Synthesis of new riboflavin modified ODNs: Effect of riboflavin moiety on the G-quadruplex arrangement and stability.
In the panorama of modified G-quadruplexes (G4s) with interesting proprieties, here, it has been reported the synthesis of new modified d(TGGGAG) sequences forming G-quadruplexes, with the insertion of a riboflavin unit (Rf, vitamin B2). Exploiting the flavin similarity with the hydrogen bond pattern of guanine and aiming at mimic a typical nucleoside scaffold, the synthesis of the riboflavin building block 3 it has been efficiently carried out. The effect of insertion of riboflavin mimic nucleoside on the G-quadruplex properties has been here, for the first time investigated. A biophysical characterization of Rf-modified sequences (A-D) has been carried out by circular dichroism (CD), fluorescence spectroscopy, differential scanning calorimetry (DSC) and native gel electrophoresis. CD and electrophoresis data have suggested that Rf-modified sequences are able to form parallel tetramolecular G4 structures similar to that of the unmodified sequence. Analysis of the DSC thermograms has revealed that all modified G-quadruplexes have a higher thermal stability compared with the natural sequence, particularly the stabilisation is higher when the Rf residue is introduced at the 3'-end. Further, DSC analysis has revealed that the Rf residues introduced at the 3'-end are able to form additional stabilising interactions, energetically almost comparable to the enthalpic contribution of a G-tetrad. Fluorescence measurement are consistent with this result showing that the Rf residues introduced at 3'-end are able to form stacking interactions with the adjacent bases within the G-quadruplex structure. The whole of data suggested that the introduction of Rf unit can stabilize G-quadruplex structures and can be a promising candidate for future theranostic applications.


CCL3/macrophage inflammatory protein-1alpha induces fever and increases prostaglandin E2 in cerebrospinal fluid of rats: effect of antipyretic drugs.
The aim of this study was to investigate whether the increase in body temperature caused by intracerebroventricular (i.c.v.) injection of recombinant mouse CCL3/MIP1alpha [C-C (two adjacent conserved cysteines) ligand 3/macrophage inflammatory protein-1alpha] constitutes solely a hyperthermic response or a true integrated fever. Additionally, we examined the effects of systemic administration of different antipyretic drugs including the glucocorticoid dexamethasone, on cerebrospinal fluid (CSF) concentration of prostaglandin (PG) E2 and on febrile response induced by CCL3/MIP1alpha. I.c.v. administration of CCL3/MIP1alpha evokes an integrated fever accompanied by a reduction in tail skin temperature and an increase in PGE2 concentration in the CSF. Dexamethasone and indomethacin markedly reduced the fever and the elevation of CSF PGE2 concentration induced by lipopolysaccharide (LPS) whereas both response evoked by i.c.v. CCL3/MIP1alpha were insensitive to this steroid. Indomethacin only blocked the PGE2 increase in the CSF whereas ibuprofen and celecoxib each blocked the fever and the elevation of CSF PGE2. In this study, we have demonstrated for the first time that CCL3/MIP1alpha evokes an integrated febrile response accompanied by an increase of PGE2 levels in the CSF. These events are dissociated, especially in animals treated with indomethacin. If PGE2 does not participate in the febrile response evoked by CCL3/MIP1alpha, the inhibition of this response by celecoxib and ibuprofen indicates additional mechanisms to the well-known inhibition of COX enzymes by these drugs. Such mechanisms do not seem to depend on cytokine synthesis and subsequent COX-2 induction.


[Community-acquired pneumonia: risk focus and family functionality].
Community-acquired pneumonia is one of the five most prevalent causes of death worldwide; in Mexico, it accounts for more than 10% of the hospital admissions. To identify the risk factors and the kind of family functionality associated to community-acquired pneumonia among adult patients. With the prior authorization of the research and bioethics committees, a study of cases and controls took place, where both groups were asked about the following variables: alcohol consumption or active smoking, conditions of house and family functionality, anti-flu and anti-pneumococcal vaccination, disablement, and chronic pulmonary disease, among others. It was found that the significant variables were active smoking, disablement, pulmonary emphysema, chronic bronchitis, overcrowding at home, and alcohol consumption; and with a protective effect for this disease: a functional family and anti-pneumococcal vaccination. There are risk factors that predispose the development of community-acquired pneumonia, and that allow us to make a population profile in which some preventive strategy could diminish the frequency and lethality of this disease.


Cleft palate secondary to an ingested foreign body: a learning experience.
Cleft palate has usually been described as a congenital anomaly. Acquired clefting of the palate is rare and is usually due to penetrating trauma. To report a case of cleft palate developing after ingestion of a coin due to prolonged impaction in the nasopharynx. A 4 1/2-year-old child presented with nasal regurgitation and nasal twang of voice. The parents reported a history of ingestion of a coin 2 years prior, which was undetectable on neck and chest X-ray study done at that time. Examination revealed a triangular cleft of soft palate. A diagnosis was made of an acquired cleft palate secondary to prolonged impaction of the coin in the nasopharynx. Under general anesthesia, the palatal defect was repaired in three layers. The case highlights the fact that ingested foreign bodies can get lodged in the nasopharynx and that nasopharynx X-ray study should always be done in cases of a disappearing foreign body in the aerodigestive tract.


The influence of the convulsant pentylenetetrazol on Ca2+-selective microelectrodes (neutral carrier ETH 1001).
Interference of the epileptogenic drug pentylenetetrazol (PTZ) on the Ca2+-selective microelectrode based on the neutral carrier ETH 1001 is described. It is suggested that tetraphenylborate, a component of the Ca2+-selective membrane, is responsible for this interference. Though the sensitivity of the Ca2+-selective microelectrode to PTZ is low, the error in measurements of the free Ca2+ concentration in biological preparations treated with PTZ has to be considered, since pathological changes in the extracellular Ca2+ concentration also produce relatively small changes in the relative electrode potential.


Experimental study of faecal continence and colostomy irrigation.
Colostomy irrigation is a useful method of achieving faecal continence in selected conditions, but remains largely underutilized because it is time consuming. This study investigated the effect of modifying irrigation technique (route, infusion regimen and pharmacological manipulation) on colonic emptying time in a porcine model. An end-colostomy and caecostomy were fashioned in six pigs. Twenty markers were introduced into the caecum immediately before colonic irrigation. Irrigation route (antegrade or retrograde), infusion regimen (tap water, polyethylene glycol (PEG), 1.5 per cent glycine) and pharmacological agent (glyceryl trinitrate (GTN) 0.25 mg/kg, diltiazem 3.9 mg/kg, bisacodyl 0.25 mg/kg) were assigned to each animal at random. Colonic transit was assessed by quantifying cumulative expelled markers (CEM) and stool every hour for 12 h. Mean CEM at 6 h for bisacodyl, GTN and diltiazem were 18.17, 12.17 and zero respectively; all pairwise differences in means were significant (P < 0.001). The difference at 12 h between the two routes (P = 0.001) and three fluids (tap water 6.75, glycine 14.83, PEG 16.33; P < 0. 001) was significant, but not for PEG versus glycine and bisacodyl versus GTN. Cumulative output was significantly more with the antegrade than retrograde route using PEG, but the difference in mean cumulative output for bisacodyl and GTN at 12 h was not significant. Colonic emptying is more efficient with antegrade than retrograde irrigation. PEG and glycine enhance emptying similar to bisacodyl and GTN solution. These findings show promise for improved faecal continence by colostomy irrigation and may justify construction of a Malone conduit at the time of colostomy in selected patients who wish to irrigate. Presented in part to the British Society of Gastroenterology in Glasgow, UK, March 1999, and published in abstract form as Gut 1999; 44(Suppl 1): A135


Responsiveness of microcirculation and local cold vasodilation to capsaicin in the intact and chronically denervated canine tongue.
Lingual blood flow and its distribution were determined at rest and in response to local cooling of the tongue (32 degrees C) in 6 anaesthetized, paralyzed and artificially ventilated dogs before and after two intraarterial (i.a.) injections of capsaicin (2.5 mg) at an interval of about 40 min. In 3 dogs, the same protocol was performed after degeneration of the chorda-lingual and glossopharyngeal nerves due to prior transection. In general the first i.a. injection of capsaicin resulted in a marked and the second injection in a smaller decrease of lingual blood flow. Local cooling of the tongue induced significant increases in lingual blood flow before as well as after capsaicin treatment, regardless of whether sensory innervation was intact or degenerated. In both the untreated and capsaicin treated dogs the increase in lingual blood flow during local cooling of the tongue was solely due to an increase in blood flow through the arteriovenous anastomoses, while blood flow through the capillaries of the mucosa and muscles even decreased. The findings suggest that capsaicin-induced vasoconstriction of the tongue vessels is due to a direct effect on vascular receptors. It is further suggested that cold vasodilatation of the canine tongue is not mediated by axon collaterals releasing substance P. Direct thermal effects on the intramural ganglia and the postganglionic vasomotor efferents innervating the AVAs, or on AVAs basal tone itself are suggested as the underlying mechanism.


In vitro antibacterial and anticancer properties of Helicteres hirsuta Lour. leaf and stem extracts and their fractions.
Helicteres hirsuta Lour. (H. hirsuta) has been considered as a herbal medicine for the treatment of malaria and diabetes but limited studies have been conducted on its anticancer and antibacterial properties. In this study, the in vitro antibacterial and anticancer properties of the leaf and stem extracts and their two sub-fractions (aqueous and saponin-enriched butanol fractions) prepared from H. hirsuta were elucidated. MTT and CCK-8 assays were employed to assess their in vitro anticancer properties against various cancer cell lines. The antibacterial activity was assessed using the disc diffusion method and minimum inhibitory concentration (MIC) values were determined. The results revealed that the saponin-enriched fractions from H. hirsuta leaves and stems showed the highest antibacterial activity against E. coli (MIC values of 2.50 and 5.00 mg/mL, respectively) and S. lugdunensis (MIC values of 0.35 and 0.50 mg/mL, respectively). Importantly, these saponin-enriched fractions possessed strong anticancer activity in vitro towards a range of cancer cell lines including MIA PaCa-2 (pancreas); A2780 (ovarian); H460 (lung); A431 (skin); Du145 (prostate); HT29 (colon); MCF-7 (breast); SJ-G2, U87, SMA (glioblastoma) and BE2-C (neuroblastoma) at low doses (GI50 values of 0.36-11.17 µg/mL). They especially revealed potent anti-pancreatic cancer activity in vitro against MIA PaCa-2, BxPC-3 and CFPAC-1 cells with IC50 values of 1.80-6.43 µg/mL. This finding provides scientific evidence of the cytotoxic activity of the extracts prepared from H. hirsuta leaves and stems, and suggests further studies to isolate active compounds for development of new anticancer agents from these plant extracts.


