International Translation of Project EX: A Teen Tobacco Use Cessation Program.
There are relatively few documented teen tobacco use cessation efforts outside the United States (U.S.). Project EX is an evidence-based program that consists of eight sessions, as a school-based clinic tobacco cessation-only version and a classroom-based prevention and cessation version. This paper provides a 'snapshot' of progress on international translation of ProjectEXpilot study work in eight countries that have been approached thus far. The program was implemented in Wuhan, China; Israel and partners; Bashkortostan, Russia; and Elche, Spain. Implementation is planned for Vienna, Austria; Mumbai, India; and Bangkok, Thailand. This work will lead eventually to a greater understanding regarding preference for type of programming (e.g., clinic versus classroom modality), challenges in recruitment and retention, program receptivity, and short-term (approximately 3-month post-program) quit rates. Convenience samples are being recruited based on previous contacts with each location. A protocol was sent to each location, proposing a controlled design, in which subjects enter cessation groups or become a wait-list control, with an immediate pretest, posttest, and 3-month follow-up. Language translation of program materials was completed in seven of the eight locations. Several variations in design and implementation were demanded though. For example, youth fear of reporting tobacco publicly mandated to researchers that the prevention/cessation classroom version be implemented in some locations (Israel and partners, and India). Program effects are suggested across countries. Ongoing partnerships with parties actively involved in tobacco control facilitate pilot testing of teen tobacco use cessation programming. The Project EX curriculum appears quite translatable, though having flexibility in implementation modality eased being able to pilot test the program. Research on this cognitive-behavioral, motivation enhancement approach continues.


The care & feeding of employees. Putting together a winning team.
Finding, training and ultimately retaining high quality employees is essential to the long-term growth and success of your dental practice. How should you begin this process? What are some of the key steps in the hiring process? Once you have found the "perfect" employee, what steps do you need to follow to insure his or her happiness as an employee? This article will explore each of these areas and provide dentists with vital information necessary for them to make the best possible hiring decisions.


[Myocardial protection of remote ischemic postconditioning during primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction].
To evaluate the cardioprotection of remote ischemic postconditioning (RIPostC) in patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). Forty-six STEMI patients undergoing primary PCI at Peking University Third Hospital from January to April 2014 were randomized to RIPostC group (n=23) and control group (n=23).The RIPostC protocol was started within 1 min after reflow by thrombus aspiration or balloon inflation and consisted of 3 cycles of 5 min/5 min ischemia/reperfusion by cuff inflation/deflation of the lower left limb. The enzymatic infarct size, rate of complete ST segment resolution, corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) in infarct-related artery (IRA) and plasma levels of malondialdehyde(MDA), endothelin-1(ET-1), tumor necrosis factor α (TNFα) of the two groups were compared. There was no significant difference in enzymatic infarct size between the two groups (P>0.05). The rate of complete ST-segment resolution was significantly higher in RIPostC group than in control group (60.9%vs. 30.4%,P=0.04). There was a trend toward lower CTFC in RIPostC group than that in control group, but the difference was not statistically significant(28 ± 11 vs. 33 ± 11, P = 0.10). However, in the subgroup of anterior wall myocardial infarction CTFC in RIPostC group was significantly lower, compared with control group (25±9 vs. 39±10, P=0.01).There were lower plasma levels of MDA,ET-1,TNFα in RIPostC group than in control group at different time points after primary PCI (P<0.05). In STEMI patients undergoing primary PCI, RIPostC may improve myocardial perfusion and attenuate ischemia reperfusion injury with the underlying mechanisms involving reduction of oxidative stress, protection of endothelial function and inhibition of inflammatory response.


Cardiopulmonary Performance During Maximal Exercise in Soccer Players with Alterations in Renal Function.
The aim of this study was to evaluate the curves of cardiorespiratory variables during cardiopulmonary exercise testing (CPET) in soccer players who had acute alterations in the glomerular filtration rate (GFR) after performing the pre-season training protocol. Sixteen male professional soccer players (25 ± 3 years; 179 ± 2 cm; and 77 ± 6 kg) were evaluated for oxygen uptake (VO2), heart rate (HR) and pulse relative oxygen (relative O2 Pulse) curves with intervals corresponding to 10% of the total duration of CPET. Athletes were grouped according to the GFR and classified as decreased GFR (dGFR; n = 8) and normal GFR (nGFR; n = 8). Athletes from the dGFR group exhibited lower VO2 values (p < 0.05) when 90% (dGFR 49.8 ± 4.0 vs. nGFR 54.4 ± 6.1 ml·kg-1·min-1) and 100% (dGFR 52.6 ± 4.1 vs. nGFR 57.4 ± 5.9 ml·kg-1·min-1) of the test was complete; HR high values (p < 0.05) when 90% (dGFR 183.7 ± 5.1 vs. nGFR 176.6 ± 4.8 bpm-1) and 100% (dGFR 188.1 ± 5.0 vs. nGFR 180.8 ± 4.8 bpm-1) of the test was complete; and lower relative O2 Pulse values (p < 0.05) when 70% (dGFR 25.6 ± 8.4 vs. nGFR 27.9 ± 9.7 ml·beat-1·kg-1), 80% (dGFR 26.6 ± 8.8 vs. nGFR 29.1 ± 10.0 ml·beat-1·kg-1), 90% (dGFR 27.1 ± 9.0 vs. nGFR 30.8 ± 10.6 ml·beat-1·kg-1) and 100% (dGFR 28 ± 9.2 vs. nGFR 31.8 ± 10.9 ml·beat-1·kg-1) of the test was complete. A correlation was found (r = -0.66, R2 = 0.44, p = 0.00) between lower VO2 peak and elevated levels of urinary protein excretion. In conclusion, soccer players with reduced kidney function after performing the pre-season training protocol also presented alterations in cardiopulmonary variables. We suggest that monitoring of renal function may be used to identify less conditioned soccer players.


Inflammatory myofibroblastic tumor associated with renal cell carcinoma.
A 46-year-old man was referred for evaluation of a 13-cm renal mass. Right radical nephrectomy was performed. Pathologic evaluation revealed inflammatory myofibroblastic tumor (IMT) and renal cell carcinoma. To our knowledge, only 28 cases of IMT associated with the kidney have been reported in published studies. This is the first reported case of IMT associated with malignancy in the urogenital tract. Some investigators have suggested that biopsy-proven IMT can be managed conservatively, but the findings of this report have demonstrated the need for radical nephrectomy in this patient population to rule out associated malignancy.


Vascular pathology in phenylbutazone intoxicated horses.
Three mature Thoroughbred geldings were given 13.63 mg phenylbutazone/Kg bodyweight intravenously for 3 days and repeated in one horse 4 days later. After 4, 7 and 10 days (double treatment), degeneration of the wall of small veins occurred in all horses. The veins were dilated and/or showed hyalin degeneration. The phlebopathy was interpreted to be paramount in phenylbutazone intoxication. All other manifestations, including erythro- and leukodiapedesis, submucosal edema and ulceration of the gastrointestinal mucosa, phlebothrombosis and significant changes in the hemogram and serum chemistry, were considered secondary to the vein lesions.


Plastid Genome Evolution of Two Colony-Forming Benthic Ochrosphaera neapolitana Strains (Coccolithales, Haptophyta).
Coccolithophores are well-known haptophytes that produce small calcium carbonate coccoliths, which in turn contribute to carbon sequestration in the marine environment. Despite their important ecological role, only two of eleven haptophyte plastid genomes are from coccolithophores, and those two belong to the order Isochrysidales. Here, we report the plastid genomes of two strains of Ochrosphaera neapolitana (Coccolithales) from Spain (CCAC 3688 B) and the USA (A15,280). The newly constructed plastid genomes are the largest in size (116,906 bp and 113,686 bp, respectively) among all the available haptophyte plastid genomes, primarily due to the increased intergenic regions. These two plastid genomes possess a conventional quadripartite structure with a long single copy and short single copy separated by two inverted ribosomal repeats. These two plastid genomes share 110 core genes, six rRNAs, and 29 tRNAs, but CCAC 3688 B has an additional CDS (ycf55) and one tRNA (trnL-UAG). Two large insertions at the intergenic regions (2 kb insertion between ycf35 and ycf45; 0.5 kb insertion in the middle of trnM and trnY) were detected in the strain CCAC 3688 B. We found the genes of light-independent protochlorophyllide oxidoreductase (chlB, chlN, and chlL), which convert protochlorophyllide to chlorophyllide during chlorophyll biosynthesis, in the plastid genomes of O. neapolitana as well as in other benthic Isochrysidales and Coccolithales species, putatively suggesting an evolutionary adaptation to benthic habitats.


The pre-launch on-ground characterization of Ma_MISS spectrometer for ExoMars-Rosalind Franklin Rover mission. II. Radiometric calibration.
The Ma_MISS miniaturized spectrometer is integrated within the Drilling System of the ExoMars Rosalind Franklin Rover for Mars exploration. Here we focus on the on ground calibration campaign to obtain radiometric and linearity calibrations of the Ma_MISS instrument, while the first paper dealt with the spectral calibration [De Angelis et al., Rev. Sci. Instrum. 93, 123704 (2022)]. The experimental setup used to carry out radiometric calibration is described, as are the methods used for data processing and key parameter retrieval. In particular, the Spectrometer Transfer Function (Responsivity), Signal-to-Noise Ratio, and detector linearity are determined. In a third paper [De Sanctis et al., Planet. Sci. J. 3, 142 (2022)], validation of the Ma_MISS calibration results through spectral measurements performed on rock and synthetic targets during the radiometric calibration campaign is described.


Cognitive and physical functions related to the level of supervision and dependence in the toileting of stroke patients.
This study aimed to clarify which cognitive and physical factors are associated with the need for toileting assistance in stroke patients and to calculate cut-off values for discriminating between independent supervision and dependent toileting ability. This cross-sectional study included 163 first-stroke patients in nine convalescent rehabilitation wards. Based on their FIMⓇ instrument score for toileting, the patients were divided into an independent-supervision group and a dependent group. Multiple logistic regression analysis and receiver operating characteristic analysis were performed to identify factors related to toileting performance. The Minimental State Examination (MMSE); the Stroke Impairment Assessment Set (SIAS) score for the affected lower limb, speech, and visuospatial functions; and the Functional Assessment for Control of Trunk (FACT) were analyzed as independent variables. The multiple logistic regression analysis showed that the FIMⓇ instrument score for toileting was associated with the SIAS score for the affected lower limb function, MMSE, and FACT. On receiver operating characteristic analysis, the SIAS score for the affected lower limb function cut-off value was 8/7 points, the MMSE cut-off value was 25/24 points, and the FACT cut-off value was 14/13 points. Affected lower limb function, cognitive function, and trunk function were related with the need for toileting assistance. These cut-off values may be useful for judging whether toileting assistance is needed in stroke patients.


