Improving searching skills and evidence retrieval.
To evaluate the effect of a three-hour training session in formulating questions and searching databases. A randomised controlled trial and before and after study, with blinded outcome assessment. Oxford University Medical School, first clinical year. Altogether 108 medical students were randomly assigned to an experimental group (54) or a control group (54), and all were given the task of searching for evidence around an ulcer related problem or a cardiac problem. Students in the experimental group were randomly allocated to research one of the two problems before training and the remaining problem afterwards. Control students received no training and were randomly allocated to search for evidence around either of these problems. Searching performance; the quality of evidence retrieved; student satisfaction. Training improved the students' search performance and the quality of evidence retrieved. Students' satisfaction with the training was high. A three-hour interactive training session improved the students' ability to search databases and retrieve evidence and was well received by the students.


Quadrivalent vaccine-targeted human papillomavirus genotypes in heterosexual men after the Australian female human papillomavirus vaccination programme: a retrospective observational study.
Australia introduced a national quadrivalent human papillomavirus (4vHPV) vaccination programme for girls and young women in April, 2007. The HPV genotypes targeted by the female vaccine could also affect the protection afforded to heterosexual men. We examined the prevalence of 4vHPV targeted vaccine genotypes and the nine-valent HPV (9vHPV)-targeted vaccines genotypes among sexually active, predominantly unvaccinated heterosexual men from 2004 to 2015. We did a retrospective, observational study of urine and urethral swab specimens from heterosexual men aged 25 years or younger attending the Melbourne Sexual Health Centre between July 1, 2004, and June 30, 2015, who tested positive for Chlamydia trachomatis. We extracted HPV DNA and used the PapType HPV assay to detect 14 high-risk HPV genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) and two low-risk genotypes (6 and 11). We calculated the prevalence of any HPV genotype, genotypes 6 or 11, genotypes 16 or 18, genotypes in the 4vHPV group (6, 11, 16, or 18), five additional genotypes in the 9vHPV group (31, 33, 45, 52, or 58), and non-vaccine-targeted genotypes (31, 33, 35, 39, 45, 51, 56, 58, 59, 66, or 68). We obtained data between July 1, 2004, and June 30, 2015, and did the data analysis in December, 2015. Of 1764 specimens obtained, we included 1466 in our final analysis (the others were excluded because they had indeterminate results or were duplicates). The prevalence of any HPV genotype and genotypes 31, 33, 45, 52, and 58 did not change from 2004-05 to 2014-15, but we noted reductions in genotypes 6 and 11 (from 12% [95% CI 6-21%], to 3% [1-7%], ptrend=0·008), 16 and 18 (from 13% [95% CI 7-22%] to 3% [1-6%], ptrend<0·0001), and 4vHPV-targeted genotypes (from 22% [95% CI 14-33%] to 6% [3-10%], ptrend<0·0001). Prevalence of non-vaccine-targeted genotypes increased from 16% [95% CI 9-26%] to 22% [17-29%], ptrend<0·0001). In Australian-born men, 4vHPV-targeted genotype prevalence decreased from 11 of 55 [20%, 95% CI 10-33%] to two of 74 [3%, 0-11%], ptrend<0·0001); an even greater decline occurred in Australian-born men aged 21 years or younger (from four of 13 [31%, 95% CI 9-61%] to none of 25; ptrend<0·0001). Genotypes 16 and 18 decreased (adjusted prevalence ratio [PR] 0·32, 95% CI 0·14-0·74; p=0·008) but not genotypes 6 and 11 (adjusted PR 0·50, 0·16-1·56; p=0·234) in the postvaccination period among men who had arrived in Australia within 2 years from countries with a bivalent vaccine (2vHPV) programme (England, Scotland, Wales, Cook Islands, Northern Ireland, or the Netherlands), compared with the prevaccination period. No change was noted in 4vHPV genotypes in men born overseas in other countries. The marked reduction in prevalence of 4vHPV genotypes among mainly unvaccinated Australian-born men suggests herd protection has occurred from the female vaccination programme. Additionally, the decline in genotypes 16 and 18, but not genotypes 6 and 11, among overseas-born men predominantly from countries with a 2vHPV vaccine programme suggests that these men received benefits from herd protection for genotypes 16 and 18 from their vaccinated female partners in their own countries. These reductions could translate to reductions in HPV-related malignant conditions in men, even in countries with female-only vaccination programmes. The Australian National Health and Medical Research Council Program.


2-(2-Fluoro-phen-yl)-3-methyl-sulfanyl-5-phenyl-1-benzo-furan.
In the title compound, C21H15FOS, the dihedral angles between the mean plane [r.m.s. deviation = 0.041 (1) Å] of the benzo-furan fragment and the pendant 2-fluoro-phenyl and phenyl rings are 46.09 (3) and 24.34 (5)°, respectively. In the crystal, mol-ecules are linked by weak C-H⋯π inter-actions, forming a three-dimensional network.


[Status of the system of hemostasis in patients with non-insulin-dependent and insulin-dependent diabetes mellitus without clinical manifestation of vessel pathology].
Analysis of 17 haemostasis indexes has been done in 10 insulin-dependent diabetes mellitus patients, 5 insulin-independent diabetes mellitus patients and in 9 healthy donors. It was determined some of the same type changes and peculiarities which must be taken into consideration both by the estimation of blood system coagulation activity of patients treatment and by definition of disease prognosis etc.


Polymerase chain reaction amplification of the Bag320 satellite family reveals the ancestral library and past gene conversion events in Bacillus rossius (Insecta Phasmatodea).
Polymerase chain reaction amplifications of genomic DNA in 17 individuals of bisexual and parthenogenetic populations of three subspecies of Bacillus rossius (Insecta Phasmatodea) revealed that the species still harbours the whole variability of the ancestral Bag320 satellite family, since monomers of all non-hybrid Bacillus taxa plus private sequences occur in it. Bag320 monomers had not been rescued as a major satellite component in B. rossius, but possibly represent the remnant of a set of diverging sequences present in the Bacillus ancestor. Following the library hypothesis, these monomer variants have been differently amplified along the evolutionary pathways leading to present taxa in agreement with the mitochondrial phylogeny of the genus. The putative converted tracts observed are explained as the results of past gene conversion events.


The Impact of Worsening Heart Failure in the United States.
In-hospital worsening heart failure represents a clinical scenario wherein a patient hospitalized for acute heart failure experiences a worsening of their condition, requiring escalation of therapy. Worsening heart failure is associated with worse in-hospital and postdischarge outcomes. Worsening heart failure is increasingly being used as an endpoint or combined endpoint in clinical trials, as it is unique to episodes of acute heart failure and captures an important event during the inpatient course. While prediction models have been developed to identify worsening heart failure, there are no known FDA-approved medications associated with decreased worsening heart failure. Continued study is warranted.


The legal setting in prescribing drugs.
By training and experience physicians generally prescribe drugs with only the patient in mind. In today's environment it is essential that the physician stop and think of himself also. We are all aware of malpractice problems, which begin in the physician's office or at the hospital and, if severe, end in court. The ophthalmologist must now consider what a disgruntled patient can find in writing to use in court. Hospital records and physician's charts are now just the beginning point. The Physician's Desk Reference (PDR), the published literature, the package insert, the promotional material of pharmaceutical companies, the internal records of drug companies, the pharmacists' records, and the data now obtainable from government agencies all provide happy hunting grounds for a competent plaintiff's attorney. The ophthalmologist needs to be keenly aware of these potentially adverse resources and how they can be used against him. He also needs to know the alternatives available to him. Once these matters are brought into clear perspective, both the patient and the ophthalmologist will be better off.


Continuous venous infusion of vindesine in metastatic breast cancer: experience with a subcutaneously implanted system and portable pump.
Fourteen patients with advanced pretreated breast cancer were treated with vindesine in continuous venous infusion (1.5 mg/sm/24 hours for 72 hours every 3 weeks). A totally implanted venous access and a portable pump were used. A total of 33 courses was administered. No objective response was observed and treatment was stopped. Drug-related toxicity consisted mainly of alopecia (64% of patients), nausea and vomiting (29%) and mucositis (29%). Catheter - related toxicity was observed in 6 patients (43%) and consisted of infection of the skin pocket in 4 patients and dislodging of the needle and catheter break in one patient. The feasibility of continuous venous infusion of vesicant drugs in outpatients is discussed.


MR imaging of flow through tortuous vessels: a numerical simulation.
A novel computer simulation technique is presented that allows the calculation of images from Magnetic Resonance Angiography (MRA) studies of blood flow in realistic curving and branching two-dimensional vessel geometries. Fluid dynamic calculations provide flow streamlines through curved or branching vessels. MR simulations generate images for specific MR pulse sequence parameters. Simulations of steady flow in carotid bifurcation and carotid siphon geometries as imaged by a standard, flow-compensated, spoiled gradient echo sequence illustrate the major features seen in clinical time of flight MRA studies. The simulations provide insight into a number of artifacts encountered in MRA such as displacement artifacts, signal pile-up, truncation artifacts, and intravoxel phase dispersion.


Early stimulation of ATP turnover induced by growth factors. Synergistic effect of EGF and insulin and correlation with DNA synthesis.
Addition of a mixture of EGF + insulin to quiescent cell cultures synergistically stimulates the cells to reinitiate DNA synthesis and cell division. We have previously demonstrated that this mixture rapidly increases ATP turnover in quiescent cells. The present work shows that each of the two growth factors, EGF and insulin, when added separately to quiescent cells was able to stimulate the phosphorylation of the organic acid-soluble compounds (Po) pool and ATP turnover. The stimulation of ATP turnover was closely correlated with the increase in phosphorylation of the Po pool which suggests that Po labelling reflects the ATP turnover. In many experiments, the synergy between the two growth factors on the early increase in phosphorylation of the Po pool was clearly shown. Doubling the concentration of EGF (12-24 ng/ml) or insulin (50-100 ng/ml) did not increase early stimulation of phosphorylation of the Po pool, whereas simultaneous addition of the two growth factors induced a greater stimulation than that of each growth factor separately added. The augmentation in Po labelling after addition of EGF or insulin alone was transient. The synergistic effect of the two growth factors was more significant when determined 150 or 300 min after growth-factor addition. In our experimental conditions, each of the two growth factors, EGF and insulin, was able to induce a stimulation of DNA synthesis. However, the best stimulatory effect was observed with the mixture of the two which synergistically increased DNA synthesis determined between 6 and 24 h after growth-factor addition. The comparison between DNA replication and Po labelling suggests a correlation between the increase in DNA replication and in the total ATP synthesized in the first 5 h after cell stimulation by growth factors added separately or in combination.


