Stereotactic radiosurgery for Spetzler-Martin Grade III arteriovenous malformations: an international multicenter study.
OBJECTIVE Because of the angioarchitectural diversity of Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs), the management of these lesions is incompletely defined. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after stereotactic radiosurgery (SRS) for SM Grade III AVMs and to determine the factors predicting these outcomes. METHODS The authors analyzed and pooled data from patients with SM Grade III AVMs treated with SRS at 8 institutions participating in the International Gamma Knife Research Foundation. Patients with these AVMs and a minimum follow-up length of 12 months were included in the study cohort. An optimal outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Data were analyzed by univariate and multivariate regression analyses. RESULTS The SM Grade III AVM cohort comprised 891 patients with a mean age of 34 years at the time of SRS. The mean nidus volume, radiosurgical margin dose, and follow-up length were 4.5 cm3, 20 Gy, and 89 months, respectively. The actuarial obliteration rates at 5 and 10 years were 63% and 78%, respectively. The annual postradiosurgery hemorrhage rate was 1.2%. Symptomatic and permanent RICs were observed in 11% and 4% of the patients, respectively. Optimal outcome was achieved in 56% of the patients and was significantly more frequent in cases of unruptured AVMs (OR 2.3, p < 0.001). The lack of a previous hemorrhage (p = 0.037), absence of previous AVM embolization (p = 0.002), smaller nidus volume (p = 0.014), absence of AVM-associated arterial aneurysms (p = 0.023), and higher margin dose (p < 0.001) were statistically significant independent predictors of optimal outcome in a multivariate analysis. CONCLUSIONS Stereotactic radiosurgery provided better outcomes for patients with small, unruptured SM Grade III AVMs than for large or ruptured SM Grade III nidi. A prospective trial or registry that facilitates a comparison of SRS with conservative AVM management might further clarify the authors' observations for these often high-risk AVMs.


BRCA-FA pathway as a target for anti-tumor drugs.
Promising research on DNA repair signaling pathways predicts a new age of anti-tumor drugs. This research was initiated through the discovery and characterization of proteins that functioned together in signaling pathways to sense, respond, and repair DNA damage. It was realized that tumor cells often lacked distinct DNA repair pathways, but simultaneously relied heavily on compensating pathways. More recently, researchers have begun to manipulate these compensating pathways to reign in and kill tumor cells. In a striking example it was shown that tumors derived from mutations in the DNA repair genes, of BRCA-FA pathway, were selectively sensitive to inhibition of the base excision repair pathway. These findings suggest that tumors derived from defects in DNA repair genes will be easier to treat clinically, providing a streamlined and targeted therapy that spares healthy cells. In the future, identifying patients with susceptible tumors and discovering additional DNA repair targets amenable to anti-tumor drugs will have a major impact on the course of cancer treatment.


Targeted risk assessment of mercury exposure of recreational fishers: Are nephrops fishers in Norway at risk?
Recreational fishers often consume their catch, which may expose them to environmental contaminants. However, targeted risk assessment for exceeding the tolerable weekly intake (TWI) of a specific contaminant is often lacking, as specific data on the extent of fishing, consumption rates, and contamination of the caught seafood is needed. This study examined recreational fishing for nephrops (Nephrops norvegicus) at several different locations in Western Norway to identify important risk factors. The combination of a field survey to examine actual catches, interviews of recreational fishers about their seafood eating habits, and the analysis of total mercury (Hg, as a proxy for methylmercury (MeHg)) in recreationally captured nephrops allowed to conduct a targeted risk assessment. Recreational fishers consumed on average seven nephrops per meal, and 73% of the fishers ate nephrops once a month or more. The average Hg concentrations in nephrops were below the legal maximum level (100 ± 50 μg/kg wet weight (mean ± SD)). Hg concentrations in female nephrops were significantly higher than in males at the same size, and differed significantly between locations. The recreational fishers in this study were not at risk of exceeding the TWI for MeHg from consuming nephrops only; however, there is a general risk of exceeding TWI for MeHg as 70% of the fishers reported a frequent consumption of fish for dinner. Targeted risk assessments on recreational fishers may reveal particularly vulnerable populations where national dietary surveys may miss the highest seafood consumers.


Two genetic lineages of sea slaters, Ligia (Crustacea: Isopoda) in South Korea: a population genetic approach.
In this study, the species composition and population genetic properties of the sea slater, Ligia, in South Korea were investigated using mitochondrial and nuclear gene sequences. Two groups of sea slaters, genetically isolated from each other, a Western Group (WG) and an Eastern Group (EG) were identified. These groups exhibited considerable genetic divergence from Ligia exotica, previously recorded as a species inhabiting this country. These results indicate that there may be two species of Ligia in South Korea, but there is a small probability that both groups are L. exotica. A comparison of their genetic properties indicates that WG has a higher effective population size than EG, and that EG may have experienced a recent expansion, implying that it has a shorter history in South Korea than WG. These findings suggest that the South Korean sea slater populations may have been established as a result of several colonization events that can be traced on a continental scale by phylogeographic studies of sea slaters.


Vision assessment and rehabilitation in low vision.
This subjective review of the year's literature on low vision, with particular emphasis on rehabilitation, attempts to search out and discuss what is new and innovative rather than to cover the year's publications with equal weight. The review covers areas of testing and assessment of children and the multiply impaired with low vision, vision stimulation, low vision aids and devices, approaches in congenital and acquired nystagmus, potential advances in high-technology applied to low vision, and psychological and educational aspects including lighting requirements for the elderly.


[Significance of the hypertensive syndrome in the clinical aspects of the late residual stage of infantile cerebral palsy (based on ultrasonic encephalographic data)].
The report is concerned with an analysis of the results of an echoencphalographic study of 201 children with infantile cerebral paralysis in the form of spastic diplegia. The examined children were from 3-14 years with different degrees of motor disturbances and intellectual defects. The echoencephalograms in 22% of the cases detected a displacement of M-echo to 2 mm and more. In 20%--there were signs of a light dilatation of the III brain ventricle and in 41%--of moderate dilatation. A correlation of echoencephalographic data with clinical symptoms demonstrated that a displacement of M-echo signs of a dilation of the III ventricle are more frequently encountered in children with a more severe motor and intellectual deficiency. The authors studied the influence of a comprehensive treatment (medicamental therapy, therapeutic physical training, corrective training, physical and mental loadings on the liquorodynamic disbalance. The study demonstrates the informativeness of the echoencephalographic method not only in the detection of the hypertensive syndrome, but in defining the degree of its expressiveness and during the development of the hypertenensive syndrome under the influence of different therapeutical measures.


[Evaluation of clinical competence in the nursing profession].
The quality of health services depends on the competence of the health service professionals. It is essential to define and evaluate professional competences in order to improve professional development, ensure the quality of, and manage, professionals in terms of their competences. To do so, it is necessary to utilize a combination of different methods. The evaluation of the diverse stages related to nursing--at the end of undergraduate studies, postgraduate studies or specialization, and during independent work--has different proposals, content and methods; and the institutions implicated in these stages should make themselves responsible to acquire the professional which society needs. Since 1994, more than 150 projects have been carried out in Catalonia which confirm the validity, trustworthiness, acceptability and utility of these evaluative methods in undergraduate and postgraduate studies and in the selection and accreditation of professionals.


Gravity increase at the South pole.
Measurements made between December 1957 and January 1966 of the gravity difference between the McMurdo Sound pendulum station, which is on bedrock, and the South Pole station, which is on the Antarctic ice sheet, show a gravity increase at the South Pole of 0.11 milligals per year. The most likely hypothesis for the increase is that it was caused by ice flowing downslope across a gravity gradient and by the sinking of the South Pole station as a result of accumulation of ice. An alternate hypothesis that the gravity increase was caused by a decrease in ice thickness, of about 40 centimeters per year, is theoretically possible but is not supported by direct evidence.


Interaction of asymmetric ABCC9-encoded nucleotide binding domains determines KATP channel SUR2A catalytic activity.
Nucleotide binding domains (NBDs) secure ATP-binding cassette (ABC) transporter function. Distinct from traditional ABC transporters, ABCC9-encoded sulfonylurea receptors (SUR2A) form, with Kir6.2 potassium channels, ATP-sensitive K+ (K ATP) channel complexes. SUR2A contains ATPase activity harbored within NBD2 and, to a lesser degree, NBD1, with catalytically driven conformations exerting determinate linkage on the Kir6.2 channel pore. While homodomain interactions typify NBDs of conventional ABC transporters, heterodomain NBD interactions and their functional consequence have not been resolved for the atypical SUR2A protein. Here, nanoscale protein topography mapped assembly of monodisperse purified recombinant SUR2A NBD1/NBD2 domains, precharacterized by dynamic light scattering. Heterodomain interaction produced conformational rearrangements inferred by secondary structural change in circular dichroism, and validated by atomic force and transmission electron microscopy. Physical engagement of NBD1 with NBD2 translated into enhanced intrinsic ATPase activity. Molecular modeling delineated a complemental asymmetry of NBD1/NBD2 ATP-binding sites. Mutation in the predicted catalytic base residue, D834E of NBD1, altered NBD1 ATPase activity disrupting potentiation of catalytic behavior in the NBD1/NBD2 interactome. Thus, NBD1/NBD2 assembly, resolved by a panel of proteomic approaches, provides a molecular substrate that determines the optimal catalytic activity in SUR2A, establishing a paradigm for the structure-function relationship within the K ATP channel complex.


Enhancement of human basophil histamine release by interleukin 5.
Substantial evidence indicates a close relationship between eosinophils and basophils. We examined whether interleukin 5 (IL-5), known to be eosinophilopoietic and capable of selectively regulating eosinophil functions, has an affect on basophil functions. IL-5 enhanced basophil histamine release evoked by anti-IgE, formyl-methionyl-leucyl-phenylalanine, or ionophore A23187 at picomolar concentrations. Direct action of IL-5 on human basophils was confirmed using highly purified basophil populations. These observations reveal the novel fact that IL-5 is able to modulate basophil functions as well as eosinophil functions, and suggest that normal human basophils possess functional receptors for IL-5.


