presence of systemic arterial hypertension and chronic obstructive pulmonary disease (COPD) is frequent. Indeed, arterial hypertension is the most common comorbid disease in COPD patients. Since many antihypertensive drugs can act on airway function the treatment of arterial hypertension in COPD patients appears complex. Moreover, in these patients, a combined therapy is required for the adequate control of blood pressure. Currently, available data are inconsistent and not always comparable. Therefore the aim of this review is to analyze how antihypertensive drugs can affect airway function in order to improve the clinical management of hypertensive patients with COPD. Thiazide diuretics and calcium channel blockers appear the first-choice pharmacological treatment for these patients.


Mangiferin glycethosomes as a new potential adjuvant for the treatment of psoriasis.
Mangiferin, a natural compound isolated from Mangifera indica L, was incorporated in glycerosomes, ethosomes and alternatively in glycerol-ethanol phospholipid vesicles (glycethosomes). Actually, only glycethosomes were able to stably incorporate the mangiferin that was loaded at increasing concentrations (2, 4, 6, 8 mg/mL). The morphology, size distribution, rheological properties, surface charge and entrapment efficiency of prepared vesicles were deeply measured. All vesicles were mainly spherical, oligolamellar, small in size (~145 nm) and negatively charged (~-40 mV), as confirmed by cryo-TEM observation and dynamic laser light scattering measurements. The higher concentration of mangiferin (8 mg/mL) allowed an increase of vesicle mean diameter up to ~288 nm. The entrapment efficiency was inversely proportional to the amount of loaded mangiferin. In vitro studies performed by using human abdominal skin, underlined that, the dose-dependent ability of vesicles to promote mangiferin retention in epidermis. In addition, glycethosomes were highly biocompatible and showed a strong ability to protect in vitro the fibroblasts against damages induced by hydrogen peroxide. In vivo results underlined the superior ability of mangiferin loaded glycethosomes respect to the mangiferin dispersion to promote the heal of the wound induced by TPA, confirming their potential application for the treatment of psoriasis or other skin disorders.


Efficiency evaluation of maxillary molar distalization using Invisalign based on palatal rugae registration.
This study aimed to compare the predicted maxillary molar distalization with the achieved clinical outcome using the palatal rugae area for registration and superimposition of digital models. Understanding Invisalign efficiency may assist clinicians in predicting changes, thus applying specific measures to minimize the chance of midcourse correction later. The study sample included 38 patients with a mean age of 25.4 years, eligible for Invisalign treatment and requiring distalization of maxillary molars. Two digital models were acquired using iTero intraoral scanner (Align Technology, Santa Clara, Calif) before treatment and after maxillary first and second molar distalization. The 2 digital models were superimposed using the palatal rugae area for registration. The predicted tooth movement compared to the achieved values. One hundred forty-two maxillary molars (71 first molar and 71 second molar) were measured for distal movement, and 228 maxillary anterior teeth were evaluated for anterior anchorage loss. The predicted distal movement of the maxillary first molar (P <0.0001) and maxillary second molar (P <0.0001) differed significantly from the actual values. There was a statistically significant correlation between the amount of distal molar movement and the amount of anchorage loss (r = 0.3900, P <0.008) for the central incisor, and (r = 0.3595, P <0.013) for the lateral incisor. Invisalign can be used successfully for adult patients requiring maxillary molar distalization when a mean distalization movement of 2.6 mm was prescribed. Clinicians should be aware of the countereffect if maxillary molars are planned to move distally, especially if the patient presented initially with a large overjet, so the need to prescribe overcorrection or the use of auxiliaries can be addressed earlier.


A randomised, blinded, controlled study of the clinical relevance of matching pulse duration to thermal relaxation time when treating facial telangiectasia.
The theory of selective photo-thermolysis (SP) suggests the occurrence of optimal damage when the laser pulse duration (PD) equals the target thermal relaxation time (Tr). This study examines the clinical relevance of this theory. The study design and methods consisted of prospective, randomised, blinded, controlled study of KTP 532-nm laser treatment of 28 telangiectatic facial vessels. The PD varied from 0.13 to 1.71 times Tr (factor of 13). All vessels achieved marked improvement or clearance. The analysis of proportions reaching clearance over marked improvement for small and large calibre vessels shows a better outcome when the PD is nearer to the Tr (86% vs 57%; P = 0.09, 95% CI for difference -3% to 60%). Logistic regression analysis shows that, as the ratio of PD to Tr increases (PD near to or higher than Tr), the chance of clearing improves (P = 0.169; 95% CI 0.34 to 341). This study has shown that, for the range of vessels investigated: (1) marked improvement or clearance may be achieved using PDs that range between 0.13 and 1.71 times the Tr; and (2) it also reveals an overall trend towards a higher proportion of clearance when the PD is near to or higher than the Tr.


Functional exercise for older adults.
Australia's population is aging. Recent figures released by the Australian Bureau of Statistics indicate that by the year 2013, 3.1 million people will be over the age of 65 as compared with 2.1 million in 1993. This trend is projected to continue well into the 21st century, and has important implications for health and fitness professionals. Age related decline in muscle power predicts falls, motor impairment and disability. The author suggests that training programs should be tailored to maximise muscle power. Explosive heavy resistance training is safe and well tolerated in healthy adults even in the eighth decade of life and elicits adaptive neuromuscular changes in physiological variables that are commonly associated with the risk of falls and disability in aged individuals.


New inversion of the pair no. 3 chromosome in the black rat.
A Japanese black rat (Rattus rattus tanezumi) with a subtelocentric pair no. 3 chromosome was found in Gotenba, Japan. By comparison of the length in both members of the chromosome pair, and from the G-band pattern, the subtelocentrics seemed to have developed from the original acrocentrics by the pericentric inversion.


Construction of a rural tourism information service management system for multi-source heterogeneous data processing.
This study offers an integrated service management system for rural tourist information based on a cloud platform to address the three main issues of high platform concurrency, difficulty storing and managing data, and trouble sharing data functions. Three levels-data, process, and architecture-are considered in the analysis and design of the platform. The Hadoop data storage system makes possible the collection, storage, administration, and exchange of data functions for large amounts of heterogeneous data from many different sources by utilising Netty data transmission technology, hybrid data storage technology, and the Web Foundation. The results demonstrate that the system's response time is low, and the CPU consumption time and the average utilisation rate meet the actual needs. They resolve issues with the current rural tourism platforms application, such as the difficulty of data collection, the low rate of reuse, the low rate of sharing, the lack of timely updates, and severe island phenomena.


Artifactual urethral stricture in male child.
Artifactual urethral obstruction at the suspensory ligament of the penis may be produced if the penis is left in its normally dependent position during a urethrogram. We present 2 such cases to re-emphasize this phenomenon so that caution is taken in interpreting distal bulbous urethral strictures.


F-19848 A, a novel inhibitor of hyaluronic acid binding to cellular receptor CD44.
In the course of our screening for inhibitors of hyaluronic acid (HA) binding to cellular receptor CD44, a novel inhibitor, F-19848 A, was isolated from the cultured broth of the fungus strain Dacrymyces sp. SANK 20204. This compound inhibited the binding of CD44 and HA with an IC50 value of 23.5 microM and CD44-dependent HA degradation was inhibited with an IC50 value of 98.6 microM in a cell-based assay. The structure was elucidated by physico-chemical properties, analysis of spectral data, and decomposition experiments.


Factors determining inpatient satisfaction with care.
The objective of the study was to identify factors associated with satisfaction among inpatients receiving medical and surgical care for cardiovascular, respiratory, urinary and locomotor system diseases. Two weeks after discharge, 533 patients completed a Patient Judgments Hospital Quality questionnaire covering seven dimensions of satisfaction (admission, nursing and daily care, medical care, information, hospital environment and ancillary staff, overall quality of care and services, recommendations/intentions). Patient satisfaction and complaints were treated as dependent variables in multivariate ordinal polychotomous and dichotomous logistic stepwise regressions, respectively. Patient sociodemographic, health and stay characteristics as well as organization/ activity of service were used as independent variables. The two strongest predictors of satisfaction for all dimensions were older age and better self-perceived health status at admission. Men tended to be more satisfied than women. Other predictors specific for certain dimensions of satisfaction were: married, Karnofsky index more than 70, critical/serious self-reported condition at admission, emergency admission, choice of hospital by her/himself, stay in a medical service, stay in a private room, length of stay less than one week, stay in a service with a mean length of stay longer than one week. The factors associated with inpatient satisfaction elucidated in this study may be helpful in interpreting patient satisfaction scores when comparing hospitals, services or time periods, in targeting patient groups at risk of worse experiences and in focusing care quality programs.


High-Efficiency Low-Lead Perovskite Photovoltaics Approaching 20% Enabled by a Vacuum-Drying Strategy.
Lead-tin mixed perovskites are excellent photovoltaic materials that can be used in single- or multi-junction perovskite solar cells (PSCs). However, most high-performance Pb-Sn mixed PSCs reported to date are still Pb-dominant. It is highly demanding to develop environmentally friendly low-lead PSCs, but the poor film quality caused by the uncontrollable crystallization kinetics has been hindering the efficiency improvement of low-lead PSCs. Here, a vacuum-drying strategy in the two-step method to fabricate low-lead PSCs (FAPb0.3 Sn0.7 I3 ) with an impressive efficiency of 19.67% is employed. The vacuum treatment induces the formation of low crystalline Pb0.3 Sn0.7 I2 films containing less solvent, thus facilitating the subsequent FAI penetration and suppressing pinholes. Compared with the conventional one-step method, the two-step fabricated low-lead perovskite films with the vacuum-drying treatment exhibit a larger grain size, lower trap density, and weaker recombination loss, thus giving rise to a record-high efficiency near 20% with better thermal stability.