Topical delivery of interferon alpha by biphasic vesicles: evidence for a novel nanopathway across the stratum corneum.
Noninvasive delivery of macromolecules across intact skin is challenging but would allow for needle-free administration of many pharmaceuticals. Biphasic vesicles, a novel lipid-based topical delivery system, have been shown to deliver macromolecules into the skin. Investigation of the delivery mechanism of interferon alpha (IFN alpha), as a model protein, by biphasic vesicles could improve understanding of molecular transport through the stratum corneum and allow for the design of more effective delivery systems. The interaction of biphasic vesicles with human skin and isolated stratum corneum membrane was investigated by confocal microscopy, differential scanning calorimetry (DSC) and small- and wide-angle X-ray scattering (SAXS and WAXS). Confocal microscopy revealed that biphasic vesicles delivered IFN alpha intercellularly, to a depth of 70 microm, well below the stratum corneum and into the viable epidermis. DSC and SAXS/WAXS data suggest that the interaction of biphasic vesicles with SC lipids resulted in the formation of a three-dimensional cubic Pn3m polymorphic phase by the molecular rearrangement of intercellular lipids. This cubic phase could be an intercellular permeation nanopathway that may explain the increased delivery of IFN alpha by biphasic vesicles. Liposomes and submicrometer emulsion (the individual building blocks of biphasic vesicles) separately and methylcellulose gel, an alternative topical vehicle, did not induce a cubic phase and delivered low amounts of IFN alpha below the stratum corneum. Molecular modeling of the cubic Pn3m phase and lamellar-to-cubic phase transitions provides a plausible mechanism for transport of IFN alpha. It is hypothesized that induction of a Pn3m cubic phase in stratum corneum lipids could make dermal and transdermal delivery of other macromolecules also possible.


Neuroanatomical study of periprostatic nerve distributions using human cadaver prostate.
We investigated the distribution and navigation of periprostatic nerve fibers and constructed a 3-dimensional model of nerve distribution. A total of 5 cadaver specimens were serially sectioned in a transverse direction with 0.5 cm intervals. Hematoxylineosin staining and immunohistochemical staining were then performed on whole-mount sections. Three representative slides from the base, mid-part, and apex of each prostate were subsequently divided into 4 sectors: two lateral, one ventral, and one dorsal (rectal) part. The number of nerve fibers, the distance from nerve fiber to prostate capsule, and the nerve fiber diameters were analyzed on each sector from the representative slides by microscopy. Periprostatic nerve fibers revealed a relatively even distribution in both lateral and dorsal parts of the prostate. There was no difference in the distances from the prostate capsule to nerve fibers. Nerve fibers in the ventral area were also thinner as compared to other areas. In conclusion, periprostatic nerve fibers were observed to be distributed evenly in the periprostatic area, with the exception of the ventral area. As the number of nerve fibers on the ventral part is fewer in comparison, an excessive high up incision is insignificant during the nerve-sparing radical prostatectomy.


Antipsychotic treatment is associated with inflammatory and metabolic biomarkers alterations among first-episode psychosis patients: A 7-month follow-up study.
Second-generation antipsychotics are commonly used to treat schizophrenia, but may cause metabolic syndrome (MetS) in a subset of patients. The mechanisms of antipsychotic-related metabolic changes remain to be established, especially in first-episode psychosis (FEP) patients. In the present study, we used a chip technology to measure metabolic (C-peptide, insulin, leptin, adiponectin and resistin) and inflammatory biomarkers (ferritin, interleukin-6, interleukin-1α, tumour necrosis factor-α and plasminogen activator inhibitor-1) in the serum samples of a population of FEP patients before and after 7 months of antipsychotic drug treatment, compared to control subjects (CS). The comparison of these markers in antipsychotic-naïve FEP patients (N = 38) and CS (N = 37) revealed significantly higher levels of ferritin (P = .004), and resistin (P = .03) and lower level of leptin (P = .03) among FEP patients group. Seven months of antipsychotic drug treatment in patients (N = 36) ameliorated clinical symptoms, but increased significantly body mass index (BMI; P = .002) and these changes were accompanied by increased levels of C-peptide (P = .03) and leptin (P = .02), as well as decreased level of adiponectin (P = .01). Seven months of antipsychotic drug treatment suppressed the clinical symptoms of psychosis whereas caused imbalance in metabolic biomarkers and increased BMI. These findings provide insight into antipsychotic-induced MetS and refer to problems in insulin processing already present in the early stage of the chronic psychotic disorder.


Proposed solutions to anthropogenic climate change: A systematic literature review and a new way forward.
Humanity is now facing what may be the biggest challenge to its existence: irreversible climate change brought about by human activity. Our planet is in a state of emergency, and we only have a short window of time (7-8 years) to enact meaningful change. The goal of this systematic literature review is to summarize the peer-reviewed literature on proposed solutions to climate change in the last 20 years (2002-2022), and to propose a framework for a unified approach to solving this climate change crisis. Solutions reviewed include a transition toward use of renewable energy resources, reduced energy consumption, rethinking the global transport sector, and nature-based solutions. This review highlights one of the most important but overlooked pieces in the puzzle of solving the climate change problem - the gradual shift to a plant-based diet and global phaseout of factory (industrialized animal) farming, the most damaging and prolific form of animal agriculture. The gradual global phaseout of industrialized animal farming can be achieved by increasingly replacing animal meat and other animal products with plant-based products, ending government subsidies for animal-based meat, dairy, and eggs, and initiating taxes on such products. Failure to act will ultimately result in a scenario of irreversible climate change with widespread famine and disease, global devastation, climate refugees, and warfare. We therefore suggest an "All Life" approach, invoking the interconnectedness of all life forms on our planet. The logistics for achieving this include a global standardization of Environmental, Social, and Governance (ESG) or similar measures and the introduction of a regulatory body for verification of such measures. These approaches will help deliver environmental and sustainability benefits for our planet far beyond an immediate reduction in global warming.


[The clinical relationship between allergic rhinitis and allergic factors and chronic rhinosinusitis with or without nasal polyps].
To investigate the clinical relationship between allergic rhinitis and allergic factors with chronic rhinosinusitis with or without nasal polyps. Two hundred patients were divided into A and B two groups. Group A of 110 patients was diagnosed allergic rhinitis. Group B of 90 patients was diagnosed chronic sinusitis with or without nasal polyps. Serums sIgE was detected with EUROIMMUN, and observe the recurrence rate of chronic sinusitis with or without nasal polyps patients who accept operation treatment and observe the incidence of allergic rhinitis superinduced chronic sinusitis with or without nasal polyps. The total positive rate of group A sIgE was 89.09%. The total positive rate of group B sIgE was 74.44%. The postoperative recurrence rate of sIgE positive group was 58.21% and the postoperative recurrence rate of sIgE negative group was 8.70% in the group B. In the group A, the positive rate of serums sIgE in allergic rhinitis with chronic sinusitis with or without nasal polyps (37.27%) was 97.56%, while the positive rate of serums sIgE in allergic rhinitis without chronic sinusitis (62.73%) was 79.71%, there is a significant difference in allergic rhinitis with or without chronic sinusitis (χ2 = 6.96, P < 0.01). There is a certain correlation between allergic rhinitis and allergic factors with chronic sinusitis with or without nasal polyps. Therefore, through avoiding allergen exposure, the treatment of allergic rhinitis can effectively control recurrence rate of chronic sinusitis and nasal polyp.


Substrate Orientation Effect in the On-Surface Synthesis of Tetrathiafulvalene-Integrated Single-Layer Covalent Organic Frameworks.
The on-surface reactions of tetrathiafulvalene equipped with four benzaldehyde groups (4ATTF) and ditopic diamine molecules are investigated. 4ATTF tends to form large-scale-ordered rhombus structures when reacted with p-phenylenediamine (PPDA). A longer ditopic diamine molecule, 1,1'-biphenyl-4,4'-diamine dihydrochloride (BPDA), causes the domain size of the regular rhombus structure to decrease and triangular and irregular rhombus structures to appear upon reaction with 4ATTF. However, in the rhombus structures formed by different-length ditopic diamine molecules, the single-layer covalent organic frameworks on the graphite surface preferentially orient in alignment with the underlying HOPG substrate lattice.


Enterovesical fistula complicating pregnancy. A case report.
Enterovesical fistula is a rare cause of recurrent urinary tract infections. This condition is unusual in young people as common etiologies include diverticular disease and cancer. When an enterovesical fistula occurs in women of childbearing age, Crohn's disease is a likely cause. To our knowledge, enterovesical fistula complicating pregnancy has not been reported before. A pregnant woman with recurrent urinary tract infections was evaluated. Cystoscopy was suggestive of an enterovesical fistula, which was confirmed by charcoaluria following oral charcoal administration. The prenatal course was complicated by two episodes of hemorrhagic cystitis despite antibiotic prophylaxis. The patient had an uncomplicated term spontaneous vaginal delivery. An upper gastrointestinal series performed postpartum was suggestive of Crohn's disease and confirmed an enterovesical fistula. Surgical repair was successfully performed three months following delivery, revealing Crohn's disease. Enterovesical fistula may be an unusual cause of recurrent urinary tract infections in pregnancy. In this case, enterovesical fistula was the presenting symptom of Crohn's disease.