DNA methylation inhibition increases T cell KIR expression through effects on both promoter methylation and transcription factors.
Killer-cell immunoglobulin-like receptor (KIR) genes are a polymorphic family expressed on NK cells, and "senescent" CD28- T cells implicated in cardiovascular disease. KIR promoters are highly homologous, and NK expression is regulated by DNA methylation. T cell KIR regulation is poorly understood. We asked if epigenetic mechanisms and/or transcription factor alterations determine T cell KIR expression. DNA methylation inhibition activated multiple KIR genes in normal T cells. KIR2DL2 and KIR2DL4 were selected for further study. Expression of both was associated with promoter demethylation, and methylation of the promoters in reporter constructs suppressed expression. KIR reporter construct expression also increased in demethylated T cells and required Ets1, Sp1 and AML sites, implying effects on transcription factors. This was confirmed for Sp1. These results indicate that KIR genes are suppressed by DNA methylation in most T cells, and DNA demethylation promotes their expression through effects on both chromatin structure and transcription factors.


Ovarian torsion and amputation resulting in partially calcified, pedunculated cystic mass.
Three children with torsion and amputation of the right ovary are presented. The detached ovary resulted in a cystic mass containing necrotic material and a solid, partially calcified mural node. The cysts were attached to the omentum, to the mesentery of the transverse colon, or to the lower edge of the liver by a long twisted pedicle containing thin-walled vascular spaces. The radiographic and sonographic findings were quite similar and clearly reflected the operative and pathologic changes.


Safety and efficacy of two-drug combination in elderly patients with locally advanced non-small cell lung cancer and validation of the Charlson Index as a predictor of survival.
The best platinum-based chemotherapy regimen remains to be determined in elderly patients treated with definitive chemoradiotherapy for advanced non-small cell lung cancer (NSCLC). Predictive indexes for toxicity and survival are also needed to give the safest and most effective treatment for this population. This is a retrospective cohort study. Patients with histologically confirmed stage IIIA, IIIB or IIIC NSCLC over 70 years of age, treated with radiotherapy and chemotherapy, were included. Patients from two cancer centers treated between 12/2006 and 08/2019 were included in the data analysis. Fifty-eight patients were enrolled in the study. The median age was 76.6 years [interquartile range (IQR): 71.6-83.4]. Thirty-nine patients were treated with concomitant chemoradiotherapy and 19 with a sequential strategy. The chemotherapy regimen consisted in a combination of platinum and taxanes. At a median follow-up of 52 months (IQR: 7-69), the 2-year progression-free survival (PFS) and overall survival (OS) were 35.5% and 66.9%, respectively. Male sex and a high Charlson index were identified as independent prognostic factors for worse OS. Acute grade 3-5 toxicities occurred in 34.4% of patients, including 1 grade 5 toxicity, and grade 3-4 late toxicities occurred in 17.2% of patients. In the whole cohort a high Charlson index was the only predictive factor for a higher risk of grade 3-5 acute toxicities (statistical trend in the concurrent cohort, P=0.06). The Charlson index correlated with toxicity and survival in elderly patients treated with chemoradiotherapy in locally advanced NSCLC. The addition of taxanes to platinum chemotherapy was safe in the present study and warrants further exploration.


Multioperation-Mode Light-Emitting Field-Effect Transistors Based on van der Waals Heterostructure.
2D semiconductors have shown great potential for application to electrically tunable optoelectronics. Despite the strong excitonic photoluminescence (PL) of monolayer transition metal dichalcogenides (TMDs), their efficient electroluminescence (EL) has not been achieved due to the low efficiency of charge injection and electron-hole recombination. Here, multioperation-mode light-emitting field-effect transistors (LEFETs) consisting of a monolayer WSe2 channel and graphene contacts coupled with two top gates for selective and balanced injection of charge carriers are demonstrated. Visibly observable EL is achieved with the high external quantum efficiency of ≈6% at room temperature due to efficient recombination of injected electrons and holes in a confined 2D channel. Further, electrical tunability of both the channel and contacts enables multioperation modes, such as antiambipolar, depletion,and unipolar regions, which can be utilized for polarity-tunable field-effect transistors and photodetectors. The work exhibits great potential for use in 2D semiconductor LEFETs for novel optoelectronics capable of high efficiency, multifunctions, and heterointegration.


The clinical application of customized 3D-printed porous tantalum scaffolds combined with Masquelet's induced membrane technique to reconstruct infective segmental femoral defect.
This study mainly exams a novel treatment for infective segmental femoral defect, and we combined the 3D printed porous tantalum prosthesis and Masquelet's induce membrane technique to reconstruct bone defect and discussed the clinical effect. The clinical research included 9 observational cases series, as a permanently implantation, the customized 3D-printed scaffolds that connected with an anatomical plate was implanted into the bone defect segment after successful formation of induced membrane, the clinical effect was evaluated by radiological exams and Paley's bone union criteria. The personalized 3D-printed porous tantalum was, respectively, manufactured and used in 9 consecutive patients to reconstruct the infective segmental bone defect of femur, the mean defect length was 16.1 ± 2.8 cm, the mean length of follow-up was 16.9 ± 4.0 months, after 2 stage operation, there was no deep infections, refractures, sensorimotor disorder, vascular injury, ankylosis and recurrence of infection occurred in all cases. postoperative radiological exams shown stable internal fixation and osseointegration, and all these results were invariable during the follow-up time in all cases. All patients significantly obtained deformity correction and length of limb. The customized 3D-printed porous tantalum prosthesis was an acceptable alternative treatment to the autogenous or allograft bone graft, the combination of the two techniques could achieve satisfactory reconstruct to infective broad bone defect in femur when other biological techniques were not suitable.


Comparative evaluation of microscopy, OptiMAL(®) and 18S rRNA gene based multiplex PCR for detection of Plasmodium falciparum & Plasmodium vivax from field isolates of Bikaner, India.
To evaluate microscopy, OptiMAL(®) and multiplex PCR for the identification of Plasmodium falciparumm (P. falciparum) and Plasmodium vivax (P. vivax) from the field isolates of Bikaner, Rajasthan (Northwest India). In this study, a multiplex PCR (P. falciparum and P. vivax) was further developed with the incorporation of Plasmodium malariae (P. malariae) specific primer and also a positive control. The performance of microscopy, plasmodium lactate dehydrogenase (pLDH) based malaria rapid diagnostic test OptiMAL(®) and 18S rRNA gene based multiplex PCR for the diagnosis of P. falciparum and P. vivax was compared. The three species multiplex PCR (P. falciparum, P. vivax and P. malariae) with an inbuilt positive control was developed and evaluated. In comparison with multiplex PCR, which showed the sensitivity and specificity of 99.36% (95%CI, 98.11%-100.00%) and 100.00% (95%CI, 100.00%-100.00%), the sensitivity and specificity of microscopy was 90.44% (95%CI, 88.84%-95.04%) and 99.22% (95%CI, 97.71%-100.00%), and OptiMAL(®) was 93.58% (95%CI, 89.75%-97.42%) and 97.69% (95%CI, 95.10%-100.00%). The efficiencies were 99.65%, 95.10% and 95.45% for multiplex PCR, microscopy and OptiMAL(®), respectively. Our results raise concerns over the overall sensitivities of microscopy and OptiMAL(®), when compared to the multiplex PCR and thus stress the need for new molecular interventions in the accurate detection of the malarial parasites. This further highlights the fact that further developments are needed to improve the performance of rapid diagnostic tests at field level.


Diltiazem efficacy and CYP2D6 gene polymorphism in patients with atrial fibrillation with rapid ventricular response.
Diltiazem stands out as one of the front-line drugs administered in the emergency department to achieve acute rate control in patients suffering from atrial fibrillation with rapid Ventricular Response. One of the cytochrome enzymes involved in the metabolism of diltiazem is cytochrome P450 2D6 (CYP2D6). Interindividual differences can act on drug metabolism and thus drug efficacy due to the genetic polymorphism induced by the CYP2D6 enzyme. This study explores the association between the efficacy of diltiazem and the genetic polymorphism of CYP2D6 in patients with atrial fibrillation with rapid ventricular response. 87 out of 93 individuals with ventricular rate > 120 beats/min constituted the patient cohort. The patients were administered 0.25 mg/kg diltiazem intravenously. As a second dose, 0.35 mg/kg diltiazem was administered to patients who reportedly did not receive adequate drug efficacy. Heart rate control was considered to be achieved in patients whose heart rate fell below 110 beats/min and did not rise above 110 beats/min for 2 h. CYP2D6 *2, *3, *4 and *10 represent allele variants and *1 represents wild type (wt) allele. Achieving rate control after one or two doses of diltiazem in normal allele (wt/wt) carriers proved significantly higher than wt/*2, wt/*4 and wt/*10 heterozygous variant carriers. No significant difference was noted in wt/*3 heterozygous variant carriers. The presence of *2, *4 and *10 alleles was observed to significantly compromise the drug efficacy. *3 allele was found to bear no relation to the effect of diltiazem on achieving rate control.


Mussel adhesion-employed water-immiscible fluid bioadhesive for urinary fistula sealing.
Urinary fistulas, abnormal openings of a urinary tract organ, are serious complications and conventional management strategies are not satisfactory. For more effective and non-invasive fistula repair, fluid tissue adhesives or sealants have been suggested. However, conventional products do not provide a suitable solution due to safety problems and poor underwater adhesion under physiological conditions. Herein, we proposed a unique water-immiscible mussel protein-based bioadhesive (WIMBA) exhibiting strong underwater adhesion which was employed by two adhesion strategies of marine organisms; 3,4-dihydroxy-l-phenylalanine (DOPA)-mediated strong adhesion and water-immiscible coacervation. The developed biocompatible WIMBA successfully sealed ex vivo urinary fistulas and provided good durability and high compliance. Thus, WIMBA could be used as a promising sealant for urinary fistula management with further expansion to diverse internal body applications.


Exclusive breast feeding versus supplementation: a prospective study in a rural south Indian community.
In a non-interventional, prospective study in three south Indian villages, exclusively breast-fed infants were compared with those given supplements in addition to breast milk. The supplements provided less than 30% of caloric requirement in most cases. Both groups grew similarly and the growth curves showed a sharp fall after the third month. Whether this fall is physiological, or a result of poor socio-economic conditions is not clear.


A computer program for the generalized chi-square analysis of competing risks grouped survival data (CRISCAT).
CRISCAT is a computer program for the analysis of grouped survival data with competing risks via weighted least squares methods. Competing risks adjustments are obtained from general matrix operations using many of the strategies employed in a previously developed program (GENCAT) for multivariate categorical data. CRISCAT computes survival rates at several time points for multiple causes of failure, where each rate is adjusted for other causes in the sense that failure due to thes other causes has been eliminated as a risk. The program can generate functions of the adjusted survival rates, to which asymptotic regression models may be fit. CRISCAT yields test statistics for hypotheses involving either these functions or estimated model parameters. Thus, this computational algorithm links competing risks theory to linear models methods for contingency table analysis and provides a unified approach to estimation and hypothesis testing of functions involving competing risks adjusted rates.


