Sunlight increases serum 25(OH) vitamin D concentration whereas 1,25(OH)2D3 is unaffected. Results from a general population study in Göteborg, Sweden (The WHO MONICA Project).
To determine serum 25-hydroxyvitamin D3 [25(OH)D3] and its 1-hydroxylated metabolite [1,25(OH)2D3] and relate them to anthropometric data, life-style habits, blood pressure and selected biochemical analytes. Random population samples of men and women. Göteborg, Sweden, population size 450,000 inhabitants. The study was performed within the framework of the WHO MONICA Project. 2000 randomly selected subjects were invited to the main MONICA screening. Out of those 1421 (71%) participated. Fifty individuals in each of four age-groups, 25-64 years, were selected at random for the present analyses (184 men and 198 women). The concentration of 25(OH)D3 was similar in both sexes whereas 1,25(OH)2D3 concentration was higher in women than in men (P = 0.01). 25(OH)D3 correlated positively to sun exposure, physical activity and negatively to intact parathyroid hormone (PTH) in both sexes, and also negatively to blood pressure in men. The remaining significant relationship for 25(OH)D3, when age and sun exposure were taken into account in multivariate analyses, was a negative correlation to intact PTH in both sexes. 1,25(OH)2D3 correlated positively to intact PTH in both men and women, negatively to height in men, positively to fibrinogen in men and positively to psychological stress and osteocalcin in women. When all variables were included in multivariate analyses 1,25(OH)2D3 concentration correlated negatively to age and positively to intact PTH and osteocalcin in both sexes together. Sunlight was the only external factor that influenced 25(OH)D3 concentration whereas 1,25(OH)2D3 was unaffected by sun exposure. 1,25(OH)2D3 was not related to environmental or life style factors but declined by age and correlated positively to intact PTH and osteocalcin. Grants from the Swedish Medical Research Council and the Swedish Heart and Lung Foundation.


Erratum to "Bullous eruption in an infant, what's your diagnosis?" [Int J Pediatr Adolesc Med 1 (2) (2014) 104-106].
[This corrects the article DOI: 10.1016/j.ijpam.2014.11.004.].


Beliefs, social normative influences, and compliance with antihypertensive medication.
We explored the relationship between beliefs and social normative influences and self-reported hypertension medication compliance using questionnaire items based on the belief intention model of Ajzen and Fishbein. Persons for whom antihypertensive medication had been prescribed were asked to agree or disagree with statements about taking their medicine. Respondents were a subset of participants in a 1980 survey of risk factors for heart disease in two Pennsylvania counties. Highly significant differences between compliant and noncompliant individuals were observed for all items except one referring to cost. A stepwise multiple logistic regression analysis was performed with age, sex, and the belief and social normative items as independent variables, and reported compliance as the dependent variable. Three variables, age, "taking my blood pressure medicine as the doctor told me would not be necessary when my blood pressure is normal," and "your family wants you to take your blood pressure medicine as the doctor told you," entering into the equation in that order, significantly improved discrimination between compliant and noncompliant persons. The questionnaire's success may have resulted from moving beyond assessing participant's knowledge or beliefs about hypertension in the abstract to ascertaining the direct relevance of these beliefs to their taking their medicine.


Maternal BCG primes for enhanced health benefits in the newborn.
Bacille Calmette-Guérin (BCG) vaccination lowers the risk of severe infection; we tested whether effects are modulated by maternal BCG in a large cohort of BCG-vaccinated newborns from Guinea-Bissau. Maternal BCG scar status were inspected at enrolment in a BCG trial conducted from 2014 to 17 in Bissau, Guinea-Bissau. We tested associations with background factors for potential confounding; maternal age affected effect estimates >5% and accordingly, all analyses were adjusted for maternal age. Hospitalization data was collected prospectively and assessed in Cox-models providing adjusted Incidence Rate Ratios (aIRRs). In-hospital risk of death (case-fatality) risk was assessed using binomial regression providing adjusted Risk Ratios (aRRs). 60% (6,309/10,598) of mothers had a scar. The maternal-scar/no-scar admission aIRR was 0.96 (0.81-1.14) from 0 to 6 weeks and 1.12 (0.97-1.28) for 6 weeks-3 years. The 6-week in-hospital case-fatality infection aRR was 0.59 (0.34-1.05); 0.40 (0.17-0.91) for males and 0.86 (0.38-1.94) for females. Protection was especially evident against sepsis, the overall 6-week aRR=0.49 (0.26-0.91); no effect was observed for non-infectious deaths or after 6 weeks of age. Effects were similar across BCG strains and multivariate models adjusted for socioeconomic status did not affect estimates. Among BCG-vaccinated newborns, there was a trend for fewer in-hospital deaths from infection associated with maternal BCG priming, especially for males. Providing BCG to adults without a vaccination scar might enhance their offspring's capacity to handle severe infections. Brief 40-word summary: Within a trial comparing BCG strains for their overall effects on morbidity and mortality in Guinea-Bissau, vertical priming with BCG (represented by the maternal BCG scar) was associated with beneficial sex-differential effects on offspring survival.


Triiodothyronine attenuates neurocognitive dysfunction induced by sevoflurane in the developing brain of neonatal rats.
Whilst concerns have been raised about the detrimental effects of general anaesthetics on the brain's development and function in the young, reports have indicated that thyroid hormones are able to promote neurogenesis in the developing brain. This present study aimed to investigate the effects of triiodothyronine (T3) on the neonatal rat brain, following sevoflurane exposure. Postnatal day 7 (P7) ratpups were treated with Triiodothyronine (T3) (1 µg/100 g body weight, i.p. injection, once/day for 3 days) after 2% sevoflurane exposure for 6 h. They were sacrificed at either P7 (immediately), P15 or P30 and their brains were harvested to assess cell death, proliferation in the hippocampus, N-methyl-D-aspartate (NMDA) receptor subunit A and B, and a post-synaptic protein (PSD-95 in the hippocampus,). Neuro-behavioral changes in other cohorts between P27 and P30 were evaluated with Morris water maze and open field tests. Sevoflurane exposure caused cell death and suppressed the proliferation of astrocytes and neurons, as well as the dendritic growth of neurons in the hippocampus which were all reversed by the administration of T3. Moreover, cognitive function, including learning, memory, and adaptability to a new environment, were impaired by sevoflurane exposure, which was also negated by T3 treatment. Furthermore, sevoflurane decreased the expression of NMDA receptor subunits NR2A and NR2B, as well as PSD-95 in the hippocampus at P15 and those effects of sevoflurane were abolished by T3 administration. A potential therapeutic role of T3 in protecting general anesthetic induced neuronal injury in the developing brain is likely to occur through enhancing expression of PSD-95 and the NMDA NR2A and NR2B expression.


Impact of microbubble-enhanced ultrasound on liver ethanol ablation.
Ethanol ablation (EA) is a safe and effective method for treating small liver cancer. However, the ethanol is rapidly washed out by blood perfusion, preventing its accumulation within tumors. Microbubble-enhanced ultrasound (MEUS) is capable of disrupting tumor and liver circulation. We hypothesized that this disruption could be used to enhance EA of normal liver tissue. We treated surgically exposed rabbit liver with a combination of MEUS and EA. The controls were treated with only MEUS or 0.05 mL EA. MEUS treatment was administered with a high-pressure-amplitude, pulsed therapeutic ultrasound device and intra-venous injection of microbubbles. Therapeutic ultrasound was delivered at an acoustic pressure of 4.3 MPa and a duty cycle of 0.22%. Contrast-enhanced ultrasound was performed to estimate liver blood perfusion. Livers were harvested for necrotic volume measurements 48 h after treatment. Contrast-enhanced ultrasound demonstrated that liver perfusion was temporally arrested, with a significant peak intensity decline from -46.9 ± 3.8 to -64.0 ± 3.3 dB, after MEUS treatment. The mean volume ablated in MEUS + EA-treated livers (3.3 ± 2.3 cm(3)) was more than 10 times larger than that in livers treated only with EA (0.3 ± 0.2 cm(3)). The volume of liver ablated by MEUS treatment alone was minor, scattered and immeasurable. These results indicate that MEUS disruption of the liver circulation can greatly promote EA of liver.


Piezoelectric and pyroelectric effects induced by interface polar symmetry.
Interfaces in heterostructures have been a key point of interest in condensed-matter physics for decades owing to a plethora of distinctive phenomena-such as rectification1, the photovoltaic effect2, the quantum Hall effect3 and high-temperature superconductivity4-and their critical roles in present-day technical devices. However, the symmetry modulation at interfaces and the resultant effects have been largely overlooked. Here we show that a built-in electric field that originates from band bending at heterostructure interfaces induces polar symmetry therein that results in emergent functionalities, including piezoelectricity and pyroelectricity, even though the component materials are centrosymmetric. We study classic interfaces-namely, Schottky junctions-formed by noble metal and centrosymmetric semiconductors, including niobium-doped strontium titanium oxide crystals, niobium-doped titanium dioxide crystals, niobium-doped barium strontium titanium oxide ceramics, and silicon. The built-in electric field in the depletion region induces polar structures in the semiconductors and generates substantial piezoelectric and pyroelectric effects. In particular, the pyroelectric coefficient and figure of merit of the interface are over one order of magnitude larger than those of conventional bulk polar materials. Our study enriches the functionalities of heterostructure interfaces, offering a distinctive approach to realizing energy transduction beyond the conventional limitation imposed by intrinsic symmetry.


The Role of Medical Conditions and Depression in the Functional Outcome of Stroke Survivors: A Review and Pilot Study.
This study is a secondary analysis conducted to describe the population of medically ill people who have had a stroke in terms of functional outcome over time. Functional outcome did not differ between stroke survivors with medical illness and those without medical illness at the two time periods studied. However, there was a difference in functional outcome over time between stroke survivors with medical illness who were depressed and those who were not.


The simultaneous removal of calcium and chloride ions from calcium chloride solution using magnesium-aluminum oxide.
We investigated the removal of Ca(2+) and Cl(-) from CaCl(2) solution at 20-60 degrees C, using magnesium-aluminum oxide, Mg(0.80)Al(0.20)O(1.10), prepared by the thermal decomposition of a hydrotalcite-like compound, Mg(0.80)Al(0.20)(OH)(2)(CO(3))(0.10).0.78 H(2)O. The degree of Ca(2+) and Cl(-) removal from the solution increased with increasing initial CaCl(2) concentration, temperature, and quantity of Mg(0.80)Al(0.20)O(1.10) added. When Mg(0.80)Al(0.20)O(1.10) was added to 0.25 M CaCl(2) solution in a Mg(0.80)Al(0.20)O(1.10)/CaCl(2) molar ratio of 20, the degree of Ca(2+) and Cl(-) removal from the solution at 60 degrees C after 0.5 h was 93.0% and 98.2%, respectively. These results reveal that Mg(0.80)Al(0.20)O(1.10) has the capacity to remove Ca(2+) and Cl(-) simultaneously from aqueous solution.


