Feeding during the first 3 days after birth other than breast milk is associated with early cessation of exclusive breastfeeding.
Exclusive breastfeeding (EBF) has significant effect on morbidity and mortality. EBF is established when breastmilk alone is exclusively fed from birth until 6 months of age. However, feeding during the first 3 days after birth is often ignored for various reasons. We aimed to assess the role of feeding during the first 3 days in respect of early cessation of EBF. Data of 1,040 children aged under 6 months was derived from the baseline survey of Suchana, a large-scale nutrition program, conducted in Sylhet, Bangladesh, and subsequently analysed. Guidelines established by World Health Organization were used to define EBF and feeding during the first 3 days. The strength of the association between feeding during the first 3 days and early cessation of EBF was established using multiple logistic regression after adjusting for other covariates. Among all children, around 62% and 13% were exclusively breastfed and were fed something other than breastmilk within the first 3 days of birth, respectively. Feeding during the first 3 days was independently and significantly associated with early cessation of breastfeeding (adjusted odds ratio: 1.94, 95% confidence interval [1.31, 2.88], p = .001). Less than four antenatal care (ANC) visits, increased child's age and increased household size were also independently associated with early cessation of EBF. Feeding during the first 3 days of birth is a significant predictor of early cessation of EBF. Simple counselling activities to discourage feeding anything within the first few days of birth may increase the prevalence of EBF in rural Bangladesh without investing additional resources.


Polymorphonuclear neutrophil chemotaxis induced and inhibited by Bacteroides spp.
A possible virulence factor for Bacteroides subcutaneous abscesses has been found. The effect of Bacteroides culture filtrate and outer membrane on chemotaxis of rabbit peritoneal polymorphonuclear (PMN) neutrophils was assayed in Boyden chambers and via exocytosis of N-acetyl-beta-glucosaminidase. Both Bacteroides culture filtrate and outer membrane elicited some chemotaxis, as measured in the Boyden chamber; however, they had little effect upon exocytosis in cytochalasin B-treated PMN neutrophils. In the presence of serum complement, they completely abolished PMN neutrophil movement in the Boyden chamber assay, yet they gave a definite positive response for the exocytosis assay in the presence of serum complement or activated complement fragment.


[State of homeostasis links in the children with intestinal colic].
The state of homeostasis links in the children with intestinal colic is represented by the following parameters and clinical characteristics. The data of investigated children's contingent with intestinal colic prevailed by following comorbidities: SARS--12 (18.18% ± 4.78%), protein-energy malnutrition--9 (12.85% ± 3.82%), pneumonia--6 (8.57% ± 3.57%), atopic dermatitis--7 (10.00% ±.3.57%). All children have a next complaints: flatulence (100%), in the 62 children (88.57% ± 3.82%) were identificated frequent regurgitation, in the 48 (80.33%)--hyperbilirubinemia. ALT levels were elevated in 25 children (41%) and 31 (51.66%) children had increased levels of AST. IL8 level were elevated in the 40 children (71.42%). The level of antibodies to elastase was greatly increased in all 56 (100%) children.


Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability.
Systemic inflammation co-activates coagulation, which unchecked culminates in a lethal syndrome of multi-organ microvascular thrombosis known as disseminated intravascular coagulation (DIC). We studied an endotoxin-induced inflammatory state in rats to identify biomarkers of hemostatic imbalance favoring hypercoagulability. Intraperitoneal injection of LPS at 15 mg/kg body weight resulted in peripheral leukopenia and widespread neutrophilic sequestration characteristic of an acute systemic inflammatory response. Early indicators of hemostatic pathway activation developed within 4 hours, including increased circulating concentrations of procoagulant extracellular vesicles (EVs), EVs expressing endothelial cell and platelet membrane markers, and high concentration of soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1), and D-dimers. Inflammation persisted throughout the 48-hour observation period; however, increases were found in a subset of serum microRNA (miRNA) that coincided with gradual resolution of hemostatic protein abnormalities and reduction in EV counts. Dose-adjusted LPS treatment in rats provides a time-course model to develop biomarker profiles reflecting procoagulant imbalance and rebalance under inflammatory conditions.


Genetic analysis of human DNA recovered from minute amounts of serum or plasma.
A rapid and inexpensive method is described where a small amount of serum or plasma was used as the source of DNA for genetic analysis. Using a silica gel matrix DNA was isolated from 50 microliters of archived serum or plasma. The specimens were collected from 13 individuals at two separate time points 3-6 years apart. The polymorphic region of second exon of the MHC class II gene HLA DQA1 was amplified using the polymerase chain reaction (PCR) to sufficient quantities to permit genetic analysis using allele-specific oligonucleotides (ASO). Allelic typing of each specimen was performed and the reproducibility of the method was demonstrated in that in all 13 cases the two independently isolated specimens produced the identical ASO binding patterns. No qualitative difference was noted in the amplified product generated from plasma or serum. This study demonstrates (a) that minute amounts of serum or plasma are able to provide sufficient quantity and quality of DNA to permit genetic analyses (b) and that the source of serum can be archived for many years.


Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data.
Pre-eclampsia is a major cause of mortality and morbidity during pregnancy and childbirth. Antiplatelet agents, especially low-dose aspirin, might prevent or delay pre-eclampsia, and thereby improve outcome. Our aim was to assess the use of antiplatelet agents for the primary prevention of pre-eclampsia, and to explore which women are likely to benefit most. We did a meta-analysis of individual patient data from 32,217 women, and their 32,819 babies, recruited to 31 randomised trials of pre-eclampsia primary prevention. For women assigned to receive antiplatelet agents rather than control, the relative risk of developing pre-eclampsia was 0.90 (95% CI 0.84-0.97), of delivering before 34 weeks was 0.90 (0.83-0.98), and of having a pregnancy with a serious adverse outcome was 0.90 (0.85-0.96). Antiplatelet agents had no significant effect on the risk of death of the fetus or baby, having a small for gestational age infant, or bleeding events for either the women or their babies. No particular subgroup of women was substantially more or less likely to benefit from antiplatelet agents than any other. Antiplatelet agents during pregnancy are associated with moderate but consistent reductions in the relative risk of pre-eclampsia, of birth before 34 weeks' gestation, and of having a pregnancy with a serious adverse outcome.


Impact of self-citation on the H index in the field of academic radiology.
The Hirsch Index (H index) is widely applied as a metric of scientific productivity. The purpose of this study was to evaluate the role of self-citation on the H index in academic radiology. Through the National Resident Matching Program's Web site, one third (47/139) of radiology residency programs were selected randomly. All chairpersons and full professors were included. Using the Scopus database, we calculated the H index as well as the number of cumulative citations with and without inclusion of self-citations. We determined the proportion of academic staff in which H index increased by one, two, or greater than two integers. We also correlated the proportional increase in H index before and after inclusion of self citations with the number of publications. A total of 487 academic staff (47 chair and 440 professors) was identified. Because of self-citation, mean ± SD of the H index increased from 13.7 ± 9.9 to 14.0 ± 10.2; mean ± SD of cumulative citations increased from 1804 ± 1889 to 1870 ± 1971. H index numbers did not change in 376/487 (77%) authors as a result of self-citation. There was no correlation between number of publications and proportional change of H index. The effect of self-citation is minimal in academic radiology, as evidenced by the fact that cumulative citations increase by only 2% and the large majority of H index values do not change by even a single integer after inclusion of self-citation.


Shape transformation and self-alignment of Fe-based nanoparticles.
New types of functional material structures will emerge if the shape and properties are controlled in three-dimensional nanodevices. Possible applications of these would be nanoelectronics and medical systems. Magnetic nanoparticles (MNPs) are especially important in electronics such as magnetic storage, sensors, and spintronics. Also, in those that are used as magnetic resonance imaging contrasts, and tissue specific therapeutic agents, as well as in the labeling and sorting of cells, drug delivery, separation of biochemical products, and in other medical applications. Most of these applications require MNPs to be chemically stable, uniform in size, and controllable in terms of their magnetic properties and shape. In this paper three new functions of iron (Fe)-based nanoparticles are reported: shape transformation, oxidation prevention, and self-alignment. The shape of the Fe nanoparticles could be controlled by changing their oxidation states and properties by using a nanocarbon coating. Full field X-ray microscopy using synchrotron radiation revealed controllable magnetic properties of MNPs at the L3 edge which depended on the oxidation states. Then, inkjet printing was successfully performed to deposit a uniform layer of MNPs by the size.


Lysolipid containing liposomes for transendothelial drug delivery.
Designing efficient 'vectors', to deliver therapeutics across endothelial barriers, in a controlled manner, remains one of the key goals of drug development. Recently, transcytosis of liposome encapsulated fluorescence marker calcein across a tight cell barrier was studied. The most efficient liposomes were found to be liposomes containing sufficient amount of alkyl phospholipid (APL) perifosine. APLs have similar structure as lysophosphatidyl choline (LPC), since APLs were synthesized as metabolically stable analogues of LPC, which increases endothelial permeability directly by inducing endothelial cell contraction, resulting in formation of gaps between endothelial cells. Since one of the unique properties of lysolipid, containing liposomal formulations is dynamic equilibrium of lysolipids, which are distributed among liposomes, micelles, and free form, such liposomes represent a reservoir of free lysolipids. On the other hand lysolipid containing liposomes also represent a reservoir of an encapsulated hydrophilic drug. We hypothesize that free lysolipids, with highest concentration in vicinity of drug carrying liposomes, compromise endothelial integrity, primarily where concentrations of liposomes is the highest, in a similar manner as LPC, by formation of gaps between endothelial cells. Liposome encapsulated drug, which leaks from liposomes, due to liposome destabilization, caused by lysolipid depletion, can therefore be efficiently transported across the locally compromised endothelial barrier. This hypothesis could be verified: by measuring binding of perifosine and other lysolipids to albumin and to lysophospholipid receptor (LPL-R) group; formation of stress fibers and subsequent cell contraction; activation of RhoA, and endothelial barrier dysfunction; by a synthesis of other LPC analogues with high critical micellar concentration and measuring their effect on transendothelial permeability in presence and absence of albumin. We propose that lysolipid containing liposomal formulations might be used as nonspecific transendothelial transport vector, since leakage of liposome encapsulated active drug occurs simultaneously with the release of the lysolipids. The concentration of the active drug is therefore expected to be the highest at the site of compromised endothelial barrier. By appropriate choice of the lysolipids an endothelial barrier would stay open only for a short time. Use of such liposomes would potentially maximize the delivery of the drug while limiting the passage of toxic substances and pathogens across the endothelial barrier. Combining lysolipid containing liposomes with superparamagnetic iron oxide nanoparticles or a targeting ligand might be required to efficiently localize drug delivery to a disease affected tissue and to avoid endothelial disruption over the entire body.


