TNF-alpha gene polymorphism and plasma TNF-alpha levels are related to lumbar spine bone area in healthy female Caucasian adolescents.
The cytokine tumor necrosis factor alpha (TNF-alpha) is an important regulator of bone metabolism. Polymorphisms in the promoter region of the TNF-alpha gene at positions -308 and -863 have been identified. We investigated whether these polymorphisms and circulating TNF-alpha levels were related to bone mineral density and bone area in adolescent girls. Bone mineral density (BMD), bone area (BA), anthropometric characteristics and biochemical analyses were measured in adolescent girls and compared with regard to TNF-alpha genotype. Allelic variants of the TNF-alpha gene in 97 girls, aged 16.9+/-1.2 years (mean+/-S.D.), were identified using polymerase chain reaction and the restriction endonucleases NcoI and TaiI. Bone mineral density and bone area of the femoral neck, lumbar spine and total body were measured using dual energy X-ray absorptiometry. Carriers of the rare -863 A allele (n=25) had higher body weight (P=0.03), lumbar spine BMD (P=0.02), and larger total BA (P=0.03), femoral neck area (P<0.05), and lumbar spine area (P=0.01). The independent predictors of BMD and BA were investigated using multiple regression. The TNF-alpha-863 genotypes (beta=0.18, P=0.03) and the TNF-alpha plasma levels (beta=0.19, P=0.04) independently predicted BA of the lumbar spine but not BA or BMD of any other measured sites. No statistically significant differences in body constitution parameters, biochemical parameters, bone density, or bone area at the measured skeletal sites were found when comparing the groups defined by the allelic variants at position -308 (P=0.17-0.84). We found the TNF-alpha-863 polymorphism and the TNF-alpha plasma levels to be independent predictors of lumbar spine area in healthy Caucasian adolescent females.


[Kolyma health resort «Talaya» (to its 80th birthday)].
The article is devoted to the history of the creation and establishment of the Far Eastern resort «Talaya», located in the Far North of Russia, in the Magadan Region among the hills of the Kolyma Range, in the valley of the Talaya River. A historical essay is presented from 1868 to the present days, including periods of the resort's development at various stages of Russia's formation (pre-revolutionary, post-revolutionary periods, the era of developed socialism, present times). The contribution of resort doctors, geologists, employees of research institutes to the study of the mechanism of action and clinical effectiveness of the use of Tal mineral water is described. The balneological characteristic of nitrogen-siliceous thermal water, the main therapeutic factor of the Talaya resort, is given. Currently, the Talaya sanatorium is providing the treatment of patients with diseases of the skin, musculoskeletal system, gynecological, neurological diseases, diseases of the digestive system, metabolism, upper respiratory tract, cardiovascular system, occupational diseases using balneotherapy, mud therapy and others methods of non-drug therapy. Hundreds of thousands of northerners were healed by the Kolyma health resort, which gained fame as the «Northern Pearl». Today, during the reorganization of health care, the Talaya sanatorium is going through a difficult but interesting period in improving the possibilities of healing the inhabitants of the northern regions of Russia.


Mechanistic deductions from multiple kinetic and solvent deuterium isotope effects and pH studies of pyridoxal phosphate dependent carbon-carbon lyases: Escherichia coli tryptophan indole-lyase.
Analysis of the pH dependence of the kinetic parameters and competitive inhibitor Ki values for tryptophan indole-lyase suggests two enzymic groups must be unprotonated in order to facilitate binding and catalysis of tryptophan. The V/K for tryptophan and the pKi for oxindolyl-L-alanine, a putative transition state analogue and competitive inhibitor, decrease below two pK values of 7.6 and 6.0, while the Ki for L-alanine, also a competitive inhibitor, is 3300-fold larger (20 mM) than that for oxindolyl-L-alanine and increases below a single pK of 7.6. A single pK of 7.6 is also observed in the V/K profile for the alternate substrate, S-methyl-L-cysteine. Therefore, the enzymic group with a pK of 7.6 is responsible for proton abstraction at the 2-position of tryptophan, while the enzymic group with a pK of 6.0 interacts with the indole portion of tryptophan and probably catalyzes formation of the indolenine tautomer of tryptophan (in concert with proton transfer to C-3 of indole from the group with pK 7.6) to facilitate carbon-carbon bond cleavage and elimination of indole. The pH variation of the primary deuterium isotope effects for proton abstraction at the 2-position of tryptophan (DV = 2.5 and D(V/Ktrp) = 2.8) are pH independent, while the Vmax for tryptophan or S-methyl-L-cysteine is the same and also pH independent. Thus, substrates bind only to the correctly protonated form of the enzyme. Further, tryptophan is not sticky, and the pK values observed in both V/K profiles are the correct ones.(ABSTRACT TRUNCATED AT 250 WORDS)


The spinal pharmacology of urinary function: studies on urinary continence in the unanaesthetized rat.
The volume-evoked micturition reflex (VEMR) is under the control of a complex vesico-spino-bulbo-spino-vesical reflex arc. When functional this system provides for the storage and retention of urine and its subsequent efficient expulsion by virtue of a joint contraction of the bladder and synergic relaxation of the urethral sphincter. Transection of the spinal cord results in an initial disruption of this organization (areflexia) followed by a time-dependent change in the characteristics of the functioning of this reflex system. The growth of knowledge of the pharmacology of spinal systems has yielded considerable information on the potential spinal neurotransmitter systems and their associated receptors. Given the possible role of such systems in mediating and modulating the VEMR, a reasonable approach has been to investigate the effects of spinally administered agonists and antagonists in unanaesthetized animals in which the VEMR can be examined. Thus, it appears that the initial state of bladder distension is signalled by larger (A type) afferent fibres. After spinal injury and the loss of this supraspinal control, smaller unmyelinated C fibres play a predominant role in controlling this reflex. On stimulation these C fibres release peptides (VIP, CCK, substance P, CGRP) and excitatory amino acids (glutamate). Studies in this laboratory have shown that whereas administration of these peptides is without effect in normal intact rats, the antagonists for glutamate and VIP receptors (but not CCK) produce a dose-dependent increase in spontaneous bladder contractions with a corresponding decrease in the volume required to evoke a VEMR. Other spinal systems, such as those for opioids and GABA, are known to exert modulatory effects upon spinal somatomotor reflex arcs. In the spinal cord these agonists (mu/delta and GABAA/B) produce discrete changes in the VEMR in intact and spinally transected animals. Thus these studies may provide insight into the coordinated mechanisms which govern the VEMR and may also allow the development of pharmacological approaches to managing the dysfunctional bladder.


Bronchiolitis obliterans organizing pneumonia (BOOP) after thoracic radiotherapy for breast carcinoma.
Common complications of thoracic radiotherapy include esophagitis and radiation pneumonitis. However, it is important to be aware of uncommon post-radiotherapy complications such as bronchiolitis obliterans organizing pneumonia (BOOP). We report on two patients with carcinoma of the breast who developed an interstitial lung disease consistent with BOOP. BOOP responds to treatment with corticosteroids and the prognosis is generally good despite of the need for long-term administration of corticosteroids as relapses can occur during tapering of steroids. This report provides guidelines for the evaluation and treatment of patients with pulmonary infiltrates after radiotherapy.


Validity and Usefulness of the Hospital Anxiety and Depression Scale in Carers of People with Dementia: Evidence from Confirmatory Factor Analysis, Concurrent Validity, and Measurement Invariance in a Large Sample.
The Hospital Anxiety and Depression Scale (HADS) is a self-report measure of anxiety and depression. It is recommended for clinical assessment and has been used as the primary outcome in large clinical trials with carers of people with dementia. Its validity and utility have never been examined in this population. The current study addresses this. In a secondary analysis of baseline data from a recent intervention trial (N = 284) with cross-validation in baseline data from a second trial (N = 230), the authors used confirmatory factor analysis to test whether a one-, two-, or three-factor structure best fit the data and used indices of model misspecification to respecify. Internal consistency, concurrent validity of obtained factors, and measurement invariance across gender, age, kinship, and cohabitation status were assessed. A three-factor structure best fit the data. Removal of one item improved model fit. The factors showed good internal consistency and high levels of concurrent validity. Measurement invariance was adequate across gender and kinship but not age or cohabitation status. Results were replicated in the cross-validation sample, enhancing reliability. In this group the HADS measured three factors; depression, anxiety, and negative affectivity. The depression scale can be used as originally intended, supporting results of large clinical trials. The HADS does not validly measure distress or anxiety. Consequently, clinical practice recommendations could be revisited, and future research trials should not use HADS anxiety or distress as outcomes. Researchers should pay attention to measurement invariance when using HADS to compare carer subgroups.


Different Growth Responses of an Invasive Weed and a Native Crop to Nitrogen Pulse and Competition.
Resource pulses are a common event in agro-ecosystems. A pot experiment was conducted to assess the effects of nitrogen (N) pulses and competition on the growth of an invasive weed, Amaranthus retroflexus, and a native crop, Glycine max. A. retroflexus and G. max were planted in pure culture with two individuals of one species in each pot and in mixed culture with one A. retroflexus and one G. max individual and subjected to three N pulse treatments. The N treatments included a no-peak treatment (NP) with N applied stably across the growing period, a single-peak treatment (SP) with only one N addition on the planting date, and a double-peak treatment (DP) with two N additions, one on the planting date and the other on the flowering date. N pulse significantly impacted biomass and height of the two species across the whole growing season. However, only the relative growth rate (RGR) of A. retroflexus was significantly affected by N pulse. A. retroflexus had the greatest biomass and height in the SP treatment at the first harvest, and in the DP treatment at the last three harvests. Pure culture G. max produced the greatest biomass in the DP treatment. In mixed culture, G. max produced the greatest biomass in the NP treatment. Biomass production of both species was significantly influenced by species combination, with higher biomass in mixed culture than in pure culture at most growth stages. Relative yield total (RYT) values were all greater than 1.0 at the last three harvests across the three N treatments, suggesting partial resource complementarity occurred when A. retroflexus is grown with G. max. These results indicate that A. retroflexus has a strong adaptive capacity to reduce interspecific competition, likely leading to its invasion of G. max cropland in China.