Bacteriorhodopsin in liposomes. II. Experimental evidence in support of a theoretical model.
In the preceding article equations describing relevant ion flows in illuminated suspensions of bacteriorhodopsin liposomes have been derived. Here these equations are subjected to experimental tests. Changes in permeability characteristics of the liposomal membrane are brought about by addition of specific ionophores and change of medium composition. Using light-driven proton uptake and electrochemical potential differences for protons across the membrane as observation parameters, ridig attempts to falsify the derived equations are unsuccessful. Agreement between equations and experimental results is established on the point of: (i) the antagonistic effect of valinomycin and nigericin on the two components of the proton-motive force, (ii) the time dependence of the changes in transmembrane electrical and chemical potential differences after the onset of illumination. In three independent experimental systems evidence was obtained for the correctness of the postulated dependence of the turnover rate of the photochemical cycle on back pressure by the transmembrane electrochemical potential difference for protons.


LTP of inhibition at PV interneuron output synapses requires developmental BMP signaling.
Parvalbumin (PV)-expressing interneurons (PV-INs) mediate well-timed inhibition of cortical principal neurons, and plasticity of these interneurons is involved in map remodeling of primary sensory cortices during critical periods of development. To assess whether bone morphogenetic protein (BMP) signaling contributes to the developmental acquisition of the synapse- and plasticity properties of PV-INs, we investigated conditional/conventional double KO mice of BMP-receptor 1a (BMPR1a; targeted to PV-INs) and 1b (BMPR1a/1b (c)DKO mice). We report that spike-timing dependent LTP at the synapse between PV-INs and principal neurons of layer 4 in the auditory cortex was absent, concomitant with a decreased paired-pulse ratio (PPR). On the other hand, baseline synaptic transmission at this connection, and action potential (AP) firing rates of PV-INs were unchanged. To explore possible gene expression targets of BMP signaling, we measured the mRNA levels of the BDNF receptor TrkB and of P/Q-type Ca2+ channel α-subunits, but did not detect expression changes of the corresponding genes in PV-INs of BMPR1a/1b (c)DKO mice. Our study suggests that BMP-signaling in PV-INs during and shortly after the critical period is necessary for the expression of LTP at PV-IN output synapses, involving gene expression programs that need to be addressed in future work.


Muscarinic acetylcholine receptors from avian retina and heart undergo different patterns of molecular maturation.
Muscarinic acetylcholine receptors (mAChRs) from the avian CNS exist in two molecular weight forms whose concentrations change during development. Here, we have compared the development of mAChRs from embryonic hearts with those of the CNS. Analysis of [3H]-propylbenzilylcholine mustard (PrBCM)-labeled retina and heart mAChRs by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two atropine-sensitive peaks for each tissue. Apparent molecular masses of retina mAChRs, 86 +/- 0.7 kilodaltons (kDa) and 72 +/- 0.7 kDa, were different from those of heart mAChRs, 77 +/- 1.0 kDa and 52 +/- 0.9 kDa. During retina development, the major receptor type changed from 86 kDa to 72 kDa. No such change occurred during heart development. Furthermore, the 52-kDa species appeared to be generated by endogenous proteolysis, as prolonged incubation of heart membranes at 37 degrees C increased the amount of 52-kDa peptide with a decrease of 77-kDa peptide. Protease inhibitors blocked this conversion. Incubation of retina membranes at 37 degrees C did not result in a conversion of the 86-kDa peptide into the 72-kDa peptide, but it did cause the appearance of a minor amount of 52-kDa peptide. The proteolysis of retina mAChRs was not enhanced by cohomogenizing them with heart tissue, arguing against the presence of releasable proteases in heart. Membrane-bound retina and heart mAChRs displayed similar sensitivity to exogenous (Staphylococcus aureus V8) protease, indicating that heart receptors were not unusually susceptible to proteolytic attack; analysis of the labeled polypeptides with the V8 protease showed different patterns of digestion for the retina and heart receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Stability of luteinizing hormone releasing hormone: effects of pH, temperature, pig skin, and enzyme inhibitors.
The purpose of this investigation was to determine the stability of luteinizing hormone releasing hormone (LHRH) as a function of solution pH, temperature, and pig skin with and without enzyme inhibitors. LHRH, incubated with a 0.1 M phosphate buffer (pH 2.5-8.1), pig skin, and pig skin with enzyme inhibitors, was analyzed using reversed-phase high performance liquid chromatography. The solution's pH affected the rate constants of LHRH, following apparent first-order kinetics. Maximum stability was achieved at pH 6.05. Therefore, the effect of various temperatures (i.e., 65, 75, 80, and 90 degrees C) was studied on the stability of LHRH at pH 6.05. The activation energy for the overall reaction was 23.4 kcal/mol at pH 6.05. The shelf-life of LHRH at 25 degrees C and pH 6.05, calculated using the Arrhenius equation, was approximately 4 years. The rate constant of LHRH in the skin (area: 9 cm2; thickness: 0.5 mm) was 0.167 hr-1. Out of three inhibitors (i.e., aprotinin, bestatin, and leupeptin), bestatin had the best stabilizing effect on the degradation of LHRH by the skin. The rate constant of LHRH in the presence of bestatin was 0.082 hr-1. Sixty percent of LHRH was found to be degraded in the skin within 5 hr in the absence of enzyme inhibitors, whereas only 33% of LHRH was degraded in the presence of bestatin (an aminopeptidase inhibitor).


Thin film research today.
Improved methods of study have contributed to a great advance in thin film research in the past twenty years. A brief survey shows that applications have spread to many advances of electronics and optics.


Measurement of environmental trace-metal levels with transplanted mussels and diffusive gradients in thin films (DGT): a comparison of techniques.
Transplanted mussels and diffusive gradients in thin films (DGT) were used to assess levels of cadmium, copper, lead and zinc at four sites situated inside and outside of two enclosed marinas, near Melbourne, Australia. Mussels accumulated all metals except cadmium. Over one year, there were large temporal differences in tissue metal levels in mussels, but differences between sites were only apparent for copper and lead. DGT showed temporal differences of the same kind as those seen in the mussels, but appeared to have more power to discriminate between sites. DGT found higher copper levels inside marinas than outside, and high levels of zinc were found inside one marina. Levels of copper and zinc were high enough to be of environmental concern for one site. The effect of fouling on DGT measurements will have to be quantified, or avoided by the use of multiple short-term exposures, if the technique is to become a widespread in situ monitoring tool.


Orexinergic modulation of breathing across vigilance states.
Basal respiration and respiratory reflex regulations are considerably different during the awake and sleep states. Tidal volume and respiratory frequency diminish during sleep, and hypoxic and hypercapnic ventilatory responses also decline during sleep. Reduced metabolic demand during sleep cannot completely explain these phenomena because PaCO2 increases during sleep. In this review, I will summarize our recent discovery of the possible contribution of orexin, a hypothalamic neuropeptide, to the vigilance state-dependent adjustment of central respiratory regulation. Orexin-deficient mice show an attenuated hypercapnic ventilatory response during the awake but not during the sleep period, whereas basal ventilation remained normal, irrespective of the vigilance state. Orexin supplementation remedied the defect, and the administration of an orexin receptor antagonist to wild-type mice mimicked the abnormality. Orexin-deficient mice also showed frequent sleep apneas and loss of repetitive intermittent hypoxia-induced ventilatory long-term facilitation. Hence, it is possible that the orexin system is one of the essential modulators required for coordinating the circuits controlling respiration and behavior.


SRY-box transcription factor 10 is a highly specific biomarker of basal-like breast cancer.
Basal-like breast cancer is an aggressive molecular subtype associated with younger age and early relapse. Most cases lack expression of oestrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2, limiting targeted therapeutic options. Basal-like breast cancer is defined by the expression of genes in the outer/basally located epithelial layer of mammary glands, including those encoding cytokeratin (CK) 5 and CK14, and epidermal growth factor receptor (EGFR). SRY-box transcription factor 10 (SOX10), for which there is a readily available immunohistochemical stain, is expressed in a subset of breast cancers, particularly triple-negative carcinomas. In this study, we sought to: (i) assess the association between SOX10 expression and intrinsic molecular subtypes as defined by Prediction Analysis of Microarray 50 (PAM50) gene expression; and (ii) compare the performance of SOX10 with that of other surrogate markers of the basal-like subtype, including CK5, EGFR, nestin, and inositol polyphosphate 4-phosphatase type II (INPP4B). SOX10 immunostaining was performed on tissue microarrays constructed from a contemporary series enriched for ER-negative and weakly ER-positive cancers that had also undergone PAM50 gene profiling. A total of 211 cases were informative for both SOX10 immunohistochemistry and PAM50 subtype, including 103 basal-like cancers. Staining for SOX10 was positive in 73 of 103 basal-like cancers and in only two of 108 cancers of other subtypes (P < 0.001), resulting in a sensitivity of 70.9% and a specificity of 98.1%. SOX10 was more specific than the other tested basal markers, and the results were independent of ER status. SOX10 is a moderately sensitive, but highly specific, immunohistochemical biomarker for the basal-like intrinsic subtype of breast cancer, which, unlike other commonly used immunohistochemical biomarkers, is independent of hormone receptor status.


Effect of domperidone on gastric emptying and secretion.
Domperidone (5 mg i.v.) was given singly or together with apomorphine (0.25 mg i.v.) to healthy volunteers. The gastric emptying rate of a test meal of 750 ml of water was then measured using a dye dilution and double sampling technique. The effect of domperidone on gastric secretion was evaluated in patients with duodenal ulcer who received domperidone (5 mg i.v.) prior to continuous aspiration of the stomach contents for 120 minutes. Domperidone markedly increased the rate of emptying of the test meal. Following apomorphine the gastric emptying rate decreased and domperidone antagonized this slowing effect. The composition of gastric juice was not affected by an intravenous dose of domperidone. Domperidone appears to modulate gastric contractile activity without affecting gastric secretion.