Heparin-induced modulation of insulin like-growth factor-I action on glucose level in control and fasted rats.
Insulin like-growth factor-I (IGF-I) circulates in serum bound to IGF-binding proteins (IGFBPs), which are important regulators of IGF's biological activity. There are at least two classes of BPs: a high molecular weight complex (HMWBPs) and low molecular weight species (LMWBPs), with different affinity for IGF-I. Their specific role in regulation of IGF-I bioactivity is still controversial. Since: a) IGF-I plays an important role in glucose counter regulation; b) heparin was shown to alter IGF-I affinity to BPs; and c) fasting is known to change quantity and quality of serum BPs, we decided to measure the in vivo effect of heparin on blood IGF-I, BPs and glucose levels in control and fasted rats. Control and fasted rats were injected i.v. with heparin (500 UI/100 g body weight) every hour during 3 hours of the experiment. Blood samples were collected before and 15 or 30 minutes after heparin injection and used for determination of free and bound IGF-I (RIA), BPs (radiometric assay) and glucose level (glucose oxidase method). Heparin treatment induced hypoglycaemia in fasted rats while it induced hyperglycemia in control one. The evidence was provided that heparin dissociates IGF-I from HMWBPs complex of control rat serum (predominant one in serum of these animals) and released IGF-I in turn is bound to LMWBPs--known as inhibitors of IGF-I dependent functions. In contrast, in fasted rat serum heparin dissociates IGF-I from LMWBPs (predominant complex in serum of these animals) making IGF-I free and available to stimulate IGF-I dependent functions. Therefore in control animals, which were administered heparin, blood glucose level was elevated and in fasted animals it was decreased. The data presented raise the possibility that IGF-BPs may have an important role in IGF-dependent glucose counter regulation and that heparin or heparin-like molecules may affect the process. Medical significance of heparin-induced hyperglycaemia in control animals should be taken into consideration since heparin is commonly used in clinical practice.


Acceptability, adherence and economic analyses of a new clinical pathway for the identification of non-responders to glaucoma eye drops: a prospective observational study.
Assess whether a new clinical pathway for glaucoma was acceptable to patients and healthcare professionals and whether it provided useful clinical information on non-responsiveness and non-adherence to the treatment of elevated intraocular pressure with latanoprost eye drops. A single arm non-randomised prospective observational study incorporating new glaucoma/ocular hypertension patients. To assess issues of acceptability, qualitative observation and interviews were conducted with patients and healthcare professionals. To determine clinical responsiveness, intraocular pressures were measured before and 4 hours after a clinician-instilled eye drop over two distinct appointments. Adherence data were collected using a Medicine Event Monitoring System. Economic analyses compared the costs between novel and standard care pathways. Of 72 patients approached, 53 entered the study (74.3%) and 50 completed all procedures (94.3%). Intraocular pressure was reduced more than 15% in 83 out of 92 study eyes by final visit (90.2%). The non-response rate was 5.1% once the effect of low adherence was minimised. For the 1376 drop instillation days under observation, eye drops were instilled as prescribed on 1004 days (73.0%), over-instilled on 137 days (9.9%) and not instilled on 235 days (17.1%). The Cardiff Model of Glaucoma Care involved negligible cost, although acceptance for healthcare professionals showed variation. The Cardiff Model of Glaucoma Care offers novel clinical and adherence insights at marginal costs while acceptable to patients. Healthcare professionals felt that 4 hour and 4 week follow-up appointments could cause administrative problems. A streamlined version of the pathway has therefore been developed to facilitate clinical adoption. ISRCTNID:ISRCTN75888393.


Machine learning with imaging features to predict the expression of ITGAV, which is a poor prognostic factor derived from transcriptome analysis in pancreatic cancer.
Radiogenomics has attracted attention for predicting the molecular biological characteristics of tumors from clinical images, which are originally a collection of numerical values, such as computed tomography (CT) scans. A prediction model using genetic information is constructed using thousands of image features extracted and calculated from these numerical values. In the present study, RNA sequencing of pancreatic ductal adenocarcinoma (PDAC) tissues from 12 patients was performed to identify genes useful in evaluating clinical pathology, and 107 PDAC samples were immunostained to verify the obtained findings. In addition, radiogenomics analysis of gene expression was performed by machine learning using CT images and constructed prediction models. Bioinformatics analysis of RNA sequencing data identified integrin αV (ITGAV) as being important for clinicopathological factors, such as metastasis and prognosis, and the results of sequencing and immunostaining demonstrated a significant correlation (r=0.625, P=0.039). Notably, the ITGAV high‑expression group was associated with a significantly worse prognosis (P=0.005) and recurrence rate (P=0.003) compared with the low‑expression group. The ITGAV prediction model showed some detectability (AUC=0.697), and the predicted ITGAV high‑expression group was also associated with a worse prognosis (P=0.048). In conclusion, radiogenomics predicted the expression of ITGAV in pancreatic cancer, as well as the prognosis.


Impaired delayed spatial win-shift behaviour on the eight arm radial maze following excitotoxic lesions of the medial prefrontal cortex in the rat.
The delayed spatial win-shift (DSWS) radial maze task requires that animals hold spatial information for reward location "on-line" both during task performance and across a delay. Temporary lidocaine inactivation of anterior cingulate (AC) and prelimbic (PL) regions of the rat medial prefrontal cortex (mPFC) has revealed dissociable effects on this task, suggesting different roles within working memory for each of these areas. However, further research has shown that mPFC deficits in the rat may only be transient in nature, particularly on the radial maze. The present study was conducted to examine the effects of permanent excitotoxic lesions of the mPFC in the DSWS task across repeated trials to assess whether change in the degree of impairment would occur over time. Results showed that rats with lesions centred on the prelimbic cortex (but with damage extending into the anterior cingulate) were impaired on the post-delay test phase of the DSWS task. This deficit was characterised by increased errors (both across and within phase), earlier error occurrence, and increased latencies. Only the number of choices correct before error improved across repeated test days. These results are consistent with the involvement of the rat mPFC in spatial working memory and response inhibition, supporting previous findings using transient lesions. However, the discovery that rats with mPFC lesions learned to delay the intrusion of errors into their choice sequence extends previous work, and provides support for studies showing that mPFC lesioned rats can improve some aspects of task performance given the opportunity to learn over repeated trials.


Comparative study of renal protective effects of allopurinol and N-acetyl-cysteine on contrast induced nephropathy in patients undergoing cardiac catheterization.
Objectives : To evaluate the difference in the renal protective effects of allopurinol and n-acetyl cysteine along with saline hydration in patients of contrast induced nephropathy (CIN) post cardiac interventions. CIN remains a common complication of cardiac procedures. Radio contrast agents can cause a reduction in renal function that may be related to oxidative stress underlining various patho- physiologies. Conflicting evidence suggests that administration of allopurinol, a xanthine oxidase inhibitor can prevent CIN. This is a study of 500 patients undergoing angiography and coronary revascularisation in patients showing significant coronary block. The angiography positive patients (275) were prospectively randomised to different treatment protocol to study for their reno-protective effect. The patients received either of the three drugs saline hydration (SH, 1ml/kg/hr), n-acetylcysteine (SH+NAC, 600 mg bd) or Allopurinol (SH+ALLP, 300 mg/day) 12 hours before and after administration of radio contrast agent. Levels of serum creatinine and blood urea of the 275 patients recorded at 24 hour interval were noted post angioplasty over a course of 5 days in patients receiving either omnipaque (125) or visipaque (150) contrast media. All the 500 patients were also assessed for development of any kind of adverse drug effects/reactions with the two contrast media. CIN occurred in 56 of 500 the patients (10.6%) who underwent angiography and 49 of 275 patients (17.8%) who underwent angioplasty. In the omnipaque group CIN occurred in 16/40, 8/40, nil/45 in patients receiving SH, NAC plus SH and SH plus ALLP respectively. In the visipaque group CIN occurred in 15/50, 10/50, nil/50 in the three treatments groups respectively. Allopurinol maintained a consistent fall in the serum creatinine & blood urea levels from the baseline values from the end of the 1(st) day (p < .01 & .001) in both the category. Visipaque proved to be better dye than omnipaque with less adverse drug effects/ reactions. Prophylactic oral administration of allopurinol (300 mg/day) along with hydration is better than n-acetylcysteine and saline hydration alone for protection against CIN in patients undergoing coronary procedures.


In vitro and in vivo evaluation of a fast-disintegrating lyophilized dry emulsion tablet containing griseofulvin.
Development of a fast-disintegrating lyophilized dry emulsion (LDE) tablet that enhanced the in vitro dissolution and in vivo absorption of griseofulvin (GF) is presented. The LDE tablets were prepared by freeze-drying o/w emulsions of GF, a drug for which bioavailability is known to be enhanced by fat co-administration. Oil-in-water emulsions were prepared using a gelatin solution (2%, w/v) as the water phase and medium chain triglycerides (Miglyol) or sesame oil as the oil phase. In addition, different emulsifiers were evaluated. The influence of formulation parameters on the disintegration and in vitro dissolution of GF from LDE tablets along with other tablet characteristics were investigated. A significant influence of the emulsifier type on the tablet disintegration time was seen (p<0.01). Results obtained from dissolution studies showed that LDE tablets of GF improved the dissolution rate of the drug compared to the plain drug. The extent of absorption of GF from a selected LDE tablet formulation as compared to an immediate release conventional tablet as reference after single oral dose (125mg) administration was determined in four healthy subjects using a randomized crossover design. In this study, the rate of absorption of GF from LDE tablet was faster than that from the reference tablet and had significantly higher (p=0.02) peak plasma concentration (more than three times higher) and shortened time to C(max) by 4h (p=0.014). The extent of absorption expressed by AUC was 85% larger as compared to the commercial tablet. Stability results, after 6 months storage of LDE tablets at 25 degrees C and 60% relative humidity, showed a slight increase in disintegration time and residual moisture content, while results from dissolution studies showed slightly slower initial drug release.


Dendritic anomalies in disorders associated with mental retardation.
Dendritic abnormalities are the most consistent anatomical correlates of mental retardation (MR). Earliest descriptions included dendritic spine dysgenesis, which was first associated with unclassified MR, but can also be found in genetic syndromes associated with MR. Genetic disorders with well-defined dendritic anomalies involving branches and/or spines include Down, Rett and fragile-X syndromes. Cytoarchitectonic analyses also suggest dendritic pathology in Williams and Rubinstein-Taybi syndromes. Dendritic abnormalities appear to have syndrome-specific pathogenesis and evolution, which correlate to some extent with their cognitive profile. The significance of dendritic pathology in synaptic circuitry and the role of animal models in the study of MR-associated dendritic abnormalities are also discussed. Finally, a model of genotype to neurologic phenotype pathway in MR, centered in dendritic abnormalities, is postulated.