Do wet suits affect swimming speed?
A randomised cross-over trial was conducted to see if wet suits increase swimming speed--a question which has been fiercely debated in the fat-growing endurance sport of Triathlon. Sixteen swimmers volunteered to undertake two 30 minute swims, one with and one without a wet suit. With wet suits the subjects swam an average of 24.9 lengths of a 66 m pool. Without wet suits they swam 23.2 lengths. A 95% confidence interval for the difference is from 0.8 to 2.6 lengths (p less than 0.001). This result suggests that regulations about the use of wet suits must be agreed internationally to ensure equal competition whilst promoting the health and safety aspects of sport.


The impact of platelet transfusion in massively transfused trauma patients.
The impact of platelet transfusion in trauma patients undergoing a massive transfusion (MT) was evaluated. The Institutional Trauma Registry and Blood Bank Database at a Level I trauma center was used to identify all patients requiring an MT (≥10 packed red blood cells [PRBC] within 24 hours of admission). Mortality was evaluated according to 4 apheresis platelet (aPLT):PRBC ratios: Low ratio (<1:18), medium ratio (≥1:18 and <1:12), high ratio (≥1:12 and <1:6), and highest ratio (≥1:6). Of 32,289 trauma patients, a total of 657 (2.0%) required an MT. At 24 hours, 171 patients (26.0%) received a low ratio, 77 (11.7%) a medium ratio, 249 (37.9%) a high ratio, and 160 (24.4%) the highest ratio of aPLT:PRBC. After correcting for differences between groups, the mortality at 24 hours increased in a stepwise fashion with decreasing aPLT:PRBC ratio. Using the highest ratio group as a reference, the adjusted relative risk of death was 1.67 (adjusted p = 0.054) for the high ratio group, 2.28 (adjusted p = 0.013) for the medium ratio group, and 5.51 (adjusted p < 0.001) for the low ratio group. A similar stepwise increase in mortality with decreasing platelet ratio was observed at 12 hours after admission and for overall survival to discharge. After stepwise logistic regression, a high aPLT:PRBC ratio (adjusted p < 0.001) was independently associated with improved survival at 24 hours. For injured patients requiring a massive transfusion, as the apheresis platelet-to-red cell ratio increased, a stepwise improvement in survival was seen. Prospective evaluation of the role of platelet transfusion in massively transfused patients is warranted.


Obesity and peripheral neuropathy risk: a dangerous liaison.
This study investigates motor (MNCS) and sensory (SNCS) nerve conduction in a sample of non-diabetic obese people without symptoms suggestive of neuropathy and looks for a possible metabolic alteration. Twenty-one patients and 20 age-matched controls underwent (a) MNCS (median, ulnar, peroneal, and tibial) and SNCS (median, ulnar, and sural); (b) quantitative sensory testing to measure sensory threshold for vibration, warm and cold sensation (WS-CS), heat and cold-induced pain; and (c) blood sample analysis to evaluate glucose and insulin levels and calculate the quantitative insulin-sensitivity check index (QUICKI). The obese group showed significantly decreased compound muscle action potential amplitude of tibial and peroneal nerves and decreased sensory action potential amplitude of all nerves. Most of the sensory thresholds were altered in obese patients. Insulin serum levels were significantly increased while QUICKI decreased in obese patients. WS and CS from the index and little fingers and WS from the big toe significantly correlated with QUICKI. Thermal and pain thresholds from the index and thermal thresholds from the little finger correlated with QUICKI values. The non-diabetic obese patients showed a subclinical involvement of different diameter sensory fibers. Such impairment was related to hyperinsulinemia and insulin sensitivity. The increase in sensory threshold of obese patients might be due to a metabolic alteration, potentially leading to a future clinical neuropathy.


Volatile organic compounds associated with Plasmodium falciparum infection in vitro.
In order to identify new ways to prevent transmission of vector-borne diseases such as malaria, efforts have been made to understand how insects are attracted to humans. Vector-host interaction studies have shown that several volatile compounds play an important role in attracting mosquitoes to human targets. A headspace solid-phase micro-extraction/gas chromatography-mass spectrometry (HSPME GC-MS) analysis of the volatile organic composition of extracellular vesicles (EVs) and supernatants of ultracentrifugation (SNUs) was carried out in Plasmodium falciparum-infected cultures with high and low parasitemias. A list of 18 volatile organic compounds (VOCs) was obtained from the EVs of both infected and uninfected RBCs with 1,2,3-Propanetriol, diacetate (diacetin) increased in the infected EVs, regardless of the parasitemia of the culture. The supernatant analysis, however, gave off 56 VOCs, with pentane 2,2,4-trimethyl being present in all the SNUs of uninfected erythrocytes but absent from the parasite-infected ones. Standing out in this study was hexanal, a reported insect attractant, which was the only VOC present in all samples from SNUs from infected erythrocytes and absent from uninfected ones, suggesting that it originates during parasite infection. The hexanal compound, reportedly a low-level component found in healthy human samples such as breath and plasma, had not been found in previous analyses of P. falciparum-infected patients or cultures. This compound has been reported as an Anopheles gambiae attractant in plants. While the compound could be produced during infection by the malaria parasite in human erythrocytes, the A. gambiae attraction could be used by the parasite as a strategy for transmission.


Positive impact of IPS supported employment on PTSD-related occupational-psychosocial functional outcomes: Results from a VA randomized-controlled trial.
Posttraumatic stress disorder (PTSD) has significant negative effects on occupational, interpersonal, and social functioning. Supported employment is highly effective in helping people with a diagnosis of PTSD obtain and maintain competitive employment. However, less is known about the impact of supported employment on functioning in work or school, social, and interpersonal areas as specifically related to the symptoms of PTSD. The Veterans Individual Placement and Support Toward Advancing Recovery study was a prospective, multisite, randomized, controlled trial that compared Individual Placement and Support (IPS) supported employment with a stepwise vocational rehabilitation involving transitional work (TW) assignments with unemployed veterans with PTSD diagnoses (n = 541) at 12 Veterans Administration (VA) medical centers. This analysis focuses on the PTSD-related functional outcomes over the 18-month follow-up period. Compared with those randomized to TW, the PTSD Related Functioning Inventory (PRFI) total score significantly improved for participants randomized to IPS (LSMeans difference = -3.92, 95% CI [-7.49, -.36]; p = .03) over 18 months. When the Work/School subscale of the PRFI was removed from the analysis, the IPS group continued to show significant improvements compared with the TW group on the PRFI relationship and lifestyle domains (LSMeans difference = -2.37, 95% CI [-4.74, .00]; p = .05), suggesting a positive impact of IPS beyond work/school functioning. Compared with the usual-care VA vocational services for veterans with PTSD, IPS supported employment is associated with greater improvement in overall PTSD-related functioning, including occupational, interpersonal, and lifestyle domains. In addition to superior employment outcomes, IPS has a positive impact on occupational-psychosocial functioning outcomes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Hexachlorobenzene and substituted pentachlorobenzenes (X-C6Cl5) as inducers of hepatic cytochrome P-450-dependent mono-oxygenases.
Hexachlorobenzene (HCB) and 2,3,4,4',5-pentachlorobiphenyl induced a similar spectrum of cytochrome-P-450-dependent mono-oxygenase activities in the rat, including 4-dimethylaminoantipyrine N-demethylase, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD). Levels of individual cytochrome P-450 isozymes and various mono-oxygenase activities in liver microsomes from rats treated with substituted pentachlorobenzene (X-C6Cl5) and 4'-substituted-2,3,4,5-tetrachlorobiphenyl (X-C12 H5Cl4) analogues demonstrated the remarkable effects of substituent structure on induction activities. The chloro- and bromopentachlorobenzenes induced hepatic microsomal 4-dimethylaminoantipyrine N-demethylase, AHH and EROD; the iodo-, fluoro-, acetamino- and nitropentachlorobenzene analogues together with pentachlorobenzene weakly induced both AHH and EROD (approximately 2-fold or less); and the remaining substituted pentachlorobenzenes tested (X = CH3, OCH3 and OH) were relatively inactive as inducers of microsomal mono-oxygenases. Substituent effects were observed for the induction of liver microsomal cytochromes P-450a, P-450b + e, P-450c, P-450d and total cytochrome P-450 by the X-C6Cl5 and X-C12H5Cl4 analogues. The chloro- and bromopentachlorobenzene analogues in both series induced total cytochrome P-450 and cytochromes P-450a to P-450d, whereas the hydroxy-, methyl- and methoxy-substituted analogues in both series were relatively inactive as inducers of cytochrome P-450. Iodo-, fluoro- and nitropentachlorobenzene were weak 3-methylcholanthrene-type inducers and, in contrast to the corresponding biphenyl analogues, had little or no effect on the induction of cytochromes P-450a, P-450c and P-450d.(ABSTRACT TRUNCATED AT 250 WORDS)


[Use of urea in the treatment of patients with suppurative diseases of the lungs and pleura].
Under analysis were results of treatment of 96 patients with suppurative diseases of the lungs and pleura. The 30% solution of urea was locally used in 59 patients as pleural punctures, introduction of the solution through drains into the purulent cavity by dropping irrigation of bronchi and tamponage of open purulent cavities. Gram-positive microorganisms were found to die in the 30% solution of urea within 30 min.--3 h, gram-negative ones--within 30 min.--1 h. The introduction of urea directly into the purulent infection focus against the background of general therapy allowed to quickly block the acute phase of the suppurative process, to prepare the patients to planned operations and to reduce the amount of postoperative complications as compared with a control group of patients who were treated by routine local antiseptic drugs.


[Application of species distribution models in the prediction of marine potential habitat: A review].
The relationship between the distribution of halobios and environmental variables has been a focus of present research in marine ecology. Species distribution models (SDMs) have been widely employed to predict the distribution patterns and potential habitat suitability assessments of marine species and provide an efficient approach for marine biodiversity conservation, invasive species prevention, and fishery management. SDMs mainly include habitat suitability index models, mechanism models, and statistical models. In this paper, the theoretical basis of SDMs was firstly concluded and summarized. Next, the exploitation and case-studies of SDMs, especially the statistical models, for predicting potential distribution of marine species were reviewed. Then, comparisons of various methods for variable selection and model validation were made. Conclusions could be drawn that Akaike information criterion showed excellent performance when it came to variable selection, while Kappa coefficient and Area Under receiver operating character Curve (AUC) were widely used in relation to model validation. Finally, problems and prospects of SDMs were discussed. With the development of research on physiological characteristics, using mechanism models to predict potential habitats of halobios would become a trend.