Exploration of biguanido-oxovanadium complexes as potent and selective inhibitors of protein tyrosine phosphatases.
The inhibitory effects of three biguanido-oxovanadium complexes ([VO(L(1-3))(2)]·nH(2)O: HL(1) = metformin, HL(2) = phenformin, HL(3) = moroxydine) against four protein tyrosine phosphatases (PTPs) and an alkaline phosphatase (ALP) were investigated. The complexes display strong inhibition against PTP1B and TCPTP (IC(50), 80-160 nM), a bit weaker inhibition against HePTP (IC(50), 190-410 nM) and SHP-1(IC(50), 0.8-3.3 μM) and much weaker inhibition against ALP (IC(50), 17-35 μM). Complex 3 is about twofold less potent against PTP1B, TCPTP and HePTP than complexes 1 and 2, while complex 2 inhibits SHP-1 more strongly (about three to fourfold) than the other two complexes. These results suggest that the structures of the ligands slightly influence the potency and selectivity against PTPs. The complexes inhibit PTP1B and ALP with a typical competitive type.


Random model for radiation shielding calculation of particle reinforced metal matrix composites and its application.
The work aimed to calculate the radiation biological shielding performance of particle reinforced metal matrix composite (PRMMCs) using more reasonable model instead of conventional Uniform Filling Model, also attempted to provide a basis for the radiation shielding optimal design of such materials. Firstly, RSA (Random Sequential Adsorption) Model and GRM (Grid Random Model) were established based on MATLAB and Monte Carlo Particle transport program MCNP, and then advantages and disadvantages of them were compared. Later, the influences of metal matrix type, particle (B4C) content, particle shape and particle shape parameters on the biological shielding performance of materials were calculated under different energy neutrons and different thickness shield using random models. Finally, the optimal aspect ratio of regular hexahedral B4C was calculated by Genetic Algorithm combined with MATLAB and MCNP. It indicated that GRM could be applied to radiation shielding calculation of PRMMCs.


p53 intronic G13964C variant in colon cancer and its association with HPV.
Inactivation of p53 is the most common change identified in human cancer. Nucleotide alterations in p53 intron 6 have been reported to be associated with the dysregulation of p53 function and tumor development. The aim of our study was to assess whether the intron 6 G13964C variant of the p53 gene is associated with the presence of human papillomavirus (HPV) as a risk factor in colon cancer. To determine whether the intronic G13964C alteration is involved in colon carcinogenesis, surgical specimens from 55 patients with colon cancer and HPV-positive tumors were examined by PCR-RFLP. Blood samples from 77 healthy subjects were used as the control group. The 13964C variant was found in 14.5% of colon cancer patients and 12.9% of the control subjects. One patient and two controls were homozygous for this base change. No evidence of a significant association between the p53 G13964C allele and colon carcinoma was found.


Decreased 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) in patients with Lesch-Nyhan syndrome.
The coagulation abnormality in patients with Lesch-Nyhan syndrome (LNS) prompted us to examine 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), a stable metabolite of prostacyclin (PGI2). Plasma levels of 6-keto PGF1 alpha were significantly low in 4 patients with LNS, but they were elevated after discontinuation of allopurinol. Other indicators of coagulation and fibrinolysis systems did not change after the discontinuation of allopurinol. PGI2 prevents the production of superoxide which is formed after cerebral ischemia. The potential source of superoxide is xanthine oxidase which is inhibited by allopurinol. It is assumed that plasma PGI2 increased in response to formed superoxide because xanthine oxidase inhibition was abolished after discontinuation of allopurinol.


Premenstrual syndrome as a western culture-specific disorder.
Premenstrual syndrome (PMS) has a phenomenology resembling many culture-bound (culture-specific) syndromes described in the anthropological literature. Viewed as a culture-specific syndrome, PMS is an appropriate symbolic representation of conflicting societal expectations that women be both productive and reproductive. By simultaneously denying either alternative, PMS translates role conflict into a standardized cultural idiom. Thus, despite obvious biopsychological determinants, PMS is best understood as a sociocultural phenomenon illustrating both the special status of women in Western culture and the ethnocentrism of Western anthropology which heretofore has only recently begun to identify culture-specific syndromes in its own back yard.


[Etiological problems of anterior tooth crowding: the role of the third molar].
The authors discussed about the extraction or not of the 3 degrees molar either to prevent or correct the dental crowding. They state that, since there is no definitive evidence of the real importance of the 3 degrees molar in creating dental crowding, it is not possible to perform without discrimination 3 degrees molar germectomy nor the extraction for prevention.


Single-centre experience with an 8-mm tip catheter for radiofrequency catheter ablation of outflow tract ventricular ectopic beats.
Radiofrequency ablation (RFA) of outflow tract ventricular ectopic beats (OTVEBs) can be performed using a 4-mm or externally-cooled tip RFA catheter, but no data are available concerning the safety and efficacy of a large-tip (8-mm) catheter. To evaluate the feasibility of using an 8-mm tip catheter in patients with OTVEBs. In this prospective cohort study, the 8-mm tip catheter was tested in patients who were referred to our centre for RFA of symptomatic OTVEBs. The mean age of the 16 patients recruited between September 2008 and March 2010 was 53±18 years and 56.3% were male. Mean left ventricular ejection fraction was 62±9%, mean ventricular ectopic beat width was 144±21 ms, and all patients had left bundle branch block. Fourteen patients had inferior axis QRS morphology and two had superior. The main symptoms were palpitations and pre-syncope. RFA parameters were: procedure time 94±35 min; duration of application 11±10 min; impedance 81±12 Ω; temperature 50±5 °C; and power 46±17 W. RFA succeeded in 15 over 16 patients (93.8%); and recurrence was seen in one patient after a mean follow-up time of 11±6 months. No complications were noted. This preliminary study suggests that an 8-mm tip catheter may represent an alternative for RFA in patients with OTVEBs in whom a 4-mm tip was not successful. Larger randomized studies are therefore warranted.


Potentiation of the NMDA receptor-mediated responses through the activation of the glycine site by microglia secreting soluble factors.
We have previously reported that both transferred microglia and microglia-conditioned medium (MCM) potentiated the N-methyl-D-aspatate (NMDA) receptor-mediated synaptic responses in cortical neurons. To elucidate the mechanism underlying the potentiation of NMDA receptor-mediated responses by microglia, we examined the effects of MCM on NMDA-induced inward currents in mechanically dissociated hippocampal CA1 neurons under whole-cell patch recordings. MCM potentiated the amplitude of NMDA-induced currents up to 10-fold in a dose-dependent manner, and this effect of MCM remained even after boiling or cutting off molecules with a molecular mass more than 3 kDa. In the presence of glycine with a concentration sufficient to saturate the NMDA receptor glycine site, MCM failed to further potentiate the NMDA-induced currents. The glycine site antagonist 5, 7-dichrolokynurenic acid, significantly inhibited the effects of MCM. The effect of MCM was still observed even after treatment with D-amino acid oxidase, a D-serine degrading enzyme. On the other hand, MCM had no significant effect on the voltage-dependent Mg(2+) blockade of NMDA receptors. Furthermore, MCM enhanced the formation of the long-term potentiation in the Schaffer collateral pathway-CA1 pyramidal cell synapses. Using a high performance liquid chromatography system, we found the levels of both glycine and L-serine in MCM to be significantly higher than those in the control medium. It was also noted that an increased glycine productivity of microglia was observed in the hippocampus in the acute phase of neuronal injury. These observations strongly suggest that glycine is a major causative molecule released from microglia that potentiates the NMDA-induced currents.


Spontaneous regression of a cystic tumor in a postpartum woman; is it a cystic lymphangioma?
Spontaneous regression of intra-abdominal cystic tumors in adults is unusual. Here, we present the case of an apparently spontaneous regression of a large intra-abdominal cystic mass found in the postpartum period of an 18-year-old woman. The regression was demonstrated using serial computed tomography (CT) examinations over a two-year period.


Foliar sieve elements: Nexus of the leaf.
In this review, a central position of foliar sieve elements in linking leaf structure and function is explored. Results from studies involving plants grown under, and acclimated to, different growth regimes are used to identify significant, linear relationships between features of minor vein sieve elements and those of 1) leaf photosynthetic capacity that drives sugar synthesis, 2) overall leaf structure that serves as the platform for sugar production, 3) phloem components that facilitate the loading of sugars (companion & phloem parenchyma cells), and 4) the tracheary elements that import water to support photosynthesis (and stomatal opening) as well as mass flow of sugars out of the leaf. Despite comprising only a small fraction of physical space within the leaf, sieve elements represent a hub through which multiple functions of the leaf intersect. As the conduits for export of energy-rich carbohydrates, essential mineral nutrients, and information carriers, sieve elements play a central role in fueling and orchestrating development and function of the plant as well as, by extension, of natural and human communities that depend on plants as producers and partners in the global carbon cycle.


Natural SARS-CoV- 2 infection in domestic cats and dogs of humans diagnosed with COVID-19 in Valle de Aburrá, Antioquia
Introducción. El síndrome respiratorio agudo grave causado por el nuevo coronavirus SARSCoV-2 es causa de la emergencia sanitaria por la pandemia de COVID-19. Si bien el humano es el el principal huésped vulnerable, en estudios experimentales y reportes de infección natural, se han encontrado casos de zoonosis inversa de SARS-CoV-2 en animales. Evaluar la infección natural por SARS-CoV-2 en gatos y perros de propietarios con diagnóstico de COVID-19 en el Valle de Aburrá, Antioquia, Colombia. Materiales y métodos. La circulación del SARS-CoV-2 se evaluó por RT-qPCR y RT-PCR en muestras de frotis nasofaríngeos y orofaríngeos de gatos y perros cuyos propietarios se encontraban dentro del periodo de los 14 días de aislamiento. Los casos positivos se verificaron amplificando fragmentos de los genes RdRp, N y E; se secuenció el gen RdRp y se analizó filogenéticamente. De 80 animales evaluados, seis gatos y tres perros fueron casos confirmados de infección natural por SARS-CoV-2. Los animales no presentaron signos clínicos y sus propietarios, que padecían la infección, reportaron únicamente signos leves de la enfermedad sin complicaciones clínicas. En el análisis de una de las secuencias, se encontró un polimorfismo de un solo nucleótido (SNP) con un cambio en la posición 647, con sustitución del aminoácido serina (S) por una isoleucina (I). Los casos se presentaron en los municipios de Caldas, Medellín y Envigado. Se infiere que la infección natural en los gatos y perros se asocia al contacto directo con un paciente con COVID-19. No obstante, no es posible determinar la virulencia del virus en este huésped, ni su capacidad de transmisión zoonótica o entre especie.