Rare solitary giant hamartomatous polyp of the stomach removed by endoscopic submucosal dissection.
Video 1Endoscopic submucosal dissection of a large solitary gastric hamartomatous polyp.


Acute and chronic animal models for the evaluation of anti-diabetic agents.
Diabetes mellitus is a potentially morbid condition with high prevalence worldwide thus being a major medical concern. Experimental induction of diabetes mellitus in animal models is essential for the advancement of our knowledge and understanding of the various aspects of its pathogenesis and ultimately finding new therapies and cure. Experimental diabetes mellitus is generally induced in laboratory animals by several methods that include: chemical, surgical and genetic (immunological) manipulations. Most of the experiments in diabetes are carried out in rodents, although some studies are still performed in larger animals. The present review highlights the various methods of inducing diabetes in experimental animals in order to test the newer drugs for their anti-diabetic potential.


Serotype 1 pneumococcus: epidemiology, genomics, and disease mechanisms.
Streptococcus pneumoniae (the 'pneumococcus') is a significant cause of morbidity and mortality worldwide, causing life-threatening diseases such as pneumonia, bacteraemia, and meningitis, with an annual death burden of over one million. Discovered over a century ago, pneumococcal serotype 1 (S1) is a significant cause of these life-threatening diseases. Our understanding of the epidemiology and biology of pneumococcal S1 has significantly improved over the past two decades, informing the development of preventative and surveillance strategies. However, many questions remain unanswered. Here, we review the current state of knowledge of pneumococcal S1, with a special emphasis on clinical epidemiology, genomics, and disease mechanisms.


Comparative study using phenotypic, genotypic, and proteomics methods for identification of coagulase-negative staphylococci.
Five methods were compared to determine the most accurate method for identification of coagulase-negative staphylococci (CoNS) (n = 142 strains). Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) showed the best results for rapid and accurate CoNS differentiation (99.3% of strains correctly identified). An alternative to this approach could be Vitek2 combined with partial tuf gene sequencing (100% of strains correctly identified when both methods are performed simultaneously).


Effect of nicotine on quinpirole-induced checking behavior in rats: implications for obsessive-compulsive disorder.
Rats treated chronically in a large, open field with the dopamine D2/D3 receptor agonist quinpirole (QNP) develop compulsive checking behavior as defined by a set of behavioral criteria. This paradigm has been suggested as an animal model of obsessive-compulsive disorder (OCD). Because nicotine blocks various behaviors induced by ontogenetic QNP administration, we asked whether nicotine could attenuate QNP-induced compulsive checking. Adult male Long-Evans rats (n = 14/group) were treated twice weekly with saline (control), or with QNP (0.5 mg/kg) for 14-16 injections. On the last two injections, rats were pretreated in random order with an acute dose of nicotine (0.3 mg/kg base) or saline 10 min before administration of QNP or saline; and the effects on checking behavior was examined. The effects of chronic QNP treatment on nicotinic receptors in discrete brain regions were also determined. Chronic QNP resulted in compulsive checking and increases in cerebellar alpha4beta2 and alpha7 nicotinic receptor densities. Nicotine pretreatment significantly reduced one of the three measures of compulsive checking behavior. Nicotine attenuates some symptoms of compulsive checking in a rat model of OCD; however, the mechanisms of this effect and therapeutic efficacy of nicotinic agonists in OCD require further study.


Intravenous Shiga toxin 2 promotes enteritis and renal injury characterized by polymorphonuclear leukocyte infiltration and thrombosis in Dutch Belted rabbits.
Enterohemorrhagic Escherichia coli (EHEC) infection causes hemolytic uremic syndrome, a leading cause of acute renal failure in children. Dutch Belted (DB) rabbits are susceptible to EHEC-induced disease. Using real-time quantitative RT-PCR we measured the renal mRNA expression of cytokines and fibrinolytic factors in DB rabbits challenged with intravenous Shiga toxin 2 (Stx2) (1200 ng/kg). Group 1 rabbits received an incremental dose during an 8-day period whereas Group 2 rabbits received a single dose. Group 1 rabbits developed mild disease. In contrast, Group 2 rabbits developed severe diarrhea, higher levels of circulating polymorphonuclear leukocytes, increased mean platelet volume, and increased fibrinogen levels. Group 2 rabbits developed polymorphonuclear leukocyte infiltration in the intestine and kidney as well as glomerular congestion, luminal constriction, and mesangial glomerulonephropathy. These renal lesions were associated with up-regulation of interleukin-8 (P<0.006), plasminogen activator inhibitor-1 (P<0.04), and tissue plasminogen activator (P<0.05). Circulating Stx2 promoted dose-dependent enteritis and renal injury characterized by inflammation and impaired fibrinolysis leading to thrombosis.


Novel recovery methods for biological materials in cases of alleged sexual assault: A word of caution.
Many believe that an increase in the public confidence in the investigation of sexual crimes, and in conviction rates, will lead to an increase in the reporting of these crimes. Consequently, Forensic Science Providers are continually striving to make improvements in evidence recovery and examination and the subsequent interpretation of evidence. One development is in methods that enable an individual to self-sample. However, in cases where a complainant has self-sampled, questions of when the samples were taken, how they were stored and so on, can be legitimately raised. Additionally the continuity and integrity of evidential samples may be questioned resulting in them not being acceptable to the courts and potential evidence could therefore be lost. There is a large emotional and psychological impact of sexual assault and rape and no complainant who reports a sexual assault and recovers material should have that evidence inadmissible to a court. Specialised units for victims of alleged sexual violence are available and offer far more than the recovery of evidential samples. This commentary on behalf of the Faculty of Forensic & Legal Medicine (FFLM) and the Association of Forensic Science Providers Body Fluid Forum (AFSP BFF) highlights the need for after care for the victims of sexual assault and why all evidence recovered in cases of alleged sexual assault and sexual violence should be obtained in line with best practice protocols.


The precise midline forehead flap in reconstruction of the nose.
The midline forehead flap has been a preferred choice for nasal repair in our practice for over 20 years, with no significant complication ever having developed (Figs. 9 to 11). The abundance and length of tissue it provides is remarkable, given the inconspicuous defect remaining in the forehead area. Its use is economical of tissue, time, and expense to the patient. Most importantly, the midline flap provides superior aesthetic and reconstructive repair in a relatively short period of time without resorting to more complicated, and therefore more risky, flap designs.


Changes in functional gastrointestinal symptoms as a result of antireflux surgery.
This study identifies how functional symptoms are altered after antireflux surgery and whether there are any predictors of such change. A total of 206 patients underwent successful laparoscopic Nissen fundoplication. A questionnaire was sent at a median of 4.3 years (range = 0.3-8.4) after fundoplication. Patients were asked to provide scores for reflux and functional symptoms that were experienced prior to surgery and at the time of the questionnaire. Eighty-one percent of patients responded. Scores for heartburn, regurgitation, and difficulty swallowing were felt to have significantly improved (p < 0.01). Flatulence was the only functional symptom to have significantly worsened (p < 0.01). A regression analysis incorporating prospectively collected data identified variables that were predictive of changes in functional symptoms following surgery. Flatulence was the only functional symptom to have worsened overall after surgery. Predictors of changes in functional symptoms may help clinicians when informing patients about gastrointestinal side effects following antireflux surgery.


A Privacy Preservation Secure Cross Layer Protocol Design for IoT Based Wireless Body Area Networks Using ECDSA Framework.
Internet of Things (IoT) provides the collection of devices in different applications in which Wireless Body Area Network (WBAN) is placed an crucial role. The WBAN is a wireless sensor network consisting of sensor nodes that is collected from IoT which is implanted in the human body to remotely monitor the patient's physiological signals without affecting their routine work. During emergency situations or life-threatening situations there is a need for a better performance to deliver the actual data with an efficient transmission and there is still a challenge in efficient remote monitoring. So, in this paper an application for cross layer protocol design architecture of Elliptic Curve Digital Signature Algorithm (ECDSA) has been proposed. It replaces the protocol architecture of WBAN (IEEE 802.15.6), WMAN (IEEE 802.16), and 3G, WLAN (IEEE 802.11) or wired networks. The lightweight secure system provides secure data transmission and access control mechanisms by using ECDA-based proxy signature algorithm. The efficiency of the system is implemented using simulation models that were developed using NS-2, and the results obtained shows an optimum solution in terms of delay, PDR, throughput, jitter, packet transmission time, dropping ratio and packet delivery. The viability of the methodology proposed is illustrated by the response.


Deep brain stimulation of terminating axons.
Deep brain stimulation (DBS) of the subthalamic region is an established treatment for the motor symptoms of Parkinson's disease. Several types of neural elements reside in the subthalamic region, including subthalamic nucleus (STN) neurons, fibers of passage, and terminating afferents. Recent studies suggest that direct activation of a specific population of subthalamic afferents, known as the hyperdirect pathway, may be responsible for some of the therapeutic effects of subthalamic DBS. The goal of this study was to quantify how axon termination affects neural excitability from DBS. We evaluated how adjusting different stimulation parameters influenced the relative excitability of terminating axons (TAs) compared to fibers of passage (FOPs). We used finite element electric field models of DBS, coupled to multi-compartment cable models of axons, to calculate activation thresholds for populations of TAs and FOPs. These generalized models were used to evaluate the response to anodic vs. cathodic stimulation, with short vs. long stimulus pulses. Terminating axons generally exhibited lower thresholds than fibers of passage across all tested parameters. Short pulse widths accentuated the relative excitability of TAs over FOPs. Our computational results demonstrate a hyperexcitability of terminating axons to DBS that is robust to variation in the stimulation parameters, as well as the axon model parameters.