Cordotomy-denervation interactions on contractile and myofibrillar properties of fast and slow muscles in the rat.
Cordotomy-denervation interactions were studied on contractile and myofibrillar properties of slow (soleus) and fast (extensor digitorum longus) muscles of the rat. The spinal cord was transected midthoracically in neonatal (2-day-old) animals. Two months after birth, a unilateral transection of the sciatic nerve was carried out in both cordotomized and control animals. Five weeks after denervation, contractile properties were tested isometrically in vitro; myofibrillar properties were assessed by histochemical staining of the muscle fibers and by electrophoretic analysis of the myosin heavy chain composition. The following results were obtained: (i) In cordotomized animals the contraction time of the soleus was significantly shorter (-23.3% on average) than that in the control animals and this shortening was accompanied by a proportional slow-to-fast shift in myofibrillar properties. (ii) The extensor digitorum longus properties were not significantly different in the control and cordotomized animals. (iii) Denervation in control animals was followed by a marked increase of contraction and half-relaxation times in the extensor digitorum longus, whereas in the soleus only the half-relaxation time was significantly increased; myofibrillar properties in the soleus showed an appreciable slow-to-fast shift, whereas in the fast muscle the main change was an increase in type 2A fibers to the detriment of type 2B. (iv) In cordotomized animals, denervation caused the soleus contraction time to increase to control values, whereas myofibrillar properties shifted to an even faster pattern; in the extensor digitorum longus denervation caused the same changes seen in the control animals. The results showed that cordotomy at birth caused the soleus to develop as a faster muscle than in the control animals. The concurrent effects of cordotomy and denervation on the myofibrillar properties of the soleus suggest that the slow-to-fast change in these properties is a common consequence of the reduction in the level of motor activity. The opposite effects of the two experimental conditions in the soleus contraction time support the view that the contractile alterations that follow denervation mainly reflect alterations in the muscle activation process.


wksl3, a New biocontrol agent for Salmonella enterica serovars enteritidis and typhimurium in foods: characterization, application, sequence analysis, and oral acute toxicity study.
Of the Salmonella enterica serovars, S. Enteritidis and S. Typhimurium are responsible for most of the Salmonella outbreaks implicated in the consumption of contaminated foods in the Republic of Korea. Because of the widespread occurrence of antimicrobial-resistant Salmonella in foods and food processing environments, bacteriophages have recently surfaced as an alternative biocontrol tool. In this study, we isolated a virulent bacteriophage (wksl3) that could specifically infect S. Enteritidis, S. Typhimurium, and several additional serovars. Transmission electron microscopy revealed that phage wksl3 belongs to the family Siphoviridae. Complete genome sequence analysis and bioinformatic analysis revealed that the DNA of phage wksl3 is composed of 42,766 bp with 64 open reading frames. Since it does not encode any phage lysogeny factors, toxins, pathogen-related genes, or food-borne allergens, phage wksl3 may be considered a virulent phage with no side effects. Analysis of genetic similarities between phage wksl3 and four of its relatives (SS3e, vB_SenS-Ent1, SE2, and SETP3) allowed wksl3 to be categorized as a SETP3-like phage. A single-dose test of oral toxicity with BALB/c mice resulted in no abnormal clinical observations. Moreover, phage application to chicken skin at 8°C resulted in an about 2.5-log reduction in the number of Salmonella bacteria during the test period. The strong, stable lytic activity, the significant reduction of the number of S. Enteritidis bacteria after application to food, and the lack of clinical symptoms of this phage suggest that wksl3 may be a useful agent for the protection of foods against S. Enteritidis and S. Typhimurium contamination.


Templates in protein de novo design.
The de novo design of polypeptide sequences with a three-dimensional structure necessary for many biological functions is limited by the complex folding process, or 'protein folding problem'. This problem can be bypassed through constructing protein-like molecules with a 'built-in' device for intramolecular folding, that is, proteins of non-natural chain architecture (template-assembled synthetic proteins, TASP). Topological templates have become a versatile tool for inducing and stabilizing secondary structures (protein loops, beta-turns, alpha-helices, beta-sheets) and are widely adopted design elements for the construction of protein-like molecules, exhibiting interesting structural and functional properties.


Preparation, characterization, and evaluation of the antitumor effect of kaempferol nanosuspensions.
Kaempferol (KAE) is a naturally occurring flavonoid compound with antitumor activity. However, the low aqueous solubility, poor chemical stability, and suboptimal bioavailability greatly restrict its clinical application in cancer therapy. To address the aforementioned limitations and augment the antitumor efficacy of KAE, we developed a kaempferol nanosuspensions (KAE-NSps) utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a stabilizing agent, screened the optimal preparation process, and conducted a comprehensive investigation of their fundamental properties as well as the antitumor effects in the study. The findings indicated that the particle size was 186.6 ± 2.6 nm of the TPGS-KAE-NSps optimized, the shape of which was fusiform under the transmission electron microscope. The 2% (w/v) glucose was used as the cryoprotectant for TPGS-KAE-NSps, whose drug loading content was 70.31 ± 2.11%, and the solubility was prominently improved compared to KAE. The stability and biocompatibility of TPGS-KAE-NSps were favorable and had a certain sustained release effect. Moreover, TPGS-KAE-NSps clearly seen to be taken in the cytoplasm exhibited a stronger cytotoxicity and suppression of cell migration, along with increased intracellular ROS production and higher apoptosis rates compared to KAE in vitro cell experiments. In addition, TPGS-KAE-NSps had a longer duration of action in mice, significantly improved bioavailability, and showed a stronger inhibition of tumor growth (the tumor inhibition rate of high dose intravenous injection group was 68.9 ± 1.46%) than KAE with no obvious toxicity in 4T1 tumor-bearing mice. Overall, TPGS-KAE-NSps prepared notably improved the defect and the antitumor effects of KAE, making it a promising nanodrug delivery system for KAE with potential applications as a clinical antitumor drug.


A light- and electron microscopic analysis of meiotic prophase in female mice.
In the paper we describe meiotic prophase of female mice on successive days of embryonic and early postnatal development. For this purpose we used three different techniques on ovarian material, i.e., Giemsa staining for the light microscopic study of chromatin, silver staining for the light microscopic study of the synaptonemal complex (SC), and agar filtration followed by uranyl acetate staining for the electron microscopic study of the SC. In all types of preparation it was impossible to distinguish leptotene stages, and we conclude that if leptotene really exists, it is of very short duration.--Two types of zygotene stages were found: the "normal" one, resembling zygotene stages in male mice, and a second type that has never been described in males and is characterized by, probably stable, unpaired regions together with totally unpaired axial elements of the SC.--The duration of pachytene was found to be 3-4 days, which is considerably shorter than in males. During early diplotene despiralization of the chromatin and disintegration of the axes of the SC were usually found together with desynapsis.--A considerable variation in distribution of meiotic stages was found between different litters in the same day of gestation. Fetuses in the same litter showed no significant variation. However, the oocytes in an ovary did not pass through meiosis synchronously, with differences up several days. The appearance of chromosomes in a highly contracted state could not be interpreted as a preleptotene condensation stage but probably is a mitotic phenomenon.


The net electric charge of proteins. A comparison of determinations by Donnan potential measurements and by gel electrophoresis.
We compare a new method for the determination of the net charge of proteins based on Donnan potential measurements, as described briefly by Ojteg, G., Nygren, K. and Wolgast, M. (1987) Acta Physiol. Scand. 129, 277-286, with a conventional method using polyacrylamide gel electrophoresis. The new technique utilizes the Donnan potential, which develops over a semipermeable membrane that separates the non-permeating protein from the surrounding bath of the same ionic composition as the protein solution, to determine the net valency. The advantages of this method, besides its simplicity, are that it can determine the charge of, e.g., a protein in a free-fluid phase and that the pH and ionic composition of the bathing fluid can be varied over a broad range. The Donnan potential decreased to half its original value when the ionic strength was doubled. Usually a protein concentration of 1-10 mg.ml-1 must be used. The Donnan potential method was applied to determine the net charges of a series of proteins with different isoelectric points. The values showed close agreement with the data obtained by gel electrophoresis.


Structure of simian virus 40 recombinants that contain both host and viral DNA sequences. I. The structure of variant CVPS/1/P2 (EcoRI res).
The entire nucleotide sequence (1210-base-pair repeating units) of a defective variant of simian virus 40 is presented. Within this variant there are deletions of large portions of the wild type genome and an inversion within the remaining wild type viral sequences. In addition, the defective variant contains DNA sequences derived from the permissive monkey cells in which the virus was propagated. The monkey sequences include a portion that is homologous to sequences within highly repeated monkey DNA (alpha component) as well as portions derived from sequences that are infrequently repeated in the monkey genome. One out of every three to four of the tandem 1210-base-pair repeat units contains in addition, a duplication of a part of the monkey sequences. The sequence information defines the structures of a number of recombinational joints which result from deletions, inversions, duplications, and insertions of host sequences into the viral genome. The data demonstrate that the various recombinational events that resulted in the formation of this defective variant did not depend on extensive homology between recombining segments.


Development and validation of a scoring system for pre-surgical and early post-surgical prediction of bariatric surgery unsuccess at 2 years.
Bariatric surgery (BS) is an effective treatment for morbid obesity. However, a simple and easy-to-use tool for the prediction of BS unsuccess is still lacking. Baseline and follow-up data from 300 consecutive patients who underwent BS were retrospectively collected. Supervised regression and machine-learning techniques were used for model development, in which BS unsuccess at 2 years was defined as a percentage of excess-weight-loss (%EWL) < 50%. Model performances were also assessed considering the percentage of total-weight-loss (%TWL) as the reference parameter. Two scoring systems (NAG-score and ENAG-score) were developed. NAG-score, comprising only pre-surgical data, was structured on a 4.5-point-scale (2 points for neck circumference ≥ 44 cm, 1.5 for age ≥ 50 years, and 1 for fasting glucose ≥ 118 mg/dL). ENAG-score, including also early post-operative data, was structured on a 7-point-scale (3 points for %EWL at 6 months ≤ 45%, 1.5 for neck circumference ≥ 44 cm, 1 for age ≥ 50 years, and 1.5 for fasting glucose ≥ 118 mg/dL). A 3-class-clustering was proposed for clinical application. In conclusion, our study proposed two scoring systems for pre-surgical and early post-surgical prediction of 2-year BS weight-loss, which may be useful to guide the pre-operative assessment, the appropriate balance of patients' expectations, and the post-operative care.


Disruption of axonal transport from olfactory epithelium by 3-methylindole.
The effects of 150, 350, and 400 mg/kg intraperitoneal 3-methylindole (3-MI) on anterograde transport of horseradish peroxidase from the olfactory epithelium to the olfactory bulb were investigated. In 400 mg/kg 3-MI-treated rats sacrificed after 7 days only about 2% of all glomeruli had normal levels of the reaction product, and most glomeruli had no detectable reaction product. Lower doses of 3-MI produced correspondingly less disruption of axonal transport, with savings located primarily in the ventral to midlateral and the ventromedial region of the bulb. There was a gradual recovery of bulbar connections in 12-, 22-, and 92-day survival rats. In all cases, the increase in axonal transport was greatest in glomeruli on the lateral, ventral, and ventromedial areas of the bulb, and least evident or absent on the dorsal and dorsomedial areas.