Halorubrum salipaludis sp. nov., isolated from the saline-alkaline soil.
A novel extremely halophilic archaeon, designated WN019T, was isolated from the natural saline-alkali wetland soil of Binhai new district, Tianjin, China. Cells of WN019T were aerobic, motile, and pleomorphic rod-shaped, 0.5-0.8 µm in width and 2.0-2.5 µm in length, and the growth occurred optimally at 33-37 °C, pH 7.5-8.0, and in the presence of 15.0-20.0% (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequence comparison showed that the isolate belonged to the genus Halorubrum and exhibited moderate sequence similarity of 97.8% to Halorubrum saccharovorum JCM 8865T. The major respiratory quinones of strain WN019T were MK-8 and MK-8 (H2), and the major polar lipids were glycolipid (GL), phospholipid (PL), phosphatidylglycerol-sulphate (PGS), phosphatidylglycerol (PG) and phosphatidylglycerol-phosphate-methyl ester (Me-PGP). The DNA G + C content of the strain was 67.4 mol%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) value based on whole genome sequences of strain WN019T and Halorubrum saccharovorum JCM 8865T were 87.5% and 35.4%, respectively. Phenotypic, chemotaxonomic, phylogenetic, and genomic analyses suggested that strain WN019T represents a novel species of the genus Halorubrum, for which the name Halorubrum salipaludis sp. nov. is proposed. The type strain is WN019T (= KCTC 4269T = ACCC 19977T).


Tear production and corneal sensitivity in diabetes.
Diabetic patients are at significant risk of developing corneal lesions such as superficial punctate keratitis, recurrent corneal erosions, persistent epithelial defects, and microbial keratitis. The aim of this study was to investigate whether diabetes mellitus is correlated with both reduced corneal sensation and reduced tear production. In 25 type II diabetic patients with a history of retinopathy only and in 25 nondiabetic control subjects (age and sex matched), we performed noncontact corneal aesthesiometry and assessed basal tear production using Schirmer's test with topical anesthesia. The noncontact corneal aesthesiometer (NCCA) is a new noninvasive device for quantifying threshold corneal sensitivity. The diabetic patients demonstrated a significantly reduced Schirmer's test result (P<.001) and significantly reduced corneal sensitivity (P<.01). Our study supports previous reports of reduced basal tear production, lending more support to the theory of a peripheral neuropathy affecting lacrimal gland function in diabetes. We also confirmed reduced threshold corneal sensitivity in diabetic patients using the NCCA.


Development of 'on-site' measurement methods for assay of plutonium isotopes.
Over the past decades, radioanalytical methods for environmental monitoring of plutonium (Pu) isotopes from contaminated soils were developed to respond in case of a nuclear accident but also for routine analyses. In this paper we prove the possibility of on-site analysis of plutonium using alpha particle spectrometry. Tests are performed with two types of soils: a "brown" soil and a "sandy" soil, both spiked with 242Pu. The proposed method starts with leaching the soil, then separating the radionuclides of interest through a TEVA column and finally preparing counting planchets for alpha-spectrometry analyses. The aim of this work was to obtain a fast and reliable procedure, from the sample preparation to the analysis, applicable directly in the field and lasting no longer than a working day. The testing involved several parameters, such as the soil-to-liquid ratio, the acid molarity, the influence of a purification step, the source preparation. For each procedure defined, the time and the recovery rates of 242Pu were recorded and compared. Results have proven that the recovery rates increase with the solid-to-liquid ratio, with the acid molarity, with the purification step but decrease with the mixing time. The two methods used for source preparation showed similar results and the sources were measured by alpha spectrometry, using two different counting devices. The final selected sample preparation procedure has a throughput of 3 h, with recovery rates of 33.8 ± 3.1% for the "brown" soil and 77.3 ± 9.2% for the "sandy" soil and is suitable for a field application.


Baked Milk and Egg Diets for Milk and Egg Allergy Management.
In baked form, cow's milk and egg are less allergenic and are tolerated by most milk- and egg-allergic children. Not only may including baked milk and egg in the diets of children who are tolerant improve nutrition and promote more social inclusion but there is also evidence that inclusion may accelerate the resolution of unheated milk and egg allergy. Further research is needed on biomarkers that can predict baked milk or egg reactivity; however, data suggest casein- and ovomucoid-specific immunoglobulin E levels may be useful. Physician-supervised introduction of baked milk and egg is recommended because anaphylaxis has occurred.


Caprazamycins, novel lipo-nucleoside antibiotics, from Streptomyces sp. II. Structure elucidation of caprazamycins.
Novel antibiotics, active against acid-fast bacteria, caprazamycins, were isolated from the culture broth of Streptomyces sp. MK730-62F2. The planar structures of the compounds were determined by 2D NMR spectroscopic study. Furthermore, the absolute structure of caprazamycin B (2) was established by NMR spectroscopy and X-ray crystallography of its degradation products and by total synthesis of the 5-amino-5-deoxy-D-ribose moiety. In the course of degradation studies of 2 under alkaline and acidic conditions, we obtained the two core components, caprazene (11) and caprazol (14), respectively, in high yield. Structurally, caprazamycins belong to a family of lipouridyl antibiotics, which have been discovered as specific inhibitors of a bacterial translocase.


A hypothetical construct to evaluate intracranial stimulation as a source of motivation.
An explanation is offered for the excessive continued responding found when intracranial stimulation is the primary source of motivation for learning. A response pattern which appears cannot be easily broken.


A unique protease responsible for selective degradation of a yolk protein in Bombyx mori. Purification, characterization, and cleavage profile.
A yolk protein, egg-specific protein, synthesized and accumulated in the developing ovaries of Bombyx mori serves not only as the nutritive source for embryogenesis but also for the reorganization of the yolk system through limited degradation. Using the purified egg-specific protein as a substrate, a protease responsible for its limited hydrolysis was identified in embryonating eggs and purified to homogeneity. The protease had an apparent molecular mass of 30,500 with one subunit of 29,000 daltons. It hydrolyzes synthetic substrates at carbonyl bonds of Arg or Lys residues, and the hydrolysis is strongly inhibited by diisopropylfluorophosphate, phenylmethanesulfonyl fluoride, and leupeptin, suggesting that it is a trypsin-like protease. The protease shows an extremely high degree (over 2,000-fold) of specificity for egg-specific protein compared to other yolk proteins. Intact egg-specific protein is cleaved into three fragments in two steps; the first releases a 8.7-kDa peptide as an end product and a 55-kDa peptide intermediate, and in the second the intermediate is cleaved into 36- and 17.2-kDa peptides. By relating the NH2-terminal amino acid sequences of these peptides to the sequence of the intact egg-specific protein, the protease was shown to cleave first at a Lys-Asn site and secondly at Arg-Asp. Proteolytic activity abruptly appears mid-way in embryogenesis and increases steeply during completion of larval differentiation.


Analogies between Drosophila and mammalian TRAF pathways.
A central event in innate immunity is the activation of the NF-kappaB signaling pathway and up-regulation of NF-kappaB-dependent defense genes. Attack of mammals as well as of insects by microorganisms leads, among other things, to the activation of receptors of the Toll-like receptor group. Various adaptor proteins involving members of the TNF receptor-associated factor (TRAF) family channel these receptor-generated signals to conserved intracellular kinase cascades that finally lead to the activation of NF-kappaB and JNK. In vertebrates, TRAF proteins link these pathways also to IL-1R-related molecules and members of the TNF receptor superfamily, which orchestrate a variety of immunoregulatory processes of the innate but also of the adaptive immune system. In this review, we will focus on the similarities but also the differences in TRAF-dependent signaling pathways of mammals and insects.


Proliferative activity and characteristics of immunocytochemically identified oligodendrocytes in embryonic mouse brain cell cultures.
Dissociated brain cell cultures of 14-day-old mouse embryos (E 14) were used for studying, during development, the proliferative activity of oligodendrocytes which express myelin basic protein (MBP) and galactocerebroside (GC). This was done using a combination of 3H-Thymidine autoradiography and immunoperoxidase or immunofluorescence. Quantitative estimates of labeled cells were made using a Leitz Texture Analysis System (T.A.S.) coupled to a P.D.P. 11-34 minicomputer. Results showed that differentiated oligodendrocytes, which express both MBP and GC, are able to proliferate. According to the intensity of the immunostaining, strong MBP positive and weak MBP positive oligodendrocytes were observed. Only the weak MBP positive cells incorporated 3H-Thymidine. The highest percentage (22.5%) of 3H-Thymidine labeled oligodendrocytes was observed at day 6 in vitro, and was reduced by half at day 9 to 13. Oligodendrocytes which have undergone a first division are still able to proliferate.


Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma.
CAR T-cells are autologous T-cells transduced with a chimeric antigen receptor which targets the modified T-cell against a specified cancer antigen. Anti-CD19 CAR T-cells currently represent transformational therapy for relapsed/refractory aggressive B-cell lymphomas where durable remissions can be induced in patients with previously incurable chemotherapy-refractory disease. Three anti-CD19 CAR T-cells are currently Food and Drug Administration and European Medicines Agency approved or in advanced-stage development: axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. Although all targeting CD19 on the surface of malignant (and healthy) B-cells, these products differ from one another in multiple ways including construct, manufacturing, dose, design of pivotal clinical trials, and toxicity profile. Efficacy and safety data for anti-CD19 CAR T-cell therapy in aggressive B-cell lymphomas will be reviewed, as well as novel CAR T-cell designs and strategies for overcoming treatment resistance.