Sensitivity enhanced recoupling experiments in solid-state NMR by gamma preparation.
In this paper, we introduce a class of dipolar recoupling experiments under magic angle spinning (MAS), which use gamma dependent antiphase polarization during the t1 evolution period. We show that this helps us to design dipolar recoupling experiments that transfer both components of the transverse magnetization of spin S to a coupled spin I in the mixing step of a 2D NMR experiment. We show that it is possible to design such transfer schemes and make them insensitive to the orientation dependency of the couplings in powders. This helps us to develop sensitivity enhanced 2D NMR experiments of powder samples under MAS.


Delayed hemorrhage from the tissue of an occluded arteriovenous malformation after stereotactic radiosurgery: report of 3 cases.
Stereotactic radiosurgery is widely used to treat cerebral arteriovenous malformations (AVMs), with the goal of complete angiographic obliteration. A number of case series have challenged the assumption that absence of residual AVM on follow-up angiograms is consistent with elimination of the risk of hemorrhage. The authors describe 3 cases in which patients who had angiographic evidence of AVM occlusion presented with late hemorrhage in the area of their prior lesions. They compare the radiographic, angiographic, and histological features of these patients with those previously described in the literature. Delayed hemorrhage from the tissue of occluded AVMs has been reported as early as 4 and as late as 11 years after initial stereotactic radiosurgery. In all cases for which data are available, hemorrhage occurred in the area of persistent imaging findings despite negative findings on conventional angiography. The hemorrhagic lesions that were resected demonstrated a number of distinct histological findings. While rare, delayed hemorrhage from the tissue of occluded AVMs may occur from a number of distinct, angiographically occult postirradiation changes. The hemorrhages in the authors' 3 cases were symptomatic and localized. The correlation of histological and imaging findings in delayed hemorrhage from occluded AVMs is an area requiring further investigation.


Neural architecture of the "transient" ON directionally selective (class IIb1) ganglion cells in rabbit retina, partly co-stratified with starburst amacrine cells.
Recent physiological studies coupled with intracellular staining have subdivided ON directionally selective (DS) ganglion cells of rabbit retina into two types. One exhibits more "transient" and more "brisk" responses (ON DS-t), and the other has more "sustained' and more "sluggish" responses (ON DS-s), although both represent the same three preferred directions and show preference for low stimulus velocity, as reported in previous studies of ON DS ganglion cells in rabbit retina. ON DS-s cells have the morphology of ganglion cells previously shown to project to the medial terminal nucleus (MTN) of the accessory optic system, and the MTN-projecting, class IVus1 cells have been well-characterized previously in terms of their dendritic morphology, branching pattern, and stratification. ON DS-t ganglion cells have a distinctly different morphology and exhibit heterotypic coupling to amacrine cells, including axon-bearing amacrine cells, with accompanying synchronous firing, while ON DS-s cells are not coupled. The present study shows that ON DS-t cells are morphologically identical to the previously well-characterized, "orphan" class IIb1 ganglion cell, previously regarded as a member of the "brisk-concentric" category of ganglion cells. Its branching pattern, quantitatively analyzed, is similar to that of the morphological counterparts of X and Y cells, and very different from that of the ON DS-s ganglion cell. Close analysis of the dendritic stratification of class IIb1 ganglion cells together with fiducial cells indicates that they differ from that of the ON DS-s cells. In agreement with one of the three previous studies, class IIb1/ON DS-t cells, unlike class IVus1/ON DS-s ganglion cells, in the main do not co-stratify with starburst amacrine cells. As the present study shows, however, portions of their dendrites do deviate from the main substratum, coming within range of starburst boutons. Parsimony favors DS input from starburst amacrine cells both to ON DS-s and to ON DS-t ganglion cells, given the similarity of their DS responses, but further studies will be required to substantiate the origin of the DS responses of ON DS-t cells. Previously reported OFF DS responses in ON DS-t cells, unmasked by pharmacological agents, and mediated by gap junctions with amacrine cells, suggests an unusual trans-sublaminar organization of directional selectivity in the inner plexiform layer, connecting sublamina a and sublamina b.


Rasch validation and refinement of the Lymphedema Life Impact Scale version 2 in an Italian cohort with secondary lymphedema.
To produce and validate an Italian version of the Lymphedema Life Impact Scale version 2 (LLISv2-It), a tool measuring the impact of lymphedema on health-related quality of life, and investigate its main psychometric characteristics. After translation and cross-cultural adaptation of the LLISv2, we administered it to 156 subjects with secondary lymphedema (upper or lower limb), together with (depending on the limb involved) either the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) or the Lower Extremity Functional Scale (LEFS). We analyzed the performance of LLISv2-It using Classical Test Theory and Rasch methods. Cronbach alpha was 0.89. Item fit statistics indicated that item #12 was underfitting (Infit MnSQ = 1.56; Outfit MnSq = 1.75). Test-retest reliability of the 17-item version (without item #18, not scored, according to the original authors) and of a 16-item version (without #12 and #18-a unidimensional item set) were both excellent (ICC2.1 = 0.93; 95%). The minimum detectable change was 8.9 points. The correlation of LLISv2-It with DASH and LEFS was r = 0.81 and -0.57, respectively. The Italian version of the LLISv2 is reliable and valid. To make the tool more psychometrically sound, we recommend to not calculate items #12 and #18 in the total score. IMPLICATIONS FOR REHABILITATIONThe Lymphedema Life Impact Scale (LLISv2) is particularly useful as a validated condition-specific health-related quality of life measure for patients with chronic edema/lymphedema. We have validated its Italian version (LLISv2-It).We also examined the psychometric properties of the LLISv2 in individuals with secondary lymphedema of either upper or lower limb, using both classical test theory and Rasch techniques, to provide insights for further refinement of the questionnaire.Based on our results, we recommend not to count item #12 in the total score (besides #18, as already suggested by the original authors). Moreover, we determined that the minimum detectable change of the LLISv2 was 9 points. This information is helpful in clinical practice to understand if the change in score is not due to chance (measurement error).Although further research is warranted, the present validation study of the LLISv2 increases the confidence in the metric quality and clinical utility of the scale to assess lymphedema-specific health-related quality of life in individuals with secondary lymphedema of either upper or lower limb.


Selective targeting of primary and secondary nucleation pathways in Aβ42 aggregation using a rational antibody scanning method.
Antibodies targeting Aβ42 are under intense scrutiny because of their therapeutic potential for Alzheimer's disease. To enable systematic searches, we present an "antibody scanning" strategy for the generation of a panel of antibodies against Aβ42. Each antibody in the panel is rationally designed to target a specific linear epitope, with the selected epitopes scanning the Aβ42 sequence. By screening in vitro the panel to identify the specific microscopic steps in the Aβ42 aggregation process influenced by each antibody, we identify two antibodies that target specifically the primary and the secondary nucleation steps, which are key for the production of Aβ42 oligomers. These two antibodies act, respectively, to delay the onset of aggregation and to block the proliferation of aggregates, and correspondingly reduce the toxicity in a Caenorhabditis elegans model overexpressing Aβ42. These results illustrate how the antibody scanning method described here can be used to readily obtain very small antibody libraries with extensive coverage of the sequences of target proteins.


Early Postoperative Results of Percutaneous Needle Fasciotomy in 451 Patients with Dupuytren Disease.
Percutaneous needle fasciotomy is a minimally invasive treatment modality for Dupuytren disease. In this study, the authors analyzed the efficacy and complication rate of percutaneous needle fasciotomy using a statistical method that takes the multilevel structure of data, regarding multiple measurements from the same patient, into account. The data of 470 treated rays from 451 patients with Dupuytren disease that underwent percutaneous needle fasciotomy were analyzed retrospectively. The authors described the early postoperative results of percutaneous needle fasciotomy and applied linear mixed models to compare mean correction of passive extension deficit between joints and efficacy of primary versus secondary percutaneous needle fasciotomy. Mean preoperative passive extension deficits at the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints were 37, 40, and 31 degrees, respectively. Mean preoperative total passive extension deficit was 54 degrees. Results were excellent, with a mean total passive extension deficit correction of 85 percent. Percutaneous needle fasciotomy was most effective for metacarpophalangeal joints and less effective for proximal interphalangeal and distal interphalangeal joints. Secondary percutaneous needle fasciotomy was as effective as primary percutaneous needle fasciotomy. Complications were rare and mostly minor. The results of this study confirm that percutaneous needle fasciotomy is an effective and safe treatment modality for patients with mild to moderate disease who prefer a minimally invasive procedure. Therapeutic, IV.


Empagliflozin Reduces Interleukin-6 Levels in Patients with Heart Failure.
Background: The inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure. The underlying mechanisms are incompletely understood. The present prospective study investigates for the first time the effect of empagliflozin on various soluble markers of inflammation in patients with reduced ejection fraction (HFrEF). Methods: We included 50 inpatients with HFrEF and diabetes mellitus type 2. A total of 25 patients received a therapy with the SGLT-2-inhibitor empagliflozin in addition to standard medication; the other 25 patients did not receive empagliflozin and were considered the control group. Quality of life, functional status and soluble immunological parameters in serum were assessed at baseline and after 3 months. Results: The baseline characteristics of both groups revealed no significant differences. Patients on empagliflozin demonstrated a significant improvement in the Minnesota living with heart failure questionnaire (baseline 44.2 ± 20.2 vs. 24 ± 17.7; p < 0.001), in distance in the 6-min walk test (baseline 343 ± 145 m vs. 450 ± 115 m; p < 0.001) and in soluble interleukin-6 level (baseline 21.7 ± 21.8 pg/mL vs. 13.7 ± 15.8 pg/mL; p = 0.008). There was no significant change of these or other parameters in the control group (p > 0.05 each). Conclusions: The empagliflozin-induced improvement of quality of life and functional capacity in patients with HFrEF and type 2 diabetes mellitus is accompanied by a substantial reduction of interleukin-6 levels. Thus, anti-inflammatory effects may contribute to the benefits of SGLT-2-inhibitors in heart failure.


The Mingle-Mangle of Wnt Signaling and Extracellular Vesicles: Functional Implications for Heart Research.
Wnt signaling is an important pathway in health and disease and a key regulator of stem cell maintenance, differentiation, and proliferation. During heart development, Wnt signaling controls specification, proliferation and differentiation of cardiovascular cells. In this regard, the role of activated Wnt signaling in cardiogenesis is well defined. However, the knowledge about signaling transmission has been challenged. Recently, the packaging of hydrophobic Wnt proteins on extracellular vesicles (EVs) has emerged as a mechanism to facilitate their extracellular spreading and their functioning as morphogens. EVs spread systemically and therefore can have pleiotropic effects on very different cell types. They are heavily studied in tumor biology where they affect tumor growth and vascularization and can serve as biomarkers in liquid biopsies. In this review we will highlight recent discoveries of factors involved in the release of Wnts on EVs and its potential implications in the communication between physiological and pathological heart cells.