Garlic peel based mesoporous carbon nanospheres for an effective removal of malachite green dye from aqueous solutions: Detailed isotherms and kinetics.
Biowaste based nanoadsorbents have gained much attention in the recent times for wastewater decolourization owing to their low cost, high surface area and high adsorption capacities. In the present research, garlic peel based nanoparticles (GCNP) were synthesized at different temperatures by a one step pyrolytic green approach for the effective removal of cationic dye, malachite green from the aqueous medium. The surface properties of Garlic nanoparticles were elucidated by N2 adsorption- desorption and all the GCNP samples were found to exhibit Type IV(a) isotherm indicating the presence of mesopores in carbon matrix. Using BET calculations, highest surface area (380 m2/g) was obtained for GCNP synthesized at 1000 ◦C. Characterization of nanoparticles was done by XRD, EDAX, SEM and FTIR studies before and after the dye treatment. Adsorption studies conducted using different parameters like contact time, concentration and pH and dosage of adsorbent showed removal efficiency above 90% for the contact time of 70 min. Best adsorption experimental results were obtained for GCNP synthesized at 1000 °C ascribable to its high surface area, higher total pore volume (0.26 cm2/g) and higher carbon content. Four adsorption isotherm models were used to validate batch equillibrium studies and the results showed data in good agreement with Langmuir and Freundlich isotherms with maximum Langmuir adsorbtion capactiy to be 373.7 mg/g. Kinetic modelling of the data showed best fit with the Pseudo second order model with rate constant value of 48.726 g mg-1 min-1. Regenerative studies were conducted conducted upto 6 cycles. Also the GC nanoparticles were tested for their compatibility in membrane form wherein, removal efficiency results were obtained for GCNP anchored in polyvinyl difluoride (PVDF) and polysulfone (PSF) membrane matrix for dye adsorption.


Mechanism of tachykinin NK3 receptor-mediated colonic ion transport in the guinea pig.
The guinea pig colon was used to elucidate the mechanism of tachykinin-induced secretion. Increased short-circuit current was observed in response to natural and synthetic tachykinins with rank orders of potency of substance P > neurokinin A = neuropeptide K>> neuropeptide gamma; and senktide (tachykinin NK3 receptor agonist)> Sar-substance P (tachykinin NK1 receptor agonist)> betaAlaneurokinin A (tachykinin NK2 receptor agonist)). A functional role of tachykinin NK1 receptors was confirmed as substance P and neurokinin A responsiveness was blocked by the tachykinin NK1 receptor antagonist GR82334. The tachykinin NK3 receptor antagonist SB222200 had no effect, leaving in doubt the identity of the natural tachykinin NK3 receptor ligand in the colon. The response to tachykinin NK3 receptor activation was abolished by tetrodotoxin and predominantly due to atropine sensitive cholinergic activation. The non-cholinergic component resulted from stimulation of tachykinin NK 1 and 5-HT receptors as the response to senktide was blocked by GR82334 and tropisetron. In conclusion, tachykinin NK3 receptor activation stimulates cholinergic and non-cholinergic (tachykinin NK1-receptor and serotonin-mediated) secretory pathways.


Common Emergencies in Pet Birds.
Treating avian emergencies can be a challenging task. Pet birds often mask signs of illness until they are critically ill and require quick initiation of supportive care with minimal handling to stabilize them. This article introduces the clinician to common avian emergency presentations and details initial therapeutics and diagnostics that can be readily performed in the small-animal emergency room. Common disease presentations covered include respiratory and extrarespiratory causes of dyspnea, gastrointestinal signs, reproductive disease, neurologic disorders, trauma, and toxin exposure. The duration and severity of the avian patient's disease and the clinician's initiation of appropriate therapy often determines clinical outcome.


Remarkable differences between copper-based sulfides and iron-based sulfides for the adsorption of high concentrations of gaseous elemental mercury: Mechanisms, kinetics, and significance.
Copper sulfides (CuSx) and iron sulfides (FeSx) have been developed to capture gaseous elemental mercury (Hg0) originating from the smelting flue gas. However, these compounds exhibit different Hg0 adsorption characteristics and Hg species adsorbed on CuSx can be spontaneously released as gaseous Hg0. Following these findings, the adsorption/desorption kinetics of Hg0 onto and from FeSx and CuSx were determined. After comparing the kinetic parameters, the mechanisms behind some of the remarkable differences between FeSx and CuSx with respect to Hg0 adsorption were discovered. The Cu-S bond in CuSx was not completely broken during Hg0 oxidation, but the SS bond in FeSx was. Hence, the activation energy for the oxidation of Hg0 physically adsorbed on CuSx was much lower than that for FeSx, resulting in a much higher efficiency of CuSx to oxidize Hg0 than FeSx. However, the bond strength of Hg-S for HgS on CuSx was weaker due to the sharing of S2- in HgS with Cu+, resulting in a decrease in the thermal stability of HgS on CuSx. Therefore, HgS adsorbed on Cu-based sulfides was metastable, and could be spontaneously decomposed to release moderate concentrations of gaseous Hg0, which was not preferable for capturing high concentrations of Hg0.


Comparative efficacy of liposome-entrapped amiloride and free amiloride in animal models of seizures and serum potassium in mice.
The present study was aimed to evaluate a liposomal formulation of amiloride on experimental seizure models including the increasing current electroshock seizure threshold test (ICES), pentylenetetrazole (PTZ)-induced seizures and PTZ-induced status epilepticus in mice. Further, the effect of liposomal amiloride on serum K(+) levels was also investigated using flame photometry. We found an improved anticonvulsant action with liposome-entrapped amiloride as compared to free amiloride. Further, free amiloride showed an increase in serum K(+) levels, however the latter was unaffected with liposomal formulation treatment. These results, together with previously published data, suggest that as drug delivery vehicles, liposomes can enhance the effectiveness of drugs in the CNS without producing peripheral toxicity (hyperkalemia).


Metal chelate affinity precipitation of RNA and purification of plasmid DNA.
The affinity of metal chelates for amino acids, such as histidine, is widely used in purifying proteins, most notably through six-histidine 'tails'. We have found that metal affinity interactions can also be applied to separation of single-stranded nucleic acids through interactions involving exposed purines. Here we describe a metal affinity precipitation method to resolve RNA from linear and plasmid DNA. A copper-charged copolymer of N-isopropyl acrylamide (NIPAM) and vinyl imidazole (VI) is used to purify plasmid from an alkaline lysate of E. coli. The NIPAM units confer reversible solubility on the copolymer while the imidazole chelates metal ions in a manner accessible to interaction with soluble ligands. RNA was separated from the plasmid by precipitation along with the polymer in the presence of 800 mM NaCl. Bound RNA could be recovered by elution with imidazole and separated from copolymer by a second precipitation step. RNA binding showed a strong dependence on temperature and on the type of buffer used.


[Prosthetic rehabilitation of a traumatic occlusion due to bulimia nervosa. Case report].
Because of the typical localisation of erosions in anorectic/bulimic patients, the dentist is frequently the first medical person to discern this general illness (anorexia and bulimia nervosa). From the dental viewpoint, the aim should be to preserve sound dental tissue and to prevent further toothwear. A restorative treatment is to be carried out only after causal therapy and after resolving the basic disease. By means of this procedure a good long-term prognosis can be expected. Considering the patient's young age, dentistry should be preservative using the adhesive technique. This case report documents the systematic procedure of the functional and esthetic rehabilitation of an eroded dentition and shows factors essential to the treatment.


Neurosurgical Residency Training in Latin America: Current Status, Challenges, and Future Opportunities.
This analysis provides an overview of neurosurgery residency programs in Latin America; it evaluates strengths, weaknesses, and limitations within the Latin American Federation for Societies in Neurosurgery countries. Considering the shared cultural background between these neighboring countries and globalization of neurosurgical education, similarities in training characteristics and equal opportunities are expected. However, program differences are inevitable and should be investigated to promote collaboration and homogenization of training. A 39-item survey was distributed to 970 neurosurgeons and residents in Latin America to assess aspects including working conditions, teaching, research, training, educational opportunities, and socioeconomics. In total, 276 neurosurgeons (28%) from 16 countries completed the survey. The average participant's age was 37 ± 7 years, and the average duration of residency programs was 5 ± 1 years. Trainees participated in around 5-10 cases during the typical 80-100 work hour week. Only 5% of survey respondents had a day off after a night shift, and 60% worked at least 3 night shifts per week. Only 34% had a mentorship program, Morbidity and mortality conferences were reported by 57% and research activities were compulsory in 45%. Satisfaction with evaluation methods was reported in 29%, although 96% reported satisfaction with their training programs overall. This study is the first of its kind to review neurosurgical training in Latin America's. Suggested areas of improvement include regulation of working hours, implementation of mentorship programs and standardized examinations, protected research time, increased support for conferences, and more opportunities for exchange rotations that will potentially bolster collaboration between programs.


Prenatal diagnosis in 100 structural rearrangements of the chromosomes.
Among 900 couples referred for prenatal diagnosis, the indication was a parental balanced structural chromosome anomaly in 94, of which 39 were Robertsonian translocations, 38 reciprocal translocations, and 17 pericentric inversions. Six fetuses were unbalanced. The methods of ascertainment of the anomaly in these couples and the gametic segregation transmitted to the concepti are analyzed. A de novo unbalanced structural anomaly was detected in fetal cells in 6 diagnoses performed in couples referred for indications other than chromosomal.


Genetic variations in vitamin D receptor were associated with the outcomes of hepatitis C virus infection among Chinese population.
Vitamin D has been considered as an immune modulator, and exerted the effect through the vitamin D receptor (VDR). This study investigated the associations of single-nucleotide polymorphisms (SNPs) of VDR with the outcomes of Hepatitis C virus (HCV) infection. Three SNPs (rs2228570, rs757343 and rs739837) were genotyped by TaqMan assay among Chinese population, including 538 HCV spontaneous clearance subjects, 834 persistent infection subjects and 1030 uninfected subjects. Binary logistic analyses were used to control the effects of confounding factors. The results showed that subjects with the rs757343 A allele and rs739837 A allele had the significantly reduced risk of HCV susceptibility (all PBonferroni<0.05 in dominant/additive model). In the stratified analysis, the protection of rs757343 A allele and rs739837 A allele against HCV infection remained effective in some subgroups. In addition, patients carrying rs739837 CA genotype were less prone to develop persistent infection (PBonferroni=0.033) and such effect still work in several subgroups in the stratified analysis. Furthermore, haplotype analysis indicated that when compared with the most frequent GC haplotype, the haplotype carrying AA (odds ratio (OR)=0.66, 95% confidence interval (CI)=0.56-0.78) and GA (OR=0.64, 95% CI=0.47-0.85) suggested a protective effect. Our findings indicated that the polymorphisms of VDR are associated with the outcomes of HCV infection among Chinese population.