Expression of cell cycle inhibitor p27 and Ki-67 in human adrenocortical neoplasms.
Recent immunohistochemical analysis of cell cycle-related proteins such as p27, a cell cycle inhibitory protein, and Ki-67, a proliferation marker, indicated their possible values in predicting the biologic behavior of various human neoplasms. In this study, we performed an immunohistochemical analysis of p27 and Ki-67 in 42 adrenocortical neoplasms (12 adrenocortical carcinomas, 24 adrenocortical adenomas) and 6 normal adrenal glands to evaluate their possible values in diagnosing adrenocortical malignancy and in predicting the biologic behavior of carcinomas. We detected Ki-67 and p27 immunoreactivity in the nuclei of all of our cases, and we observed a significant negative correlation (r = -0.572, P < .001) between the p27 and Ki-67 labeling indexes (LIs). The LIs of p27 and Ki-67 were 61.7+/-2.6 and 0.28+/-0.08 in the normal adrenal cortex and 59.4+/-6.5 and 0.33+/-0.11 in the adenomas, respectively, with no significant differences between the LIs of the adenomas and normal adrenals. The LIs of p27 and Ki-67 in the carcinomas were 48.9+/-7.5 and 630+/-6.21, respectively. The LI of p27 in the carcinomas was significantly lower than that in the adenomas. The LI of Ki-67 in the carcinomas was significantly higher than that in the adenomas (P < .01). Among carcinoma cases, the Ki-67 LI in living cases tended to be lower than that in deceased cases, and the p27 LI in living cases tended to be higher than that in deceased cases, but these differences did not reach statistical significance. These results indicated that decreased p27 protein expression might cause increased cell proliferation in adrenocortical carcinoma cells in combination with other positive and/or negative regulators of the cell cycle. These results also suggested that immunohistochemical analysis of p27 and Ki-67 might be useful in distinguishing between adrenocortical adenoma and carcinoma


[Surgical treatment of primary hyperhidrosis and post-surgical satisfaction. Our 5-year experience].
Primary palmar hyperhidrosis is a pathology that begins during childhood and can represent a significant reduction in the quality of life of adolescents. The current treatment of choice is thoracoscopic sympathicolysis. The aim of our study is to evaluate the results of surgery in paediatric patients. Retrospective study of patients with primary palmar or palmo-axillary hyperhidrosis who underwent thoracoscopic sympathicolysis in our hospital during the last 5 years. We operated and included in the study 28 patients, 10 men and 18 women. Mean age was 13.8 (8-18) years. Bilateral thoracoscopic sympatholysis was performed with monopolar cautery, between T2-T4 ribs. Mean operative time was 63 minutes and mean hospitalisation time was 1.1 days. The incidence on intraoperative complications was zero. 2 patients presented postoperative subcutaneous emphysema. There were no other postoperative complications. 1 patient presented partial recurrence. In all the rest, sweating completely disappeared and they were totally satisfied with the surgery (96.42%). Temporary compensatory sweating appeared in 57.14% of the cases, a collateral effect that did not change their level of satisfaction. Palmar hyperhidrosis can be a major problem for socialization and quality of life for the child or adolescent who suffers it. Thoracoscopic sympatholysis in the pediatric patient is an effective treatment, highly resolutive and with low morbidity. Despite compensatory sweating, patients are highly satisfied with the results of surgical treatment.


Association between the IgG subclass response, inflammation and disease status in Helicobacter pylori infection.
In many viral, bacterial and parasitic infections the Immunoglobulin G (IgG) subclass response has been shown to correlate with severity of inflammation and disease outcome. The aim of the present study was to investigate the association between the IgG subclass response to Helicobacter pylori infection and disease and inflammation. Eighty-three symptomatic patients undergoing endoscopic examination were included in the study. Upon endoscopic examination, the presence of ulceration was noted and biopsy specimens were collected from the gastric antrum, body and transitional zone. Blood was also collected from each patient. Gastric biopsy sections were graded using the Sydney system. H. pylori specific IgG, IgG1, IgG2, IgG3 and IgG4 were measured by ELISA. The IgG subclass was also examined retrospectively in sera collected from 20 patients previously proven to have duodenal ulcer (DU). The results of histological examination and IgG serology showed 35 subjects to be H. pylori negative and 48 to be H. pylori positive. Of the 48 H. pylori positive subjects, 25 were diagnosed with functional dyspepsia (FD), 14 with current DU and 9 with evidence of past DU. Significantly higher levels of IgG2 antibodies were found in patients with DU as compared with patients with FD (P < 0.01). In addition, significantly higher IgG3 subclass antibody levels were associated with chronic inflammatory cells in the body (P < 0.05) and active inflammatory cells in the transitional zone (P < 0.01). A significantly increased level of IgG1 antibodies was associated with lower levels of colonization in the gastric antrum. The results of this study suggest that the IgG subclass response in subjects infected with H. pylori may be a marker of DU disease as well as increased levels of inflammation.


Influence of rejection on graft survival after renal transplantation.
The clinical course was reviewed of 102 renal allograft recipients between December 1967 and December 1973. Only 4 of 21 patients (19 per cent) who had 2 or more episodes of rejection during the first 2 months had a functioning graft at the end of 1 year, compared to 24 of 30 patients (83 per cent) who had no rejection episodes. A similar trend was seen 2 to 6 months after transplantation. During the first 2 years vigorous immunosuppressive therapy for rejection in the first few months resulted in 12 deaths (44 per cent) of 27 patients. Subsequent to this immunosuppressive therapy was modified and grafts were removed if there was not a prompt recovery of function after treatment, which resulted in a significant decrease in mortality rate to 16 per cent. There also was improvement in the over-all survival of patients with functioning grafts from 37 to 56 per cent. Serious complications and mortality could be related to high dosage of steroids and severe leukopenia. A white blood count of less than 1,000 m m.3 on 3 successive days was associated with a mortality rate of 52 per cent, compared to 15 per cent in those without leukopenia. Serious consideration should be given to early graft removal in patients who have 2 or more episodes of rejection in the first few months after transplantation, particularly when there is not a prompt improvement in renal function after immunosuppressive therapy. High doses of steroids (greater than 1 mg. per kg. for more than 26 days during the first 60 days) should be avoided to decrease morbidity and mortality rates from serious infections. The results of histocompatibility (HL-A) matching in 72 donor-recipient pairs indicated an improved graft survival when there was a match of 2 or more antigens, which is supported by the results recently reported by the Transplant Registry. The results of mixed lymphocyte reactions in 20 live donor-recipient pairs showed a marked improvement in graft survival when there was less than 20 per cent stimulation and it appeared that this reaction was of more important prognostic significance than the results of histocompatibility (HL-A) matching in these patients.


Soybean meal induces intestinal inflammation in zebrafish larvae.
The necessary replacement of fish meal with other protein source in diets of commercially important fish has prompted the study of the effect of the inclusion of different vegetable proteins sources on growth performance and on the gastro-intestinal tract. Currently, soybean meal is the primary protein source as a fish meal replacement because of its low price and high availability. Likewise, it is been documented that the ingestion of soybean meal by several fish species, such as salmonids and carp, triggers a type of intestinal inflammation called enteritis. In this paper, we analyzed the effects of the ingestion of soybean meal and two of its components, soy protein and soy saponin, on zebrafish to establish the basis for using zebrafish larvae as a model for fish nutrition. We took advantage of the existence of different transgenic lines, which allowed us to perform in vivo analysis. Our results indicated that larvae that were feed with soybean meal developed a clear intestinal inflammation as early as two day after beginning the diet. Moreover, we determined that is not the soy protein present in the diet but the soy saponin that is primarily responsible for triggering the immune response. These findings support the use of zebrafish screening assays to identify novel ingredients that would to improved current fish diets or would formulate new ones.


A novel type of light-harvesting antenna protein of red algal origin in algae with secondary plastids.
Light, the driving force of photosynthesis, can be harmful when present in excess; therefore, any light harvesting system requires photoprotection. Members of the extended light-harvesting complex (LHC) protein superfamily are involved in light harvesting as well as in photoprotection and are found in the red and green plant lineages, with a complex distribution pattern of subfamilies in the different algal lineages. Here, we demonstrate that the recently discovered "red lineage chlorophyll a/b-binding-like proteins" (RedCAPs) form a monophyletic family within this protein superfamily. The occurrence of RedCAPs was found to be restricted to the red algal lineage, including red algae (with primary plastids) as well as cryptophytes, haptophytes and heterokontophytes (with secondary plastids of red algal origin). Expression of a full-length RedCAP:GFP fusion construct in the diatom Phaeodactylum tricornutum confirmed the predicted plastid localisation of RedCAPs. Furthermore, we observed that similarly to the fucoxanthin chlorophyll a/c-binding light-harvesting antenna proteins also RedCAP transcripts in diatoms were regulated in a diurnal way at standard light conditions and strongly repressed at high light intensities. The absence of RedCAPs from the green lineage implies that RedCAPs evolved in the red lineage after separation from the the green lineage. During the evolution of secondary plastids, RedCAP genes therefore must have been transferred from the nucleus of the endocytobiotic alga to the nucleus of the host cell, a process that involved complementation with pre-sequences allowing import of the gene product into the secondary plastid bound by four membranes. Based on light-dependent transcription and on localisation data, we propose that RedCAPs might participate in the light (intensity and quality)-dependent structural or functional reorganisation of the light-harvesting antennae of the photosystems upon dark to light shifts as regularly experienced by diatoms in nature. Remarkably, in plastids of the red lineage as well as in green lineage plastids, the phycobilisome based cyanobacterial light harvesting system has been replaced by light harvesting systems that are based on members of the extended LHC protein superfamily, either for one of the photosystems (PS I of red algae) or for both (diatoms). In their proposed function, the RedCAP protein family may thus have played a role in the evolutionary structural remodelling of light-harvesting antennae in the red lineage.