Total thyroidectomy, without prophylactic central lymph node dissection, in the treatment of differentiated thyroid cancer. Clinical retrospective study on 221 cases.
Total thyroidectomy (TT) is the standard of care for differentiated thyroid cancer (DTC), but still there is no consensus about the role of routine use of prophylactic central lymph node dissection. The aim of this study was to analyze our results of TT without prophylactic central lymphadenectomy in the treatment of DTC. Clinical records, between January 1998 and December 2005, of 221 patients undergoing TT, without prophylactic central lymph node dissection, were retrospectively evaluated. Two hundred and eleven patients (95.47 %) also underwent radioiodine (RAI) ablation followed by thyroid stimulating hormone (TSH) suppression therapy. In patients with loco-regional lymph nodal recurrence, lateral and central lymph node dissection was performed. The incidence of permanent hypoparathyroidism (iPTH <10 pg/ml) and permanent vocal fold paralysis were, respectively, 0.91 and 0.91 %. After a 9.6 ± 3.5 years mean follow-up, the rate of loco-regional recurrence, with positive cervical lymph nodes, was 3.16 % (7/221 patients). In these cases a lateral and central lymphadenectomy was carried out without significant complications. Our results showed that TT without prophylactic central lymph node dissection, followed by RAI ablation, was associated with low morbidity and low loco-regional recurrence rate, even if the lack of a control group treated with TT plus prophylactic central lymphadenectomy suggests caution against generalization of our assumption. Such last combined procedure could be indicated in high-risk patients, in whom loco-regional recurrence is more frequent. However, given the trend in the literature toward prophylactic lymphadenectomy and the avoidance of RAI treatment, prospective randomized trials should be conducted to better clarify this issue.


Nasotracheal intubation: an unusual cause of palatal perforation in an insulin dependent diabetes mellitus patient.
A case of palatal perforation occurring in 7-year-old girl with IDDM due to nasotracheal intubation is reported. The child, who was not previously diagnosed of IDDM, was brought to hospital in comatose stage and was put on nasotracheal tube for maintaining respiration. This paper highlights the link between IDDM and palatal perforation communicating the nasal cavity due to naso-tracheal intubation.


Immunoglobulin G responses to Malassezia pachydermatis in healthy dogs and dogs with Malassezia dermatitis.
Serum immunoglobulin G (IgG) responses of healthy dogs and dogs with Malasseziapachydermatis dermatitis were compared by Western immunoblotting. M pachydermatis CBS 1879 was disrupted mechanically and its proteins were separated and blotted on to nitrocellulose membranes before being incubated with sera from eight healthy beagles, eight Irish setters with gluten-sensitive enteropathy, 15 healthy basset hounds, and 30 dogs with Mpachydermatis-associated dermatitis, 20 of which were basset hounds. The mean (se) numbers of bands of immunoreactivity observed in the seborrhoeic basset hounds (10.7 [0.4]) and affected mixed-breed dogs (9.4 [0.9]) were significantly greater than in the beagles (3-0 [1.0]), Irish setters (5.5 [1.1]) and healthy basset hounds (5.6 [0.7]). The number of bands identified was correlated (r(s) = 0.76, P < 0.001) with the anti-M pachydermatis IgG values measured by ELISA in a previous study. Most of the dogs were immunoreactive towards the 132, 66 and 50 to 54 kDa proteins and the affected dogs were also usually reactive towards the 219, 110, 71 and 42 kDa proteins.


The vault exterior shell is a dynamic structure that allows incorporation of vault-associated proteins into its interior.
Vaults are 13 million Da ribonucleoprotein particles with a highly conserved structure. Expression and assembly by multimerization of an estimated 96 copies of a single protein, termed the major vault protein (MVP), is sufficient to form the minimal structure and entire exterior shell of the barrel-shaped vault particle. Multiple copies of two additional proteins, VPARP and TEP1, and a small untranslated vault RNA are also associated with vaults. We used the Sf9 insect cell expression system to form MVP-only recombinant vaults and performed a series of protein-mixing experiments to test whether this particle shell is able to exclude exogenous proteins from interacting with the vault interior. Surprisingly, we found that VPARP and TEP1 are able to incorporate into vaults even after the formation of the MVP vault particle shell is complete. Electrospray molecular mobility analysis and spectroscopic studies of vault-interacting proteins were used to confirm this result. Our results demonstrate that the protein shell of the recombinant vault particle is a dynamic structure and suggest a possible mechanism for in vivo assembly of vault-interacting proteins into preformed vaults. Finally, this study suggests that the vault interior may functionally interact with the cellular milieu.


Antidiabetic Compounds in Syzygium cumini Decoction and Ready to Serve Herbal Drink.
Herbal beverages with desirable sensory attributes are an ideal way to offer consumers with phytochemicals having specific health promoting functionalities. Syzygium cumini bark decoction is used in treating diabetes mellitus in Ayurveda medicine. This work attempted to prove the presence of antidiabetic compounds in the S. cumini decoction and the ready to serve (RTS) herbal drink developed using the decoction. Activity guided fractionation of the decoction of the S. cumini was carried out by sequential extraction with organic solvents of different polarities. Thin Layer Chromatography (TLC) with authentic compounds and HPLC were performed for identification and confirmation of the compounds in the decoction and the RTS herbal drink. Presence of gallic and ellagic acids in the decoction and RTS herbal drink was proven and confirmed with HPLC. The LC UV-VIS spectra of the two compounds were identical with the corresponding spectra of the library. Further, gallic acid and umbelliferone were determined as the active compounds in the decoction by TLC and were confirmed by cochromatography with authentic compounds. The present investigation confirmed the presence of gallic acid, ellagic acid, and umbelliferone which are proven to have antidiabetic activities in the decoction and the RTS herbal drink prepared with the decoction.


Rapid response teams: a proactive critical care approach.
Time and again, hospital code teams are dispatched to a patient in cardiac arrest only to find their resuscitative efforts unsuccessful. Are there earlier interventions that may have saved the patient? Do any warning signs exist before the patient actually goes into a full code or cardiac arrest event? The answer is a repeated yes, and the solution is a rapid response team.


Phase-space networks of geometrically frustrated systems.
We illustrate a network approach to the phase-space study by using two geometrical frustration models: antiferromagnet on triangular lattice and square ice. Their highly degenerated ground states are mapped as discrete networks such that the quantitative network analysis can be applied to phase-space studies. The resulting phase spaces share some comon features and establish a class of complex networks with unique Gaussian spectral densities. Although phase-space networks are heterogeneously connected, the systems are still ergodic due to the random Poisson processes. This network approach can be generalized to phase spaces of some other complex systems.


Case report: A preterm infant with rubinstein-taybi syndrome and Marmorata telangiectatica harboring a frameshift mutation in the CREBBP gene.
Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominantly inherited disease characterized by slow mental and physical growth, skeletal abnormalities (broad thumbs and big toes), and dysmorphic facial features. RSTS is associated with de novo variants of the epigenetic-associated gene CREBBP. RSTS is primarily diagnosed based on clinical manifestations and genetic testing. Cutis marmorata telangiectatica congenita (CMTC) is a rare, congenital, and typically benign vascular anomaly of unknown etiology; it is described as persistent reticulated marbled erythema. The diagnosis of CMTC is largely based on clinical features, and GNA11 mutations are associated with CMTC. In this case report, we describe the case of a preterm infant (boy) with RSTS and CMTC who had a novel frameshift mutation leading to a premature stop codon in the CREBBP gene. This study adds the novel mutation c.5837dupC to the known molecular spectrum of disease-causing CREBBP gene mutations.


Evaluation of an X-ray microprobe technique as a possible aid to detect salmonellae.
The X-ray microprobe was examined as a possible aid in the detection of salmonellae. Results obtained indicate that specific bacterial antigen (Salmonella) increased in phosphorus and sulfur after reaction with the fluorescein isothiocyanate tagged specific antibody. Nonspecific antigen (Escherichia coli) did not increase in phosphorus and sulfur after reaction with fluorescein isothiocyanate tagged anti-Salmonella antibody. The technique developed supports the hypothesis that X-ray microprobe analysis may be useful in detecting salmonellae, or other bacteria, by determining increases in the elemental constituents of bacterial cells when reacted with elemental-tagged antibodies.


Proteins from the prokaryotic nucleoid. High-resolution 1H NMR spectroscopic study of Escherichia coli DNA-binding proteins NS1 and NS2.
The 1H-NMR spectra of the two Escherichia coli basic, low-Mr (approximately equal to 9000) DNA-binding proteins NS1 and NS2 and of their native complex NS were studied at 400 MHz and a number of resonances and resonance peaks were assigned. As in the case of some eukaryotic histones, the presence of a large number of high-field perturbed Phe resonances, several shielded and deshielded methyl resonances and backbone NH protons quite inaccessible to the solvent clearly indicate the existence of extensive tertiary and, even more so, quaternary structures involving hydrophobic interactions. These structures are lost upon heating, but readily reform upon cooling. Spectral differences between NS1, NS2 and NS and the greater thermal stability of NS indicate that molecules of the heterologous subunits (NS1 and NS2) aggregate (dimerize) preferentially in comparison to the self-aggregation of the homologous subunits. Unlike those of the eukaryotic histones, the tertiary and quaternary structures of NS are insensitive to extensive variations of the ionic strength.


Observation of magnetically tunable Feshbach resonances in ultracold 23Na40K + 40K collisions.
Resonances in ultracold collisions involving heavy molecules are difficult to simulate theoretically and have proven challenging to detect. Here we report the observation of magnetically tunable Feshbach resonances in ultracold collisions between potassium-40 (40K) atoms and sodium-23-potassium-40 (23Na40K) molecules in the rovibrational ground state. We prepare the atoms and molecules in various hyperfine levels of their ground states and observe the loss of molecules as a function of the magnetic field. The atom-molecule Feshbach resonances are identified by observing an enhancement of the loss. We have observed 11 resonances in the magnetic field range of 43 to 120 gauss. The observed atom-molecule Feshbach resonances at ultralow temperatures probe the three-body potential energy surface with exceptional resolution and will help to improve understanding of ultracold collisions.


