Peptide YY. Structure of the precursor and expression in exocrine pancreas.
Peptide YY is a 36-residue gastrointestinal hormone which inhibits both pancreatic and gastric secretion. We have isolated a cDNA encoding the peptide YY precursor by screening a rat intestinal lambda gt11 cDNA library with an antiserum directed against the porcine hormone. The nucleotide sequence of the cDNA encodes a 98-residue protein (molecular weight, 11, 121) which has an amino acid sequence identical to that of porcine peptide YY. Rat peptide YY is preceded immediately by a signal sequence and followed by a cleavage-amidation sequence Gly-Lys-Arg plus 31 additional amino acids. Thus the peptide YY precursor is similar in structure to that of two related peptides, pancreatic polypeptide and neuropeptide Y. RNA blot hybridizations reveal that the peptide YY gene is much more actively expressed in pancreas than previously realized. In situ hybridizations localized peptide YY cells exclusively to the exocrine pancreas. The abundance of peptide YY in one of its target organs, the pancreas, suggests a paracrine mechanism for peptide YY in regulating pancreatic enzyme secretion.


Determination of nalidixic acid and its two major metabolites in human plasma and urine by reversed-phase high-performance liquid chromatography.
This paper describes a precise and sensitive method for analysis of nalidixic acid and its two major metabolites in plasma and urine following the oral administration of a therapeutic dose in humans. After addition of an internal standard (oxolinic acid), 1-ml samples of plasma or urine are extracted at acidic pH with chloroform. The extracts are purified by re-extraction with sodium hydroxide solution and then chloroform. The final extracts are evaporated to dryness, reconstituted in mobile phase and injected into a high-performance liquid chromatograph equipped with RP-8 column and UV detector operating at 254 nm. The limit of sensitivity of the method is lower than 0.5 micrograms/ml of plasma or urine for each compound. The applicability of the method to pharmacokinetic studies of nalidixic acid in humans is demonstrated.


T helper cell-mediated interferon-gamma expression after human parvovirus B19 infection: persisting VP2-specific and transient VP1u-specific activity.
Human parvovirus B19 is a small non-enveloped DNA virus with an icosahedral capsid consisting of proteins of only two species, the major protein VP2 and the minor protein VP1. VP2 is contained within VP1, which has an additional unique portion (VP1u) of 227 amino acids. We determined the ability of eukaryotically expressed parvovirus B19 virus-like particles consisting of VP1 and VP2 in the ratio recommended for vaccine use, or of VP2 alone, to stimulate, in an HLA class II restricted manner, peripheral blood mononuclear cells (PBMC) to proliferate and to secrete interferon gamma (IFN-gamma) and interleukin (IL)-10 cytokines among recently and remotely B19 infected subjects. PBMC reactivity with VP1u was determined specifically with a prokaryotically expressed VP1u antigen. In general, B19-specific IFN-gamma responses were stronger than IL-10 responses in both recent and remote infection; however, IL-10 responses were readily detectable among both groups, with the exception of patients with relapsed or persisting symptoms who showed strikingly low IL-10 responses. Whereas VP1u-specific IFN-gamma responses were very strong among the recently infected subjects, the VP1u-specific IFN-gamma and IL-10 responses were virtually absent among the remotely infected subjects. The disappearance of VP1u-specific IFN-gamma expression is surprising, as B-cell immunity against VP1u is well maintained.


CaMKK2 alleviates myocardial ischemia/reperfusion injury by inhibiting oxidative stress and inflammation via the action on the AMPK-AKT-GSK-3β/Nrf2 signaling cascade.
Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) can regulate numerous biological processes and is implicated in diverse pathological processes. Yet its role in myocardial ischemia/reperfusion (MI/R) injury remains unknown. This project explored the possible functions and mechanisms of CaMKK2 in MI/R injury. A rat model of MI/R in vivo was established using the left anterior descending coronary artery ligation method. Rat cardiomyocytes were exposed to hypoxia/reoxygenation (H/R) in vitro to establish a cell model. Overexpression of CaMKK2 was achieved by infecting recombinant adeno-associated virus or adenovirus expressing CaMKK2. Real-time quantitative PCR, immunoblotting, TTC staining, TUNEL assay, ELISA, oxidative stress detection assays, flow cytometry, and CCK-8 assay were carried out. A decline in CaMKK2 levels was induced by MI/R in vivo or H/R in vitro. Up-modulation of CaMKK2 in rats ameliorated the cardiac injury evoked by MI/R injury accompanied by suppression of cardiac apoptosis, oxidative stress, and proinflammatory response. Rat cardiomyocytes with CaMKK2 overexpression were also protected from H/R damage by inhibiting apoptosis, oxidative stress, and proinflammatory response. CaMKK2 overexpression led to increased phosphorylation of AMPK, AKT, and GSK-3β, and enhanced activation of Nrf2 under MI/R or H/R conditions. Inhibition of AMPK abolished CaMKK2-mediated Nrf2 activation and relevant cardioprotective effect. Restraint of Nrf2 also diminished CaMKK2-mediated relevant cardioprotective effect. Up-regulation of CaMKK2 provides a therapeutic benefit in the rat model of MI/R injury by boosting the Nrf2 pathway through regulation of AMPK/AKT/GSK-3β, which suggests CaMKK2 as a new molecular target for the treatment of MI/R injury.


1H and 13C NMR characterization and secondary structure of the K2 polysaccharide of Klebsiella pneumoniae strain 52145.
The complete (1)H and (13)C NMR characterization of the tetrasaccharide repeating unit from the K2 polysaccharide of Klebsiella pneumoniae strain 52145 is reported. [chemical structure] In addition a model for its secondary structure was suggested on the basis of dynamic and molecular calculations.


Determination of the Fe content of embedded Cu-rich particles in ferritic alloys using energy-filtered TEM.
A novel technique for the quantification of the iron content of copper precipitates in ferritic steels is presented. Energy-filtered (EF) imaging has been used to extract elemental maps with high spatial resolution. These maps contain enough information to attempt the quantification of the signal produced by the precipitates when either a line profile is measured across them or the whole image signal is integrated. Assumptions such as sphericity of the precipitates and composition variations are discussed. Special attention to the assessment of drift on the information extracted from EF images has been taken. Minimum detectability and optimum acquisition conditions are discussed.


Predicting Regional Lymph Node Recurrence in the Modern Age of Tumor-Positive Sentinel Node Melanoma: The Role of the First Postoperative Ultrasound.
The Multicenter Selective Lymphadenectomy Trial II (MSLT-II) led to a change in the management of tumor-positive sentinel lymph nodes (SLNs) from completion node dissection (CLND) to nodal observation. This study aimed to evaluate prognostic factors for predicting sentinel node basin recurrence (SNBR) using data from MSLT-II trial participants. In MSLT-II, 1076 patients were treated with observation. Patients were included in the current study if they had undergone a post-sentinel node basin ultrasound (PSNB-US) within 4 months after surgery. The study excluded patients with positive SLN by reverse transcription-polymerase chain reaction (RT-PCR) or incomplete SLN pathologic data. Primary tumor, patient, PSNB-US, and SLN characteristics were evaluated. Multivariable regression analyses were performed to determine independent prognostic factors associated with SNBR. The study enrolled 737 patients: 193 (26.2%) patients with SNBR and 73 (9.9%) patients with first abnormal US. The patients with an abnormal first US were more likely to experience SNBR (23.8 vs. 5.0%). In the multivariable analyses, increased risk of SNBR was associated with male gender (adjusted hazard ratio [aHR], 1.38; 95% confidence interval [CI], 1.00-1.9; p = 0.049), increasing Breslow thickness (aHR, 1.10; 95% CI, 1.01-1.2; p = 0.038), presence of ulceration (aHR, 1.93; 95% CI, 1.42-2.6; p < 0.001), sentinel node tumor burden greater than 1 mm (aHR, 1.91; 95% CI, 1.10-3.3; p = 0.022), lymphovascular invasion (aHR, 1.53; 95% CI, 1.00-2.3; p = 0.048), and presence of abnormal PSNB-US (aHR, 4.29; 95% CI, 3.02-6.1; p < 0.001). The first postoperative US together with clinical and pathologic factors may play an important role in predicting SNBR.


Immunocytochemical localization of estrogen receptors within neurotensin cells in the rostral preoptic area of the rat hypothalamus.
In situ hybridization procedures indicate that estrogen selectively increases neurotensin and neuromedin (NT/N) mRNA levels in the rostral preoptic area of the rat hypothalamus (RPH). Using the co-localization procedures of Axelson and Van Leeuwen, J. Neuroendocrinol., 2 (1990) 209-216, the present study examined whether NT cells in the RPH contained estrogen receptors (ER). Vibratome sections of brains from adult ovariectomized, colchicine-treated rats were first incubated with estrogen receptor antibody and stained with diaminobenzidine (DAB)-Ni+ producing a blue-black nucleus. Subsequently, NT antisera were used to provide a brown reaction product with DAB as chromogen. Approximately 25% of the NT cells in the RPH contained ER. These data support the hypothesis that NT cells in the RPH that play a role in luteinizing hormone release from the pituitary are, in part, influenced directly by estrogen feedback via nuclear ER and may act as interneurons controlling luteinizing hormone releasing hormone turnover.


Influence of solution viscosity and injection protocol on distribution patterns of jet injectors: application to photodynamic tumour targeting.
Photodynamic therapy of deep or nodular skin tumours is currently limited by the poor tissue penetration of the porphyrin precursor 5-aminolevulinic acid (ALA) and preformed photosensitisers. In this study, we investigated the potential of jet injection to deliver both ALA and a preformed photosensitiser (meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate, TMP) into a defined volume of skin. Initial studies using a model hydrogel showed that as standoff distance is increased, injection depth decreases. As the ejected volume is increased, injection depth increases. It was also shown, for the first time, that, as injection solution viscosity was increased, for a given injection setting and standoff distance, both total depth of jet penetration, L(t), and depth at which the maximum width of the penetration pattern occurred, L(m), decreased progressively. For a standoff distance of zero, the maximum width of the penetration pattern, L(w), increased progressively with increasing viscosity at each of the injection settings. Conversely, when the standoff distance was 2.5 mm, L(w) decreased progressively with increasing viscosity. Studies with neonate porcine skin revealed that an injection protocol comprising an 8.98 mPas solution, an arbitrary injection setting of 8 and a standoff distance of zero was capable of delivering photosensitisers to a volume of tissue (L(t) of 2.91 mm, L(m) of 2.14 mm, L(w) of 5.10 mm) comparable to that occupied by a typical nodular basal cell carcinoma. Both ALA and TMP were successfully delivered using jet injection, with peak tissue concentrations (67.3 mg cm(-3) and 5.6 mg cm(-3), respectively) achieved at a depth of around 1.0mm and substantial reductions in drug concentration seen at depths below 3.0 mm. Consequently, jet injection may be suitable for selective targeting of ALA or preformed photosensitisers to skin tumours.