Modal frequency degeneracy in thermally loaded optical resonators.
We observe power coupling from the fundamental mode to frequency-degenerate higher-order spatial modes in optical resonators illuminated with a 30 W laser. Thermally-induced modal frequency degeneracy facilitates power transfer from the fundamental mode to higher-order modes, reduces power coupling into the cavity, and triggers power fluctuations. Modeling thermoelastic deformation of a mirror's surface shows predicted modal frequency degeneracy to be in reasonable agreement with experimental observations. Predictions for the Laser Interferometer Gravitational-wave Observatory (LIGO) show that the circulating fundamental-mode power necessary for gravitational-wave detection is compromised at coating absorptions of 3.8 and 0.44 ppm for Enhanced and Advanced LIGO Fabry-Pérot cavities, respectively.


Development of mucoadhesive modified kappa-carrageenan/pectin patches for controlled delivery of drug in the buccal cavity.
In this study, modified kappa-carrageenan/pectin hydrogel patches were fabricated for treatment of buccal fungal infections. For this purpose, kappa-carrageenan-g-acrylic acid was modified with different thiolated agents (L-cysteine and 3-mercaptopropionic acid), and the thiol content of the resulting modified kappa-carrageenan was confirmed by elemental analyzer. Then, the hydrogel patches were fabricated, and characterized by Fourier-transform infrared spectroscopy, thermogravimetric analysis, ex vivo mucoadhesion test, and swelling behavior. Triamcinolone acetonide was added either directly or by encapsulating within the poly(lactic-co-glycolic acid) nanoparticles. The release amount of the drug from the directly loaded patch was 7.81 mg/g polymer, while it was 3.28 mg/g polymer for the encapsulated patch with the same content at 7 hr. The hydrogel patches had no cytotoxicity by cell culture studies. Finally, the drug loaded hydrogel patches were demonstrated antifungal activity against Aspergillus fumigatus and Aspergillus flavus. These results provide that the novel modified kappa-carrageenan and pectin based buccal delivery system has promising antifungal property, and could have advantages compared to conventional buccal delivery systems.


Hippocampal injection of the exercise-induced myokine irisin suppresses acute stress-induced neurobehavioral impairment in a sex-dependent manner.
Stress disrupts a variety of neural processes, including reducing levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. In contrast, exercise increases BDNF and is beneficial for health and cognition. Irisin is a myokine that is released into circulation during exercise. Although its main known functions are browning white adipose tissue and improving glucose homeostasis, Irisin also mediates the activation of an exercise-induced BDNF-mediated neuroprotective pathway in the hippocampus. Therefore, we tested the hypothesis that Irisin can counteract the deleterious effects of acute stress when directly injected into the hippocampus. To test our hypothesis, we used a 3-hr long physical restraint stress event in adult female and male mice. Acute stress resulted in sex-dependent increased anxiety-like behaviors and memory impairment in a combined open field/novel object recognition (OF/NOR) test, affecting male mice only. Moreover, acute stress also reduced skin temperature and body weight in both females and males. We then injected Irisin into the hippocampus via bilateral stereotaxic injection and repeated the acute stress paradigm and combined OF/NOR test. We found that Irisin partially blocked stress-induced anxiety-like behavior and memory impairment in male mice, while also preventing the reduction in skin temperature and body weight. In females Irisin only prevented the body weight reduction but showed no beneficial effects on neurobehaviors. Our results suggest a novel role for Irisin in counteracting acute stress-induced neurobehavioral and physiological abnormalities. Also, our results support the idea that exercise can be a potentially effective tool to promote the maintenance of healthy neural function. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


[Expression of cation-chloride cotransporters KCC2 and NKCC1 in brainstem of para- chlorophenylalanine-induced acute insomnia rats].
To explore the possible roles of KCC2 and NKCC1 in the pathological mechanism of acute insomnia in rats. A total of 18 Sprague-Dawley rats were randomly selected into model, interference and normal control groups.The expressions of KCC2 and NKCC1 in brainstem were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.The concentration of intracellular Cl(-) ([Cl(-)]i) in brainstem was detected by fluorescence probe MQAE with laser confocal microscopy. (1) Comparing with the control group, both KCC2 mRNA and protein expression were down-regulated in the model and interference groups (mRNA:0.196 ± 0.021 vs 0.939 ± 0.109, P < 0.05; 0.485 ± 0.026 vs 0.939 ± 0.109, P < 0.05; protein expression:0.363 ± 0.058 vs 0.967 ± 0.155, P < 0.05; 0.663 ± 0.106 vs 0.967 ± 0.155, P < 0.05).However they became up-regulated in the interference group versus the model group (mRNA: 0.485 ± 0.026 vs 0.196 ± 0.021, P < 0.05; protein expression:0.663 ± 0.106 vs 0.363 ± 0.058, P < 0.05). (2) Comparing with the control group, both NKCC1 mRNA and protein expression in the model group were slightly up-regulated.But statistical difference was insignificant (mRNA: 0.344 ± 0.026 vs 0.320 ± 0.019, P > 0.05; protein expression:0.244 ± 0.010 vs 0.230 ± 0.021, P > 0.05).There was down-regulation in the interference group versus the model and control groups (mRNA: 0.066 ± 0.031 vs 0.320 ± 0.019, P < 0.05; 0.066 ± 0.031 vs 0.344 ± 0.026, P < 0.05; protein expression:0.131 ± 0.012 vs 0.230 ± 0.021, P < 0.05; 0.131 ± 0.012 vs 0.244 ± 0.010, P < 0.05). (3) Comparing with the control group, [Cl(-)]i became up-regulated in the model group (0.0315 ± 0.0039 vs 0.0164 ± 0.0019, P < 0.05).It was down-regulated in the interference group versus the model group (0.0182 ± 0.0013 vs 0.0315 ± 0.0039, P < 0.05), but higher than control group without statistical difference (0.0182 ± 0.0013 vs 0.0164 ± 0.0019, P > 0.05). The down-regulation of KCC2 and rise of [Cl(-)]i in brainstem may participate in the pathological mechanism of acute insomnia in rats. And the mechanism of sedative-hypnotic diazepam may be operate through an up-regulation of KCC2, a down-regulation of NKCC1 and decreased [Cl(-)]i.


Mars' surface is not universally biocidal.
The Mars surface/near-surface is often considered to be biocidal. Here, diverse lines of evidence are presented indicating that some terrestrial microbes can survive the in-situ conditions albeit in an inactive state. For the purposes of planetary protection, it is important to consider what we mean by a planetary 'surface'; this term has qualitatively distinct definitions fordifferent scientific disciplines, and can also have different meanings from a humanviewpoint versus that of a microbial cell. Most microbial cells spores or other cells deposited on Mars, even those that initially fall on the outward-facing part of the absolute surface, will fall within pores of the regolith or become covered by its dust. They are, therefore, protected from ultra-violet radiation. Desiccating conditions and low temperatures (-40 to -70°C) can act to preserve rather than kill all microbes, potentially maintaining cellular viability - especially for certain extremophiles - over geological timescales. Whereas salts are ubiquitous on Mars, many terrestrial microbes are highly tolerant to NaCl and other salts, and these substances (including potentially inhibitory chaotropes such as MgCl2 and perchlorates) cannot access cells in the absence of a liquid milieu. Whereas the Mars regolith is nutrient-deplete and conditions may be acidic in places, oligotrophic conditions per se are not biocidal and many terrestrial microbes can thrive in acidic conditions (some acidophiles can proliferate at or below pH 0). The low temperatures of Mars' surface are not conducive to metabolic activity, but the biophysical sophistication and robust stress biology of many terrestrial microbes, and the protection afforded by Martian conditions, are likely to ensure the long-term viability of some extremophilic microbes if transported to Mars.


The effect of prostaglandin and gonadotrophins (GnRH and hCG) injection combined with the ram effect on progesterone concentrations and reproductive performance of Karakul ewes during the non-breeding season.
The effect of prostaglandin and gonadotrophins (GnRH and hCG) combined with the ram effect on the progesterone (P4) concentrations and reproductive performance of Karakul ewes was investigated during non-breeding season. Ewes (n = 93) received a male effect and were divided into two treatment groups including GnRH - hCG (hCG, n = 32), GnRH - GnRH (GnRH, n = 30) and a control (n = 31) group. This study was carried out from April (hormonal injection) to October (lambing). The first doses of GnRH (4.2 μg, Buserelin) were injected at the beginning of the study in treatment groups. These ewes were treated with hCG (250 IU) or the second GnRH dose five days later. All animals received two injections (ten days apart) of 150 μg PGF2α five days after the hCG or the second GnRH injection. Mating was initiated two days after the second prostaglandin injection and lasted for 34 days. Blood samples were collected by jugular venipuncture on days -10, -5, 0 (first PGF2α injection), 17 and 30 during the study. Pregnancy diagnosis was performed through transabdominal ultrasonography on day 40 after the removing of ram. Conception rate was 93.8, 90 and 87.1% in the hCG, GnRH and control groups, respectively. Lambing rate tended to increase in the hCG group compared with the control group (87.1 versus 58.1%; p < .1). There was no significant difference in P4 concentrations among studied groups in identical sampling times (p > .05). In conclusion, the administration of prostaglandin and hCG in combination with the ram effect tended to decrease lambing period. In other words this protocol tended to increase lambing rate at the first cycle. Treatment with hCG or GnRH did not increase serum P4 concentrations of treated Karakul ewes during the non-breeding season.