Time course changes of estrogen receptor alpha expression in the adult rat hippocampus after kainic acid-induced status epilepticus.
Although estrogens possess neuroprotective and epileptogenic properties, the expression pattern of the estrogen receptor (ER) following status epilepticus (SE) remains unclear. We therefore examined the expression pattern of ER alpha in the adult rat hippocampus after SE. SE was induced in rats by kainic acid (KA; 12 mg/kg, i.p.). ER alpha expression was assessed by immunostaining and Western blotting at various times (24 h, and 7, 14, and 21 days) after SE onset. Immunohistochemistry disclosed ER alpha expression in the CA1 and CA3 pyramidal cells of control rats, whereas, after SE, ER alpha-immunoreactive neurons decreased in number due to neuronal death in the CA1 from days 7 to 21. On the other hand, ER alpha-immunoreactive cells with astrocytic morphology were observed in the CA1 beginning on day 7 after SE. This immunoreactivity increased in proportion to the hypertrophy of astrocytes up to day 21. Western blotting revealed a significant decrease in ER alpha expression on day 7 after SE in comparison with control level. However, ER alpha expression on days 14 and 21 were similar when comparing KA-treated and control rats. These results indicate that reactive astrocytes are important sites of estrogen action in the hippocampal CA1 after SE.


Light-response quantitative trait loci identified with composite interval and eXtreme array mapping in Arabidopsis thaliana.
Genetic analysis of natural variation in ecotypes of Arabidopsis thaliana can facilitate the discovery of new genes or of allelic variants of previously identified genes controlling physiological processes in plants. We mapped quantitative trait loci (QTL) for light response in recombinant inbred lines (RILs) derived from the Columbia and Kashmir accessions via two methods: composite interval mapping and eXtreme array mapping (XAM). After measuring seedling hypocotyl lengths in blue, red, far-red, and white light, and in darkness, eight QTL were identified by composite interval mapping and five localized near photoreceptor loci. Two QTL in blue light were associated with CRY1 and CRY2, two in red light were near PHYB and PHYC, and one in far-red light localized near PHYA. The RED2 and RED5 QTL were verified in segregating lines. XAM was tested for the identification of QTL in red light with pools of RILs selected for extreme phenotypes. Thousands of single feature polymorphisms detected by differential DNA hybridized to high-density oligo-nucleotide arrays were used to estimate allele frequency differences between the pools. The RED2 QTL was identified clearly; differences exceeded a threshold of significance determined by simulations. The sensitivities of XAM to population type and size and genetic models were also determined by simulation analysis.


Very High-Frequency Ultrasonography Signs in Bilateral Acute Choroidal Effusion Associated with Systemic Sulphonamide Medications: 2 Cases.
Sulphonamides are commonly used in medicine for several purposes; however, they can lead to significant adverse effects, including idiosyncratic reactions and choroidal detachment corresponding to a forward rotation of the iris-lens diaphragm; this could also evolve into acute transient myopia with possible acute angle closure glaucoma. The risk of such reactions to sulphonamides is approximately 3%. In our communication, we have reported on 2 cases involving patients who suffered choroidal detachments after starting sulphonamide treatments and who were diagnosed with the help of ultrasound biomicroscopy. Patient 1 was an 87-year-old male with bilateral pseudophakia who developed an acute change in vision in both eyes after he started taking chlorthalidone, a classic thiazide diuretic antihypertensive that is characterized by having a sulpha-based group. Patient 2 was a 42-year-old female who developed dramatic visual loss after beginning a new treatment (topiramate) for weight loss. We were able to successfully detect the choroidal detachments in these patients with ultrasound biomicroscopy, which aided us in quickly diagnosing the condition. Subsequently, the drugs were immediately discontinued, and appropriate treatment was administered resulting in the full recovery of both patients.


The critical role of protein kinase C-theta in Fas/Fas ligand-mediated apoptosis.
A functional immune system not only requires rapid expansion of antigenic specific T cells, but also requires efficient deletion of clonally expanded T cells to avoid accumulation of T cells. Fas/Fas ligand (FasL)-mediated apoptosis plays a critical role in the deletion of activated peripheral T cells, which is clearly demonstrated by superantigen-induced expansion and subsequent deletion of T cells. In this study, we show that in the absence of protein kinase C-theta (PKC-theta), superantigen (staphylococcal enterotoxin B)-induced deletion of Vbeta8(+) CD4(+) T cells was defective in PKC-theta(-/-) mice. In response to staphylococcal enterotoxin B challenge, up-regulation of FasL, but not Fas, was significantly reduced in PKC-theta(-/-) mice. PKC-theta is thus required for maximum up-regulation of FasL in vivo. We further show that stimulation of FasL expression depends on PKC-theta-mediated activation of NF-AT pathway. In addition, PKC-theta(-/-) T cells displayed resistance to Fas-mediated apoptosis as well as activation-induced cell death (AICD). In the absence of PKC-theta, Fas-induced activation of apoptotic molecules such as caspase-8, caspase-3, and Bid was not efficient. However, AICD as well as Fas-mediated apoptosis of PKC-theta(-/-) T cells were restored in the presence of high concentration of IL-2, a critical factor required for potentiating T cells for AICD. PKC-theta is thus required for promoting FasL expression and for potentiating Fas-mediated apoptosis.


Conformational behavior of giant DNA through binding with Ag+ and metallization.
The conformational behavior of a long single-chain double-stranded DNA in solutions of free silver ions and silver nanoparticles generated via the reduction of AgNO3 by NaBH4 was monitored by fluorescence and electron microscopies and UV spectroscopy. The interaction of monovalent silver ions with DNA induces shrinking of a DNA-coiled polymer chain as a result of a decrease in the DNA persistence length through the complexation of Ag+ with DNA bases. In contrast, the reduction of silver ions by NaBH4 in DNA solutions triggers DNA compaction: a DNA transition from elongated coil state into a compact state. This transition is continuous, unlike the all-or-none discrete DNA compaction that is commonly seen with multications. It is suggested that the collapse of DNA is accompanied by growth aggregation of silver nanoparticles generated on the DNA template.


Epidemiological Features and Forecast Model Analysis for the Morbidity of Influenza in Ningbo, China, 2006-2014.
This study aimed to identify circulating influenza virus strains and vulnerable population groups and investigate the distribution and seasonality of influenza viruses in Ningbo, China. Then, an autoregressive integrated moving average (ARIMA) model for prediction was established. Influenza surveillance data for 2006-2014 were obtained for cases of influenza-like illness (ILI) (n = 129,528) from the municipal Centers for Disease Control and virus surveillance systems of Ningbo, China. The ARIMA model was proposed to predict the expected morbidity cases from January 2015 to December 2015. Of the 13,294 specimens, influenza virus was detected in 1148 (8.64%) samples, including 951 (82.84%) influenza type A and 197 (17.16%) influenza type B viruses; the influenza virus isolation rate was strongly correlated with the rate of ILI during the overall study period (r = 0.20, p < 0.05). The ARIMA (1, 1, 1) (1, 1, 0)12 model could be used to predict the ILI incidence in Ningbo. The seasonal pattern of influenza activity in Ningbo tended to peak during the rainy season and winter. Given those results, the model we established could effectively predict the trend of influenza-related morbidity, providing a methodological basis for future influenza monitoring and control strategies in the study area.


Identification of a novel cellular TPR-containing protein, SGT, that interacts with the nonstructural protein NS1 of parvovirus H-1.
The nonstructural protein NS1 of autonomous parvoviruses is essential for viral DNA amplification and gene expression and is also the major cytopathic effector of these viruses. NS1 acts as nickase, helicase, and ATPase and upregulates P38-driven transcription of the capsid genes. We report here the identification of a novel cellular protein that interacts with NS1 from parvovirus H-1 and which we termed SGT, for small glutamine-rich tetratricopeptide repeat (TPR)-containing protein. The cDNA encoding full-length SGT was isolated through a two-hybrid screen with, as bait, the truncated NS1dlC69 polypeptide, which lacks the C-terminal transactivation domain of NS1. Full-length NS1 and SGT interacted in the two-hybrid system and in an in vitro interaction assay. Northern blot analysis revealed one major transcript of about 2 kb that was present in all rat tissues investigated. Rat sgt cDNA coded for 314 amino acids, and the protein migrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular mass of 34 kDa. SGT could be detected in both the nucleus and the cytoplasm of rat cells, as determined by indirect immunofluorescence analysis and Western blotting of fractionated cellular extracts with an affinity-purified antiserum raised against recombinant SGT (AC1.1). In H-1 virus-infected rat and human cells, compared to mock-infected controls, differences in the migration of SGT polypeptides were revealed after Western blot analysis of total cellular extracts. Moreover, the transient expression of NS proteins was sufficient to induce SGT modification. These results show that cellular SGT, which we have identified as an NS1-interacting protein, is modified by parvovirus infection as well as NS expression.


Bullying, its effects on attitude towards class attendance and the contribution of physical and dentofacial features among adolescents in Northern Nigeria.
Background Bullying is a worldwide problem with varying consequences. Victims of school bullying may be targeted for many reasons including their appearance. They may also fear school and have difficulties in concentration. Objective This study aimed to determine the prevalence of bullying amongst adolescents in Kano, Northern Nigeria, the contribution of physical features and the perceived effect of bullying on their academic performance and school attendance. Subjects and methods Eight hundred and thirty-five students aged between 12 years and 17 years from eight randomly selected secondary schools in Kano, Nigeria took part in this study. Data collection was by self-administered questionnaires and analysis was by SPSS version 17. Results The pupils' mean age and standard deviation was 14.79 + 1.53 years. There were more male and private school pupils with 55.1% and 62%, respectively. About 43% of respondents reported being victims of bullying while about 32% had bullied someone else. There was more bullying in public schools than in private schools (p-value = 0.003). However, there was no significant gender difference (p > 0.05). More bullied pupils hated being in or outside the classroom (p < 0.05). Similarly, significantly higher number of bullied pupils played truant than non-bullied (p < 0.001). One-fifth of the victims of bullying felt it had consequences on their academic performance. Bullies frequently targeted general physical and dento-facial appearance. Conclusion The prevalence of bullying was high among the sampled population especially within public schools. This also had a significant negative effect on the students' academic performance.