[Infant food diversification: Is the information available on the Internet valid?].
The Internet provides easy access to information on health, but the quality and validity of this information are variable. To evaluate the quality of websites and the information provided on the timing and consequences of food diversification for infants. We analyzed the websites addressing infant food diversification that appeared on the first two pages of the search engines Google, Yahoo, and Bing. The websites were selected from four different queries. We initially assessed (a) the structure of the websites with two instruments (the Criteria for Assessing the Quality of Health Information on the Internet (HITI) and NetScoring) and (b) the presence of certification (quality label Health on the Net [HON] Code). Secondly, we evaluated the content of the websites concerning the time of introducing five classes of foods (gluten, fat, allergenic foods, solid foods, and animal protein), the duration of breastfeeding, and four potential consequences of food diversification (allergy, nutritional, autoimmune, and cardiovascular). Our repository was based on the most recent recommendations of the French Society of Pediatrics published in 2008. In all, 19 websites were included. Six of 19 websites scored above average on the two instruments (average: 131.26/312 with NetScoring and 46.73/104 with HITI). No correlation was observed between the referencing of websites analyzed and the notes obtained with both instruments. A majority of the websites analyzed were consistent with the recommendation favoring breast milk (100%), the age of introducing meat proteins (74%), and the age of introducing gluten (63%). A majority of the websites disagreed on the age of introducing solid foods (16%). As four consequences, only the risk of allergy (63%) was cited by a majority of the sites. There was a small nonsignificant correlation between the results obtained for the website about introducing solid foods and the results obtained for the websites analyzed with the NetScoring and HITI instruments (Pearson coefficient 41%, p=0.07). The websites were in partial agreement with the French recommendations. To date, the pediatrician remains the main actor in guiding parents on food diversification.


Developmental time and mortality of the reduviid bug Triatoma infestans with differential exposure to coprophagic infections with Blastocrithidia triatomae (Trypanosomatidae).
Developmental time and survival in larvae of the reduviid bug Triatoma infestans were studied in uninfected groups and in those exposed to a coprophagic infection with Blastocrithidia triatomae. Addition to young uninfected larvae of (a) different numbers of infected bugs, (b) infected and uninfected bugs, and (c) fresh or dry infectious feces were compared. Retardation of development was evident in groups given infected larvae or fresh feces. Mortality rates were correlated with infection rates and were higher in groups given more infected bugs, independent of the presence of uninfected bugs. Therefore, bugs did not discriminate between feces from infected and uninfected bugs, or they did not reject infectious feces. Dry feces had to be redissolved with fresh feces before infection was possible.


The tragedy of the uncommon: understanding limitations in the analysis of microbial diversity.
Molecular microbial community analysis methods have revolutionized our understanding of the diversity and distribution of bacteria, archaea and microbial eukaryotes. The information obtained has adequately demonstrated that the analysis of microbial model systems can provide important insights into ecosystem function and stability. However, the terminology and metrics used in macroecology must be applied cautiously because the methods available to characterize microbial diversity are inherently limited in their ability to detect the many numerically minor constituents of microbial communities. In this review, we focus on the use of indices to quantify the diversity found in microbial communities, and on the methods used to generate the data from which those indices are calculated. Useful conclusions regarding diversity can only be deduced if the properties of the various methods used are well understood. The commonly used diversity metrics differ in the weight they give to organisms that differ in abundance, so understanding the properties of these metrics is essential. In this review, we illustrate important methodological and metric-dependent differences using simulated communities. We conclude that the assessment of richness in complex communities is futile without extensive sampling, and that some diversity indices can be estimated with reasonable accuracy through the analysis of clone libraries, but not from community fingerprint data.


Innovation in lignocellulosics dewatering and drying for energy sustainability and enhanced utilization of forestry, agriculture, and marine resources - A review.
Efficient utilization of forestry, agriculture, and marine resources in various manufacturing sectors requires optimizing fiber transformation, dewatering, and drying energy consumption. These processes play a crucial role in reducing the carbon footprint and boosting sustainability within the circular bioeconomy framework. Despite efforts made in the paper industry to enhance productivity while conserving resources and energy through lower grammage and higher machine speeds, reducing thermal energy consumption during papermaking remains a significant challenge. A key approach to address this challenge lies in increasing dewatering of the fiber web before entering the dryer section of the paper machine. Similarly, the production of high-value-added products derived from alternative lignocellulosic feedstocks, such as nanocellulose and microalgae, requires advanced dewatering techniques for techno-economic viability. This critical and systematic review aims to comprehensively explore the intricate interactions between water and lignocellulosic surfaces, as well as the leading technologies used to enhance dewatering and drying. Recent developments in technologies to reduce water content during papermaking, and advanced dewatering techniques for nanocellulosic and microalgal feedstocks are addressed. Existing research highlights several fundamental and technical challenges spanning from the nano- to macroscopic scales that must be addressed to make lignocellulosics a suitable feedstock option for industry. By identifying alternative strategies to improve water removal, this review intends to accelerate the widespread adoption of lignocellulosics as feasible manufacturing feedstocks. Moreover, this review aims to provide a fundamental understanding of the interactions, associations, and bonding mechanisms between water and cellulose fibers, nanocellulosic materials, and microalgal feedstocks. The findings of this review shed light on critical research directions necessary for advancing the efficient utilization of lignocellulosic resources and accelerating the transition towards sustainable manufacturing practices.


Effects of Cr III and Pb on the bioaccumulation and toxicity of Cd in tropical periphyton communities: Implications of pulsed metal exposures.
Metal exposure pattern, timing, frequency, duration, recovery period, metal type and interactions, has obscured effects on periphyton communities in lotic systems. The objective of this study was to investigate the effects of intermittent exposures of Cr III and Pb on Cd toxicity and bioaccumulation in tropical periphyton communities. Natural periphyton communities were transferred to artificial stream chambers and exposed to metal mixtures at different pulse timing, duration, frequency and recovery periods. Chlorophyll a, dry mass and metal accumulation kinetics were recorded. Cr and Pb decrease the toxic effects of Cd on periphyton communities. Periphyton has high Cd, Cr and Pb accumulation capacity. Cr and Pb reduced the levels of Cd sequestrated by periphyton communities. The closer the frequency and duration of the pulse is to a continuous exposure, the greater the effects of the contaminant on periphyton growth and metal bioaccumulation. Light increased toxic and accumulative effects of metals on the periphyton community.


Prospective randomized comparison of endonasal endoscopic dacryocystorhinostomy and external dacryocystorhinostomy.
The advent of the rigid endonasal endoscope and the development of functional endoscopic sinus surgery (FESS) technique have awakened interest in an endonasal endoscopic dacryocystorhinostomy (EESC-DCR) in treating nasolacrimal obstruction. This prospective, randomized study compares EESC-DCR with traditional external dacryocystorhinostomy (EXT-DCR) for their success rates, surgical duration, and postoperative symptoms. Sixty-four cases in 60 patients with primary acquired nasolacrimal sac or duct obstruction were divided into two subgroups by symptoms (simple epiphora/chronic dacryocystitis). These patients were randomized within both subgroups into two operation groups. Altogether 32 EESC-DCRs and 32 EXT-DCRs were performed. The final follow-up visit was at 1 year. The patency of the lacrimal passage was investigated by irrigation and patients were questioned about their symptoms. The success rate at 1 year after surgery was 75% for EESC-DCR and 91% for EXT-DCR after primary surgery. The difference was not statistically significant (P = .18). The success rate after secondary surgery with a follow-up time of 1 year was 97% in both study groups. The average duration for EESC-DCR was 38 minutes, and 78 minutes for EXT-DCR, (P < .001). EXT-DCR, when compared with EESC-DCR, appears to give a higher, although not statistically significant, primary success rate, but the secondary success rates are equal, indicating that these two different DCR techniques are acceptable alternatives.


Effect of Calcium Ions on Dewaterability of Enzymatic-Enhanced Anaerobic Digestion Sludge.
Waste-activated sludge (WAS) solubilized remarkably after enzymatic-enhanced anaerobic digestion, but its dewaterability was deteriorated. In this study, a novel method was performed to improve the dewaterability of enzymatic-enhanced anaerobic digestion sludge by adding CaCl2 (0.01~1.00 g/g total sludge). The capillary suction time (CST), moisture content, and filtrate turbidity were employed to characterize the dewaterability of WAS, and the possible mechanisms involved were clarified. The results showed the dewaterability did not worsen when CaCl2 was added before sludge digestion, and the CST, moisture content, and filtrate turbidity were notably reduced with the increase of CaCl2 dosage. It also shown that calcium ions played an important role in the bioflocculation of digested sludge by neutralizing negative charges on the surface of sludge. In addition, soluble protein initially lowered a little and then observably improved with the addition of CaCl2, while soluble carbohydrate was reduced sharply first and then bounced back afterwards. The interactions between calcium ions and the biopolymer further enhanced the dewatering of sludge through bridging of colloidal particles together.


Specific and nonspecific humoral defense factors in the epithelium of normal and inflamed gastric mucosa. Immunohistochemical localization of immunoglobulins, secretory component, lysozyme, and lactoferrin.
Epithelial distributions of immunoglobulin A, secretory component, lysozyme, and lactoferrin were studied by paired immunofluorescence staining in ethanol-fixed biopsy specimens from gastric antral and body mucosa. Fluorescence scores were assigned semiquantitatively for the epithelium in three mucosal zones (foveolar, isthmus, and glandular). In each case, degree of inflammation was graded blindly after conventional histologic staining of serial sections. The results showed that the overall epithelial expression of local defense factors was significantly enhanced in association with gastritis, both with regard to nonspecific antimicrobial substances (lysozyme and lactoferrin) and the external transfer of immunoglobulin A (mediated by secretory component) as a potential carrier of protective antibodies. The antral isthmus and glandular zones were most active in both respects. Despite the expression of relatively large amounts of epithelial immunoglobulin A and secretory component in metaplastic glands, these elements lacked the nonspecific defense factors (except for lysozyme in Paneth cells)--even when they occurred in the antral mucosa--and may, therefore, represent particularly vulnerable areas.