The effector AvrRxo1 phosphorylates NAD in planta.
Gram-negative bacterial pathogens of plants and animals employ type III secreted effectors to suppress innate immunity. Most characterized effectors work through modification of host proteins or transcriptional regulators, although a few are known to modify small molecule targets. The Xanthomonas type III secreted avirulence factor AvrRxo1 is a structural homolog of the zeta toxin family of sugar-nucleotide kinases that suppresses bacterial growth. AvrRxo1 was recently reported to phosphorylate the central metabolite and signaling molecule NAD in vitro, suggesting that the effector might enhance bacterial virulence on plants through manipulation of primary metabolic pathways. In this study, we determine that AvrRxo1 phosphorylates NAD in planta, and that its kinase catalytic sites are necessary for its toxic and resistance-triggering phenotypes. A global metabolomics approach was used to independently identify 3'-NADP as the sole detectable product of AvrRxo1 expression in yeast and bacteria, and NAD kinase activity was confirmed in vitro. 3'-NADP accumulated upon transient expression of AvrRxo1 in Nicotiana benthamiana and in rice leaves infected with avrRxo1-expressing strains of X. oryzae. Mutation of the catalytic aspartic acid residue D193 abolished AvrRxo1 kinase activity and several phenotypes of AvrRxo1, including toxicity in yeast, bacteria, and plants, suppression of the flg22-triggered ROS burst, and ability to trigger an R gene-mediated hypersensitive response. A mutation in the Walker A ATP-binding motif abolished the toxicity of AvrRxo1, but did not abolish the 3'-NADP production, virulence enhancement, ROS suppression, or HR-triggering phenotypes of AvrRxo1. These results demonstrate that a type III effector targets the central metabolite and redox carrier NAD in planta, and that this catalytic activity is required for toxicity and suppression of the ROS burst.


[Urinary tract infections characterization in a spinal cord injury rehabilitation unit].
Urinary tract infection (UTI) is a common problem among patients with spinal cord injury (SCI) accounting for 50% of nosocomial infections in some international studies. There are several risk identified like: increased residual urine and bladder pressure, bladder overfilled and catheter use. Protocols for UTI's diagnosis and management, used in our Unit, are based on criteria for bladder dysfunction of the National Institute of Disability and Rehabilitation Research (NIDRR). Identify and characterize the bacterial spectrum and susceptibility to antibiotics; determinate the infection frequency according to voiding method and American Spinal Injury Association (ASIA) classification; check the possibility of cross infections between inpatients. 158 urine samples were obtained and microbiologically evaluated from 27 inpatients (10 woman and 17 men) during 19 consecutive weeks. Mean age of the patients was 46 years old; 10 could void spontaneously, 9 used indwelling urethral catheters and 8 intermittent catheterization. The most common bacteria were E. coli (49%) and Klebsiella (22%). Most of the agents were more sensitive to Amoxicilin than Fluoroquinolones. We found 24,6% of UTI's in our patients with spinal cord injury, mainly in the ones using a catheterization technique. Patients in indwelling catheterization had a higher number of UTI's than those with intermittent catheters. No definite cross infections could be found. E. coli continues to be the most frequent bacteria causing this infection. Fluoroquinolones resistance is rising. Amoxicilin/Clavulanic acid is an alternative for immediate empiric treatment. Intermittent catheterization is the best method of bladder management since most of the UTI's were found in patients with indwelling catheters. ASIA D spontaneously voiding patients were the ones with fewer infections. Asymptomatic bacteriúrias should not be treated since we observed a weekly change in microbiological studies of 47% without any therapeutic intervention The small number of UTI's, compared to other SCI Rehabilitation Units, may be due to the strictly fulfilment of the hospital infection preventive program. Moreover, the care given to prompt identification and surveillance of the neurogenic bladder seems to be crucial to prevention and management of UTI's.


[Guideline principle and technical requirement for preparing traditional Chinese medicine reference drug].
Traditional Chinese medicine (TCM) reference drug is a new form of TCM standard reference substance. The purpose of this guideline is to guide the establishment of the reference drug and standardize its investigation and application in national drug standards. Definition of TCM reference drug was specified and relating guideline and technical requirement were introduced in this paper. Its application in quality control of TCM was analyzed and the developing train was proposed. There is a wide prospect for the application of reference drug in quality control of TCM. Thus it has practical significance to explore and conduct the quality evaluation system by using TCM reference drug as the reference substance.


Implant-supported versus implant-natural-tooth-supported fixed partial dentures.
The use of implants with fixed partial dentures requires that the restorative dentist address a new set of concerns when planning treatment. This paper presents some important issues and evaluates the advantages and disadvantages of each choice, including the decision whether to treat the patient as a totally implant-supported or as a combination case. The special problems of posterior restorations include occlusion, rigid versus nonrigid coupling mechanisms, root intrusion, and screw versus cement retention.


Beta-blockers in intensive care medicine: potential benefit in acute brain injury and acute respiratory distress syndrome.
Sympathetic activation is a well-known phenomenon after acute brain injury and in critical illness. In this review we describe pathophysiological considerations that may help in elucidating the potential role of beta (β)-adrenergic antagonists to block some of the adverse sympathetic effects in acute brain injury (subarachnoid hemorrhage and traumatic brain injury) and the acute respiratory distress syndrome. In acute brain injury cardiac dysfunction has been studied most extensively but its pathophysiology is only partly elucidated in man. Further, several adverse consequences of sympathetic activation on the brain itself may occur. Clinical and preclinical studies are described in this review that lend support to the idea that β blockers may have beneficial effects on both cardiac, cerebral and other adverse consequences of sympathetic overactivation after acute brain injury. Second, the acute respiratory distress syndrome (ARDS) may also respond to β blocker therapy, albeit through a different mechanism than in acute brain injury. Some studies reported on beneficial effects of these drugs on ARDS through the mitigation of pulmonary blood flow, without a decrease in systemic hemodynamics. However, in both acute brain injury and ARDS further studies are needed to distinguish those patients who are most likely to benefit from β blockers from those more likely to be harmed by them. Furthermore, recent patents of β blockers relevant to the content of this paper are referenced.


Cellular and molecular effects of non-ionizing electromagnetic fields.
The way that living cells respond to non-ionizing electromagnetic fields (EMF), including static/extremely-low frequency and radiofrequency electromagnetic fields, fits the pattern of 'cellular stress response' - a mechanism manifest at the cellular level intended to preserve the entire organism. It is a set pattern of cellular and molecular responses to environmental stressors, such as heat, ionizing radiation, oxidation, etc. It is triggered by cellular macromolecular damage (in proteins, lipids, and DNA) with the goal of repairing and returning cell functions to homeostasis. The pattern is independent of the type of stressor encountered. It involves cell cycle arrest, induction of specific molecular mechanisms for repair, damage removal, cell proliferation, and cell death if damage is too great. This response could be triggered by EMF-induced alternation in oxidative processes in cells. The concept that biological response to EMF is a 'cellular stress response' explains many observed effects of EMF, such as nonlinear dose- and time-dependency, increased and decreased risks of cancer and neurodegenerative diseases, enhanced nerve regeneration, and bone healing. These responses could be either detrimental or beneficial to health, depending on the duration and intensity of the exposure, as well as specific aspects of the living organism being exposed. A corollary to electromagnetic hypersensitivity syndrome (EHS) could be an inappropriate response of the hippocampus/limbic system to EMF, involving glucocorticoids on the hypothalamic-pituitary-adrenal axis.


Wearable Sleep Technology in Clinical and Research Settings.
: The accurate assessment of sleep is critical to better understand and evaluate its role in health and disease. The boom in wearable technology is part of the digital health revolution and is producing many novel, highly sophisticated and relatively inexpensive consumer devices collecting data from multiple sensors and claiming to extract information about users' behaviors, including sleep. These devices are now able to capture different biosignals for determining, for example, HR and its variability, skin conductance, and temperature, in addition to activity. They perform 24/7, generating overwhelmingly large data sets (big data), with the potential of offering an unprecedented window on users' health. Unfortunately, little guidance exists within and outside the scientific sleep community for their use, leading to confusion and controversy about their validity and application. The current state-of-the-art review aims to highlight use, validation and utility of consumer wearable sleep-trackers in clinical practice and research. Guidelines for a standardized assessment of device performance is deemed necessary, and several critical factors (proprietary algorithms, device malfunction, firmware updates) need to be considered before using these devices in clinical and sleep research protocols. Ultimately, wearable sleep technology holds promise for advancing understanding of sleep health; however, a careful path forward needs to be navigated, understanding the benefits and pitfalls of this technology as applied in sleep research and clinical sleep medicine.


How different are composite and traditional TTO valuations of severe EQ-5D-5L states?
Different variants of time trade-off (TTO) have been employed to elicit health state preferences and to create value sets for preference-based instruments. We compared composite TTO (cTTO) with traditional TTO (tTTO) in valuing severe EQ-5D-5L health states. cTTO uses tTTO to elicit values for health states better than dead and the lead-time TTO for states worse than dead. Eighteen severe states were valued using both cTTO and tTTO. Participants meeting predefined inconsistency criteria were excluded from the analyses. Histograms were used to examine the distributions of cTTO and tTTO values. Mean difference between the cTTO and tTTO values was calculated. Bland-Altman plots were used to examine the agreement between the cTTO and tTTO values for each health state. We used a logistic mixed effects model with random intercepts to identify variables that were associated with the directional change between the two TTO values. A total of 1024 participants were included in the analysis with the mean age (SD) being 47.1 (17.4) years and 54.9 % female. For cTTO, 25 % of the values clustered at zero and there were few values between 0 and -0.5. In contrast, tTTO had fewer values at zero and more falling between -0.5 and 0. The distribution of positive values was similar between cTTO and tTTO. For worse than dead health states, the cTTO values tended to be higher than the tTTO values. In the logistic mixed effects model, those who did not agree that it was easy to understand the cTTO questions more likely changed from positive values in cTTO to zero or negative values in tTTO or change from zero cTTO values to negative values in tTTO compared with those who agreed (odds ratio 1.314, p = 0.037). cTTO is an appealing technique in eliciting health state preferences, but further evidence is needed for its performance in valuing EQ-5D health states on a wide spectrum of health state severity.


Biology and treatment of Burkitt's lymphoma.
Burkitt's lymphoma is a unique hematological malignancy remarkable for its biological characteristics, including aberrant expression of the MYC oncogene, and its requirement for intensive treatment regimens. This review will focus on those features, and discuss recent advances in the molecular biology and advancing treatment options for the disease. Advances in molecular biology have provided many new insights into the biology and treatment options for Burkitt's lymphoma. Microarray technology has recently been used to define a molecular gene expression signature for Burkitt's lymphoma. This signature allows for the differentiation of Burkitt's lymphoma from other forms of non-Hodgkin's lymphoma such as diffuse large B-cell lymphoma. Recent advances in the use of biological agents, such as rituximab, have also allowed for a reduction in treatment toxicities while still offering comparable survival outcomes for patients. Burkitt's lymphoma is an interesting mature B-cell non-Hodgkin's lymphoma that has numerous distinct features and clinical variants depending on factors such as geographical location, immunological status and patient's age. Although the role of the MYC oncogene has been well studied, we are only now appreciating the defining molecular characteristics of this disease, and using these advances to improve treatment options for patients.


