Diversity and Host Relationships of the Mycoparasite Sepedonium (Hypocreales, Ascomycota) in Temperate Central Chile.
We present the first major survey of regional diversity, distribution and host-association of Sepedonium. Whereas the rather scarce worldwide records of this mycoparasitic fungus suggested no specific distribution pattern of most species before, we provide new evidence of endemic and specific host-parasite guilds of Sepedonium in Southern South America, including the description of a new species. The corresponding inventory was performed in temperate central Chile. The regional landscape, a mosaic of exotic timber plantations and remnants of native Nothofagus forests, facilitates a unique combination of endemic and adventitious Boletales hosts. During a two-year survey, 35 Sepedonium strains were isolated and cultured from infected basidiomata of allochthonous Chalciporus piperatus, Paxillus involutus, Rhizopogon spp. and Suillus spp., as well as from the native Boletus loyita, B. loyo, B. putidus and Gastroboletus valdivianus. Taxonomic diagnosis included morphology of conidia and conidiophores, sequences of ITS, RPB2 and EF1 molecular markers and characteristics of in vitro cultures. Phylogenetic reconstructions were performed using Bayesian methods. Four Sepedonium species could be identified and characterized, viz.: S. ampullosporum, S. chrysospermum, S. laevigatum and the newly described species S. loyorum. The most frequent species on introduced Boletales was S. ampullosporum, followed by S. chrysospermum and S. laevigatum. S. loyorum sp. nov. was found exclusively on native boletacean hosts, separated from its closest relative S. chalcipori by micromorphological and molecular attributes. Species descriptions and identification keys are provided. Ecological and biogeographical aspects of endemic and allochthonous symbiotic units consisting of mycoparasite, ectomycorrhizal fungal host and respective mycorrhizal tree are discussed.


[Pain management in subarachnoid haemorrhage: a survey of French analgesic practices].
Pain management in patients having a subarachnoid haemorrhage was assessed in French intensive care unit of neurosurgical centres. Nationwide survey. A standardized postal questionnaire was sent to senior doctor of every neurosurgical centres in France inquiring pain scores assessment, analgesics used and their routes of administration, centre's opinion about efficacy of pain management. Of the 34 centres, 24 returned completed questionnaires. Fifty four per cent of the centres evaluated pain intensity with a non valid pain score. In the case of patients in the comatose, pain was not evaluated in fifty four per cent of the centres. Paracetamol and morphine were the most currently used analgesics drugs. Morphine was administered subcutaneously by 75% of the centres. Six centres used also PCA. Thirty-seven percent of the centres were reluctant to use opioids and 75% to use NSAIDS. The majority of the centres considered pain management in patient suffering from subarachnoid haemorrhage (SAH) was not optimal and stressed the need to establish a well validated pain rating scale dedicated to SAH patients.


Heart check: the development and evolution of an organizational heart health assessment.
The purpose of this article is to document the development, testing, and application of an organizational assessment tool used to measure employer support for heart health. Additional information is presented on its future research and applications plan. This article represents the pooling of results from multiple studies using a variety of designs, including pilot tests, cross-sectional analyses, and quasi-experiments. Worksites covering the spectrum of employers across industry types and size, and throughout all of New York State. Over 10,000 New York employees and 1000 New York employers are represented in the multiple phases of this research. Heart Check is a 226-item inventory designed to measure such features in the worksite as organizational foundations, administrative supports, tobacco control, nutrition support, physical activity support, stress management, screening services, and company demographics. Additional side studies used professional judgments and behavioral surveys. As an assessment tool Heart Check shows evidence for reliability and validity. Applications of the instrument show characteristics that define high-scoring companies, quasi standards for New York employers, and, when applied during interventions, positive changes in organizational support levels. A relatively inexpensive, easy-to-use, and metrically tested instrument exists for measuring the construct of organizational support for employee heart health. The instrument shows promise as part of a system to enhance heart health through public health-based interventions in the workplace.


Effect of progestogens on estrogen-induced lipoprotein changes.
A study was performed to evaluate the role of progestogens, on estrogen-induced changes in lipoprotein levels. Sixty postmenopausal symptomatic women, aged 36-59, were included in the study. They were prospectively randomized to a sequential schedule (n = 20), 17 beta-estradiol transdermally 0.05 mg/day on days 1-24 and medroxyprogesterone acetate 10 mg/day orally on days 15-24 or a continuous schedule (n = 20), 17 beta-estradiol transdermally 0.05 mg/day and medroxyprogesterone acetate 2.5 mg/day orally on days 1-24. Patients who had total abdominal hysterectomy+bilateral salphingooopherectomy (n = 20) received only 17 beta-estradiol 0.05 mg/day continuously. Serum total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglyceride (TG) levels were determined prior to and at the 3rd, 6th and 9th month of therapy in all groups. Mean TC, TG and LDL cholesterol levels did not change significantly during therapy (P > 0.05). Only the mean HDL cholesterol levels showed significant increases in all groups; from 42.30 +/- 9.97 mg/dl to 64.10 +/- 6.81 mg/dl in group I (P < 0.001), from 41.85 +/- 9.09 mg/dl to 60.65 +/- 7.41 mg/dl in group II (P < 0.001) and from 40.70 +/- 11.26 mg/dl to 58.80 +/- 7.74 mg/dl in group III (P < 0.001). It is concluded that medroxyprogesterone acetate, whether used continuously or sequentially, does not oppose the beneficial effects of transdermal 17 beta-estradiol on the lipoprotein profile.