Biochemical and molecular characterization of an acido-thermostable endo-chitinase from Bacillus altitudinis KA15 for industrial degradation of chitinous waste.
This paper reports the isolation and identification of an acido-thermostable chitinase (ChiA-Ba43) which was purified, from the culture liquid of Bacillus altitudinis strain KA15, and characterized. Purification of ChiA-Ba43 produced a 69.6-fold increase in the specific activity (120,000 U/mg) of the chitinase, with a yield of 51% using colloidal chitin as substrate. ChiA-Ba43 was found to be a monomeric protein with a molecular mass of 43,190.05 Da as determined by MALDI-TOF/MS. N-terminal sequence of the first 27 amino-acids (aa) of ChiA-Ba43 displayed homology to chitinases from other Bacillus species. Interestingly, ChiA-Ba43 exhibited optimum pH and temperature of 4-5.5 and 85 °C, respectively. Thin-layer chromatography (TLC) showed that the final hydrolyzed products of the enzyme from chitin-oligosaccharides and colloidal chitin are a mixture of (GlcNAc)2, (GlcNAc)3, (GlcNAc)4, and (GlcNAc)5, which indicates that ChiA-Ba43 possesses an endo-acting function. More interestingly, compared to ChiA-Mt45, ChiA-Hh59, Chitodextrinase®, N-acetyl-β-glucosaminidase®, and ChiA-65, ChiA-Ba43 demonstrated a high level of catalytic efficiency and outstanding tolerance towards various organic solvents. The chiA-Ba43 gene (1332 bp) encoding ChiA-Ba43 (409 aa) was cloned, sequenced, and expressed in Escherichia coli strain HB101. The biochemical properties of the recombinant chitinase (rChiA-Ba43) were equivalent to those of the natively expressed enzyme. These properties make ChiA-Ba43 an ideal candidate for industrial bioconversion of chitinous waste.


Photodynamic therapy pre-treated by fire needle combined with isotretinoin in the treatment of refractory perifolliculitis capitis abscedens et suffodiens: Case report.
Perifolliculitis capitis abscedens et suffodiens (PCAS) is a rare chronic inflammatory dermatosis of the scalp, which is a refractory and recrudescent disease. Symptoms of PCAS include follicular papules, suppurative nodules, cysts, sinuses, fistulas, and these usually evolve into patchy alopecia or cicatricial alopecia, which seriously affects the beauty and quality of life of patients. In this paper, we report 3 cases of PCAS each of whom received 5% 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with isotretinoin. Fire needle intervention was used as a pretreatment for ALA-PDT. All pretreatments and ALA-PDT were well tolerated. All patients showed complete clearance of skin lesions and 1 patient attained significant improvement of symptoms after 1 month of treatment. No patients had recurrence with minimum one year follow up. This suggests that topical ALA-PDT pre-treated by fire needle combined with oral isotretinoin could be an eff ;ective, non-invasive, safe method with low recurrence for PCAS.


A rare case of duodenal variceal bleeding due to extrahepatic portal vein obstruction successfully treated with endoscopic injection sclerotherapy.
Primary extra-hepatic portal vein obstruction (EHPVO) is a disease that develops ectopic varices due to portal hypertension and obstruction of the portal vein. Since bleeding from ectopic varices is life-threatening, the management of ectopic varices is important for patients with primary EHPVO. Here, we report a case of duodenal variceal bleeding in a patient with primary EHPVO. A 39-year-old man was diagnosed with F2-shaped duodenal varices (DV) due to primary EHPVO and was first treated with endoscopic variceal ligation for temporary hemostasis. We then performed angiography to understand the detailed hemodynamics and subsequently conducted endoscopic injection sclerotherapy (EIS) with a sclerosing agent containing N-butyl-2-cyanoacrylate for further hemostasis. After the treatment, dynamic computed tomography and endoscopic ultrasound revealed that the blood flow to the causative DV disappeared, although the DV itself remained. The patient was discharged without any re-bleeding or adverse events. Since treatment for DV due to primary EHPVO differs depending on hemodynamics (hepatofugal or hepatopetal blood flow), evaluating detailed hemodynamics for optimal treatment selection is crucial. Although EIS for this patient was not a radical treatment, it was effective in managing acute bleeding from the DV. This case will serve as a reference for successful treatment in future cases.


Drug-DNA recognition: energetics and implications for design.
In this article we review thermodynamic studies designed to examine the interaction of low molecular weight ligands or drugs with DNA. Over the past 10 years there has been an increase in the number of rigorous biophysical studies of DNA-drug interactions and considerable insight has been gained into the energetics of these binding reactions. The advent of high-sensitivity calorimetric techniques has meant that the energetics of DNA-drug association reactions can be probed directly and enthalpic and entropic contributions to the binding free energy established. There are two principal consequences arising from this type of work, firstly three-dimensional structures of DNA-drug complexes from X-ray and NMR studies can be put into a thermodynamic context and the energetics responsible for stabilizing the observed structures can be more fully understood. Secondly, any rational approach to structure-based drug design requires a fundamental base of knowledge where structural detail and thermodynamic data on complex formation are intimately linked. Therefore these types of studies allow a set of general guidelines to be established, which can then be used to develop drug design algorithms. In this review we describe recent breakthroughs in duplex DNA-directed drug design and also discuss how similar principles are now being used to target higher-order DNA molecules, for example, triplex (three-stranded) and tetraplex (four-stranded) structures.


Characterization of edible starch-chitosan film and its application in the storage of Mongolian cheese.
The physicochemical, mechanical, optical and structural properties based on different amylose content starch-chitosan films with the addition of hydrophilic glycerol and hydrophobic perilla oil were investigated, and the effects of the starch-chitosan coating on the physicochemical and microbial properties of Mongolian cheese were evaluated. The films were formed by casting method. Results showed that the incorporation of perilla oil resulted in a decrease in moisture content, solubility and mechanical properties and an increase in total color difference (ΔE*). High water vapor permeability (WVP), good transparency and low solubility were observed with the addition of glycerol. Meanwhile, the film based on mung bean starch-chitosan (MSC) exhibited higher moisture content, WVP values, ΔE* and less transparency than that based on water chestnut starch-chitosan (WSC). The morphology of films was also different based on MSC/WSC. The shelf life extension of Mongolian cheese was evaluated at 8 °C. The results showed that the cheese coated by WSC film containing perilla oil presented better treatment performance in terms of microbial growth delay, weight loss and shelf life length.


Sequence squeeze: an open contest for sequence compression.
Next-generation sequencing machines produce large quantities of data which are becoming increasingly difficult to move between collaborating organisations or even store within a single organisation. Compressing the data to assist with this is vital, but existing techniques do not perform as well as might be expected. The need for a new compression technique was identified by the Pistoia Alliance who commissioned an open innovation contest to find one. The dynamic and interactive nature of the contest led to some novel algorithms and a high level of competition between participants.


The use of concentrated heat after insect bites/stings as an alternative to reduce swelling, pain, and pruritus: an open cohort-study at German beaches and bathing-lakes.
Swelling, pain, and pruritus are the most relevant symptoms after insect bites/stings. Glucocorticoids and antihistamines are well established in insect sting treatment. Bite Away(®) is a CE-certified medical device of class 2A (noninvasive device intended for administration to the body, which exchanges energy with the patient in a therapeutic manner) to reduce swelling, pruritus, and pain after insect bites/stings via non-invasive administration of concentrated heat to the skin. We therefore performed a prospective, non-interventional, single-arm cohort study with 146 volunteers using the visual analog scale (VAS) for insect bites/stings to study the reduction of swelling, pruritus, and pain. Demographic data, time from insect sting to treatment, number and duration of administrations of concentrated heat, relevant symptoms, and the development of a VAS score of swelling, pruritus, and pain on baseline, after 2, 5, and 10 minutes after administration, were registered. In total 146 subjects with a mean age of 29.4 ± 20.7 years (range 2-81) were enrolled in the study. Ninety-three (63.7%) of the subjects were stung by wasps, 33 (22.6%) of the subjects were bitten by mosquitoes, and eight suffered bee stings (5.3%). VAS score swelling decreased with statistical significance after the use of Bite Away(®) from 4 before treatment to 2 and 1 after 2-5 and 10 minutes, respectively. VAS pain score was 6 before treatment, 2 after 2 minutes, 1 after 5 minutes, and 0 after 10 minutes (median). VAS pruritus score was only available for 52 (35.2%) of the patients. The score decreased from 5 before treatment, to 2 after 2 minutes, and 0 after 5 and 10 minutes. Locally administrated concentrated heat leads to fast amelioration of symptoms. Usually an absence of symptoms is noticeable 10 minutes after administration. Pain reduction is the dominant effect. Compared with alternatives of pruritus and pain treatment after insect bites/stings, Bite Away(®) seems to be the fastest treatment option available.


Thermodynamic properties of molecular borane phosphines, alane amines, and phosphine alanes and the [BH(4)(-)][PH(4)(+)], [AlH(4)(-)][NH(4)(+)], and [AlH(4)(-)][PH(4)(+)] salts for chemical hydrogen storage systems from ab initio electronic structure theory.
The heats of formation for the molecules BH(3)PH(3), BH(2)PH(2), HBPH, AlH(3)NH(3), AlH(2)NH(2), HAlNH, AlH(3)PH(3), AlH(2)PH(2), HAlPH, AlH(4)(-), PH(3), PH(4), and PH(4)(+), as well as the diatomics BP, AlN, and AlP, have been calculated by using ab initio molecular orbital theory. The coupled cluster with single and double excitations and perturbative triples method (CCSD(T)) was employed for the total valence electronic energies. Correlation consistent basis sets were used, up through the augmented quadruple-zeta, to extrapolate to the complete basis set limit. Additional d core functions were used for Al and P. Core/valence, scalar relativistic, and spin-orbit corrections were included in an additive fashion to predict the atomization energies. Geometries were calculated at the CCSD(T) level up through at least aug-cc-pVTZ and frequencies were calculated at the CCSD(T)/aug-cc-pVDZ level. The heats of formation of the salts [BH(4)(-)][PH(4)(+)](s), [AlH(4)(-)][NH(4)(+)](s), and [AlH(4)(-)][PH(4)(+)](s) have been estimated by using an empirical expression for the lattice energy and the calculated heats of formation of the two component ions. The calculations show that both AlH(3)NH(3)(g) and [AlH(4)(-)][NH(4)(+)](s) can serve as good hydrogen storage systems that release H(2) in a slightly exothermic process. In addition, AlH(3)PH(3) and the salts [AlH(4)(-)][PH(4)(+)] and [BH(4)(-)][PH(4)(+)] have the potential to serve as H(2) storage systems. The hydride affinity of AlH(3) is calculated to be -70.4 kcal/mol at 298 K. The proton affinity of PH(3) is calculated to be 187.8 kcal/mol at 298 K in excellent agreement with the experimental value of 188 kcal/mol. PH(4) is calculated to be barely stable with respect to loss of a hydrogen to form PH(3).