Heparan sulfate proteoglycans exert positive and negative effects in Shh activity.
Hedgehog (Hh) proteins are morphogens involved in short- and long-range effects during early embryonic development. Genetic analysis in fly and vertebrate embryos showed that heparan sulfate proteoglycans (HSPGs) are required for Hh transport and signaling. To further understand how HSPGs regulate Sonic hedgehog (Shh), we performed experiments using cell culture and biochemical assays. When the synthesis of HSPGs was reduced, a decrease in Shh activity was observed. Contrary to that, addition of a peptide that competes the binding of Shh to HSPGs resulted in augmentation of Shh activity. From these results, we concluded that HSPGs exert positive and negative effects in Shh activity. This dual effect correlates with the finding that Shh interacts preferentially with two HSPGs. The current model for the role of HSPGs in Shh diffusion is discussed in view of our findings.


Differential regulation of the mitogen-activated protein kinases by pathogenic and nonpathogenic mycobacteria.
Mycobacteria are the etiologic agents of numerous diseases which account for significant morbidity and mortality in humans and other animal species. Many mycobacteria are intramacrophage pathogens and therefore the macrophage response to infection, which includes synthesis of cytokines such as tumor necrosis factor alpha (TNF-alpha) and production of nitric oxide, has important consequences for host immunity. However, very little is known about the macrophage cell signaling pathways initiated upon infection or how pathogenic mycobacteria may modulate the macrophage responses. Using primary murine bone marrow macrophages, we established that p38 and extracellular signal-regulated kinases 1 and 2 of the mitogen-activated protein kinase (MAPK) pathways are activated upon infection with different species of mycobacteria. However, we observed decreased MAPK activity over time in macrophages infected with pathogenic Mycobacterium avium strains relative to infections with nonpathogenic mycobacteria. Furthermore, macrophages infected with M. avium produced lower levels of TNF-alpha, interleukin 1beta, and inducible nitric oxide synthase 2 than macrophages infected with nonpathogenic species. Inhibitor studies indicate that the MAPKs are required for the Mycobacterium-mediated induction of these effector proteins. Our data indicate that MAPKs are activated in macrophages upon invasion by mycobacteria and that this activation is diminished in macrophages infected with pathogenic strains of M. avium, resulting in decreased production of important immune effector proteins. The decreased MAPK activation associated with M. avium infections suggests a novel point of immune intervention by this mycobacterial species.


Assessing efficient patient care: should length of stay be calculated independently of local admission rates?
To compare the length of hospitalisation for infants with bronchiolitis across the Eastern region and to assess the impact of the varying admission rates in each hospital. Data collection through the Hospital Episode Statistics (HES) using the ICD clinical coding for bronchiolitis across all hospitals in east of England for three winter seasons (October to March for the years 2009/10, 2010/11 and 2011/12). Length of hospital stay, corrected to adjust for local population. Seventeen hospitals across the east of England were included in this study. Overall admission rate (as a percentage of the population) for the region was 3.3% and consistent with national data, but rates within individual hospitals varied between 1.5% and 5.7% over the 3-year period. Bed days per 1000 population ('standardised bed days') per year varied almost fourfold, from 34.5 to 122.3 in different hospitals. Corrected length of stay showed high discordance when compared to average length of stay. The average length of stay is substantially affected by admission rates, with hospitals who admit a greater proportion of infants appearing to have a shorter uncorrected length of stay. We propose that a single corrected measure for length of stay should be used when assessing the efficiency of care because it is unaffected by variations in local admission rates and is adjusted for local population size.


Hierarchical self-assembly of chiral complementary hydrogen-bond networks in water: reconstitution of supramolecular membranes.
Spontaneous formation of complementary hydrogen-bond pairs and their hierarchical self-assembly (reconstitution) into chiral supramolecular membranes are achieved in water by mixing amphiphilic pairs of glutamate-derived melamine 6 and ammonium-derivatized azobenzene cyanuric acid 4. Electron microscopy is used to observe formation of helical superstructures, which are distinct from the aggregate structures observed for each of the single components in water. In addition, a spectral blue-shift and induced circular dichroism (ICD) with exciton coupling are observed for the pi-pi* absorption of the azobenzene chromophores. These observations are consistent with the reconstitution of the hydrogen-bond-mediated supramolecular membrane 6-4. Spectral titration experiments indicate the stoichiometric integration of the complementary subunits with an association constant of 1.13 x 10(5) M(-1). This value is considerably larger than those reported for the artificial hydrogen-bonding complexes in aqueous media. The remarkable reconstitution efficiency is ascribed to the hydrophobically driven self-organization of the amphiphilic, linear hydrogen-bond networks in water. Molecular structure of the complementary subunits plays an important role in the complexation process since it is restricted by the photoisomerized cis-azobenzene subunit. On the other hand, thermally regenerated trans-isomer 4 undergoes facile complexation with the counterpart 6. The present reconstitution of supramolecular membranes provides the first example of complementary hydrogen-bond-directed formation of soluble, mesoscopic supramolecular assemblies in water.


Self-reported chemical sensitivity and wartime chemical exposures in Gulf War veterans with and without decreased global health ratings.
This cross-sectional telephone survey study assessed prevalence rates of current chemical sensitivity, frequency of chemical odor intolerance, and self-reported Persian Gulf chemical exposures among 41 randomly sampled Department of Veterans Affairs outpatients who were Persian Gulf War (PGW) and PGW-era veterans. The participants were drawn from an initial random list of 100 veterans, of whom 28 PGW and 20 era veterans had correct telephone data on file. Of those contacted, 86% of PGW veterans (24/28) and 85% of era veterans (17/20) agreed to participate. Significantly more PGW veterans with poorer global health after military service reported considering themselves now "especially sensitive to certain chemicals" (86%, 12/14) than did the PGW veterans or era veterans in stable health (both comparison groups 30%, 3/10). Among PGW veterans, the subset with worse health associated with marked increases in chemical odor intolerance since their military service had a significantly higher odds ratio for exposure to multiple chemicals, notably wartime pesticides and insect repellent, than did comparison groups. The high rate of chemical sensitivity of PGW veterans with deteriorated health is almost three times that in PGW-era veterans and in elderly primary care outpatient veterans at the same Department of Veterans Affairs medical center and in community-based civilian samples (i.e., 30%). These preliminary findings suggest the need for further study of chemical sensitivity, including tests for acquired increases in neural sensitizability to multiple low-level chemicals, in ill PGW veterans.


Effect of sulfate and lactate loading rates on the respiration process and microbial population changes measured by ecological indices.
In a sulfate reducing process, increasing loading rates and sulfide accumulation may induce population changes resulting in decreasing effectiveness of the process. Thus, the relationship between microbial metabolism changes and population dynamics was studied. An upflow anaerobic sludge blanket reactor was operated at different sulfate loading rates (SLR), from 290 to 981 mg SO4-S/L d at a constant carbon/sulfur ratio of 0.75. When the SLR was increased, the total organic carbon and sulfate consumption efficiencies decreased to nearly 30% and 25%, respectively. The acetate and propionate yields increased with increasing SLR and 385±7 mg sulfide-S/L d was reached. The ecological indices, determined by random amplified polymorphic DNA and denaturing gradient gel electrophoresis techniques, diversity and evenness were found to be constant, and similarity coefficient values remained higher than 76%. The results suggest that the microbial population changes were negligible compared with metabolic changes when SLR was increased. The sulfide accumulation did not modify the microbial diversity. The sequencing of 16S rRNA genes showed strains related to sulfate reducing, fermentation, and methanogenesis processes. The results indicated that the decreasing of effectiveness, under the experimental conditions tested, was dependent more on operational parameters than microbial changes.


Effect of borohydride reduction on antibodies.
The effect of borohydride reducing reagents on monoclonal and polyclonal antibodies was examined by enzyme-linked immunosorbent assay (ELISA). Each antibody showed different stability characteristics to the reducing reagents. Sodium cyanoborohydride was at least five times milder toward immunological activity than sodium borohydride, however, sodium cyanoborohydride with a catalytic amount of metal ion (Zn2+ or Al3+) can be as harsh as sodium borohydride. Activated hydrophobic borohydrides, 9BBN-pyridine, did not have any advantages in respect to the stabilities of antibodies. Antibodies to be used for immunosorbent purification must be evaluated individually to determine whether their structure is stable to immobilization reagents and conditions prior to their linkage to the column support.


When less is more: validating a brief scale to rate interprofessional team competencies.
There is a need for validated and easy-to-apply behavior-based tools for assessing interprofessional team competencies in clinical settings. The seven-item observer-based Modified McMaster-Ottawa scale was developed for the Team Objective Structured Clinical Encounter (TOSCE) to assess individual and team performance in interprofessional patient encounters. We aimed to improve scale usability for clinical settings by reducing item numbers while maintaining generalizability; and to explore the minimum number of observed cases required to achieve modest generalizability for giving feedback. We administered a two-station TOSCE in April 2016 to 63 students split into 16 newly-formed teams, each consisting of four professions. The stations were of similar difficulty. We trained sixteen faculty to rate two teams each. We examined individual and team performance scores using generalizability (G) theory and principal component analysis (PCA). The seven-item scale shows modest generalizability (.75) with individual scores. PCA revealed multicollinearity and singularity among scale items and we identified three potential items for removal. Reducing items for individual scores from seven to four (measuring Collaboration, Roles, Patient/Family-centeredness, and Conflict Management) changed scale generalizability from .75 to .73. Performance assessment with two cases is associated with reasonable generalizability (.73). Students in newly-formed interprofessional teams show a learning curve after one patient encounter. Team scores from a two-station TOSCE demonstrate low generalizability whether the scale consisted of four (.53) or seven items (.55). The four-item Modified McMaster-Ottawa scale for assessing individual performance in interprofessional teams retains the generalizability and validity of the seven-item scale. Observation of students in teams interacting with two different patients provides reasonably reliable ratings for giving feedback. The four-item scale has potential for assessing individual student skills and the impact of IPE curricula in clinical practice settings. IPE: Interprofessional education; SP: Standardized patient; TOSCE: Team objective structured clinical encounter.