Evaluation of immunomagnetic separation and plating media for recovery of Salmonella from meat.
Immunomagnetic separation (IMS) was compared with selective enrichment in selenite cystine (SC) broth for isolation of Salmonella from 86 artificially contaminated ground beef samples. Both Rambach agar (RA) and Hektoen enteric (HE) agar were used as selective plating media. The highest count of Salmonella colonies per plate was obtained after enrichment in SC broth and plating on RA (mean value: 111.1+/-58.1 CFU per plate); the lowest count was obtained after IMS and plating on HE agar (mean value: 65.4+/-36.6 CFU per plate). Salmonella in preenrichment was concentrated 1.7-fold by IMS and represented 31% of the microbial population captured by the beads, but nonspecific binding was high. As a result of the large numbers of competing bacteria, isolations on both RA and HE agar following IMS were quite difficult (mean value for Salmonella colonies: 79.9+/-42.7 CFU per plate; mean value for non-Salmonella colonies: 144.1+/-75.7 CFU per plate; ratio of Salmonella to non-Salmonella colonies: 0.8). This study indicates that SC broth is superior to IMS in the isolation of Salmonella from raw ground meat.


Assessing the risk factors for suicidal thoughts at a nontraditional commuter school.
The sample of students completing the National College Health Assessment (NCHA) Survey at the University of Utah differs from the national reference group for the NCHA 2003 in age, employment, residence, and marital status. The purpose of this study is to determine if the defining characteristics of a commuter school increase the risk for suicidal thoughts. During the fall semester of 2004, the University of Utah implemented a randomized electronic survey assessing the student body's health status in several areas. The authors compared 88 respondents who endorsed seriously considered suicide in the previous 12 months were with the remaining 954 respondents to identify discriminating variables. Those students who seriously considered suicide more likely lived off campus, indicated they were emotionally abused, were in only fair health, experienced being assaulted, experienced unwanted sexual touching, or were not heterosexual. Students who were employed were significantly less likely to consider suicide.


Density-functional-theory investigation of pressure induced semiconductor-metal transitions in the ferromagnetic semiconductor HgCr2Se4.
We investigate the electronic structures of the ferromagnetic semiconductor HgCr(2)Se(4) by using a modified Becke and Johnson exchange potential. The energy gap calculated with the experimental lattice structure is in good agreement with the experimental value. When the pressure reaches 9.0 GPa, HgCr(2)Se(4) becomes a so-called spin gapless semiconductor due to the closure of the spin non-conservation energy gap, and when the pressure increases to 11.4 GPa, the spin conservation energy gap closes, leading to a semiconductor-semimetal transition.


Molecular features of thyroid hormone-regulated skin remodeling in Xenopus laevis during metamorphosis.
Amphibian body skin provides an opportunity to investigate the molecular mechanism of thyroid hormone (TH)-dependent organ remodeling during metamorphosis. Global gene expression changes in the TH-dependent body skin remodeling were studied with microarray analysis. We identified 401 genes that were differentially expressed more than fourfold for 7 days after TH-treatment. As expected, larval- and adult-type keratin genes were significantly inactivated and activated, respectively. The expression changes of the Gene Ontology annotated genes demonstrated significant correlation with the morphological and physiological changes in body skin metamorphosis. The 'transcription and proteolysis' category genes were first upregulated 1 day after TH-treatment. Subsequently, the 'cell cycle' category genes were activated at 3 days. The 'defense response' and 'immune response' category genes were the late TH-response genes, which were downregulated and upregulated at 5 and 7 days, respectively. From these genes, adult-type keratin-c (xak-c) gene was selected as a suitable gene to visually monitor the emergence of adult-type epidermal cells during skin remodeling, because the gene is specifically expressed in adult epidermal basal cells. We generated enhanced green fluorescent protein (EGFP)-transgenic Xenopus laevis driven by the promoter of xak-c gene. The keratin promoter faithfully expressed the EGFP gene in adult-type basal cells. Spatial and temporal EGFP-fluorescence patterns of filial 1 (F1)-offspring tadpoles visually demonstrated an event of sequential replacement of larval keratinocytes with the newly generated adult counterparts.


Michigan Neural Distinctiveness (MiND) study protocol: investigating the scope, causes, and consequences of age-related neural dedifferentiation.
Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway). The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity. By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines. This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .


Perimedullary arteriovenous fistulas of the craniovertebral junction: A systematic review.
Perimedullary arteriovenous fistulas (PMAVFs) are uncommon vascular malformations, and they rarely occur at the level of the craniovertebral junction (CVJ). The therapeutic management is challenging and can include observation alone, endovascular occlusion, or surgical exclusion, depending on both patient and malformation characteristics. A systematic literature search was conducted using MEDLINE, Scopus, and Google Scholar databases, searching for the following combined MeSH terms: (perimedullary arteriovenous fistula OR dural arteriovenous shunt) AND (craniocervical junction OR craniovertebral junction). We also present an emblematic case of PMAVF at the level of the craniovertebral junction associated to a venous pseudoaneurysm. A total of 31 published studies were identified; 10 were rejected from our review because they did not match our inclusion criteria. Our case was not included in the systematic review. We selected 21 studies for this systematic review with a total of 58 patients, including 20 females (34.5%) and 38 males (65.5%), with a female/male ratio of 1:1.9. Thirty-nine out of 58 patients underwent surgical treatment (67.2%), 15 out of 58 patients were treated with endovascular approach (25.8%), 3 out of 58 patients underwent combined treatment (5.2%), and only 1 patient was managed conservatively (1.7%). An improved outcome was reported in 94.8% of cases (55 out of 58 patients), whereas 3 out of 58 patients (5.2%) were moderately disabled after surgery and endovascular treatment. In literature, hemorrhagic presentation is reported as the most common onset (subarachnoid hemorrhage in 63% and intramedullary hemorrhage in 10%), frequently caused either by venous dilation, due to an ascending drainage pathway into an intracranial vein, or by the higher venous flow rates that can be associated with intracranial drainage. Hiramatsu and Sato stated that arterial feeders from the anterior spinal artery (ASA) and aneurysmal dilations are associated with hemorrhagic presentation. In agreement with the classification by Hiramatsu, we defined the PMAVF of the CVJ as a vascular lesion fed by the radiculomeningeal arteries from the vertebral artery and the spinal pial arteries from the ASA and/or lateral spinal artery. Considering the anatomical characteristics, we referred to our patient as affected by PMAVF, even if it was difficult to precisely localize the arteriovenous shunts because of the complex angioarchitecture of the fine feeding arteries and draining veins, but we presumed that the shunt was located in the point of major difference in vessel size between the feeding arteries and draining veins. PMAVFs of CVJ are rare pathologies of challenging management. The best diagnostic workup and treatment are still controversial: more studies are needed to compare different therapeutic strategies concerning both long-term occlusion rates and outcomes.