Factors initiating algal life-form shift from sediment to water.
In enclosure and whole-lake experiments, I tested whether life-form shift (recruitment) is a passive process induced by turbulence, a seasonal phenomenon, or a behavior that can be induced by alterations in environmental variables. The number of algal cells recruited from the sediment varied considerably during the experimental period. The most important migrating genera in this study were: Cryptomonas, Dinobryon, Gonyostomum, Gymnodinium, Peridinium, and Synura. An obvious conclusion is that it is not the same factor in each case that causes life-form shift, but that different triggering factors operate in different algal species. Turbulence and temperature were similar in all treatments and therefore did not cause the considerable fluctuations and trends in algal recruitment in the enclosures. This suggests that life0form shift is not a passive process driven by wind and temperature-induced currents. In the enclosure experiment, alterations in the light régime explained a major part (up to 53%) of the variation in recruitment for most genera. For Gymnodinium this was corroborated in the whole-lake experiment, where the depth of the euphotic zone explained 41% of the variation in recruitment. For Cryptomonas, however, 64% of the variation in recruitment was explained by the depth of the "oxycline", whereas 52% of the variation in recruitment of Synura were explained by the depths of the euphotic zone and the oxyline. Peridinium pusillum and P. wisconsinense showed low recruitment at high zooplankton abundance and high recruitment at low zoo-plankton abundance in the lake experiment, as well as in the enclosure experiment. Thus, the hypothesis that the presence of grazers can induce shifts in behaviour of some algal groups cannot be rejected.


Declining in-hospital mortality in patients undergoing coronary bypass surgery in the United States irrespective of presence of type 2 diabetes or congestive heart failure.
Significant advances in surgical techniques and postsurgical care have been made in the last 10 years. The goal of this study was to evaluate any decline in the age-adjusted in-hospital mortality rate of patients undergoing coronary artery bypass grafting (CABG) using a national database from 1989 to 2004 in the United States. Reduction in CABG related mortality in recent years. Using the Nationwide Inpatient Sample (NIS) database, we obtained specific ICD-9-CM codes forCABG to compile the data. To exclude nonatherosclerotic cause of coronary disease, we studied only patients older than 40 years. We calculated total and age-adjusted mortality rate per 100,000 for this period. The NIS database contained 1 145 285 patients who had CABG performed from 1988 to 2004. The mean age for these patients was 71.05 ± 9.20 years. From 1989, the age-adjusted rate for all CABG-related mortality has been decreasing steadily and reached the lowest level in 2004: 300.3 per 100 000 in 1989, (95%confidence interval [CI], 20.4-575.9) and 104.69 per 100 000 (95% CI, 22.6-186.7) in 2004. Total death also declined from 5.5% to 3.06%. This decline occurred irrespective of comorbidities such as congestive heart failure, diabetes, or acute myocardial infarction, albeit increasing the number of CABG procedures performed in high-risk patients. The age-adjusted in-hospital mortality rate from CABG has been declining steadily and reached its lowest level in 2004, irrespective of comorbidities. This decline most likely reflects advances in surgical techniques and the use of evidence-based medicine in patients undergoing CABG.


Interactions between Bordetella bronchiseptica and toxigenic Pasteurella multocida in atrophic rhinitis of pigs.
Three strains of Bordetella bronchiseptica were compared for their ability to assist colonisation of the nasal cavity of gnotobiotic pigs by toxigenic Pasteurella multocida. Toxigenic P multocida (counted in nasal washings) colonised the cavity in large numbers in pigs previously infected with a cytotoxic phase I strain of B bronchiseptica (B58), whereas it colonised only in small numbers in those previously infected with B65, a phenotypic phase III variant of B58. Toxigenic P multocida colonised pigs infected with a non-cytotoxic phase I strain of B bronchiseptica (PV6) in fewer numbers than were seen in pigs infected with the cytotoxic phase I strain but in greater numbers than in pigs infected with the phase III strain. The turbinates of pigs infected with the cytotoxic phase I strain of B bronchiseptica and toxigenic P multocida were most severely affected and those in pigs infected with the non-cytotoxic phase I strain and toxigenic P multocida were moderately reduced in size. The turbinates of pigs infected with the phase III strain and toxigenic P multocida were slightly reduced in size except for one piglet whose turbinates were severely affected. Pigs infected with the non-cytotoxic phase I strain of B bronchiseptica alone showed no signs of atrophy and their turbinates were used to calculate reductions (per cent) in those infected with P multocida. The reduction (per cent) in size of turbinates and total numbers of P multocida isolated from the nasal washings of each pig were linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)


Inhibitors of Advanced Glycation End Product (AGE) Formation and Accumulation.
A range of chemically different compounds are known to inhibit the formation and accumulation of advanced glycation end products (AGEs) or disrupt associated signalling pathways. There is evidence that some of these agents can provide end-organ protection in chronic diseases including diabetes. Whilst this group of therapeutics are structurally and functionally different and have a range of mechanisms of action, they ultimately reduce the deleterious actions and the tissue burden of advanced glycation end products. To date it remains unclear if this is due to the reduction in tissue AGE levels per se or the modulation of downstream signal pathways. Some of these agents either stimulate antioxidant defence or reduce the formation of reactive oxygen species (ROS), modify lipid profiles and inhibit inflammation. A number of existing treatments for glucose lowering, hypertension and hyperlipidaemia are also known to reduce AGE formation as a by-product of their action. Targeted AGE formation inhibitors or AGE cross-link breakers have been developed and have shown beneficial effects in animal models of diabetic complications as well as other chronic conditions. However, only a few of these agents have progressed to clinical development. The failure of clinical translation highlights the importance of further investigation of the advanced glycation pathway, the diverse actions of agents which interfere with AGE formation, cross-linking or AGE receptor activation and their effect on the development and progression of chronic diseases including diabetic complications. Advanced glycation end products (AGEs) are (1) proteins or lipids that become glycated as a result of exposure to sugars or (2) non-proteinaceous oxidised lipids. They are implicated in ageing and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney and Alzheimer's disease. Several antihypertensive and antidiabetic agents and statins also indirectly lower AGEs. Direct AGE inhibitors currently investigated include pyridoxamine and epalrestat, the inhibition of the formation of reactive dicarbonyls such as methylglyoxal as an important precursor of AGEs via increased activation of the detoxifying enzyme Glo-1 and inhibitors of NOX-derived ROS to reduce the AGE/RAGE signalling.


Neuronal degeneration induced by stereotaxic injection of beta-bungarotoxin into rat brain.
The presynaptic protein neurotoxin beta-bungarotoxin (beta-bgt) caused degeneration of neurons, following stereotaxic administration into rat brain. Focal lesions were induced with as little as 0.1 ng (5 fmol) of beta-bgt; indicating that the toxin is over 10(6) times more potent than kainic acid. More extensive studies in the septo-hippocampal system showed beta-bgt lesions affected both cell bodies and nerve terminals and were not neurotransmitter-specific. The endogenous phospholipase A2 activity of beta-bgt did not simply account for the creation of lesions since an acidic phospholipase A isoenzyme from Vipera russellii was virtually inactive in causing neuronal damage.


Adenosine modulates depolarization-induced release of 3H-noradrenaline from slices of rat brain neocortex.
The effects of adenosine and some related purines on the K+-induced release of 3H-noradrenaline from rat cerebral cortex slices were determined in a superfusion system. Adenosine and ATP caused a dose-dependent inhibition of 3H-NA release with a maximal effect of 35% at 10(-4) M. Theophylline, 10(-4) M, antagonized the inhibitory effect of adenosine. The results support the hypothesis that at least some of the central stimulant effects of the methylxanthines could be related to blockade of a purinergic inhibitory tone on noradrenergic synaptic output.


Postural deviation in pregnancy: A significant debilitating balance problem which can be rectified by physiotherapeutic intervention.
The purpose of this study was to evaluate the effect of physiotherapeutic intervention to improve the deviated balance of pregnant women. A total of 174 subjects were included in the study out of which 62 had postural deviation. They were divided into three groups, two intervention groups and one control group. The target population consisted of women in the antenatal stage, randomly selected from Obstetrics and Gynecology OPD, PGIMER, Chandigarh. The study was conducted over a period of 3 years (2014-2017). They were advised exercises, postural correction, regular walking, and hot water fomentation. Six follow-ups were taken into consideration throughout the pregnancy and postnatal stage. The impact of the intervention package on both ante-natal and postnatal women with balance problems showed significant improvement. Postural deviations, pain, heaviness in the lower limb, incontinence, breathlessness, etc., are common complaints during and after pregnancy. The problem starts early in pregnancy and increased over time and may persist throughout life if treatment does not start early in the pregnancy. This intervention can be practiced in primary care setting after giving proper training to the health care workers by experienced physiotherapists.


Purification, characterisation and distribution of ovine neuronal nitric oxide synthase.
Nitric oxide (NO) is an ubiquitous intercellular messenger molecule synthesised from the amino acid L-arginine by the enzyme nitric oxide synthase (NOS). A number of NOS iso-enzymes have been identified, varying in molecular size, tissue distribution and possible biological role. To further understand the role of NO in the regulation of neuroendocrine function in the sheep, we have purified and characterised ovine neuronal NOS (nNOS) using anion exchange, affinity and size-exclusion chromatography. SDS-PAGE reveals that ovine nNOS has an apparent denatured molecular weight of 150 kDa which correlates well with the other purified nNOS forms such as rat, bovine and porcine. The native molecular weight predicted by size-exclusion chromatography was 200 kD which is in close agreement with that found for porcine and rat nNOS. Internal amino acid sequences generated from tryptic digests of the purified ovine nNOS are highly homologous to rat nNOS. There was no significant difference in the cofactor dependence and kinetic characteristics of ovine nNOS when compared to rat and bovine nNOS, (K(m) for L-arginine 2.8, 2.0 and 2.3 microM respectively). A polyclonal anti-peptide antibody directed toward the C-terminal end of the rat nNOS sequence showed full cross-reactivity with the purified ovine nNOS. Immunohistochemical and Western analysis using this antiserum demonstrate the expression of nNOS in the cortex, cerebellum, hypothalamus and pituitary of the sheep. The lack of staining in the neural and anterior lobes of the pituitary seems to suggest that NOS plays a varied role in the control of endocrine systems between species.


New findings on the action of hypericin in hypoxic cancer cells with a focus on the modulation of side population cells.
The presence of key hypoxia regulators, namely, hypoxia-inducible factor (HIF)-1α or HIF-2α, in tumors is associated with poor patient prognosis. Hypoxia massively activates several genes, including the one encoding the BCRP transporter that proffers multidrug resistance to cancer cells through the xenobiotic efflux and is a determinant of the side population (SP) associated with cancer stem-like phenotypes. As natural medicine comes to the fore, it is instinctive to look for natural agents possessing powerful features against cancer resistance. Hypericin, a pleiotropic agent found in Hypericum plants, is a good example as it is a BCRP substrate and potential inhibitor, and an SP and HIF modulator. Here, we showed that hypericin efficiently accumulated in hypoxic cancer cells, degraded HIF-1/2α, and decreased BCRP efflux together with hypoxia, thus diminishing the SP population. On the contrary, this seemingly favorable result was accompanied by the stimulated migration of this minor population that preserved the SP phenotype. Because hypoxia unexpectedly decreased the BCRP level and SP fraction, we compared the SP and non-SP proteomes and their changes under hypoxia in the A549 cell line. We identified differences among protein groups connected to the epithelial-mesenchymal transition, although major changes were related to hypoxia, as the upregulation of many proteins, including serpin E1, PLOD2 and LOXL2, that ultimately contribute to the initiation of the metastatic cascade was detected. Altogether, this study helps in clarifying the innate and hypoxia-triggered resistance of cancer cells and highlights the ambivalent role of natural agents in the biology of these cells.