Genetic evaluation of childhood acute lymphoblastic leukemia in Iraq using FTA cards.
Genetic examination of childhood leukemia has not been available in Iraq. We here report the frequency of TEL-AML1, E2A-PBX1, MLL-AF4, and BCR-ABL chimeric transcripts in 264 Iraqi children newly diagnosed with acute lymphoblastic leukemia (ALL), using FTA cards impregnated with bone marrow aspirate or whole blood. The diagnosis of ALL was made according to standard French-American-British morphologic criteria. Based on the results of storage temperature and duration, most of the FTA samples were preserved at 4°C for up to 6 weeks in five Iraqi hospitals and then transferred to Japan for molecular analysis. Nested reverse transcription-polymerase chain reaction was adopted for the analysis. TEL-AML1 chimeric transcript product was found in 32 (12.1%) of 264 ALL patients. Eleven (4.2%) patients, 4 (1.5%) patients, and 11 (4.2%) patients had E2A-PBX1 mRNA, MLL-AF4 mRNA, and BCR-ABL mRNA, respectively. One patient had both TEL-AML1 and E2A-PBX1 fusion genes. The incidence of TEL-AML1 in Iraqi ALL children appears to be similar to or slightly higher than those of Jordan (12%) and Kuwait (7%). The prevalence and clinical findings of ALL patients with either E2A-PBX1 or BCR-ABL were comparable to the data reported elsewhere. International collaboration via FTA cards may be helpful to improve diagnosis and management of patients with hematological malignancies in low-income and underdeveloped countries.


DNA vaccination for prostate cancer, from preclinical to clinical trials - where we stand?
Development of various vaccines for prostate cancer (PCa) is becoming an active research area. PCa vaccines are perceived to have less toxicity compared with the available cytotoxic agents. While various immune-based strategies can elicit anti-tumour responses, DNA vaccines present increased efficacy, inducing both humoural and cellular immunity. This immune activation has been proven effective in animal models and initial clinical trials are encouraging. However, to validate the role of DNA vaccination in currently available PCa management paradigms, strong clinical evidence is still lacking. This article provides an overview of the basic principles of DNA vaccines and aims to provide a summary of preclinical and clinical trials outlining the benefits of this immunotherapy in the management of PCa.


LncRNA SNHG14 promotes hepatocellular carcinoma progression via H3K27 acetylation activated PABPC1 by PTEN signaling.
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. LncRNA small nucleolar RNA host gene 14 (SNHG14) functions as an oncogene in a variety of cancers. However, the role of SNHG14 in HCC remains elusive. The aim of this study is to unravel the functional role and regulatory mechanism of SNHG14 in HCC. A cohort of 40 HCC tumor tissues and paired adjacent normal tissues were collected. Histopathological changes were analyzed by hematoxylin and eosin and immunohistochemistry. qRT-PCR and western blotting were performed to determine the levels of SNHG14, PABPC1, and PTEN signaling molecules. CCK-8, immunofluorescence, and colony formation assays were conducted to monitor cell proliferation. Wound healing and tube formation assays were employed to determine cell migration and angiogenesis. ChIP assay was performed to investigate the enrichment of H3K27 acetylation in PABPC1 promoter. Xenograft mice model was constructed to further verify the SNHG14/PABPC1 axis in vivo. SNHG14 was highly expressed in HCC tissues and cells, which promoted cell proliferation, migration, and angiogenesis in Hep3B and HepG2 cells. PABPC1 functioned as a downstream effector of SNHG14. SNHG14 dramatically induced upregulation of PABPC1 via H3K27 acetylation. In addition, SNHG14/PABPC1 promoted cell proliferation and angiogenesis via PTEN signaling pathway in vitro and in vivo. SNHG14 promoted cell proliferation and angiogenesis via upregulating PABPC1 through H3K27 acetylation and modulating PTEN signaling in the tumorigenesis of HCC.


[New morphometric parameter for analyzing changes in the ultrastructure of cardiomyocytes--the relative volume fraction].
Analysing the processes accompanied by changes in cardiomyocyte volume without the formation or loss of myofibrils, it has been proposed to use a new parameter "relative volume fraction" that denotes the volume occupied by the ultrastructure under investigation, as related to primary cell volume, and permits to estimate changes of the ultrastructural volume proper. The value of this parameter may be calculated according to the formula: (Formula: see text).


Hemostatic abnormalities and leukocyte activation caused by infection in patients with malignant lymphoma during chemotherapy.
Hemostatic parameters were examined before and during 102 courses of chemotherapy in 42 patients with malignant lymphoma with high risk for infection. The white blood cell count was significantly reduced in all patients at days 1 and 3, but significantly increased at days 7 and 9, compared to before chemotherapy. At day 7 of chemotherapy, tissue factor (TF) mRNA levels in leukocytes were significantly increased in all patients, especially those with infection. Plasma concentrations of granulocyte elastase derived-XDP (GE-XDP) levels correlated with D-dimer levels during chemotherapy in patients with malignant lymphoma, suggesting that the elevated D-dimer is fibrin products degraded by granulocyte elastase. GE-XDP, C-reactive protein (CRP), GE-XDP and D-dimer were significantly higher in patients with infection, disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS) than those without. In patients with DIC or ARDS, TF mRNA correlated with D-dimer, and GE-XDP correlated with leukocyte count, CRP and D-dimer, suggesting that inflammatory changes due to thrombosis may cause the activation of leukocytes in patients with malignant lymphoma during chemotherapy. Activated leukocytes and granulocyte elastase may elicit a hypercoagulable state and ARDS in patients with malignant lymphoma during chemotherapy.


[Comparison of kinetic behavior in both plasma and tissue after intravenous administration of alpha-asarone in lipid emulsion and aqueous solution in rats and mice].
To compare the pharmacokinetics and tissue distribution of alpha-asarone in lipid emulsion and aqueous solution for injection and study the feasibility of lipid emulsion of alpha-asarone as the parenteral drug delivery system. HPLC was used to determine the drug concentration in rat plasma and mice tissues after intravenous (i.v.) administration of lipid emulsion and aqueous solution of alpha-asarone at a single dose (40 mg x kg(-1)), respectively. The plasma concentration-time profiles of lipid emulsion and aqueous solution of alpha-asarone after intravenous administration of them are similar and the drug concentration-time data were fitted to a two-compartment open model. The results of tissues distribution showed that distribution contents of alpha-asarone from lipid emulsion and aqueous solution in vivo are similar in lungs but lipid emulsion increased the uptake in livers and spleens, and decreased the uptake in hearts and kidneys for alpha-asarone. The plasma concentration-time profiles of alpha-asarone in lipid emulsion and aqueous solution are similar, but lipid emulsion significantly altered the tissue distribution of alpha-asarone, which may be beneficial to decrease its potential toxicity to heart and kidney.


Sex-Specific Pathways Lead to Statural Growth Impairment in Children with Crohn's Disease.
To examine the underlying mechanisms that lead growth impairment to occur more commonly in males than females with Crohn's disease (CD). Children and adolescents with CD were enrolled in a prospective multicenter longitudinal cohort study. Height Z-score difference was computed as height Z-score based on chronological age (height chronological age-Z-score) minus height Z-score based on bone age (height bone age-Z-score) using longitudinal data. Specific serum cytokines were measured, hormone Z-scores were calculated based on bone age (bone age-Z), and their longitudinal associations were examined. There were 122 children with CD (63% male) who completed 594 visits. The mean ± SD chronological age was 11.70 ± 1.79 years. The mean ± SD height chronological age-Z-score was -0.03 ± 0.99 in males and -0.49 ± 0.87 in females. The mean ± SD height bone age-Z-score was 0.23 ± 0.93 in males and 0.37 ± 0.96 in females. The magnitude of the mean height Z-score difference was greater in females (-0.87 ± 0.94) than males (-0.27 ± 0.90; P = .005), indicating growth was better in females than males. The following negative associations were identified: in females, interleukin (IL)-8 (P < .001) and IL-12p70 (P = .035) with gonadotropin-bone age-Z-scores; IL-8 (P = .010), IL-12p70 (P = .020), and interferon-γ (P = .004) with sex hormone-bone age-Z-scores, and IL-8 (P = .044) and interferon-γ (P < .001) with insulin-like growth factor 1-bone age-Z-scores; in males, IL-1 beta (P = .019) and IL-6 (P = .025) with insulin-like growth factor 1-bone age-Z-scores. Our data suggest that sex-specific molecular pathways lead to growth impairment in children with CD (primarily growth hormone/insulin-like growth factor-1 axis in males and primarily hypothalamic-pituitary-gonadal axis in females). Mapping these sex-specific molecular pathways may help in the development of sex-specific treatment approaches targeting the underlying inflammation characteristic of CD.


Exosomal lncRNA UCA1 from cancer-associated fibroblasts enhances chemoresistance in vulvar squamous cell carcinoma cells.
In the current work, we aimed to explore whether Cancer-associated fibroblasts (CAF) exosomes played crucial roles in vulvar squamous cell carcinoma (VSCC) chemoresistance via mediating long noncoding RNAs (lncRNA). The IC50 value and cell apoptosis were assessed by the Cell Counting-8 Kit (CCK-8) assay and flow cytometry, respectively. Western blot analysis was used for the measurement of protein levels. The levels of urothelial cancer-associated 1 (UCA1), miR-103a and WEE1 G2 checkpoint kinase (WEE1) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships among miR-103a, UCA1 and WEE1 were confirmed by dual-luciferase reporter assays. Xenograft model mice were established to observe the impact of exosomal UCA1 on cisplatin (CDDP) resistance in vivo. Our data indicated that CAF enhanced CDDP resistance of VSCC cells in vitro. Extracellular UCA1 was transferred by exosomes derived from CAF. Exosomal UCA1 derived from CAF conferred VSCC cell resistance to CDDP. Moreover, UCA1 functioned as a miR-103a sponge in VSCC cells. The promotion of exosomal UCA1 on VSCC cell resistance to CDDP was mediated by miR-103a. WEE1 was a direct target of miR-103a, and exosomal miR-103a from CAF weakened CDDP resistance of VSCC cells by WEE1. Furthermore, exosomal UCA1 regulated WEE1 expression through sponging miR-103a. Additionally, exosomal UCA1 enhanced tumor growth and CDDP resistance in vivo. Our findings suggested exosomal UCA1 derived from CAF conferred VSCC cell resistance to CDDP in vitro and in vivo at least partly through the miR-103a/WEE1 axis, highlighting a novel therapeutic method for improving the clinical benefits of CDDP chemotherapy in VSCC patients.