Shock wave therapy for lateral elbow pain.
This review is one in a series of reviews of interventions for lateral elbow pain. To determine the effectiveness and safety of extracorporeal shock wave therapy (ESWT) for lateral elbow pain. Searches of the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2004), MEDLINE, EMBASE, CINAHL, and Science Citation Index (SCISEARCH) were conducted in February 2005, unrestricted by date. We included nine trials that randomised 1006 participants to ESWT or placebo and one trial that randomised 93 participants to ESWT or steroid injection. For each trial two independent reviewers assessed the methodological quality and extracted data. Methodological quality criteria included appropriate randomisation, allocation concealment, blinding, number lost to follow up and intention to treat analysis. Where appropriate, pooled analyses were performed. If there was significant heterogeneity between studies or the data reported did not allow statistical pooling, individual trial results were described in the text. Eleven of the 13 pooled analyses found no significant benefit of ESWT over placebo. For example, the weighted mean difference for improvement in pain (on a 100-point scale) from baseline to 4-6 weeks from a pooled analysis of three trials (446 participants) was -9.42 (95% CI -20.70 to 1.86) and the weighted mean difference for improvement in pain (on a 100-point scale) provoked by resisted wrist extension (Thomsen test) from baseline to 12 weeks from a pooled analysis of three trials (455 participants) was -9.04 (95% CI -19.37 to 1.28). Two pooled results favoured ESWT. For example, the pooled relative risk of treatment success (at least 50% improvement in pain with resisted wrist extension at 12 weeks) for ESWT in comparison to placebo from a pooled analysis of two trials (192 participants) was 2.2 (95% CI 1.55 to 3.12). However this finding was not supported by the results of four other individual trials that were unable to be pooled. Steroid injection was more effective than ESWT at 3 months after the end of treatment assessed by a reduction of pain of 50% from baseline (21/25 (84%) versus 29/48 (60%), p<0.05). Minimal adverse effects of ESWT were reported. Most commonly these were transient pain, reddening of the skin and nausea and in most cases did not require treatment discontinuation or dosage adjustment. Based upon systematic review of nine placebo-controlled trials involving 1006 participants, there is "Platinum" level evidence that shock wave therapy provides little or no benefit in terms of pain and function in lateral elbow pain. There is "Silver" level evidence based upon one trial involving 93 participants that steroid injection may be more effective than ESWT.


Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice.
Rift Valley fever virus (RVFV) is an emerging arbovirus found in Africa. While RVFV is pantropic and infects many cells and tissues, viral replication and necrosis within the liver play a critical role in mediating severe disease. The low-density lipoprotein receptor-related protein 1 (Lrp1) is a recently identified host factor for cellular entry and infection by RVFV. The biological significance of Lrp1, including its role in hepatic disease in vivo, however, remains to be determined. Because Lrp1 has a high expression level in hepatocytes, we developed a mouse model in which Lrp1 is specifically deleted in hepatocytes to test how the absence of liver Lrp1 expression affects RVF pathogenesis. Mice lacking Lrp1 expression in hepatocytes showed minimal RVFV replication in the liver, longer time to death, and altered clinical signs toward neurological disease. In contrast, RVFV infection levels in other tissues showed no difference between the two genotypes. Therefore, Lrp1 is essential for RVF hepatic disease in mice.


Impact of Medication Adherence on the Effect of Renal Denervation: The SYMPATHY Trial.
Randomized trials of catheter-based renal denervation (RDN) as therapy for resistant hypertension showed conflicting results in blood pressure (BP) lowering effect. Adherence to medication is modest in this patient group and may importantly drive these conflicting results. SYMPATHY is a prospective open label multicenter trial in Dutch patients with resistant hypertension. Primary outcome was change in daytime systolic ambulatory BP at 6 months. Patients were randomly assigned to RDN on top of usual care. Adherence to BP lowering drugs was assessed at baseline and follow-up, using blood samples drawn synchronously with BP measurements. Patients and physicians were unaware of the adherence assessment. Primary analyses showed a mean difference between RDN (n=95) and control (n=44) in changes in daytime systolic ambulatory BP after 6 months of 2.0 mm Hg (95% confidence interval, -6.1 to 10.2 mm Hg) in favor of control. In 80% of patients, fewer medications were detected than prescribed and adherence changed during follow-up in 31%. In those with stable adherence during follow-up, mean difference between RDN and control for daytime systolic ambulatory BP was -3.3 mm Hg (-13.7 to 7.2 mm Hg) in favor of RDN. RDN as therapy for resistant hypertension was not superior to usual care. Objective assessment of medication use shows that medication adherence is extremely poor, when patients are unaware of monitoring. Changes over time in adherence are common and affect treatment estimates considerably. Objective measurement of medication adherence during follow-up is strongly recommended in randomized trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850901.


MicroRNA-182 targets protein phosphatase 1 regulatory inhibitor subunit 1C in glioblastoma.
Glioblastoma (GBM) is an incurable cancer, with mean post-diagnosis survival time of 14-16 months. Metagenomic analysis by The Cancer Genome Atlas (TCGA) program has identified microRNA-182-5p (miR-182-5p or miR-182) as the only miRNA associated with favorable disease prognosis and temozolomide (TMZ) susceptibility. Previous reports have indicated that miR-182 down regulates expression of BCL2L12, c-MET, and HIF2A. However, other messenger RNA (mRNA) targets of miR-182 have not been validated which would explain its association with a favorable disease prognosis. In situ analysis revealed that protein phosphatase 1 regulatory inhibitor subunit 1C (PPP1R1C) is a putative target of miR-182. PPP1R1C protein and RNA expression as assessed by tissue microarray and quantitative real time PCR, respectively, was inversely correlated to miR-182 expression in glioblastoma patients and in the metastatic glioblastoma cell line U87-MG. Reporter assays using PPP1R1C 3' untranslated region (UTR) showed that miR-182 can interact with the wild-type but not a miR-182-5-seed mutant. Ectopic expression of miR-182 mimic in the U87-MG cell line significantly decreased proliferation as well as suppressed in vitro migration and invasion. Opposite observations were made when the non-malignant neuronal cell line HCN-2 was transfected with anti-miR-182 antagomir. The miR-182 mimic or siRNA targeting PPP1R1C induced TMZ susceptibility indicating that decreased susceptibility to TMZ in GBM patients might be attributed to high expression of PPP1R1C. Inverse correlation of PPP1R1C mRNA and miR-182 levels in 20 GBM patients confirmed the same. Cumulatively, our results indicate that loss of miR-182 leads to increased expression of PPP1R1C which in part explain disease progression and resistance to TMZ therapy.


Traffic jam hypothesis: Relationship between endocytic dysfunction and Alzheimer's disease.
Membrane trafficking pathways, like the endocytic pathway, carry out fundamental cellular processes that are essential for normal functioning. One such process is regulation of cell surface receptor signaling. A growing body of evidence suggests that β-amyloid protein (Aβ) plays a key role in Alzheimer's disease (AD) pathogenesis. Cleavage of Aβ from its precursor, β-amyloid precursor protein (APP), occurs through the endocytic pathway in neuronal cells. In early-stage AD, intraneuronal accumulation of abnormally enlarged endosomes is common, indicating that endosome trafficking is disrupted. Strikingly, genome-wide association studies reveal that several endocytosis-related genes are associated with AD onset. Also, recent studies demonstrate that alteration in endocytosis induces not only Aβ pathology but also the propagation of tau protein pathology, another key pathological feature of AD. Endocytic dysfunction can disrupt neuronal physiological functions, such as synaptic vesicle transport and neurotransmitter release. Thus, "traffic jams" in the endocytic pathway may be involved in AD pathogenesis and may serve as a novel target for the development of new therapeutics.


Fate of Asymptomatic Limb after Kissing Stents in Aortoiliac Occlusive Disease.
Kissing stent angioplasty is an established endovascular treatment strategy for stenosis at the aortic bifurcation but not without its detractors. This study aimed to analyze the outcomes of kissing stents with regard to stent occlusion and complications in which an asymptomatic limb was treated. A total of 106 patients undergoing aortic bifurcation intervention from January 2015 to November 2020 were retrospectively reviewed. Only patients with at least one common iliac artery (CIA) ostium and undergoing bilateral CIA intervention were included in the study. Patients were followed up for a median period of 26 months (interquartile range, 21-51 months). The TransAtlantic InterSociety Consensus (TASC)-II classification of lesions was as follows: A, 49%; B, 41%; C, 6%; and D, 5%. The treatment indication was limited to one side in 53% of patients. Technical and procedural success rates were 99% and 90%, respectively. Ischemic events in an asymptomatic limb occurred in 6% of cases, 3% due to late stent thrombosis >30 days, and 3% due to progression of downstream infrainguinal disease. Primary and secondary patency rates at 1, 3, and 5 years were 98%, 87%, and 85%, and 99%, 94%, and 94%, respectively. Periprocedural mortality developed in two patients with no amputation. Kissing stent deployment is a safe and effective strategy for the treatment of aortoiliac bifurcation disease. Unfavorable outcomes due to stenting in the asymptomatic iliac artery are very rare. Long-term surveillance is necessary due to the risk of late thrombosis or downstream disease progression.


Successful bone marrow transplantation in an 8-month-old patient with chronic granulomatous disease.
An eight-month-old boy with chronic granulomatous disease (CGD) received HLA identical sibling bone marrow transplantation (BMT) following busulphan and cyclophosphamide conditioning. No graft-versus-host disease was demonstrated. Five years after transplantation, mixed chimerism was 60% in peripheral blood, and 85% of his neutrophils had normal oxidative burst activity. He is now six years old, in very good health and growing well. In this period, he experienced no severe infectious diseases. To our knowledge, this is the first case of CGD who had BMT in Turkey. His successful outcome illustrates that BMT in a patient with CGD in the first years of life should be considered early if an HLA-matched donor is already available, before development of any recurrent life-threatening infections or irreversible organ damage.


Childhood blindness.
Eighty five visually handicapped children who attended the eye department were assessed. The children had a mean age of 3.6 years--range 0.3-14.7 years. The aetiological factors for severe visual handicap (visual acuity less than 3/60) were evaluated into prenatal factors; factors operating at birth and the immediate perinatal period; or factors operating in childhood. Genetic counselling and improvements in the management of pre-term infants is recommended in the reduction of childhood blindness. A national computerised childhood blind register should be established.


Words in discourse: a dialectical approach to the acquisition of meaning and use.
Word learning by young children is viewed as a problem of deriving meaning from the use of forms in discourse contexts. Uses of causal and temporal terms in private speech by a child studied longitudinally from 1;9 to 3;0 are analysed from this perspective. Evidence is presented that words are first constrained to uses in specific discourse contexts, and later used more flexibly and with greater control over the semantics of the terms. Derivation of meaning from discourse is described as a dialectical process, and as such it is claimed to be more consistent with the full range of observational data, and with theories of word learning applicable to older children and adults, than other current theories of lexical acquisition in early childhood.


Chemical components of heartwood and sapwood of common Yew (Taxus baccata L.).
Cell-wall components and solubility characteristics of the heartwood and sapwood of Taxus baccata L. were determined by methods of wood analysis and the differences between heartwood and sapwood were established. When we observe the data obtained, it is seen that the amount of extractive material found in the heartwood is substantially higher than the sapwood. The extractive material in Taxus baccata L. is originated from the hidden epithelial cells surrounded by resin canals.