The comparison of in vivo properties of water-soluble HPMA-based polymer conjugates with doxorubicin prepared by controlled RAFT or free radical polymerization.
Two conjugates of anticancer drug doxorubicin (Dox) covalently bound by the hydrolytically degradable hydrazone bond to the polymer carrier based on water-soluble N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers were synthesized and their properties were compared, namely their behavior in vivo. The polymer carriers differed in dispersity due to different methods of synthesis; the carrier with relatively high dispersity (HD) was prepared by free radical polymerization (Mw=29,900 g/mol, D=1.75) and the carrier with low dispersity (LD) by controlled radical polymerization (Mw=30,000 g/mol, D=1.13). Both polymer-Dox conjugates showed prolonged blood circulation and tumor accumulation of the drug in comparison with the free drug; e.g. the tumor-to-blood ratio for the polymer-bound Dox was 3-5 times higher. The LD polymer-Dox conjugate exhibited moderately higher tumor accumulation than the HD one at a dose of 1x15 mg Dox (eq.)/kg. Also, their anti-tumor activity did not differ when injected at this dose. However, the increase of the dose to 1x25 mg Dox (eq.)/kg resulted in the enhanced therapeutic activity of the conjugates, especially of the LD one with 100% of long-term survivals. The dispersity of polymer drug carriers influenced the tumor accumulation rate, which affected the overall anti-cancer activity of polymer-drug conjugates.


Corrigendum: Evaluation of lung function in a German single center cohort of young patients with sickle cell disease using EIT and standard techniques.
[This corrects the article DOI: 10.3389/fmed.2023.1100180.].


Cedrol-loaded dissolvable microneedles based on flexible backing for promoting hair growth.
The dissolvable microneedles loaded with cedrol based on flexible backing were developed to deliver cedrol directly and continuously to the dermis, where the drug concentration in the hair follicle can be increased locally. The tip-layer matrix solution was prepared by mixing cedrol and polyvinylpyrrolidone K25 (PVP K25), and the pedestal matrix solution was prepared with aqueous hyaluronic acid. The cedrol-loaded dissolvable microneedles (cedrol-DMNs) were prepared under vacuum conditions. The mechanical properties, pig skin penetration efficiency, in vitro cutaneous permeation test, and the amount of drug in the skin and receptor chamber were evaluated. Pharmacodynamical studies were performed with C57BL/6 mice. The mechanical properties of cedrol-DMNs were good. In vitro cutaneous permeation tests and pharmacodynamical studies demonstrated that cedrol-DMN could efficiently deliver the drug to the deep dermis and effectively promote hair growth. The cedrol-DMNs offer a promising strategy for treating patients suffering from hair loss.


Reconstruction After Tumor Resection in the Growing Child.
Limb preservation surgery has gained acceptance as a viable alternative to amputation for the treatment of extremity bone tumors in the growing child. There are several options for reconstructing the potential loss of a physis and the defect created by tumor excision. Metallic endoprosthesis, massive allograft, and allograft-prosthesis composites have been described in the skeletally immature population. With the development of expandable prostheses, even those far from skeletal maturity may be candidates for limb salvage. However, improvements in the literature are needed, including reporting surgical and functional outcomes in a rigorous manner, specific to age, anatomic location, and reconstruction.


The feasibility and promise of mobile technology with community health worker reinforcement to reduce rural preterm birth.
(1) Assess feasibility of a smartphone platform intervention combined with Community Health Worker (CHW) reinforcement in rural pregnant women; (2) Obtain data on the promise of the intervention on birth outcomes, patient activation, and medical care adherence; and (3) Explore financial implications of the intervention using return on investment (ROI). A total of 98 rural pregnant women were enrolled and assigned to intervention or control groups in this two-group experimental design. The intervention group received usual prenatal care plus a smartphone preloaded with a tailored prenatal platform with automated texting, chat function, and hyperlinks and weekly contact from the CHW. The control group received usual prenatal care and printed educational materials. Demographics, health risk data, interaction with platform, medical records, hospital billing charges, Client Satisfaction Questionnaire-8, satisfaction comments, and the Patient Activation Measure. A total of 77 women completed the study. The intervention was well-received, showed promise for improving birth outcomes, patient activation, and medical care adherence. Financial analysis showed a positive ROI under two scenarios. Despite several practical issues, the study appears feasible. The intervention shows promise for extending prenatal care and improving birth outcomes in rural communities. Further research is needed with a larger and more at-risk population to appreciate the impact of the intervention.


Downregulation of human endometrial IL-18 by exogenous ovarian steroids.
To evaluate the influence of ovarian steroids on IL-18, IL-15 and angiopoietin-2 mRNA expression in the endometrium in the mid luteal phase. We quantified IL-18/GAPDH, IL-18 BP/GAPDH, IL-15/GAPDH and angiopoietin-2/GAPDH in the endometrium by quantitative polymerase chain reaction on day 21 of the cycle. We first compared cytokines expression over two natural cycles (n = 15) then between natural and oestrogen-progestin replacement treatment (n = 18). Endometrial IL-18, IL-18 BP, IL-15 and angiopoietin-2 mRNA expression did not change over two natural cycles. Addition of exogenous hormones significantly decreased IL-18 and IL-18 BP mRNA expression but not influence IL-15 or angiopoietin-2 ratios. This was also observed with immunohistochemistry. Exogenous oestro-progestative hormones influence endometrial IL-18 system expression involved in angiogenesis and in the uterine natural killer (uNK) cell activation pathway during the implantation process.


Population attributable fraction in textbooks: Time to revise.
The population attributable fraction is an important measure for assessing the impact of intervention on the disease risk in populations, but it is frequently misused in the research literature. In this study, we review the definition, calculation, interpretation and assumptions of PAF in 43 textbooks and highlight important shortcomings. While the Levin formula was proposed as a method of calculation in 29 (67%) textbooks, only in 4 (9%) was the Miettinen formula or its generalization for multilevel exposure recommended to calculate a confounding-adjusted population attributable fraction. Other concepts such as generalized impact fraction and prevented and preventable fractions were briefly discussed in few textbooks. We recommend the authors revise the textbooks in light of our proposed framework for teaching the population attributable fraction.


Tunneled infusion catheter breakage: frequency and repair kit outcomes.
To determine the frequency of tunneled infusion catheter breakage and the durability of a repair kit used to repair damage to the external catheter segment, avoiding catheter replacement. With use of a quality assurance database, 724 silicone tunneled infusion catheters placed between July 2002 and September 2005 were identified. The repair kit outcomes portion of the study focused on 10-F triple-lumen catheters (n = 433), the type placed most frequently in our practice and that with the most repairs available for analysis. To compare durability, nonrepaired catheters and those requiring repair were compared by using Cox proportion hazard regression. Breakage occurred in 53 of 443 (12%) 10-F triple-lumen catheters, three of 64 (5%) 10-F dual-lumen catheters, four of 159 (3%) 11-F triple-lumen catheters, four of 12 (33%) 9.6-F single-lumen catheters, and eight of 56 (14%) 9-F double-lumen catheters. In the 10-F subset, the mean time to catheter breakage was 60 days. The mean catheter days for the nonrepaired group (143 days) and the repaired group (145 days) were not significantly different (chi2, 0.071; hazard ratio, 1.07; P = .79). Mean catheter dwell after repair was 79 days. The failure rate for the repair kit was 14% (seven of 51 attempts). Tunneled infusion catheter breakage is common. Given the high breakage rates observed for many catheter designs, the development of more durable catheters should be a priority for catheter manufacturers. Until more durable catheters are developed, the catheter repair kit studied is an easy, effective, durable, and relatively inexpensive solution for the repair of external segment damage in tunneled infusion catheters.


Rewarding and aversive effects of stimulant drugs in infant rats.
Four experiments investigated the reinforcing effects of cocaine, amphetamine, and phenylpropanolamine using odor as the conditioned stimulus and infant rats as the subjects. At the age of 2 days the rats were injected with saline or with one of the three drugs and placed for 30 min in a plastic bag with almond-scented shavings. At the age of 18 days the rats were deprived of water for 12 hr and then given two tests that required different responses. In the consumption test they were given 30 min access to two water spouts, one surrounded by almond-scented cotton and the other surrounded by plain cotton. In the place test, they spent 5 min in a shuttle box with almond-scented shavings under one side and plain shavings under the other side. Compared to saline, all three drugs decreased water intake from the almond-scented spout and increased time spent over the almond-scented shavings.


Molecular characterization of Staphylococcus aureus bloodstream isolates collected in a Dutch University Hospital between 1999 and 2006.
We observed that, between 1999 and 2006, up to 50% of the methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream isolates in our hospital had a genetic background common to endemic methicillin-resistant S. aureus clones (clonal complex 5 [CC5], CC8, CC22, CC30, and CC45). Furthermore, several successful MSSA lineages, such as CC7 and CC15, were observed.


Determinants of hospital costs in community-acquired pneumonia.
Community-acquired pneumonia (CAP) has a high incidence and involves an important consumption of healthcare resources. The present authors analysed the influence of comorbidity, initial severity and complications upon the direct costs associated with hospitalised CAP patients. Direct hospitalisation costs (room cost, treatment, laboratory and diagnostic tests) were assessed in a prospective, observational study of 271 patients admitted to a hospital ward due to CAP. The mean+/-SD patient age was 70+/-15 yrs. The mortality rate was 11.1%. Complications were found in 72.3% and comorbidities in 74.9%. The median (interquartile range) total cost was 1,683 euros (1,291-2,471 euros) and the component costs were: room cost 1,286 euros (857-1,714 euros); laboratory tests 212 euros (171-272 euros); treatment 187 euros (114-304 euros); and diagnostic procedures 58 euros (29-122 euros). Complications and higher Pneumonia Severity Index increased the costs, but age and comorbidity did not. A logistic regression analysis to predict high cost (>1,683 euros) showed that infectious (odds ratio 6.8, 95% confidence interval 1.3-36), digestive (5.9 (1.5-22.8)), pulmonary (2.6 (1.4-4.7)) and other complications (3.9 (1.8-8.4)) were independent risk factors, as were previous hospitalisation (2.3 (1.2-4.3)) and hypoalbuminaemia (2 (1.1-3.6)). Complications, hypoalbuminaemia and previous hospitalisation were the main determinants of high direct costs of hospitalisation due to community-acquired pneumonia. Neither age nor comorbidities were independently associated with cost.