Root anoxia effects on physiology and emissions of volatile organic compounds (VOC) under short- and long-term inundation of trees from Amazonian floodplains.
Volatile organic compound (VOC) emissions are affected by a variety of biotic and abiotic factors such as light intensity, temperature, CO2 and drought. Another stress factor, usually overlooked but very important for the Amazon region, is flooding. We studied the exchange of VOCs in relation to CO2 exchange and transpiration of 8 common tree species from the Amazonian floodplain forest grown up from seeds using a dynamic enclosure system. Analysis of volatile organics was performed by PTR-MS fast online measurements. Our study confirmed emissions of ethanol and acetaldehyde at the beginning of root anoxia after inundation, especially in less anoxia adapted species such as Vatairea guianensis, but not for Hevea spruceana probably due to a better adapted metabolism. In contrast to short-term inundation, long-term flooding of the root system did not result in any emission of ethanol or/and acetaldehyde. Emission of other VOCs, such as isoprenoids, acetone, and methanol exhibited distinct behavior related to the origin (igapó or várzea type of floodplain) of the tree species. Also physiological activities exhibited different response patterns for trees from igapó or várzea. In general, isoprenoid emissions increased within the course of some days of short-term flooding. After a long period of waterlogging, VOC emissions decreased considerably, along with photosynthesis, transpiration and stomatal conductance. However, even under long-term testing conditions, two tree species did not show any significant decrease or increase in photosynthesis. In order to understand ecophysiological advantages of the different responses we need field investigations with adult tree species.


Estimating divergence times of lizardfishes and their allies (Euteleostei: Aulopiformes) and the timing of deep-sea adaptations.
The divergence times of lizardfishes (Euteleostei: Aulopiformes) are estimated utilizing a Bayesian approach in combination with knowledge of the fossil record of teleosts and a taxonomic review of fossil aulopiform taxa. These results are integrated with a study of character evolution regarding deep-sea evolutionary adaptations in the clade, including simultaneous hermaphroditism and tubular eyes. Divergence time estimations recover that the stem species of the lizardfishes arose during the Early Cretaceous/Late Jurassic in a marine environment with separate sexes, and laterally directed, round eyes. Tubular eyes have arisen independently at different times in three deep-sea pelagic predatory aulopiform lineages. Simultaneous hermaphroditism evolved a single time in the stem species of the suborder Alepisauroidei, the clade of deep-sea aulopiforms during the Early Cretaceous. This result indicates the oldest known evolutionary event of simultaneous hermaphroditism in vertebrates, with the Alepisauroidei being the largest vertebrate clade with this reproductive strategy.


Exploring bioactivity potential of polyphenolic water-soluble lignin derivative.
Many natural substances exhibit anti-inflammatory activity and considerable potential in prophylaxis and treatment of allergies. Knowing exact molecular targets, which is required for developing these as medicinal products, is often challenging for multicomponent compositions. In the present study we examined novel polyphenolic substance, a water-soluble fraction of wood lignin (laboratory code BP-Cx-1). In our previous study, a number of polyphenolic components of BP-Cx-1 (flavonoids, sapogenins, phenanthrenes etc.) were identified as the major carriers of biological activity of BP-Cx drug family, and several molecular targets involved in cancer and/or inflammation signaling pathways were proposed based on the results of the in vitro and in silico screening studies. In the present study, half maximal inhibitory concentration (IC50) of BP-Cx-1 was established with a radioligand method and a range of IC50 values between 22.8 and 40.3 μg/ml were obtained for adenosine receptors A1, A2A and prostaglandin receptors EP2, IP (PGI2). IC50 for serotonin 5-HT1 and for glucocorticoid GR receptors were 3.0 μg/ml and 12.6 μg/ml, respectively, both being within the range of BP-Cx-1 concentrations achievable in in vivo models. Further, distribution of [3H] labelled BP-Cx-1 in NIH3T3 murine fibroblasts and MCF7/R carcinoma cells was studied with autoradiography. [3H]-BP-Cx-1 (visualized as silver grains produced by tritium beta particles) was mainly localized along the cell membrane, in the perinuclear region and in the nucleus, suggesting ability of BP-Cx-1 to enter cells and bind to membrane or cytosol receptors. In our experiment, we observed the effect of BP-Cx-1 on maturation of dendritic cells (DCs): downregulation of expression of the lipid-presentation molecule CD1a, co-stimulatory molecules CD80, CD83 and CD 40, decreased production of pro-inflammatory cytokines IL-4 and TNF-α and increased production of anti-inflammatory cytokine IL-10. It is hypothesized that [3H]-BP-Cx-1 detectable in the nucleus is part of the activated GR complex, known to be involved in regulation of transcription of genes responsible for the anti-inflammatory response. Based on IC50, cell distribution data and results of the experiment with DCs it is suggested that the in vivo effects of BP-Cx-1 are mediated via GR and 5-HT1 receptors thus promoting development of tolerogenic effector function in dendritic cells.


Operative blood loss during common urological operations.
The knowledge of mean blood loss during common urological procedures may be of some help for the surgeon in the appraisal of the magnitude of bleeding and planning blood transfusion. In 9 types of common urological operations (160 patients) the operative blood loss was determined. Results were mathematically evaluated.


Subcutaneous fat index: a reliable tool for lumbar spine studies.
Obesity has been proposed as a risk factor for low back pain (LBP), and the body mass index (BMI) has been used for obesity; however, a more reliable tool is required to assess obesity-related health issues. A recent study depicted the subcutaneous fat tissue thickness (SFTT) at the L1-L2 level as superior to BMI in predicting LBP and spine degeneration. However, the study failed to answer the following questions: (1) What was the cutoff value for the SFTT to predict LBP and spine degeneration? (2) Could this new index be adjusted according to gender? (3) Could this new index predict fatty infiltration in the paraspinal muscles, severe intervertebral disk degeneration (IVDD), and Modic changes in the lumbar spine? Therefore, the current study aimed to answer these questions by developing and validating a new anthropometric index-the subcutaneous fat index (SFI). This study retrospectively reviewed the magnetic resonance imaging database of patients with LBP and compared them with asymptomatic volunteers. Appropriate cutoff values for females and males were 8.45 mm and 9.4 mm, respectively. Females and males with the SFI of > 8.45 mm and > 9.4 mm, respectively, had significantly higher rates of spine degeneration. The SFI reliably distinguished patients with LBP from the asymptomatic subjects and could reliably distinguish patients with severe IVDD/Modic changes at the lower lumbar levels and those with moderate-to-severe fat-infiltrated paraspinal muscles at all lumbar levels with reliable cutoff values for males and females. • The subcutaneous fat tissue thickness at L1-L2 level (subcutaneous fat index [SFI]) was superior to BMI in predicting LBP and spine degeneration. However, a reliable cutoff value has not been previously defined. • The subcutaneous fat index had reliable cutoff values of 8.45 mm and 9.4 mm for females and males, respectively. • Females with an SFI of > 8.45 mm and males with > 9.4 mm had significantly higher rates of severe IVDD, Modic changes, and fatty infiltration in their paraspinal muscles.


Treatment for Post-Slipped Capital Femoral Epiphysis Deformity.
In situ pinning of slipped capital femoral epiphysis (SCFE) is a safe and effective treatment modality, but often results in residual deformity leading to femoroacetabular impingement, which may limit patient activities and predispose to early onset arthritis. Enhanced understanding of the implications of femoroacetabular impingement and new surgical techniques have prompted interest in treating post-slipped capital femoral epiphysis deformity to both improve current symptoms and delay or prevent hip arthrosis.


Molecular insights on the binding of chlortetracycline to bovine casein and its effect on the thermostability of chlortetracycline.
Bovine casein was selected as a model protein to evaluate the impact of food matrix on the thermal degradation of antibiotics. Fluorescence quenching and isothermal titration calorimetry experiments revealed that chlortetracycline (CTC) could spontaneously bind to casein via hydrogen bonding and hydrophobic interactions. The amino acid residues forming the binding pocket were further identified using molecular docking, while saturation transfer difference NMR deciphered that the binding of CTC engages its -N(CH3)2 group. Moreover, the degradation behavior of free CTC versus that bound in casein-CTC complex was compared during thermal treatment. Compared with free CTC, a lower first-order rate constant was observed in the presence of casein. Removal of casein shortened the half-life of CTC by at least 48.1% at low concentrations. Elucidating that the formation of protein-antibiotic complexes alters the amenability of antibiotics to degradative reactions, which could help eliminate residual antibiotics and guarantee the safety of dairy products.


Comparative study of bacteriological contamination between primary and secondary exploration of missile head wounds.
Aerobic and anaerobic bacterial contamination of scalp wounds, indriven bone fragments, and brain tracks were studied in two groups (A and B) of nonrandomized patients with missile head wounds in a 20-month study of patients from the front lines of the Iran-Iraq war. In the 53 Group B patients, the primary debridements, most of which had been performed within 24 hours after injury, were deemed insufficient and a secondary definitive exploration was performed. Group A patients (62) had primary definitive explorations at Nemazee Hospital after a mean of 66.5 hours since injury. All of the patients had been started on dexamethasone and a combination of either ampicillin and chloramphenicol or crystalline penicillin G and chloramphenicol after field evacuation. The contamination rate of scalp wounds, bone fragments and brain tracks was slightly higher in Group A (38.4%, 22.2%, and 29.6% respectively, for Group A and 31.9%, 19.5%, and 27% for Group B, respectively). Staphylococcus albus among the gram-positive and Acinetobacter among gram-negative bacteria were the most common infecting organisms. Fifty per cent of the bacteria cultured from the brain tracks of Group A and 30.8% of those cultured from Group B patients were gram-negative. A total of 125 patients in four groups was included in our overall study of victims of missile wounds that violated the dura mater. Four patients developed meningitis at Nemazee Hospital (3 postoperatively and 1 after facial penetration). Two patients in Group B were admitted with meningitis (1 with an accompanying abscess), 1 of them 20 days and the other 60 days after exploration at two different centers.(ABSTRACT TRUNCATED AT 250 WORDS)


Fortified whey beverage for improving muscle mass in chronic obstructive pulmonary disease: a single-blind, randomized clinical trial.
The development of effective nutritional supports for patients with chronic obstructive pulmonary diseases (COPD) is still challenging. This study was conducted to investigate the efficacy of daily consumption of fortified whey on inflammation, muscle mass, functionality, and quality of life in patients with moderate-to-severe COPD. A single-blind, randomized trial study was performed on patients with COPD (n = 46). Participants in the intervention group (n = 23) daily received 250 ml of whey beverage fortified with magnesium and vitamin C for 8 weeks. Any changes in inflammatory cytokines (including interleukin- 6 (IL-6) and tumor necrosis factor (TNFα)) were the primary outcomes and the secondary outcomes were fat-free mass, handgrip strength, malnutrition, glutathione and malondialdehyde serum concentrations, and health-related quality of life (HRQoL). Body composition and muscle strength were measured by Bioelectrical Impedance Analysis (BIA) and hydraulic hand dynamometer, respectively. Fat-free mass index (FFMI) was also calculated. At the end of the study, 44 patients were analyzed. There were significant decreases in IL-6 concentrations in the intervention group compared to the control group. Also, FFMI, body protein, and handgrip strength increased significantly in the intervention group with significant changes between two groups. Moreover, improvement in health-related quality of life was observed in the intervention group compared to the control group. There were no significant changes in other study variables. This novel nutritional intervention decreased inflammatory cytokines levels, improved indices of skeletal muscle mass and muscle strength, and ultimately, increased HRQoL in patients with moderate-to-severe COPD. Thus, it is suggested to do further studies to assess the effects of nutrition intervention on COPD progression. IR.SUMS.REC.1396.85 ( https://www.irct.ir/ ).