Benzophenone-1 stimulated the growth of BG-1 ovarian cancer cells by cell cycle regulation via an estrogen receptor alpha-mediated signaling pathway in cellular and xenograft mouse models.
2,4-Dihydroxybenzophenone (benzophenone-1; BP-1) is an UV stabilizer primarily used to prevent polymer degradation and deterioration in quality due to UV irradiation. Recently, BP-1 has been reported to bioaccumulate in human bodies by absorption through the skin and has the potential to induce health problems including endocrine disruption. In the present study, we examined the xenoestrogenic effect of BP-1 on BG-1 human ovarian cancer cells expressing estrogen receptors (ERs) and relevant xenografted animal models in comparison with 17-β estradiol (E2). In in vitro cell viability assay, BP-1 (10(-8)-10(-5)M) significantly increased BG-1 cell growth the way E2 did. The mechanism underlying the BG-1 cell proliferation was proved to be related with the up-regulation of cyclin D1, a cell cycle progressor, by E2 or BP-1. Both BP-1 and E2 induced cell growth and up-regulation of cyclin D1 were reversed by co-treatment with ICI 182,780, an ER antagonist, suggesting that BP-1 may mediate the cancer cell proliferation via an ER-dependent pathway like E2. On the other hand, the expression of p21, a regulator of cell cycle progression at G1 phase, was not altered by BP-1 though it was down-regulated by E2. In xenograft mouse models transplanted with BG-1 cells, BP-1 or E2 treatment significantly increased the tumor mass formation compared to a vehicle (corn oil) within 8 weeks. In histopathological analysis, the tumor sections of E2 or BP-1 group displayed extensive cell formations with high density and disordered arrangement, which were supported by the increased number of BrdUrd positive nuclei and the over-expression of cyclin D1 protein. Taken together, these results suggest that BP-1 is an endocrine disrupting chemical (EDC) that exerts xenoestrogenic effects by stimulating the proliferation of BG-1 ovarian cancer via ER signaling pathway associated with cell cycle as did E2.


Wayfinding in Complex Medical Facilities: The Indexicality of Directional Arrows.
The aim of this article is to contribute to the better design of wayfinding systems by explicating the indexical properties of directional arrows and their consequences for wayfinding behavior. The challenges associated with designing for the wayfinding needs of the different groups of users continue to be documented with the poor design of built environments being largely to blame for the wayfinders' inability to navigate complex settings. Directional arrows have been found to be especially problematic in such settings. Ethnographic data were collected and analyzed over a period of 3 years in three overlapping phases. The unique adequacy requirement of methods, which stipulates that the methods used to produce a description of a situation should originate from the situation they describe, was adopted. Directional arrows derive their meaning from the position they occupy within the physical environment and from three sources: the spatial configuration of the setting, the positioning of the sign within the setting, and the directional arrow itself. The affordance closest to the sign will be taken as the one which the sign refers to. Wayfinders treat that affordance as being indicated by the arrow until such time as it becomes apparent that it is not. In response to the need to find lasting solutions to the enduring problems of wayfinding, this article demonstrates how better design of wayfinding systems can be achieved by explicating the indexical properties of directional arrows and their consequences for wayfinding behavior.


HPTLC and GC-MS finger-printing of two potential multifunctional siddha tailams: Mathan and maha megarajanga tailam.
The Siddha system of medicine is an ancient medical lineage that is practiced primarily in the southern part of India. Siddha system of medicine has been in practice for thousands of years with documented evidence dating back to the 6th century BCE. According to siddha system of medicine's basic fundamental principle, the human body is made up of 96 thathuvam (primary components), which encompass physical, physiological, psychological, and intellectual aspects. Medicine (marunthu) is classified as a wide range of internal and external medicines. The major components of its medical formulations include plant parts, minerals and animal products. Various methods were carried out for the purification process to eliminate the toxins. Choornam, Guligai, Tailam, Parpam, Chendooram, Kattu, Pasai and Poochu are the most common medicines used in Siddha system of medicine for the treatment of various diseases. The pathophysiological classification of diseases is elaborated in detail in the classical Siddha literature. Siddha system of medicine plays an important role in protecting people from diseases such as COVID-19 by providing immune-protecting and immune-boosting medicines in today's world. Mathan tailam and maha megarajanga tailam are the two unique preparations used widely for various skin diseases including chronic wounds and burns. Scientific validation of both medicines will help in understanding their effectiveness against a typical wound condition. In the present study physio-chemical and phytochemical, HPTLC, and GC-MS analyses were carried out and discussed in detail on the multifunctional properties exhibited in the patient communities.


How does inactivation change timing of replication in the human X chromosome?
The kinetics of replication of the inactive (late replicating) X chromosome (LRX) were studied in karyotypically normal lymphocytes and human amniotic fluid cells. Both cell types were successively pulse labeled with 1-h or 1/2-h thymidine pulses in an otherwise BrdU-substituted S phase after partial synchronization of the cultures at G1/S. For the first time with this technique, the entire sequence of replication was analyzed for the LRX from the beginning to the end of the S phase, with special reference to mid S (R-band to G-band transition replication). The inactive X is the last chromosome of the metaphase to start replication, with a delay of 1 or 2 h, after which time a thymidine pulse results in R-type patterns. In mid S, the inactive X is the first chromosome to switch to G-type replication (without overlapping of both types and without any detectable replication pause). Until the end of S, a thymidine pulse results in G-type patterns. To rule out artifacts that might arise by the synchronization of cultures in these experiments, controls were carried out with BrdU pulses and the BrdU antibody technique without synchronization. In the course of replication, no fundamental difference was seen between the two different cell types examined. In contrast to studies using continuous labeling, this study did not reveal an interindividual difference of replication kinetics in the LRXs of the seven individuals studied; thus it is concluded that the inactive X chromosome shows only one characteristic course of replication.


Comparative studies of the effects of chlorpromazine and 5,6-dihydroxytryptamine on locomotion, defensive reactions in the snail Helix lucorum, and command neuron excitability in long-term sensitization.
The actions of the neuroleptic chlorpromazine (CPZ) and the neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) on defensive reactions, locomotion, formation of long-term sensitization, and the electrical characteristics of command neurons in the common snail were compared. Prolonged (chronic) treatment with CPZ led to a significant increase in the pneumostoma closure time, as well as changes in motor behavior, with a decrease in the rate of locomotion. Administration of 5,6-DHT in small daily doses for one week was accompanied by gradual decreases in the rate of locomotion of the snails, which persisted for one week. A similar effect was seen after administration of the same total dose of neurotoxin, 30 mg/kg, as a single injection. Administration of CPZ prevented the formation of long-term sensitization, as did treatment with 5,6-DHT. The procedures of treatment with CPZ, long-term sensitization, long-term sensitization followed by CPZ, and acquisition of long-term sensitization on the background of treatment with CPZ gave a locomotion speed which was directly proportional to the length of the sole. No such relationship was seen during the acquisition of long-term sensitization on the background of treatment with 5,6-DHT. Electrophysiological studies showed that chronic CPZ led to a depolarization shift in the membrane potential and a decreased action potential generation threshold in command neurons, which also occurred on treatment with 5,6-DHT. It is concluded that the actions of the neuroleptic CPZ on defensive behavior and locomotion in the common snail, as well as on the electrical characteristics of identified neurons, were similar to the toxic actions of serotonin.


New approach to recycle and valorize the first filtrate of the LignoForce system™: Lignin extraction and its use in rigid lignin-based polyurethane foams.
In this work, we report on the fractionation, recovery and characterization of softwood kraft lignin from the first filtrate of the LignoForce™ process. It is estimated that the lignin content in this stream could be >20-30 % of the lignin present initially in the black liquor. The use of a membrane filtration system was experimentally validated as an effective method for fractionating the first filtrate. Two membranes with different nominal molecular weight cut-offs (4000 and 250 Da) were tested. Higher lignin retention and recovery was obtained using the 250-Da membrane. This lignin (lignin_250) was found also to have a lower molecular weight and a tighter molecular weight distribution compared to the lignin obtained using the 4000-Da membrane (lignin_4000). The lignin_250 was characterized for it's hydroxyl group content and used to produce polyurethane (PU) foams. Up to 30 wt% petroleum-based polyol replacement by lignin_250, the resulting lignin-based PU (LBPU) foams presented the same thermal conductivity as the control (0.0303 W/m.K (control) vs 0.029 W/m.K (30 wt%)), as well as comparable mechanical (max stress: 145.8 kPa (control) vs 222.7 KPa (30 wt%), modulus 64.3 kPa (control) vs 75.1 (30 wt%)) and morphological properties to the petroleum polyol-based PU foams.


Current educational reforms in nursing in the United Kingdom and their impact on the role of nursing lecturers in practice: a case study approach.
This paper explores major developments in nurse education in the UK in the last 5 years and examines their impact on the role of nursing lecturers in practice. It builds upon the findings of an earlier study that described significant changes in the UK in the role and work of nurse teachers resulting from Project 2000 initiatives. Empirical data were collected over a 2.5-year period, through observations of student-teacher interaction and in-depth interviews with experienced nurse teachers and senior health professionals (n = 41). A case study approach using qualitative techniques was adapted for the study. The results of the study showed that, in the light of current educational reforms, nursing lecturers were expected to maintain closer links with the service sector and spend more time on clinical teaching and learner contact. Also considered important was the need for nursing lecturers to support clinical staff in creating an effective learning environment. Using the findings of the study, the author has mapped what was perceived to be the development of an effective model for the role of nursing lecturers in practice: a model that reflects the expected changes to a higher educational environment.


Sand ripple dynamics in the case of out-of-equilibrium aeolian regimes.
From a phenomenological hydrodynamical model, we analyze the aeolian sand ripple evolution in an out-of-equilibrium aeolian regime where erosion exceeds accretion (and vice versa). We find, in particular, that the ripple structure can be destroyed in favor of a flat sand bed. In the ripple regime we report on a new class of generic dynamics described by the Benney equation. This equation reveals either order or disorder depending on whether wave dispersion is strong or weak. In both cases, the average wavelength of the pattern is fixed in time. This markedly contrasts with the regime of equilibrium aeolian regime -reached when erosion balances deposition- where ripples undergo a coarsening process at long time (i.e., the wavelength increases indefinitely with time).