The release of a compound-chromosome stock in a vineyard cellar population of Drosophila melanogaster.
The prospect of autocidal insect control was investigated in a cellar population of D. melanogaster using a compound-chromosome stock. The released stock was synthesized by irradiating virgin female progeny derived from the cellar and crossing to a second-chromosome compound laboratory stock. Incorporation of an appropriate genetic background into the compound stock was tested in laboratory studies. Larval development to adult emergence and adult survival studies indicated the compound release stock to be relatively similar to the wild population, while behavioral tests detected no mating isolation between wild or compound genotypes. An unstable equilibrium point of compound frequency 0.7 was observed in population cage experiments with the two genotypes. Adults were released into the cellar at a 50:1 ratio in favor of the compound. Five hundred newly hatched compound-chromosome larvae were also released. Adult, larval and pupal samples were regularly made. The compound stock successfully bred in the cellar maintaining an adult frequency of at least 90% for 108 days after the release. The rapid decline in compound frequency after this period is thought to be due to the migration of inseminated wild-type females from wine storage areas adjacent to the cellar. The results indicate that a compound stock may limit the rate of population expansion in an area and may be a useful mechanism of autocidal control. It cannot be overemphasized that the probability of a successful release will be related to the level of understanding of the adaptive strategy of the population into which the release is made.


Clinical treatment efficiency of mechanical thrombectomy combined with rhPro-UK thrombolysis for acute moderate/severe cerebral infarction.
This study aims to compare clinical efficiency of mechanical thrombectomy combined with rhPro-UK thrombolysis on moderate or severe acute brain infarction. A total of 90 acute cerebral infarction patients due to artery stenosis or blockade from May 2016 to May 2017 were recruited and randomly assigned into thrombolysis group (N = 30), mechanical thrombectomy (N = 30), and combined treatment group (N = 30). Clinical information was collected. Thrombolysis group received rhPro-UK, mechanical thrombectomy group received Solitaire scaffold, and combined group received rhPro-UK after Solitaire scaffold. Barthel scale and NIHSS scale were used to evaluate the quality of life and mental deficit of patients. Modified thrombolysis in cerebral infarction (mTICI) was compared among three groups, along with the observation of hemorrhage, neurological recovery within 90 days, and adverse effects. No significant difference was found in NIHSS within 24 h of treatment among three groups (p > 0.05), but the decreasing levels were shown at 24 h, 7 days, and 90 days comparing to those before treatment (p < 0.05). In combined treatment group, lower NIHSS at 7 d and 90 d were detected comparing to other two groups (p < 0.05). Recanalization rates were 53.33% and 60.00% in thrombolysis and mechanical groups (p > 0.05), respectively, which were significantly lower than that in combined group (83.33%) (p < 0.05). Curative rate in combined group was 70%, significantly higher than thrombolysis (46.67%) and mechanical group (53.33%) (p < 0.05). No statistical difference of curative rate was observed between thrombolysis and mechanical groups (p > 0.05). Moreover, neither significant difference of coagulation function nor platelet count was found among three groups (p > 0.05). Mechanical thrombectomy combined with thrombolysis presented favorable efficiency in the treatment of moderate to severe acute cerebral infarction than single treatment, among which the occurrence of adverse effects were similar.


Neural innovations and the diversification of African weakly electric fishes.
In African mormyrid fishes, evolutionary change in a sensory region of the brain established an ability to detect subtle variation in electric communication signals. In one lineage, this newfound perceptual ability triggered a dramatic increase in the rates of signal evolution and species diversification. This particular neural innovation is just one in a series of nested evolutionary novelties that characterize the sensory and motor systems of mormyrids, the most speciose group of extant osteoglossomorph fishes. Here we discuss the behavioral significance of these neural innovations, relate them to differences in extant species diversity, and outline possible scenarios by which some of these traits may have fueled diversification. We propose that sensory and motor capabilities limit the extent to which signals evolve and, by extension, the role of communication behavior in the process of speciation. By expanding these capabilities, neural innovations increase the potential for signal evolution and species diversification.


[Functional renal effects of cyclosporin. Physiopathological mechanisms].
Animals and humans undergoing a treatment with cyclosporin (CsA) show a reversible increase in renal vascular resistance and decrease in glomerular filtration rate. The causes of these abnormalities have not yet been established. In animals potential mechanisms for CsA induced renal functional impairment are an increase in urinary thromboxane A2 excretion, plasma renin activity and renal sympathetic nervous system activity and an enhancement of vasopressin stimulated Ca++ mobilisation and cell contraction in vascular smooth muscle cells. In human, the problem is far less clear. CsA induces an inhibition in PRA and urinary prostaglandins excretion. Furthermore CsA does not modify urinary and plasma levels of catecholamines. Whatever the mechanism underlying the vasoconstriction induced by CsA, the inhibition of PGI2 synthesis and angiotensin II formation may participate in the decrease in renal blood flow and glomerular filtration rate which is observed in patients receiving CsA.


[Glycogenolysis indices in the skeletal muscles of rats with experimental rickets].
Content of glycogen and lactic acid was decreased in sceletal muscles of growing male rats during the acute periof of experimental rachitis. In developing rachitis an increase in locomotions, maintained during the experimental period, fostered the normalization of these patterns.


The efficacy and tolerability of an 8-day administration of intravenous and oral meloxicam: a comparison with intramuscular and oral diclofenac in patients with acute lumbago. German Meloxicam Ampoule Study Group.
In this controlled, randomized, parallel and open multicentre study, the efficacy and tolerability of a regimen comprising intravenous (i.v.) meloxicam followed by oral therapy was compared with a standard regimen of intramuscular (i.m.) diclofenac followed by oral dosing in patients with acute lumbago. Of a total of 183 patients, 92 were randomized to receive meloxicam 15 mg i.v. on day 1 followed by 7 days oral treatment with one 15 mg tablet daily, and 91 patients received diclofenac 75 mg i.m. on day 1 followed by 7 days treatment with one 100 mg slow release tablet daily. Pain on movement and limitation of activities were assessed by patients and physicians using questionnaires. Meloxicam i.v. demonstrated a significantly faster median time of onset of analgesic action (30 minutes), compared with diclofenac i.m. (60 minutes). The reduction in pain during movement 30 minutes after injection was also significantly in favour of meloxicam. Assessments of global efficacy indicated that meloxicam was significantly better than diclofenac as rated by investigators (p = 0.02) and patients (p = 0.01). Moreover, the rating of investigators and patients for local and global tolerance was significantly in favour of meloxicam (p < 0.05) and improvements in the quality of life were almost significant (p = 0.053). Fewer adverse events, particularly of a gastrointestinal (GI) nature, occurred in the meloxicam group compared with the diclofenac group. This study therefore demonstrates that meloxicam 15 mg i.v. followed by oral therapy is both efficacious and well tolerated in the treatment of acute lumbago, and compares favourably with the standard NSAID, diclofenac, in this indication.


Synthesis and determination of configuration of natural 25-hydroxyvitamin D(3) 26,23-lactone.
The four stereoisomers of 25-hydroxyvitamin D(3) 26,23-lactone were synthesized by a stereoselective lactonization method. Natural 25-hydroxyvitamin D(3) 26,23-lactone was produced from 25-hydroxy-[3alpha-(3)H]vitamin D(3) by in vitro incubation of kidney homogenate prepared from vitamin D-supplemented chickens or was isolated from the serum of rats given 1,25-dihydroxyvitamin D(3) and 25-hydroxy-[3alpha-(3)H]vitamin D(3). The four synthetic isomers and the naturally produced 25-hydroxyvitamin D(3) 26,23-lactone were subjected to high-performance liquid chromatography in a system capable of separating the four isomers. The natural lactone comigrated with synthetic (23S,25R)-25-hydroxyvitamin D(3) 26,23-lactone, establishing it as the natural vitamin D(3) metabolite.


Analysis of autoantibodies to plasminogen in the serum of patients with rheumatoid arthritis.
Sera from patients with rheumatoid arthritis containing high titers of anti-streptokinase antibodies were found to contain anti-plasminogen antibodies of the IgG and IgA classes. High titers of anti-plasminogen autoantibodies of the IgA class were also found in sera from patients with systemic lupus erythematosus and Sjögren syndrome. Studies of the immune response to thrombolytic therapy with streptokinase in patients with no prior history of autoimmune disease suggest a strong correlation between streptokinase administration and the appearance of autoantibodies to plasminogen of the IgA class. The IgA anti-plasminogen autoantibody is specific for an epitope in a region of plasminogen which binds streptokinase and the IgG autoantibody reacts with an epitope in the C-terminal region corresponding to the catalytic domain of the plasminogen zymogen. Our findings suggest a different origin for the two classes of anti-plasminogen immunoglobulins in rheumatoid arthritis patients. Since plasminogen binding to rheumatoid synovial fibroblasts is enhanced, the high titers of both classes of anti-plasminogen autoantibodies may add to the localization and perpetuation of the immune response. We suggest that plasminogen may be a target of the immune response in autoimmune disease.


Helicobacter pylori and Helicobacter heilmannii in untreated Bulgarian children over a period of 10 years.
The aims of the study were to evaluate the incidence of Helicobacter pylori and Helicobacter heilmannii in untreated Bulgarian children from 1996 to 2006, to analyse the performance of diagnostic tests, and to look at H. pylori density in specimens by culture. Antral specimens from children with chronic gastritis (n=513), peptic ulcers (n=54) and other diseases (n=91) were evaluated by direct Gram staining (DGS), in-house rapid urease test (RUT) and culture. The living environment and semi-quantitative H. pylori density were assessed in 188 and 328 children, respectively. H. pylori infection was found in children with ulcers (77.8 %), chronic gastritis (64.5 %) and other diseases (36.3 %). Half (51.4 %) of patients aged 1-5 years and 77.4 % of those aged 16-17 years were H. pylori-positive. Of all children, 328 (49.8 %) showed positive DGS, 184 (28 %) had a positive RUT, and 386 (58.7 %) were culture-positive. Unlike gastric mucus specimens, frozen biopsy specimens provided reliable diagnosis. H. heilmannii was observed in two (0.3 %) children. High H. pylori density (growth into all quadrants of plates) was found in 18 % of 328 children evaluated, involving 31 % of ulcer and 16.7 % of non-ulcer patients. H. pylori infection was more common in rural children with chronic gastritis (91.3 %) than in the remainder (66.7 %). In conclusion, H. pylori infection was common in symptomatic Bulgarian children. The infection prevalence was >77 % in patients aged 16-17 years, in children with a duodenal ulcer, and in rural patients. H. heilmannii infection was uncommon. The performance of the bacterial culture was good. The impact of H. pylori density on the clinical expression and eradication of the infection requires further evaluation. The results highlight the need for routine H. pylori diagnosis in rural children with chronic gastritis.