Protein spreading kinetics at liquid-solid interfaces via an adsorption probe method.
We report the areal growth kinetics of fibrinogen adsorbed on model hydrophobic and hydrophilic surfaces measured via an adsorption probe method. This approach exploits the adsorption of probe molecules to determine the evolution of fibrinogen test molecules under conditions where the fibrinogen test molecules adsorb at relatively dilute surface conditions, minimizing interactions between them. It is found that fibrinogen test molecules spread from an average initial footprint of 100 nm2 to a final footprint near 500 nm2 per molecule on the hydrophobic surface, with a single-exponential decay of 1735 s. On a hydrophilic monolayer, the area increases from 100 to 160 nm2 with a characteristic time of 6740 s. These results demonstrate the power of the adsorption probe approach and comprise the first measurements of the averaged area relaxations of adsorbed proteins. The observation of single-exponential dynamics is remarkable, given the extensive relaxation on the hydrophobic surface, which must involve fibrinogen denaturing.


[Study on the susceptibility of the cervical carcinoma cells to CTL lysis under the stimulation of rSIFN-co and its mechanism].
To investigate the susceptibility of cervical carcinoma cells (HPV16+) to CTL lysis affected by rSIFN-co, consensus Interferon (Infergen), IFNalpha-2b and DDP. After CaSki cervical cancer cells were induced by rSIFN-co, Infergen, IFNalpha-2b and DDP at the concentration of 0.156 microg/mL, 0.625 microg/mL, 2.500 microg/mL for 72 hours, CaSki cells which had been induced were effected by CTL, the cytotoxicity was determined and calculated by MTT assay. The expression intensity of adhesion molecules on Caski cell such as CD54 and CD40 was also determined by flow cytometry. The susceptibility of CaSki cell to CTL lysis under the stimulation of rSIFN-co was better than Infergen, IFNalpha-2b and DDP induced. The expression of CD54 and CD40 on cervical cancer cell was also increased. And this effect had positive correlation to the drug concentration. rSIFN-co can increase the expression of CD54 and CD40 on the cervical cancer cell surface, and increase the susceptibility of CaSki cell to specific effective cell lysis in a dose-dependent manner. The effect of rSIFN-co is better than same type interferon, general I type interferon and chemotherapeutic drug induced.


Relation between vitamin D and impulse behaviours in patients with eating disorder: a pilot observational study.
There is growing evidence that vitamin D levels have a role not only in bone health and energy metabolism, but also for supporting nervous system and brain functions, including impulsivity. Impulsive behaviours are considered characteristics of great relevance in patients with Eating Disorders (ED) both for the course of the illness and for the treatment. The aim of this study is to examine the relationship between impulsive behaviours and vitamin D in patients with ED. 236 patients with a diagnosis of ED, consecutively recruited at an ED ward between 2014 and 2018, were enrolled. Patients were classified as impulsive or non-impulsive based on the presence of clinically relevant impulsive behaviours. Impulsive patients were found to have statistically significant lower levels of vitamin D than non-impulsive (p = .007). A threshold value of 20.4 ng/ml for discriminating impulsive from non-impulsive patients was found. This hypothesis generating study partially confirmed a relationship between vitamin D deficiency and impulsive behaviours in ED spectrum mediated by body weight, even if results were not confirmed after corrected by obesity. No definitive conclusion may be taken on whether the effect is reduced due to the loss of power. Future directions are discussed.


Lack of benefit from premedication for pegylated asparaginase during pediatric acute lymphoblastic leukemia/lymphoma therapy: A side-by-side comparison.
Pegylated l-asparaginase (PEG) is integral to treatment regimens for acute lymphoblastic leukemia (ALL) and lymphoma. Hypersensitivity reactions (HSRs) to PEG are common and can preclude continued administration. Data supporting recommendations for universal premedication (UPM) prior to PEG infusion to reduce incidence of HSRs are limited; UPM has become common practice. Two free-standing children's hospitals independently implemented UPM prior to PEG infusions in 2016 and 2019, respectively. In a side-by-side retrospective analysis, incidence and severity of HSRs were analyzed pre- and postimplementation of UPM in youth ≥1 years old treated with frontline PEG-containing ALL regimens (2015-2018, 2016-2020). All HSRs were centrally reviewed within each institution to confirm and grade the HSR (Common Terminology Criteria for Adverse Events, v5). Planned analyses of subsets at potentially greater risk for HSRs included intensive PEG regimens (≥5 doses), adolescent and young adults (AYA), Hispanic/Latinx ethnicity, and obesity. In 410 patients (by institution, n = 282 and n = 128), the overall incidence of Grade ≥ 3 HSRs was 20% (56 out of 282) and 18% (23 out of 128), respectively. No difference in incidence of Grade ≥ 3 HSRs in patients with versus without UPM was found at either institution (23 vs. 19%, p = .487 and 19 vs. 17%, p = .845). UPM also did not reduce the severity of HSRs, nor influence HSR risk within any patient subset. UPM prior to PEG infusion did not alter incidence or severity of HSRs at either institution. HSR remains a common complication of PEG therapy, impacting the patient experience. Alternative strategies to reduce HSRs are urgently required.


Toward safe accessibility of opioid pain medicines in Vietnam and other developing countries: a balanced policy method.
Moderate or severe pain is common among people with advanced cancer and other life-threatening illnesses. Yet despite agreement that pain relief is a human right, the poorest 80% of the world's population rarely have access to strong opioid analgesics. Excessively restrictive opioid policies, especially in developing countries, both stem from and propagate misguided fears about opioids, so-called opiophobia. Because opiophobia, like any norm, is historically, socially, and culturally situated, efforts to change opiophobic policies will be most effective if guided by awareness of their historical, social, and cultural determinants. We describe some of these determinants in Vietnam and report on results of an ongoing project there to allay opiophobia and improve safe access to opioids for medical uses. We used a method that entails working with committed local partners, including a high-level official from the Ministry of Health, to review all Vietnamese policies governing opioid accessibility to identify the barriers; devising an action plan to safely reduce or circumnavigate the barriers; obtaining buy-in for the plan from all stakeholders, including drug regulators and the police; and assisting the Ministry of Health to implement the plan. Since the start of the project, morphine consumption has increased each year and as of 2010 was ninefold greater than in 2003, and the number of hospitals offering palliative care has increased from three to 15. We conclude that this balanced policy method appears to be helping to reduce barriers to opioid access in Vietnam and should be used in other developing countries.


Return to play after hamstring injuries in football (soccer): a worldwide Delphi procedure regarding definition, medical criteria and decision-making.
There are three major questions about return to play (RTP) after hamstring injuries: How should RTP be defined? Which medical criteria should support the RTP decision? And who should make the RTP decision? The study aimed to provide a clear RTP definition and medical criteria for RTP and to clarify RTP consultation and responsibilities after hamstring injury. The study used the Delphi procedure. The results of a systematic review were used as a starting point for the Delphi procedure. Fifty-eight experts in the field of hamstring injury management selected by 28 FIFA Medical Centres of Excellence worldwide participated. Each Delphi round consisted of a questionnaire, an analysis and an anonymised feedback report. After four Delphi rounds, with more than 83% response for each round, consensus was achieved that RTP should be defined as 'the moment a player has received criteria-based medical clearance and is mentally ready for full availability for match selection and/or full training'. The experts reached consensus on the following criteria to support the RTP decision: medical staff clearance, absence of pain on palpation, absence of pain during strength and flexibility testing, absence of pain during/after functional testing, similar hamstring flexibility, performance on field testing, and psychological readiness. It was also agreed that RTP decisions should be based on shared decision-making, primarily via consultation with the athlete, sports physician, physiotherapist, fitness trainer and team coach. The consensus regarding aspects of RTP should provide clarity and facilitate the assessment of when RTP is appropriate after hamstring injury, so as to avoid or reduce the risk of injury recurrence because of a premature RTP.


Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-γ-producing cells.
Mucosal innate lymphoid cell (ILC) subsets promote immune responses to pathogens by producing distinct signature cytokines in response to changes in the cytokine microenvironment. We previously identified human ILC3 distinguished by interleukin-22 (IL-22) secretion. Here we characterized a human ILC1 subset that produced interferon-γ (IFN-γ) in response to IL-12 and IL-15 and had a unique integrin profile, intraepithelial location, hallmarks of TGF-β imprinting, and a memory-activated phenotype. Because tissue-resident memory CD8(+) T cells share this profile, intraepithelial ILC1 may be their innate counterparts. In mice, intraepithelial ILC1 were distinguished by CD160 expression and required Nfil3- and Tbx21-encoded transcription factors for development, but not IL-15 receptor-α, indicating that intraepithelial ILC1 are distinct from conventional NK cells. Intraepithelial ILC1 were amplified in Crohn's disease patients and contributed to pathology in the anti-CD40-induced colitis model in mice. Thus, intraepithelial ILC1 may initiate IFN-γ responses against pathogens but contribute to pathology when dysregulated.


[Anesthetic Management of a Patient with Quasi-moyamoya Disease Undergoing Total Thyroidectomy for Graves' Disease].
Quasi-moyamoya disease defined as moyamoya disease combined with autoimmune diseases such as Graves' disease is rare. We report anesthetic management of a patient with quasi-moyamoya disease undergoing total thyroidectomy for Graves' disease resistant to medical therapy. This disease is characterized by the aggravation of cerebral ischemic symptoms with hyperthyroidism. We, therefore, applied steroid pulse therapy before the operation to induce temporal normalization of the thyroid function, and could perform safe anesthetic management of this patient with quasi-moyamoya disease.


The sigma-1 receptor-TAMM41 axis modulates neuroinflammation and attenuates memory impairment during the latent period of epileptogenesis.
Therapy in the latent period is favorable for retarding the process of epileptogenesis. Recently, we have discovered that the activated sigma-1 receptor (Sig-1R) attenuates the hippocampus pathological injury and memory impairment in the latent period of epileptogenesis. But the molecular mechanism needs further investigation. PRE-084 was utilized as a research tool to highly selectively activate Sig-1R in epileptic mice. After the treatment of PRE-084, the pro-inflammatory cytokines, neuropathological traits, and the level of mitochondrial translocator assembly and maintenance 41 homolog (TAMM41) in the hippocampus were examined. The mode in which the Sig-1R interacts with TAMM41 was explored. The role of TAMM41 in the protecting effect of PRE-084 was established. PRE-084 inhibited the growth of pro-inflammatory cytokines, reduced the formation of gliosis, alleviated neuronal damage in the hippocampus, and attenuated memory impairment in the latent period of epileptogenesis. The protein level of TAMM41 decreased in the hippocampi of epileptic mice and increased in the PRE-084-treated mice. The Sig-1R bound with TAMM41 directly, maintaining the stability of TAMM41. Knockdown of TAMM41 reversed the protective effect of PRE-084, and overexpression of TAMM41 exhibited a similar protective action to that of PRE-084. We presented the concept of the "sigma-1 receptor-TAMM41 axis" and proposed that augmenting this axis can attenuate neuroinflammation and memory impairment in the process of epileptogenesis.