Serologic evidence of hepatitis A and B virus infections in thalassemia patients: a retrospective study.
To determine the current risk of hepatitis B virus (HBV) infection in multiply transfused thalassemia patients, we tested sera from such patients in New York City for the hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs) using radioimmunoassay techniques. Altogether 48 per cent of the patients had either HBsAg (4.5%) or anti-HBs (43.9%) positive sera. The prevalence of these HBV markers was related to both the number of units transfused and the year blood transfusion therapy was begun, although evidence suggested that the latter factor had the greatest influence. Donor HBsAg screening began in New York in 1969, and only one patient first transfused since that time had HBV marker positive serum. Thus, multiply-transfused thalassemia patients now appear to be at little risk of HBV infection from transfusions. Sera were also tested for antibody to the hepatitis A virus (anti-HA) using immune adherence hemaglutination. Anti-HA prevalence was only 4.9 per cent, no greater than rates reported among nontransfused children, providing evidence against a significant role for blood transfusions in hepatitis A virus transmission.


The therapeutic alliance in medical-based interventions impacts outcome in treating alcohol dependence.
This study examined the relationship of the therapeutic alliance and treatment outcomes for alcohol-dependent patients receiving naltrexone or placebo and one of three different types of clinical interventions, including two medical-based (non-specialty) treatments. This is a secondary analysis of a 24-week randomized, placebo-controlled, clinical trial of 100mg/day of naltrexone or placebo for patients with DSM-IV alcohol dependence. Patients were also randomized to one of three interventions: (1) medication clinic only, (2) medication clinic plus BRENDA (an intervention promoting pharmacotherapy), or (3) medication clinic plus cognitive behavioral therapy (CBT). Early in treatment, patients and clinicians completed the working alliance inventory (WAI). Regression analyses were conducted to determine the predictive validity of the WAI on percent days abstinent and percent of sessions attended over the clinical trial. In the medication clinic only condition, the clinicians' WAI total score was marginally correlated to percent of visits attended (p=.057) but not percent days abstinent. In the medication clinic plus BRENDA condition, clinicians' WAI total score was positively correlated with percent days abstinent (p=.013) but not percent visits attended. No significant relationships were found between the WAI scores and either outcome measure in the CBT condition or for any of the patient rated assessments. To our knowledge, this is the first published report providing some support for the importance of the therapeutic alliance in medical interventions for alcohol dependence but only in the context of the clinicians' ratings. The absence of other effects underscores the need for further research.


Adverse rearing environments and neural development in children: the development of frontal electroencephalogram asymmetry.
Children raised in institutional settings experience marked deprivation in social and environmental stimulation. This deprivation may disrupt brain development in ways that increase risk for psychopathology. Differential hemispheric activation of the frontal cortex is an established biological substrate of affective style that is associated with internalizing psychopathology. Previous research has never characterized the development of frontal electroencephalogram asymmetry in children or evaluated whether adverse rearing environments alter developmental trajectories. A sample of 136 children (mean age = 23 months) residing in institutions in Bucharest, Romania, and a sample of community control subjects (n = 72) participated. Half of institutionalized children were randomized to a foster care intervention. Electroencephalogram data were acquired at study entry and at ages 30, 42, and 96 months. A structured diagnostic interview of psychiatric disorders was completed at 54 months. Children exhibited increases in right relative to left hemisphere frontal activation between the second and fourth years of life, followed by an increase in left relative to right hemisphere activation. Children reared in institutions experienced a prolonged period of increased right hemisphere activation and a blunted rebound in left frontal activation. Foster care placement was associated with improved developmental trajectories but only among children placed before 24 months. The development trajectory of frontal electroencephalogram asymmetry in early childhood predicted internalizing symptoms at 54 months. Exposure to adverse rearing environments can alter brain development, culminating in heightened risk for psychopathology. Interventions delivered early in life have the greatest potential to mitigate the long-term effects of these environments.


Diffusion-tensor imaging for differentiating uterine sarcoma from degenerative uterine fibroids.
To explore the applicability of diffusion-tensor imaging (DTI) sequence quantitative parameters in differentiating uterine sarcoma (USr) from degenerative uterine fibroids (DUF). Fourteen cases of USr and 30 cases of DUF were analysed retrospectively. The diffusion-weighted imaging (DWI) and DTI images were analysed by two observers using Functool software on a ADW4.6 workstation. The images were post-processed to generate an apparent diffusion coefficient (ADC) map of DWI, ADC map of DTI (ADCT map), and fractional anisotropy (FA) map. Three regions of interest (ROI) were selected from the ADC, ADCT, and FA maps to obtain the ADC, ADCT, and FA values. The receiver operating characteristic (ROC) curves of all parameters were used to analyse and compare the diagnostic value of USr and DUF. The ADC value, ADCT value, and FA value of USr (1.190 ± 0.262 × 10-3mm2/s, 1.165 ± 0.270 × 10-9mm2/s, 0.168 ± 0.063) were significantly lower compared to the values for DUF (1.525 ± 0.314 × 10-3mm2/s, 1.650 ± 0.332 × 10-9mm2/s, 0.254 ± 0.111; all p<0.001). The diagnostic threshold values for USr were: ADC ≤1.290 × 10-3mm2/s, ADCT ≤1.322 × 10-9mm2/s and FA ≤0.192. The corresponding sensitivities and specificities were 78.6%/90%, 96.7%/92.9%, and 86.7%/85.7%, respectively. The areas under the curve (AUC) were 0.875, 0.974, and 0.831, respectively. DTI quantitative parameters can be used to differentiate USr from DUF. The ADCT value had the highest diagnostic efficacy.


Purification, characterization, and identification of novel inhibitors of the beta-ketoacyl-acyl carrier protein synthase III (FabH) from Staphylococcus aureus.
Staphylococcus aureus is a versatile and dangerous pathogen and one of the major causes of community-acquired and hospital-acquired infections. The rise of multidrug-resistant strains of S. aureus requires the development of new antibiotics with previously unexploited mechanisms of action, such as inhibition of the beta-ketoacyl-acyl carrier protein (ACP) synthase III (FabH). This enzyme initiates fatty acid biosynthesis in a bacterial type II fatty acid synthase, catalyzing a decarboxylative condensation between malonyl-ACP and an acyl coenzyme A (CoA) substrate and is essential for viability. We have identified only one fabH in the genome of S. aureus and have shown that it encodes a protein with 57, 40, and 34% amino acid sequence identity with the FabH proteins of Bacillus subtilis (bFabH1), Escherichia coli (ecFabH), and Mycobacterium tuberculosis (mtFabH). Additional genomic sequence analysis revealed that this S. aureus FabH (saFabH) is not mutated in certain methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) strains. saFabH was expressed in E. coli with an N-terminal polyhistidine tag and subsequently purified by metal chelate and size exclusion chromatography. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a molecular mass of 37 kDa, while gel filtration demonstrated a mass of 66.7 kDa, suggesting a noncovalent homodimeric structure for saFabH. The apparent K(m) for malonyl-ACP was 1.76 +/- 0.40 microM, and the enzyme was active with acetyl-CoA (k(cat), 16.18 min(-1); K(m), 6.18 +/- 0.9 microM), butyryl-CoA (k(cat), 42.90 min(-1); K(m), 2.32 +/- 0.12 microM), and isobutyryl-CoA (k(cat), 98.0 min(-1); K(m), 0.32 +/- 0.04 microM). saFabH was weakly inhibited by thiolactomycin (50% inhibitory concentration [IC50], >100 microM) yet was efficiently inhibited by two new FabH inhibitors, 5-chloro-4-phenyl-[1,2]-dithiol-3-one (IC50, 1.87 +/- 0.10 microM) and 4-phenyl-5-phenylimino-[1,2,4]dithiazolidin-3-one (IC50, 0.775 +/- 0.08 microM).


The Safety After Fifty Evaluation trial: evaluation of the safety and efficacy of antihypertensive therapy with metoprolol in patients 50 to 75 years of age: study design.
Hypertension increases in prevalence with advancing age and is a major risk factor for the development of cardiovascular disease in elderly patients. However, the presence of coexisting illness, altered drug metabolism, enhanced susceptibility to drug side effects, and physiologic changes such as reduced plasma volume and lower plasma renin levels make treatment of hypertension in elderly patients more difficult. Nonetheless, several studies have now demonstrated the beneficial effects of antihypertensive drug therapy in older patients. The Safety After Fifty Evaluation trial was designed to determine the short-term efficacy and tolerability of once-daily therapy with the cardioselective beta-blocker metoprolol alone or in combination with hydrochlorothiazide in the treatment of mild hypertension in patients 50 to 75 years of age. A total of 24,816 patients were enrolled in the trial by 2821 practicing physicians from across the United States. This article describes the details of the Safety After Fifty Evaluation study design. Results of the trial will be reported separately.


Activation of NMDA receptors prevents excessive metabolic decrease in hypoxic rat pups.
We tested the hypothesis that glutamate NMDA receptors may help maintain metabolic rate and body temperature during acute or chronic hypoxic exposure in newborn rats. We recorded ventilation, metabolism ((.)V(O(2)) -- ((.)V(CO(2)) and rectal temperature, under normoxia, acute hypoxia (30 min -- 12% O(2)), or following 10 days of chronic hypoxia, in 10 days old male and female rats, receiving saline i.p. injection or the NMDA receptor antagonist MK-801. Acute hypoxia decreased rectal temperature and metabolism, and increased ventilation, and (.)V(E)/((.)V(O(2) and (.)V(E)/((.)V(CO(2) to the same extent in males and females. MK-801 injection amplified the metabolic decrease under acute (in males and females) and chronic (in males) hypoxia, prevented the increase of minute ventilation, while (.)V(E)/((.)V(O(2) or (.)V(E)/((.)V(CO(2)remained constant. Hence, NMDA glutamate receptors help to maintain metabolic rate, minute ventilation and body temperature at a determined level in acute (males and females) and chronic hypoxia (males only).


A practical approach to the management of nocturia.
To raise awareness on nocturia disease burden and to provide simplified aetiologic evaluation and related treatment pathways. A multidisciplinary group of nocturia experts developed practical advice and recommendations based on the best available evidence supplemented by their own experiences. Nocturia is defined as the need to void ≥1 time during the sleeping period of the night. Clinically relevant nocturia (≥2 voids per night) affects 2%-18% of those aged 20-40 years, rising to 28%-62% for those aged 70-80 years. Consequences include the following: lowered quality of life; falls and fractures; reduced work productivity; depression; and increased mortality. Nocturia-related hip fractures alone cost approximately €1 billion in the EU and $1.5 billion in the USA in 2014. The pathophysiology of nocturia is multifactorial and typically related to polyuria (either global or nocturnal), reduced bladder capacity or increased fluid intake. Accurate assessment is predicated on frequency-volume charts combined with a detailed patient history, medicine review and physical examination. Optimal treatment should focus on the underlying cause(s), with lifestyle modifications (eg, reducing evening fluid intake) being the first intervention. For patients with sustained bother, medical therapies should be introduced; low-dose, gender-specific desmopressin has proven effective in nocturia due to idiopathic nocturnal polyuria. The timing of diuretics is an important consideration, and they should be taken mid-late afternoon, dependent on the specific serum half-life. Patients not responding to these basic treatments should be referred for specialist management. The cause(s) of nocturia should be first evaluated in all patients. Afterwards, the underlying pathophysiology should be treated specifically, alone with lifestyle interventions or in combination with drugs or (prostate) surgery.