Familial idiopathic fibrosing alveolitis.
Case reports of two sisters with idiopathic fibrosing alveolitis are presented. On the basis of reports in the literature it seems that developmental anomalies and immunopathological changes occur more frequently in familial fibrosing alveolitis than in the general population.


Membrane domain structures of three classes of histidine kinase receptors by cell-free expression and rapid NMR analysis.
NMR structural studies of membrane proteins (MP) are hampered by complications in MP expression, technical difficulties associated with the slow process of NMR spectral peak assignment, and limited distance information obtainable for transmembrane (TM) helices. To overcome the inherent challenges in the determination of MP structures, we have developed a rapid and cost-efficient strategy that combines cell-free (CF) protein synthesis, optimized combinatorial dual-isotope labeling for nearly instant resonance assignment, and fast acquisition of long-distance information using paramagnetic probes. Here we report three backbone structures for the TM domains of the three classes of Escherichia coli histidine kinase receptors (HKRs). The ArcB and QseC TM domains are both two-helical motifs, whereas the KdpD TM domain comprises a four-helical bundle with shorter second and third helices. The interhelical distances (up to 12 A) reveal weak interactions within the TM domains of all three receptors. Determined consecutively within 8 months, these structures offer insight into the abundant and underrepresented in the Protein Data Bank class of 2-4 TM crossers and demonstrate the efficiency of our CF combinatorial dual-labeling strategy, which can be applied to solve MP structures in high numbers and at a high speed. Our results greatly expand the current knowledge of HKR structure, opening the doors to studies on their widespread and pharmaceutically important bacterial signaling mechanism.


Social inequalities in protective behaviour uptake at the start of the COVID-19 pandemic: results from a national survey.
We aimed to assess social patterns of handwashing, social distancing, and working from home at the start of the COVID-19 pandemic in Canada, and determine what proportions of the overall prevalence and social inequalities in handwashing and social distancing are related to inequalities in the opportunity to work from home, to guide pandemic preparedness and response. Using cross-sectional data from the Canadian Perspectives Survey Series, collected between March 29 and April 3, 2020, among Canadian adults (N=4455), we assessed prevalence of not working from home, social distancing in public, or practicing frequent handwashing, according to age, sex, marital status, immigration, education, chronic disease presence, and source of COVID-19 information. Multivariate regression, population attributable fraction estimation, and generalized product mediation analysis were applied. Absence of frequent handwashing and distancing was more common among those working outside than within the home (prevalence differences of 7% (95% CI: 4, 10) and 7% (95% CI: 3, 10), respectively). Inequalities in handwashing and distancing were observed across education and immigration status. Over 40% of the prevalence of non-uptake of handwashing and distancing was attributable to populations not being able to work from home. If all worked from home, over 40% (95% CI: 8, 70) of education-based inequalities in handwashing and distancing could be eliminated, but differences by immigration status would likely remain. For pandemic response, both workplace safety initiatives and mechanisms to address the inequitable distribution of health risks across socio-economic groups are needed to reduce broader inequalities in transmission risk.


Improving the capacity of complex-valued neural networks with a modified gradient descent learning rule.
Jankowski et al. proposed (1996) a complex-valued neural network (CVNN) which is capable of storing and recalling gray-scale images. The convergence property of the CVNN has also been proven by means of the energy function approach. However, the memory capacity of the CVNN is very low because they use a generalized Hebb rule to construct the connection matrix. In this letter, a modified gradient descent learning rule (MGDR) is proposed to enhance the capacity of the CVNN. The proposed technique is derived by applying gradient search over a complex error surface. Simulation shows that the capacity of CVNN with MGDR is greatly improved.


Temporal and spatial changes of monocarboxylate transporter 4 expression in the hippocampal CA1 region following transient forebrain ischemia in the Mongolian gerbil.
Transient forebrain ischemia depletes glucose and oxygen levels in the brain. In this pathological condition, lactate serves an important role in cellular metabolism as the end product of glycolysis. The present study investigated the expression of monocarboxylate transporter 4 (MCT4) in lactate metabolism in the hippocampal CA1 region following induction of transient forebrain ischemia. MCT4 immunoreactivity was detected in CA1 pyramidal cells of the sham-operated group. Animals from the ischemic group exhibited a transient decrease in MCT4 immunoreactivity in the CA1 region between 30 min and 3 h following ischemia compared with the sham‑operated group. The initial decrease in immunoreactivity observed between 30 min and 3 h following ischemia was followed by an increase at 2 days after the treatment. A significant increase in MCT4 immunoreactivity levels was observed 2 days after ischemia compared with the sham‑operated group. Limited MCT4 immunoreactivity was observed in the pyramidal neurons 3 days after ischemia. At 4‑10 days after ischemia, MCT4 immunoreactivity was detected in the strata radiatum, oriens and pyramidale. Furthermore, MCT4 immunoreactivity levels in the CA1 region exhibited a time‑dependent increase following ischemia. The results indicated that there were transient alterations observed in the localization of MCT4 following the induction of ischemia, and further studies are required to investigate the association between MCT4 expression and lactate metabolism in providing energy to the post‑ischemic brain.


Advanced Medical Technology Capacity Building and the Medical Mentoring Event: A Unique Application of SOF Counterinsurgency Medical Engagement Strategies.
Background The Medical Civic Assistance Program (MEDCAP) is a military commander?s tool developed during the Vietnam War to gain access to and positively influence an indigenous population through the provision of direct medical care provided by military medical personnel, particularly in Counter Insurgency Operations (COIN). An alternative to MEDCAPs is the medical seminar (MEDSEM). The MEDSEM uses a Commander?s military medical assets to share culturally appropriate medical information with a defined indigenous population in order to create a sustainable training resource for the local population?s health system. At the heart of the MEDSEM is the ?train the trainer? concept whereby medical information is passed to indigenous trainers who then pass that information to an indigenous population. The MEDSEM achieves the Commander?s objectives of increasing access and influence with the population through a medical training venue rather than direct patient care. Previous MEDSEMS conducted in Afghanistan by military forces focused on improvement of rural healthcare through creation of Village Health Care Workers. This model can also be used to engage host nation (HN) medical personnel and improve medical treatment capabilities in population centers. The authors describe a modification of the MEDSEM, a Medical Mentorship (MM), conducted in November 2010 in Kabul, Afghanistan, at the Afghan National Army (ANA) National Medical Hospital. This training was designed to improve intubation skills in Afghan National Army Hospitals by ANA medical providers, leave residual training capability, and build relationships within the institution that not only assist the institution, but can also be leveraged to foster Commanders? objectives, such as health and reconstruction initiatives and medical partnering for indigenous corps and medical forces described below. Methods We, the authors, developed a culturally appropriate endotracheal intubation training package including a Dari and Pashto instruction manual, Dari video training program, video laryngoscope and difficult airway training mannequin to be used by indigenous medical personnel to train other indigenous medical personnel in the skill of endotracheal intubation. Utilizing Special Operations medical personnel, University of Nebraska medical personnel and local Afghan medical instructors, we coordinated with local authorities and ISAF medical authorities. We trained approximately 100 ANA physician assistant (PA) students and ten ANA intensive care unit (ICU) and Anesthesia medical staff in endotracheal intubation. The video laryngoscope was used as a training aid to guide each student?s direct intubation technique. Results We validated the Medical Mentorship (MM) concept as a means to engage an indigenous population?s medical personnel. The indigenous medical training facilities capability was augmented by use of the video laryngoscope as a training aid. This improvement was sustained over the observable period. Relationships were developed and enhanced for medical support of coalition partner forces supporting SOF operations. Introducing the video laryngoscope to the ICU increased direct care capabilities within the medical institution. Conclusions The MEDSEM is a viable option for military commanders to leverage medical assets to positively engage an indigenous population during COIN operations. MEDSEMs leave residual sustainable medical capabilities, in contrast to MEDCAP models. This report describes a modification of the MEDSEM concept?Medical Mentoring Event (MME)?a short term focused intervention designed to insert medical technology or techniques into an indigenous medical facility that creates sustainable, tangible benefits to patient care while fostering a SOF Commanders objectives. Follow up with embedded NATO trainers at National Military Hospital (NMH) shows that the video laryngoscope continues to be used successfully in airway management training and in difficult intubations, enhanced the teaching impact of imbedded NATO medical mentors, left a residual training capability for Afghan medical instructors and created relationships between SOF medical providers and the host institution that can facilitate healthcare for SOF partner forces.


A Real-world Prospective Study of Mother-to-child Transmission of HBV in China Using a Mobile Health Application (Shield 01).
Background and Aims: The World Health Organization (WHO) Western Pacific Region set a target of eliminating mother-to-child transmission (MTCT) of hepatitis B virus (HBV) by 2030. To assess the feasibility of this target in China, we carried out an epidemiological study to investigate the status quo of MTCT in the real-world setting. Methods: One thousand and eight hepatitis B surface antigen-positive pregnant women were enrolled at 10 hospitals. Immunoprophylaxis was administered to infants. In addition, mothers with HBV DNA level >2,000,000 IU/mL were advised to initiate antiviral therapy during late pregnancy. A health application called SHIELD was used to manage the study. Results: Nine hundred and five of the enrolled mothers, with 924 infants, completed the follow-up. Birth-dose hepatitis B vaccine and hepatitis B immunoglobulin were received by 99.7% and 99.7% of infants, respectively, within 24 h after birth. There were 446 mothers who received antiviral therapy, including 72.3% of the mothers with HBV DNA level >2,000,000 IU/mL and 21.0% of the mothers with HBV DNA level <2,000,000 IU/mL. Eight infants were infected with HBV. The overall rate of MTCT was 0.9%. Birth defects were rare (0.5% among infants with maternal antiviral exposure versus 0.7% among infants without exposure; p=1.00). Conclusions: The MTCT rate was lower than the WHO Western Pacific Region elimination MTCT target in this real-world study, indicating that a comprehensive management composed of immunoprophylaxis to infants and antiviral prophylaxis to mothers may be a feasible strategy to achieve the 2030 WHO elimination goal.