Utilization of Cervical Cancer Screening Among Hispanic Immigrant Women in Coastal South Carolina.
This study aims to examine prevalence and correlates of cervical cancer screening utilization and adherence among a growing population of Hispanic immigrant women in coastal South Carolina. We conducted a cross-sectional survey of 196 women to assess recency of screening and hypothesized study predictors (health status, beliefs, self-efficacy, having a regular provider, barriers to screening, and trust in providers). Multiple ordinal logistic regressions identified final covariates which would predict recency of screening. Approximately 84% of women were up-to-date with their Pap tests and 47% had received a Pap test in the previous year. In the adjusted analyses, having a regular provider and having a chronic medical condition were significantly associated with recency of Pap test. Differences in cervical cancer screening for participants were partially explained by psychosocial factors, health status, and individual and structural barriers to healthcare.


Retrospective Analysis of the first 100 Kidney Transplants at the Istanbul Okan University, Health Application and Research Center.
The renal transplant program of Istanbul Okan University Hospital started in August 2017. Five cadaveric and 95 living donor kidney transplants have been performed for over 16 months. In this study, we aimed to share our experiences regarding kidney transplantation. In this study, a retrospective analysis of 100 patients who underwent kidney transplantation at the Istanbul Okan University over 16 months, the Health Application and Research Center was carried out. Patients' demographics, creatinine levels of donors and recipients, co-morbid conditions, postoperative complications, features of arterial anastomosis and arterial variations observed on computed tomography angiography of donor-patient were assessed. Mean age of donor patients was 44.05±13.76 (18-71) years. All living donors had computed tomography angiography for assessment of the vascular structure of both kidneys. Accessory right kidney artery was the most dominant vascular variation (16.5%). The primary cause of chronic renal disease was diabetes mellitus (36.4%) and hypertension (15.6%). Mean warm and cold ischemia time was 1.82±0.44 (1-3) and 40.25±6.12 (31-57) minutes, respectively. The most observed postoperative complication was stenosis of ureter anastomosis (4.1%). End-to-end arterial anastomosis between renal and internal iliac arteries was the most preferred anastomosis (57.2%). Increasing kidney transplantation, which is the most appropriate treatment in terms of cost-effectiveness, will be beneficial for patient health and economy of the country.


Analysis of the drug resistance profile of multidrug resistance protein 7 (ABCC10): resistance to docetaxel.
The multidrug resistance protein (MRP) family consists of nine members that can be categorized according to whether or not a third (NH(2)-terminal) membrane-spanning domain is present. Three (MRP1, MRP2, and MRP3) of the four members that have this structural feature are able to confer resistance to natural product anticancer agents. We previously established that MRP7, the remaining family member that has three membrane-spanning domains, possesses the cardinal biochemical activity of MRPs in that it is able to transport amphipathic anions such as 17beta-estradiol 17-(beta-d-glucuronide). However, the drug resistance profile of the pump has not been determined. In this study, the drug resistance capabilities of MRP7 are evaluated by analyzing the resistance profiles of two clones of HEK293 cells in which the pump was ectopically expressed. MRP7-transfected HEK293 cells exhibited the highest levels of resistance toward docetaxel (9-13-fold). In addition, lower levels of resistance were observed for paclitaxel (3-fold), vincristine (3-fold), and vinblastine (3-4-fold). Consistent with the operation of an ATP-dependent efflux pump, MRP7-transfected cells exhibited reduced accumulation of radiolabeled paclitaxel compared with HEK293 cells transfected with parental plasmid. These results indicate that MRP7, unlike other MRPs, is a resistance factor for taxanes.


Lysozyme-rich muciphages surrounding colorectal adenomas.
Muciphages are mucin-rich phagocytes believed to evolve as a result of the disruption of colorectal crypts. In a previous work we found, in rectal biopsies from patients with chronic ulcerative colitis, muciphages having not only mucin but also lysozyme, an enzyme with a potent antimicrobial activity. Recently we detected lysozyme-rich muciphages in the normal mucosa of the stalk of colonic adenomas. Filed hematoxylin and eosin (H&E)-stained sections from 30 consecutive colorectal adenomas with a stalk (lined by normal colorectal mucosa) were stained with PAS (for mucopolysaccharides), with CD68 (to label macrophages) and with lysozyme (Muramidase). Of the 30 adenomas, 16 (40%) showed muciphages in the mucosa of the stalk. Those muciphages were PAS- CD68- and lysozyme-positive. Although the significance of these findings remains elusive, it is conceivable that lysozyme-rich muciphages mirror increased cell destruction in colorectal adenomas with a high cell turnover. The possibility that lysozyme-rich muciphages surrounding adenomas are instrumental in a novel molecular mechanism of host defense, effective at the early stages of colorectal carcinogenesis, was also entertained. Such a mechanism would prevent the lateral expansion of the dysplastic epithelium of the adenoma into the surrounding normal mucosa of the stalk.


Drug treatment of overactive bladder: efficacy, cost and quality-of-life considerations.
Overactive bladder (OAB) syndrome has been recognised by the International Continence Society as an important symptom syndrome that affects millions of people worldwide. Quality of life is affected in most people with OAB; however, the aetiology is unknown. Some researchers suggest that it is because of a damage to central inhibitory pathways or sensitisation of peripheral afferent terminals in the bladder, others suggest that it is a bladder muscle problem; the reality is probably a spectrum encompassing these two main explanations. Therefore, treatment is difficult and is aimed at alleviating symptoms (being those of urgency, with or without urge incontinence, usually with frequency and nocturia) rather than treating the cause. A thorough patient history and physical examination are required to establish a possible diagnosis. Frequency/volume charts form an important aid to the diagnosis. Once a presumptive diagnosis is made, conservative management forms the first line of treatment and includes lifestyle modifications, bladder training and pelvic floor exercises. If this fails, pharmacotherapy, in the form of anticholinergic drugs, is initiated. There are many antimuscarinic drugs, for example oxybutynin, tolterodine and trospium chloride. Each has a different specificity to bladder muscarinic receptors, thus producing different adverse effect profiles (e.g. dry mouth, blurred vision and constipation). Different individuals experience these adverse effects to different extents. New anticholinergic drugs, that have undergone phase III trials and are more specific to the muscarinic M3 human bladder receptor, are being introduced to the market in 2004 (e.g. solifenacin succinate and darifenacin). In addition to adverse effect profile, cost and improvement in quality of life are important factors in choosing treatment. Further research is being conducted on other types of drugs and different administration modalities, for example intravesical botulinum toxin A. Sacral nerve neuromodulation is emerging as a potential treatment, but if all treatments fail then surgery is the last resort.


BLM and the FANC proteins collaborate in a common pathway in response to stalled replication forks.
Fanconi anaemia (FA) and Bloom syndrome (BS) are autosomal recessive diseases characterised by chromosome fragility and cancer proneness. Here, we report that BLM and the FA pathway are activated in response to both crosslinked DNA and replication fork stall. We provide evidence that BLM and FANCD2 colocalise and co-immunoprecipitate following treatment with either DNA crosslinkers or agents inducing replication arrest. We also find that the FA core complex is necessary for BLM phosphorylation and assembly in nuclear foci in response to crosslinked DNA. Moreover, we show that knock-down of the MRE11 complex, whose function is also under the control of the FA core complex, enhances cellular and chromosomal sensitivity to DNA interstrand crosslinks in BS cells. These findings suggest the existence of a functional link between BLM and the FA pathway and that BLM and the MRE11 complex are in two separated branches of a pathway resulting in S-phase checkpoint activation, chromosome integrity and cell survival in response to crosslinked DNA.


Temperature-dependent solvent reorganization entropies, free energies, and transition dipole strengths for the photoexcitation of Reichardt's dye B30.
Absorption spectra of the solvatochromic dye 2,6-diphenyl-4-2,4,6-triphenyl-1-pyridinophenolate (B30) were measured in seven solvents of varying polarity over temperature ranging from each solvent's freezing point to 300 K. The excitation energies and their variances allowed calculations of the solvent reorganization energies, reorganization free energies and reorganization entropies as functions of temperature. The entropies of solvent packing around the chromophore are found to make major contributions to the reorganization free energies. The variances of the excitation energies depend only weakly on temperature, in disagreement with an expression that is often used for solvent reorganization free energies. Polar solvents reduce the transition dipole strength of B30's long-wavelength absorption band, probably because interactions with the solvent enhance the charge-transfer character of the transition. The dipole strength drops further at low temperatures.


Effect of repeated treatment with tianeptine and fluoxetine on central dopamine D(2) /D(3) receptors.
Tianeptine (TIA) is an antidepressant drug that has been shown to decrease extracellular serotonin level and reveals no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated TIA treatment induced any adaptive changes in the central dopamine D(2)/D(3) system (behavioural and biochemical) similar to those reported earlier for tricyclic antidepressants. Experiments were carried out on male Wistar rats. TIA was administered at a dose of 5 and 10 mg/kg once or repeatedly (twice daily for 14 days). Fluoxetine (FLU), used as a reference compound, was also administered at a dose of 10 mg/kg. The results obtained showed that TIA or FLU administered repeatedly increased the hyperlocomotion induced by D-amphetamine and 7-hydroxy-dipropylaminotetralin (7-OH-DPAT). Biochemical study revealed a decrease in the [(3)H]7-OH-DPAT binding sites after acute and repeated treatment with TIA or FLU in the islands of Calleja minor, as well as in the shell part of nucleus accumbens septi. On the other hand, both TIA and FLU administered repeatedly increased the binding of [(3)H]quinpirole (a D(2)/D(3) receptor agonist) in the nucleus caudatus as well as in the core part of the nucleus accumbens septi. Similar effects have been observed when dopamine D(2)/D(3) receptors were visualized with the use of [3H]raclopride, a dopamine D(2)/D(3) receptor antagonist. However, TIA and FLU induced a decrease in the level of mRNA encoding for dopamine D(2) receptors, not only after repeated but also after acute treatment. These results indicate that repeated TIA and FLU administration induces adaptive changes in the dopaminergic D(2)/D(3) system and especially enhances the functional responsiveness of dopamine D(2) and D(3) receptors. However, the question of whether this increased responsiveness is important for clinical antidepressant efficacy remains open.