Outcome of second trimester amniocentesis in singleton pregnancy at Songklanagarind Hospital.
To evaluate the outcome of genetic amniocentesis in singleton gestation at Songklanagarind Hospital. This was a descriptive study that included all singleton pregnant women who had a second trimester amniocentesis for chromosome studies at the Maternal Fetal Medicine Unit, Department of Obstetrics and Gynecology, Songklanagarind Hospital between January 1998 and 2006 to assess the outcome including risk of fetal loss in such cases. Advanced maternal age was the most common indication for amniocentesis. Amniocentesis after positive screening aneuploidy test increased. The fetal loss within 14 days after the procedure was 0.12% (10/8,073). Leakage of amniotic fluid occurred 0.1% (5/8,073) but only one case aborted. Fever occurred in two cases and a case of chorioamnionitis was diagnosed. The rate of fetal loss within 14 days after amniocentesis in singleton pregnant women was lower than the authors' previous 10 years. The anxiety of the family and difficulty of counseling to the family will be reduced because of a lower complication rate. Moreover the pregnant women who have a high degree of anxiety for genetic abnormalities are a likely choice for genetic amniocentesis if the risk rate regarding the patient's age, ultrasonographic finding, or maternal serum screening is around 0.1%.


Adherence to Option B+ Care for the Prevention of Mother-to-Child Transmission Among Pregnant Women in Ethiopia.
Even if progressive efforts were made in Ethiopia, half of new HIV infections result from mother-to-child transmission. Limited studies assessed the level and factors of adherence that differ among different populations across the country. So, this study aimed to investigate the level and predictors of adherence to the prevention of mother-to-child transmission (PMTCT) Option B+ care among pregnant women in central Ethiopia. A facility-based cross-sectional study design was conducted to interview 347 HIV positive pregnant women. Using a multistage sampling technique, participants were recruited from twelve health facilities based on probability proportional to the number of clients. The collected data on socio-demographics, healthcare delivery, clinical and individual factors were entered into EpiInfo v126.96.36.199, and further analysis was done using SPSS v23 software. Adherence was measured based on client self-report either as adherent and non-adherent. Bivariate and multivariate logistic regressions were undertaken to see the association between variables. Statistically significant variables were declared using an adjusted odds ratio with a 95% confidence interval. The overall adherence to option B+ was 80.2% (95% CI: 76.3-84.5%). Time of ART initiation (AOR=3.23; 95% CI: 1.09-6.59), fear of stigma for taking ARV (AOR=5.06; 95% CI: 1.79-10.26), ANC appointment (AOR=4.62; 95% CI: 1.48-6.42), male partner support (AOR=2.23; 95% CI: 1.11-4.50), and counseling (AOR=5.36: 95% CI: 1.00-8.58) were the associated factors with level of adherence. The overall adherence level to Option B+ care in this study was inadequate to suppress the viral load during pregnancy. The result revealed that keeping adherence to ARVs during pregnancy is still challenging. So, all concerned bodies need to give attention to minimize the barriers from the client, environment, and health system perspectives.


Mobility and speciation of arsenic in the coal fly ashes collected from the Savannah River Site (SRS).
Arsenic (As) leaching from coal fly ash stockpiled at waste disposal sites is a source of environmental concern. An array of techniques including batch extraction and column leaching tests, in combination with speciation analysis of chemically specific As species, was employed to evaluate the mobility of As in fly ashes collected from the U.S. DOE Savannah River Site. The results obtained using the U.S. EPA Toxicity Characteristic Leaching Procedure (TCLP), a two-step sequential extraction technique, and continuous column leaching experiments suggest that only a small portion of total As in the fly ashes was mobile, but mobilizable As could be a considerable fraction (3.1-43%), varying inversely with alkalinity of fly ash. Speciation analysis by using phosphate extraction suggests that arsenate (As(V)) was the major extractable species in the fly ash samples. During the column leaching experiment, however, it was observed that arsenite (As(III)) was an important species leached out of the fly ashes, indicating species conversion during the leaching process. The matrix-bound As(V) within the fly ash, once being released from the solid matrix, could be converted to As(III) during its transport inside the column. The pHs of leachates and fly ashes (both acidic in column leaching experiments here) could be related to the dominance of As(III) in the effluents.


Intraperitoneal leakage of technetium-99m-DTPA following renal transplantation: a sign of chylous ascites.
A 7-yr-old girl developed persistent ascites following renal transplantation. Renal scintigraphy periodically performed to monitor renal function of the transplanted kidney showed increased 99mTc-DTPA in the abdominal cavity on delayed imaging. Paracentesis demonstrated a cloudy yellow, odorless fluid which was identified as chylous ascites, an extremely rare complication of abdominal vascular surgery. Technetium-99m-DTPA in the peritoneal cavity following renal transplantation should be recognized as a sign suggestive of chylous ascites.


Comparison of the Inguinal and High Scrotal Approaches for the Treatment of Inguinal Hernias in Boys.
The conventional groin incision herniotomy is still being adhered to despite high success rate of high scrotal approach. Hence, the aim of this study was to compare the outcomes of high scrotal and conventional approaches for the treatment of inguinal hernia in boys. A prospective study of 100 boys with 108 inguinal hernias whose ages were less than 15 years. They were randomized into 2 groups; high scrotal and conventional approaches. Ninety-four patients with 101 hernias were analyzed. The operative time, conversion rate (high scrotal approach), and postoperative complications were reported. A total of 100 boys with 108 hernias were enrolled but 94 patients with 101 hernias were analyzed. They comprised of 48 patients with 51 hernias in the high scrotal group and 46 patients with 50 hernias in the conventional group. Their age range was between 2 months and 168 months with a mean of 47.9 ± 46.7 months. The conversion rate of high scrotal approach was 1.9%. The mean duration of operation in the high scrotal group was 37.1 ± 13.3 minutes compared with 37.2 ± 15.1 minutes in the conventional group, p = 0.982. Early postoperative scrotal edema was more in the high scrotal group compared to the conventional group, p = 0.018. The Hollander wound evaluation score was better in the high scrotal incision compared to the conventional approach, p = 0.003. The high scrotal approach may be an alternative to conventional herniotomy in boys.


A randomised controlled trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion up to 13 weeks of gestation.
To assess women's acceptability, the efficacy and side effects of sublingual versus vaginal administration of misoprostol in combination with mifepristone for medical abortion up to 13 weeks of gestation. Randomised controlled trial. Aberdeen Royal Infirmary. Women undergoing medical abortion under the terms of the 1967 Abortion Act. Mifepristone (200 mg) was given orally followed 36-48 hours later by misoprostol administration (sublingual: 600 microg; vaginal: 800 microg). A second dose of misoprostol 400 microg was given 3 hours later (sublingually or vaginally). Women between 9 and 13 weeks of gestation received a further (third) dose of misoprostol 400 microg (sublingually or vaginally), 3 hours later if abortion had not occurred. Women's acceptability, efficacy of the regimen and side effects experienced. A total of 340 women were recruited (171 sublingual and 169 vaginal). A total of 70% of women in the sublingual group expressed satisfaction with the route of misoprostol administration; 18% answered 'Don't know' while 12% were dissatisfied, compared with 68%, 28% and 4%, respectively, in the vaginal group (P= 0.02). There was no significant difference in the need for surgical evacuation for women in the sublingual (3/158, 1.9%) and vaginal groups (4/156, 2.6%) (P= 0.70). Women receiving misoprostol sublingually were more likely to experience diarrhoea (P < 0.01), shivering (P < 0.01) and unpleasant mouth taste (P < 0.01). Sublingual administration of misoprostol is an effective alternative to vaginal administration for medical abortion up to 13 weeks of gestation. The prevalence of prostaglandin-related side effects, however, was higher with this route of administration.


Evidence for regulation of endothelial plasminogen-activating system by polymorphonuclear leukocyte elastase.
Incubation of unstimulated polymorphonuclear leukocytes with cultured bovine pulmonary artery endothelial cells increased the activity of endothelial plasminogen activator. On the other hand, polymorphonuclear leukocytes stimulated by serum-opsonized zymosan decreased the plasminogen activator activity. A specific elastase inhibitor increased the enhancing effect of the unstimulated polymorphonuclear leukocytes and reversed the suppressing effect of the stimulated polymorphonuclear leukocytes. Catalytically active elastase suppressed the plasminogen activator activity and increased the activity of plasminogen activator inhibitor. In contrast, inactivated elastase enhanced the activity of plasminogen activator. Both, active and inactive forms of elastase bound to the endothelial cells. These findings suggest that elastase modulates the endothelial plasminogen-activating system, apparently by binding to the endothelial cells.


Psychosocial predictors and correlates for chronic post-surgical pain (CPSP) - a systematic review.
Chronic post-surgical pain (CPSP) is a serious problem. Incidence as high as 50% has been reported, depending on type of surgery undergone. Because the etiology of chronic pain is grounded in the bio-psychosocial model, physical, psychological, and social factors are implicated in the development of CPSP. Biomedical factors such as pre-operative pain, severe acute post-operative pain, modes of anesthesia, and surgical approaches have been extensively examined, therefore this systematic review focuses on psychosocial elements. A systematic search was performed using the PubMed, PsychINFO, Embase, and Cochrane Databases. Fifty relevant publications were selected from this search, in which psychosocial predictors for and correlates to CPSP were identified. The level of evidence was assessed for each study, and corresponding score points were awarded for ease of comparison. The grade of association with CPSP for each predictor/correlate was then determined. Depression, psychological vulnerability, stress, and late return to work showed likely correlation with CPSP (grade of association=1). Other factors were determined to have either unlikely (grade of association=3) or inconclusive (grade of association=2) correlations. In addition, results were examined in light of the type of surgery undergone. This review is intended as a first step to develop an instrument for identifying patients at high risk for CPSP, to optimize clinical pain management.