Management of interstitial pregnancy in the era of laparoscopy: a meta-analysis of 855 case studies compared with traditional techniques.
Interstitial pregnancy is a rare, life-threatening condition that requires high clinical suspicion for diagnosis. Most cases are discovered after complications have occurred. Many authors have described laparoscopic management. Although previous systematic reviews have compared the attributes and complications associated with interstitial pregnancy, we endeavored to complete the first systematic review and meta-analysis to compare the laparoscopic treatment of interstitial pregnancy with the open approach in the modern age of laparoscopic surgery. We systematically searched PubMed, ClinicalTrials.gov, Scopus, Web of Science, and Cochrane until June 2020 using relevant keywords and screened them for eligibility. We found a statistically significant difference in blood loss between laparoscopic and open surgery (168 mL compared to 1,163 mL). Further, cumulative meta-analysis has revealed that blood loss in laparoscopy has been decreasing over time from 1991 to 2020. Laparoscopic patients took less operative time (63.2 minutes) compared to laparotomy patients (78.2 minutes). Patients in the laparoscopic group spent less time hospitalized (3.7 days) compared to laparotomy patients (5.2 days). Our findings add strength to the position that laparoscopic approaches to interstitial pregnancy can be considered first-line in most situations. The laparoscopic approach was found to have a mean blood loss of 168 mL, and this blood loss seems to decrease over time. Increased gravidity and duration of amenorrhea are positive factors that increase bleeding during the procedure. We are unable to find enough high-quality data to significantly compare successful pregnancy following surgery or risk of mortality in these populations.


Repellency of oils of lemon eucalyptus, geranium, and lavender and the mosquito repellent MyggA natural to Ixodes ricinus (Acari: Ixodidae) in the laboratory and field.
MyggA Natural (Bioglan, Lund, Sweden) is a commercially available repellent against blood-feeding arthropods. It contains 30% of lemon-scented eucalyptus, Corymbia citriodora (Hook.) K. D. Hill & L. A. S. Johnson (Myrtaceae), oil with a minimum of 50% p-menthane-3,8-diol. MyggA Natural also contains small amounts of the essential oils of lavender, Lavandula angustifolia Mill. (Lamiaceae), and geranium, Pelargonium graveolens L'Her. (Geraniaceae). In laboratory bioassays, MyggA Natural and C. citriodora oil exhibited 100% repellency against host-seeking nymphs of Ixodes ricinus (L.) (Acari: Ixodidae). Lavender oil and geranium oil, when diluted to 1% in 1,2-propanediol, had weak repellent activities on I. ricinus nymphs, but when diluted to 30% in 1,2-propanediol had 100% repellencies. 1,2-Propanediol (100%) had no significant repellent activity in comparison with that of the control. In field tests in tick-infested areas in central Sweden, tick repellency of MyggA Natural and C. citriodora oil was tested by the blanket-dragging technique for 4 d during a 6-d period. The repellencies (74 and 85%, respectively) on day 1 are similar (89%) to that of blankets treated in a similar manner with 19% diethyl-methyl-benzamide, based on previous work. Repellencies declined significantly from day 1 to day 6 (74 to 45% for MyggA Natural; 85 to 42% for C. citriodora oil).


Comparison of 81mKrypton and 99mTc-Technegas for ventilation single-photon emission computed tomography in severe chronic obstructive pulmonary disease.
Ventilation and perfusion single-photon emission computed tomography combined with computed tomography (SPECT/CT) is a powerful tool to assess the state of the lungs in chronic obstructive pulmonary disease (COPD). 81mKrypton is a gaseous ventilation tracer and distributes similarly to air, but is not widely available and relatively expensive. 99mTc-Technegas is cheaper and has wider availability, but is an aerosol, which may deposit in hot spots as the severity of COPD increases. In this study, 81mKrypton and 99mTc-Technegas were compared quantitatively in patients with severe COPD. The penetration ratio, the heterogeneity index (with and without band filtering for relevant clinical sizes) and hot spot appearance were assessed in eleven patients with severe COPD that underwent simultaneous dual-isotope ventilation SPECT/CT with both 99mTc-Technegas and 81mKrypton. Significant differences were found in the penetration ratio for the medium energy general purpose (MEGP) collimators, but not for the low energy general purpose (LEGP) collimators. The difference in the overall and the band filtered heterogeneity index was significant in most cases. All patients suffered from 99mTc-Technegas hot spots in at least one lung. Comparison of MEGP 81mKrypton and LEGP Technegas scans revealed similar results as the comparison for the MEGP collimators. Caution should be taken when replacing 81mKrypton with 99mTc-Technegas as a ventilation tracer in patients with severe COPD as there are significant differences in the distribution of the tracers over the lungs. Furthermore, this patient group is prone to 99mTc-Technegas hot spots and might need additional scanning if hot spots severely hamper image interpretation.