The effect of gender on transformational leadership and job satisfaction among Saudi nurses.
To compare nurses' job satisfaction and perceptions of transformational leadership style of their manager among four different nurse/manager gender dyads in Saudi Arabia. Women and men differ on many behavioural characteristics and are influenced by the cultural environment. Understanding these differences may have an impact on leadership behaviours and job satisfaction. A descriptive analysis of one-time survey data collected in 2011 from Saudi nurses employed in six general public hospitals located in three cities. Three hundred and eight (51.3%) of 600 Saudi nurses solicited to participate completed anonymous questionnaires that measured their job satisfaction and perceptions of transformational leadership style of their manager. Factorial ANOVA tested the main effects of gender of the nurse, gender of the manager and the interaction term on the nurse's job satisfaction, and perceived transformational leadership style of their manager. These analyses indicated a main effect of gender of the manager on both job satisfaction and perceived transformational leadership style of the manager (p < .05) with no significant effect of the gender of the nurse or the interaction term on these variables. Post hoc analysis indicated that nurses regardless of their gender reported higher job satisfaction and perceived transformational leadership style of their manager when their manager was male. These findings contrast with what other researchers have reported that nurse job satisfaction and perceived leadership characteristics of their manager are independent of the gender of the manager. These perceptions of Saudi nurses may be a result of "sex-role spillover" in a male-dominated, gender-segregated society.


Biliary administration of naked DNA encoding Fas-Fc protein prevents acute liver failure in mice.
Acute liver failure (ALF) of infectious origin results from massive Fas-mediated hepatocyte apoptosis. To cure Fas-induced ALF in mice, we have designed a noninvasive procedure for intrahepatic transfer of a plasmid that encodes a molecule inhibiting Fas-Fas ligand interaction. For that purpose, naked pDNA encoding green fluorescent protein (GFP) or the Fas-Fc chimeric protein was transferred into mice by the biliary route. Ten percent of hepatocytes expressed GFP. After pFas-Fc transfer, about 40 ng of Fas-Fc protein per milliliter could be detected in sera from day 4 to day 28. Serum recombinant Fas-Fc could neutralize Fas-induced cell death in vitro. Furthermore, pFas-Fc biliary transfer efficiently protected mice against Fas-mediated ALF, because survival rates (p < 0.01), serum transaminase activities (p < 0.05), and histological data (p < 0.02) were improved versus control pTNFR-Fc-transfected mice. In conclusion, naked pDNA encoding Fas-Fc is efficiently expressed by hepatocytes after biliary gene transfer in mice. This method, devoid of virus-related risks, could be considered for the treatment of Fas-mediated ALF in humans.


Evaluation of two cold thermoregulatory models for prediction of core temperature during exercise in cold water.
Cold thermoregulatory models (CTM) have primarily been developed to predict core temperature (T(core)) responses during sedentary immersion. Few studies have examined their efficacy to predict T(core) during exercise cold exposure. The purpose of this study was to compare observed T(core) responses during exercise in cold water with the predicted T(core) from a three-cylinder (3-CTM) and a six-cylinder (6-CTM) model, adjusted to include heat production from exercise. A matrix of two metabolic rates (0.44 and 0.88 m/s walking), two water temperatures (10 and 15 degrees C), and two immersion depths (chest and waist) were used to elicit different rates of T(core) changes. Root mean square deviation (RMSD) and nonparametric Bland-Altman tests were used to test for acceptable model predictions. Using the RMSD criterion, the 3-CTM did not fit the observed data in any trial, whereas the 6-CTM fit the data (RMSD less than standard deviation) in four of eight trials. In general, the 3-CTM predicted a rapid decline in core temperature followed by a plateau. For the 6-CTM, the predicted T(core) appeared relatively tight during the early part of immersion, but was much lower during the latter portions of immersion, accounting for the nonagreement between RMSD and SD values. The 6-CTM was rerun with no adjustment for exercise metabolism, and core temperature and heat loss predictions were tighter. In summary, this study demonstrated that both thermoregulatory models designed for sedentary cold exposure, currently, cannot be extended for use during partial immersion exercise in cold water. Algorithms need to be developed to better predict heat loss during exercise in cold water.


Stroke prognosis and abnormal nocturnal blood pressure falls in older hypertensives.
It remains uncertain whether abnormal dipping patterns of nocturnal blood pressure influence the prognosis for stroke. We studied stroke events in 575 older Japanese patients with sustained hypertension determined by ambulatory blood pressure monitoring (without medication). They were subclassified by their nocturnal systolic blood pressure fall (97 extreme-dippers, with >/=20% nocturnal systolic blood pressure fall; 230 dippers, with >/=10% but <20% fall; 185 nondippers, with >/=0% but <10% fall; and 63 reverse-dippers, with <0% fall) and were followed prospectively for an average duration of 41 months. Baseline brain magnetic resonance imaging (MRI) disclosed that the percentages with multiple silent cerebral infarct were 53% in extreme-dippers, 29% in dippers, 41% in nondippers, and 49% in reverse-dippers. There was a J-shaped relationship between dipping status and stroke incidence (extreme-dippers, 12%; dippers, 6.1%; nondippers, 7.6%; and reverse-dippers, 22%), and this remained significant in a Cox regression analysis after controlling for age, gender, body mass index, 24-hour systolic blood pressure, and antihypertensive medication. Intracranial hemorrhage was more common in reverse-dippers (29% of strokes) than in other subgroups (7.7% of strokes, P=0.04). In the extreme-dipper group, 27% of strokes were ischemic strokes that occurred during sleep (versus 8.6% of strokes in the other 3 subgroups, P=0.11). In conclusion, in older Japanese hypertensive patients, extreme dipping of nocturnal blood pressure may be related to silent and clinical cerebral ischemia through hypoperfusion during sleep or an exaggerated morning rise of blood pressure, whereas reverse dipping may pose a risk for intracranial hemorrhage.


Self-assembly processes in the prebiotic environment.
An important question guiding research on the origin of life concerns the environmental conditions where molecular systems with the properties of life first appeared on the early Earth. An appropriate site would require liquid water, a source of organic compounds, a source of energy to drive polymerization reactions and a process by which the compounds were sufficiently concentrated to undergo physical and chemical interactions. One such site is a geothermal setting, in which organic compounds interact with mineral surfaces to promote self-assembly and polymerization reactions. Here, we report an initial study of two geothermal sites where mixtures of representative organic solutes (amino acids, nucleobases, a fatty acid and glycerol) and phosphate were mixed with high-temperature water in clay-lined pools. Most of the added organics and phosphate were removed from solution with half-times measured in minutes to a few hours. Analysis of the clay, primarily smectite and kaolin, showed that the organics were adsorbed to the mineral surfaces at the acidic pH of the pools, but could subsequently be released in basic solutions. These results help to constrain the range of possible environments for the origin of life. A site conducive to self-assembly of organic solutes would be an aqueous environment relatively low in ionic solutes, at an intermediate temperature range and neutral pH ranges, in which cyclic concentration of the solutes can occur by transient dry intervals.


Synergy of anomalous transport and radiation in the density limit.
The critical plasma density n(cr) above which the edge anomalous transport in tokamaks is dominated by drift resistive ballooning instability is found analytically. In this transport regime, the drastic increase of particle losses and drop of the edge temperature provoke a strong increase in impurity radiation, and thermal equilibrium does not exist if the density is ramped up above the ultimate limit n(max). Because of the nonlinear character of impurity radiation, this density limit n(max) is very close to n(cr) and practically does not change with the ion effective charge. The importance of the synergy between the anomalous transport and impurity radiation for the density limit phenomenon is confirmed by the results of numerical simulations.


The influence of alcohol on basic motoric and cognitive disinhibition.
It has been proposed that alcohol weakens control processes, which in turn supports the occurrence of disinhibited behaviours. Two studies were run, in parallel (both with 32 participants) using a between-subject design to investigate any disinhibiting effects of a moderate dose of alcohol (0.6 g/kg compared to placebo), previously found to trigger increased desire for alcohol. Disinhibiting effects were tested on basic motoric and cognitive control processes, using a go/no-go (GNG) and the Stroop task (ST) respectively. Although a higher proportion of participants wanted more alcohol under the alcohol preload (priming effect), this effect was not found to be significant. In the GNG task, correct response latency (RL) decreased from baseline [P = 0.008] while number of incorrect hits increased [P = 0.030] irrespective of treatment, indicating the formation of a habit-like response and motoric disinhibition. Although error rate did not differ between groups, an interaction occurred with regard to erroneous RL: participants under alcohol became quicker, while those under placebo became slower [P = 0.014]. In the ST, those preloaded with alcohol made significantly more errors [P = 0.021] and were quicker to complete the task [P = 0.044] compared with those preloaded with placebo, indicating a strong alcohol effect on cognitive disinhibition. The data suggest that a moderate dose of alcohol, which induces priming to want more alcohol, had disinhibiting effects both on a basic motoric and a cognitive inhibitory task. Thus the idea that priming may be mediated by the disinhibitory effects of alcohol is supported.


Thoughts on fiber utilization in swine.
There is continued incentive for the development of alternative feed resources for use in swine production. The availability of distillery by-products may be expected to increase as the use of corn and cereal grains for ethanol production expands. The acceptability of distillery by-products, milling by-products, forages and other fibrous feeds as energy sources for swine depends on such factors as cell wall content of the plant, degree of microbial fermentation in the large intestine, and extent of absorption and utilization of the volatile fatty acids produced. Physiological effects of dietary fiber, including effects on gastric emptying, rate of transit of digesta, gut motility, digestive secretions, and absorption and utilization of breakdown products need quantification. Limited evidence suggests that there are genetic differences in the response of pigs to dietary fiber and in their ability to utilize it as an energy source. Recombinant DNA technology offers the possibility of cloning cellulase genes from microorganisms for application in swine feeding programs. The extent to which biotechnology will be applied in swine feeding will depend ultimately on the economic incentive for developmental effort and on unknown biological limitations of the pig and its gastrointestinal microbial ecosystem.