Comparison of hematologic data in world elite junior speed skaters and in non-athletic juniors.
During the world junior speed skating championship 2002 all athletes (60 males, 56 females) were subjected to hematologic blood testing one day before the competition as requested by International Skating Union--ISU. This study aimed to obtain hematological reference values for junior athletes, whilst the influence of endurance training on hematologic variables of young athletes was studied. Hematologic results of athletes were compared to results of non-athletes matched by age and gender (14 males, 17 females). The blood analysis was done on an ADVIA 120. To compare measurement of ferritin, erythropoietin, and soluble transferrin receptor in serum as well as in EDTA-plasma, serum and EDTA-blood was obtained from the control group. In hemoglobin and hematocrit we found no significant difference between the two groups, whereas the number of erythrocytes was lower in athletes. The mean corpuscular volume was higher in athletes, whilst the corpuscular hemoglobin content was only marginally higher in athletes than in non-athletes. Consequently corpuscular hemoglobin concentration mean was lower in athletes than in non-athletes. There was no difference of erythropoietin and soluble transferrin receptor, whilst in ferritin we found a difference between the groups. Endurance training does not change the values of hemoglobin and hematocrit. Increased mean corpuscular volume and decreased corpuscular hemoglobin concentration mean could be a result of changed properties of red blood cell-membrane caused by acidosis and higher osmolality during the training. In junior athletes we did not find an iron overload as described in some adult athletes.


Isolation of Staphylococcus sciuri from horse skin infection.
Staphylococcus sciuri is known as an opportunistic pathogen colonizing domesticated animals and has also been associated with wound infections in humans. Particularly over the last decade, oxacillin (methicillin) resistant strains had been emerged, which now increase the medical relevance of this species. This report describes the identification of an oxacillin-resistant S. sciuri isolate from a wound infection of a horse. We determined the absence of coagulase and hyaluronidase activity and analysed the antibiotic resistance profile.


Toenail selenium status and risk of subtypes of head-neck cancer: The Netherlands Cohort Study.
There is limited prospective data on the relationship between selenium status and the risk of head-neck cancer (HNC) and HNC subtypes (i.e., oral cavity cancer [OCC], oro-/hypopharyngeal cancer [OHPC] and laryngeal cancer [LC]). Therefore, we investigated the association between toenail selenium, reflecting long-term selenium exposure, and HNC risk within the Netherlands Cohort Study. At baseline, 120,852 participants completed a self-administered questionnaire about diet and other cancer risk factors and were asked to provide toenail clippings. After 20.3 years of follow-up, 294 cases of HNC (95 OCC, 62 OHPC, two oral cavity/pharynx unspecified or overlapping and 135 LC) and 2,164 subcohort members were available for case-cohort analysis using Cox proportional hazards models. Toenail selenium status was statistically significantly associated with a decreased risk of HNC overall (multivariate RR for quartile four versus one: 0.55, 95% confidence interval [CI] 0.37-0.82, P trend = 0.001). The association between toenail selenium and risk of HNC overall was stronger among men than women, but no statistically significant interaction with sex was found. Toenail selenium level was also associated with a decreased risk of all HNC subtypes, with statistically significant associations in OHPC and LC. No statistically significant interaction was found between toenail selenium level and cigarette smoking or alcohol consumption for HNC overall. In this large cohort study, we found an inverse association between toenail selenium level and HNC risk. Among HNC subtypes, this association was strongest for OHPC and LC. Furthermore, the association of toenail selenium status with HNC risk was stronger among men than women.


Analyzing gene expression data in terms of gene sets: methodological issues.
Many statistical tests have been proposed in recent years for analyzing gene expression data in terms of gene sets, usually from Gene Ontology. These methods are based on widely different methodological assumptions. Some approaches test differential expression of each gene set against differential expression of the rest of the genes, whereas others test each gene set on its own. Also, some methods are based on a model in which the genes are the sampling units, whereas others treat the subjects as the sampling units. This article aims to clarify the assumptions behind different approaches and to indicate a preferential methodology of gene set testing. We identify some crucial assumptions which are needed by the majority of methods. P-values derived from methods that use a model which takes the genes as the sampling unit are easily misinterpreted, as they are based on a statistical model that does not resemble the biological experiment actually performed. Furthermore, because these models are based on a crucial and unrealistic independence assumption between genes, the P-values derived from such methods can be wildly anti-conservative, as a simulation experiment shows. We also argue that methods that competitively test each gene set against the rest of the genes create an unnecessary rift between single gene testing and gene set testing.


Relationship between air quality and asthma-related emergency hospital admissions in Mexico City 2017-2019.
Previous studies found exposure to air pollution leads to exacerbations of asthma in paediatric and adult patients and increases asthma-related emergency hospital admissions (AREHA). AREHAs and levels of air pollutants (PM10, PM2.5 and NO2) were obtained from Mexico City for the period 2017-2019. A time-series approach was used to explore the relationship between air pollutants and AREHA. Relative risks of AREHA were estimated using a negative binomial regression in young children (less than 5 years) and adults (greater than 18 years). There was a positive association between AREHA and PM10, PM2.5 and NO2 in adults, which remained after mutual adjustment for these pollutants. The relative risk (RR) of admission in adults increased by 3% (95% CI 1% to 4%) for a 10 µg/m3 increase in PM10, 1% (0.03% to 3%) for a 5 µg/m3 increase in PM2.5 and by 1% (0.06% to 2%) for a 5 µg/m3 increase in NO2. In contrast, in young children, AREHAs were negatively associated with PM10 after adjustment for NO2 (RR 0.97 (0.95 to 0.99) for a 10 µg/m3 and with NO2 after adjustment for PM10 and PM2.5 (RR 0.98 (0.96 to 0.99) and 0.97 (0.96 to 0.99), respectively, for a 5 µg/m3 increase in NO2). AREHAs in children were not associated with PM2.5 after adjustment for NO2. Ambient air pollution, within the previous week, was associated with emergency hospital admissions for asthma to public hospitals in adults in Mexico City. The relationship in children was less consistent. Further work is needed to explore why differences between adults and children exist to inform appropriate interventions to benefit public health.


Gallic acid is an active component for the anticarcinogenic action of grape seed procyanidins in pancreatic cancer cells.
The aim of the present work was to evaluate the effects of a grape seed procyanidin extract (GSPE) on proliferation and apoptosis in the pancreatic adenocarcinoma cell line MIA PaCa-2 and identify the components of the extract with higher activity. The effects of the extract were analyzed on the proliferation and apoptosis processes in MIA PaCa-2 cells, as well as in the levels of the apoptosis markers Bcl-2 and Bax, the mitochondrial membrane potential, and reactive oxygen species levels. Finally, the components of the extract with higher effects were elucidated using enriched fractions of the extract and pure compounds. The results showed that GSPE inhibits cell proliferation and increases apoptosis in MIA PaCa-2 cells, which is primarily mediated by the downregulation of the antiapoptotic protein Bcl-2 and the depolarization of the mitochondrial membrane. GSPE also reduced the formation of reactive oxygen species. The component of the extract that possesses the highest antiproliferative and proapoptotic activity was gallic acid. In conclusion, GSPE acts as anticarcinogenic in MIA PaCa-2 cells, with gallic acid as the major single active constituent of the extract.


Dopaminergic therapy in aphasia.
The dopaminergic system is involved in a wide range of cognitive functions including motor control, reward, memory, attention, problem-solving and learning. This has stimulated interest in investigating the potential of dopaminergic drugs as cognitive enhancers in aphasic patients. To discuss the evidence for the use of dopaminergic agents in patients with aphasia. Levodopa (L-dopa) and the dopamine agonist bromocriptine are the two drugs that have been trialled to date. We discuss, in some detail, the 15 studies that have been published on this topic from the first case report in 1988 to the present (2012), and assess the evidence from each. In addition to summarising the effectiveness of the drugs that have been tried, we examine the possible cognitive mechanisms by which dopaminergic drugs may act on language function and aphasia recovery. Given the wide range of dopaminergic drugs, it is surprising that such a narrow range has been trialled in aphasic patients. Important lessons are to be learned from published studies and we discuss optimal trial designs to help guide future work. The evidence for the efficacy of dopaminergic agents in aphasia therapy is mixed. Further trials with better tolerated agents are required. Optimal trial designs with appropriate control groups or blocks should be used. The mechanism of action is unclear, but at the cognitive level the evidence points towards either (re)learning of word-forms or their improved retrieval.


Glycyrrhizin inhibits highly pathogenic H5N1 influenza A virus-induced pro-inflammatory cytokine and chemokine expression in human macrophages.
Hypercytokinaemia is thought to contribute to highly pathogenic H5N1 influenza A virus disease. Glycyrrhizin is known to exert immunomodulatory and anti-inflammatory effects and therefore a candidate drug for the control of H5N1-induced pro-inflammatory gene expression. Here, the effects of an approved parenteral glycyrrhizin preparation were investigated on H5N1 virus replication, H5N1-induced pro-inflammatory responses, and H5N1-induced apoptosis in human monocyte-derived macrophages. Glycyrrhizin 100 μg/ml, a therapeutically achievable concentration, impaired H5N1-induced production of CXCL10, interleukin 6, and CCL5 and inhibited H5N1-induced apoptosis but did not interfere with H5N1 replication. Global inhibition of immune responses may result in the loss of control of virus replication by cytotoxic immune cells including natural killer cells and cytotoxic CD8(+) T-lymphocytes. Notably, glycyrrhizin concentrations that inhibited H5N1-induced pro-inflammatory gene expression did not affect cytolytic activity of natural killer cells. Since H5N1-induced hypercytokinaemia is considered to play an important role within H5N1 pathogenesis, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.


Appraisal of the treatment of carcinoma of the anus and anal canal.
Anal bleeding and pain were the symptoms in half of 53 patients with carcinoma within and around the area of the anus treated from 1950 to 1974. Twenty-seven carcinomas were exclusively located in the anal canal and six, in the perianal skin. Vaginal invasion was present in 13 of the women. There were 39 squamous cell carcinomas and nine basaloid cell carcinomas. More than 37 of the patients had an abdominoperineal resection as part of the treatment. The resection margins were positive for carcinomas in 11 patients. Radiation as the primary treatment was used only once. Palpably enlarged inguinal lymph nodes were treated by subsequent radical groin dissection. The crude over-all survival rate was 42 per cent; the adjusted five year survival rate was 38 per cent. Significant correlates of death were symptoms for longer than six months' duration bleeding, inguinal adenopathy and presence of hemorrhoids. In general, abdominoperineal resection is the operation of choice for carcinoma of the anal verge or anal canal. Inguinal lymphadenectomy at a later time should be reserved for patients with signs of metastases to the inguinal nodes.