Our ultrasonographic experience in the management of symptomatic hydronephrosis during pregnancy.
The aim of the present study was to document the role of ultrasound in the diagnosis and management of symptomatic hydronephrosis during pregnancy. In this study, we reviewed 36 consecutive cases of pregnant women whose pregnancy was complicated by symptomatic hydronephrosis. In all patients, management was initially conservative (analgesics and fluids) after hospitalization. The following criteria were used to indicate double-J stent placement under US guidance rather than a conservative treatment: persistent pain with no improvement after conservative treatment, progressive hydronephrosis (>2 cm dilatation of the renal pelvis) or presence of uterine contractions. The mean patient's age was 25 years (17-35) and gestational age at clinical presentation was 24 weeks (13-37). 81 % of cases had a renal pelvis dilatation >2 cm, while in only 19 % of cases there was a hydronephrosis between 1 and 2 cm in diameter; however, calculi were confirmed only in 25 patients. 28 patients required an invasive management with double-J stent insertion under US guidance. The sensitivity and specificity of US in the etiological diagnosis of hydronephrosis during pregnancy was 83 and 91 %, respectively. Conservative management with medical therapy and observation should be the first-line treatment approach. In our opinion a rapid ureteral decompression with the insertion of a ureteral double-J stent, under US visualization, is the safest method in the treatment of pregnant women with obstructed renal systems.


The characterisation of human respiratory epithelial cells cultured on resorbable scaffolds: first steps towards a tissue engineered tracheal replacement.
In this study we have used lectin histochemistry and scanning electron microscopy (SEM) to assess the growth and characterise the differentiation of human respiratory epithelial cells (REC) cultured on two biomaterial scaffolds. The first scaffold, based on a hyaluronic acid derivative, was observed to be non-adhesive for REC. This lack of adhesion was found to be unrelated to the presence of the hyaluronic acid binding domain on the surface of isolated REC. The other scaffold, consisting of equine collagen. was observed to encourage REC spreading and adhesion. Positive Ulex Europaeus agglutinin (UEA) lectin staining of this preparation indicated the presence of ciliated REC on the scaffold surface. However, the marked decrease in peanut agglutinin (PNA) positive staining, relative to that of control cultures and native tissue, indicates a dedifferentiation of the secretory cells of the REC monolayer. SEM analysis of REC cultured on the collagen scaffold confirmed the presence of ciliated cells thereby validating the UEA positive staining. The presence of both established and developing cilia was also verified. This study indicates that collagen biomaterials are appropriate for the tissue engineering of REC. Furthermore, that UEA and PNA staining is a useful tool in the characterisation of cells cultured on biomaterials, therefore helpful in identifying biomaterials that are suitable for specific tissue engineering purposes.


Delayed neurotoxicity of excitatory amino acids in vitro.
The acute neurotoxicity produced by glutamate and related excitatory amino acids is probably caused by depolarization leading to excessive anionic and cationic fluxes and osmotic lysis. Recently, a more delayed form of glutamate neurotoxicity, which is critically dependent upon calcium influx, has been described in cultured neocortex. We investigated this phenomenon in cultures of dispersed rat hippocampal neurons. When these cultures were briefly incubated with various excitatory amino acids in low extracellular chloride, there was no acute toxicity, but a gradual drop-out of neurons occurred over the next day. When calcium was removed from the extracellular medium during amino acid incubation, this late neuronal loss was not seen. Interestingly, blocking excitatory amino acid receptors in cultures after the amino acid exposure also prevented this delayed neuronal death. In addition, these treated cultures contained neurons with normal physiological properties, and had concentrations of adenosine triphosphate that were close to control values. The findings suggest an amino acid-induced calcium influx may elevate the release of endogenous excitatory transmitter, likely glutamate, and/or increase the sensitivity of these neurons to glutamate. These in vitro observations may partially explain the delayed neuronal loss seen in some pathological conditions affecting man.


Estimated effects of Asian dust storms on spatiotemporal distributions of clinic visits for respiratory diseases in Taipei children (Taiwan).
Increases in certain cause-specific hospital admissions have been reported during Asian dust storms (ADS), which primarily originate from north and northwest China during winter and spring. However, few studies have investigated the relationship between the ADS and clinic visits for respiratory diseases in children. We investigated the general impact to children's health across space and time by analyzing daily clinic visits for respiratory diseases among preschool and schoolchildren registered in 12 districts of Taipei City during 1997-2007 from the National Health Insurance dataset. We applied a structural additive regression model to estimate the association between ADS episodes and children's clinic visits for respiratory diseases, controlling for space and time variations. Compared with weeks before ADS events, the rate of clinic visits during weeks after ADS events increased 2.54% (95% credible interval = 2.43, 2.66) for preschool children (≤ 6 years of age) and 5.03% (95% credible interval = 4.87, 5.20) for schoolchildren (7-14 years of age). Spatial heterogeneity in relative rates of clinic visits was also identified. Compared with the mean level of Taipei City, higher relative rates appeared in districts with or near large hospitals and medical centers. To our knowledge, this is the first population-based study to assess the impact of ADS on children's respiratory health. Our analysis suggests that children's respiratory health was affected by ADS events across all of Taipei, especially among schoolchildren.


C-terminal substance P fragments elicit histamine release from a murine mast cell line.
Incubation of mouse mast cells with C-terminal substance P fragments in the micromolar range caused a release of histamine. Maximum release was observed with the tetrapeptide SP(8-11), followed by the tripeptide SP(9-11). SP(6-11) and SP(5-11) were nearly equipotent, while SP(4-11) caused only a slight histamine release. The substance P parent molecule and the N-terminal substance P fragments SP(1-4), SP(1-6) and SP(1-7) evoked no release of histamine. In confirmation of our previous findings, incubation with neurokinin A caused a release comparable to that of SP(8-11). Whereas neurokinin A-induced release was partially preventable by pretreating the cells with the NK2 receptor-selective antagonist cyclo(Gln-Trp-Phe-(R)Gly[ANC-2]Leu-Met), SP(8-11)-induced release was completely abolished by such treatment. The results provide the first evidence for the involvement of NK2 tachykinin receptors in the release of histamine by C-terminal substance P fragments.


Characterization of dualtropic type C retroviruses isolated from spontaneous non-T lymphomas of SJL/J(V+) mice.
Endogenous XC- viruses were isolated from non-T spontaneous lymphomas of SJL/J(v+) mice. These isolates were cloned by limiting dilution procedure and characterized for biological and immunological properties. At the electron microscope these isolates showed typical retrovirus type C morphology. Reverse transcriptase and immunofluorescence assays showed that these viruses were infectious for mouse and heterologous cell lines. Since some of the isolates induced cytopathic foci in mink lung cultures, they had properties similar to those described for other recombinant dualtropic viruses. Using a panel of monoclonal antibodies against gp 70 and p 15 (E) viral proteins, it was observed that the dualtropic XC- viral isolates had an antigenic profile different from that of SJL ecotropic XC+ virus.


The Neurophysiological Lesion: A Scoping Review.
The purpose of this study was to examine the extent of the literature on the neurophysiological lesion as referenced in functional neurology. A literature search was performed within the period from 2010 to March 2021. Search terms included central sensitization, central sensitivity syndrome, nociplastic pain, cold hyperalgesia, heat hyperalgesia, mechanical hyperalgesia, dynamic mechanical allodynia, temporal summation, spatial summation, and descending inhibition. A qualitative synthesis summarized the research findings, including clinical conditions and effect of spinal manipulation. There were 30 studies, which included 7 high-level studies (meta-analysis or systematic reviews), 22 randomized controlled studies, and 1 scoping review. The findings suggest the existence of the changes in the central integrated state of a population of neurons with various disorders, experimentally induced stimulation, and treatment. The current literature suggests plasticity of the central integrative state (CIS) with the onset of pathologies and the changes in the CIS with different conservative nonpharmacologic treatments. This review suggests changes in the resting state of the CIS of a population of neurons that exist in the physiologic lesion may change in response to various therapies, including manipulative therapy. The findings from this review provide support of the hypothesis that nonpharmacologic conservative care may affect the neurophysiological lesion. However, studies were heterogeneous and evidence was lacking in the translation of targeting the therapies to distinct neuronal areas for clinical outcomes to treat specific disease states.


Local and peripheral cell-mediated immune response to influenza virus in mice.
Presentation of different influenza virus antigens generates different immune responses. Intranasal immunization with either live (VA) or formalin-inactivated (VF) A/PR/8/34 (HON1) influenza virus induced local as well as peripheral cell-mediated immune response (CMI), as evidenced by elevation in 3H-thymidine incorporation. Cell-mediated immune response was detected as soon as 24-48 hr following the application of VA and 4-5 days following VF. Cell-mediated immune response in both instances peaked on the 12th day and disappeared between 16 and 20 days after application. Local CMI response was threefold higher after immunization with VA (SI = 28.6) than with VF (SI = 9.4), while VF induced higher peripheral response (32.0 vs 17.7). The mononuclear cell population in the lungs increased, correlating with a rise in the stimulation index (SI). The percentage of IgA surface-bearing B lymphocytes was significantly higher following IN administration of VA, but not following VF instillation. This corroborated the finding that VF failed to induce local antibody response in the lungs in spite of its capacity to stimulate humoral antibody and CMI responses. Mice immunized intramuscularly with both viral preparations developed a fair humoral antibody response without detectable CMI (peripheral or local).


Motor complications of herpes zoster.
Motor involvement is uncommon in herpes zoster. Of 14 subjects observed over an arbitrary period of five years, nine had flaccid limb paralyses, involving the upper limb in eight patients. Recovery was not always complete and occurred over a period of nine weeks to four years.


Parental support during young adulthood: Why does assistance decline with age?
Previous research has found that financial transfers from parents to young adult children decline as children age and that age is one of the strongest predictors of support. Using data collected from young adults (ages 18 to 34) and their parents (ages 40 to 60; N=536 parent-child dyads), we explore the possibility that the relationship between age and financial support is mediated by offspring needs, acquisition of adult roles, or geographical and emotional closeness. We find that age-related declines in offspring's needs help to explain why financial support falls with age. However, offspring age remains a robust predictor of financial support after controlling for a wide range of factors, suggesting that age norms condition support from parents to offspring.