A randomized, double-blind, placebo-controlled study to assess efficacy of mirtazapine for the treatment of diarrhea predominant irritable bowel syndrome.
Ample evidence indicates the efficacy of serotonin type 3 (5-HT3) receptor antagonists in the treatment of patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Mirtazapine is an atypical antidepressant with a well-known 5-HT3 receptor antagonist property. This study, therefore, was undertaken to investigate whether compared to placebo, mirtazapine would be efficacious and safe in the treatment of patients with IBS-D. From November 2019 until July 2020, 67 patients meeting Rome IV criteria for IBS-D were randomized in a double-blind fashion into either the mirtazapine treatment group (n = 34) or the placebo treatment group (n = 33). Patients started with mirtazapine 15 mg/day at bedtime for one-week; after which the dose was increased to 30 mg/day for an additional 7-week. Outcomes included changes in the total IBS symptom severity score (IBS-SSS), Hospital anxiety and depression scale score (HADS), and IBS Quality of Life. Additionally, changes in the diary-based symptoms scores including pain, urgency of defecation, bloating, stool frequency, and stool consistency based on the 7-point Bristol Stool Form Scale (BSFS), and a number of days per week with pain, urgency, diarrhea, or bloating, once during the 1-week run-in period, and once during the last week of treatment were recorded. All analyses were performed on an Intention-to-Treat (ITT) analysis data set. The results showed compared to placebo, mirtazapine is more efficacious in decreasing the severity of IBS symptoms (P-value = 0.002). Further, at the end of the treatment period, all diary-derived symptoms except bloating showed significantly more improvement in the mirtazapine-treated subjects compared to the placebo-treated subjects. While was well-tolerated, mirtazapine also significantly improved the patients' quality of life (P-value = 0.04) and anxiety symptoms (P-value = 0.005). Overall, mirtazapine seems to have a potential benefit in the treatment of patients with IBS-D, particularly those with concomitant psychological symptoms. However, further studies are warranted to determine whether these findings are replicated. Trial registration: Registration number at Iranian Registry of Clinical Trials: IRCT20120215009014N311 . Registration date: 2019-10-21.


Impaired glucose metabolism in heroin and methadone users.
Plasma glucose and insulin responses to both oral and intravenous glucose stimulation were evaluated in heroin and methadone addicts, compared to healthy control subjects. Both groups of addicts had an altered response to oral and intravenous glucose load. These phenomena were linked to a reduced insulin response. Moreover, increased fasting insulin levels in both groups of addicts were observed. These data show that both heroin and methadone addiction may alter glucose metabolism, and, furthermore, stress the findings of similarities between opiate addicts and non-insulin dependent diabetics.


Super-resolution labelling with Action-PAINT.
Recent advances in localization-based super-resolution microscopy have enabled researchers to visualize single molecular features down to individual molecular components (~5 nm), but do not yet allow manipulation of single-molecule targets in a user-prescribed, context-dependent manner. Here we report an 'Action-PAINT' (PAINT, point accumulation for imaging in nanoscale topography) strategy for super-resolution labelling upon visualization on single molecules. This approach monitors and localizes DNA binding events in real time with DNA-PAINT, and upon visualization of binding to a desired location, photo-crosslinks the DNA to affix the molecular label. We showed the efficiency of 3-cyanovinylcarbazole nucleoside photo-inducible crosslinking on single molecular targets and developed a software package for real-time super-resolution imaging and crosslinking control. We then benchmarked our super-resolution labelling method on synthetic DNA nanostructures and demonstrated targeted multipoint labelling on various complex patterns with 30 nm selectivity. Finally, we performed targeted in situ labelling on fixed microtubule samples with a 40 nm target size and custom-controlled, subdiffraction spacing.


Tuberculosis control in Kyrgyzstan--an opportunity.
Tuberculosis incidence and mortality rates are rising steeply, reflecting economic hardship and the deterioration of the health infrastructure. The human and technical resources needed to reverse this trend are on hand, but cannot be used effectively without an adequate financial input. The cost of controlling tuberculosis now is modest compared with the cost of allowing it to increase.


1,25-(OH)2D3 ameliorates renal interstitial fibrosis in UUO rats through the AMPKα/mTOR pathway.
To investigate the effects of 1,25(OH)2D3 on renal fibrosis associated with the AMP-activated protein kinase (AMPK)α/mechanistic target of rapamycin (mTOR) signalling pathway in a rat model of unilateral ureteral obstruction (UUO). A total of 54 male Sprague Dawley rats were randomly divided into three groups: sham-operation group, UUO group, and UUO plus calcitriol (3 ng/100 g) group. Renal tissue was excised for histological examination by immunohistochemistry and Western blot, and for gene expression analysis using real-time polymerase chain reaction. 1,25(OH)2D3 enhanced AMPKα levels, inhibited mTOR levels and slowed the development of interstitial fibrosis in kidney tissue. Compared with the UUO plus calcitriol group, UUO rats demonstrated more severe renal damage characterized by marked tubular atrophy, interstitial fibrosis and significant induction of fibrogenic transforming growth factor-β1 and increased extra-cellular matrix proteins (α-smooth muscle actin and collagen type III), and decreased E-cadherin. Treatment with 1,25(OH)2D3 altered the AMPKα/mTOR signalling pathway to suppress excessive fibroblast activation observed in UUO rats. This may serve as a novel mechanism to ameliorate renal dysfunction and fibrotic lesions.