Erythromycin attenuates MUC5AC synthesis and secretion in cultured human tracheal cells infected with RV14.
The common cold is a major cause of asthma exacerbation and chronic obstructive lung disease. Rhinovirus is reported to be responsible for more than 50% of cases of the common cold. In a previous study, we reported that rhinovirus infection of cultured airway cells induced MUC5AC mucin overproduction and hypersecretion by activating the p44/42 mitogen-activated protein kinase (p44/42 MAPK) pathway. The aim of this study was to examine the effect of erythromycin on RV14-induced airway mucin overproduction and hypersecretion. RV14-infected human tracheal epithelial cells were treated with erythromycin. Erythromycin blocked RV14-induced MUC5AC protein overproduction and hypersecretion, and also blocked RV14-induced p44/42 MAPK activation in the cells. Erythromycin may attenuate RV14-induced MUC5AC overproduction and hypersecretion by blocking the p44/42 MAPK pathway or its upstream regulators.


Microscopic versus macroscopic tubal anastomosis in rabbit fallopian tubes.
The importance of the operating microscope in rabbit tubal anastomosis was assessed by operating on 36 rabbits, half with the aid of the operating microscope and half with the aid of low-magnification loupes. The surgeons' operating comfort and sense of assuredness that the anastomoses were being done properly were increased by the operating microscope. However, the outcome of the anastomoses as measured by pregnancy rates, adhesion scores, and microscopic pathologic findings were not significantly different in the two groups.


Distribution of immunoreactive substance P neurons in the hypothalamus and pituitary of the rhesus monkey.
The distribution of immunoreactive substance P (IR-SP) neurons was examined in the hypothalamus and pituitary gland of the rhesus monkey by using the peroxidase-antiperoxidase immunocytochemical technique. Immunoreactive SP cell bodies were observed in the arcuate nucleus, in the region lateral to the arcuate nucleus, and in the median eminence (ME). Immunoreactive SP cells were also seen in the periventricular area of the dorsal tuberal region. A rich network of SP fibers was concentrated in the arcuate region, and the fiber stain was particularly dense in the external zone of the median eminence and in the external layer of the infundibular stalk. Also, substance P fibers were seen in the internal layer of the pituitary stalk and in the neural lobe of the pituitary gland. Outside the hypothalamus a dense network of IR-SP fibers was observed in the globus pallidus.


Esophageal metastasis from a peripheral lung carcinoma masquerading as a primary esophageal tumor.
A 65-year-old man presented with progressive dysphagia, which proved to be the first clinical manifestation of a peripheral lung carcinoma (secondary to a submucosal metastasis in the esophagus). The lung tumor, hidden by the diaphragm on chest x-ray, was not suspected until a thoracotomy was done. Although dysphagia is known to be the first manifestation of bronchogenic carcinomas, such presentation in a case of a peripheral lung carcinoma has not been well described. This case is reported with a review of the literature for cases with dysphagia secondary to a metastatic tumor in the esophagus.


Two new species of Acanthocinini (Coleoptera, Cerambycidae, Lamiinae) from the Neotropical Region.
Two new species of Acanthocinini are described from the Neotropical region: Leptostylus skillmani, from Guatemala; and Anisopodus morrisi, from French Guiana. Additionally, the holotype of Leptostylus lilliputanus Thomson, 1865 is illustrated for the first time.


Unsymmetrical diarylethenes as molecular keypad locks with tunable photochromism and fluorescence via Cu2+ and CN- coordinations.
New unsymmetrical diarylethenes were synthesized and their photochromic and fluorescent properties are tailored by Cu(2+) and CN(-) coordinations. A novel molecular logic keypad lock is constructed based on the fluorescence emission changes by the inputs of UV/visible irradiation, Cu(2+) and CN(-).


Enhancement of dielectric and electric-field-induced polarization of bismuth fluoride nanoparticles within the layered structure of carbon nitride.
A single-pot, wet chemical method has been reported for the synthesis of bismuth fluoride nanoparticles (BF) and functionalized BF within the network of carbon nitride (BFCN). In BFCN, a structural transformation of BF, from cubic to pseudo-cubic (as evidenced by Rietveld refinement analysis), confirmed the contribution of carbon nitride (CN) on functionalization. The effect of functionalization of BF has been investigated through dielectric and field-induced polarization studies under different temperature and frequency conditions. Enhancement of dielectric constant values was noticed in BFCN as compared with BF system, in the order of 2.5 (30 °C) and 8.0 (100 °C) at 100 Hz. Fatigue-free maximum polarization values of 0.041 µC/cm2 and 0.054 µC/cm2, under the electric field of 5 kV/mm, were achieved for BF and BFCN samples, respectively, for 5 × 103 cycles.


Feasibility and safety of single-incision laparoscopic colectomy: a systematic review.
The aim of this review was to evaluate the feasibility, safety, and potential benefits of single-incision laparoscopic colectomy (SILC). We conducted a comprehensive review for the years 1983 to March 2011 to retrieve all relevant articles. A total of 23 studies with 378 patients undergoing SILC were reviewed. All studies except 2 used a commercially available single-port device. Range of body mass index was 20.9 to 30.0 kg/m². Ranges of operative times and estimated blood losses were 83 to 225 minutes and 0 to 115 mL, respectively. Of 378 cases, a total of 6 cases (1.6%) were converted to open, 6 (1.6%) to hand-assisted laparoscopic (HALC), and 14 (4.0%) to conventional (multiport) laparoscopic colectomy (MLC) (overall conversion rate, 6.9%). An additional laparoscopic port was used in 4.9% (12/247) cases. Range of harvested lymph nodes number for malignant cases was 13.5 to 27 and surgical margins were negative in all cases. Overall mortality and morbidity rates were 0.5% (2/378) and 12.9% (45/349), respectively. The length of hospital stay (LOS) varied across reports (1.9-9.8 days). Among 4 case-matched studies, 2 showed shorter LOS after SILC than after HALC (2.7 vs 3.3 days) or after MLC/HALC (3.4 vs 4.6/4.9 days). Furthermore, one of these studies reported that maximum pain score on postoperative days 1 and 2 was significantly lower in SILS than in MLC and HALC. In early series of highly selected patients, SILC appears to be feasible and safe when performed by surgeons who are highly skilled in laparoscopy. Despite technical difficulties, there may be potential benefits associated with SILC over MLC/HALC but it is yet to be proven objectively.


Dynamic Brain Connectivity in Resting State Functional MR Imaging.
Dynamic functional connectivity adds another dimension to resting-state functional MR imaging analysis. In recent years, dynamic functional connectivity has been increasingly used in resting-state functional MR imaging, and several studies have demonstrated that dynamic functional connectivity patterns correlate with different physiologic and pathologic brain states. In fact, evidence suggests that dynamic functional connectivity is a more sensitive marker than static functional connectivity; therefore, it might be a promising tool to add to clinical functional neuroimaging. This article provides a broad overview of dynamic functional connectivity and reviews its general principles, techniques, and potential clinical applications.


Ambient Temperature is A Strong Selective Factor Influencing Human Development and Immunity.
Solar energy, which is essential for the origin and evolution of all life forms on Earth, can be objectively recorded through attributes such as climatic ambient temperature (CAT), ultraviolet radiation (UVR), and sunlight duration (SD). These attributes have specific geographical variations and may cause different adaptation traits. However, the adaptation profile of each attribute and the selective role of solar energy as a whole during human evolution remain elusive. Here, we performed a genome-wide adaptation study with respect to CAT, UVR, and SD using the Human Genome Diversity Project-Centre Etude Polymorphism Humain (HGDP-CEPH) panel data. We singled out CAT as the most important driving force with the highest number of adaptive loci (6 SNPs at the genome-wide 1 × 10-7 level; 401 at the suggestive 1 × 10-5 level). Five of the six genome-wide significant adaptation SNPs were successfully replicated in an independent Chinese population (N = 1395). The corresponding 316 CAT adaptation genes were mostly involved in development and immunity. In addition, 265 (84%) genes were related to at least one genome-wide association study (GWAS)-mapped human trait, being significantly enriched in anthropometric loci such as those associated with body mass index (χ2; P < 0.005), immunity, metabolic syndrome, and cancer (χ2; P < 0.05). For these adaptive SNPs, balancing selection was evident in Euro-Asians, whereas obvious positive and/or purifying selection was observed in Africans. Taken together, our study indicates that CAT is the most important attribute of solar energy that has driven genetic adaptation in development and immunity among global human populations. It also supports the non-neutral hypothesis for the origin of disease-predisposition alleles in common diseases.


[Establishing a FEM of mandibular first molar and stress analysis].
Establishing a finite element model of mandibular first molar with analysis of the stress distribution to each of the tooth parts on the model. The right mandibular first molar in vitro was scanned and the image was processed. The three dimensional finite-element model was established by the special software and loaded on it. Stress distribution on each part of the tooth was obtained. The maximum values of compressive stress, tensile stress and mises stress were calculated. In the research and analysis of the tooth stress, the finite element method is simple, effective, safe and reliable.