Standardized ileal amino acid digestibility of plant feedstuffs in broiler chickens and turkey poults using a nitrogen-free or casein diet.
The standardized ileal amino acid digestibility (SIAAD) of 5 plant-based ingredients was determined in 5- and 21-d-old broiler chicks and turkey poults. Two diets (N-free diet, NFD, and a highly digestible protein diet 10% casein, HDP) were fed to determine ileal endogenous amino acid flow, and each was used for endogenous amino acid correction for the plant-based ingredients. The plant-based ingredients evaluated were 2 samples of corn distillers dried grains with solubles (light and dark DDGS), canola meal, corn, and soybean meal. Each diet was fed for 5 d to 6 replicate cages containing 30 or 8 birds, which were sampled on d 5 or 21, respectively. For chicks, apparent ileal amino acid digestibility increased with age for all the feed ingredients. After standardization, SIAAD increased with age when chicks were fed DDGS and corn, but not soybean meal or canola meal. For all the feed ingredients evaluated, SIAAD values for both methods of standardization were not different at d 5. However, the HDP method resulted in greater SIAAD values for most of the amino acids in light DDGS, canola meal, and corn (d 21). In poults, the apparent ileal amino acid digestibility values increased with age for all the feed ingredients except the dark DDGS and canola meal. After standardization, there was no effect of age on amino acid digestibility in all the feed ingredients evaluated, with the exception of corn. Within a particular age (d 5 or 21), both methods of standardization resulted in similar amino acid digestibility values except for corn, for which the SIAAD values were greater (NFD method) in 11 amino acids. Results from this study showed that age-appropriate endogenous amino acid standardization is necessary and, in some cases, results in no age-associated differences in amino acid digestibility. With the exception of corn, standardization of amino acid digestibility with ileal endogenous amino acid flow from birds fed an NFD or HDP did not differ for most plant feedstuffs.


Quantification of molecules in (1)H-NMR metabolomics with formate as a concentration standard.
Quantitative analysis of metabolites is important in (1)H-nuclear magnetic resonance (NMR)-based metabolomics of plasma. Human plasma contains a high density of proteins which heavily adsorb the commonly-used standard compound of sodium 3-(trimethylsilyl) propionate 2, 2, 3, 3-d(4) (TSP). We have evaluated calcium formate as an alternative standard in 1D single-pulse (1)H-NMR spectra to quantify plasma metabolites. Formate did not interact with either plasma metabolites or proteins under adequate conditions. Linear relations between the signal intensities and the added formate have been demonstrated in (1)H spectra. The quantifications of glucose and creatinine by this method have shown good accordance with biochemical analysis. Calcium formate is applicable as a concentration standard to NMR metabolomics of plasma.


De Novo Human Cardiac Myocytes for Medical Research: Promises and Challenges.
The advent of cellular reprogramming technology has revolutionized biomedical research. De novo human cardiac myocytes can now be obtained from direct reprogramming of somatic cells (such as fibroblasts), from induced pluripotent stem cells (iPSCs, which are reprogrammed from somatic cells), and from human embryonic stem cells (hESCs). Such de novo human cardiac myocytes hold great promise for in vitro disease modeling and drug screening and in vivo cell therapy of heart disease. Here, we review the technique advancements for generating de novo human cardiac myocytes. We also discuss several challenges for the use of such cells in research and regenerative medicine, such as the immature phenotype and heterogeneity of de novo cardiac myocytes obtained with existing protocols. We focus on the recent advancements in addressing such challenges.


Heterogeneity of rat tropoelastin mRNA revealed by cDNA cloning.
A lambda gt11 library constructed from poly(A+) RNA isolated from aortic tissue of neonatal rats was screened for rat tropoelastin cDNAs. The first screen, utilizing a human tropoelastin cDNA clone, provided rat tropoelastin cDNAs spanning 2.3 kb of carboxy-terminal coding sequence and extended into the 3'-untranslated region. A subsequent screen using a 5' rat tropoelastin cDNA clone yielded clones extending into the amino-terminal signal sequence coding region. Sequence analysis of these clones has provided the complete derived amino acid sequence of rat tropoelastin and allowed alignment and comparison with published bovine cDNA sequence. While the overall structure of rat tropoelastin is similar to bovine sequence, numerous substitutions, deletions, and insertions demonstrated considerable heterogeneity between species. In particular, the pentapeptide repeat VPGVG, characteristic of all tropoelastins analyzed to date, is replaced in rat tropoelastin by a repeating pentapeptide, IPGVG. The hexapeptide repeat VGVAPG, the bovine elastin receptor binding peptide, is not encoded by rat tropoelastin cDNAs. Variations in coding sequence between rat tropoelastin cDNA clones were also found which may represent mRNA heterogeneity produced by alternative splicing of the rat tropoelastin pre-mRNA.


Molecular insights into the dynamics of pharmacogenetically important N-terminal variants of the human β2-adrenergic receptor.
The human β2-adrenergic receptor (β2AR), a member of the G-protein coupled receptor (GPCR) family, is expressed in bronchial smooth muscle cells. Upon activation by agonists, β2AR causes bronchodilation and relief in asthma patients. The N-terminal polymorphism of β2AR at the 16th position, Arg16Gly, has warranted a lot of attention since it is linked to variations in response to albuterol (agonist) treatment. Although the β2AR is one of the well-studied GPCRs, the N-terminus which harbors this mutation, is absent in all available experimental structures. The goal of this work was to study the molecular level differences between the N-terminal variants using structural modeling and atomistic molecular dynamics simulations. Our simulations reveal that the N-terminal region of the Arg variant shows greater dynamics than the Gly variant, leading to differential placement. Further, the position and dynamics of the N-terminal region, further, affects the ligand binding-site accessibility. Interestingly, long-range effects are also seen at the ligand binding site, which is marginally larger in the Gly as compared to the Arg variant resulting in the preferential docking of albuterol to the Gly variant. This study thus reveals key differences between the variants providing a molecular framework towards understanding the variable drug response in asthma patients.


Pressure wave propagation in a granular bed.
The transmission of pressure waves in granular materials is complicated by the heterogeneity and nonlinearity inherent in these systems. Such waves are propagated through particle contacts primarily along the "force chains" which carry most of the load in granular materials. These fragile and ephemeral chains coupled with irregular particle packing lead to the observed heterogeneity. Nonlinearity in these systems is largely the result of the force-deformation characteristic at particle contacts. Through experiments and simulations, we study the effects of heterogeneity and nonlinearity on the properties of pressure waves through a granular bed.


Fragmentation pathways and structural characterization of 14 nerve agent compounds by electrospray ionization tandem mass spectrometry.
Organophosphate nerve agents (OPNAs) are some of the most widely used and proliferated chemical warfare agents. As evidenced by recent events in Syria, these compounds remain a serious military and terrorist threat to human health because of their toxicity and the ease with which they can be used, produced and stored. There are over 2,000 known, scheduled compounds derived from common parent structures with many more possible. To address medical, forensic, attribution, remediation and other requirements, laboratory systems have been established to provide the capability to analyze 'unknown' samples for the presence of these compounds. Liquid chromatography/mass spectrometric methods have been validated and are routinely used in the analysis of samples for a very limited number of these compounds, but limited data exist characterizing the electrospray ionization (ESI) and mass spectrometric fragmentation pathways of the compound families. This report describes results from direct infusion ESI/MS, ESI/MS(2) and ESI/MS(3) analysis of 14 G and V agents, the major OPNA families, using an AB Sciex 4000 QTrap. Using a range of conditions, spectra were acquired and characteristic fragments identified. The results demonstrated that the reproducible and predictable fragmentation of these compounds by ESI/MS, ESI/MS(2) and ESI/MS(3) can be used to describe systematic fragmentation pathways specific to compound structural class. These fragmentation pathways, in turn, may be useful as a predictive tool in the analysis of samples by screening and confirmatory laboratories to identify related compounds for which authentic standards are not readily available.


MicroRNA-mediated transformation by the Kaposi's sarcoma-associated herpesvirus Kaposin locus.
The human oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) expresses a set of ∼20 viral microRNAs (miRNAs). miR-K10a stands out among these miRNAs because its entire stem-loop precursor overlaps the coding sequence for the Kaposin (Kap) A/C proteins. The ectopic expression of KapA has been reported to lead to transformation of rodent fibroblasts. However, these experiments inadvertently also introduced miR-K10a, which raises the question whether the transforming activity of the locus could in fact be due to miR-K10a expression. To answer this question, we have uncoupled miR-K10a and KapA expression. Our experiments revealed that miR-K10a alone transformed cells with an efficiency similar to that when it was coexpressed with KapA. Maintenance of the transformed phenotype was conditional upon continued miR-K10a but not KapA protein expression, consistent with its dependence on miRNA-mediated changes in gene expression. Importantly, miR-K10a taps into an evolutionarily conserved network of miR-142-3p targets, several of which are expressed in 3T3 cells and are also known inhibitors of cellular transformation. In summary, our studies of miR-K10a serve as an example of an unsuspected function of an mRNA whose precursor is embedded within a coding transcript. In addition, our identification of conserved miR-K10a targets that limit transformation will point the way to a better understanding of the role of this miRNA in KSHV-associated tumors. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human tumor virus. The viral Kaposin locus has known oncogenic potential, which has previously been attributed to the encoded KapA protein. Here we show that the virally encoded miR-K10a miRNA, whose precursor overlaps the KapA-coding region, may account for the oncogenic properties of this locus. Our data suggest that miR-K10a mimics the cellular miRNA miR-142-3p and thereby represses several known inhibitors of oncogenic transformation. Our work demonstrates that functional properties attributed to a coding region may in fact be carried out by an embedded noncoding element and sheds light on the functions of viral miR-K10a.