Sexing of in vitro-fertilized preimplantation mouse embryos by the PCR method.
The applicability of the dual PCR method to embryo sexing was examined with the aim of establishing a noninvasive method of preimplantation diagnosis for human genetic disorders. Mouse pre-embryos obtained by in vitro fertilization were studied. The Sry gene sequence and the myogenin sequence were amplified as the Y-specific and internal control sequences, respectively. Amplification of as little as 10 pg of mouse genomic DNA was possible with the dual PCR method, the sensitivity being 10-fold greater than that of the single PCR method. The sex was identified in 100% (24/24) and 96% (23/24) of the pre-embryos tested at the 16- and 4-cell stages, respectively. In addition, the sex of all four single blastomeres dissociated from 4-cell pre-embryos agreed in 76% (16/21) of the specimens tested and 94% (79/84) of dissociated blastomeres could be sexed. The sex of single blastomeres biopsied from pre-embryos at the 8-cell stage could be identified. After transfer of 13 male and 25 female sexed pre-embryos, six viable fetuses were obtained. Histological examination showed that all these fetuses were of the predicted sex. Sexing of biopsied single blastomeres by the dual PCR method was rapid and reliable, suggesting its feasibility for preimplantation diagnosis of in vitro fertilized human pre-embryos.


The blockade of transient receptor potential ankyrin 1 (TRPA1) protects against PTZ-induced seizure.
Treatment of epilepsy remains a major problem as some epileptic patients do not respond to the current therapeutics. Transient receptor potential ankyrin 1 (TRPA1) belongs to the TRP channels and has diverse physiological functions in the body. Considering its physiological properties, we aimed to evaluate its role in two experimental models of epilepsy, including pentylenetetrazol (PTZ)-induced acute seizure and PTZ-evoked kindling. Furthermore, the TRPA1 protein levels were assessed in the cerebral cortex, hippocampus, and cerebellum after seizure induction. Three groups of Wistar rats received acute intraperitoneal injection of pentylenetetrazol (PTZ, 85 mg/kg). The groups received intraventricular injections of vehicle (dimethyl sulfoxide, Tween 80, and sterile 0.9% saline), valproate (30 µg/rat), or HC030031 (TRPA1 antagonist, 14 µg/rat) before PTZ injection. In the PTZ-induced kindling model, PTZ was administrated 35 mg/kg every other day for 24 days. PTZ gradually provoked seizure-related behaviors. After experiments, the TRPA1 levels in the brain were assessed using western blot. The results showed that HC030031 reduced the median of seizure scores and S5 duration while increasing S2 and S5 latencies in acute and kindling models. The anticonvulsant effect of HC030031 was comparable with valproate as a standard anticonvulsant drug. Furthermore, induction of seizure, either acute or kindling, enhanced TRPA1 levels in the cerebral cortex, hippocampus, and cerebellum that were prevented by HC030031 or valproate administration. The results of this study showed that HC030031 as a TRPA1 receptor antagonist promoted a significant anticonvulsant effect comparable with valproate. Both drugs prevented TRPA1 upregulation during seizures. These findings imply that TRPA1 is a potential target in treating epilepsy.


Identifying Type III Sulcus: Patient Characteristics and Endoscopic Findings.
Type III sulcus is a pathologic structural deformity of the vocal folds that is challenging to accurately diagnose without endoscopic examination under anesthesia. This study aims to further define the clinical presentation and examination features shared among a patient cohort intraoperatively diagnosed with type III sulcus. Case series with chart review. Tertiary laryngology practice. All patients diagnosed intraoperatively with type III sulcus from 2002 to 2014 at a tertiary laryngology practice were included. Clinical history of presenting symptoms, videostroboscopy, and intraoperative and histologic findings were reviewed. Twenty-two patients were included in the study. A majority were female (77%) and had a mean age of 32.4 years. All patients endorsed hoarseness, and 86% were defined as professional voice users. Endoscopic examination revealed bilateral type III sulcus in 23% of patients. The most common preoperative stroboscopic findings included decreased mucosal wave (100%), dilated vessel (95%), phase asymmetry (91%), additional benign lesion (91%), and cyst (82%). Histology revealed epithelial changes of atypia and keratosis. Both the severity of dysphonia and the difficulty observing structural malformations of the vocal folds make type III sulcus challenging to preoperatively diagnose. This study reports the clinical and endoscopic features seen within a cohort of patients with type III sulcus.


Correction: Using mechanical testing to assess texturing of prosthetic sockets to improve suspension in the transverse plane and reduce rotation.
[This corrects the article DOI: 10.1371/journal.pone.0233148.].


Computed tomography of pulmonary metastases from osteosarcoma: the less poor technique. A study of 51 patients with histological correlation.
The purpose is to evaluate the accuracy of computed tomography (CT) in the pulmonary staging of osteosarcoma. Fifty-one patients presenting with osteosarcoma and at initial CT considered metastatic to the chest had lung surgery. Two teams of two senior radiologists independently reviewed all CT examinations. Their results were compared to the histological studies. One hundred nineteen CT's were reviewed. The 2 teams found 247 and 268 nodules on the initial. and 143 and 146 nodules on the preoperative CT. Histological studies confirmed metastatic nodules in 29 patients. Two hundred four nodules were excised and studied. One hundred nine were metastases. The 22 patients without metastases had 53 negative nodules removed. In the 29 patients with metastases, 151 nodules were removed, and 42 were non-metastatic. The positive predictive value was 53% with regard to 'nodules', and 57% with regard to 'patients'. Only 4 out of 13 patients with one nodule at surgery were metastatic, but all patients with more than 7 nodules were metastatic. The 46 cases with several available CT's, showed that no change in the number of nodules was more frequent in benign lesions. Other criteria revealed no significant difference. CT positive predictive value is limited, but as surgery is the only way to cure metastatic patients, CT will still be used as the reference technique until a more specific approach can be found.


[In vitro maturation, fertilization and embryo transfer of human immature oocyte].
To try a new method for treating infertile women by in vitro maturation technique. To set up in vitro maturation (IVM) program, including stimulating regimen, oocyte retrieval technique, and culture system of the immature oocytes with the medium consisted of essential supplements and human mature follicular fluid. IVM was performed in 30 infertile patients (35 cycles), (1) with polycystic ovary syndrome (POCS) (14/30), (2) ovary hyperstimulation syndrome (OHSS) in the previous stimulating cycles (6/30), and (3) retardation of the oocyte growth in conventional IVF cycles (10/30). Totally 203 oocytes were obtained, with a mean of 5.8 oocytes each cycle. First polar bodies were observed in 156 oocytes, maturation rate was 76.8%. There were 120 oocytes getting into pronucleus stage, normal fertilization rate was 76.9%. Embryo transfer was performed in 33 cycles. Eight pregnancies were established, pregnancy rate was 24%. Five patients have delivered 7 healthy babies. The result of our study indicated that IVM is one of the new assisted reproductive technologies for the infertile women with PCOS, poor response to stimulation and the history of OHSS. Human mature follicular fluid would be an ideal component in the maturation medium for oocyte maturation in vitro and provides a much simplified and practical method for clinical use.


Respiratory syncytial virus, infants and intensive therapy.
The aims of this study were to determine the presence of respiratory syncytial virus (RSV) and to assess the clinical features of the disease in infants with acute low respiratory tract infection hospitalized at pediatric intensive care units (PICU) of two university teaching hospitals in São Paulo State, Brazil. Nasopharyngeal secretions were tested for the RSV by the polymerase chain reaction. Positive and negative groups for the virus were compared in terms of evolution under intensive care (mechanical pulmonary ventilation, medications, invasive procedures, complications and case fatality). Statistical analysis was performed using the Mann Whitney and Fisher's exact tests. A total of 21 infants were assessed, 8 (38.1%) of whom were positive for RSV. The majority of patients were previously healthy while 85.7% required mechanical pulmonary ventilation, 20/21 patients presented with at least one complication, and the fatality rate was 14.3%. RSV positive and negative groups did not differ for the variables studied. Patients involved in this study were critically ill and needed multiple PICU resources, independently of the presence of RSV. Further studies involving larger cohorts are needed to assess the magnitude of the impact of RSV on the clinical evolution of infants admitted to the PICU in our settings.


Noninvasive quantification of regional myocardial blood flow and ammonia extraction fraction using nitrogen-13 ammonia and positron emission tomography.
This report describes the theoretical basis and a method to quantitate regional myocardial blood flow (RMBF) and ammonia extraction fraction (E) in man, noninvasively, with N-13 ammonia and positron emission tomography (PET). Two patients with hypertrophic cardiomyopathy, whose left ventricular (LV) walls were markedly thick, were employed in this study to avoid partial volume effects and cross contamination between LV walls and blood pool. RMBF and E were calculated from time-activity curves of myocardial tissue and left atrium derived from serial 6-second PET images of the heart. The time-activity curve of left atrium was used as an arterial input function. The results were RMBF = 67 +/- 4 ml/min/100 g, E = 80 +/- 13% and 65 +/- 10 ml/min/100 g, 81 +/- 16% for each patient. The validity of the present method was discussed.


An Assessment of Nutrition Education in Endocrinology Fellowship Programs in the United States.
Counseling patients about nutrition significantly improves chronic disease outcomes. Endocrinologists are uniquely positioned to educate patients regarding nutrition. The purpose of this study was to define the current state of nutrition education in endocrinology fellowship programs in the United States and assess the needs for future nutrition training. Endocrinology program directors were surveyed via an online questionnaire between February and April 2021. Thirty-eight program directors responded (25% response rate) to the survey. Twenty-two (58%) programs offered nutrition education. Existing nutrition education offerings were 1 to 5 total hours (13, 34%), primarily didactic (20, 53%), and often led by registered dietitian nutritionists (15, 39%). Only 3 (8%) programs rated their current nutrition education as extremely effective; 95% of respondents believed that further nutrition education was needed. According to respondents, the ideal nutrition education for endocrine trainees should be 1 to 5 total hours (19, 50%) over multiple sessions (25, 66%), be interactive (24, 63%), and be led by registered dietitian nutritionists (26, 68%). The most important topics for independent practice included diet-related behavior modification (21, 55%), components of a healthful diet (19, 50%), and energy expenditure/intake (18, 47%). Although the majority of the program directors believe that further nutrition education is needed, almost half of the surveyed programs do not offer such training. Programs that offer nutrition education primarily rely on a didactic format. There is an unmet need for interactive, multidisciplinary nutrition education in these programs.