Fluorescence studies of the interaction of calmodulin with myosin light chain kinase.
The interaction of calmodulin with myosin light chain kinase produces an approximately 30% increase in myosin light chain kinase tryptophan fluorescence. This represents the first report of calmodulin-induced structural changes in a protein which it activates. We fund that the calmodulin-myosin light chain kinase interaction is: 1) dependent on [Ca2+] (half-maximal binding at pCa 6.2) and essentially independent of [Mg2+], 2) occurs before saturation of all four reported Ca2+-specific sites on calmodulin. 3) saturates with 1 mol of calmodulin bound per mol of kinase with an apparent affinity of approximately 2.0 X 10(7) M-1, 4) is specific for calmodulin over troponin-C, 5) is directly related to the activation of myosin light chain kinase for phosphorylation of myosin light chain. Fluorescence stopped flow studies of these calmodulin-induced fluorescence changes in myosin light chain kinase indicate that Ca2+ binding to calmodulin occurs very rapidly and is not rate-limiting while the calmodulin-induced fluorescence increase in myosin light chain kinase occurs as a biphasic process with rates of approximately 65 s-1 and 6 s-1. The fluorescence increase produced by calmodulin binding to myosin light chain kinase is completely reversed by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid at a rate of approximately 2 s-1.


Randomized phase II trial comparing axitinib with the combination of axitinib and lomustine in patients with recurrent glioblastoma.
Axitinib is a small molecule tyrosine kinase inhibitor with high affinity and specificity for the family of vascular endothelial growth factor receptors. It has previously demonstrated anti-tumor activity in a small cohort of patients with recurrent glioblastoma (rGB). We conducted a non-comparative randomized phase II clinical trial investigating axitinib monotherapy versus axitinib plus lomustine (LOM) in patients with rGB. Primary endpoint was 6 month progression-free survival (6mPFS). Patients who progressed on axitinib-monotherapy were allowed to cross-over. Between August 2011 and July 2015, 79 patients were randomized and initiated axitinib monotherapy (n = 50; AXI) or axitinib plus lomustine (n = 29; AXILOM). Median age was 55y [range 18-80], 50M/28F. Baseline characteristics were well balanced between study arms. Nineteen patients in the AXI-arm crossed-over at the time of progression. Treatment was generally well tolerated. AXILOM patients were at higher risk for grade 3/4 neutropenia (0 vs. 21%) and thrombocytopenia (4 vs. 29%). Best Overall Response Rate (BORR) in the AXI-arm was 28 vs. 38% in the AXILOM-arm. 6mPFS was 26% (95% CI 14-38) versus 17% (95% CI 2-32) for patients treated in the AXI versus AXILOM-arms, respectively. Median overall survival was 29 weeks (95% CI 20-38) in the AXI-arm and 27.4 weeks (95% CI 18.4-36.5) in the AXILOM-arm. MGMT-promoter hypermethylation and steroid treatment at baseline correlated significantly with PFS and OS. We conclude from these results that axitinib improves response rate and progression-free survival in patients with rGB compared to historical controls. There is no indication that upfront combination of axitinib with LOM improves results (European Clinical Trials Database (EudraCT) Study Number: 2011-000900-16).


Are there any sex differences in fatty liver? A study of glucose metabolism and body fat distribution.
Fatty liver is a common condition found more often in males. Whether sex differences affect its development is presently unknown. The hypothesis that glucose metabolism alterations or central body fat distribution are gender-related in fatty liver was investigated. Overall 199 consecutive subjects seen in the Division of Internal Medicine and Gastroenterology, Modena City Hospital, were enrolled. In the main arm of the present study, 44 men with sonographic fatty liver and 47 controls without, and 18 women with and 19 without fatty liver had their body mass index (an index of overall adiposity), hepatobiliary serum enzymes, serum cholesterol and triglycerides determined. All underwent oral glucose tolerance tests (estimated through the glucose area under the curve with the trapezoidal method). In the ancillary arm study, 17 other men with and 14 without, and 11 other women with and 29 without fatty liver had anthropometric measurements of body fat distribution (waist/hip, waist/height and skinfold thickness). Following statistical evaluation including univariate and multivariate analyses (main study), elevated body mass index was found to be an independent predictor of fatty liver in either sex. Glucose area under the curve and a central-type body fat distribution (ancillary study) predicted FL only in women. Fatty liver could be gender-related in the present series.


Impacts of COVID-19 on global tourism industry: A cross-regional comparison.
The tourism industry was one of the world's greatest markets; until the world met a pandemic in the 21st century, COVID-19. This study aims to present the reactions of travelers during the pandemic trends outlined by adopting text mining techniques. Between December 30, 2019-March 15, 2020, approximately 75,000 comments are retrieved from the TripAdvisor forums, and 23,515 cases from the US, Europe, and Asia forums are employed for analyses. The results reveal that the tourism sector is easily affected by global crises. It is almost the same day that travelers decide to cancel or delay their trips, with the spread of the news. More in-depth analyses uncovered several topics consisted of comments on benefiting from travel insurance and refund due to the travel cancellations. Travel insurance has become a hot topic, which may be a way of reanimating the industry by offering travel packages, including travel insurance services.


In vitro analysis of cisplatin functionalized magnetic nanoparticles in combined cancer chemotherapy and electromagnetic hyperthermia.
A novel platform has been developed for combined cancer chemotherapy and hyperthermia based on iron oxide magnetic nanoparticles functionalized with cis-diamminedichloroplatinum(II) (cisplatin). The capabilities of this system for heating and controlled drug release were investigated, and the system was tested in vitro by the treatment of BP6 rat sarcoma cells, where we demonstrated a synergism between the effects of cisplatin-targetMAG nanoparticles and the application of electromagnetic field.


Percutaneous biopsy of thoracic lesions in children.
Over the last 6 years, 15 percutaneous thoracic biopsies have been performed in 15 children. The peripheral nature of most of the lesions allowed ultrasound guidance in ten and needles larger than 21 gauge in ten. No pneumothorax developed. Of the 15, 12 biopsies were sufficient for final diagnosis; 3 required surgical biopsy for more definitive tissue typing.


Association between livelihood capital and catastrophic health expenditure among patients with critical illness: a cross-sectional study in rural Shandong, China.
The objective of this study is to examine the association between livelihood capital and catastrophic health expenditure (CHE). Between July and August 2019, a cross-sectional study was conducted in critically ill patients. Shandong, China. 1041 households with critically ill patients from 77 villages. We defined expenditure as being catastrophic if a household's out-of-pocket payments were greater than or equal to 40% of their capacity to pay. Using the sustainable livelihoods framework, this study explored the associations between CHE and the various forms of livelihood capital-inclusive of human capital, natural capital, physical capital, financial capital and social capital. χ2 tests, t-tests, Wilcoxon tests and binary logistic regression analysis were performed to examine these associations. The incidence of CHE among households with critically ill patients was 76.37% in this study. Better livelihood capital was significantly associated with lower incidence of CHE. After controlling for confounding factors, households with healthier patients (OR 0.47, 95% CI 0.23 to 0.96), more real estate ownership (OR 0.35, 95% CI 0.19 to 0.67) and better economic status (OR 0.33, 95% CI 0.18 to 0.62) were associated with a reduction in the occurrence of CHE. Livelihood capital was significantly associated with CHE in rural families with critically ill patients. This association suggests that, in addition to providing health insurance to the critically ill, more attention should be paid to their ability to create and preserve livelihood capital.


Respiratory Complications of Pediatric Neuromuscular Diseases.
Respiration is an event of oxygen consumption and carbon dioxide production. Respiratory failure is common in pediatric neuromuscular diseases and the main cause of morbidity and mortality. It is a consequence of lung failure, ventilatory pump failure, or their combination. Lung failure often is due to chronic aspiration either from above or from below. It may lead to end-stage lung disease. Ventilatory pump failure is caused by increased respiratory load and progressive respiratory muscles weakness. This article reviews the normal function of the respiratory pump, general pathophysiology issues, abnormalities in the more common neuromuscular conditions and noninvasive interventions.


New insights in the chemical profiling of major metabolites in different pigeon pea cultivars using UPLC-QqQ-MS/MS.
As one of the major non-conventional edible legumes, different cultivars of pigeon pea have different uses according to their specificity. For the first time, the main phenotype and plant physiological parameters of ten different pigeon pea cultivars were evaluated in detail, and then a novel method using UPLC-QqQ-MS/MS has been investigated for the qualitative and quantitative analysis of eighteen active constituents originating from pigeon peas. After systematic optimization of MRM parameters, the developed method showed a good precision (RSD < 7.28%) and high recovery (91.27-113.62%) within 6 min. It was found that pigeon pea 11Y21, R7 and R10 exhibited superiority in contents of the unique active compounds of cajaninstilbene acid, cajanuslactone, longistylin A and longistylin C. Moreover, combined with the main plant physiological parameters, we can find that excessive plant growth may affect the metabolites content in pigeon pea. Meanwhile, the gene expression levels indicating that the metabolite profiles of different cultivars can be strongly influenced by genetic variation. Overall, the present work developed a valid method for the detection of various phenolic compounds, which could be applied for applicability and variety breeding of pigeon pea and also providing sufficient evidences for other utilization in the future.


Influence of Clinical Communication on Parents' Antibiotic Expectations for Children With Respiratory Tract Infections.
The purpose of this study was to understand clinicians' and parents' perceptions of communication within consultations for respiratory tract infections (RTI) in children and what influence clinician communication had on parents' understanding of antibiotic treatment. We video recorded 60 primary care consultations for children aged 3 months to 12 years who presented with RTI and cough in 6 primary care practices in England. We then used purposive sampling to select 27 parents and 13 clinicians for semistructured video-elicitation interviews. The videos were used as prompts to investigate participants' understanding and views of communication within the consultations. We analyzed the interview data thematically. While clinicians commonly told parents that antibiotics are not effective against viruses, this did not have much impact on parents' beliefs about the need to consult or on their expectations concerning antibiotics. Parents believed that antibiotics were needed to treat more severe illnesses, a belief that was supported by the way clinicians accompanied viral diagnoses with problem-minimizing language and antibiotic prescriptions with more problem-oriented language. Antibiotic prescriptions tended to confirm parents' beliefs about what indicated illness severity, which often took into account the wider impact on a child's life. While parents understood antimicrobial resistance poorly, most held beliefs that supported reduced antibiotic prescribing. A minority attributed it to resource rationing, however. Clinician communication and prescribing behavior confirm parents' beliefs that antibiotics are needed to treat more severe illnesses. Interventions to reduce antibiotic expectations need to address communication within the consultation, prescribing behavior, and lay beliefs.


The use of a pragmatic protocol with normal preschool children.
The purpose of the present study was to examine the use of language functions in a structured setting in normal preschool children. Subjects were 240 males and females between the ages of two and five years. Results indicated statistically significant differences in the appropriateness of responses among several different age groups. The results are discussed relative to the assessment of the preschool child with a possible language disorder.