A Systematic Review of Arts-Based Interventions Delivered to Children and Young People in Nature or Outdoor Spaces: Impact on Nature Connectedness, Health and Wellbeing.
The time that children and young people spend in nature and outdoor spaces has decreased significantly over the past 30 years. This was exacerbated with a further 60% decline post-COVID-19. Research demonstrating that natural environments have a positive impact on health and wellbeing has led to prescription of nature-based health interventions and green prescribing, although evidence for its use is predominantly limited to adults. Growing evidence also shows the impact of arts on all aspects of health and wellbeing. However, what has received scant attention in literature is the interconnection between the two: arts and nature. This review synthesizes the literature surrounding the interconnectedness between arts and nature, and their impact on the health and wellbeing of children and young people. Eight major electronic databases were systematically searched, while hand-searching included 20 journals, six books, and contact with experts. The review was conducted using the Cochrane handbook for systematic reviews, PRISMA guidelines and TIDieR template. All stages were conducted independently by two researchers and the protocol was published on PROSPERO (Registration no.: CRD42021286574). Although 9,314 records were identified, only 11 records were included as most studies focused either on arts or nature, but not both. Studies were conducted in United Kingdom, United States, Ireland, Australia, and Hong Kong, in a range of spaces such as forests, woodlands, beaches, parks, fields, gardens, and school playgrounds. The review encompasses data from 602 participants in total. Arts-in-nature offered an inclusive medium to engage all children and young people, especially those who might otherwise remain disinterested about environmental issues and disengaged with educational programs. Further, arts-in-nature provided stimuli to increase nature connectivity, understand environmental issues and explore ways to prevent environmental disasters. This led to higher environmental awareness and pro-environmental behaviors, and potential decrease in eco-anxiety. Although the quality of qualitative studies was high, the quality of quantitative studies was low or unclear, thus quantitative evidence is still at its infancy. Implications for research, policy, and practice are discussed, such as methods and activities to strengthen future interventions. Scaling-up existing interventions may lead to wider recognition and inclusion of arts-in-nature in future health guidelines, including green prescribing.


Highly Efficient Synthesis and Assay of Protein-Imprinted Nanogels by Using Magnetic Templates.
We report an approach integrating the synthesis of protein-imprinted nanogels ("plastic antibodies") with a highly sensitive assay employing templates attached to magnetic carriers. The enzymes trypsin and pepsin were immobilized on amino-functionalized solgel-coated magnetic nanoparticles (magNPs). Lightly crosslinked fluorescently doped polyacrylamide nanogels were subsequently produced by high-dilution polymerization of monomers in the presence of the magNPs. The nanogels were characterised by a novel competitive fluorescence assay employing identical protein-conjugated nanoparticles as ligands to reversibly immobilize the corresponding nanogels. Both nanogels exhibited Kd <10 pM for their respective target protein and low cross-reactivity with five reference proteins. This agrees with affinities reported for solid-phase-synthesized nanogels prepared using low-surface-area glass-bead supports. This approach simplifies the development and production of plastic antibodies and offers direct access to a practical bioassay.


Medical therapy for renovascular hypertension: a review.
Early medical treatment of renovascular hypertension with diuretics, vasodilators, and centrally acting agents was disappointing, with extended control of blood pressure achieved in only about 40% of patients treated. beta-Adrenergic blockers promised some improvement, but a high failure rate was still apparent. Because converting-enzyme inhibition appeared promising in early studies, we reviewed and analyzed the records of 269 patients with documented renovascular hypertension who were treated with captopril in worldwide trials. Captopril produced complete control of blood pressure in 74% of patients assessed at three months and partial control in an additional 8%. Thirteen percent of patients were discontinued for side effects that occurred, in part, due to the aggressive early captopril-dosing regimen. The drug was clearly ineffective in only 5% of patients. Progressive renal failure sufficient to warrant discontinuation of treatment occurred in only 5% of patients, generally in association with bilateral disease or a solitary kidney. Diagnostic and treatment issues are discussed. Medical therapy with a converting-enzyme inhibitor represents a viable alternative in selected patients with renovascular hypertension, especially those in whom there is a contraindication to surgery or angioplasty.


Different composition of leucocytes in cortical and cancellous bone healing in a mouse model.
Cortical and cancellous bone healing processes appear to be histologically different. They also respond differently to anti-inflammatory agents. We investigated whether the leucocyte composition on days 3 and 5 after cortical and cancellous injuries to bone was different, and compared changes over time using day 3 as the baseline. Ten-week-old male C56/Bl6J mice were randomized to either cancellous injury in the proximal tibia or cortical injury in the femoral diaphysis. Regenerating tissues were analyzed with flow cytometry at days 3 and 5, using panels with 15 antibodies for common macrophage and lymphocyte markers. The cellular response from day 3 to 5 was compared in order to identify differences in how cancellous and cortical bone healing develop. Between day 3 and 5, the granulocytes increased in the cancellous model, whereas the lymphocytes (T cells, B cells, NK cells) and monocytes (CD11b+, F4/80+, CD206+, CD14+) increased in the cortical model. These results suggest an acute type of inflammation in cancellous bone healing, and a more chronic inflammation in cortical healing. This might explain, in part, why cancellous healing is faster and more resistant to anti-inflammatory drugs than are diaphyseal fractures.Cite this article: L. Tätting, O. Sandberg, M. Bernhardsson, J. Ernerudh, P. Aspenberg. Different composition of leucocytes in cortical and cancellous bone healing in a mouse model. Bone Joint Res 2018;7:620-628. DOI: 10.1302/2046-3758.712.BJR-2017-0366.R2.


Ethics in public health research: protecting human subjects: the role of community advisory boards.
Increasingly, researchers grapple with meaningful efforts to involve communities in research, recognizing that communities are distinct from individuals. We also struggle to ensure that individual participants in research are fully protected. Community advisory boards (CABs) offer an opportunity to adopt a relationships paradigm that enables researchers to anticipate and address the context in which communities understand risks and benefits, and individuals give consent. CABs provide a mechanism for community consultation that contributes to protecting communities and fostering meaningful research. Furthermore, CABs can help us to re-create informed consent as a process. It is critical that we conduct research to understand the role of CABs in the informed consent process.


[Association of adiponectin gene polymorphism with obesity in children].
To study the distribution characteristics of adiponectin gene +45 single nucleotide polymorphisms (SNP) in Chinese children, and to determine the role of adiponectin gene +45 polymorphisms in the pathogenesis of childhood obesity. A total of 147 Chinese obese and 118 healthy children were randomly selected and enrolled to identify adiponectin gene SNP+45 polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Plasma adiponectin levels were determined using ELISA. Waist circumference (WC), waist to hip ratio (WHR), percentage of body fat (%BF), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), serum triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), plasma fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. The allelic frequency of adiponectin gene SNP+45 in children with obesity and healthy controls were 40.5% and 25.4%, respectively. There were significant differences in the distribution of genotypes and the allelic frequency between the two groups (P<0.05). The plasma adiponectin levels were significantly higher, in contrast, %BF, HOMA-IR, TC and LDL-C levels were significantly lower in obese children with TT genotype than those in obese children with TG or GG genotype. The adiponectin gene SNP+45 polymorphism may be associated with pathogenesis of obesity in children. T→G variance may be associated an increased risk of childhood obesity and result in a decreased level of adiponectin.


Cephalic phase of insulin secretion in response to a meal is unrelated to family history of type 2 diabetes.
The pre-absorptive cephalic phase of insulin secretion is elicited during the first ten min of a meal and before glucose levels rise. Its importance for insulin release during the post-absorptive phase has been well documented in animals but its presence or importance in man has become increasingly controversial. We here examined the presence of an early cephalic phase of insulin release in 31 well matched individuals without (n = 15) or with (n = 16) a known family history of type 2 diabetes (first-degree relatives; FDR). We also examined the potential differences in individuals with or without impaired fasting (IFG) and impaired glucose tolerance (IGT). We here demonstrate that a cephalic phase of insulin secretion was present in all individuals examined and without any differences between control persons and FDR or IFG/IGT. However, the overall importance of the cephalic phase is conjectural since it was unrelated to the subsequent post-absorptive insulin release or glucose tolerance. One of the best predictors of the incremental cephalic phase of insulin release was fasting insulin level and, thus, a relation to degree of insulin sensitivity is likely. In conclusion, an early pre-absorptive and cephalic phase of insulin release is robustly present in man. However, we could not document any relation to family history of Type 2 diabetes nor to the post-absorptive phase and, thus, confirm its importance for subsequent degree of insulin release or glucose tolerance.


Mesoporous silicas impregnated with cobalt and nickel oxide nanoparticles and the growth of carbon nanotubes there from.
Metal oxide-based nanoparticles of cobalt or nickel were deposited inside the pores and on the surface of hexagonal mesoporous silicas by a direct synthesis technique using Pluronic P85 and P123 surfactants as structure directing agents with the appropriate metal phthalocyanine as a metal precursor. Metal loadings were between 0.4-3.2 wt.%. XPS studies showed that the initial form of the metal oxide nanoparticles were [CoO] and [NiO] respectively. Samples of these materials formed from the P85 surfactant and 3.0 wt.% were used to grow carbon nanotubes (CNTs) from acetylene feedstock in a catalytic chemical vapour deposition (CCVD) reactor at 800 degrees C. CNT growth appeared to be random and the CNTs had diameters ranging from < 10 to > 90 nm. Treatment of the metal impregnated silicas with nitric acid produced materials which, under the same CNT growth conditions, afforded more uniform CNTs with diameters between 5-15 nm. No significant loss in mesophase ordering was seen in the TEM, PXRD or nitrogen physisorption analysis of the acid washed samples. CNTs grown with cobalt impregnated silicas formed with the P123 surfactant had diameters in the range 15-25 nm. Raman spectroscopy of the CNT products showed the nanotubes were highly graphitised and of good quality.


Effect of long-term manure slurry application on the occurrence of antibiotic resistance genes in arable purple soil (entisol).
The application of animal manure is a highly recommended traditional agricultural practice for soils of relatively low fertility. However, for the farmland purple soils that are widely distributed in the upper Yangtze River region, little knowledge has been established in previous studies about the changes in the antibiotic resistome upon manure amendment. In the present study, the impact of long-term pig manure slurry application on the occurrence of antibiotic resistance genes (ARGs) and bacterial community was assessed in arable calcareous purple soil using high-throughput quantitative polymerase chain reaction and Illumina sequencing. Four treatments, including a non-fertilization control (CK) and pig manure (OM), OM plus mineral N fertilizer (OMN) and OM plus mineral NPK fertilizer (OMNPK) treatments were investigated. Across all the soil samples receiving different treatments, a total of 139 unique ARGs and 6 mobile genetic element genes were detected, with multidrug and beta-lactam the two most dominant types of ARGs. The results of the principal coordinate analysis (PCoA) suggest that the profiles of soil ARGs in the two treatments of OM combined with mineral fertilizer(s) (i.e., OMN and OMNPK) were similar to those in the control treatment, while the soil receiving only pig manure application had a different pattern of ARGs from the soils in the other three treatments. A clear reduction of soil ARGs was observed in the OM treatment. Significant and positive relationships were found not only among ARGs but also between mobile genetic elements (MGEs) and ARGs. However, no significant relationships were detected between ARG patterns and bacterial community composition. These results imply that the long-term application of pig manure slurry to purple soil does not lead to the prevalence of ARGs; however, the potential for the horizontal transfer of ARGs in calcareous purple soil should not be ignored.