Sulfide-induced reduction of nitrobenzene mediated by different size fractions of rice straw-derived black carbon: A key role played by reactive polysulfide species.
Here we investigated the mediation efficiency of different size fractions of rice straw-derived black carbon (BC) using sulfide-induced nitrobenzene reduction as a model system. The bulk BC was divided into three size fractions: dissolved BC (size <0.45 μm), colloidal BC (0.45 μm < size < 1 μm), and particulate BC (size > 1 μm). With the presence of BC fractions (250 mg/L) nitrobenzene reduction by Na2S was significantly facilitated, wherein the mediation efficiency was positively correlated with the BC fraction's oxygen group content in an order of particulate BC < colloidal BC ≪ dissolved BC. Consistently, the oxidation treatment of particulate BC with O3 or HNO3 improved the mediation efficiency, whereas the reduction treatment with NaBH4 reduced the mediation efficiency. The supernatant collected with dialysis or filtration of suspension of BC materials pre-reacted with Na2S could effectively reduce nitrobenzene, suggesting that reactive reducing sulfur species were produced in aqueous solutions by reacting sulfide only with BC materials. This was evidenced by the fact that polysulfides and polysulfide radicals were both detected in the supernatant. As demonstrated by electron paramagnetic resonance analysis, the quinone moieties at the surface of BC materials accepted electrons from sulfide and turned into semiquinone free radicals, consequently leading to formation of reactive reducing sulfur species and thus enhanced nitrobenzene reduction. The strong mediation efficiency on redox reactions observed for colloidal BC and dissolved BC combined with their significant mobility in subsurface environments indicate that these carbonaceous materials may play an important role in the fate process of organic contaminants as both carriers and catalysts. CAPSULE: The surface quinone moieties of BC induce the formation of reactive reducing sulfur species by acting as one-electron acceptors and facilitate nitrobenzene reduction by sulfide.


Reflected light from sand grains in the terrestrial zone of a protoplanetary disk.
In the standard model of terrestrial planet formation, the first step in the process is for interstellar dust to coagulate within a protoplanetary disk surrounding a young star, forming large grains that settle towards the disk plane. Interstellar grains of typical size approximately 0.1 microm are expected to grow to millimetre- (sand), centimetre- (pebble) or even metre-sized (boulder) objects rather quickly. Unfortunately, such evolved disks are hard to observe because the ratio of surface area to volume of their constituents is small. We readily detect dust around young objects known as 'classical' T Tauri stars, but there is little or no evidence of it in the slightly more evolved 'weak-line' systems. Here we report observations of a 3-Myr-old star, which show that grains have grown to about millimetre size or larger in the terrestrial zone (within approximately 3 au) of this star. The fortuitous geometry of the KH 15D binary star system allows us to infer that, when both stars are occulted by the surrounding disk, it appears as a nearly edge-on ring illuminated by one of the central binary components. This work complements the study of terrestrial zones of younger disks that have been recently resolved by interferometry.


Use of individualized learning plans among fourth-year sub-interns in pediatrics and internal medicine.
Individualized Learning Plans (ILPs) are an effective tool for promoting self-directed learning among residents. However, no literature details ILP use among medical students. Fifty fourth-year sub-interns in pediatrics and internal medicine created ILPs, including a self-assessment of strengths and weaknesses based on ACGME core competencies and the setting of learning objectives. During weekly follow-up meetings with faculty mentors and peers, students discussed challenges and revised goals. Upon completion of the rotation, students completed a survey of Likert-scale questions addressing satisfaction with and perceived utility of ILP components. Students most often self-identified strengths in the areas of Professionalism and Interpersonal and Communication Skills and weaknesses in Patient Care and Systems-Based Practice. Eighty-two percent set at least one learning objective in an identified area of weakness. Students expressed high confidence in their abilities to create achievable learning objectives and to generate strategies to meet those objectives. Students agreed that discussions during group meetings were meaningful, and they identified the setting learning objectives and weekly meetings as the most important elements of the exercise. Fourth-year sub-interns reported that ILPs helped them to accomplish rotation goals, with the setting of learning objectives and weekly discussions being the most useful elements.


Polybrominated diphenylethers (PBDEs) act as apoptotic factors in the corpus luteum in addition to having a short-term stimulatory effect on progesterone secretion by luteal cells.
To the best of our knowledge, there is a lack of data showing effect of polybrominated diphenyl ethers (PBDEs) on the corpus luteum (CL), a mini-endocrine gland responsible for a normal estrous cycle and the maintenance of pregnancy. Luteal cells obtained from corpora lutea (8-10 days after ovulation) were exposed to PBDE 47, 99, and 100 at doses of 50, 250, and 500 ng/ml for 24 and 48 hours. The progesterone (P4) level in the culture medium and caspase-3, -8, and -9 activities in the cells were estimated by ELISA. CYP11A1 and 3β-HSD protein expression were evaluated by western blot. A 2-fold increase in P4 secretion after 24 hours and no effect after 48 hours of exposure were observed. We demonstrated that the increase in P4 secretion was the result of the stimulatory action of all PBDEs on 3β-HSD protein expression and additionally, PBDE 99 alone on 3β-HSD activity (measured by the conversion of P5 into P4). In contrast, the activation of caspase-8 and -9 but not caspase-3 during 24 hours of exposure, and activation of all investigated caspases during 48 hours was observed. In conclusion, the present findings provide evidence that despite the initial stimulatory effect of PBDEs on the secretion of progesterone (due to the fact that the biochemical apparatus responsible for the conversion of cholesterol into pregnenolone remains uninterrupted). PBDEs are also a key executor of apoptosis (by activating both the extrinsic and intrinsic pathways of apoptosis after longer exposure periods) which can lead to premature dysfunction of the corpus luteum.


Severe anal intraepithelial neoplasia trends and subsequent invasive anal cancer in the United States.
Anal intraepithelial neoplasia grade III (AIN3) is a precursor to squamous cell carcinoma of the anus (SCCA), for which rates are nearly 20-fold higher in people with HIV (PWH) than in the general population in the US. We describe trends in AIN3 diagnosis and risk of SCCA following AIN3 by HIV status and sex. We utilized data from a population-based linkage between cancer and HIV registries in 11 US states, Puerto Rico, and Washington DC during 1996-2019. We identified all individuals with a diagnosis of AIN3 and determined their HIV status. We estimated the average annual percentage change (AAPC) of AIN3 using Poisson regression stratified by HIV status and sex. We estimated the 5-year cumulative incidence of SCCA following an AIN3 diagnosis stratified by sex, HIV status, and prior AIDS diagnosis. Among PWH, AAPCs for AIN3 were 15% (95%CI=12-17%) per year among females 12% (95%CI=11-14%) among males. AAPCs for those without HIV were 8% (95%CI=7-8%) for females and 8% (95%CI=6-9%) for males. Among PWH, a prior AIDS diagnosis was associated with a 2.7-fold (95%CI=2.23-3.40) and 1.9-fold (95%CI=1.72-2.02) increased risk of AIN3 diagnosis for females and males, respectively. 5-year cumulative incidence of SCCA following AIN3 for PWH with a prior AIDS diagnosis were 3.4% and 3.7% for females and males, respectively. Rates of AIN3 diagnoses have increased since 1996, particularly for PWH, likely influenced by increased screening. A prior AIDS diagnosis was strongly associated with risk of AIN3 diagnosis.


Adherence to Swedish guidelines for pain treatment in relation to pediatric tonsil surgery: A survey of the multidisciplinary team.
Pain management in children after tonsil surgery is essential, and optimal pain treatment has been discussed for many years. Data from the National Tonsil Register in Sweden (NTRS) and a national mapping have demonstrated the need for national pain treatment guidelines for pediatric tonsil surgery. As a result, Swedish national guidelines, together with updated patient information on the website tonsilloperation.se, were developed and implemented in 2013. The objective of this study was to evaluate the professionals' opinions of and adherence to pain treatment guidelines for pediatric tonsil surgery patients in a two-year follow-up. This descriptive cross-sectional study was based on data from an inter-professional questionnaire, which was validated by an expert group using a content validity index (S-CVI 0.93). The questionnaire was sent to all Swedish ear, nose and throat (ENT) departments (n = 49) that the NTRS identified as performing tonsil surgery on children younger than 18 years of age. In each clinic, we asked for responses from staff in each of the following professions: ENT physicians, anesthesia physicians, registered nurse anesthetists, and registered nurses in the ENT departments. Respondents from 48 ENT departments participated, and 139/163 (85%) completed questionnaires were returned. The guidelines were reported as being clear, ensuring patient safety and providing optimal pharmacological treatment. Treatment was given according to the guidelines: Half of the departments gave pre- or intraoperative treatment with clonidine, betamethasone and high-dose paracetamol (acetaminophen). A multimodal pain approach (paracetamol and COX-inhibitors) after hospital discharge was prescribed by all departments after tonsillectomy and, extensively, after tonsillotomy. One-third of the departments prescribed paracetamol with a higher normal dose for the first three postoperative days. Half of the departments prescribed rescue analgesics, clonidine or opioids after tonsillectomy. None of the departments prescribed codeine or tramadol, drugs that are discouraged in the guidelines. The majority of the departments used the website tonsilloperation.se to provide information to the patients and their caregivers. The respondents' opinions of and the ENT departments adherence to the Swedish national guidelines were considered to be good. The national implementation process in Sweden has impacted the manner in which ENT departments treat pain after tonsil surgery.


Diffusion of gelation clusters in the Zimm model.
Starting from a Zimm model, we study self-diffusion in a solution of crosslinked monomers. We focus on the effects of the hydrodynamic interaction on the dynamics and the critical behaviour at the sol-gel point. Hydrodynamic interactions cause the clusters' diffusion constant to depend not only on the cluster's size but also on the cluster's shape --in contrast to the Rouse model. This gives rise to a non-trivial scaling of the Kirkwood diffusion constant averaged over all clusters of fixed size n, Dn approximately equal to n(-b) with b = 1/d(s) - 1/2 given in terms of the spectral dimension d(s) of critical percolation clusters. The long-time decay of the incoherent scattering function is determined by the diffusive motion of the largest clusters. This implies the critical vanishing D(eff) approximately equal to epsilon(a) of the cluster-averaged effective diffusion constant at the gel point with exponent a = (3/2 - tau + 1/d(s))/sigma.