Gait performance of adolescent mice assessed by the CatWalk XT depends on age, strain and sex and correlates with speed and body weight.
The automatization of behavioral tests assessing motor activity in rodent models is important for providing robust and reproducible results and evaluating new therapeutics. The CatWalk system is an observer-independent, automated and computerized technique for the assessment of gait performance in rodents. This method has previously been used in adult rodent models of CNS-based movement disorders such as Parkinson's and Huntington's diseases. As motor and gait abnormalities in neuropsychiatric disorders are observed during infancy and adolescence, it became important to validate the CatWalk XT in the gait analysis of adolescent mice and unravel factors that may cause variations in gait performance. Three adolescent wild-type inbred mouse strains, C57BL/6N, DBA/2 and FVB/N, were tested using the CatWalk XT (Version 10.6) for suitable detection settings to characterize several gait parameters at P32 and P42. The same detection settings being suitable for C57BL/6N and DBA/2 mice allowed a direct comparison between the two strains. On the other hand, due to their increased body weight and size, FVB/N mice required different detection settings. The CatWalk XT reliably measured the temporal, spatial, and interlimb coordination parameters in the investigated strains during adolescence. Additionally, significant effects of sex, development, speed and body weight within each strain confirmed the sensitivity of motor and gait functions to these factors. The CatWalk gait analysis of rodents during adolescence, taking the effect of age, strain, sex, speed and body weight into consideration, will decrease intra-laboratory discrepancies and increase the face validity of rodent models of neuropsychiatric disorders.


Glutathione Peroxidase 3 induced mitochondria-mediated apoptosis via AMPK /ERK1/2 pathway and resisted autophagy-related ferroptosis via AMPK/mTOR pathway in hyperplastic prostate.
Benign prostatic hyperplasia (BPH) is a common disease in elderly men, mainly resulted from an imbalance between cell proliferation and death. Glutathione peroxidase 3 (GPX3) was one of the differentially expressed genes in BPH identified by transcriptome sequencing of 5 hyperplastic and 3 normal prostate specimens, which had not been elucidated in the prostate. This study aimed to ascertain the mechanism of GPX3 involved in cell proliferation, apoptosis, autophagy and ferroptosis in BPH. Human prostate tissues, GPX3 silencing and overexpression prostate cell (BPH-1 and WPMY-1) models and testosterone-induced rat BPH (T-BPH) model were utilized. The qRT-PCR, CCK8 assay, flow cytometry, Western blotting, immunofluorescence, hematoxylin and eosin, masson's trichrome, immunohistochemical staining and transmission electron microscopy analysis were performed during in vivo and in vitro experiments. Our study indicated that GPX3 was localized both in the stroma and epithelium of prostate, and down-regulated in BPH samples. Overexpression of GPX3 inhibited AMPK and activated ERK1/2 pathway, thereby inducing mitochondria-dependent apoptosis and G0/G1 phase arrest, which could be significantly reversed by MEK1/2 inhibitor U0126 preconditioning. Moreover, overexpression of GPX3 further exerted anti-autophagy by inhibiting AMPK/m-TOR and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4, mitochondrial GPX4 and cytoplasmic GPX4) to antagonize autophagy-related ferroptosis. Consistently, GPX3 deficiency generated opposite changes in both cell lines. Finally, T-BPH rat model was treated with GPX3 indirect agonist troglitazone (TRO) or GPX4 inhibitor RAS-selective lethal 3 (RSL3) or TRO plus RSL3. These treatments produced significant atrophy of the prostate and related molecular changes were similar to our in vitro observations. Our novel data manifested that GPX3, which was capable of inducing apoptosis via AMPK/ERK1/2 pathway and antagonizing autophagy-related ferroptosis through AMPK/m-TOR signalling, was a promising therapeutic target for BPH in the future.


Association of Patient Experience of Care and Radiation Therapy Initiation Among Women With Early-Stage Breast Cancer.
For women diagnosed with early-stage breast cancer, lumpectomy followed by radiation therapy (RT) has been a guideline-recommended treatment. However, lumpectomy followed by hormonal therapy is also an approved treatment for certain women. It is unclear what patient-driven factors are related to decisions to receive RT. This study examined relationships between patient-reported experience of care, an important dimension of health care quality, and receipt of RT after lumpectomy. We used National Cancer Institute Surveillance, Epidemiology, and End Results data linked to the CMS Medicare Consumer Assessment of Healthcare Providers and Systems patient surveys (SEER-CAHPS) to examine experiences of care among women diagnosed with local/regional stage breast cancer 2000 to 2017 who received lumpectomy, were enrolled in fee-for-service Medicare, completed a CAHPS survey ≤18 months after diagnosis, and survived for this study period. Experience of care was assessed by patient-provided scores for physicians, doctor communication, care coordination, and other aspects of care. Multivariable logistic regression models assessed associations of receipt of external beam RT with care experience and patient sociodemographic and clinical characteristics. The study population included 824 women; 655 (79%) received RT. Women with higher experience of care scores for their personal doctor were significantly more likely to have received any RT (odds ratio [OR], 1.18; P = .033). Nonsignificant trends were observed for associations of increased RT with higher CAHPS measures of doctor communications (OR, 1.15; P = .055) and care coordination (OR, 1.24; P = .051). In contrast, women reporting higher scores for Part D prescription drug plans were significantly less likely to have received RT (OR, 0.78; P = .030). Patient experience of care was significantly associated with receipt of RT after lumpectomy among women with breast cancer. Health care organization leaders may want to consider incorporating experience of care into quality improvement initiatives and other activities that aim to improve patient decision-making, care, and outcomes.


Optimal torque distribution of distributed driving AGV under the condition of centroid change.
The torque distribution is researched under the condition of the centroid position of distributed drive automatic guided vehicle (AGV) with load platform and is uncertain due to the unknown movable load. The whole vehicle model under centroid variation, the efficiency model of the hub motor and the torque distribution control strategy based on a PID neural network are established. A hierarchical controller is designed to accurately ensure the economy and stability of the vehicle. Simulations of the proposed control strategy are conducted, the results show that the total power and lateral deviation distance of the driving wheels are reduced by 17.63% and 61.54% under low load conditions and 15.54% and 61.39% under high load conditions, respectively, compared with those of the driving wheels under the average torque distribution, and the goal of close slip rates of the driving wheels is achieved. A system prototype is developed and tested, and the experimental results agree with the simulation within error permissibility. The margin of error is less than 5.8%, the results demonstrate that the proposed control strategy is effective. This research can provide a theoretical and experimental basis for the torque optimization distribution of distributed drive AGVs under centroid variation conditions.


COVID-19 Case Investigation and Contact Tracing in New York City, June 1, 2020, to October 31, 2021.
Contact tracing is a core strategy for preventing the spread of many infectious diseases of public health concern. Better understanding of the outcomes of contact tracing for COVID-19 as well as the operational opportunities and challenges in establishing a program for a jurisdiction as large as New York City (NYC) is important for the evaluation of this strategy. To describe the establishment, scaling, and maintenance of Trace, NYC's contact tracing program, and share data on outcomes during its first 17 months. This cross-sectional study included people with laboratory test-confirmed and probable COVID-19 and their contacts in NYC between June 1, 2020, and October 31, 2021. Trace launched on June 1, 2020, and had a workforce of 4147 contact tracers, with the majority of the workforce performing their jobs completely remotely. Data were analyzed in March 2022. Number and proportion of persons with COVID-19 and contacts on whom investigations were attempted and completed; timeliness of interviews relative to symptom onset or exposure for symptomatic cases and contacts, respectively. Case investigations were attempted for 941 035 persons. Of those, 840 922 (89.4%) were reached and 711 353 (75.6%) completed an intake interview (women and girls, 358 775 [50.4%]; 60 178 [8.5%] Asian, 110 636 [15.6%] Black, 210 489 [28.3%] Hispanic or Latino, 157 349 [22.1%] White). Interviews were attempted for 1 218 650 contacts. Of those, 904 927 (74.3%) were reached, and 590 333 (48.4%) completed intake (women and girls, 219 261 [37.2%]; 47 403 [8.0%] Asian, 98 916 [16.8%] Black, 177 600 [30.1%] Hispanic or Latino, 116 559 [19.7%] White). Completion rates were consistent over time and resistant to changes related to vaccination as well as isolation and quarantine guidance. Among symptomatic cases, median time from symptom onset to intake completion was 4.7 days; a median 1.4 contacts were identified per case. Median time from contacts' last date of exposure to intake completion was 2.3 days. Among contacts, 30.1% were tested within 14 days of notification. Among cases, 27.8% were known to Trace as contacts. The overall expense for Trace from May 6, 2020, through October 31, 2021, was approximately $600 million. Despite the complexity of developing a contact tracing program in a diverse city with a population of over 8 million people, in this case study we were able to identify 1.4 contacts per case and offer resources to safely isolate and quarantine to over 1 million cases and contacts in this study period.


Low doses of naltrexone reduce palatability and consumption of ethanol in outbred rats.
The opioid antagonist naltrexone, at doses of 1 and 3 mg/kg, has been shown to decrease the palatability and consumption of 10% ethanol in rats. However, a dose of 0.5 mg/kg of naltrexone has produced equivocal results. The purpose of the present study was to clarify the effects of low doses of naltrexone (0.0 [control], 0.25, 0.50, 0.75, and 1.0 mg/kg) on palatability and consumption of 10% ethanol. Sixty-four, male, Long-Evans hooded rats were divided into five groups matched for ethanol consumption. Each rat was injected over four consecutive days with one of five doses of naltrexone exactly 30 min before taste reactivity testing with 10% ethanol. When reactivity testing was completed, rats were acclimated to drink during a period of restricted access to fluid under conditions of mild fluid deprivation. Then, on four consecutive test days, rats were injected with naltrexone 10 min before 10% ethanol was made available for 30 min. Although each dose of naltrexone decreased ingestive responding to 10% ethanol over four days, this effect was not statistically reliable. However, all doses of naltrexone produced significant increases in aversive responding to the ethanol solution. Naltrexone, at the three highest doses, produced significant decreases in consumption of 10% ethanol. These results were consistent with the interpretation that naltrexone, even at low doses, reliably reduces palatability and consumption of 10% ethanol.