Dental adhesion with resin composites: a review and clinical tips for best practice.
Modern restorative dentistry would not be possible without the ability to bond to tooth structure. The development of dental adhesives has a lengthy gestation, from the beginnings around 1950, to the latest generation: modern universal adhesives, which were introduced during the 2010s. The foundation for these developments was a deeper understanding of the mechanisms of adhesion to the tooth structure, and to restoration materials. Typically, the performance of an adhesive does not depend on the use of a single ingredient, but on an overall balanced and optimised formulation that contains various components with different roles, such as functional adhesive monomers.While a wealth of literature exists on adhesives that have a long and successful clinical history ('gold standards'), some universal adhesives have also accumulated a lot of scientific evidence while offering benefits like ease of use, low technique sensitivity and versatility.To achieve reliable results with a modern adhesive, several tips should be kept in mind regardless of the product, which result in a homogeneous adhesive layer, proper cure and ultimately high bond strength. Although high performance is already achieved with the adhesives currently available, this is still an exciting area of ongoing research.


A Review of Spinal Lesions in Neurofibromatosis Type 1 in a Large Neurofibromatosis Type 1 Center.
Spinal lesions are a known manifestation of neurofibromatosis type 1 (NF1). The aim of this retrospective review was to analyze and report the prevalence of spinal lesions on imaging in a large NF1 center. The data were collected from a period of 62 months from a cohort of 514 patients. Data were collected from multidisciplinary team meeting reports that included radiologic reports of each patient investigating 20 distinct variables. The prevalence of each of these lesions was calculated, and any statistically significant associations were investigated using the χ2 test. Four-hundred forty-seven patients had classic NF1, and 67 patients had spinal NF1. Many of the patients had spinal abnormalities; 25.7% of these patients were found to have dural ectasia, whereas 44.9% of patients had a spinal deformity. A statistically significant association between dural ectasia and spinal neurofibromatosis was established (P < 0.05). An additional statically significant association was established between dural ectasia and spinal deformity (P < 0.00001). The patients with spinal nerve root tumors were identified, and it was found that 49.8% of patients possessed these tumors, whereas 56.3% of these tumors were intraspinal tumors. The most common region affected was the cervical spine, and the most common spinal level was C2. This high prevalence of spinal tumours in mobile areas of the spine is possibly the result of a combination of genetic predisposition and repeated microtraumas resulting in tumor formation. This is the largest reported study of spinal lesions in NF1 based on imaging and offers insights into the etiology and relationships between lesions.


Identification of a small-molecule inhibitor of dengue virus using a replicon system.
Dengue virus (DENV) is a mosquito-borne human pathogen that causes a serious public-health threat in tropical and subtropical regions of the world. Neither a vaccine to prevent nor an effective therapeutic agent to treat DENV infection is currently available. We established a stable cell line harboring a luciferase-reporting DENV subgenomic replicon to screen for inhibitors of DENV. A total of 14,400 small-molecule (MW < 500 Da) chemicals were evaluated for their ability to reduce luciferase reporter activity in cell lysates. One effective compound was identified from the screening. This compound was found to reduce virus production but did not block virus entry in virus-based assay. Mode-of-action analysis revealed that this inhibitor suppressed viral RNA replication but did not affect replicon translation. This compound potentially could be developed as an anti-DENV agent and might be useful for dissecting the molecular mechanism of DENV replication.


Liver disease in the HIV-infected individual.
Since the advent of effective antiretroviral therapy (ART) for human immunodeficiency virus-1 (HIV), there has been a substantial decrease in deaths related to acquired immunodeficiency syndrome (AIDS). However, in the ART era, liver disease is now the most common non-AIDS-related cause of death among HIV-infected patients, accounting for 14%-18% of all deaths in this population and almost half of deaths among hospitalized HIV-infected patients. Just as the burden of non-AIDS morbidity and mortality has changed in the ART era, the types of liver disease the clinician is likely to encounter among these patients have changed as well. This review will discuss the causes of liver disease in the HIV-infected population in the ART era, including chronic hepatitis C virus, chronic hepatitis B virus, medication-related hepatotoxicity, alcohol abuse, nonalcoholic fatty liver disease, and AIDS-related liver diseases.


Corticosterone and dexamethasone potentiate cytotoxicity associated with oxygen-glucose deprivation in organotypic cerebellar slice cultures.
Many patients display elevated levels of serum cortisol following acute ischemic stroke. Given that glucocorticoids may potentiate some forms of insult, these studies examined the effects of corticosterone or dexamethasone exposure on cytotoxicity following oxygen-glucose deprivation in the cerebellum, a brain region susceptible to stroke. In organotypic cerebellar slice cultures prepared from neonatal rat pups, 90-min of oxygen-glucose deprivation at 15 days in vitro resulted in significant cytotoxicity at 24-, 48-, and 72-h post-oxygen-glucose deprivation, as measured by uptake of propidium iodide. Exposure of cultures following oxygen-glucose deprivation to the antioxidant trolox (500 microM), but not to the glucocorticoid receptor antagonist RU486 (10 microM), completely blocked oxygen-glucose deprivation-induced cytotoxicity. Corticosterone (1 microM) or dexamethasone (10 microM) exposure alone did not significantly increase propidium iodide uptake above levels observed in control cultures. However, corticosterone or dexamethasone exposure after oxygen-glucose deprivation potentiated oxygen-glucose deprivation-mediated propidium iodide uptake at each time point. Trolox, as well as RU486, co-exposure of cultures to corticosterone or dexamethasone after oxygen-glucose deprivation abolished all cytotoxicity. In conclusion, these data demonstrated that glucocorticoid exposure modulated oxygen-glucose deprivation-mediated propidium iodide uptake, which likely involved glucocorticoid receptor activation and pro-oxidant effects.


The contribution of genetics to addiction therapy approaches.
Addictions, including alcohol dependence, which is the focus of this article, are complex genetic diseases. Recently, several individual genes that contribute to the risk for alcohol dependence have been identified, and more are expected to be in the near future. Among these are genes encoding alcohol and aldehyde dehydrogenases and GABA(A) receptor subunits. These reveal pathways of vulnerability and provide targets for rational drug design. It is likely that response to particular therapies is also a complex trait influenced by genetics, but studies to explore this are just beginning. We discuss some studies on bromocriptine, naltrexone, and serotonergic agents. Adding a genetic component to treatment trials could greatly help to understand the biological basis of variations in the efficacy of therapies and, in the future, could lead to individualized choices of therapy.


Recent developments in thyroid hormone metabolism: interpretation and significance of measurements of reverse T3, 3,3'T2, and thyroglobulin.
The development of specific radioimmunoassays has allowed measurements of 3,3',5'-triiodothyronine (reverse T3), 3,3'-diiodothyronine (3,3'T2), and thyroglobulin to be performed in serum and in various biological fluids both in normal and in altered states of thyroidal economy. The physiology, kinetics, and metabolic actions of reverse T3, 3,3'T2 and thyroglobulin are reviewed. Presently, it appears that reverse T3 and 3,3'T2 measurements in amniotic fluid and cord serum may potentially be useful in diagnosing fetal or neonatal thyroid dysfunction, and serum thyroglobulin measurements appear to be important as a measure of the efficacy of treatment of patients with differentiated thyroid carcinoma.


Crystal structure, solid state and solution conformation of 1d-1,4-di-O-[(S)-O-acetylmandeloyl]-2,3:5,6-di-O-isopropylidene-myo-inositol.
The X-ray crystal structure of 1d-1,4-di-O-[(S)-O-acetylmandeloyl]-2,3:5,6-di-O-isopropylidene-myo-inositol is described. Both inositol ring and OAM (O-acetylmandeloyl) moiety deviate from their respective ideal conformations. Inositol ring adopts a flattened chair conformation while OAM adopts an ap (antiperiplanar) conformation. A comparison of its conformation in solution with that in solid was made by the use of NOESY and anisotropic shielding effect in (1)H NMR. This conformational study revealed that the title compound adopts similar conformations in both the states.


Management of the Regional Lymph Nodes in Early-Stage Breast Cancer.
The management of regional nodes in early-stage invasive breast cancer continues to evolve. Improved systemic therapy has contributed to better local regional control, and at the same time it has drawn more attention to its importance. Axillary dissections have decreased, in part because of the increased efficacy of systemic therapy, and also because adjuvant therapy decisions are increasingly driven by biologic characterization of the tumor rather than pathologic nodal information. The trend toward less axillary surgery and a shift toward increased reliance on systemic and radiation therapy to address nodal disease has created interesting questions that were subsequently addressed in recent trials. We review the controversies in regional nodal management, the benefits of current treatment paradigms, the balance between less surgery and more radiation, and the potential tradeoffs vs toxicity.


Feeding practices of HIV-1-infected mothers: the role of counsellors.
In this issue of Acta Paediatrica, Chopra et al. report that voluntary counselling is central to preparing mothers for making a proper informed choice about adequate feeding practices to prevent their infants from acquiring HIV infection. The recommendations given and the way in which counselling is performed are the most important determinants of a mother's decision about how to feed her infant. In this article, we summarize the main arguments for and against breastfeeding by HIV-infected mothers. Further studies are needed to determine the alternatives to breastfeeding in countries where there is no access to safe formula feeding or to antiretroviral drugs. HIV-positive mothers should be made aware of the available feeding alternatives through adequate counselling from properly trained persons.