The crystal structure of vaccinia virus protein E2 and perspectives on the prediction of novel viral protein folds.
The morphogenesis of vaccinia virus (VACV, family Poxviridae), the smallpox vaccine, is a complex process involving multiple distinct cellular membranes and resulting in multiple different forms of infectious virion. Efficient release of enveloped virions, which promote systemic spread of infection within hosts, requires the VACV protein E2 but the molecular basis of E2 function remains unclear and E2 lacks sequence homology to any well-characterised family of proteins. We solved the crystal structure of VACV E2 to 2.3 Å resolution, revealing that it comprises two domains with novel folds: an N-terminal annular (ring) domain and a C-terminal globular (head) domain. The C-terminal head domain displays weak structural homology with cellular (pseudo)kinases but lacks conserved surface residues or kinase features, suggesting that it is not enzymatically active, and possesses a large surface basic patch that might interact with phosphoinositide lipid headgroups. Recent deep learning methods have revolutionised our ability to predict the three-dimensional structures of proteins from primary sequence alone. VACV E2 is an exemplar 'difficult' viral protein target for structure prediction, being comprised of multiple novel domains and lacking sequence homologues outside Poxviridae. AlphaFold2 nonetheless succeeds in predicting the structures of the head and ring domains with high and moderate accuracy, respectively, allowing accurate inference of multiple structural properties. The advent of highly accurate virus structure prediction marks a step-change in structural virology and beckons a new era of structurally-informed molecular virology.


Patient experience in fast-track hip and knee arthroplasty--a qualitative study.
To explore the lived experience of patients in fast-track primary unilateral total hip and knee arthroplasty from the first visit at the outpatient clinic until discharge. Fast-track has resulted in increased effectiveness, including faster recovery and shorter length of stay to about two days after hip and knee arthroplasty. However, the patient perspective in fast-track with a median length of stay of less than three days has been less investigated. A qualitative design. A phenomenological-hermeneutic approach was used, inspired by Paul Ricoeur's theory of narrative and interpretation. Eight patients were included. Semi-structured interviews and participant observation were performed. Three themes emerged: dealing with pain; feelings of confidence or uncertainty - the meaning of information; and readiness for discharge. Generally, the patients were resistant to taking analgesics and found it difficult to find out when to take supplementary analgesics; therefore, nursing staff needed enough expertise to take responsibility. Factors that increased patients' confidence: information about fast-track, meeting staff before admission and involving relatives. In contrast, incorrect or conflicting information and a lack of respect for privacy led to uncertainty. In preparing for early discharge, sufficient pain management, feeling well-rested and optimal use of time during hospitalisation were important. The study shows the importance of dealing with pain and getting the right information and support to have confidence in the fast-track programme, to be ready for discharge and to manage postoperatively at home. In fast-track focusing on early discharge, there is an increased need for evidence-based nursing practice, including a qualified judgement of what is best for the patient in certain situations. The knowledge should be gleaned from: research; the patients' expertise, understanding and situation; and nurses' knowledge, skills and experience.


Vesicular stomatitis virus matrix protein impairs CD1d-mediated antigen presentation through activation of the p38 MAPK pathway.
Natural killer T (NKT) cells are unique T lymphocytes that recognize CD1d-bound lipid antigens and play an important role in both innate and acquired immune responses against infectious diseases and tumors. We have already shown that a vesicular stomatitis virus (VSV) infection results in the rapid inhibition of murine CD1d-mediated antigen presentation to NKT cells. In the present study, it was found that the VSV matrix (VSV-M) protein is an important element in this decrease in antigen presentation postinfection. The VSV-M protein altered the intracellular distribution of murine CD1d molecules, resulting in qualitative (but not quantitative) changes in cell surface CD1d expression. The M protein was distributed throughout the infected cell, and it was found to activate the mitogen-activated protein kinase (MAPK) p38 very early postinfection. Infection of CD1d(+) cells with a temperature-sensitive VSV-M mutant at the nonpermissive temperature both substantially reversed the inhibition of antigen presentation by CD1d and delayed the activation of p38. Thus, the VSV-M protein plays an important role in permitting the virus to evade important components of the innate immune response by regulating specific MAPK pathways.


Photocrosslinking of glycoconjugates using metabolically incorporated diazirine-containing sugars.
Transient interactions among glycoconjugates underlie developmental, immunological and metastatic recognition. Glycan-mediated interactions have low binding affinities and rapid dissociation rates. As a result, these complexes dissociate when removed from their cellular context, complicating characterization. Photocrosslinkers introduce a covalent bond between glycoconjugates and their binding partners, allowing physiologically relevant complexes to be isolated. This protocol describes metabolic incorporation of a diazirine photocrosslinker into sialic acids in cellular glycoconjugates. Subsequent irradiation results in photocrosslinking of sialic acid to neighboring macromolecules, providing a photochemical 'snapshot' of binding events. As photocrosslinking sugars are light activated, these reagents have the potential to be used for temporally and/or spatially restricted crosslinking. We provide instructions for the synthesis of photocrosslinking sugar precursors, cell culture for metabolic incorporation, flow cytometry to evaluate metabolic incorporation, photoirradiation and analysis of the crosslinked complexes. Synthesis of photocrosslinking sugars requires 4-6 d, and photocrosslinking experiments can be completed in an additional 6 d.


Adenosine: a physiological modulator of superoxide anion generation by human neutrophils.
The effects of adenosine were studied on human neutrophils with respect to their generation of superoxide anion, degranulation, and aggregation in response to soluble stimuli. Adenosine markedly inhibited superoxide anion generation by neutrophils stimulated with N-formyl methionyl leucyl phenylalanine (FMLP), concanavalin A (Con A), calcium ionophore A23187, and zymosan-treated serum; it inhibited this response to PMA to a far lesser extent. The effects of adenosine were evident at concentrations ranging from 1 to 1,000 microM with maximal inhibition at 100 microM. Cellular uptake of adenosine was not required for adenosine-induced inhibition since inhibition was maintained despite the addition of dipyridamole, which blocks nucleoside uptake. Nor was metabolism of adenosine required, since both deoxycoformycin (DCF) and erythro-9-(2-hydroxy-3-nonyl) adenine did not interfere with adenosine inhibition of superoxide anion generation. The finding that 2-chloroadenosine, which is not metabolized, resembled adenosine in its ability to inhibit superoxide anion generation added further evidence that adenosine metabolism was not required for inhibition of superoxide anion generation by neutrophils. Unexpectedly, endogenously generated adenosine was present in supernatants of neutrophil suspensions at 0.14-0.28 microM. Removal of endogenous adenosine by incubation of neutrophils with exogenous adenosine deaminase (ADA) led to marked enhancement of superoxide anion generation in response to FMLP. Inactivation of ADA with DCF abrogated the enhancement of superoxide anion generation. Thus, the enhancement was not due to a nonspecific effect of added protein. Nor was the enhancement due to the generation of hypoxanthine or inosine by deamination of adenosine, since addition of these compounds did not affect neutrophil function. Adenosine did not significantly affect either aggregation or lysozyme release and only modestly affected beta-glucuronidase release by neutrophils stimulated with FMLP. These data indicate that adenosine (at concentrations that are present in plasma) acting via cell surface receptors is a specific modulator of superoxide anion generation by neutrophils.


Anterior thalamic lesions stop immediate early gene activation in selective laminae of the retrosplenial cortex: evidence of covert pathology in rats?
Lesions involving the anterior thalamic nuclei stopped immediate early gene (IEG) activity in specific regions of the rat retrosplenial cortex, even though there were no apparent cytoarchitectonic changes. Discrete anterior thalamic lesions were made either by excitotoxin (Experiment 1) or radiofrequency (Experiment 2) and, following recovery, the rats foraged in a radial-arm maze in a novel room. Measurements made 6-12 weeks postsurgery showed that, in comparison with surgical controls, the thalamic lesions produced the same, selective patterns of Fos changes irrespective of method. Granular (caudal granular cortex and rostral granular cortex), but not dysgranular (dysgranular cortex), retrosplenial cortex showed a striking loss of Fos-positive cells. While a loss of between 79 and 89% of Fos-positive cells was found in the superficial laminae, the deeper layers appeared normal. In Experiments 3 and 4, rats 9-10 months postsurgery were placed in an activity box for 30 min. Anterior thalamic lesions (Experiment 3) led to a pronounced IEG decrease of both Fos and zif268 throughout the retrosplenial cortex that now included the dysgranular area. These IEG losses were found even though the same regions appeared normal using standard histological techniques. Lesions of the postrhinal cortex (Experiment 4) did not bring about a loss of retrosplenial IEG activity even though this region is also reciprocally connected with the retrosplenial cortex. This selective effect of anterior thalamic damage upon retrosplenial activity may both amplify the disruptive effects of anterior thalamic lesions and help to explain the posterior cingulate hypoactivity found in Alzheimer's disease.


Collagen Type II is produced in healing pars tensa of perforated tympanic membranes: an experimental study in the rat.
Type II collagen is synthesized in the tympanic membrane during healing of a perforation. The time course and appearance of Type II collagen regrowth in the newly healed tympanic membrane is the subject of the present study. The arrangement of Type II collagen fibers in the tympanic membrane gives it a unique tensile strength important for sound conduction. Healing after tympanic membrane perforation can cause the tympanic membrane to lose its characteristic. At what phase Type II collagen in tympanic membrane is replaced during healing of a perforation has previously not been studied. Rat tympanic membranes were perforated, and the animals were sacrificed 9 to 16 days after perforation. Tympanic membranes were stained with a Type II collagen antibody. At Day 9, a majority of the tympanic membranes had healed. Keratinizing epithelium and connective tissue had formed, but there was no Type II collagen. At Day 10, all tympanic membranes had healed, and staining for Type II collagen appeared. After Day 10, staining was more intense. Newly formed collagen did not show the parallel bundle arrangement seen in normal tympanic membranes but was more scattered in the tissue. Type II collagen was seen in tympanic membranes only after closure of the perforation. The fiber arrangement after healing was disturbed, which presumably has an impact on the function of the tympanic membrane. Understanding the formation of Type II collagen in the healing of tympanic membrane perforations could enable further research toward treating tympanic membrane perforations.