Assessment of Joint Impact of Iodine, Selenium, and Zinc Status on Women's Third-Trimester Plasma Thyroid Hormone Concentrations.
Iodine is essential for synthesizing thyroid hormones, but other micronutrients are also required for optimal thyroid function. However, there is a lack of data on combined micronutrient status in relation to thyroid hormones in pregnancy. We aimed to assess the joint associations of iodine, selenium, and zinc status with plasma concentrations of thyroid hormones and thyroid-stimulating hormone (TSH) in pregnancy. We included 531 pregnant women (aged 22-40 y) participating in a Swedish birth cohort who provided blood and spot urine samples in gestational weeks 27-33 (mean: 29). Associations of urinary iodine concentration (UIC), plasma selenium concentration, and plasma zinc concentration (measured by inductively coupled plasma mass spectrometry) with plasma hormone concentrations [total and free thyroxine (tT4, fT4), total and free triiodothyronine (tT3, fT3), and TSH] were explored with Bayesian kernel machine regression (BKMR; n = 516; outliers excluded) and multivariable-adjusted linear regression (n = 531; splined for nonlinear associations). Median (IQR) micronutrient concentrations were 112 μg/L (80-156 μg/L) for UIC, 67 μg/L (58-76 μg/L) for plasma selenium, and 973 μg/L (842-1127 μg/L) for plasma zinc; the former 2 median values were below recommended concentrations (150 μg/L and 70 μg/L, respectively). Mean ± SD TSH concentration was 1.7 ± 0.87 mIU/L, with 98% < 4 mIU/L. BKMR showed a positive trend of joint micronutrient concentrations in relation to TSH. Plasma zinc was most influential for all hormones but tT3, for which plasma selenium was most influential. In adjusted linear regression models, zinc was positively associated with tT4, tT3, and TSH, and <1200 μg/L also with fT4 and fT3. Selenium was inversely associated with fT3, and <85 μg/L with tT3. Pregnant women's plasma TSH concentrations in the early third trimester increased with increasing joint status of iodine, selenium, and zinc. Zinc and selenium were more influential than iodine for the hormone concentrations. Multiple micronutrients need consideration in future studies of thyroid hormone status.


One preventable cause of spontaneous deflation of inflatable mammary prostheses.
Spontaneous "overnight" deflation of inflatable prostheses is rather uncommon, but we have had a 5.7% incidence of it in a 24-month period in which we used implants with a suturable tab and fastened them to the subjacent fascia. At exploration we found these tabs had torn the bag of the implant, usually at the vulcanized seam. We now believe that fixing a suture tab on a breast implant to underlying fascia may cause undue stresses upon the implant at that point and result in an otherwise avoidable deflation.


DNA binding activity of CREB transcription factors during ontogeny of the central nervous system.
During the early postnatal period, the rat brain contains high basal levels of AP-1 DNA binding activity which declines to the low levels found in the adult by the third postnatal week. Although the individual transcription factors that comprise this AP-1 DNA binding complex had not been identified, we discovered that these proteins were immunoreactive to the cAMP responsive element binding protein (CREB) and also recognized the CRE element. The 45 kDa CREB-immunoreactive protein was detected at high levels only during the first postnatal week. CRE and AP-1 DNA binding activities were studied in the olfactory bulb, striatum, hindbrain, hippocampus, hypothalamus and cerebellum. In general, the DNA binding activity correlated with the stage of maturation of the particular brain region. However, basal AP-1 DNA binding in the olfactory bulb from adults remained slightly elevated relative to other brain regions. Interestingly, the DNA binding complex in the olfactory bulb began to include fos-related antigen as well as CREB by the third postnatal week. The fra-containing complex only recognizes the AP-1 element, while the CREB complex can bind to either CRE or AP-1 sequences. Thus, there is crosstalk between the signal transduction systems that activate CREB and AP-1 transcription factors. This elevated CREB DNA binding activity may be a sensitive index for studying the development of the brain and could be involved in modulating the genomic program in differentiating cells.


Correction to: Effectiveness of lidocaine/prilocaine cream on cardiovascular reactions from endotracheal intubation and cough events during recovery period of older patients under general anesthesia: prospective, randomized placebo-controlled study.
An amendment to this paper has been published and can be accessed via the original article.


The relationship of pain and depression to cognitive function in rheumatoid arthritis patients.
The purpose of this study was to assess the hypothesis that pain and depression negatively impact the cognitive functioning of individuals with rheumatoid arthritis (RA). One hundred twenty-one community-dwelling RA patients (ages 34-84) completed a battery of cognitive tasks and multiple measures of pain and depression. Structural equation modeling techniques were used to assess the relative contributions of pain, depression, and age to cognitive performance. Individuals who performed poorly on cognitive tasks reported more pain and depression and were older than those individuals who performed well on cognitive tasks. Moreover, high levels of pain were associated with depression. Further analyses revealed that depression mediated the relationship between pain and cognition. That is, when depression was entered into the analyses, the previously significant effects of pain on cognition were no longer found. Interestingly, depression still mediated the pain-cognition relationship even after controlling for age. These findings suggest the importance of both pain and depression for understanding cognitive function in RA and may have important implications for treating this disease.


Comparative cytotoxic study of silica materials functionalised with essential oil components in HepG2 cells.
This work evaluated the cytotoxic effect of different EOCs-functionalised silica particle types. The in vitro toxicity of eugenol and vanillin-immobilised SAS, MCM-41 microparticles and MCM-41 nanoparticles was evaluated on HepG2 cells, and compared to free EOCs and pristine materials. The results revealed that free essential oil components and bare silica had a mild cytotoxic effect on HepG2 cells. However, the comparative study showed that free eugenol and vanillin had a milder cytotoxic effect than the equivalent concentrations of immobilised components on the different silica particles, while differences in cell viability between the bare and functionalised particles relied on the type of analysed material. The most cytotoxic materials were eugenol and vanillin-functionalised MCM-41 micro with IC50 values of 0.19 and 0.17 mg/mL, respectively, at 48 h exposure. Differences in cytotoxicity between functionalised particles may be attributed to the density of the functional components on their surface as a result of the functionalisation reaction performance for different materials. The study of the physico-chemical properties of particles demonstrated that cationic nature and increased hydrophobicity could be responsible for promoting cell-particle interactions for the eugenol and vanillin functionalised silica particles, enhancing their cytotoxic behaviour.


A gut feeling: The stressed brain drives intestinal inflammation.
Communication between the central nervous system and the periphery contributes to stress responses and mood disorders. In a recent issue of Cell, Schneider et al. report that psychological stress exacerbates gut inflammation and dysmotility by modifying enteric glia and neurons.


Association between Thalamocortical Functional Connectivity Abnormalities and Cognitive Deficits in Schizophrenia.
Cognitive deficits are considered a core component of schizophrenia and may predict functional outcome. However, the neural underpinnings of neuropsychological impairment remain to be fully elucidated. Data of 59 schizophrenia patients and 72 healthy controls from a public resting-state fMRI database was employed in our study. Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery was used to measure deficits of cognitive abilities in schizophrenia. Neural correlates of cognitive deficits in schizophrenia were examined by linear regression analysis of the thalamocortical network activity with scores of seven cognitive domains. We confirmed the combination of reduced prefrontal-thalamic connectivity and increased sensorimotor-thalamic connectivity in patients with schizophrenia. Correlation analysis with cognition revealed that in schizophrenia (1) the thalamic functional connectivity in the bilateral pre- and postcentral gyri was negatively correlated with attention/vigilance and speed of processing (Pearson's r ≤ -0.443, p ≤ 0.042, FWE corrected), and positively correlated with patients' negative symptoms (Pearson's r ≥ 0.375, p ≤ 0.003, FWE corrected); (2) the thalamic functional connectivity in the right cerebellum was positively correlated with speed of processing (Pearson's r = 0.388, p = 0.01, FWE corrected). Our study demonstrates that thalamic hyperconnectivity with sensorimotor areas is related to the severity of cognitive deficits and clinical symptoms, and extends our understanding of the neural underpinnings of "cognitive dysmetria" in schizophrenia.


The effects of dexmedetomidine preconditioning on aged rat heart of ischaemia reperfusion injury.
To assess the effect of dexmedetomidine on myocardial ischemia reperfusion injury in vivo aged rat heart. 40 healthy male, 20month aged, 350-400g Sprague-Dawley rats. Rats were divided into four groups randomly(n=10): group of ischemic preconditioning(IP group), group of Sham(CS group), group of dexmedetomidine(DP group), Ischemia-reperfusion injury group(IR group). The date of HR and ±dp/dtmax were detected before and after the occur of ischemia reperfusion. Superoxide dismutase (SOD) and malondialdehyde (MDA) activity were recorded; myocardial infarct size was calculated at the end of reperfusion. HR in each group decreased after thoracotomy. Compared with CS group, the HR in IR group reduced significantly (P<0.05). After given dexmedetomidine, HR in the DP group began to decrease significantly. Left heart function in IR group compared with the CS group showed that a statistically reduce of left ventricular function happened in IR group. ±dp/dtmax of the IR groups compared with the CS group were increased. SOD activity reduced and MDA in myocardial tissue homogenates increased in IR group (P<0.05); SOD activity in DP group compared with IR group deduced, MDA increased (P<0.05). Dexmedetomidine preconditioning can effectively reduce ischemia reperfusion injury of the aged rat in vivo, have a protective effect on aged rat heart.


A guide to developing a systematic review.
Systematic reviews are used to gather information from a variety of sources and distill information based on best evidence synthesis, while also excluding poor quality studies via explicit validity checks. This article provides a roadmap to conducting a systematic review with the Cochrane Collaboration and uses an example of a completed systematic review. The literature is drawn upon to provide rationale for the processes undertaken. The aim of the sample systematic review was to identify and review all randomized controlled trials evaluating disposable surgical face masks worn by surgical team members during clean surgery to prevent postoperative surgical wound infection.