Histone deacetylase (HDAC) inhibitors and regulation of TRAIL-induced apoptosis.
Evasion of apoptosis represents a key mechanism leading to treatment resistance of human cancers. Abnormal regulation of chromatin remodeling has been implied in tumorigenesis as well as treatment resistance. Acetylation of histones represents one of the key posttranslational modifications that contribute to the regulation of chromatin remodeling. Histone acetylation is governed by the balance between enzymes that put acetyl groups on histone tails or, alternatively, remove them. Since a disturbed regulation of histone acetylation plays an important role in cancer formation and progression, a variety of histone deacetylase (HDAC) inhibitors have been developed in recent years to target aberrant HDAC activity. HDAC inhibitors also represent a promising strategy to lower the threshold of cancer cells for apoptosis induction. For example, synergistic induction of apoptosis has been documented for the concomitant use of HDAC inhibitors together with the death receptor ligand TRAIL in a panel of human cancers. Understanding the molecular mechanism that mediates this synergistic drug interaction will be critical to further optimize this approach in order to successfully translate it into a clinical setting.


Rationalisation and modification of a germ-free isolator design.
A modified design of polyvinyl chloride isolator, suitable for small laboratory animals utilises room space more effectively than previous models and is particularly useful where accommodation is restricted. The standard attachments and ancillary equipment used with other flexible isolators are compatible with the modified isolator.


A Fast and Accurate Method for Genome-wide Scale Phenome-wide G × E Analysis and Its Application to UK Biobank.
The etiology of most complex diseases involves genetic variants, environmental factors, and gene-environment interaction (G × E) effects. Compared with marginal genetic association studies, G × E analysis requires more samples and detailed measure of environmental exposures, and this limits the possible discoveries. Large-scale population-based biobanks with detailed phenotypic and environmental information, such as UK-Biobank, can be ideal resources for identifying G × E effects. However, due to the large computation cost and the presence of case-control imbalance, existing methods often fail. Here we propose a scalable and accurate method, SPAGE (SaddlePoint Approximation implementation of G × E analysis), that is applicable for genome-wide scale phenome-wide G × E studies. SPAGE fits a genotype-independent logistic model only once across the genome-wide analysis in order to reduce computation cost, and SPAGE uses a saddlepoint approximation (SPA) to calibrate the test statistics for analysis of phenotypes with unbalanced case-control ratios. Simulation studies show that SPAGE is 33-79 times faster than the Wald test and 72-439 times faster than the Firth's test, and SPAGE can control type I error rates at the genome-wide significance level even when case-control ratios are extremely unbalanced. Through the analysis of UK-Biobank data of 344,341 white British European-ancestry samples, we show that SPAGE can efficiently analyze large samples while controlling for unbalanced case-control ratios.


GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration.
Previous studies showed that the activation of Wnt signaling reduced high glucose (HG)-mediated fibroblast damage, but the molecular basis for this phenomenon remains elusive. This study aimed to analyze the level of phosphorylation of GSK3β Ser9 (pGSK3β Ser9) during HG damage. Moreover, the phosphomimic form of pGSK3β Ser9 was expressed to analyze its effect on cell migration via the phosphorylation of Ikaros. The results revealed that HG treatment significantly reduced the pGSK3β Ser9 level. The overexpression of GSK3β Ser9D and GSK3β Ser9A accelerated and inhibited fibroblast cell migration, respectively. P110α knockdown or treatment with SP600125, an inhibitor of JNK, also reduced the pGSK3β Ser9 level under HG condition. Treatment with SP600125 inhibited the migration of fibroblasts, but not in GSK3β Ser9D-expressing cells. Further, yeast two-hybrid screening and biochemical analysis identified that GSK3β interacted and phosphorylated Ikaros at Ser391. Besides, GSK3β Ser9D, but not GSK3β Ser9A, activated Ikaros Ser391 phosphorylation. Expressing Ikaros or β-catenin significantly promoted cell migration, suggesting that GSK3β modulated cell migration partially via the activation of Ikaros besides β-catenin signaling under HG condition. The expression of the phosphomimic form of Ikaros Ser391D resulted in a significant increase in the extent of cell migration compared with Ikaros under HG condition. Moreover, the Ikaros Ser391D DNA-binding affinity toward the ANXA4 promoter increased, and ANXA4 suppression promoted cell migration. In conclusion, the results of this study provided a new regulatory mechanism by which GSK3β negatively regulated human skin fibroblast cell migration.


Selective synaptic actions of thiopental and its enantiomers.
There is conflicting evidence concerning the extent to which the intravenous general anesthetic thiopental acts by enhancing inhibitory gamma-aminobutyric acid-mediated (GABAergic) synaptic transmission or by inhibiting excitatory glutamatergic transmission. Yet there are remarkably few studies on the effects of thiopental on functional synapses. In addition, the degree of stereoselectivity of thiopental acting at synapses has yet to be tested. The actions of thiopental and its enantiomers on GABAergic and glutamatergic synapses were investigated using voltage clamp techniques on microisland cultures of rat hippocampal neurons, a preparation that avoids the confounding effects of complex neuronal networks. Racemic thiopental markedly enhanced the charge transfer at GABAergic synapses without significantly affecting the peak of the postsynaptic current. At a surgically relevant concentration (25 microm), charge transfer was increased by approximately 230%. However, even at twice this concentration there were no significant effects on glutamatergic postsynaptic currents. At GABAergic synapses, thiopental acted stereoselectively, with the S(-) enantiomer being approximately twice as effective as the R(+) enantiomer at enhancing charge transfer. Thiopental stereoselectively enhances inhibitory GABAergic synaptic transmission in a way that reflects animal potencies, supporting the idea that this is a principal mode of action for this drug. The absence of any effect on glutamatergic synapses at surgically relevant concentrations suggests that the inhibition of these excitatory synapses is not an important factor in producing thiopental general anesthesia.


Feeding practice of infants and their correlates in urban areas of Beijing, China.
Optimal feeding practice in the first year of life is crucial for the survival and health of infants, and has long-term consequences in later life. However, non-optimal feeding practices exist widely. The present study aims to explore various constraints to optimal feeding practices in the first year of life of infants in urban areas of Beijing, China. A cross-sectional study was conducted in urban areas of Beijing from 4 July to 20 August, 1998. Two hundred and fifty-one mothers of infants aged 6-12 months were chosen from six child health centers in three different urban districts in Beijing. A self-administered structured questionnaire was used to collect data regarding feeding practices and potentially related factors. Feeding practice for most of the infants was in accordance with the national and international recommendations. However, the rate of incidence of exclusive breast-feeding at 3 months of age was lower than that recommended by the World Health Organisation (WHO) (55.8%), and the introduction of solid/semisolid food before 4 months of age was found in approximately 19.3% of the infants. Cow's milk was given to 21.2% of infants from 6 months of age as the sole source of milk or as a supplement. Maternal education level (OR = 2.44, 95% CI: 1.42-4.19, P < 0.05), employment (OR = 2.05, 95% CI: 1.13-3.74, P < 0.05) and antenatal nonexclusive breast-feeding plans (OR = 4.10, 95% CI: 2.24-7.50, P < 0.001) were found to be correlated to inappropriate feeding practices. The feeding practices for most of the urban infants was found to be in accordance with the Chinese government and WHO recommendations; however, non-optimal feeding practices presenting as the early cessation of breast-feeding and the introduction of solid/semisolid foods existed. Information regarding optimal feeding practices should be disseminated to mothers and medical professionals in China, to ensure optimal infant health.


Interleukin-1-induced expression of nitric oxide synthase in insulin-producing cells is preceded by c-fos induction and depends on gene transcription and protein synthesis.
The cytokine interleukin 1 beta (IL-1 beta) induces the expression of an isoform of nitric oxide synthase (NOS) in insulin-producing cells which is similar to that expressed in activated macrophages. In the present study we show that IL-1 beta-induced expression of NOS mRNA in these cells is preceded by expression of c-fos mRNA. Moreover, the stimulatory effects of recombinant IL-1 beta on NOS mRNA expression are prevented by co-incubation with an inhibitor of gene transcription (actinomycin D) or an inhibitor of protein synthesis (cycloheximide). These data suggest that IL-1 beta-induced NOS mRNA expression may be mediated by transcription of immediate early response genes, and that c-fos may be one of these genes.


Four- and five-year follow-up results from four seventh-grade smoking prevention strategies.
Recent studies have suggested that a prevention program that addresses the social influences that encourage smoking can be effective in deterring cigarette use by adolescents. This study presents 4- and 5-year follow-up results from two studies which evaluated three variations of this social influences model and compared them to a health consequences program and an existing-curriculum condition. The results suggest that a seventh-grade program, built around the social influences model and taught jointly by same-age peer leaders and local classroom teachers, may reduce 4-year weekly- and daily-smoking cumulative incidence rates, providing the first evidence for any long-term effects for the social influences model. However, the results also suggest that any long-term effects from such interventions are probably limited and may depend heavily on the manner in which the social influences model is translated during the intervention. Additional follow-up studies are needed to clarify the long-term effects of these intervention programs.