A Moxifloxacin-based Regimen for the Treatment of Recurrent, Drug-sensitive Pulmonary Tuberculosis: An Open-label, Randomized, Controlled Trial.
The substitution of moxifloxacin for ethambutol produced promising results for improved tuberculosis treatment outcomes. We conducted an open-label, randomized trial to test whether a moxifloxacin-containing treatment regimen was superior to the standard regimen for the treatment of recurrent tuberculosis. The primary and secondary outcomes were the sputum culture conversion rate at the end of 8 weeks and the proportion of participants with a favorable outcome, respectively. We enrolled 196 participants; 69.9% were male and 70.4% were co-infected with human immunodeficiency virus (HIV). There was no significant difference between the study groups in the proportion of patients achieving culture conversion at the end of 8 weeks (83.0% [moxifloxacin] vs 78.5% [control]; P = .463); however, the median time to culture conversion was significantly shorter (6.0 weeks, interquartile range [IQR] 4.0-8.3) in the moxifloxacin group than the control group (7.9 weeks, IQR 4.0- 11.4; P = .018). A favorable end-of-treatment outcome was reported in 86 participants (87.8%) in the moxifloxacin group and 93 participants (94.9%) in the control group, for an adjusted absolute risk difference of -5.5 (95% confidence interval -13.8 to 2.8; P = .193) percentage points. There were significantly higher proportions of participants with Grade 3 or 4 adverse events (43.9% [43/98] vs 25.5% [25/98]; P = .01) and serious adverse events (27.6% [27/98] vs 12.2% [12/98]; P = .012) in the moxifloxacin group. The replacement of ethambutol with moxifloxacin did not significantly improve either culture conversion rates at the end of 8 weeks or treatment success, and was associated with a higher incidence of adverse events. NCT02114684.


Elimination of chloramphenicol, sulphamethoxazole and oxytetracycline in shrimp, Penaeus chinensis following medicated-feed treatment.
Muscle residue depletion of chloramphenicol (CAP), sulphamethoxazole (SMZ) and oxytetracycline (OTC) following oral administration was evaluated in shrimp, Penaeus chinensis under field conditions. Three groups of shrimps were cultured in tanks filled with seawater and fed a commercial medicated diet containing 2000 mg kg(-1) CAP, SMZ and OTC, respectively, twice daily for 3 days. Sampling was conducted at different intervals (0, 0.5, 1, 1.5, 2, 3, 4, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168 h) after the cessation of medication. Drug analysis was carried out by HPLC. The elimination half-life (t(1/2)) of CAP was 10.04 h, the elimination half-life (t(1/2)) of SMZ was 5.68 h and that of OTC was 16.12 h. If the EU MRPL value of 0.3 ng/g for CAP and MRL value of 0.1 microg/g for SMZ and OTC quoted for muscle from finfish is extended to shrimp muscle, extrapolation of the data indicates that it would be passed after a 139.7 h (95% CI=132.0-144.4 h), 30.6 h (95% CI=27.2-33.1 h), 90.3 h (95% CI=87.9-92.5 h) withdrawal period for CAP, SMZ and OTC in shrimp muscle, respectively.


Characterization of phenolic and other polar compounds in peel and flesh of pink guava (Psidium guajava L. cv. 'Criolla') by ultra-high performance liquid chromatography with diode array and mass spectrometric detection.
Pink guava (Psidium guajava L.) is a highly consumed fruit in tropical countries. Despite of interesting research on health effects of this fruit, investigations into the profile of secondary plant metabolites are scarce. In this study, the phenolic compounds in the peel and flesh of pink guava were characterized by ultra-high performance liquid chromatography with diode array and mass spectrometric detection. Sixty phenolic compounds were characterized by MS2 and classified as ellagitannins, flavones, flavonols, flavanols, proanthocyanidins, dihydrochalcones, and anthocyanidins, and non-flavonoids such as phenolic acid derivatives, stilbenes, acetophenones, and benzophenones. Forty-two polyphenols are reported for the first time in both peel and flesh, and twenty-four compounds were detected for the first time in P. guajava, e.g., phlorizin, nothofagin, astringin, chrysin-C-glucoside, valoneic acid bilactone, cinnamoyl-glucoside, and two dimethoxycinnamoyl-hexosides.


Database search post-processing by neural network: Advanced facilities for identification of components in protein mixtures using mass spectrometric peptide mapping.
Database search post-processing by neural network was employed in peptide mapping experiments. The database search was performed using both the known algorithms and score functions, such as Bayesian, MOWSE, Z-score, correlations between calculated and actual peptide length fractional abundance, and, in addition, the probability of protein digest pattern in peptide fingerprint, all embedded in locally developed program. The new signal-processing algorithm based on neural network improves signal-noise separation and is acceptable for automatic protein identification in mixtures. Its power was tested on Helicobacter pylori protein inventory after preceding protein separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Increase in protein identification success rate was observed, and about 100 proteins were identified with no need of human participation in database search estimation.


Strength-duration properties of cathodal pulses eliciting spreading depression in rat cerebral cortex.
Strength-duration curves for the threshold stimulus for initiation of spreading depression were determined for durations of 2 ms to 120 s, using cathodal surface stimulation through a well-defined area. With the dura open, the strength-duration curve was of the form I square root t = constant. With extradural stimulation, the slope of the log-log plot relating current intensity to pulse duration increased gradually as the pulse duration increased.


[Some aspects of the resistance of natural foci of zoonosis infections with an example of the tick-borne encephalitis].
Epidermiological material reflecting some spatio-temporal aspects of the natural foci of tick-born encephalitis resistance has been analysed. The investigation carried out can used as a base for elaboration and realisation of factor prognoses concerning natural foci of zoonosis infection.


Associations of perceived community environmental attributes with walking in a population-based sample of adults with type 2 diabetes.
No studies have yet examined the associations of physical environmental attributes specifically with walking in adults with type 2 diabetes. The purpose of this study was to examine associations of perceived community physical environmental attributes with walking for transport and for recreation among adults living with type 2 diabetes. Participants were 771 adults with type 2 diabetes who completed a self-administered survey on perceived community physical environmental attributes and walking behaviors. Based on a criterion of a minimum of 120-min/week, some 29% were sufficiently active through walking for transport and 33% through walking for recreation. Significantly higher proportions of those actively walking for transport and for recreation had shops or places to buy things close by (67.8% and 60.9%); lived within a 15-min walk to a transit stop (70.6% and 71.0%); did not have dead-end streets close by (77.7% and 79.8%); reported interesting things to look at (84.8% and 84.4%); and lived close to low-cost recreation facilities (81.3% and 78.8%). In addition, those actively walking for transport reported living in a community with intersections close to each other (75.6%) and with sidewalks on their streets (88.1%). When these variables were entered simultaneously into logistic regression models, living close by to shops was positively related to walking for transport (OR = 1.92, 99% CI = 1.11-3.32). Consistent with findings from studies of healthy adult populations, positive perceptions of community environmental attributes are associated with walking for transport among adults with type 2 diabetes. The now-strong public health case for environmental innovations to promote more walking for transport is further reinforced by the potential to benefit those living with diabetes.


Highly increased risk of fracture in patients with myeloproliferative neoplasm.
The risk for hip and vertebral fracture was determined in 10,752 patients diagnosed with myeloproliferative neoplasms (MPN) in Sweden 1995-2015. The mean follow-up time were 6.34 years. Five percent developed hip fracture and 1.3% a vertebral fracture. There was a significant increased risk for fracture among the MPN patients compared with the Swedish population. The ratio of observed (obs) and expected (exp) number of hip fracture in all MPN patients, polycythemia vera (PV), essential thrombocythemia and MPN undetermined (MPNu) was 1.20 (95% confidence interval (CI): 1.10-1.31), 1.37 (95% CI: 1.19-1.58), 1.02 (95% CI: 0.87-1.19), and 1.28 (95% CI: 1.07-1.52), respectively. Corresponding figures for vertebral fractures were 1.94 (95% CI: 1.64-2.29), 2.09 (95% CI: 1.56-2.75), 1.50 (95% CI: 1.06-2.07) and 2.47 (95% CI: 1.77-3.35), respectively. Patients with MPN had an increased risk of hip and vertebral fracture, especially patients with PV and MPNu in comparison with the entire Swedish population.


On allosteric modulation of P-type Cu(+)-ATPases.
P-type ATPases perform active transport of various compounds across biological membranes and are crucial for ion homeostasis and the asymmetric composition of lipid bilayers. Although their functional cycle share principles of phosphoenzyme intermediates, P-type ATPases also show subclass-specific sequence motifs and structural elements that are linked to transport specificity and mechanistic modulation. Here we provide an overview of the Cu(+)-transporting ATPases (of subclass PIB) and compare them to the well-studied sarco(endo)plasmic reticulum Ca(2+)-ATPase (of subclass PIIA). Cu(+) ions in the cell are delivered by soluble chaperones to Cu(+)-ATPases, which expose a putative "docking platform" at the intracellular interface. Cu(+)-ATPases also contain heavy-metal binding domains providing a basis for allosteric control of pump activity. Database analysis of Cu(+) ligating residues questions a two-site model of intramembranous Cu(+) binding, and we suggest an alternative role for the proposed second site in copper translocation and proton exchange. The class-specific features demonstrate that topological diversity in P-type ATPases may tune a general energy coupling scheme to the translocation of compounds with remarkably different properties.


Two putative glutamate decarboxylases of Streptococcus pneumoniae as possible antigens for the production of anti-GAD65 antibodies leading to type 1 diabetes mellitus.
Type 1 diabetes mellitus (T1DM) has been increasing in prevalence in the last decades and has become a global burden. Autoantibodies against human glutamate decarboxylase (GAD65) are among the first to be detected at the onset of T1DM. Diverse viruses have been proposed to be involved in the triggering of T1DM because of molecular mimicry, i.e., similarity between parts of some viral proteins and one or more epitopes of GAD65. However, the possibility that bacterial proteins might also be responsible for GAD65 mimicry has been seldom investigated. To date, many genomes of Streptococcus pneumoniae (the pneumococcus), a prominent human pathogen particularly prevalent among children and the elderly, have been sequenced. A dataset of more than 9000 pneumococcal genomes was mined and two different (albeit related) genes (gadA and gadB), presumably encoding two glutamate decarboxylases similar to GAD65, were found. The various gadASpn alleles were present only in serotype 3 pneumococci belonging to the global lineage GPSC83, although some homologs have also been discovered in two subspecies of Streptococcus constellatus (pharyngis and viborgensis), an isolate of the group B streptococci, and several strains of Lactobacillus delbrueckii. Besides, gadBSpn alleles are present in > 10% of the isolates in our dataset and represent 16 GPSCs with 123 sequence types and 20 different serotypes. Sequence analyses indicated that gadA- and gadB-like genes have been mobilized among different bacteria either by prophage(s) or by integrative and conjugative element(s), respectively. Substantial similarities appear to exist between the putative pneumococcal glutamate decarboxylases and well-known epitopes of GAD65. In this sense, the use of broader pneumococcal conjugate vaccines such as PCV20 would prevent the majority of serotypes expressing those genes that might potentially contribute to T1DM. These results deserve upcoming studies on the possible involvement of S. pneumoniae in the etiopathogenesis and clinical onset of T1DM.