[Discovery of a unique strain-specific idiotypic antigenic determinant of mouse T-lymphocyte antigen-recognizing receptors].
The cellular radioimmunoassay using rabbit anti-CBA-anti-C57BL/6 antiidiotypic serum was performed to detect a private strain-specific antigenic idiotypic determinant (s) on activated CBA-anti-C57BL/6 T cells. This private idiotype was not expressed on other activated T cells under study: CBA-anti-BALB/C; C3H-anti-C57BL/6; AKR-anti-C57BL/6; A/Sn-anti-C57BL/6; BALB/C-anti-C57BL/6; DBA/2-anti-C57BL/6. It is suggested that gene (s) coding the private strain-specific idiotypic antigenic determinant of the antigen-recognition receptor of T cells is not localized on the H-2 complex of mice.


Hematological and Immunological Changes Due to Short-term Oral Administration of Acephate.
To evaluate immunotoxicological effects of environmental chemical, subacute toxicity of repeated (28 day) oral administration of acephate (Ace) in BALB/c mice was assessed. Thirty two (sixteen male and sixteen female) mice were divided into four different groups with each group containing eight (four male and four female) mice. Mice of Group C1 were administered normal saline only and served as control. Group T1 was given 1/40(th) of apparent LD(50) (ALD(50)) (8.78 mg/kg), and group T2 was put on 1/30(th) of ALD(50) [11.7 mg/kg], while group T3 received 1/20(th) of ALD(50) [17.55 mg/kg] of Ace suspended in normal saline. The blood samples were collected from mice after 28 days of oral administration and analyzed for hematological, biochemical, and immunological parameters. The study showed that hematological parameters (monocytes and granulocytes) remained unaffected except total leukocyte count and lymphocyte which were decreased highly significantly [P≤0.01] in mice of group T3 on the 28(th) day of experiment. Serum total protein (TP) and serum globulin decreased significantly in mice of treatment groups dose dependently; however, no significant change was seen in serum albumin. Progressive increase in live body weight of mice decreased significantly in extremely toxic group only while spleen:body weight ratio decreased significantly in dose-dependent manner. Furthermore, Ace produced suppressed humoral immune response and the delayed-type hypersensitivity response to Sheep red blood cells (SRBCs) was altered nonsignificantly. The results of this study describe the suppression of immune responses following exposure to Ace at low concentrations in experimental mice.


Midline lumbar fusion with cortical bone trajectory screw.
A novel cortical bone trajectory (CBT) screw technique provides an alternative fixation technique for lumbar spine. Trajectory of CBT screw creates a caudo-cephalad path in sagittal plane and a medio-lateral path in axial plane, and engages cortical bone in the pedicle. The theoretical advantage is that it provides enhanced screw grip and interface strength. Midline lumbar fusion (MIDLF) is composed of posterior midline approach, microsurgical laminectomy, and CBT screw fixation. We adopted the MIDLF technique for lumbar spondylolisthesis. Advantages of this technique include that decompression and fusion are available in the same field, and it minimizes approach-related damages. To determine whether MIDLF with CBT screw is as effective as traditional approach and it is minimum invasive technique, we studied the clinical and radiological outcomes of MIDLF. Our results indicate that MIDLF is effective and minimum invasive technique. Evidence of effectiveness of MIDLF is that patients had good recovery score, and that CBT screw technique was safety in clinical and stable in radiological. MIDLF with CBT screw provides the surgeon with additional options for fixation. This technique is most likely to be useful for treating lumbar spondylolisthesis in combination with midline decompression and insertion of an interbody graft, such as the transforaminal lumbar interbody fusion or posterior lumbar interbody fusion techniques.


A novel retinoid X receptor-independent thyroid hormone response element is present in the human type 1 deiodinase gene.
We identified two thyroid hormone response elements (TREs) in the 2.5-kb, 5'-flanking region of the human gene encoding type 1 iodothyronine deiodinase (hdio1), an enzyme which catalyses the activation of thyroxine to 3,5,3'-triiodothyronine (T3). Both TREs contribute equally to T3 induction of the homologous promoter in transient expression assays. The proximal TRE (TRE1), which is located at bp -100, has an unusual structure, a direct repeat of the octamer YYRGGTCA hexamer that is spaced by 10 bp. The pyrimidines in the -2 position relative to the core hexamer are both essential to function. In vitro binding studies of TRE1 showed no heterodimer formation with retinoid X receptor (RXR) beta or JEG nuclear extracts (containing RXR alpha) and bacterially expressed chicken T3 receptor alpha 1 (TR alpha) can occupy both half-sites although the 3' half-site is dominant. T3 causes dissociation of TR alpha from the 5' half-site but increases binding to the 3' half-site. Binding of a second TR to TRE1 is minimally cooperative; however, no cooperativity was noted for a functional mutant in which the half-sites are separated by 15 bp, implying that TRs bind as independent monomers. Nonetheless, T3 still causes TR dissociation from the DR+15, indicating that dissociation occurs independently of TR-TR contact and that rebinding of a T3-TR complex to the 3' half-site occurs because of its slightly higher affinity. A distal TRE (TRE2) is found at bp -700 and is a direct repeat of a PuGGTCA hexamer spaced by 4 bp. It has typical TR homodimer and TR-RXR heterodimer binding properties. The TRE1 of hdio1 is the first example of a naturally occurring TRE consisting of two relatively independent octamer sequences which do not require the RXR family of proteins for function.


Analysis of nucleosides and monophosphate nucleotides from mushrooms with reversed-phase HPLC.
The retention characteristics of five stationary phases were tested by using a selection of 5'-mononucleotides and nucleosides with the aim to develop a simple, rapid and sensitive reversed-phase liquid chromatography method without ion-pair reagent usage. The method was optimized by changes in temperature, pH and ionic strength on a column showing a superior performance. The mobile phase consisted of a mixture of 0.05 M phosphate buffer and methanol, delivered at a flow rate of 0.4 mL/min and based on a gradient program. UV detection was used at a 254 nm wavelength. The method was validated for a quantitative analysis of 5'-mononucleotides and nucleosides in wild edible mushrooms. For all nucleosides and nucleotides, the LOD and LOQ were less than 0.02 and 0.07 microg/mL, respectively. Validation parameters yielded recovery rates between 68.6 and 98.2%, with a precision expressed as a relative standard deviation of 7.6-15.3%. The content of 5'-mononucleotides and nucleosides was determined for 10 samples of wild edible mushrooms found in Croatia and, accordingly, the equivalent umami concentrations were calculated.


Insulin stimulates human skeletal muscle protein synthesis via an indirect mechanism involving endothelial-dependent vasodilation and mammalian target of rapamycin complex 1 signaling.
Our objective was to determine whether endothelial-dependent vasodilation is an essential mechanism by which insulin stimulates human skeletal muscle protein synthesis and anabolism. Subjects were healthy young adults (n=14) aged 31+/-2 yr. Subjects were studied at baseline and during local leg infusion of insulin alone (control, n=7) or insulin plus the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, n=7) to prevent insulin-induced vasodilation. We measured skeletal muscle protein metabolism with stable isotope tracers, blood flow with indocyanine green, capillary recruitment with contrast enhanced ultrasound, glucose metabolism with stable isotope tracers, and phosphorylation of proteins associated with insulin (Akt) and amino acid-induced mammalian target of rapamycin (mTOR) complex 1 (mTORC1) signaling (mTOR, S6 kinase 1, and eukaryotic initiation factor 4E-binding protein 1) with Western blot analysis. No basal differences between groups were detected. During insulin infusion, blood flow and capillary recruitment increased in the control (P<0.05) group only; Akt phosphorylation and glucose uptake increased in both groups (P<0.05), with no group differences; and mTORC1 signaling increased more in control (P<0.05) than in L-NMMA. Phenylalanine net balance increased (P<0.05) in both groups, but with opposite mechanisms: increased protein synthesis (basal, 0.051+/-0.006 %/h; insulin, 0.077+/-0.008 %/h; P<0.05) with no change in proteolysis in control and decreased proteolysis (P<0.05) with no change in synthesis (basal, 0.061+/-0.004 %/h; insulin, 0.050+/-0.006 %/h; P value not significant) in L-NMMA. Endothelial-dependent vasodilation and the consequent increase in nutritive flow and mTORC1 signaling, rather than Akt signaling, are fundamental mechanisms by which insulin stimulates muscle protein synthesis in humans. Additionally, these data underscore that insulin modulates skeletal muscle proteolysis according to its effects on nutritive flow.


Facet violation with the placement of percutaneous pedicle screws.
Independent review and classification of therapeutic procedures performed on cadavers by surgeons blinded to purpose of study. The objective of this study is to determine the rate of facet violation with the placement of percutaneous pedicle screws. Improvements in percutaneous instrumentation and fluoroscopic imaging have led to a resurgence of percutaneous pedicle screw insertion in lumbar spine surgery in an attempt to minimize many of the complications associated with open techniques of pedicle screw placement. Rates of pedicle breech and neurologic injury resulting from percutaneous insertion are reportedly similar to those of open techniques. Postoperative pain because of impingement and instability is believed to result from violation of the facet capsule or facet joint. To the authors' knowledge, however, the rate of facet injury associated with the placement of percutaneous pedicle screws is unreported in the literature. Percutaneous pedicle screw placement was performed on 4 cadaveric specimens by 4 certified orthopedic surgeons who had clinical experience in the procedure and who were blinded to the study's purpose. The surgeons were instructed to place pedicle screws from L1-S1 using their preferred clinical techniques and a 5.5-mm screw system with which they were all familiar. All surgeons utilized 1 OEC C-arm for fluoroscopic imaging. After insertion, 2 independent spine surgeons each reviewed and classified the placement of all facet screws. A total of 48 screws were inserted and classified. The placement of 28 screws (58%) resulted in violation of facet articulation, with 8 of these screws being intra-articular. Interobserver reliability of the classification system was 100%. Percutaneous pedicle screw placement may result in a high rate of facet violation. Facet injury can be reliability classified and therefore, perhaps, easily prevented.