Possible HIV transmission modes among at-risk groups at an early epidemic stage in the Philippines.
A concentrated human immunodeficiency virus (HIV) epidemic might have started in the Philippines. A subsequent characterization of viruses was carried out to estimate HIV transmission modes. Most HIV strains from injecting drug users belonged to subtype-B. CRF-01 was a major subtype harbored by three other at-risk populations: male visa applicants who had sex with men, "men who have sex with men," and visa applicants. An HIV phylogeny suggested that two strain groups of injecting drug users and others circulated separately. In contrast, there was substantial genetic overlap between two strain groups from "men who have sex with men" and visa applicants. Mean nucleotide distance within strains was shorter among subtype-B strains harbored by the injecting drug users (0.010) than among CRF-01 strains of the other three populations: male visa applicants who had sex with men (0.034), "men who have sex with men" (0.023), and visa applicants (0.032). Closely related strains of hepatitis C virus were derived from not only HIV-positive but also -negative individuals. These results suggest that there is potential for transmission from visa applicants to "men who have sex with men," and that once HIV occurs in injecting drug users, it spreads rapidly among them. Close contacts of hepatitis C virus carriers composed of HIV-negative and -positive individuals indicated ongoing HIV spread via blood and possible intervention points. Large-scale analysis is needed to provide more precise information on the transmission directions and to help curb the growth of this HIV epidemic in the Philippines.


Systematic review of the evidence of a relationship between chronic psychosocial stress and C-reactive protein.
C-reactive protein (CRP) is an acute-phase reactant with an increasing number of clinical functions. Studies in recent years have identified several social, economic, demographic, and psychological factors that contribute to baseline inflammation. Psychosocial stress represents a significant contributor to baseline inflammation. Given the importance of understanding background drivers of CRP levels, we conducted this review to assess the impact of chronic psychosocial stress on CRP levels. Medline was searched through February 2013 for human studies examining CRP levels with respect to chronic psychosocial stress. The initial search identified 587 articles from which 129 potentially appropriate articles were reviewed. Of these 129 articles, 41 articles were included in the review. These studies were published between 2003 and 2013. Of these studies, 6 analyzed employment stress, 2 analyzed unemployment stress, 6 analyzed burnout and vital exhaustion, 6 analyzed caregiver stress, 3 analyzed interpersonal stress, 17 analyzed socioeconomic position, and 2 analyzed discrimination. We conclude that psychosocial stress significantly impacts CRP and should be considered when interpreting the meaning of CRP elevations.


Blunted kaliuresis after an acute oral potassium load in diabetes mellitus.
It is unknown whether diabetic patients without renal failure or aldosterone deficiency respond normally to potassium administration. Acute oral potassium-loading was carried out in eight diabetic patients with modestly reduced creatinine clearance (Ccr) and in 11 diabetic patients and 13 controls with normal clearances. Only one diabetic patient manifested an inappropriately low upright plasma aldosterone level (6 ng/dL). The percentage of potassium excreted in 4 hour by both groups of diabetic patients was significantly less than that of the controls (decreased Ccr:21% +/- 6%, normal Ccr:36% +/- 5%, controls:54% +/- 5%; p less than 0.01 and 0.05 respectively). On the other hand, the estimated amount of potassium translocated intracellularly tended to be greater in the diabetic patients (18 +/- 3 mmol; 11 +/- 3 mmol) than controls(7 +/- 2 mmol; p less than 0.005 and 0.1 respectively), and the ratio of the increase in plasma (K) to the amount of potassium retained, was lower in diabetic patients, probably indicating enhanced intracellular potassium translocation. The authors conclude that diabetic patients with normal or only slightly reduced renal function (and no aldosterone deficiency) may have a reduced capacity to excrete an acute potassium load but an enhanced capacity to transfer potassium intracellularly.


Active and inactive renin in normal human plasma. Comparison between acid activation and cryoactivation.
Inactive renin in human plasma is converted to active renin in vitro by acid activation or by cryoactivation. Renin activity was measured at pH 5.5 and renin concentration at pH 7.4. The plasma renin activity before and after cryo-treatment is termed active (APRA) and total (TPRA) plasma renin activity; the plasma renin concentration before and after acid treatment active (APRC) and total (TPRC) plasma renin concentration. In this study we demonstrated that in normal subjects the proportion of active to total renin after cryo-treatment averaged 61%, which was significantly (p less than 0.001) higher than the mean percentage active renin of 34 found with the acid activation procedure. Plasma angiotensin II correlated significantly with APRA, TPRA, TPRC and plasma angiotensin I (PA I), but not with inactive renin, which suggests that inactive renin does not produce angiotensin II in vivo. Cold treatment after acid activation and acid treatment after cryoactivation did not provoke a significant change in the measured renin concentration. Our data support the view that acidification of the plasma activates more than does cryo-treatment, and that inactive renin does not contribute to plasma angiotensin II.


Methylation of arenes via Ni-catalyzed aryl C-O/F activation.
Aryl C-O and C-F can be transformed into C-Me via Ni-catalyzed coupling with MeMgBr under mild conditions.


Wetting behavior of flax fibers as reinforcement for polypropylene.
The wetting behavior of several flax (cellulose as reference) and polypropylene fibers is characterized by measuring the wetting rates (penetration velocities) of a series of liquids using the capillary rise technique. This present paper aims to provide a deeper understanding of the complex nature of natural fibers and their surface properties. The fiber surface tensions are estimated from plots of the normalized wetting rate as a function of the surface tension of the liquids assuming, in analogy to Zisman's method, that the maximum of the normalized wetting rate corresponds to the solid surface tension. The estimated surface tensions of the investigated flax fibers indicate that all the fibers are quite "hydrophobic." The method used to separate the fibers from the rest of the plants has a large influence on the estimated fiber surface tensions. In the case of polypropylene (PP) fibers, the estimated surface tension corresponds well with literature data. Grafting small amounts of maleic acid anhydrite (MAH) onto the PP surfaces will not affect the wetting behavior and, therefore, the surface tension, whereas grafting larger amounts (10 wt%) of MAH causes the polymer surface tension to increase significantly. Additional pH-dependent zeta-potential measurements show that even the "pure" PP-fibers contain acidic surface functions, possibly due to further processing at elevated temperatures (thermal degradation or other aging processes).


Early (300-100 B.C.) temple precinct in the Valley of Oaxaca, Mexico.
Archaeological investigations during the past two decades in Mexico's Valley of Oaxaca have documented the appearance of key public buildings, such as the royal palace and multiroom temple, associated with the rise of an archaic state at ca. 300-100 B.C. A fuller picture is now emerging from the site of El Palenque, where recent excavations have defined a temple precinct on the east side of the site's plaza. This precinct exhibits characteristics similar to those of the temple precincts of later Mesoamerican states described by Colonial period sources. The excavation data document a walled enclosure containing three multiroom temples, two special residences identified as priests' residences, and an array of ritual features and activity areas. The temple precinct's components are interpreted as comprising a hierarchy of temples staffed by a specialized priesthood. A series of radiocarbon dates indicate that the precinct's differentiated components were all in use during the 300-100 B.C. period of archaic state emergence. The El Palenque temple precinct is the earliest temple precinct excavated thus far in the Valley of Oaxaca.


The female carrier of haemophilia--a problem for the anaesthetist.
Three case histories reflect the difficulties of pre-operative assessment and management of female obligatory carriers for Factor VIII or Factor IX deficiency (haemophilia). The dangers of operation in these individuals is emphasized in view of the often confusing laboratory and clinical findings in this group of patients. A protocol is presented which, if used by the anaesthetist, will provide for logical and safe diagnostic and therapeutic approaches for these patients.


Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts.
Cytokine-induced killer (CIK) cells are CD3(+)CD56(+) non-major histocompatibility complex (MHC)-restricted immune effector cells. The present report demonstrates that it was possible to expand CIK cells obtained at diagnosis from patients with acute leukaemia. The percentage of CD3(+)CD56(+) CIK cells generated following culture ranged between 7.6% and 65% (median of 35.3%) and these cells were able to kill the human natural killer target K562 cells. Although the same effector cells were able to lyse autologous acute myeloid leukaemia (AML) target cells, they were not able to lyse autologous acute lymphoblastic leukaemia target cells. Pre-absorption of the CIK effector cells by K562 cells did not completely abrogate the cytotoxicity of CIK cells against autologous blasts in 9 out of 12 samples tested. Moreover, it was observed that the cytotoxicity generated by the CIK effector cells against allogeneic leukaemic blasts was similar to that against autologous blasts. The present study suggests the potential application of CIK cells in the immunotherapy of AML, either in minimal disease state, as donor lymphocyte infusion in relapse post allogeneic transplant, or in cases of chemotherapy refractory leukaemia.


Maternal probiotics supplementation improves immune and antioxidant function in suckling piglets via modifying gut microbiota.
Probiotics could improve the health, growth, and development of host or their foetuses/offspring via regulating gut microbiota. The present study was conducted to determine the effects of maternal probiotics supplementation on gut microbiota and metabolites of sows and their suckling piglets, as well as plasma biochemical parameters, oxidative/anti-oxidative indexes, and inflammatory cytokine levels of suckling piglets. A total of 32 pregnant Bama mini-pigs were selected and randomly divided into two groups. The sows were fed a basal diet (control group) or a basal diet supplemented with probiotics (probiotics group) from mating to day 21 of lactation. Samples from sows were collected on day 105 of pregnancy and day 21 of lactation and from piglets on day 21 of lactation. The results showed that probiotics supplementation increased the faecal abundances of Ruminococcus, Bacteroides, and Anaeroplasma and decreased Tenericutes on day 105 of pregnancy while increased the abundances of Actinobacteria and Anaerostipes and decreased Proteobacteria and Desulfovibrio on day 21 of lactation. In addition, probiotics supplementation decreased the faecal levels of tryptamine, putrescine, and cadaverine on day 105 of pregnancy and isovalerate and skatole on day 21 of lactation while increased butyrate level on day 21 of lactation. Further studies showed that maternal probiotics supplementation decreased the plasma levels of AMM, TC, LDL-C, Ala, Tau, MDA, H2 O2 , IL-1β, IL-2, IL-6, and IFN-α of suckling piglets. Moreover, maternal probiotics supplementation increased the abundances of Deferribacteres, Fusobacteria, and Fusobacterium while decreased Anaerostipes in piglet's colon. Spearman's correlation analysis revealed a potential link between gut microbiota alterations and their metabolites. Dietary probiotics supplementation during pregnancy and lactation periods could improve sow status, alleviate oxidative stress and inflammation response, and improve nutrient metabolism of piglets by altering the gut microbiota. The probiotics alter maternal and offspring's gut microbiota involving in offspring's physiological and metabolic changes, and present a new perspective that the effects of gut microbiota changes induced by probiotics supplementation will help in addressing the growth and development and health problem of their foetuses/offspring.