Assessing gender identity concerns in children and adolescents: evaluation, treatments, and outcomes.
Child and adolescent psychiatrists are increasingly evaluating youth who present with gender-nonconforming behaviors and identities. The lack of discipline-specific guidelines has made assessment and treatment of children and adolescents presenting with these concerns more difficult. Several new guidelines have recently been published, and research efforts are advancing to broaden the scope of understanding of gender identity assessment and treatment in children and adolescents. Familiarity with the latest standards of care, recent research advances, and current knowledge gaps is important to help improve clinical competency in treating mental health issues in this population.


Attention control moderates the relationship between social media use and psychological distress.
Research has suggested a potential link between social media use and psychological distress, though findings have been somewhat inconsistent. Importantly, relatively few studies have examined potential moderators of this relationship, and the majority have relied upon self-report social media use. The present study examined the potential moderating role of attention control, in the relationship between social media use and anxiety and employed an objective measure of social media use via smartphone data. Social media use was captured via participants smartphones over a one-week period. Inhibitory attention control was assessed via antisaccade task performance. In addition to a measure of psychological distress that was completed by participants (final n = 69, female = 35, male = 31, did not specify = 3). Attention control, as indexed via total antisaccade accuracy, moderated the relationship between social media use and psychological distress. This relationship was such that those with lower levels of attention control showed a significant positive relationship between social media use and psychological distress, whereas no relationship was observed among those with average or high attention control. While capturing objective mobile social media data, future research could also benefit from incorporating usage data from computers and other devices. The findings of this study highlight a potential important factor that may alter the impact of social media use on emotional wellbeing. One possible implication of this finding is that heavy social media use may have problematic mental health consequences specifically for those who experience difficulties with attention control.


Treatment of open fracture of the forearm in osteogenesis imperfecta.
An open fracture of the forearm in a patient with osteogenesis imperfecta is reported. Immediate operative debridement and open reduction, combined with rigid external fixation, provided the patient with an excellent functional result.


Determination of fumonisins and hydrolyzed fumonisin B1 in microbial culture media by LC/ESI-MS.
In order to analyze liquid growth media for fumonisin B1, B2 and hydrolyzed fumonisin B1 (HFB1) after incubation with microorganisms for degradation studies, a liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS) method was developed. The use of phytosphingosine hydrochloride (PSH) and T-2-toxin-d3 (T2d3) as internal standard has been tested. The detection limit established with PSH as an internal standard was about 20 ng/mL for FB1 and FB2 and about 50 ng/mL for HFB1. The developed method allows the rapid, simultaneous and quantitative determination of these analytes in microbial culture media without any cleanup.


Free musculocutaneous flap transfer of extensor digitorum brevis muscle by microvascular anastomosis for restoration of function of thenar and adductor pollicis muscles.
This article reports 3 cases of surgical restoration of function of the thenar muscle and the adductor pollicis muscle of the thumb with free musculocutaneous flaps of the extensor digitorum brevis muscle of the toe by microsurgical technique. Two years' follow-up revealed good functional recovery of the hand with normal electromyographic findings and grade 3-4 muscular power.


Prognostic value of galectin-3 and right ventricular function for long-term mortality in heart failure patients treated with cardiac resynchronization therapy.
Recently, associations between the biomarker galectin-3 and numerous pathological processes involved in heart failure (HF) and right ventricular (RV) function have been observed. We aimed to assess the long-term prognostic ability of galectin-3 and RV function parameters for all-cause mortality in HF patients treated with cardiac resynchronization therapy (CRT). We prospectively studied 63 symptomatic HF patients with a left ventricular (LV) ejection fraction (EF) ≤ 35%. The median serum galectin-3 concentration was 13.4 ng/mL (IQR 11.05, 17.15). A detailed assessment of LV and RV geometry and function was performed with echocardiography. CRT defibrillator implantation was achieved in all patients without major complications. The follow-up lasted 5 years. In the multivariable Cox regression model, independent predictors for all-cause mortality were log baseline galectin-3 and baseline RV function expressed as tricuspid annular plane systolic excursion with HR 2.96 (p = 0.037) and HR 0.88 (p = 0.023), respectively. Analysis of subgroups defined by galectin-3 concentration and CRT response showed that patients with high baseline galectin-3 concentrations and a lack of response to CRT had a significantly lower probability of survival. In our patient cohort, the baseline galectin-3 concentration and RV function were independent predictors of long-term all-cause mortality in HFrEF patients following CRT implantation.


Tissue-plastinated vs. celloidin-embedded large serial sections in video, analog and digital photographic on-screen reproduction: a preliminary step to exact virtual 3D modelling, exemplified in the normal midface and cleft-lip and palate.
This study analyses tissue-plastinated vs. celloidin-embedded large serial sections, their inherent artefacts and aptitude with common video, analog or digital photographic on-screen reproduction. Subsequent virtual 3D microanatomical reconstruction will increase our knowledge of normal and pathological microanatomy for cleft-lip-palate (clp) reconstructive surgery. Of 18 fetal (six clp, 12 control) specimens, six randomized specimens (two clp) were BiodurE12-plastinated, sawn, burnished 90 microm thick transversely (five) or frontally (one), stained with azureII/methylene blue, and counterstained with basic-fuchsin (TP-AMF). Twelve remaining specimens (four clp) were celloidin-embedded, microtome-sectioned 75 microm thick transversely (ten) or frontally (two), and stained with haematoxylin-eosin (CE-HE). Computed-planimetry gauged artefacts, structure differentiation was compared with light microscopy on video, analog and digital photography. Total artefact was 0.9% (TP-AMF) and 2.1% (CE-HE); TP-AMF showed higher colour contrast, gamut and luminance, and CE-HE more red contrast, saturation and hue (P < 0.4). All (100%) structures of interest were light microscopically discerned, 83% on video, 76% on analog photography and 98% in digital photography. Computed image analysis assessed the greatest colour contrast, gamut, luminance and saturation on video; the most detailed, colour-balanced and sharpest images were obtained with digital photography (P < 0.02). TP-AMF retained spatial oversight, covered the entire area of interest and should be combined in different specimens with CE-HE which enables more refined muscle fibre reproduction. Digital photography is preferred for on-screen analysis.


Arterial blood flow measurement: assessment of velocity estimation methods.
Three methods are presented which provide statistically acceptable estimates of mean transit time of opacified blood during angiography. While the methods vary in precision, the selection of the method appropriate for any particular experimental model depends on the degree of precision required to demonstrate the effect under investigation. As the day follows the night, the cost of equipment increases with increasing precision and the inexpensive method may provide sufficient accuracy for most clinical situations.


Assay for β-Galactosidase in Extracts of Mammalian Cells.
This protocol contains a method for the detection of β-galactosidase expressed from reporter vectors that have been transfected into mammalian cells. The assay is both simple and rapid and can be performed using a visible light spectrophotometer.


The role of antimullerian hormone in prediction of outcome after IVF: comparison with the antral follicle count.
To assess the value of antimullerian hormone (AMH) as a test to predict poor ovarian response and pregnancy occurrence after IVF and to compare it with the performance of the antral follicle count (AFC). A systematic review of existing literature and a meta-analysis were carried out. After a comprehensive search, studies were included if 2 x 2 tables for outcomes poor response and pregnancy in IVF patients in relation to AMH or AFC could be constructed. Academic referral center for tertiary care. Cases indicated for IVF. None. Poor response and nonpregnancy after IVF. A total of 13 studies were found reporting on AMH and 17 on AFC. Because of heterogeneity among studies, calculation of a summary point estimate for sensitivity and specificity was not possible. However, for both tests summary receiver operating characteristic curves for the outcome measures poor response and nonpregnancy could be estimated and compared. The curves for the prediction of poor response indicated no significant difference between the performances of AMH and AFC. For the prediction of nonpregnancy, poor performance for both AMH and AFC was found. In this meta-analysis it was shown that AMH has at least the same level of accuracy and clinical value for the prediction of poor response and nonpregnancy as AFC.


Nuclease activity in human metaphase chromosomes substituted with 5'-bromodeoxyuridine.
Human metaphase chromosomes, substituted with 5'-bromodeoxyuridine (BrdUrd) for one, two or three rounds of replication, were briefly pretreated with ultraviolet light (UV), in the presence of 33258 Hoechst, and subsequently digested with either exonuclease III or S1 nuclease. Pretreatment alone was not sufficient to induce sister chromatid differential staining (SCD), but allowed subsequent digestion with exonuclease III or S1. Such enzymes were found to induce SCD with ethidium bromide, as unifilarly BrdUrd-substituted chromatids (TB) were more resistant than bifilarly substituted chromatids (BB). Other experiments with DNase I or the AluI and HaeIII restriction endonucleases showed that only HaeIII was capable of inducing SCD by attacking BB more than TB chromatids preincubated with UV in the presence of Hoechst. SCD with exonuclease III/S1 nuclease seems to be due to (1) UV-induced DNA debromination occurring twice in BB as opposed to TB chromatids, and (2) alteration of chromatin protein structure occurring to a different extent in differently BrdUrd-substituted chromatids. Our findings with endonucleases, on the contrary, may depend on the capacity of enzymatic cleavage to cancel the different protein alterations induced differentially by UV in TB as opposed to BB chromatids.


Optic tract injury after anterior temporal lobectomy.
Three patients had complete homonymous hemianopia with clinical and neuroimaging characteristics of ipsilateral optic tract infarction after anterior temporal lobectomy for seizure control. This injury presumably resulted from irritative vasospasm of the anterior choroidal artery. The features of this pure optic tract syndrome should be distinguished from the more common compressive optic tract syndrome which generally also impairs ipsilateral optic nerve function.


Comparative evaluation of obesity-related parameters in junior sumo wrestlers and children with obesity.
Exercise is a key factor in preventing obesity and metabolic syndrome. Sumo wrestlers increase their body size from childhood for athletic advantage; however, the risk of metabolic syndrome in junior sumo wrestlers is undetermined. Preventive measures against pediatric obesity should be initiated during childhood to prevent obesity in adulthood, considering its high global incidence. We comparatively evaluated the risk factors for metabolic syndrome in junior sumo wrestlers and children with obesity. We enrolled 70 male children (age 9-17 years [sumo group, n = 14] and 9-14 years [other sports and non-exercise groups, n = 28 each]) and evaluated their anthropometric parameters (height, weight, body mass index z-score, obesity rate, waist circumference, waist to height ratio) and hematological parameters (total, low-density, high-density, and non-high-density lipoprotein-cholesterol; triglycerides; plasma glucose, and glycated hemoglobin levels). The BMI z-score, obesity rate, waist circumference (p < 0.05, along with the non-exercise group), and systolic blood pressure were significantly higher and the high-density cholesterol level was lower in the sumo group than in the other sports group (p < 0.05). The waist to height ratio was significantly higher in the non-exercise group than in the other sports group (p < 0.05). No significant difference was found in other blood lipid, plasma glucose (significantly lower level than the reference range in the sumo group, p < 0.05), and glycated hemoglobin (within the reference range in all groups) levels among the three groups. Junior sumo wrestlers had a larger body size and higher blood pressure than children with obesity who exercised regularly. This provides direction for future research into targeted preventive interventions against metabolic syndrome for junior sumo wrestlers with large body size.