Study on the use and effectiveness of malaria preventive measures reported by employees of chinese construction companies in Western Africa in 2021.
As malaria continues to be a significant global public health concern, especially in Sub-Saharan Africa, Chinese workers in Africa are at increased risk of malaria. The effectiveness of malaria prevention measures implemented by Chinese companies and workers is a question that may correlate with the malaria infection rate in this population. This study explored the use and effectiveness of malaria prevention measures for Chinese employees in West Africa to provide a reference for companies and individuals on improving malaria prevention and control. Using a cross-sectional approach, we surveyed 256 participants in 2021, mainly from Nigeria, Mali, Côte d'Ivoire, Ghana, Guinea, Sierra Leone, and Senegal in West Africa. The survey duration is from July to the end of September 2021. We selected two companies from the 2020 ENR "World's Largest 250 International Contractors" list, which featured 6 Chinese companies, all of which are state-owned and have a 61.9% market share in Africa. The participants were Chinese workers with more than a year of work experience in construction companies in Africa. A 20-minute WeChat-based structured online questionnaire was used to obtain information on malaria infection status and malaria prevention measures. Descriptive statistical analysis, chi-square test, principal components analysis, and ordinal logistic regression analysis are used to analyze the data obtained. The difference in Statistical significance was set at P < 0.05. Ninety six (37.5%) participants contracted malaria more than once within a year. The principal components analysis found a low correlation between public and individual preventive measures. No significant correlation was found between public preventive measures and malaria infection (p > 0.05), while standardized use of mosquito nets (P = 0.016) and pesticide spraying (P = 0.047) contributed significantly to fewer malaria infections at the individual level, but the removal of vegetation around houses (P = 0.028) at the individual level related to higher malaria infection. In our sample of Chinese construction workers going to Africa, some individual preventive measures had a stronger association with malaria prevention than a variety of public environmental measures. Furthermore, individual and public preventive measures were not associated with each other. Both of these findings are surprising and require further investigation in larger and more diverse samples. This- study provides important clues about the challenges that risk reduction programs face for migrant workers from China and elsewhere.


Preoperative Simulation of the Trajectory for L5/S1 Percutaneous Endoscopic Transforaminal Discectomy: A Novel Approach for Decision-Making.
We simulated the trajectory for an L5/S1 percutaneous endoscopic transforaminal discectomy (PETD) to guide decision-making for the surgery approach. Twenty-three patients with L5/S1 lumbar disc herniation were included in the study. The patients all underwent thin-section computed tomography scans, after which data were collected for 3-dimensional reconstruction. Simulations of the trajectory for the L5/S1 PETDs were generated and the hindrance of surrounding anatomic structures was evaluated. Preoperative simulation showed that 14 patients were considered suitable for lumbar PETD. Nine patients were not considered suitable for PETD surgery according to the simulation. Factors affecting the trajectory included high iliac crest in 5 patients, L5 transverse process in 3 patients, and hypertrophic L5-S1 facet joint in 1 patient. Preoperative simulation of the trajectory for L5/S1 PETD was helpful in the decision-making for the surgical approach.


Primary care residents self assessment skills in dementia.
The ability to accurately self-assess is a critical component of professionalism and is included in the newly required Accreditation Council of Graduate Medical Education (ACGME) core competencies. To assess residents' ability to accurately self-assess their competencies related to a commonly presenting problem in geriatrics, a Standardized Patient, portraying an individual with early signs of dementia, was inserted into family medicine residents' clinic schedules. Immediately post the encounter, each resident self-assessed his/her performance using a four category (Communication, History of Present Illness, Social History, Functional Assessment), 17-item behavioral checklist. The items in each category highlighted items specific to a dementia-screening interview (e.g., HPI: Used a standardized exam which includes orientation, memory, recall and registration). Resident ratings were compared to ratings from two faculty assessors who independently viewed the videotape of each resident's SP interview. While statistically significant differences between the self-assessment and expert assessors appeared in only one of the four major checklist categories (functional assessment), item specific analysis revealed significant differences on discrete items within the dementia screening interview. Implications for teaching and assessment consistent with the ACGME required competency assessment category of professionalism are discussed.


The influence of gastrointestinal infusion of fats on regulation of food intake in pigs.
1. The influence of gastrointestinal infusions of fat on short-term and 24 h control of food intake were studied in twenty-four pigs fed twice per day and seventeen fed three times per day. The pigs were fitted with up to four catheters placed in the stomach, the duodenum, and at 2, 4 and 8 m from the ligament of Treitz. 2. Various infusions were given into the catheters beginning 30 min before the first meal (two feeds) or second meal (three feeds) of the day and continuing until the end of the feeding period or until the pigs stopped eating. 3. Infusions of a fat emulsion (Intralipid) into the stomach, of oleic acid or glycerol into the duodenum, or of glycerol into the ileum (8 m from the ligament of Treitz) inhibited food intake during the infusion according to the amount of energy infused. 4. Food intake was inhibited by more than the amount of energy infused with duodenal infusion of Intralipid or monoglyceride, or with infusion of Intralipid mixed with bile salts and lipase (but not with Intralipid alone) into 2 or 4 m from the ligament of Treitz. 5. Duodenal infusion of glycerol, and ileal (8 m from the ligament of Treitz) infusion of monoglyceride or glycerol inhibited food intake at the following meal according to the amount of energy infused. 6. It is concluded that fats can exert both pre- and post-absorptive control of food intake and that since Intralipid infusion to the stomach but not to the duodenum inhibits food intake according to the amount of energy infused, it is likely that control of food intake is related to control of stomach emptying. 7. The inhibition of food intake by more than the amount of energy infused during upper intestinal infusion of fat is likely to be a result of digestion of the fat to monoglycerides, and interaction of monoglycerides with receptors in the proximal 4 m of intestine.


Subsurface low dissolved oxygen occurred at fresh- and saline-water intersection of the Pearl River estuary during the summer period.
Estuarine oxygen depletion is one of the worldwide problems, which is caused by the freshwater-input-derived severe stratification and high nutrients loading. In this study we presented the horizontal and vertical distributions of dissolved oxygen (DO) in the Pearl River estuary, together with temperature, salinity, chlorophyll a concentration and heterotrophic bacteria abundance obtained from two cruises during the summer (wet) and winter (dry) periods of 2015. In surface water, the DO level in the summer period was lower and varied greater, as compared to the winter period. The DO remained unsaturated in the summer period if salinity is <12 and saturated if salinity is >12; while in the winter period it remained saturated throughout the estuary. In subsurface (>5m) water, the DO level varied from 0.71 to 6.65mgL-1 and from 6.58 to 8.20mgL-1 in the summer and winter periods, respectively. Particularly, we observed an area of ~1500km2 low DO zone in the subsurface water with a threshold of 4mgDOL-1 during this summer period, that located at the fresh- and saline-water intersection where is characterized with severe stratification and high heterotrophic bacteria abundance. In addition, our results indicate that spatial DO variability in surface water was contributed differently by biological and physio-chemical variables in the summer and winter periods, respectively.


[Treatment strategy for ulcerative gastrointestinal bleeding from the upper gastrointestinal tract].
The deep statistical analysis of patients treatment with the ulcerous gastroduodenal bleeding set 2 years works of Center of the gastroduodenal bleeding of Dnepropetrovsk is conducted. It is exposed, that wide application of methods of endoscopic haemostasis and endoscopic monitoring allowed substantially to reduce the amount of operations at this category of patients and improve the results.


Correction of hallux abducto valgus by scarf osteotomy. A ten-year retrospective multicentre review of patient reported outcomes shows high satisfaction rates with podiatric surgery.
Corrective surgery for hallux abducto valgus is one of the most performed elective procedures in foot and ankle practice. Numerous methods of surgical correction have been reported within the literature, with varying clinical and patient reported outcomes. This study reviews the patient experience and outcomes in five podiatric surgery centres using the scarf diaphyseal osteotomy. Patient reported outcome measures (PROMs) were captured using the Patient Satisfaction Questionnaire 10 (PSQ-10), part of the PASCOM-10 podiatric surgery audit tool. PROMs were collated across five hospital sites over a 10-year period. Of 1351 patients reported during the period, 1189 had complete retrospective data. The most common patient aim of surgery was 'no/less pain' reported in 70% of patients. 96.8% of patients reported their original foot complaint as 'better' or 'much better' after surgery. 92.8% of patients reported their expectations had been met with 96.6% reporting they would have surgery again under the same conditions. 98.5% of patients noted that the risks, complications, and expectations had been discussed prior to surgery. The most common complication was metatarsal fracture (4.6%). The scarf osteotomy (with or without an Akin phalangeal osteotomy) consistently showed high patient satisfaction with low complication rates using PSQ-10 and this information can be used as part of the pre-operative consenting process. Patient expectations for surgery were often achieved, which may be attributed to the pre-operative work up of the patient. Further investigation into this correlation is suggested. IV (retrospective review).


A comparison of HPLC and bioassay methods for plasma melanotan-II (MT-II) determination: application to a pharmacokinetic study in rats.
The pharmacokinetic profile of the melanotropic peptide, melanotan-II (MT-II), was determined in rats following a 0.3 mg kg-1 intravenous dose. Regression analysis of the plasma MT-II concentrations determined using HPLC and bioassay methods indicated the existence of a significant linear correlation (r = 0.90, p < 0.001). The plasma concentration versus time plots determined using the two assay methods yielded biphasic disposition profiles that were essentially superimposable. The following pharmacokinetic parameters were assessed from plasma concentration versus time data using both methods: Cmax, AUC, CLs, t1/2 beta, MRT, Vd beta, and Vss. Statistical comparison showed that the parameters measured by each method were not significantly different (at the 0.05 level) except for t1/2 beta, MRT and Vss. The presence of even one aberrant data point in the beta-phase can significantly influence t1/2 beta when only a few data points are available in the beta-phase. Since MRT and Vss were calculated from t1/2 beta it is not surprising that these two parameters also differed between methods.


Three practical approaches to POPULATION HEALTH.
Start now, experts advise, with strategies that marry the technical with the personal. Here's a trio of pop health approaches that may hold useful lessons for everyone.