Investigating the impact of design characteristics on statistical efficiency within discrete choice experiments: A systematic survey.
This study reviews simulation studies of discrete choice experiments to determine (i) how survey design features affect statistical efficiency, (ii) and to appraise their reporting quality. Statistical efficiency was measured using relative design (D-) efficiency, D-optimality, or D-error. For this systematic survey, we searched Journal Storage (JSTOR), Since Direct, PubMed, and OVID which included a search within EMBASE. Searches were conducted up to year 2016 for simulation studies investigating the impact of DCE design features on statistical efficiency. Studies were screened and data were extracted independently and in duplicate. Results for each included study were summarized by design characteristic. Previously developed criteria for reporting quality of simulation studies were also adapted and applied to each included study. Of 371 potentially relevant studies, 9 were found to be eligible, with several varying in study objectives. Statistical efficiency improved when increasing the number of choice tasks or alternatives; decreasing the number of attributes, attribute levels; using an unrestricted continuous "manipulator" attribute; using model-based approaches with covariates incorporating response behaviour; using sampling approaches that incorporate previous knowledge of response behaviour; incorporating heterogeneity in a model-based design; correctly specifying Bayesian priors; minimizing parameter prior variances; and using an appropriate method to create the DCE design for the research question. The simulation studies performed well in terms of reporting quality. Improvement is needed in regards to clearly specifying study objectives, number of failures, random number generators, starting seeds, and the software used. These results identify the best approaches to structure a DCE. An investigator can manipulate design characteristics to help reduce response burden and increase statistical efficiency. Since studies varied in their objectives, conclusions were made on several design characteristics, however, the validity of each conclusion was limited. Further research should be conducted to explore all conclusions in various design settings and scenarios. Additional reviews to explore other statistical efficiency outcomes and databases can also be performed to enhance the conclusions identified from this review.


[The optimization of the batch cultivation process for Pseudomonas aeruginosa to produce exotoxin A].
The experimental study of conditions for the optimization of the batch cultivation of P. aeruginosa has been made. As revealed in this study the aim of this cultivation can be achieved by using exponentially growing culture in a dose of 1.10(9) cells/ml as seed material and by ensuring the conditions of rational air supply during the main cultivation process.


Rehabilitation in the context of HIV: an interprofessional multi-stakeholder process for curriculum development.
With longer survival, individuals living with human immunodeficiency virus (HIV) infection are facing a multitude of health-related challenges due to HIV, its associated concurrent health conditions, and treatments. Despite the need for rehabilitation, few rehabilitation professionals work with people living with HIV, with many feeling they lack adequate knowledge and skills to assess and treat this population. We describe a national multi-stakeholder consultation used to inform the development of an interprofessional curriculum for rehabilitation professionals on HIV/AIDS. We conducted a series of focus groups and key informant interviews (either in person or by telephone) with people living with HIV, rehabilitation professionals, physicians, curriculum experts, and other HIV stakeholders. Participants were asked to describe their perceived learning needs of rehabilitation professionals and to identify relevant content and delivery methods for a future interprofessional HIV/AIDS curriculum. Seven focus groups and 31 interviews with a total of 74 key informants were conducted, resulting in recommendations for content to include in HIV rehabilitation professional curricula and ways to deliver these curricula effectively. A national multi-stakeholder environmental scan was a useful preliminary step to inform the development of an interprofessional curriculum for rehabilitation professionals on HIV/AIDS. Recommendations serve as scaffold from which to build content and delivery of future curricula.


Combined BCR-ABL inhibition with lentiviral-delivered shRNA and dasatinib augments induction of apoptosis in Philadelphia-positive cells.
This study investigated two approaches, short hairpin RNA (shRNA) and the potent ABL inhibitor, dasatinib, alone and together, to achieve complete inhibition of BCR-ABL activity in Philadelphia-positive (Ph(+)) cells. shRNA specific for BCR-ABL b3a2 were delivered, by lentiviral transduction or electroporation, to K562 cells, with or without dasatinib. mRNA and protein knockdown were measured by quantitative reverse transcriptase polymerase chain reaction, flow cytometry, and Western blotting. BCR-ABL activity was assessed by intracellular flow cytometry for pCrkL. Cell death and apoptosis were assayed using trypan blue exclusion, Annexin-V, and active caspase-3 staining. Forty-eight hours after transduction or electroporation of shRNA, BCR-ABL mRNA, and protein were reduced by 75% and >90%, respectively, and sustained for 5 days. Lentiviral delivery and electroporation were equally effective. pCrkL was inhibited in association with cell death. By 5 days after transduction or electroporation, viable cells represented 50% of input, with a 12-fold reduction vs control, which expanded 6-fold. When shRNA, titrated by green fluorescent protein into low and high, was combined with dasatinib (concentration range, 0-10 nM), low shRNA was additive with low dasatinib (0.6 and 1 nM), leading to inhibition of pCrkL, induction of activated caspase-3, expression of Annexin-V, and marked reduction in viable cells. These results confirm that by lowering BCR-ABL levels with shRNA, complete inhibition of oncoprotein activity can be achieved with a lower concentration of dasatinib, thus providing a rationale for combining these approaches in the setting of high target expression, such as found in advanced phase disease and in the stem cell compartment.


Vitiligo: where do we stand?
Vitiligo is a puzzling disorder characterized by a disappearance of epidermal and/or follicular melanocytes by unknown mechanisms. This very common disorder involving 1-4% of the world population is thus of great importance for the practicing dermatologist. The cellular and molecular mechanisms leading to the destruction of melanocytes in this disorder have not yet been elucidated, making it of major interest for the cell biologist involved in melanocyte research. Recent advances in this field, due largely to the availability of techniques for culturing normal human melanocytes, opened new perspectives in the understanding of vitiligo. Although vitiligo has long been considered a disorder confined to the skin, there is now good evidence that it also involves the extracutaneous compartment of the "melanocyte organ." It is also clear that vitiligo is not only a melanocyte disorder, but that it also involves cells, such as keratinocytes and Langerhans cells, found in the epidermis and follicular epithelium. The three prevailing theories of the pathogenesis of vitiligo are the immune hypothesis, the neural hypothesis, and the self-destruct hypothesis. New hypotheses suggest that vitiligo may be due to (1) a deficiency in an unidentified melanocyte growth factor, (2) an intrinsic defect of the structure and function of the rough endoplasmic reticulum in vitiligo melanocytes, (3) abnormalities in a putative melatonin receptor on melanocytes and (4) a breakdown in free radical defense in the epidermis. None of these hypotheses has been demonstrated, and according to the available data, it is likely that the loss of epidermal and follicular melanocytes in vitiligo may be the result of several different pathogenetic mechanisms.


Eagle Syndrome as a Cause of Cerebral Venous Sinus Thrombosis.
A 15-year-old teenager presented with a 2-month history of headache. Neurological examination was normal except for papilledema. Further lumbar puncture indicated intracranial hypertension (330 mm H2O). Brain magnetic resonance imaging (MRI) was normal but phase contrast-magnetic resonance venography (PC-MRV) (Figure 1(A)) suggested possible left transverse-sigmoid sinus thrombosis; subsequent contrast-enhanced 3D fat-saturated T1 volumetric isotropic turbo spin echo acquisition (VISTA) MRI (Figure 1(B)) confirmed the pathology. Hyper-coagulable panel results (including six steroid sex hormones, antithrombin III, protein C, protein S, lupus anticoagulant, and anticardiolipin antibodies) were all within normal range. In further examination, computed tomography (CT) venography images (Figure 1(C) and (D)) showed that the left jugular vein was compressed by the styloid process, consistent with Eagle syndrome.1 The patient who refused the recommended surgical treatment, however, chose anticoagulant therapy consisting of low-molecular weight heparin subcutaneous injection in addition to new oral anticoagulant. At 18-month follow-up, the patient reported no symptoms remained.


Autochthonous transmission of Trypanosoma cruzi, Louisiana.
Autochthonous transmission of the Chagas disease parasite, Trypanosoma cruzi, was detected in a patient in rural New Orleans, Louisiana. The patient had positive test results from 2 serologic tests and hemoculture. Fifty-six percent of 18 Triatoma sanguisuga collected from the house of the patient were positive for T. cruzi by PCR.


Ionizable lipid nanoparticles deliver mRNA to pancreatic β cells via macrophage-mediated gene transfer.
Systemic messenger RNA (mRNA) delivery to organs outside the liver, spleen, and lungs remains challenging. To overcome this issue, we hypothesized that altering nanoparticle chemistry and administration routes may enable mRNA-induced protein expression outside of the reticuloendothelial system. Here, we describe a strategy for delivering mRNA potently and specifically to the pancreas using lipid nanoparticles. Our results show that delivering lipid nanoparticles containing cationic helper lipids by intraperitoneal administration produces robust and specific protein expression in the pancreas. Most resultant protein expression occurred within insulin-producing β cells. Last, we found that pancreatic mRNA delivery was dependent on horizontal gene transfer by peritoneal macrophage exosome secretion, an underappreciated mechanism that influences the delivery of mRNA lipid nanoparticles. We anticipate that this strategy will enable gene therapies for intractable pancreatic diseases such as diabetes and cancer.


Low molecular weight proteins in children with renal disease.
Low molecular weight proteins are of interest in children because their increased urinary excretion is a sign of renal tubular disease and their increased plasma concentration is inversely related to glomerular filtration rate. These proteins include beta 2-microglobulin (B2M), retinol-binding protein (RBP), alpha 1-microglobulin (A1M) and lysozyme. B2M is unstable in acid urine, in contrast to RBP and A1M which are more stable. Any increase in the urinary excretion of B2M or RBP is highly specific for tubular disease, whereas increased excretion of A1M may be seen with glomerular proteinuria. Areas of clinical application include tubular and glomerular diseases, detection of drug toxicity, reflux nephropathy, birth asphyxia and insulin-dependent diabetes mellitus. Methods of sample collection and analysis of these proteins are discussed.