Prognostic significance of the number of lymph nodes examined in node-negative Siewert type II esophagogastric junction adenocarcinoma.
Involvement status of lymph node (LN) is one of the most important prognostic factors for esophagogastric junction (EGJ) adenocarcinoma. However, the prognostic value of the number of examined LNs remains unclear in node-negative (pN0) Siewert type II EGJ adenocarcinoma. A cohort of 262 patients who underwent curative surgery for pN0 Siewert type II EGJ adenocarcinoma from January 2000 to August 2013 were retrospectively analyzed from high-volume center database. All enrolled patients were categorized into 3 groups according to the number of examined LNs (≤14, 15 to 21, ≥22). Kaplan-Meier curves were used for comparing the differences of cancer-specific survival among groups; Correlation between survival and the number of examined LNs were analyzed by using stratified, uni- and multivariate analyses. The hazard ratio for cancer-specific mortality decreased sequentially with increasing number of LNs examined. The 5-year cancer-specific survival rates were 45.1%, 58.4% and 65.7% for patients with ≤14 LNs, 15 to 21 and ≥ 22 LNs removed, respectively. The number of removed LNs was significantly correlated with survival in stratified analyses according to T stage. In multivariate model controlling for gender, age, surgical approach, tumor grade, and postoperative chemotherapy, the number of removed LNs and T stage were confirmed to be independent prognostic factors and significantly correlated with disease-specific survival. The number of examined LNs is an independent prognostic factor of survival for patients with pN0 Siewert type II EGJ adenocarcinoma. Adequate dissection of LNs (more than 15 LNs) is recommended for patients undergoing curative resection.


Succinyl derivatives of N-tris (hydroxymethyl) methyl-2-aminoethane sulphonic acid: their effects on the frog neuromuscular junction.
Succinic anhydride (SA) dissolved in Ringer solution buffered with N-tris (hydroxymethyl) methyl-2-aminoethane sulphonic acid (SA-TES solution) potentiates the depolarizing action of acetylcholine (ACh, 10-40 microM) on frog muscle and the tension induced by bath application of this agonist. Applied from one side of a double-barrelled micropipette, SA-TES increases the amplitude of iontophoretically elicited ACh potentials. The potentiation of the effects of ACh by SA-TES does not involve changes in either the activity of the ACh esterase or the input resistance of the muscle membrane. For depolarizations of frog sartorius muscle, dose-response relationships obtained for ACh concentrations from 0.5 to 20 microM indicate that SA-TES increases the apparent affinity of ACh by a factor of 3. SA-TES exerts an "accelerating' effect on the responses elicited by bath-applied ACh; i.e., it increases the rate of depolarization when ACh is added to the bath and the rate of repolarization upon washing out. These effects are particularly marked in preparations treated with neostigmine (3 microM). SA-TES does not potentiate the depolarizing action of agonists which do not contain an ester group. Moreover, the time course of the responses elicited by these compounds is not influenced by SA-TES. SA-TES fails to influence significantly the effects of the neurally released transmitter. Only a 10% increase in the average amplitude of the endplate potentials was observed. SA hydrolyzes in about 30 min at room temperature; however the SA-TES solution retains its activity for several weeks. Succinate is inactive, and so is SA in Ringer buffered with phosphate. The SA-TES solution contains seven succinyl-TES derivatives, which were separated by ion-exchange chromatography and paper chromatography. At concentrations between 1 to 150 microM, these succinyl-TES derivatives affected the ACh-induced contraction of frog rectus abdominus muscle. The most abundant derivative potentiated the action of high doses of ACh, but was inhibitory at lower ones. The other derivatives were mostly inhibitory. These results are discussed in terms of two hypotheses. One postulates the presence of a diffusion barrier formed by groups that bind ACh and are saturated by SA-TES. The other assumes that SA-TES acts directly on the ACh receptor exerting its potentiating effect through a cooperative mechanism.


Characteristics of rapid-biofiltering anammox reactor (RBAR) for low nitrogen wastewater treatment.
This research provides an important approach for rapid treatment of low nitrogen wastewater through anaerobic ammonium oxidation (anammox), which was realized in a rapid-biofiltering anammox reactor (RBAR). The operation mode of continuous upward flow and gradually shortened hydraulic retention time (HRT) accumulated anammox bacteria effectively in RBAR, where carmine anammox granular sludge and thick biofilm were co-existed, leading the biomass concentration and the specific anammox activity to reach 21.61 gSS/L and 0.82 gN/gVSS·d in the main functional zone. Moreover, the relative abundance of anammox bacteria in the whole reactor was more than 50%, and the relative abundance of Candidatus Brocadia in the biofilm of 20-47 cm zone reached 71.10%. Results showed that the removal rate and effluent concentration of total nitrogen remained stable at 86.24% and 14.20 mg/L (below 15 mg/L) averagely, under HRT of 32 min when the the nitrogen loading rate was 4.86 kgN/m3·d.


Frequency of and risk factors for intensive care unit-acquired sacrum pressure injuries in critically ill patients: A multicenter cross-sectional study in China.
Hospital-acquired pressure injuries (HAPI) prolong hospital stays and are an important health problem worldwide. The aim of this study was to assess the frequency of and risk factors for intensive care unit (ICU)-acquired pressure injuries (IAPI) on the sacrum in critically ill patients in China. We performed a multicenter, cross-sectional survey of IAPI on the sacrum in 23 adult ICUs in 19 hospitals in China. Data for 421 critically ill patients were collected on December 13, 2019, and January 13, 2020, including patient characteristics, physiological, and clinical information. Logistic regression was used to analyze the risk factors for IAPI on the sacrum in the ICU. Forty-one patients presented sacrum pressure injuries in the ICU, with a frequency of 9.74%. Risk factors that significantly increased the risk of IAPI on the sacrum were lower body mass index (BMI, odds ratio [OR] = 1.115, confidence interval [CI]: 1.011-1.229, P = .029), chronic obstructive pulmonary disease (COPD, OR = 3.183, CI: 1.261-8.037, P = .014), multiple organ dysfunction syndrome (MODS, OR = 2.670, CI: 1.031-6.903, P = .043), and a lower Braden risk score (OR = 1.409, CI: 1.197-1.659, P < .001). Lower BMI, COPD, MODS, and lower Braden risk score are independent risk factors for sacrum IAPI in China.


Multicenter collaborative randomized parallel group comparative study of pitavastatin and atorvastatin in Japanese hypercholesterolemic patients: collaborative study on hypercholesterolemia drug intervention and their benefits for atherosclerosis prevention (CHIBA study).
To compare the efficacy and safety of pitavastatin and atorvastatin in Japanese patients with hypercholesterolemia. Japanese patients with total cholesterol (TC) > or = 220 mg/dL were randomized to receive pitavastatin 2 mg (n=126) or atorvastatin 10 mg (n=125) for 12 weeks. The primary endpoint was percent change from baseline in non-HDL-C level after 12 weeks of treatment. Reduction of non-HDL-C by pitavastatin treatment (39.0%, P=0.456 vs. atorvastatin) was non-inferior to that by atorvastatin (40.3%). Both pitavastatin and atorvastatin also significantly reduced LDL-C by 42.6% and 44.1%, TC by 29.7% and 31.1%, and TG by 17.3% and 10.7%, respectively, at 12 weeks without intergroup differences. HDL-C showed a significant increase at 12 weeks with pitavastatin treatment (3.2%, P=0.033 vs. baseline) but not with atorvastatin treatment (1.7%, P=0.221 vs. baseline). Waist circumference, body weight and BMI were significantly correlated with percent reduction of non-HDL-C in the atorvastatin group, whereas pitavastatin showed consistent reduction of non-HDL-C regardless of the body size. In patients with metabolic syndrome, LDL-C was reduced significantly more in patients receiving pitavastatin when compared with those receiving atorvastatin. AST, ALT and gammaGTP increased significantly in patients receiving atorvastatin but not in those receiving pitavastatin. Both treatments were well tolerated. Pitavastatin 2 mg and atorvastatin 10 mg are equally effective in improving the lipid profile and were well tolerated in Japanese patients with hypercholesterolemia.


The Course of Headache in Patients With Moderate-to-Severe Headache Due to Aneurysmal Subarachnoid Hemorrhage: A Retrospective Cross-Sectional Study.
The purpose of this study was to evaluate the course of headache in patients with moderate-to-severe headache due to aneurysmal subarachnoid hemorrhage (aSAH) and to identify its predisposing factors. Little is known about the long-term course of headache in patients with aSAH. Since September 2009, patients with aSAH have had their headaches prospectively rated using a numeric rating scale (NRS). From this database containing 838 patients, 217 were included and all included patients met the following criteria: (1) presence of ruptured intracranial aneurysms on computed tomography angiography or magnetic resonance angiography; (2) alert consciousness (Glasgow Coma Scale 15); (3) newly onset moderate-to-severe headache (NRS ≥ 4) due to ruptured intracranial aneurysms; and (4) good clinical outcome at discharge (modified Rankin Scale 0, 1, or 2). We observed the changes in NRS scores from initial to 12-month follow-up and identified the predisposing factors of NRS changes. Of the 217 patients, 182 (83.9%) experienced improvement in NRS score ≤ 3 upon discharge. The NRS scores at discharge were significantly lower than those on admission (P < .001). The independent predisposing factors for headache improvement included previous stroke (odds ratio [OR] = 0.141; 95% CI 0.051-0.381; P < .001), previous headache treated with medication (OR = 0.079; 95% CI 0.010-0.518; P = .008), and endovascular treatment (EVT; OR = 2.531; 95% CI 1.141-5.912; P = .026). The NRS scores tended to decrease continuously until the 12-month follow-up. EVT and symptomatic vasospasm were independently associated with a decrease of NRS in the follow-up periods. The course of headache in patients with aSAH continuously improved during the 12 months of follow-up. Headache improvement might be expected in patients who were treated with EVT and in those who did not have previous stroke or headache.