Right Upper Lobe Torsion after Right Lower Lobectomy: A Rare and Potentially Life-Threatening Complication.
An 84-year-old woman was referred to our institution with suspected right lung cancer. Subsequently, she underwent thoracoscopic right lower lobectomy without mediastinal lymph node dissection. Postoperatively, she complained of dyspnea and developed arterial oxygen desaturation after 12 h and acute respiratory failure (ARF). An emergency chest computed tomography revealed the right upper bronchial stenosis with hilar peribronchovascular soft tissue edema because the middle lung lobe had been pushed upward and forward and the right upper lung lobe had twisted dorsally. Emergency bronchoscopy revealed severe right upper bronchial stenosis with an eccentric rotation and severe edema. The bronchia stenosis was successfully treated with glucocorticoids and noninvasive positive pressure ventilation for ARF.


Analysis of radio wave propagation for ISM 2.4 GHz Wireless Sensor Networks in inhomogeneous vegetation environments.
The use of wireless networks has experienced exponential growth due to the improvements in terms of battery life and low consumption of the devices. However, it is compulsory to conduct previous radio propagation analysis when deploying a wireless sensor network. These studies are necessary to perform an estimation of the range coverage, in order to optimize the distance between devices in an actual network deployment. In this work, the radio channel characterization for ISM 2.4 GHz Wireless Sensor Networks (WSNs) in an inhomogeneous vegetation environment has been analyzed. This analysis allows designing environment monitoring tools based on ZigBee and WiFi where WSN and smartphones cooperate, providing rich and customized monitoring information to users in a friendly manner. The impact of topology as well as morphology of the environment is assessed by means of an in-house developed 3D Ray Launching code, to emulate the realistic operation in the framework of the scenario. Experimental results gathered from a measurement campaign conducted by deploying a ZigBee Wireless Sensor Network, are analyzed and compared with simulations in this paper. The scenario where this network is intended to operate is a combination of buildings and diverse vegetation species. To gain insight in the effects of radio propagation, a simplified vegetation model has been developed, considering the material parameters and simplified geometry embedded in the simulation scenario. An initial location-based application has been implemented in a real scenario, to test the functionality within a context aware scenario. The use of deterministic tools can aid to know the impact of the topological influence in the deployment of the optimal Wireless Sensor Network in terms of capacity, coverage and energy consumption, making the use of these systems attractive for multiple applications in inhomogeneous vegetation environments.


Effects of nutrient supply and dietary bulk on O2 uptake and nutrient net fluxes across rumen, mesenteric- and portal-drained viscera in ewes.
We assessed the effects of nutrient supply and dietary bulk, both increasing with hay intake, on O2 uptake and nutrient net fluxes across the portal-(PDV) and mesenteric- (MDV) drained viscera, and the rumen in adult ewes. Four ewes, fitted with a ruminal cannula, with catheters in the mesenteric artery, the portal, mesenteric and right ruminal veins, and with a blood flow probe around the right ruminal artery, were used in a 4 x 4 Latin square design. Treatments consisted of 500 g DM/d hay (LL, low bulk and low nutrient supply), 500 g DM/d hay + infused nutrients (LH, low bulk and high nutrient supply), 750 g DM/d hay + infused nutrients (MH, medium bulk and high nutrient supply), and 1,000 g DM/d hay (HH, high bulk and high nutrient supply). Infused nutrients consisted of volatile fatty acids (VFA) and casein dissolved in salts and infused continuously in the rumen to provide the same amount of metabolizable energy (7.6 MJ/d) and digestible protein (63 g/d) for LH, MH, and HH. Both increases in bulk and nutrient supply increased O2 uptake in the MDV and PDV. Dietary bulk stimulated mainly blood flow, whereas nutrient supply stimulated mainly O2 extraction rate. The O2 uptake by the rumen was not significantly affected by hay intake, although blood flow increased due to nutrient supply. Increase in hay intake had no effects on portal net release of lactate and net uptake of glucose but increased VFA, 3-D-hydroxybutyrate, ammonia, and amino acids (AA) net release and urea net uptake across PDV. The increase in portal nutrient net fluxes with hay intake was entirely related to the increase of nutrient supply for VFA, 3-D-hydroxybutyrate, ammonia, and urea, irrespective of the amount of casein infused for AA. Dietary bulk had no effect on total energy net release in the portal vein. We conclude that despite the increase in portal O2 uptake, increasing dietary bulk had no significant impact on portal recovery of energy. In ruminal tissues, which were the main site of energy absorption, O2 uptake appeared low and was not sensitive to dietary manipulation. In contrast, in mesenteric tissues, which contribute poorly to energy absorption with forage diets, O2 uptake appeared high and very sensitive to dietary manipulation.


A naturally occurring outbreak of tuberculosis in a group of imported cynomolgus monkeys (Macaca fascicularis).
This case report describes the diagnosis of tuberculosis (caused primarily by Mycobacterium bovis) in a group of newly imported Chinese origin cynomolgus monkeys. We also describe the use of sedation to enhance the accuracy of evaluation of the intrapalpebral tuberculin skin test using the mammalian old tuberculin reagent and report the first known diagnosis of Mycobacterium paraffinicum in a nonhuman primate. By 48 h after injection during the second tuberculin skin test, 6 of the 80 macaques had developed eyelid reactions ranging from mild (grade 1) to severe (grade 4). Given the range and severity of reactions, we suspected an outbreak of tuberculosis in the group. Because of the nature of the reactions, we sedated the animals at the 72-h evaluation to more closely observe and then palpate the injected eyelid. Evaluation of unsedated animals revealed 22 with a reaction to mammalian old tuberculin. We confirmed these 22 cases and identified an additional 11 animals with reactions when the monkeys were sedated. Mycobacterial culture of tissue from 6 macaques with reactions confirmed M. bovis in 3 animals. In addition, 1 of these 3 animals was culture-positive for both M. bovis and M. paraffinicum, and another was culture-positive for M. avium complex only. The addition of sedation to facilitate visual inspection and then palpation of the injected eyelid of these macaques increased the accuracy of evaluation and understanding of the number and severity of reactions to tuberculin skin testing.


Metformin in the treatment of clomiphene citrate-resistant women with high BMI and primary infertility: clinical results and reproductive outcome.
The objective of this study was to evaluate the clinical and reproductive outcome in clomiphene-citrate (CC)-resistant women with high body mass index (BMI) and primary infertility. This was a case series based at the King Hussein Medical center, Amman, Jordan. Nineteen CC-resistant women with polycystic ovary syndrome (PCOS) who had high BMI and primary infertility were studied. All women received metformin monotherapy; 850 mg twice daily for a period of 6 months. If pregnancy occurred, metformin was continued for the first 12 weeks of pregnancy. The main outcome measures were a reduction in the BMI, resumption of regular menses, ovulation and pregnancy rates. Resumption of regular cycles was observed in 13 of 19 (68.4%) women. Ovulation and pregnancy were achieved in 9 (47.4%) and 6 (31.6%) of the 19 women, respectively. A significant reduction in the body weight after treatment reflected by a significant reduction in the BMI was noted. Metformin monotherapy is effective in CC-resistant women with morbid obesity and primary infertility and should be considered as first-line treatment in these patients.


Cytologic diagnosis of mastocytosis by fine needle aspiration biopsy: a case report.
Mastocytosis is an abnormal proliferation of mast cells and their subsequent accumulation in various organs. Diagnosis of mast cell disease relies on proper identification of abnormal mast cells. A 55-year-old man presented with a history of fever for several months, associated with night sweats, involuntary 20lb weight loss, progressive fatigue, weakness, worsening abdominal distention, shortness of breath, and diffuse lymphadenopathy. Physical examination and computed tomography (CT) showed hepatosplenomegaly, massive ascites, and generalized lymphadenopathy. Bone marrow biopsy with immunohistochemistry (ICH) studies revealed mastocytosis. CT-guided fine needle aspiration biopsy (FNAB) of the retroperitoneal lymphadenopathy was performed. The smears were cellular for a mixed population of mature plasma cells, eosinophils, left-shifted granular and lymphoid cells, and abundant abnormal mast cells. The mast cells had round to oval lobulated nuclei, some of which were binucleated or eccentrically located, with coarse, evenly distributed chromatin. Abundant pale cytoplasm contained numerous metachromatic granules. IHC studies and flow cytometry confirmed the cytologic diagnosis of mastocytosis. This case highlights the cytologic features of mastocytosis in FNA specimens. IHC stains and flow cytometry are helpful to confirm the cytologic diagnosis. To the best of our knowledge, this is the second case that describes the cytologic characteristics of mastocytosis.


Partial purification and characterization of a thermostable xylanase from Bacillus licheniformis isolated from hot water geyser.
Thermo-alkali stable xylanases were purified from the extracellular broth of newly isolated Bacillus licheniformis strain produced in a 5-L stirred-tank bioreactor with wheat bran as a carbon source. A high degree of purity was achieved using size exclusion chromatography resulting in 16-fold purification and 69% recovery for fraction 5 which had the highest activity. The recovery obtained after pooling fractions 5 and 6 was 99%. The Km value of xylanase was calculated as 0.05 mM, and Vmax was 125 μmol/min/mg protein. Purified xylanase had a high thermal and pH stability. Xylanase was found to be suitable for application in the de-inking of paper and for saccharification of lignocellulosic waste biomass.


Protein ligand and nanotopography separately drive the phenotype of mouse embryonic stem cells.
Biochemical and biomechanical signals regulate stem cell function in the niche environments in vivo. Current in vitro culture of mouse embryonic stem cells (mESC) uses laminin (LN-511) to provide mimetic biochemical signaling (LN-521 for human systems) to maintain stemness. Alternative approaches propose topographical cues to provide biomechanical cues, however combined biochemical and topographic cues may better mimic the in vivo environment, but are largely unexplored for in vitro stem cell expansion. In this study, we directly compare in vitro signals from LN-511 and/or topographic cues to maintain stemness, using systematically-varied submicron pillar patterns or flat surfaces with or without preadsorbed LN-511. The adhesion of cells, colony formation, expression of the pluripotency marker,octamer-binding transcription factor 4 (Oct4), and transcriptome profiling were characterized. We observed that either biochemical or topographic signals could maintain stemness of mESCs in feeder-free conditions, indicated by high-level Oct4 and gene profiling by RNAseq. The combination of LN-511 with nanotopography reduced colony growth, while maintaining stemness markers, shifted the cellular phenotype indicating that the integration of biochemical and topographic signals is antagonistic. Overall, significantly faster (up to 2.5 times) colony growth was observed at nanotopographies without LN-511, suggesting for improved ESC expansion.