Giant Piezomagnetism in Mn3NiN.
Controlling magnetism with electric field directly or through strain-driven piezoelectric coupling remains a key goal of spintronics. Here, we demonstrate that giant piezomagnetism, a linear magneto-mechanic coupling effect, is manifest in antiperovskite Mn3NiN, facilitated by its geometrically frustrated antiferromagnetism opening the possibility of new memory device concepts. Films of Mn3NiN with intrinsic biaxial strains of ±0.25% result in Néel transition shifts up to 60 K and magnetization changes consistent with theory. Films grown on BaTiO3 display a striking magnetization jump in response to uniaxial strain from the intrinsic BaTiO3 structural transition, with an inferred 44% strain coupling efficiency and a magnetoelectric coefficient α (where α = d B/d E) of 0.018 G cm/V. The latter agrees with the 1000-fold increase over Cr2O3 predicted by theory. Overall, our observations pave the way for further research into the broader family of Mn-based antiperovskites where yet larger piezomagnetic effects are predicted to occur at room temperature.


BEHAVIOR OF INFANT MONKEYS: DIFFERENCES ATTRIBUTABLE TO MODE OF BIRTH.
A comparison of behavior of infant monkeys shortly after birth reveals differences in reactivity which can be related to the route of delivery, whether vaginal or cesarean section. The depression of behavior in the surgically delivered infants persists through day 5 postpartum and ultimately appears as lowered conditionability. Anesthetics or other drugs are not causal factors.


Differential effects of IL-2 and IL-15 on the death and survival of activated TCR gamma delta+ intestinal intraepithelial lymphocytes.
TCR gamma delta+ cells are enriched in the intestine mucosa and constitute approximately half of the intestinal intraepithelial lymphocytes (iIEL) in mice. They are likely activated by self and foreign Ags in situ, but little is known about how the activated gamma delta iIEL are regulated. In the iIEL compartment, IL-2 is produced by activated TCR alpha beta+ iIEL, and IL-15 message is detected in iIEL and in the epithelial cells. We found surface expression of IL-2 as well as IL-15Rs on activated gamma delta iIEL, and examined the effects of IL-2 and IL-15 on the survival and death of gamma delta iIEL during secondary stimulation through TCR. We found that both cytokines supported growth of the restimulated gamma delta iIEL, but exerted different effects on their survival. A significant higher number of live cells were recovered from the gamma delta iIEL cultures restimulated in IL-15 than in IL-2. Quantitation of apoptotic cells showed more cell death in the IL-2 group than in the IL-15 group. The cell death was associated with restimulation through TCR and was not caused by insufficient growth factor, thus representing activation-induced cell death. Western blot analyses found no difference in the levels of Bcl-2 and Bax proteins between the two groups. However, the level of Bcl-xL protein diminished with time in the IL-2 group whereas the level was sustained in the IL-15 group, which may contribute to the pro-survival effect of IL-15. These results demonstrated that the survival of activated gamma delta iIEL is differentially regulated by IL-2 and IL-15.


Support Vector Machine Analysis of Functional Magnetic Resonance Imaging of Interoception Does Not Reliably Predict Individual Outcomes of Cognitive Behavioral Therapy in Panic Disorder with Agoraphobia.
The approach to apply multivariate pattern analyses based on neuro imaging data for outcome prediction holds out the prospect to improve therapeutic decisions in mental disorders. Patients suffering from panic disorder with agoraphobia (PD/AG) often exhibit an increased perception of bodily sensations. The purpose of this investigation was to assess whether multivariate classification applied to a functional magnetic resonance imaging (fMRI) interoception paradigm can predict individual responses to cognitive behavioral therapy (CBT) in PD/AG. This analysis is based on pretreatment fMRI data during an interoceptive challenge from a multicenter trial of the German PANIC-NET. Patients with DSM-IV PD/AG were dichotomized as responders (n = 30) or non-responders (n = 29) based on the primary outcome (Hamilton Anxiety Scale Reduction ≥50%) after 6 weeks of CBT (2 h/week). fMRI parametric maps were used as features for response classification with linear support vector machines (SVM) with or without automated feature selection. Predictive accuracies were assessed using cross validation and permutation testing. The influence of methodological parameters and the predictive ability for specific interoception-related symptom reduction were further evaluated. SVM did not reach sufficient overall predictive accuracies (38.0-54.2%) for anxiety reduction in the primary outcome. In the exploratory analyses, better accuracies (66.7%) were achieved for predicting interoception-specific symptom relief as an alternative outcome domain. Subtle information regarding this alternative response criterion but not the primary outcome was revealed by post hoc univariate comparisons. In contrast to reports on other neurofunctional probes, SVM based on an interoception paradigm was not able to reliably predict individual response to CBT. Results speak against the clinical applicability of this technique.


Impact of accidental hypothermia in trauma patients: A retrospective cohort study.
Trauma patients with hypothermia have substantial increases in mortality and morbidity. In severely injured patients, hypothermia is common with a rate up to 50% in various geographic areas. This study aims to elucidate the incidence, predictors, and impact of hypothermia on outcomes in severely injured patients. This was a retrospective cohort study which included trauma patients with an Injury Severity Score (ISS) ≥ 16 admitted to a level 1 trauma center in the Netherlands between January 1, 2015 and December 31, 2021. Primary outcome was incidence of hypothermia on arrival at the emergency department. Factors associated with hypothermia were identified. Secondary outcomes were transfusion requirement, mortality, and intensive care unit (ICU) admission. Logistic regression analysis was used to identify associations. A total of 2032 severely injured patients were included of which 257 (12.6%) were hypothermic on hospital arrival. Predictors for hypothermia on hospital arrival included higher ISS, prehospital intubation, cervical spine immobilization, winter months, systolic blood pressure (SBP) < 90 mmHg and Glasgow Coma Scale (GCS) ≤ 8. Hypothermia was independently associated with transfusion requirement (OR, 2.68; 95% CI, 1.94 - 3.73; p < 0.001), mortality (OR, 2.12; 95% CI, 1.40 - 3.19; p < 0.001) and more often ICU admission (OR, 1.81; 95% CI, 1.10 - 2.97, p = 0.019). In this study, hypothermia was present in 12.6% of severely injured patients. Hypothermia was associated with increased transfusion requirement, mortality, and ICU admission. Identified predictors for hypothermia included the severity of injury, intubation, and immobilization, as well as winter season, SBP < 90 mmHg, and GCS ≤ 8.


Overriding native cell coordination enhances external programming of collective cell migration.
As collective cell migration is essential in biological processes spanning development, healing, and cancer progression, methods to externally program cell migration are of great value. However, problems can arise if the external commands compete with strong, preexisting collective behaviors in the tissue or system. We investigate this problem by applying a potent external migratory cue-electrical stimulation and electrotaxis-to primary mouse skin monolayers where we can tune cell-cell adhesion strength to modulate endogenous collectivity. Monolayers with high cell-cell adhesion showed strong natural coordination and resisted electrotactic control, with this conflict actively damaging the leading edge of the tissue. However, reducing preexisting coordination in the tissue by specifically inhibiting E-cadherin-dependent cell-cell adhesion, either by disrupting the formation of cell-cell junctions with E-cadherin-specific antibodies or rapidly dismantling E-cadherin junctions with calcium chelators, significantly improved controllability. Finally, we applied this paradigm of weakening existing coordination to improve control and demonstrate accelerated wound closure in vitro. These results are in keeping with those from diverse, noncellular systems and confirm that endogenous collectivity should be considered as a key quantitative design variable when optimizing external control of collective migration.


A determinant in the cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor prevents trafficking to lysosomes.
The bovine cation-dependent mannose 6-phosphate receptor (CD-MPR) is a type 1 transmembrane protein that cycles between the trans-Golgi network, endosomes, and the plasma membrane. When the terminal 40 residues were deleted from the 67-amino acid cytoplasmic tail of the CD-MPR, the half-life of the receptor was drastically decreased and the mutant receptor was recovered in lysosomes. Analysis of additional cytoplasmic tail truncation mutants and alanine-scanning mutants implicated amino acids 34-39 as being critical for avoidance of lysosomal degradation. The cytoplasmic tail of the CD-MPR was partially effective in preventing the lysosomal membrane protein Lamp1 from entering lysosomes. Complete exclusion required both the CD-MPR cytoplasmic tail and transmembrane domain. The transmembrane domain alone had just a minor effect on the distribution of Lamp1. These findings indicate that the cytoplasmic tail of the CD-MPR contains a signal that prevents the receptor from trafficking to lysosomes. The transmembrane domain of the CD-MPR also contributes to this function.


The dental referral process. New insights.
Doctor-patient, doctor-doctor dental relationships are discussed. The dental referral process is a triad of patient, general practitioner and specialist and, in many ways, is dependent upon Freud's concept of transference-countertransference. The unconscious distortions of this process may affect the patient's treatment, as well as interpersonal and intraprofessional relationships.


The follicular distribution and abundance of resident bacteria on human skin.
A cryostat sectioning procedure was used to determine quantitative viable counts of microorganisms both on the surface and in successive layers of human cadaver skin biopsies. Also, using a previously described xenograft model, we investigated the dependence of microorganisms on the presence of sebaceous glands by using full thickness (1.5-2.0 mm) and split thickness (0.6 mm, ensuring sebaceous gland exclusion) human skin. Our results show substantial variation in the distribution and abundance of skin bacteria, even amongst biopsies from the same cadaver. In general, propionibacteria were distributed within a narrow band at varying depths beneath the skin surface whereas staphylococci were more broadly distributed. The importance of this with respect to topically applied antiseptics and antimicrobial agents is indicated. The xenograft studies demonstrated that propionibacteria were dependent on the presence of sebaceous glands whereas staphylococci were not.


Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair.
Mammalian barrier surfaces are constitutively colonized by numerous microorganisms. We explored how the microbiota was sensed by the immune system and the defining properties of such responses. Here, we show that a skin commensal can induce T cell responses in a manner that is restricted to non-classical MHC class I molecules. These responses are uncoupled from inflammation and highly distinct from pathogen-induced cells. Commensal-specific T cells express a defined gene signature that is characterized by expression of effector genes together with immunoregulatory and tissue-repair signatures. As such, non-classical MHCI-restricted commensal-specific immune responses not only promoted protection to pathogens, but also accelerated skin wound closure. Thus, the microbiota can induce a highly physiological and pleiotropic form of adaptive immunity that couples antimicrobial function with tissue repair. Our work also reveals that non-classical MHC class I molecules, an evolutionarily ancient arm of the immune system, can promote homeostatic immunity to the microbiota.