The Pluto system: Initial results from its exploration by New Horizons.
The Pluto system was recently explored by NASA's New Horizons spacecraft, making closest approach on 14 July 2015. Pluto's surface displays diverse landforms, terrain ages, albedos, colors, and composition gradients. Evidence is found for a water-ice crust, geologically young surface units, surface ice convection, wind streaks, volatile transport, and glacial flow. Pluto's atmosphere is highly extended, with trace hydrocarbons, a global haze layer, and a surface pressure near 10 microbars. Pluto's diverse surface geology and long-term activity raise fundamental questions about how small planets remain active many billions of years after formation. Pluto's large moon Charon displays tectonics and evidence for a heterogeneous crustal composition; its north pole displays puzzling dark terrain. Small satellites Hydra and Nix have higher albedos than expected.


The construct of cuteness: A validity study for measuring content and evoked emotions on social media.
Social media users are often exposed to cute content that evokes emotional reactions and influences them to feel or behave certain ways. The cuteness phenomenon in social media has been scarcely studied despite its prevalence and potential to spread quickly and affect large audiences. The main framework for understanding cuteness and emotions related to cuteness outside of social media is baby schema (having juvenile characteristics), which triggers parental instincts. We propose that baby schema is a necessary but not sufficient component of explaining what constitutes cuteness and how people react to it in the social media context. Cute social media content may also have characteristics that evoke approach motivations (a desire to interact with an entity, generally with the expectation of having a positive experience) that can manifest behaviorally in sharing and other prosocial online behaviors. We developed and performed initial validation for measures in social media contexts of: (1) cute attributes that encompass both baby schema and other proposed cuteness characteristics (the Cuteness Attributes Taxonomy, CAT) and (2) the emotional reactions they trigger (Heartwarming Social Media, HSM). We used the Kama Muta Multiplex Scale (KAMMUS Two), as previously validated measure of kama muta (an emotion akin to tenderness; from Sanskrit, "moved by love") as a measure of emotional reaction to cute stimuli and the dimension Cute Content of the Social Media Emotions Annotation Guide (SMEmo-Cute Content) as a developed measure of gestalt cute content to help validate our newly developed measures. Using 1,875 Polish tweets, our results confirmed that cute social media content predicted a kama muta response, but not all KAMMUS Two subscales were sensitive to cute content, and that the HSM measure was a better indicator of the presence of cute content. Further, the CAT measure is an effective means of categorizing cute attributes of social media content. These results suggest potential differences between in-person, online, and social media experiences evoking cute emotional reactions, and the need for metrics that are developed and validated for use in social media contexts.


CATHETER-ASSOCIATED URINARY TRACT INFECTIONS AFTER CAESAREAN SECTION IN UKRAINE: RESULTS A MULTICENTER STUDY (2020-2022).
The aim: To obtain the first national estimates of the current prevalence rate of catheter-associated urinary tract infections (CAUTIs) after caesarean section (CSEC) and antimicrobial resistance of causing pathogens in Ukraine. Materials and methods: Prospective multicentre surveillance was conducted from January 2020 to December 2022 in 15 women hospitals of Ukraine. Definitions of CAUTIs were adapted from the CDC/NHSN. Antibiotic susceptibility was done by the disc diffusion test as recommended by European Committee on Antimicrobial Susceptibility Testing guidelines. Results: A total of 15,892 catheterized women undergoing primary CSEC and 13.6% CAUTI were identified. The most common uropathogen was Escherichia coli, Proteus mirabilis, and Enterococcus species followed by Providencia stuartii and Pseudomonas aeruginosa. Many uropathogens isolated from CAUTI cases were found to be multidrug resistant. Conclusions: This study showed that CAUTIs in catheterized women undergoing primary CSEC in Ukraine is a common occurrence and many cases are caused by pathogens that are resistant to antibiotics. Optimizing the management and empirical antimicrobial therapy may reduce the burden of CAUTIs in catheterized women undergoing primary CSEC, but prevention is the key element.


Dietary Choline and Betaine and Risk of CVD: A Systematic Review and Meta-Analysis of Prospective Studies.
Studies implicate choline and betaine metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD). We conducted a systematic review and random-effects meta-analysis to quantify a summary estimated effect of dietary choline and betaine on hard CVD outcomes (incidence and mortality). Eligible studies were prospective studies in adults with comprehensive diet assessment and follow-up for hard CVD endpoints. We identified six studies that met our criteria, comprising 18,076 incident CVD events, 5343 CVD deaths, and 184,010 total participants. In random effects meta-analysis, incident CVD was not associated with choline (relative risk (RR): 1.00; 95% CI: 0.98, 1.02) or betaine (RR: 0.99; 95% CI: 0.98, 1.01) intake. Results did not vary by study outcome (incident coronary heart disease, stroke, total CVD) and there was no evidence for heterogeneity among studies. Only two studies provided data on phosphatidylcholine and CVD mortality. Random effects meta-analysis did not support an association between choline and CVD mortality (RR: 1.09, 95% CI: 0.89, 1.35), but one study supported a positive association and there was significant heterogeneity (I² = 84%, p-value < 0.001). Our findings do not support an association between dietary choline/betaine with incident CVD, but call for further research into choline and CVD mortality.


Kalman filtration of radiation monitoring data from atmospheric dispersion of radioactive materials.
A Kalman filter method using off-site radiation monitoring data is proposed as a tool for on-line estimation of the source term for short-range atmospheric dispersion of radioactive materials. The method is based on the Gaussian plume model, in which the plume parameters including the source term exhibit a 'random walk' process. The embedded parameters of the Kalman filter are determined through maximum-likelihood estimation making the filter essentially free of external parameters. The method is tested using both real and simulated radiation monitoring data. For simulated data, the method is shown to retrieve the embedded parameters employed in generating the data and to reconstruct the plume model parameters, including the source term. When tested against experimental radiation monitoring data the method is found accurately to uncover the known source term.


Intrarenal oxygen and hypertension.
The kidney has a unique environment that results in relatively low tissue oxygen tension (Po2). However, recent studies have shown that renal hypoxia is more severe during hypertension and may reflect changes in the way O2 is used. The present review summarizes studies that explore the relationship between renal oxygen tension (Po2), oxygen consumption and hypertension. More recent studies suggest that oxidative stress accompanying hypertension, rather than the elevated blood pressure per se reduces Po2. The Po2 in various sections of the kidney often reflects the level of oxygen consumption, which varies depending on the sites of Na+ reabsorption, a process that consumes nearly 90% of total renal oxygen. The efficient use of oxygen for the transport of Na+ in the kidney is reduced during hypertension, which may contribute to the resulting hypoxia. Conversely, the defect in renal oxygen usage due to oxidative stress may exacerbate hypertension in animal models. The goal of many of these studies is to determine the impact of renal hypoxia in the generation of hypertension.


Rates of return to sorghum and millet research investments: A meta-analysis.
Sorghum and millet grow in some of the most heterogeneous and austere agroecologies around the world. These crops are amongst the top five cereal sources of food and feed. Yet, few studies document the impact of sorghum and millet genetic enhancement. The Internal Rate of Return (ROR) is one of the most popular metrics used to measure the economic return on investment on agricultural research and development (R&D). This study conducted a meta-analysis of 59 sorghum and millet ROR estimates obtained from 25 sources published between 1958 and 2015. The average rate of return to sorghum and millet R&D investment is between 54-76 percent per year. All studies computed social rather than private RORs because the technologies were developed using public funds originating from host country National Agricultural Research Systems (NARS) and international organizations such as the INTSORMIL CRSP, ICRISAT and others. Nearly three quarter of the studies focused only on sorghum (72 percent) and around one tenth of the studies (8 percent) on millet. Regression models analyzed the determinants of variation in the reported RORs. Results show that ex-ante type and self-evaluated type of analyses are positively and significantly associated with the ROR estimates. Compared to estimates conducted by a university, results from international institutions and other mixed organizations provided significantly smaller estimates. Estimates conducted at national level also are significantly lower than those conducted at sub-national levels. The ROR is higher for studies conducted in the United States and for those conducted more recently. The study also reconstructed modified internal rate of return (MIRR) for a sub-sample of the reported RORs following recent methods from the literature. These results show that the MIRR estimates are significantly smaller than the reported ROR estimates. Both results indicate that investment in sorghum and millet research generates high social rates of return.


Neurocognitive course at 2-year follow-up in a Swiss cohort of people with well-treated HIV.
The aim of this study was to examine neurocognitive course over time among people with well treated HIV. The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is an ongoing, prospective, longitudinal, multicenter and multilingual study within the Swiss HIV Cohort Study (SHCS). Participants undergo neuropsychological assessment at baseline and two-yearly follow-up. Seven SHCS centres. Patients aged at least 45 years enrolled in the SHCS with fluency in the local language (French, German or Italian) and agreeing to participate in the NAMACO study: 981 participants at baseline, 720 at 2-year follow-up of whom 644 had complete data sets. Standardized neuropsychological assessment at baseline and 2-year follow-up. Neurocognitive performance using Frascati criteria and mean z-scores. Four participants (of 644, 0.6%) had plasma HIV-1 RNA more than 50 copies/ml; median CD4+ cell count was 660 cells/μl. According to Frascati criteria, 204 participants (31.7%) had neurocognitive impairment (NCI) at baseline. NCI severity in these participants changed little over 2 years and comprehensive models based on Frascati criteria were not feasible. Examining mean z-scores, however, we observed neurocognitive stability or improvement over two years in five of seven neurocognitive domains assessed. Age at least 65 years (P = 0.02) and cognitive complaints (P = 0.004) were associated with neurocognitive decline, while black race (P = 0.01) and dolutegravir treatment (P = 0.002) were associated with improvement. Frascati criteria were less sensitive in measuring NCI change and therefore unsuitable for following neurocognitive course in our cohort of people with well treated HIV. Examining neurocognitive course by mean z-score change, we observed stability or improvement.