Effect of Serum Lipoprotein (a) [Lp(a)] in Menopausal Women.
The behavior of LP during the menopausal trinities and their relationship with sex hormones and body fat distribution is still unclear. The aim of this case control study was to estimate the serum lipoprotein (a) in postmenopausal women and women in reproductive age group and comparison of the above mention serum lipids between the two groups and was carried out in the Department of Biochemistry, Dhaka Medical College (DMC), Dhaka, in co-operation with the Department of Immunology, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka from July-2005 to June 2006. A total number of 70 women were selected. Selected women were grouped as Group A and Group B. In Group A 30 postmenopausal women were selected with age range 55-70 years. In Group B, 40 women within reproductive age were selected. Group B was again divided into two groups - Group B1 & Group B2 according to their ages. In Group B1 20 women were selected with age range 25-35 years, and in Group B2 another 20 women were selected with age range 36-45 years. Serum lipoprotein (a) or Lp(a) and lipid profile of all groups were measured. Mean sLp(a) concentration were compared between groups by" Mann Whitney U" test. Mean concentrations of every individual components of lipid profile (sTAG, sTc, sLDL & sHDL) were compared with different groups. sLp(a) concentration of Group A compared to Group B1 was found to be significantly higher (p<0.001). In the same way mean serum Lp(a) concentration of Group A compared to Group B2 was also significantly higher (p<0.001). Mean sLp(a) concentration of B1 compared B2 did not differ significantly. Mean values of lipid profiles were slightly elevated in Group A compared to Group B1 and Group B2 except sHDL-c level. Mean concentrations HDL-c was significantly lower in Group A compared to Group B1 and Group B2. Thus the present study has revealed that there is increased Lp(a) in menopause & decreased HDL in menopause.


Enhancement of albumin production by hepatocyte growth factor in rat hepatocytes: distinction in mode of action from stimulation of DNA synthesis.
Hepatocyte growth factor (HGF) has been shown to enhance albumin production as well as stimulate DNA synthesis in hepatocytes. The mode of action of HGF in exerting both effects is to be elucidated. We previously observed that hepatocyte proliferation occurred in normal rats given recombinant human HGF (rhHGF) intravenously. When rats received rhHGF similarly, serum albumin levels were significantly increased compared to controls. In primary culture of rat hepatocytes, albumin concentration in culture medium was significantly increased by rhHGF added at 24 h of culture compared to controls, increasing with time of culture. This effect of rhHGF was dose-related. When actinomycin D was added to the medium, the albumin concentration was reduced in a dose-related manner, but its enhancement by rhHGF was maintained. Albumin mRNA levels were not increased by rhHGF. When rhHGF was added similarly to the medium, immunocytochemically positive hepatocytes for 5-bromo-2'-deoxyuridine (BrdU) incorporation appeared 30 h later. Of these labeled hepatocytes, 12.5% were concomitantly stained for albumin. In contrast, albumin-positive hepatocytes were seen in 77% of BrdU-non-labeled hepatocytes (p<0.01). We conclude that HGF may enhance albumin production through post-transcriptional regulation in non-proliferating hepatocytes, but not in proliferating hepatocytes.


Preservation of red blood cells with purines and nucleosides. II. Uptake and utilization of purines and nucleosides by stored red blood cells.
The uptake of adenine, guanine, guanosine and inosine by stored red cells was investigated in whole blood and red cell resuspensions at initial concentrations of 0.25, 0.5 and 0.75 mM for adenine and 0.5 mM for the other additives using a rapid ion-exchange chromatographic microanalysis of purines and nucleosides in plasma and whole blood. Increasing adenine concentrations from 0.25 to 0.75 mM in blood elevated the adenine uptake from 0.3 up to 0.8 mmol/l red cells during 2 hours after collecting blood. The intra-/extracellular distribution ratio changed from 1 : 1.3 to 1: 1.7. Some 2 hours after withdrawing blood into CPD--solution with purines and nucleosides the uptake of adenine and guanine resulted in 40 per cent and 70 per cent respectively and of guanosine and inosine in 80 and 90 per cent respectively. The replacement of plasma by a resuspending solution gave the same uptake rates for purines and nucleosides. The nucleosides were rapidly split to purines and R-1-P and disappeared from blood during one week. Adenine and guanine were utilized to 80 to 90 per cent only after 3 weeks. During the same period the utilization of guanine was smaller by 40 per cent than that of adenine due to the different activity of the purine nucleoside phosphorylase for these substrates. The plasma of all analyzed blood samples contained hypoxanthine and inosine, but guanine and guanosine were detected only in those samples to which one of them was added. After 3 weeks of storage the highest concentration of hypoxanthine was found in CPD-AI blood with 600 microM in plasma and the highest concentration of synthesized inosine in CPD-AG blood with a concentration of 100 microM in plasma. Three ways of utilization of purines by stored red cells were discussed : the synthesis of nucleotide monophosphates, the formation of nucleosides, and the deamination. The portions of these ways change during storage. The most effective concentrations of adenine and guanosine in stored blood seems to be 0.25 and 0.5 mM respectively. The full utilization of the nucleoside requires the addition of inorganic phosphate.


3D segmentation of annulus fibrosus and nucleus pulposus from T2-weighted magnetic resonance images.
Computational medicine aims at employing personalised computational models in diagnosis and treatment planning. The use of such models to help physicians in finding the best treatment for low back pain (LBP) is becoming popular. One of the challenges of creating such models is to derive patient-specific anatomical and tissue models of the lumbar intervertebral discs (IVDs), as a prior step. This article presents a segmentation scheme that obtains accurate results irrespective of the degree of IVD degeneration, including pathological discs with protrusion or herniation. The segmentation algorithm, employing a novel feature selector, iteratively deforms an initial shape, which is projected into a statistical shape model space at first and then, into a B-Spline space to improve accuracy.The method was tested on a MR dataset of 59 patients suffering from LBP. The images follow a standard T2-weighted protocol in coronal and sagittal acquisitions. These two image volumes were fused in order to overcome large inter-slice spacing. The agreement between expert-delineated structures, used here as gold-standard, and our automatic segmentation was evaluated using Dice Similarity Index and surface-to-surface distances, obtaining a mean error of 0.68 mm in the annulus segmentation and 1.88 mm in the nucleus, which are the best results with respect to the image resolution in the current literature.


Comparison of glucose determinations on blood samples collected in three types of tubes.
Because of the metabolism of serum glucose in collection tubes containing blood samples, serum glucose levels may be found to decrease over time. Several types of collection tubes have been designed to, at least partially, block glucose metabolism by red blood cells in blood collection tubes that may not be analyzed immediately after blood collection. These include red-top collection tubes with serum separator, grey-top tubes with a fluoride glycolysis inhibitor, and heparin-containing green-top tubes which prevent clot formation. As part of a quality assurance project, we investigated whether glucose levels differed in the three tube types from each of 18 volunteers on a prolonged standing of 4 hours. We then determined the glucose concentrations of all three tubes from each of the 18 volunteers. We used refrigerated samples over a five-day period to determine if the initial values were reproducible. Surprisingly, after standing for four hours at room temperature, we found that the glucose levels in the three tubes from each volunteer were statistically indistinguishable from one another using the two-tailed paired t-test. Also, a linear regression analysis showed that the values of glucose for the three pairs of two tube types were closely correlated with one another, with correlation coefficients of >0.97, slopes close to 1, and Y-intercepts close to 0. These results suggest that blood collection in any of these tubes will render similar values for serum glucose even after standing for four hours. The tubes were then refrigerated at 4°C and re-analyzed after another six hours and then once per day for the next four days. Beginning at the first day at the six-hour determination, the glucose levels in the red- and grey-top tubes were statistically indistinguishable from one another but not in the red- and green-top tubes and in the grey- and green-top tubes. This was due to a steady decrease in the glucose levels in the green-top tubes. The glucose levels in the red- and grey-top tubes from each volunteer remained constant over the five-day period so that the coefficients of variation (CV) were low. In contrast, due to the decrease of glucose levels in the green-top tubes, the CVs for repeated glucose determinations in these tubes were high. Interestingly, a regression analysis of the glucose values for all three sets of paired tubes showed high (> 0.97) correlation coefficients and slopes close to 1. However, a regression analysis of the glucose values in the red- and green-top and grey- and green-top tubes at day five showed Y-intercepts of about -32 suggesting that there is a constant decrease of glucose in the green-top tubes that amounts to approximately 6 mg/dL per day over five days. These results suggest that red-top tubes with serum separator or grey-top tubes with a fluoride glycolysis inhibitor may be used for reproducible glucose determinations.


Squamous upper tract carcinoma presenting as a perinephric abscess.
Perinephric abscesses are life-threatening conditions, which are rarely associated with neoplasms of the kidney or upper tract collecting system. We report, to our knowledge, the first case of squamous carcinoma of the upper tract presenting as a perinephric abscess, diagnosed after radical nephrectomy.


Phosphoethanolamine addition to the Heptose I of the Lipopolysaccharide modifies the inner core structure and has an impact on the binding of Polymyxin B to the Escherichia coli outer membrane.
Phosphoethanolamine (pEtN) decoration of E. coli Lipopolysaccharide (LPS) provides resistance to the antimicrobial Polymyxin B (PolB). While EptA and EptB enzymes catalyze the addition of pEtN to the Lipid A and Kdo (pEtN-Kdo-Lipid A), EptC catalyzes the pEtN addition to the Heptose I (pEtN-HeptI). In this study, we investigated the contribution of pEtN-HeptI to PolB resistance using eptA/eptB and eptC deficient E. coli K12 and its wild-type parent strains. These mutations were shown to decrease the antimicrobial activity of PolB on cells grown under pEtN-addition inducing conditions. Furthermore, the 1-N-phenylnapthylamine uptake assay revealed that in vivo PolB has a reduced OM-permeabilizing activity on the ΔeptA/eptB strain compared with the ΔeptC strain. In vitro, the changes in size and zeta potential of LPS-vesicles indicate that pEtN-HeptI reduce the PolB binding, but in a minor extent than pEtN-Kdo-Lipid A. Molecular dynamics analysis revealed the structural basis of the PolB resistance promoted by pEtN-HeptI, which generate a new hydrogen-bonding networks and a denser inner core region. Altogether, the experimental and theoretical assays shown herein indicate that pEtN-HeptI addition promote an LPS conformational rearrangement, that could act as a shield by hindering the accession of PolB to inner LPS-targets moieties.