Arabidopsis CPK3 plays extensive roles in various biological and environmental responses.
Plant Ca(2+)-dependent protein kinase (CPK) signaling is involved in a wide array of intracellular signaling pathways involved in stomatal movement and plant adaptation to various environmental challenges including drought, salt and cold stress. Arabidopsis CPK3 appears to be extensively involved in such a wide range of aspects, and has been shown to function in mediating the signaling following Ca(2+) influx after insect herbivory. The results reveal the involvement of CPK3 in the herbivory-induced signaling network through phosphorylating the substrate target HsfB2a (heat shock transcription factor) for transcriptional activation of the plant defensin gene PDF1.2. Proteomic studies based on the cell-free protein production system allowed us to mine CPK3 targets more extensively and clarify the nature of multifunctional CPK3.


Restoration of p53 gene function in 12-O-tetradecanoylphorbor 13-acetate-resistant human leukemia K562/TPA cells.
The human leukemia K562 cell line does not express wild-type p53 protein. Due to the loss of one p53 allele and an insertion mutation in exon 5 of the other allele resulting in a frameshift mutation, K562 cells express a truncated p53 protein of 148 amino acids. A human leukemia phorbol ester-resistant subline, K562/TPA, is cross-resistant to some anticancer agents. A remarkable difference in cell cycle progression at G1/S phase was observed in the synchronised K562/TPA cells as compared with K562 cells. Southern blot and DNA sequence analysis revealed no mutation in exon 5 of the p53 gene in K562/TPA cells. p21Cip1 expression was also restored in K562/TPA cells confirming that the reversal of this p53 gene mutation restored wild-type p53 function in these cells. This is a unique report describing reversal of p53 gene mutation by drugs. This was associated with the expression of wild-type p53 mRNA and protein in K562/TPA cells. The K562/TPA cell line may provide a very useful tool for the investigation of the relationship between p53 status and chemosensitization.


Enhancing the detection of natural thermal entanglement with disorder.
Physical systems have some degree of disorder present in them. We discuss how to treat natural, thermal entanglement in any random macroscopic system from which a thermodynamic witness bounded by a constant can be found. We propose that functional many-body perturbation theory be applied to allow either a quenched or an annealed average over the disorder to be taken. We find, when considering the example of an XX Heisenberg spin chain with a random coupling strength, that the region of natural entanglement detected by both witnesses can be enhanced by the disorder.


UCS1025A and B, new antitumor antibiotics from the fungus Acremonium species.
[structure: see text] UCS1025A and B, novel pentacyclic polyketides with an unprecedented furopyrrolizidine skeleton, were isolated from the fungus Acremonium sp. KY4917. The structures and stereochemistry were elucidated by a combination of two-dimensional NMR and X-ray crystallographic analysis. UCS1025A showed unique chemical equilibria involving three tautomeric isomers and exhibited antimicrobial activity and antiproliferative activity against human tumor cell lines.


Looking for the best immune-checkpoint inhibitor in pre-treated NSCLC patients: An indirect comparison between nivolumab, pembrolizumab and atezolizumab.
Immune-checkpoint inhibitors represent the new standard of care in patients with advanced NSCLC who progressed after first-line treatment. This work aim to assess any difference in both efficacy and safety profiles among Nivolumab, Pembrolizumab and Atezolizumab in pre-treated NSCLC patients. Randomized clinical trials comparing immune-checkpoint inhibitor versus docetaxel in pre-treated patients with advanced NSCLC were included and direct comparison meta-analysis of selected trials have been performed. Subsequently the summary estimates of Nivolumab, Pembrolizumab and Atezolizumab emerging from the direct meta-analysis were selected to provide the pooled estimates of hazard ratio (HR) and relative risk (RR) for the indirect comparisons among these agents. A total of 5 studies met the selection criteria and were included in the meta-analysis. Indirect comparisons for efficacy outcomes showed the RR for ORR nivolumab versus atezolizumab 1.66 (95% CI 1.07-2.58), pembrolizumab versus atezolizumab 1.94 (95% CI 1.30-2.90). No significant differences in both PFS and OS have been observed. Indirect comparisons for safety showed the RR for G3-5 AEs nivolumab versus pembrolizumab 0.41 (95% CI 0.29-0.60), nivolumab versus atezolizumab 0.50 (95% CI 0.35-0.72). No significant differences in both pneumonitis and discontinuation rate have been observed. The results of this work revealed that nivolumab and pembrolizumab are associated with a significant increase of ORR as compared to atezolizumab and nivolumab is associated with a significant lower incidence of G3-5 AEs as compared to the other drugs. These evidences could support the oncologists to select the best drug for each patient.


[Reabsorption syndrome after transurethral resection (TUR) of the prostate: review of physiologic, diagnostic, and therapeutic features].
In spite of the development of non-invasive strategies, surgical treatment of the prostate (TURP) and, mostly transurethral resection, is the most effective choice for patients suffering from benign prostatic hyperplasia who do not respond properly to pharmacological treatment. Absorption of hypotonic fluids used during TURP may cause hemodynamic and central nervous system disturbances. These symptoms, both taken separately or as a whole, are best known as "Transurethral prostatic resection syndrome" or "TURP syndrome". The original description of this syndrome dates from half a century ago; however, a number of items regarding its physiopathology and treatment remain unclear. We present a review of this pathological entity, compiling diagnostic and therapeutical approaches.