Induced concealed dissimilar atrial rhythms.
Electrophysiologic studies, including intra-atrial recordings and atrial stimulation, were performed in two patients with suspected sick sinus syndrome. Premature atrial stimuli induced atrial flutter in both patients. The arrhythmia was concealed, i.e., it was recordable only by intracavitary electrogram and invisible on surface electrocardiogram. In one case, simultaneous atrial fibrillation could be recorded in a segment of the right atrium. In this patient, the rhythm on the surface electrocardiogram changed during the study to "upper nodal" rhythm, though the atrial electrogram showed continuation of A waves at the same rate as before during sinus rhythm. It seems that atrial changes, which are frequently encountered in sick sinus syndrome, are a predisposing factor for spontaneous or inducible concealed atrial arrhythmias.


Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a.
Glioma is one of the most common and aggressive primary malignant tumor in the brain. Accumulating evidences indicated that aberrantly expressed non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), contribute to tumorigenesis. However, potential mechanisms between lncRNAs and miRNAs in glioma remain largely unknown. Long non-coding RNA activated by TGF-β (LncRNA-ATB) expression in glioma tissues and cells was quantified by quantitative reverse transcription-PCR. Glioma cell lines U251 and A172 were transfected with sh-ATB, miR-200a mimics, miR-200a inhibitors, after we assayed the cell phenotype and expression of the relevant molecules. Dual-luciferase reporter assay, RIP and a xenograft mouse model were used to examine the expression of sh-ATB and its target gene miR-200a. ATB is abnormally up-regulated both in glioma tissues and cell lines compared with normal brain tissues, and glioma patients with high ATB expression had shorter overall survival time. Knockdown of ATB significantly inhibits glioma malignancy, including cell proliferation, colony formation, migration, invasion in vitro, and the xenograft tumor formation in vivo. In addition, ATB was confirmed to target miR-200a, and miR-200a inhibition reversed the malignant characteristics of ATB knockdown on glioma cells. In particular, ATB may act as a ceRNA, effectively becoming a sink for miR-200a, thereby modulating the derepression of TGF-β2. Our findings suggest that ATB plays an oncogenic role of glioma cells by inhibiting miR-200a and facilitating TGF-β2 in glioma, thereby may represent a potential therapeutic target for the treatment of human glioma.


[Causes and incidence of self-mutilation in severely mentally handicapped patients].
Without regard to early childhood self-injurious behaviour is as a rule therapeutic difficulty to influence. Therefore analysis of the joint of causes is relevant for prevention. Among 87 hospitalized oligophrenic patients there were 10 with self injury, their sensibility for pain was considerably diminished at least. Early hospitalization resp. missing or very early deficit of maternal affection and of familiar contacts on the whole are considered to be a risk for later severe self injury.


Three-dimensional inversion rendering in the first- and early second-trimester fetal brain: its use in holoprosencephaly.
To explore the feasibility and added value of three-dimensional (3D) inversion rendering of the developing embryonic/fetal ventricular system, and to apply this display technique to enhance the sonographic examination of holoprosencephaly. 3D volumes of the embryonic/fetal brain were acquired from four normal fetuses at 8-11 postmenstrual weeks, and four fetuses diagnosed with holoprosencephaly between 9 and 14 postmenstrual weeks. The volumes were then analyzed offline to obtain inversion rendered 3D shapes of the ventricular systems. All inversion rendering displays were successful and provided the opportunity to study normal as well as pathological aspects of the early fetal brain. Inversion rendering of early fetal brain ventricles is feasible and should be attempted if additional information about the early normal or pathological fetal brain is needed. It may have scientific value in embryologic or genetic studies.


Acid-Catalyzed RNA-Oligomerization from 3',5'-cGMP.
The assembly of ancient informational polymers from nucleotide precursors is the central challenge of life's origin on our planet. Among the possible solutions, dry polymerization of 3',5'-cyclic guanosine monophosphate (3',5'-cGMP) has been proposed as a candidate to create oligonucleotides of 15-20 units in length. However, the reported sensitivity of the reaction to the presence of cations raised questions of whether this chemistry could be relevant in a geological context. The experiments in this study show that the presence of cations is not restrictive as long as the reaction is conducted in an acidic environment, in contrast to previous reports that suggested optimal conditions at pH 9.


Microbial keratitis following accelerated corneal collagen cross-linking.
A deep stromal infiltrate with hypopyon appeared in central cornea of right eye of a 15-year-old boy postoperatively after 2 days, who underwent uneventful accelerated corneal collagen crosslinking (C3R) with riboflavin and ultraviolet-A (UVA) for the treatment of keratoconus. Staphylococcus aureus keratitis was confirmed by the microbiological studies, which guided intense treatment with topical and systemic antibiotics. Before C3R, the best corrected visual acuity (BCVA) in the ocular dexter was 20/30 with the refraction of - 1.00 DS/-5.00 DC × 30° with drop to 20/400 following the infection. After intensive treatment BCVA recovered to 20/40 with the refraction of -4.0 DC × 60° at 6 months postprocedure. Slit lamp examination at this stage revealed a faint nebulo-macular grade scar in the central cornea involving visual axis. Collagen crosslinking with riboflavin-UVA is a minimally invasive method, but traditionally requires epithelial removal, which could be a predisposing factor to bacterial keratitis.


New concepts in perinatal hypoxia ischemia encephalopathy.
This article summarizes recent insights into perinatal hypoxic-ischemic brain injury in the neonate. Before effective treatments can be offered, diagnosis, timing, and an understanding of the pathogenesis are imperative. The analysis of appropriate animal models is also summarized in this review. These models have provided interesting evidence that after hypoxia ischemia, progenitor cells in the postnatal brain are stimulated to generate new neurons and oligodendrocytes. The role of these newly generated cells is unclear, and mechanisms of migration and survival are currently being elucidated. A discussion of more recent imaging techniques, such as diffusion tensor imaging, is provided. This allows for improved understanding of the microstructural organization of white matter and how this is altered by hypoxic-ischemic injury. Neuroprotection with hypothermia is now occurring in full-term neonates that meet clinical criteria; however, specific therapies such as inhibition of non-N-methyl-D-aspartate receptors may offer improved outcomes by targeting specific pathways and populations of cells.


Visual Assessment of Chest Computed Tomography Findings in Anti-cyclic Citrullinated Peptide Antibody Positive Rheumatoid Arthritis: Is it Associated with Airway Abnormalities?
We aimed to evaluate the association between specific anti-cyclic citrullinated peptide antibody (ACCPA) and pulmonary abnormalities in rheumatoid arthritis (RA) subjects. Computed tomography (CT) images of 83 subjects with RA were evaluated in a blind fashion. Enrolled subjects underwent autoantibody testing to determinate titer of ACCPA and rheumatoid factor, and pulmonary function testing. Visual CT assessment included lobar analysis for extent of semi-quantitative total interstitial lung disease score (ILDS) and each airway abnormality score (bronchiectasis, bronchial wall thickening, centrilobular nodules, and expiratory air trapping). Correlation tests, and simple and multiple regression analyses were performed to determine the relationship between the visual CT abnormalities, physiologic parameters, and autoantibody titers. ACCPA-positive subjects had a greater extent and higher prevalence of small airway abnormalities including centrilobular nodules and air trapping compared to ACCPA-negative subjects (all p < 0.05). Bronchiectasis and bronchial wall thickening correlated with the ratio of forced expiratory volume in 1 s and forced vital capacity (FVC) (r = -0.236 and r = -0.329, all p < 0.05), and ILDS correlated with FVC and the diffusing capacity of the lung for carbon monoxide (r = -0.218 and r = -0.366, all p < 0.05). Bronchial wall thickening and air trapping correlated with ACCPA titers (r = 0.235 and r = 0.264, all p < 0.05). Air trapping and bronchial wall thickening were significantly associated with ACCPA titers. In ACCPA (+) RA, visual CT assessment of large and small airways beyond RA-ILD, which is attributable to RA-related autoimmunity, can provide valuable information regarding airway abnormalities, regardless of the patients' physiologic airflow limitations.


Colon cancer and solar ultraviolet B radiation and prevention and treatment of colon cancer in mice with vitamin D and its Gemini analogs.
It has been recognized that people who live at higher latitudes and who are vitamin D deficient are at higher risk of dying from many common cancers including colon cancer. To evaluate the role of vitamin D deficiency on colon tumor growth, Balb/c adult male mice were fed either a vitamin D sufficient or vitamin D deficient diet for 10 weeks. Mice were arranged into groups of six and each animal received subcutaneously 10(4) MC-26 cells in the posterior trunk. The tumor size was recorded daily. By day 9 there was a significant difference in tumor volume between the vitamin D sufficient and vitamin D deficient mice. By day 18 the vitamin D deficient animals had a tumor size that was 56% larger compared to the animals that were vitamin D sufficient. To determine whether treatment with active vitamin D analogs could further decrease colon tumor growth in a vitamin D sufficient state, groups of mice were treated with the novel 19-nor-Gemini compounds. The mice were fed a low calcium diet. Twenty-four hours after tumor implantation, the mice received, three times weekly, one of the vitamin D analogs or the vehicle. The group that received Gemini 1,25-dihydroxy-21(3-hydroxy-3-trifluoromethyl-4-trifluoro-butynyl)-19-nor-20S-cholecalciferol (3) showed a dose-dependent decrease in tumor volume. On day 19, at the dose level of 0.02microg molar equivalents (E), the tumor volume was reduced by 41% when compared to the control group. At the same time point, the hexadeuterated analog 1,25-dihydroxy-21(3-hydroxy-3-trifluoromethyl-4-trifluoro-butynyl)-26,27-hexadeutero-19-nor-20S-cholecalciferol (4), administered at the 10-fold lower dose of 0.002microgE, showed a 52% reduction in tumor volume (p<0.05), compared to the control group. Animals that received 1,25(OH)(2)D(3) at 0.002 and 0.02microg showed a trend in tumor volume reduction at the highest dose but the changes were not statistically significant. An evaluation of serum calcium concentrations revealed that the calcium levels were normal in all groups, except the group receiving 0.02microgE of 4. The results from these studies demonstrate that vitamin D deficiency may accelerate colon cancer growth and that novel Gemini analogs of 1,25(OH)(2)D(3) may be an effective new approach for colon cancer treatment.


Discovery and functional analysis of a 4th electron-transferring tryptophan conserved exclusively in animal cryptochromes and (6-4) photolyases.
A 4th electron transferring tryptophan in animal cryptochromes and (6-4) photolyases is discovered and functionally analyzed by transient absorption. It yields a much longer-lived flavin-tryptophan radical pair than the mere tryptophan triad in related flavoproteins, questioning the putative role of the primary light reaction of cryptochrome in animal magnetoreception.