Smear misclassification in a cervical cancer screening programme.
A nested case-control study was undertaken in the Maribo County cohort of 27,811 women with negative Pap smears. Sixty women who later developed invasive cervical cancer constituted the cases, and five matched controls were selected from the cohort for each case. A total of 633 previous, negative smears for the cases and controls were reviewed independently by two pathologists. The review showed misclassification to be frequent in these smears collected in the period 1966-82. Thirty-five smears were considered positive at the review. The misclassification was differential in respect to the women's later disease status. The odds ratio for patients compared with controls for having at least one positive smear was 22.12 (95% CI 7.54-64.94). We were unable to identify specific characteristics of misclassified smears coming from later cases. Koilocytosis/dyskeratosis, herpes virus changed cells and hyperkeratosis were equally rare in smears from patients and controls. The Maribo County data indicate that the fraction of preventable cases of invasive cervical cancer in women aged 30-64 within the first 5 years after a negative smear could be increased from 62-72% to 83-86%, if misclassification of true positive smears could be eliminated. As a rough estimate, this would be at the cost of a 2% increase in the work load. It should be remembered that there is a large element of extrapolation in applying these results based on relatively poor quality specimens from 1966-82 as compared to a modern screening service.


A critique of the ACOEM statement on mold: undisclosed conflicts of interest in the creation of an "evidence-based" statement.
In 2003, the American College of Occupational and Environmental Medicine (ACOEM) published its evidence-based statement, "Adverse Human Health Effects Associated with Molds in the Indoor Environment," in its Journal of Occupational and Environmental Medicine (JOEM). ACOEM's author selection, development, peer review, and publication of its mold position paper involved a series of seemingly biased and ethically dubious decisions and ad hoc methods. The resulting position paper resembled a litigation "defense report" which omitted or inadequately acknowledged research validating the association between mold and building-related symptoms. ACOEM nonetheless released the paper as an "evidence-based" statement and then published it in JOEM without any further changes or conflict disclosure. The Mold Statement has been relied upon by attorneys and expert witnesses representing defendants in mold litigation to disclaim and invalidate individuals', families', and workers' claims of building-related health effects from indoor mold exposure.


Comparison of 3190 alcohol-dependent individuals with and without suicide attempts.
Suicidal behaviors are often seen in alcohol-dependent individuals. The aim of this study is to identify and confirm risk factors for suicide attempts in a large, family-based sample of alcoholics. Semistructured, detailed interviews were administered to 3190 alcohol-dependent individuals as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Information about suicidal behavior, socioeconomic characteristics, psychiatric comorbidity, substance use disorders, and characteristics of alcohol dependence were obtained from alcohol-dependent probands, controls, and their relatives. As determined by both univariate comparison and multivariate logistic regression analysis, alcohol-dependent individuals with a history of suicide attempts were found to have a significantly more severe course of alcohol dependence and a higher prevalence of both independent and substance-induced psychiatric disorders and other substance dependence. First-degree relatives of subjects with suicide attempts showed a significantly higher rate of suicide attempts, even after controlling for additional relevant diagnoses. These results support the hypothesis that alcohol-dependent individuals with a history of suicide attempts are more severely impaired. Screening and subsequent treatment of alcohol use disorder, psychiatric comorbidity, and substance use disorders among alcoholics may be crucial in preventing suicide attempts and completions.


Mitochondria as a Source and a Target for Uremic Toxins.
Elucidation of molecular and cellular mechanisms of the uremic syndrome is a very challenging task. More than 130 substances are now considered to be "uremic toxins" and represent a very diverse group of molecules. The toxicity of these molecules affects many cellular processes, and expectably, some of them are able to disrupt mitochondrial functioning. However, mitochondria can be the source of uremic toxins as well, as the mitochondrion can be the site of complete synthesis of the toxin, whereas in some scenarios only some enzymes of the pathway of toxin synthesis are localized here. In this review, we discuss the role of mitochondria as both the target and source of pathological processes and toxic compounds during uremia. Our analysis revealed about 30 toxins closely related to mitochondria. Moreover, since mitochondria are key regulators of cellular redox homeostasis, their functioning might directly affect the production of uremic toxins, especially those that are products of oxidation or peroxidation of cellular components, such as aldehydes, advanced glycation end-products, advanced lipoxidation end-products, and reactive carbonyl species. Additionally, as a number of metabolic products can be degraded in the mitochondria, mitochondrial dysfunction would therefore be expected to cause accumulation of such toxins in the organism. Alternatively, many uremic toxins (both made with the participation of mitochondria, and originated from other sources including exogenous) are damaging to mitochondrial components, especially respiratory complexes. As a result, a positive feedback loop emerges, leading to the amplification of the accumulation of uremic solutes. Therefore, uremia leads to the appearance of mitochondria-damaging compounds, and consecutive mitochondrial damage causes a further rise of uremic toxins, whose synthesis is associated with mitochondria. All this makes mitochondrion an important player in the pathogenesis of uremia and draws attention to the possibility of reducing the pathological consequences of uremia by protecting mitochondria and reducing their role in the production of uremic toxins.


Early intervention for alcohol problems.
Despite awareness of the wide variety of clinical and laboratory abnormalities associated with alcohol abuse, drinking problems often remain undetected in clinical practice. There is increasing evidence that problem drinking can be successfully treated by brief intervention. The general practitioner is in a good position to identify patients who drink excessively, and to intervene with brief counselling at an early stage when prognosis is more favourable. A practical strategy is described for diagnosis and intervention that could be readily implemented in clinical practice.


Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group.
Purpose Intermediate-risk rhabdomyosarcoma (RMS) includes patients with either nonmetastatic, unresected embryonal RMS (ERMS) with an unfavorable primary site or nonmetastatic alveolar RMS (ARMS). The primary aim of this study was to improve the outcome of patients with intermediate-risk RMS by substituting vincristine and irinotecan (VI) for half of vincristine, dactinomycin, and cyclophosphamide (VAC) courses. All patients received a lower dose of cyclophosphamide and earlier radiation therapy than in previous trials. Patients and Methods Patients were randomly assigned at study entry to either VAC (cumulative cyclophosphamide dose, 16.8 g/m2) or VAC/VI (cumulative cyclophosphamide dose, 8.4 g/m2) for 42 weeks of therapy. Radiation therapy started at week 4, with individualized local control plans permitted for patients younger than 24 months. The primary study end point was event-free survival (EFS). The study design had an 80% power (5% one-sided α-level) to detect an improved long-term EFS from 65% (with VAC) to 76% (with VAC/VI). Results A total of 448 eligible patients were enrolled in the study. At a median follow-up of 4.8 years, the 4-year EFS was 63% with VAC and 59% with VAC/VI ( P = .51), and 4-year overall survival was 73% for VAC and 72% for VAC/VI ( P = .80). Within the ARMS and ERMS subgroups, no difference in outcome by treatment arm was found. Severe hematologic toxicity was less common with VAC/VI therapy. Conclusion The addition of VI to VAC did not improve EFS or OS for patients with intermediate-risk RMS. VAC/VI had less hematologic toxicity and a lower cumulative cyclophosphamide dose, making VAC/VI an alternative standard therapy for intermediate-risk RMS.


Enhancement in irradiated mononuclear cells in culture of mitogen-induced incorporation of [3H]thymidine by homologous conditioned medium.
Incorporation of [3H]thymidine in irradiated peripheral blood mononuclear cell cultures irradiated in vitro was stimulate significantly by either concanavalin A or phytohemagglutinin only in the presence of homologous conditioned medium. Production of this activity by mononuclear cells was enhanced by irradiation and/or pulsed exposure to puromycin but was abolished by actinomycin D. Addition of anti-interleukin 1 or anti-interleukin 2 monoclonal antibodies to the conditioned medium before assay did not influence the stimulatory action. A similar significant stimulation of mononuclear cell cultures irradiated with 5 Gy by concanavalin A was obtained when purified preparations of homologous conditioned medium were used in the assay. Purification was done by ultrafiltration and concentration, heparin agarose chromatography, ammonium sulfate precipitation, concanavalin A agarose chromatography, DEAE-ion exchange chromatography and HPLC gel filtration chromatography. With SDS-PAGE and silver staining, the active HPLC fraction gave one band of 50 kDa, suggesting that this protein is responsible for the co-stimulatory effect of homologous conditioned medium for both mitogen-induced irradiated and nonirradiated mononuclear cell cultures.


[CXCL10/IP-10 as a new biomarker for Mycobacterium tuberculosis infection].
In low prevalence countries, where identification and treatment of latent TB infection (LTBI) are basis of national programmes against tuberculosis, the diagnosis is focused mainly on tuberculin skin test (TST) and interferon gamma release assay (IGRA), both of which seem to be imperfect. This is why searches for a new, more specific biomarker for TB infection have been conducted. A promising candidate for the new marker is interferon gamma induced protein (IP-10). IP-10 is a chemokine, which can be detected in increased amounts in patients with active tuberculosis, latent TB infection and in individuals who had contact with an index case. It has been commonly suggested that a simultaneous analysis of IGRA and IP-10 level increases the effectiveness of IGRA, however it is still not certain whether measurement of IP-10 level might help distinguish between the above mentioned forms of tuberculous infection. Hopes are high as the protein is proved to be a good marker for treatment monitoring in adults, though there is no available data on its usefulness in monitoring therapy in paediatric population. More studies are still needed to fully assess the benefits of IP-10 level measurement as a biomarker for tuberculous infection, especially in children.


Recent advances in hypertrophic scar.
Hypertrophic scars (HTS) are predominant diseases after burn and trauma, which cause severe physiological and psychological problems. HTS have been researched for decades, and our knowledge about the mechanisms of HTS formation process has been increasing. However, the effects of currently available prevention and treatment strategies are limited. In this review, we summarize currently known mechanisms and recent studies of HTS, including extracellular matrix, matrix metalloproteinases, fibroblasts, myofibroblasts and their contraction ability, keratinocytes, growth factors, inflammatory and immune response, and stem cell treatment, hoping for a better understanding of HTS generation, development and effective translation to treatment strategies.