Gastrointestinal absorption of the strongly acidic drug proxicromil.
Gastrointestinal absorption of the strongly acidic drug proxicromil has been studied with respect to its physical organic chemistry. The lipophilicity of the drug above pH 6 in octanol-buffer partition experiments is dependent on ion pair formation. Similar trends were demonstrated for the in vitro partition of the compound into GI tissue. The absorption of the compound from the perfused GI tract of rats in vivo was not consistent with classical un-ionized drug absorption theories and indicated the operation of other processes, especially ion pair formation, as major mechanisms of proxicromil absorption.


Exploring potential use of internet, E-mail, and instant text messaging to promote breast health and mammogram use among immigrant Hispanic women in Los Angeles County.
Breast cancer is now the leading cause of death in Hispanic women (HW). Internet, e-mail, and instant text messaging may be cost-effective in educating HW about breast health and in reducing breast cancer mortality. We surveyed 905 HW women attending a free health fair about their technology use, acculturation, insurance status, mammography use, and breast cancer knowledge. Data were analyzed by t test or χ(2) tests. Mean age was 51.9 ± 14.2 years (range, 18 to 88 years). Ninety-two per cent were foreign-born. Most had completed some high school (39%) or elementary (38%) education. Most (62%) were uninsured. The majority spoke (67%) and read (66%) only Spanish. Only 60 per cent of HW older than 40 years had a recent mammogram. HW older than 40 years who had not had a recent mammogram were younger (mean 54.9 ± 10.8 vs 58 ± 10.4 years) and less likely to have health insurance (25 vs 44%; P < 0.001). Most HW never use the Internet (58%) or e-mail (64%). However, 70 per cent have mobile phones (66% older than 40 years), and 65 per cent use text messaging daily (58% older than 40 years, P = 0.001). In fact, 45 per cent wish to receive a mammogram reminder by text. Text messaging may be an inexpensive way to promote breast health and screening mammography use among uninsured HW.


Morphometric changes in the prepubertal female rat thyroid gland following acute exposure to 2,2',4,4'-tetrachlorobiphenyl and Aroclor 1242.
Weanling female Sprague-Dawley rats were given either 2 or 5 consecutive daily doses of 30 mg/kg 2,2',4,4'-tetrachlorobiphenyl (CB 47) or a total dose of 120 mg/kg Aroclor 1242 divided into 2, 3, or 5 daily doses by intraperitoneal injection. One day after the final dose, serum total thyroxine (T4) was determined and thyroid glands were collected and prepared for morphometric analysis. Serum T4 increased between 20 and 25 d of age, but declined to 35-52% of controls by d 25 in PCB-treated rats. In rats receiving only 2 doses of CB 47, the declines in serum T4 were more modest but the thyroid follicular epithelial cell height increased from 9 microns to 10-12 microns and the colloid area decreased from 1100 microns2 to 800-900 microns2. In Aroclor 1242-treated rats, follicular cell height increases and colloid area decreases were somewhat greater; serum T4 was higher (partially restored) in the rats having received earlier doses. The rapid response of the thyroid gland to moderate decreases in serum T4 attenuates the observed decrease in T4 and may mask effects on T4 metabolism in short-term structure-activity studies. Morphometric measurements may be helpful in characterizing early and/or transient responses to toxicants such as PCBs that have multiple endocrine disrupting effects.


[The effect of low-dose whole-body gamma-irradiation on the activity of enzyme systems in the rat adrenal medulla].
A study was made of the pattern of changes in histochemical indices of key enzymes of the tricarboxylic acid cycle (succinate dehydrogenase) and glycolysis (lactate dehydrogenase) as well as of catecholamines (monoamine oxidase) in cells of the adrenal medulla of young and adult albino rats subjected to external whole-body gamma-irradiation with doses of 0.5 and 1.0 Gy (dose-rate of 2.7 X 10(-4) Gy/s). Radiosensitivity of the enzyme systems under study in the adrenal gland cells of young animals was higher than in that of adults. Changes of their levels in different periods of observation were mainly of phase nature and indicated the development of adaptation syndrome in the animal organism.


Interpretation of cardiac pathophysiology from pressure waveform analysis: simultaneous left and right ventricular pressure measurements.
In addition to demonstrating constrictive and restrictive cardiac physiology, simultaneous right and left ventricular pressure measurements can be helpful to identify various aspects of myocardial dysfunction. Intracardiac conduction defects will displace the right ventricular pressure under the left ventricular pressure upstroke and identify differences in the timing of ventricular contraction. Right ventricular dysfunction will also produce abnormal right ventricular pressure waveforms which may overlap left ventricular pressure and contribute to abnormalities in right atrial and ventricular pressure waveforms.


Transposon insertions in the promoter of the Zea mays a1 gene differentially affect transcription by the Myb factors P and C1.
The understanding of control of gene regulation in higher eukaryotes relies heavily on results derived from non-in vivo studies, but rarely can the significance of these approximations be established in vivo. Here, we investigated the effect of Mutator and Spm insertions on the expression of the flavonoid biosynthetic gene a1, independently regulated by the transcription factors C1 and P. The a1-mum2 and a1-m2 alleles carry Mu1 and Spm insertions, respectively, in a cis-element (ARE) of unknown function located between the P- and C1-binding sites. We show that the insertions of Mu1 and Spm similarly influence the expression of a1 controlled by C1 or P. The P-controlled a1 expression in a1-m2 is Spm dependent, and the mutant phenotype of a1-mum2 is suppressed in the pericarp in the absence of the autonomous MuDR element. Footprints within the ARE affect the regulation of a1 by C1 and P differently, providing evidence that these factors control a1 expression using distinct cis-acting regulatory elements. Together, our findings contribute significantly to one of the best-described plant regulatory systems, while stressing the need to complement with in vivo experiments current approaches used for the study of control of gene expression.