Calcium-activated DNA fragmentation in rat liver nuclei.
Incubation of isolated rat liver nuclei with ATP, NAD+, and submicromolar Ca2+ concentrations resulted in extensive DNA hydrolysis. Half-maximal activity occurred with 200 nM Ca2+, and saturation of the process was observed with 1 microM Ca2+. ATP stimulated a calmodulin-dependent nuclear Ca2+ uptake system which apparently mediated endonuclease activation. Ca2+-activated DNA fragmentation was inhibited by the inhibitor of poly(ADP-ribose) synthetase, 3-aminobenzamide, and was associated with poly(ADP-ribosyl)ation of nuclear protein. The characteristics of this endonuclease activity indicate that it may be responsible for the Ca2+-dependent fragmentation of DNA involved in programmed cell death (apoptosis) and in certain forms of chemically induced cell killing.


4',5-Dihy-droxy-7-meth-oxy-flavanone dihydrate.
The title compound, C(16)H(14)O(5)·2H(2)O [systematic name: 5-hy-droxy-2-(4-hy-droxy-phen-yl)-7-meth-oxy-chroman-4-one dihydrate], is a natural phytoalexin flavone isolated from the native chilean species Heliotropium taltalense and crystallizes with an organic mol-ecule and two water mol-ecules in the asymmetric unit. The 5-hy-droxy group forms a strong intra-molecular hydrogen bond with the carbonyl group, resulting in a six-membered ring. In the crystal, the components are linked by O-H⋯O hydrogen bonds, forming a three-dimensional network. The 4-hy-droxy-phenyl benzene ring is bonded equatorially to the pyrone ring, which adopts a slightly distorted sofa conformation. The title compound is the hydrated form of a previously reported structure [Shoja (1990 ▶). Acta Cryst. C46, 1969-1971]. There are only slight variations in the mol-ecular geometry between the two compounds.


Gastroesophageal resuscitative occlusion of the aorta prolongs survival in a lethal liver laceration model.
Noncompressible torso hemorrhage management remains a challenge especially in the prehospital setting. We evaluated a device designed to occlude the aorta from the stomach (gastroesophageal resuscitative occlusion of the aorta [GROA]) for its ability to stop hemorrhage and improve survival in a swine model of lethal liver laceration and compared its performance to resuscitative endovascular balloon occlusion of the aorta (REBOA) and controls. Swine (n = 24) were surgically instrumented and a 30% controlled arterial hemorrhage over 20 minutes was followed by liver laceration. Animals received either GROA, REBOA, or control (no treatment) for 60 minutes. Following intervention, devices were deactivated, and animals received whole blood and crystalloid resuscitation. Animals were monitored for an additional 4 hours. The liver laceration resulted in the onset of class IV shock. Mean arterial blood pressure (MAP) (standard deviation) decreased from 84.5 mm Hg (11.69 mm Hg) to 27.1 mm Hg (5.65 mm Hg) at the start of the intervention. Seven of eight control animals died from injury prior to the end of the intervention period with a median survival (interquartile) time of 10.5 minutes (12 minutes). All GROA and REBOA animals survived the duration of the intervention period (60 minutes) with median survival times of 86 minutes (232 minutes) and 79 minutes (199 minutes) after resuscitation, respectively. The GROA and REBOA animals experienced a significant improvement in survival compared with controls (p = 0.01). Resuscitative endovascular balloon occlusion of the aorta resulted in higher MAP at the end of intervention 114.6 mm Hg (22.9 mm Hg) compared with GROA 88.2 mm Hg (18.72 mm Hg) (p = 0.024), as well as increased lactate compared with GROA 13.2 meq·L-1 (1.56 meq·L-1) versus 10.5 meq·L-1 (1.89 meq·L-1) (p = 0.028). Histological examination of the gastric mucosa in surviving animals revealed mild ischemic injury from both GROA and REBOA. The GROA and REBOA devices were both effective at temporarily stanching lethal noncompressible torso hemorrhage of the abdomen and prolonging survival.


[How I investigate...the age of adolescents using panoramic radiography].
Stage of dental development gives an assessment of young adults chronological age. This is used in forensic medicine when birth data are lacking or doubted. The following method improves the accuracy of age determination in comparison with the commonly used method of Nolla.


The regulation and functional impact of actin assembly at cadherin cell-cell adhesions.
Cadherin adhesion receptors are critical components for the maintenance of tissue architecture and organisation during development and in post-embryonic life. These receptors influence the actin cytoskeletal network by controlling its assembly at the junctions. Likewise, the actin cytoskeleton is required for cadherin integrity at cell-cell contacts. The junctional cytoskeleton is intrinsically dynamic and undergoes constant assembly and reorganisation to maintain a morphologically stable structure. This is governed by a host of molecular players that regulate actin assembly during nucleation and at post-nucleation stages. This review highlights the molecular machinery implicated in actin organisation at various stages of junctional assembly and its functional impact in simple epithelia and other model systems.


Ruminal Fluid Transplantation Accelerates Rumen Microbial Remodeling and Improves Feed Efficiency in Yaks.
A relatively stable microbial ecological balance system in the rumen plays an important role in rumen environment stability and ruminant health maintenance. No studies have reported how rumen fluid transplantation (RFT) affects the composition of rumen microorganisms and yak growth performance. In this experiment, we transplanted fresh rumen fluid adapted to house-feeding yaks to yaks transitioned from natural pastures to house-feeding periods to investigate the effects of rumen fluid transplantation on rumen microbial community regulation and production performance. Twenty yaks were randomly divided into the control group (CON; n = 10) and the rumen fluid transplantation group (RT; n = 10). Ten yaks that had been adapted to stall fattening feed in one month were selected as the rumen fluid donor group to provide fresh rumen fluid. Ruminal fluid transplantation trials were conducted on the 1st, 3rd, and 5th. Overall, 1 L of ruminal fluid was transplanted to each yak in the RT and CON group. The formal trial then began with both groups fed the same diet. After this, growth performance was measured, rumen fluid was collected, and rumen microbial composition was compared using 16s rRNA sequencing data. The results showed that rumen fluid transplantation had no significant effect on yak total weight gain or daily weight gain (p > 0.05), and feed efficiency was higher in the RT group than in the CON group at 3 months (treatment × month: p < 0.01). Ruminal fluid transplantation significantly affected rumen alpha diversity (p < 0.05). Up to day 60, the RT group had significantly higher OTU numbers, Shannon diversity, and Simpson homogeneity than the CON group. Principal coordinate analysis showed that the rumen microbiota differed significantly on days 4 and 7 (p < 0.05). Bacteroidota, Firmicutes, Proteobacteria, and Spirochaetes were the most abundant phyla in the rumen. The relative abundances of Bacteroidota, Proteobacteria, and Spirochaetes were lower in the RT group than in the CON group, with a decrease observed in Bacteroidota in the RT group on days 7 and 28 after rumen fluid transplantation (p = 0.013), while Proteobacteria showed a decreasing trend in the CON group and an increasing trend in RT; however, this was only at day 4 (p = 0.019). The relative abundance of Firmicutes was significantly higher in the RT group than in the CON group on days 4, 7, and 28 (p = 0.001). Prevotella and Rikenellaceae_RC9_gut_group were the predominant genera. In conclusion, our findings suggest that rumen fluid transplantation improves yak growth performance and rumen microbial reshaping. The findings of this study provide new insights into yak microbial community transplantation and a reference for improving feed efficiency in the yak industry.


Analysis of extracellular vesicle DNA at the single-vesicle level by nano-flow cytometry.
It has been demonstrated recently that extracellular vesicles (EVs) carry DNA; however, many fundamental features of DNA in EVs (EV-DNA) remain elusive. In this study, a laboratory-built nano-flow cytometer (nFCM) that can detect single EVs as small as 40 nm in diameter and single DNA fragments of 200 bp upon SYTO 16 staining was used to study EV-DNA at the single-vesicle level. Through simultaneous side-scatter and fluorescence (FL) detection of single particles and with the combination of enzymatic treatment, present study revealed that: (1) naked DNA or DNA associated with non-vesicular entities is abundantly presented in EV samples prepared from cell culture medium by ultracentrifugation; (2) the quantity of EV-DNA in individual EVs exhibits large heterogeneity and the population of DNA positive (DNA+ ) EVs varies from 30% to 80% depending on the cell type; (3) external EV-DNA is mainly localized on relatively small size EVs (e.g. <100 nm for HCT-15 cell line) and the secretion of external DNA+ EVs can be significantly reduced by exosome secretion pathway inhibition; (4) internal EV-DNA is mainly packaged inside the lumen of relatively large EVs (e.g. 80-200 nm for HCT-15 cell line); (5) double-stranded DNA (dsDNA) is the predominant form of both the external and internal EV-DNA; (6) histones (H3) are not found in EVs, and EV-DNA is not associated with histone proteins and (7) genotoxic drug induces an enhanced release of DNA+ EVs, and the number of both external DNA+ EVs and internal DNA+ EVs as well as the DNA content in single EVs increase significantly. This study provides direct and conclusive experimental evidence for an in-depth understanding of how DNA is associated with EVs.


Effects of arachidonic acid on leptin secretion and expression in primary cultured rat adipocytes.
Leptin, a hormone produced in adipocytes, is a key signal in the regulation of food intake and energy expenditure. Several studies have suggested that leptin can be regulated by macronutrients intake. Arachidonic acid is a dietary fatty acid known to affect cell metabolism. Controversial effects of this fatty acid on leptin have been reported. The aim of this experimental trial was to evaluate the effect of the arachidonic acid on basal and insulin-stimulated leptin secretion and expression in isolated rat adipocytes. Because insulin-stimulated glucose metabolism is an important regulator of leptin expression and secretion by the adipocytes, the effects of the arachidonic acid on indices of adipocyte metabolism were also examined. Isolated adipocytes were incubated with arachidonic acid (1-200 microM) in the absence and presence of insulin (1.6 nM). Leptin secretion and expression, glucose utilization and lactate production were determined at 96 h. The arachidonic acid (200 microM) inhibited both the basal and insulin stimulated leptin secretion and expression. Glucose utilization was not affected by the acid. Basal lactate production was increased by the fatty acid at the highest concentration used (200 microM), however lactate production in presence of insulin was not modified. Finally, the percentage of glucose carbon released as lactate was significantly increased (200 microM). These results suggest that the inhibitory effect of the arachidonic acid on leptin secretion and expression may be due, al least in part, to the increase in the anaerobic utilization of glucose.


Update on Epidemiology and Outcomes of Infection in Pediatric Organ Transplant Recipients.
Pediatric solid organ transplant (SOT) recipients are at risk for infection following transplantation. Data from adult SOT recipients are often used to guide prevention and treatment of infections associated with organ transplantation in children. This article highlights key recent pediatric SOT-specific publications for an array of infectious complications of organ transplantation. Attention is given to areas of need for future study.