Purification and characterization of the oxygenase component of biphenyl 2,3-dioxygenase from Pseudomonas sp. strain LB400.
The iron-sulfur protein of biphenyl 2,3-dioxygenase (ISPBPH) was purified from Pseudomonas sp. strain LB400. The protein is composed of a 1:1 ratio of a large (alpha) subunit with an estimated molecular weight of 53,300 and a small (beta) subunit with an estimated molecular weight of 27,300. The native molecular weight was 209,000, indicating that the protein adopts an alpha 3 beta 3 native conformation. Measurements of iron and acid-labile sulfide gave 2 mol of each per mol of alpha beta heterodimer. The absorbance spectrum showed peaks at 325 and 450 nm with a broad shoulder at 550 nm. The spectrum was bleached upon reduction of the protein with NADPH in the presence of catalytic amounts of ferredoxinBPH and ferredoxinBPH oxidoreductase. The electron paramagnetic resonance spectrum of the reduced protein showed three signals at gx = 1.74, gy = 1.92, and gz = 2.01. These properties are characteristic of proteins that contain a Rieske-type [2Fe-2S] center. Biphenyl was oxidized to cis-(2R,3S)-dihydroxy-1-phenylcyclohexa-4,6-diene by ISPBPH in the presence of ferredoxinBPH, ferredoxinBPH oxidoreductase, NADPH, and ferrous iron. Naphthalene was also oxidized to a cis-dihydrodiol, but only 3% was converted to product under the same conditions that gave 92% oxidation of biphenyl. Benzene, toluene, 2,5-dichlorotoluene, carbazole, and dibenzothiophene were not oxidized. ISPBPH is proposed to be the terminal oxygenase component of biphenyl 2,3-dioxygenase where substrate binding and oxidation occur via addition of molecular oxygen and two reducing equivalents.


[Hydroxyproline content in blood and urine in ischemic heart disease].
The content of protein-bound oxyproline in blood and the total oxyproline content in urine were studied in 70 healthy individuals between the ages of 20 and 60 and in 124 patients with chronic ischemic heart disease whose ages ranged from 32 to 74. No age dependence of the protein-bound oxyproline level in blood plasma was revealed in healthy individuals. The concentration of oxyproline excreted in the urine was higher in individuals between the ages of 20 and 30 than among older individuals. In patients with chronic ischemic heart disease the level of protein-bound oxyproline in blood plasma was normal, excretion of oxyproline with the urine was increased. In patients with myocardial infarction a period of increased content of oxyproline in blood and urine was observed, the duration of which was determined by the extent and depth of infarction and the clinical course of the disease.


Pretreatment of donor islets with the Na(+) /Ca(2+) exchanger inhibitor improves the efficiency of islet transplantation.
Pancreatic islet transplantation is an attractive therapy for the treatment of insulin-dependent diabetes mellitus. However, the low efficiency of this procedure necessitating sequential transplantations of islets with the use of 2-3 donors for a single recipient, mainly due to the early loss of transplanted islets, hampers its clinical application. Previously, we have shown in mice that a large amount of HMGB1 is released from islets soon after their transplantation and that this triggers innate immune rejection with activation of DC, NKT cells and neutrophils to produce IFN-γ, ultimately leading to the early loss of transplanted islets. Thus, HMGB1 release plays an initial pivotal role in this process; however, its mechanism remains unclear. Here we demonstrate that release of HMGB1 from transplanted islets is due to hypoxic damage resulting from Ca(2+) influx into β cells through the Na(+) /Ca(2+) exchanger (NCX). Moreover, the hypoxia-induced β cell damage was prevented by pretreatment with an NCX-specific inhibitor prior to transplantation, resulting in protection and long-term survival of transplanted mouse and human islets when grafted into mice. These findings suggest a novel strategy with potentially great impact to improve the efficiency of islet transplantation in clinical settings by targeting donor islets rather than recipients.


Sex and pubertal influences on the neurodevelopmental underpinnings of schizophrenia: A case for longitudinal research on adolescents.
Sex is a significant source of heterogeneity in schizophrenia, with more negative symptoms in males and more affective symptoms and internalizing comorbidity in females. In this narrative review, we argue that there are likely sex differences in the pathophysiological mechanisms of schizophrenia-spectrum disorders (SZ) that originate during puberty and relate to the sex-specific impacts of pubertal maturation on brain development. Pubertal maturation might also trigger underlying (genetic or other) vulnerabilities in at-risk individuals, influencing brain development trajectories that contribute to the emergence of SZ. This review is the first to integrate links between pubertal development and neural development with cognitive neuroscience research in SZ to form and evaluate these hypotheses, with a focus on the frontal-striatal and frontal-limbic networks and their hypothesized contribution to negative and mood symptoms respectively. To test these hypotheses, longitudinal research with human adolescents is needed that examines the role of sex and pubertal development using large cohorts or high risk samples. We provide recommendations for such studies, which will integrate the fields of psychiatry, developmental cognitive neuroscience, and developmental endocrinology towards a more nuanced understanding of the role of pubertal factors in the hypothesized sex-specific pathophysiological mechanisms of schizophrenia.


The dependence of behavioral auditory thresholds on the delay of echo-like signals in noctuid moths (lepidoptera, noctuidae).
The auditory system of noctuoid moths capable to respond to ultrasounds has long been a model for anti-predator studies in neuroethology. Many moths avoid hunting bats by listening for their echolocation calls and taking evasive manoeuvres to escape predation. Besides these flight defences, certain tiger moths (Arctiidae) emit high-frequency clicks to jam the echolocator of an attacking bat. Another suggested function for ultrasonic audition in moths along with their capability to emit loud ultrasonic clicks was pulse echolocation. However, it seemed difficult to arrange sufficient temporal resolution in a simple invertebrate auditory system. Here we present an evidence of moth's capability to perceive an echo following its own click with a very short delay. The behavioral responses of moths to the acoustic pulses imitating echoes of their own clicks were investigated under conditions of tethered flight. It has been found that such echo-like stimulation evokes an increase in average emission rate of own acoustic signals in moths. Auditory thresholds were measured in two noctuid species (Enargia paleacea Esp. and Blepharita satura Schiff.) at stimulus delays 0.2, 0.3, 0.5 and 1 ms in relation to the respective moth clicks. Our findings reveal the ability of these moths to perceive echoes of their own signals, thus demonstrating potential possibility for use of pulse echolocation.


Theoretical investigations of novel Janus Pb2SSe monolayer as a potential multifunctional material for piezoelectric, photovoltaic, and thermoelectric applications.
Two-dimensional Janus nanomaterials, due to their unique electronic, optical, and piezoelectric characteristics resulting from the antisymmetric structures, exhibit great prospects in multifunctional energy application to alleviate the energy crisis. Monolayer Janus Pb2SSe, with a black phosphorus-like structure and an indirect band gap of 1.59 eV as well as high carrier mobility (526-2105 cm2 V-1 s-1), displays outstanding potentials in the energy conversion between nanomechanical energy, solar energy, waste heat, and electricity, which has been comprehensively studied utilizing DFT-based simulations. The research results reveal that monolayer Pb2SSe not only possesses giant in-plane piezoelectricity of d11 = 75.1 pm V-1 but also superhigh out-of-plane piezoelectric coefficients (d31 = 0.5 pm V-1 and d33 = 15.7 pm V-1). Meanwhile, by constructing Pb2SSe bilayers, the out-of-plane piezoelectric coefficients can be significantly enhanced (d31 = 19.2 pm V-1 and d33 = 194.7 pm V-1). In addition, owing to the small conduction band offset, suitable donor band gap and excellent light absorption capability in the Pb2SSe/SnSe (Pb2SSe/GeSe) heterostructure, the power conversion efficiencies were calculated to be up to 20.02% (Pb2SSe/SnSe) and 19.28% (Pb2SSe/GeSe), making it a promising candidate for solar energy collection. Furthermore, from the thermoelectric electron and phonon transport calculations, it can be found that the Pb2SSe monolayer is an n-type thermoelectric material with ultrahigh ZT = 2.19 (1.52) at room temperature, which can be traced back to its ultralow κL = 0.78 (0.99) W m-1 K-1, and superhigh PF = 10.18 (8.25) mW m-1 K-2 along the x(y) direction at the optimal doping concentration at 300 K. The abovementioned versatile characteristics in the Janus Pb2SSe monolayer, along with its comprehensive stabilities (energy, dynamic, thermal, and mechanical stabilities), highlight its potential in clean energy harvesting.


Antihypertensive drugs and incidence of type 2 diabetes: evidence and implications for clinical practice.
The major antihypertensive drug classes appear to exert differing effects on glycemic control and diabetes incidence. Thiazide diuretic and beta-blockers are potentially diabetogenic, whereas calcium channel blockers appear neutral. Inhibitors of the renin-angiotensin system are associated with improvements in glycemic control and may lower diabetes incidence, but it is not clear if this represents a truly preventive effect. Also, it should be noted that previous studies have reported inconsistent results, and the data to date are not definitive. We suggest that inhibitors of the renin-angiotensin system be used as first-line agents in uncomplicated hypertensive patients who are at high risk for developing type 2 diabetes. Thiazides and beta-blockers should not be avoided in patients with compelling indications for these drugs. Many hypertensive patients (particularly those who are obese or have prediabetes) require several agents to achieve target blood pressure levels. Therefore, the choice of initial agent is far less important than ensuring that target blood pressure goals are reached.


A roadmap to define and select aquatic biological traits at different scales of analysis.
Trait-based approaches are a powerful tool, as they not only improve understanding of ecological complexity and functioning but also allow comparison across different ecosystems and biogeographical regions. They may be used to unveil ecosystem processes and assess community structures, but their great potential becomes limited when dealing with scattered trait data and historically unstandardised trait nomenclature. The lack of standardisation allows authors to use the terminology of their preference, which inevitably leads to ambiguous misunderstandings and limits comparison between different studies. There have been some attempts to organise the trait vocabulary, but even these are mostly created from the perspective of a single ecosystem, which limits their applicability. In this work, we conducted a systematic literature review that identified and compiled 1127 traits across 37 datasets of fishes, invertebrates and zooplankton from freshwater, marine and transitional ecosystems. This dataset was then used to build on the Marine Species Traits Wiki and to propose a new, unified approach to a trait vocabulary based directly on readily available trait data. We propose a single standardised designation for all the different traits identified and provide a list of all the different synonyms commonly used for these traits. A roadmap to help the trait selection process is also provided, offering a guide through four main steps and important questions for choosing an adequate set of traits at the beginning of any study, which constitutes one of the main challenges in functional ecology research. Overall, this proposal will provide a solid baseline for tackling gaps in trait nomenclature and ensuring a clearer future for functional ecology studies.