Amelioration of lung ischemic injury with prostacyclin.
The single-flush technique of lung preservation is thought to be enhanced by prostaglandin treatment. In order to test this hypothesis, ten beagle dogs underwent thoracotomy and in situ flush perfusion of the excluded left lung with 30 ml/kg of cold, modified Euro-Collins' solution. Group 1 (n = 5) received pretreatment with 30 ng/kg/min of PGI2 by infusion and as an additive to the flush (20 micrograms/L). Group 2 (n = 5) received no PGI2 and served as controls. Following 60 min of warm ischemia, the left lung was reperfused, the contralateral lung excluded, and the animal ventilated at a fixed FiO2 of 0.4 for 4 hr. The severity of reperfusion injury was assessed by arterial oxygenation and hemodynamic measurements and, following sacrifice, by lung weight gain and bronchoalveolar lavage and ultrastructural studies. PGI2 therapy resulted in significant amelioration of reperfusion injury, with superior oxygenation at both 1 and 4 hr (PaO2 at 1 and 4 hr, respectively; PGI2: 145 mmHg +/- 17.0 and 114 +/- 11.2; no PGI2: 59 mmHg +/- 5.8 and 51 +/- 4.5; P less than 0.01 at both times), lower pulmonary vascular resistance index at 4 hr (PVRI; PGI2: 913 dynes sec cm-5m-2 +/- 91; no PGI2: 1239 +/- 68; P less than 0.05) and lower lung weight (PGI2: 76 g +/- 4; no PGI2: 146 +/- 10; P less than 0.001). Bronchoalveolar lavage studies revealed an influx of neutrophils following reperfusion that was less marked in the PGI2 group (increase in % neutrophils; PGI2: 50.4 +/- 6.7; no PGI2: 76.9 +/- 6.0; P less than 0.05). Lung injury score assessed by electron microscopy was lower in the PGI2 group (PGI2: 5.2 +/- 1.1; no PGI2; 8.1 +/- 0.5; P less than 0.05). It is concluded that PGI2 treatment is protective against ischemic lung injury in this model.


The evidence for an anomeric effect of the proton.
The significant excess in conformational free-energy at position 2 of an oxane ring and other chemical and physical properties are explained by an anomeric effect of the proton.


Stability enhancement of cytochrome c through heme deprotonation and mutations.
The chemical denaturation of Pseudomonas aeruginosa cytochrome c(551) variants was examined at pH 5.0 and 3.6. All variants were stabilized at both pHs compared with the wild-type. Remarkably, the variants carrying the F34Y and/or E43Y mutations were more stabilized than those having the F7A/V13M or V78I ones at pH 5.0 compared with at pH 3.6 by ~3.0-4.6 kJ/mol. Structural analyses predicted that the side chains of introduced Tyr-34 and Tyr-43 become hydrogen donors for the hydrogen bond formation with heme 17-propionate at pH 5.0, but less efficiently at pH 3.6, because the propionate is deprotonated at the higher pH. Our results provide an insight into a stabilization strategy for heme proteins involving variation of the heme electronic state and introduction of appropriate mutations.


A review and quantitative assessment of cattle-related thermal indices.
Many thermal indices have been developed to assess the levels of heat stress imposed on cattle during hot weather. In this paper, the 16 cattle-related thermal indices are critically reviewed. The primary emphasis is to evaluate each index's coherence to the typical heat transfer characteristics of a cow. Other perspectives including incorporated environmental parameters in the equation(s), experimental data, correlated physiological responses, heat-stress thresholds, scope of application, specific cattle breed involved, and experiment location(s) are also well categorised and discussed. The coherence evaluation indicates that the main effects of environmental parameters on heat stress have been properly reflected, while some interactions between the parameters have been treated differently. Given the variety of the equations used to define the 16 indices and the wide range of information used to develop each index, we conclude that each thermal index is distinct to an extent that it should be selected and employed carefully.


Identification of candidate genes for prostate cancer-risk SNPs utilizing a normal prostate tissue eQTL data set.
Multiple studies have identified loci associated with the risk of developing prostate cancer but the associated genes are not well studied. Here we create a normal prostate tissue-specific eQTL data set and apply this data set to previously identified prostate cancer (PrCa)-risk SNPs in an effort to identify candidate target genes. The eQTL data set is constructed by the genotyping and RNA sequencing of 471 samples. We focus on 146 PrCa-risk SNPs, including all SNPs in linkage disequilibrium with each risk SNP, resulting in 100 unique risk intervals. We analyse cis-acting associations where the transcript is located within 2 Mb (±1 Mb) of the risk SNP interval. Of all SNP-gene combinations tested, 41.7% of SNPs demonstrate a significant eQTL signal after adjustment for sample histology and 14 expression principal component covariates. Of the 100 PrCa-risk intervals, 51 have a significant eQTL signal and these are associated with 88 genes. This study provides a rich resource to study biological mechanisms underlying genetic risk to PrCa.


Comment on "Theory of the double-edge molecular technique for Doppler lidar wind measurement".
A theory of the double-edge technique for lidar measurement of wind speed Doppler shifts was recently presented by Flesia and Korb [Appl. Opt. 38, 432 (1999)]. It is shown here that the technique proposed by Flesia and Korb to achieve equal responsivity to aerosol and Rayleigh backscatter signals was previously conceived and demonstrated by another group.


Corollary discharge function in healthy controls: Evidence about self-speech and external speech processing.
As we speak, corollary discharge mechanisms suppress the auditory conscious perception of the self-generated voice in healthy subjects. This suppression has been associated with the attenuation of the auditory N1 component. To analyse this corollary discharge phenomenon (agency and ownership), we registered the event-related potentials of 42 healthy subjects. The N1 and P2 components were elicited by spoken vowels (talk condition; agency), by played-back vowels recorded with their own voice (listen-self condition; ownership) and by played-back vowels recorded with an external voice (listen-other condition). The N1 amplitude elicited by the talk condition was smaller compared with the listen-self and listen-other conditions. There were no amplitude differences in N1 between listen-self and listen-other conditions. The P2 component did not show differences between conditions. Additionally, a peak latency analysis of N1 and P2 components between the three conditions showed no differences. These findings corroborate previous results showing that the corollary discharge mechanisms dampen sensory responses to self-generated speech (agency experience) and provide new neurophysiological evidence about the similarities in the processing of played-back vowels with our own voice (ownership experience) and with an external voice.


Analysis of the Epidemiologic Characteristics of Children with Hand, Foot and Mouth Disease in China.
We aimed to investigate the epidemiological characteristics of hand, foot and mouth disease (HFMD) and provide recommendations for its control and prevention. A descriptive epidemiological analysis was designed for HFMD in children through direct network report from 2015 to 2019. From 2015 to 2019, a total 27,395 HFMD cases were reported at Infection Clinic of Shanghai Children's Hospital, Shanghai, China, accounting for 79.24% of the number of reported notifiable infectious disease cases (34,573). The cases number increased since May and reached a peak from June to September, then decreased from October to December with a second small peak in some years. The proportion of cases in boys is higher than in girls (59.7% vs. 40.3%). The cases number of stay-at-home children was higher in 2016 and 2018 (60.07% and 60.95%) than in 2019 (33.47%), and that of kindergarten children and students in 2019 (51.73% and 9.75%) was significantly higher than in other years. Overall, 22606 cases were reported in <5 years group, accounting for 82.52% of the total number of cases during 2015-2019. The proportion of the cases in 5-10 and >10 years groups increased year by year from 2015 to 2019, which is statistically significant. (χ2=71.105, P=0.00; χ2=78.413, P=0.00). The epidemiological characteristics of HFMD had changed during 2015-2019. Analysis of these data can provide helpful evidence to prevention and early treatment of the HFMD, and identification severe cases and handling the outbreaks.


Groundwater protection from cadmium contamination by permeable reactive barriers.
This work studies the reliability of an activated carbon permeable reactive barrier in removing cadmium from a contaminated shallow aquifer. Laboratory tests have been performed to characterize the equilibrium and kinetic adsorption properties of the activated carbon in cadmium-containing aqueous solutions. A 2D numerical model has been used to describe pollutant transport within a groundwater and the pollutant adsorption on the permeable adsorbing barrier (PRB). In particular, it has been considered the case of a permeable adsorbing barrier (PAB) used to protect a river from a Cd(II) contaminated groundwater. Numerical results show that the PAB can achieve a long-term efficiency by preventing river pollution for several months.


Experimental confirmation in rats of the mixed type proteinuria observed in workers exposed to cadmium.
Recently we have reported that the proteinuria developed by workers exposed to cadmium was characterized by an increased excretion of high and low molecular weight proteins. These observations were confirmed experimentally. Female rats which were injected intraperitoneally with CdCl2 (1 mg Cd2+/kg) 5 times a week developed after 2 months of treatment a proteinuria qualitatively similar to that observed in workers exposed to cadmium. The analysis of this proteinuria by electrophoresis and gel filtration revealed an increased excretion of low and high molecular weight proteins. This animal study, which confirms previous observations on man, strengthens our hypothesis that the cadmium-induced proteinuria, classically considered as a tubular type proteinuria, is in fact a mixed type proteinuria, involving not only the tubule but also the glomerulus.


Influence of pH on the dissolution of folic acid supplements.
The vitamin folic acid has received considerable attention because of its role in decreasing the risk of neural tube birth defects, and its potential role in reducing the risks of cardiovascular and psychiatric diseases. A significant concern is the quality of commercially available folic acid products. We evaluated the pharmaceutical performance of 15 currently available folic acid products in terms of meeting the USP standards for disintegration and dissolution, and showed that there has been significant improvement in the past decade in the quality of these products. However, at least one product failed to meet the requirement of each test performed. Since folic acid absorption is maximal at the proximal jejunum, dissolution was further evaluated in simulated gastric fluid. All the products failed to release more than 75% of the active ingredient in 60min. While some excipient-related factors were preliminarily considered, it was ultimately proposed that the failure may be related to the pH-dependency of the solubility of folic acid, a premise supported by faster dissolution of laboratory prepared buffered folic acid tablets. The more limited solubility of folic acid in acidic medium should be taken into consideration in the required dissolution testing methods, as well as in product formulation to optimize release.