A New Paradigm for KIM-PTP Drug Discovery: Identification of Allosteric Sites with Potential for Selective Inhibition Using Virtual Screening and LEI Analysis.
The kinase interaction motif protein tyrosine phosphatases (KIM-PTPs), HePTP, PTPSL and STEP, are involved in the negative regulation of mitogen-activated protein kinase (MAPK) signalling pathways and are important therapeutic targets for a number of diseases. We have used VSpipe, a virtual screening pipeline, to identify a ligand cluster distribution that is unique to this subfamily of PTPs. Several clusters map onto KIM-PTP specific sequence motifs in contrast to the cluster distribution obtained for PTP1B, a classic PTP that mapped to general PTP motifs. Importantly, the ligand clusters coincide with previously reported functional and substrate binding sites in KIM-PTPs. Assessment of the KIM-PTP specific clusters, using ligand efficiency index (LEI) plots generated by the VSpipe, ascertained that the binders in these clusters reside in a more drug-like chemical-biological space than those at the active site. LEI analysis showed differences between clusters across all KIM-PTPs, highlighting a distinct and specific profile for each phosphatase. The most druggable cluster sites are unexplored allosteric functional sites unique to each target. Exploiting these sites may facilitate the delivery of inhibitors with improved drug-like properties, with selectivity amongst the KIM-PTPs and over other classical PTPs.


Isosulfan blue causes factitious methemoglobinemia in an infant.
A 9 month-old girl was given subcutaneous isosulfan blue to outline lymphatic channels during surgery for thoracic duct ligation. Her pulse oximetry values rapidly declined to a nadir of 85%, 35 min after dye injection. Arterial blood gases revealed methemoglobinemia ([MetHb] = 6.5%). Although abnormal pulse oximetry has already been reported in association with isosulfan blue, methemoglobinemia has not previously been reported. The absorption spectrum for isosulfan blue was determined and when superimposed on that of methemoglobin it was found to have an overlying peak. Interference by the dye was postulated to have caused the abnormal methemoglobin result. The phenomenon was simulated in vitro by adding isosulfan blue to whole blood, and analysing it in the same blood gas analyser as was used for the case, as well as another for comparison. One blood gas analyser reported elevated methemoglobin concentration and the other did not. The samples were sent to a reference laboratory using a chemical method to detect methemoglobin to confirm that the elevated methemoglobin level was spurious.


Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure: a prospective, randomized, multicenter analysis of 170 patients with pancreatic and periampullary tumors.
A prospective randomized multicenter study was performed to assess whether the results of pylorus-preserving pancreaticoduodenectomy (PPPD) equal those of the standard Whipple (SW) operation, especially with respect to duration of surgery, blood loss, hospital stay, delayed gastric emptying (DGE), and survival. PPPD has been associated with a higher incidence of delayed gastric emptying, resulting in a prolonged period of postoperative nasogastric suctioning. Another criticism of the pylorus-preserving pancreaticoduodenectomy for patients with a malignancy is the radicalness of the resection. On the other hand, PPPD might be associated with a shorter operation time and less blood loss. A prospective randomized multicenter study was performed in a nonselected series of 170 consecutive patients. All patients with suspicion of pancreatic or periampullary tumor were included and randomized for a SW or a PPPD resection. Data concerning patients' demographics, intraoperative and histologic findings, as well as postoperative mortality, morbidity, and follow-up up to 115 months after discharge, were analyzed. There were no significant differences noted in age, sex distribution, tumor localization, and staging. There were no differences in median blood loss and duration of operation between the 2 techniques. DGE was observed equally in the 2 groups. There was only a marginal difference in postoperative weight loss in favor of the standard Whipple procedure. Overall operative mortality was 5.3%. Tumor positive resection margins were found for 12 patients of the SW group and 19 patients of the PPPD group (P < 0.23). Long-term follow-up showed no significant statistical differences in survival between the 2 groups (P < 0.90). The SW and PPPD operations were associated with comparable operation time, blood loss, hospital stay, mortality, morbidity, and incidence of DGE. The overall long-term and disease-free survival was comparable in both groups. Both surgical procedures are equally effective for the treatment of pancreatic and periampullary carcinoma.


Phase diagram of polydisperse Na-fluorohectorite-water suspensions: a synchrotron small-angle x-ray scattering study.
Systems of platelet-shaped nanostacks of the synthetic clay Na-fluorohectorite, suspended in saline solutions of various salt concentrations, exhibit a rich phase behavior with up to four phases coexisting in a single sample tube. They are studied here using small-angle x-ray scattering: the anisotropy of the obtained images is quantified, and, together with x-ray absorption measurements, this provides a precise determination of the phase boundaries, as well as a measure of the orientational ordering of the clay colloids in the various gel phases. The coexistence of different phases results from a sedimentation-induced vertical gradient in particle fraction. Quantitative relation of the vertical coordinate to the clay particle fraction in these samples allows determination of a phase diagram for these Na-fluorohectorite systems, as a function of the particle fraction and salt concentration.