HTS Shim Coils Energized by a Flux Pump for the MIT 1.3-GHz LTS/HTS NMR magnet: Design, Construction, and Results of a Proof-of-Concept Prototype.
In this paper we present design, construction, and preliminary results of a proof-of-concept prototype of high-temperature superconductor (HTS) shim coils operated at 77 K and energized, for the first time among all shim coils, by a flux pump, here called digital flux injector (DFI). Although the prototype shims were wound with 2-mm wide REBCO tape, and DFI with Bi2223 and REBCO tapes, the HTS Z1 and Z2 shims to be installed in the MIT 1.3-GHz LTS/HTS NMR magnet (1.3G) currently under construction and operated at 4.2 K will be wound with reinforced Bi2212 wire and DFI with Nb3Sn tape. The paper concludes with two sets of Bi2212 Z1 and Z2 shims for 1.3G.


The role of thoracoscopy in the evaluation and management of pleural effusions.
Diagnostic thoracoscopy is indicated in every patient where the usual investigations (including biochemistry, cytology, bacteriology, occasionally needle biopsy of the pleura) do not achieve a precise diagnosis. The percentage of so-called "idiopathic" effusions, amounting to approximately 20% in many published series, can be reduced to 4% after thoracoscopy. The sensibility of thoracoscopic biopsy reaches 93-97% of malignant or tuberculous pleural effusions. The procedure requires a short hospitalization of about 36 hr, and complications are rare. Therapeutic thoracoscopy is frequently performed in chronic, malignant, recurrent effusions in order to achieve a pleurodesis by means of a talc poudrage under visual control. The efficacy of the poudrage in the published randomized studies is better than tetracycline. About 90% of patients are cured, the effusion being totally suppressed. Side effects are rare if the quantity of talc does not exceed 10 ml.


Residential swimming pools maintenance under an environmental perspective.
Swimming pools provides various benefits for users, but their owners need to carry out constant maintenance to ensure water quality and user safety. This paper goal was to assess the maintenance process of residential swimming pools, through Life Cycle Assessment based on NBR ISO 14040:2014 and NBR 14044:2014. The standard steps were followed and primary data on materials and quantities for the treatments were collected during 2022. The purchase costs of the treatment process were obtained, which based the cost analysis. The Impact Assessment Method used was the ReCiPe Endpoint (H) 2016, which assesses damage across three categories. The water, electricity and hypochlorite production processes were the most impactful in the categories of damage to human health, ecosystems and resources availability. These inputs production have an intense natural resources consumption and causes emissions into the environment. The highest expenses in pool maintenance were associated to human resources (worker) and chlorine purchase, followed by electricity. Scenarios were created to identify feasible changes to reduce the impacts. The waiver of water for replacement in the rainy season had greater potential for reducing impacts than the consumption changes in electricity and chlorine.


Artificial Intelligence Platform Demonstrates High Adherence in Patients Receiving Fixed-Dose Ledipasvir and Sofosbuvir: A Pilot Study.
This study evaluated health outcomes among people who inject drugs who are infected with hepatitis C virus using an artificial intelligence platform. Mean (SD) cumulative adherence (visual confirmation of administration) was 91.3% (10.5%). Most subjects (88.2%) achieved ≥80% adherence to treatment, and 88.2% (15 of 17) achieved a sustained virologic response.


Immunomodulatory activity of thunberginol A and related compounds isolated from Hydrangeae Dulcis Folium on splenocyte proliferation activated by mitogens.
We investigated the immunomodulatory effects of antiallergic constituents from Hydrangeae Dulcis Folium, the processed leaves of Hydrangea macrophylla SERINGE var. thunbergii MAKINO, on splenocyte proliferation in mice. Thunberginol A and hydrangenol significantly suppressed T lymphocyte proliferation induced by concanavalin A. Thunberginol A also suppressed B lymphocyte proliferation induced by lipopolysaccharide, but other constituents induced significant increases. These inhibitory effects of thunberginol A on splenocyte proliferation seemed to contribute to the suppressive effect on type IV allergy.


Seasonal changes in the prevalence of Haemonchus and Trichostrongylus hypobiotic larvae in tracer goats in Malaysia.
An investigation into the seasonal changes in the population structure of Haemonchus and Trichostrongylus in tracer goats was conducted over 12 months at Serdang, an area in southern West Malaysia with year-round tropical rainfall. Successive groups of parasite-free tracer goats were grazed for a month alongside naturally infected adult goats and necropsied for worm counts 14 days after their removal from pasture. No hypobiotic larvae of Trichostrongylus were recovered. Hypobiotic larvae of Haemonchus were evident during each month of the year but accounted for only a very small proportion of the total Haemonchus burden. Very low levels were encountered from December through to June. Comparatively higher levels of hypobiosis were observed thereafter with a peak of 7.4% in September. The factors responsible for hypobiosis were not clearly defined but the phenomenon was associated with increasing levels of soil moisture storage. Host resistance, adult worm population of tracers and population of ingested L3 were ruled out as possible inducing factors.


The impact of a computerized decision aid on empowering pregnant women for choosing vaginal versus cesarean section delivery: study protocol for a randomized controlled trial.
Cesarean delivery on maternal request (CDMR) is one of the main reasons for cesarean delivery in Iran, and women often need help in making a decision about the delivery options available to them. The main objective of this study is to evaluate the effect of a computerized decision aid (CDA) system on empowering pregnant women in choosing an appropriate mode of delivery. This CDA contrasts the advantages and disadvantages of vaginal versus cesarean section delivery in terms of their value to the individual woman. The protocol concerns a randomized trial study that will be performed among Iranian women. Four hundred pregnant women will be recruited from two private and two public prenatal centers in Mashhad, Iran. They will be randomly assigned to either an intervention or a control group. The designed CDA will be provided to the intervention group, whereas the control group will only receive routine care. The CDA provides educational contents as well as some recommendations. The CDA's knowledge base is obtained from the results of studies on predictors of cesarean delivery. The CDA's software will be installed on women's computers for use at home. The two primary outcomes for the study are O'Connor's Decisional Conflict Scale and knowledge as measured by true/false questions. Actual mode of delivery (vaginal versus cesarean) will be compared in the two groups. We investigate the effect of a CDA on empowering pregnant women in terms of reducing their decisional conflict as well as on improving their clinical knowledge pertaining to mode of delivery. This trial is registered with the Iran Trial Registrar under registration number IRCT2015093010777N4 and registration date 26 October 2015.


Intracranial haemodynamics in diffuse and focal brain injuries. Evaluation with transcranial Doppler (TCD) ultrasound.
Intracranial haemodynamics were studied in 20 patients with diffuse and focal brain injury and experimental animals with acute intracranial hypertension by the use of TCD ultrasound. The mean flow velocity in the middle cerebral artery (MCA) commonly decreased on the side of the haematoma depending on intracranial pressure (ICP) elevation and cerebral perfusion pressure (CPP) reduction in focal injury. The decrease of the MCA flow velocity returned to normal after treatment. The flow velocities decreased bilaterally and there was no difference between the right and left side in diffuse injury. But the velocities increased in spite of ICP elevation when diffuse cerebral swelling developed. Cerebrovascular CO2 reactivity was impaired in two groups of patients with low Glasgow Coma Scale (GCS) scores. The mean velocity of the MCA and blood flow in the internal carotid artery exhibited flow patterns which changed correlatively depending on CPP reduction in experimental animals. Noninvasive study by use of TCD ultrasound can provide valuable information on variant haemodynamic phenomena in patients with diffuse and focal brain injury.


Structural basis of organic cation transporter-3 inhibition.
Organic cation transporters (OCTs) facilitate the translocation of catecholamines, drugs and xenobiotics across the plasma membrane in various tissues throughout the human body. OCT3 plays a key role in low-affinity, high-capacity uptake of monoamines in most tissues including heart, brain and liver. Its deregulation plays a role in diseases. Despite its importance, the structural basis of OCT3 function and its inhibition has remained enigmatic. Here we describe the cryo-EM structure of human OCT3 at 3.2 Å resolution. Structures of OCT3 bound to two inhibitors, corticosterone and decynium-22, define the ligand binding pocket and reveal common features of major facilitator transporter inhibitors. In addition, we relate the functional characteristics of an extensive collection of previously uncharacterized human genetic variants to structural features, thereby providing a basis for understanding the impact of OCT3 polymorphisms.


Protein kinase activity of purified components of the chicken oviduct progesterone receptor.
Preparations of the 90K and 110K components of the chick oviduct progesterone receptor (PR) purified to near homogeneity were tested for protein kinase activity. The 90K component was shown to incorporate radioactive phosphate from [gamma-32P]-ATP in the presence of Ca2+ but not of Mg2+ ions, while the 110K component was phosphorylated in the presence of Mg2+, but not of Ca2+. The enzymatic activity of the 90K polypeptide appeared selective, since added proteins (histones) did not become phosphorylated. However, all proteins present in the 110K preparations were phosphorylated in the presence of Mg2+. These data suggest that components of the chick oviduct PR display protein kinase activity.


Development of Trityl Group Anchored Solubilizing Tags for Peptide and Protein Synthesis.
Recently, solubilizing tag methods (Trt-K and Trt-R method) were developed for the challenging synthesis of peptides/proteins by means of native chemical ligation. In this system, the solubilizing tag can be attached to the Cys side chain by simply mixing the tag-introducing reagent under acidic conditions. The tagged peptides/proteins exhibited high water solubility thanks to the introduction of redundant oligo-Lys/Arg. In the final reaction, the tag can be quickly and cleanly detached by a standard deprotection reaction with trifluoroacetic acid. Herein, the development and application of these methods are described.


Changing Landscape of Systemic Therapy in Biliary Tract Cancer.
Biliary tract cancers (BTC) are often diagnosed at advanced stages and have a grave outcome due to limited systemic options. Gemcitabine and cisplatin combination (GC) has been the first-line standard for more than a decade. Second-line chemotherapy (CT) options are limited. Targeted therapy or TT (fibroblast growth factor 2 inhibitors or FGFR2, isocitrate dehydrogenase 1 or IDH-1, and neurotrophic tyrosine receptor kinase or NTRK gene fusions inhibitors) have had reasonable success, but <5% of total BTC patients are eligible for them. The use of immune checkpoint inhibitors (ICI) such as pembrolizumab is restricted to microsatellite instability high (MSI-H) patients in the first line. The success of the TOPAZ-1 trial (GC plus durvalumab) is promising, with numerous trials underway that might soon bring targeted therapy (pemigatinib and infrigatinib) and ICI combinations (with CT or TT in microsatellite stable cancers) in the first line. Newer targets and newer agents for established targets are being investigated, and this may change the BTC management landscape in the coming years from traditional CT to individualized therapy (TT) or ICI-centered combinations. The latter group may occupy major space in BTC management due to the paucity of targetable mutations and a greater toxicity profile.