Brain Magnetic Resonance Imaging of Intracerebral Hemorrhagic Rats after Alcohol Consumption.
Alcoholism is one of the risk factors for cerebrovascular diseases. Our previous study demonstrated that acute alcohol intoxication enhances brain injury and neurological impairment in rats suffering from intracerebral hemorrhage (ICH). We plan to investigate the effect of chronic alcohol consumption (CAC) in rats with ICH by magnetic resonance imaging (MRI). Sixteen Sprague-Dawley male rats were divided into 2 groups: CAC group (fed with 10% alcohol drinking water for 4 weeks, n = 8), and Control group (plain drinking water, n = 8). ICH was induced by collagenase infusion into the right striata of all rats. Coronal T1-weighted imaging, T2-weighted imaging, T2*-weighted imaging, and diffusion-weighted imaging were generated with a 3.0T MRI scanner to investigate the changes of hemorrhagic volume and edema throughout the injury and recovery stages of ICH in rats. T2-weighted imaging is ideal for monitoring hematoma volume in rats. The hematoma volume was larger in the CAC group than in the control group (P < .001), however, did not correlate to post-ICH progressive edema formation (P > .7), and neurological impairment (P > .28) between the 2 groups, respectively. Although our findings indicate that CAC induces larger hematoma in rats with ICH, the underlying mechanism should be studied in the future.


Development of reference intervals for pupillometry in healthy dogs.
Pupillometry, the measurement of pupil size and reactivity to a stimulus, has various uses in both human and veterinary medicine. These reflect autonomic tone, with the potential to assess nociception and emotion. Infrared pupillometry reduces inaccuracies that may occur when the pupillary light reflex is determined subjectively by the examiner. To our knowledge, there are no published studies outlining normal reference intervals for automated pupillometry in dogs. The objective of this study was to develop de novo automated pupillometry reference intervals from 126 healthy canine eyes. The pupillary light reflex (PLR) was measured with a handheld pupillometer (NeurOptics™ PLR-200™ Pupillometer). Parameters recorded included maximum pupil diameter (MAX), minimum pupil diameter (MIN), percent constriction (CON), latency (LAT), average constriction velocity (ACV), maximum constriction velocity (MCV), average dilation velocity (ADV) and time to 75% pupil diameter recovery (T75). One measurement was obtained for each eye. The following reference intervals were developed: MAX (6.05-11.30 mm), MIN (3.76-9.44 mm), CON (-37.89 to -9.64 %), LAT (0.11-0.30 s), ACV (-6.39 to -2.63 mm/ s), MCV (-8.45 to -3.75 mm/s), ADV (-0.21-1.77 mm/s), and T75 (0.49-3.20 s). The reference intervals developed in this study are an essential first step to facilitate future research exploring pupillometry as a pain assessment method in dogs.


Orthopedic Care of Patients with Parkinson Disease.
This article summarizes existing literature examining orthopedic interventions for patients with Parkinson disease (PD). It reviews complications and functional outcomes of shoulder, spine, knee, and hip surgeries in PD. Causes of fall-related fractures in PD and the risk of postoperative cognitive decline after orthopedic interventions in PD are also briefly discussed.


Investigation of unirhinal olfactory identification in antipsychotic-free patients experiencing a first-episode schizophrenia.
Although olfactory deficits have been reported in patients with schizophrenia, few studies have examined whether these deficits are lateralized or investigated their possible clinical correlates. In this study, we administered the University of Pennsylvania Smell Identification Test (UPSIT) unirhinally (one nostril at a time) to 15 patients experiencing a first-episode of schizophrenia and 17 healthy comparison subjects. Clinical and olfactory assessments were conducted on the same day in patients while they were antipsychotic drug-free. Patients performed more poorly compared to healthy volunteers in their ability to identify odors across both nostrils, but there were no group differences in right and left nostril impairment. Among patients, greater deficits in grooming and hygiene correlated significantly and more strongly with poorer ability in identifying odors presented to the left compared to the right nostril. Our findings suggest that deficits in grooming and hygiene, including poor body odor, observed in patients experiencing a first-episode of schizophrenia are associated with an impairment in left nostril, and possibly left hemisphere, olfactory processing.


[Photoinduced peroxidase reduction. Reaction with indolylacetic acid].
Kinetics of photoinduced reaction of HRP reduction by indolil acetic acid and dependence of the reaction rate and fluorescence of indoliol acetic acid on quenchers (I, Cst concentration was investigated. It was demonstrated that both I- and Cst action on the reaction differed from that on fluorescence. So the most probable reaction pathway is that through metastable triplet state of the substrate.


Peer, parent and media influences on adolescent smoking by developmental stage.
Previous studies of social influences on adolescent smoking have focused on peers and parents, using data collected prior the 1998 Master Settlement Agreement. This study used the 2004 wave of the National Youth Tobacco Survey to examine associations between peer smoking, smoking at home, tobacco-related media exposure, and smoking behavior during early and middle adolescence. Findings indicate that peer smoking and smoking at home remain strongly associated with current smoking among early and middle adolescents, controlling for gender, race/ethnicity and exposure to tobacco industry and anti-tobacco media. The magnitude of the association between peer smoking and current smoking decreases from early adolescence to middle adolescence while the association between smoking at home and current smoking is static across developmental stage. Exposure to tobacco-related media is associated with increased current and former smoking in both early and middle adolescence.


Profiling the U.S. Sick Leave Landscape: Presenteeism among Females.
To profile the sick leave landscape in the United States. The 2011 Leave Supplement of the American Time Use Survey. Bivariate and multivariate analyses to identify (i) employees without sick pay coverage and (ii) employees who attend work sick. Sixty-five percent of full-time employees have sick pay coverage. Coverage rates are below 20 percent for employees with hourly wages below $10, part-time employees, and employees in the hospitality and leisure industry. Each week, up to 3 million U.S. employees go to work sick. Females, low-income earners, and those aged 25 to 34 years have a significantly elevated risk of presenteeism behavior.


Prospective evaluation of clinical and ultrasound findings in ankle disease in juvenile idiopathic arthritis: importance of ankle ultrasound.
To prospectively compare clinical examination of the ankle structures with ultrasound (US) findings. In 42 children with juvenile idiopathic arthritis (JIA; 25 girls, 17 boys, mean age 11.3 yrs, range 2.3-22.3 yrs), a total of 61 swollen/painful ankles were assessed clinically and ultrasonographically. Accurate clinical examination of the entire ankle joint was performed, focusing especially on 3 regions - tibiotalar joint and medial and lateral tendons. Clinical and US findings were both scored 0-3 (normal-severe). US demonstrated no signs of tibiotalar joint effusion in 14 out of 43 ankles considered clinically involved. For the medial tendons, US showed tenosynovitis in 13 ankles out of 31 thought to be clinically normal; and for the lateral tendons, of the 19 deemed to be clinically involved, less than 50% had involvement on US. Very poor agreement was observed comparing the clinical and US scores for the 3 regions: tibiotalar joint, kappa = 0.3; medial tendons, kappa = 0.24; lateral tendons, kappa = 0.25. With regard to other ankle structures, only 39% of the subtalar (talocalcaneal) joints considered clinically involved were deemed abnormal on US. Finally, of the 10 ankles with talonavicular US effusion, only 2 were considered clinically involved. Using US findings as the "gold standard," clinical examination of the ankle in children with JIA was found to be inadequate in identifying the structures involved. US assessment prior to any glucocorticoid injection should be considered to improve the outcome. A prospective study comparing the outcome following clinical- versus US-guided ankle joint injection should be undertaken, to confirm our findings.


Glycosylated low density lipoprotein is more sensitive to oxidation: implications for the diabetic patient?
Oxidised low density lipoprotein (LDL) is considered to be atherogenic. This study examined the relationship between glycosylation and oxidation of LDL from 10 normocholesterolaemic Type 2 diabetic patients, 10 hypercholesterolaemic Type 2 diabetic patients, and 10 normocholesterolaemic non-diabetic subjects. LDL was isolated by sequential ultracentrifugation and susceptibility to oxidation assessed by measuring thiobarbituric reactive substances (TBARS) during a 4-h oxidation period. LDL glycosylation was measured by aminophenylborate gel chromatography. Results demonstrated an increased susceptibility to oxidation in LDL from both diabetic groups, the mean 3-h TBARS values being 35.2 +/- 2.1 and 36.4 +/- 2.6 nmol MDA/mg LDL protein for normocholesterolaemic and hypercholesterolaemic diabetic patients compared with 24.5 +/- 2.5 nmol MDA/mg LDL protein for control subjects. LDL glycosylation of 2.20% +/- 0.11% and 2.89% +/- 0.46% for normocholesterolaemic and hypercholesterolaemic diabetic LDL was significantly higher than that for the non-diabetic control subjects of 1.60% +/- 0.12% (P < 0.02). There was a significant positive correlation (P < 0.005) between LDL glycosylation and LDL oxidation. The esterified/free cholesterol ratio which correlated positively with oxidation (P < 0.01) was significantly higher in LDL from both diabetic groups compared with LDL from control subjects (P < 0.01). Thus the increased incidence of atherosclerosis in diabetes may be related to glycosylation of LDL through its increased susceptibility to oxidation.


[Investigation of osteoporotic changes of the long tubular leg bones for identification of human biological age].
The authors propose to introduce into expert practice a number of methods estimating age-related osteoporosis by such quantitative characteristics as coefficient of optical transmission, optic density, porosity. The data confirm nonlinear dependence of age dynamics of osteoporotic changes which can be more effectively described by equations of polynomial regression.


Harmful Effects of Granulocytic Myeloid-Derived Suppressor Cells on Tuberculosis Caused by Hypervirulent Mycobacteria.
The role of myeloid-derived suppressor cells (MDSCs) in patients with severe tuberculosis who suffer from uncontrolled pulmonary inflammation caused by hypervirulent mycobacterial infection remains unclear. This issue was addressed using C57BL/6 mice infected with highly virulent Mycobacterium bovis strain MP287/03. CD11b+GR1int population increased in the bone marrow, blood and lungs during advanced disease. Pulmonary CD11b+GR1int (Ly6GintLy6Cint) cells showed granularity similar to neutrophils and expressed immature myeloid cell markers. These immature neutrophils harbored intracellular bacilli and were preferentially located in the alveoli. T-cell suppression occurred concomitantly with CD11b+GR1int cell accumulation in the lungs. Furthermore, lung and bone marrow GR1+ cells suppressed both T-cell proliferation and interferon γ production in vitro. Anti-GR1 therapy given when MDSCs infiltrated the lungs prevented expansion and fusion of primary pulmonary lesions and the development of intragranulomatous caseous necrosis, along with increased mouse survival and partial recovery of T-cell function. Lung bacterial load was reduced by anti-GR1 treatment, but mycobacteria released from the depleted cells proliferated extracellularly in the alveoli, forming cords and clumps. Granulocytic MDSCs massively infiltrate the lungs during infection with hypervirulent mycobacteria, promoting bacterial growth and the development of inflammatory and necrotic lesions, and are promising targets for host-directed therapies.