EPR studies of nitric oxide interactions of alkoxyl and peroxyl radicals in in vitro and ex vivo model systems.
A model compound of lipid peroxidation, tert-butyl hydroperoxide (tBOOH), was used in vitro to investigate (i) the generation of tBOOH-derived free radicals by hematin or rat enterocytes and (ii) the modulation of cell-generated free radical production by a nitric oxide (NO) donor, or when these cells were primed to produce NO. In hematin-catalyzed decomposition of tBOOH, NO from nitrosoglutathione, or S-nitroso-N-acetylpenicillamine suppressed the generation of peroxyl radicals (measured by direct electron paramagnetic resonance) and tert-butylalkoxyl, methoxyl, and methyl radicals (measured by electron paramagnetic resonance spin trapping). Similarly, co-incubation of S-nitroso-N-acetylpenicillamine or nitrosoglutathione with tBOOH caused significant decreases in tBOOH-derived free radical generation catalyzed by enterocytes. Epithelial cells are the known source of the inducible form of NO synthase in the intestine of rats challenged with lipopolysaccharide (LPS). Enterocytes isolated from LPS-treated rats produced decreased levels of tBOOH-derived radicals. These decreases in free radical production were further decreased when these cells were treated with LPS in vitro. These findings demonstrated that exogenously added or endogenously produced NO could modulate the extent of tBOOH-derived free radical generation in enterocytes. These decreases in free radical production could, at least in part, describe the protective role of NO from hydroperoxide-induced injury.


HGF-induced DNA synthesis in hepatocytes is suppressed by p38.
Previous studies in rat hepatocytes have shown that the MEK/ERK, PI3K/Akt and p38 pathways are all involved in the activation of DNA synthesis by EGF and that sustained activation of MEK/ERK is required. Here, we show that although HGF stimulated DNA synthesis and activated signaling in the same manner as EGF, the contribution of the signaling pathways to the induction of DNA synthesis differed. While HGF-induced DNA synthesis was dependent on MEK/ERK, with no significant contribution from PI3K/Akt, p38 suppressed HGF-induced DNA synthesis. The p38 inhibitor SB203580 increased HGF-induced DNA synthesis and enhanced the phosphorylation of ERK. In contrast, SB203580 decreased EGF-induced ERK phosphorylation. This suggests that p38 has distinct effects on DNA synthesis induced by EGF and HGF. Due to differential regulation of signaling through the MEK/ERK pathway, p38 acts as an enhancer of EGF-induced DNA synthesis and as a suppressor of HGF-induced DNA synthesis.


Treatment of the localized pain of postherpetic neuralgia.
Postherpetic neuralgia (PHN) is a neuropathic pain condition that can arise as a complication following herpes zoster infection, with pain often localized to the affected dermatome. Patients are initially likely to seek treatment for PHN pain from their primary care practitioner; however, adequate pain relief is difficult to achieve in many patients. Combination therapies are often used and have shown promise, but there is still limited clinical evidence in the literature to support them. This article reviews the recent literature and guidelines on PHN treatment, with a focus on combination therapies, and seeks to help primary health care practitioners select treatment strategies that provide immediate relief for patients with localized PHN pain.


Vitamin D receptor gene polymorphisms, bone mineral density and bone turnover: FokI genotype is related to postmenopausal bone mass.
The relationship between vitamin D receptor (VDR) intragenic polymorphisms FokI, BsmI, ApaI and TaqI and bone mineral density (BMD) or biochemical markers of bone remodeling were investigated in 114 Czech postmenopausal women, on the average 62.5+/-8.9 years of age. Restriction fragment length polymorphisms in the VDR gene were assessed by PCR amplification and digestion with restriction enzymes FokI, BsmI, ApaI, and TaqI recognizing polymorphic sites in the VDR locus. Bone mineral density was measured at the lumbar spine and at the hip by dual-energy X-ray absorptiometry (DEXA, g/cm2). After adjusting for age and the body mass index (BMI), subjects with the ff genotype had 9.4% lower BMD at the hip than those with the Ff genotype (p=0.0459, Tukey's test). FF individuals had an intermediate BMD at the hip. A similar pattern of lower lumbar spine BMD was also found in ff individuals, but it did not reach statistical significance. There was no relationship between BsmI, ApaI and TaqI VDR polymorphisms and BMD at any skeletal site. Subjects with Aa (ApaI) genotypes had higher levels of propeptide of type I collagen (PICP) than homozygous AA (p=0.0459, Tukey's test). In FokI, BsmI and TaqI restriction sites the biochemical markers of bone remodeling did not differ by genotype. In addition, no significant difference was observed in VDR genotypic distribution between osteoporotic women and non-osteoporotic controls in the study group. To conclude, the FokI genotype of the vitamin D receptor gene is related to bone mass at the hip in Czech postmenopausal women, whereas the importance of remaining VDR genotypes was not evident.


Radionuclide Therapy of Unresectable Tumors with AvidinOX and (90)Y-biotinDOTA: Tongue Cancer Paradigm.
Local treatment of unresectable tumors is challenging, particularly with radioactivity. Current practice relies on external beam irradiation or on a variety of medical devices for brachytherapy. Both approaches proved useful in controlling tumor growth, but are characterized by poor compliance of the patient, significant side-effects, high costs, and technological complexity, which hamper widespread use. The authors recently described a novel form of radionuclide therapy based on the oxidized form of avidin that, chemically reacting with tissue proteins, can secure radioactive biotin within the injected tissue, either when precomplexed or when taken from the blood stream after intravenous administration. AvidinOX-pretargeted (177)Lu-biotinDOTA ((177)Lu-ST2210) is currently under clinical investigation for the treatment of liver oligometastases from colorectal cancer (clinicaltrials.gov/NCT02053324). In the present work, the authors show that injected AvidinOX can link tissues of various natures such as prostate, kidney, breast, or brain and can react by contact with scraped tissues such as skin or urinary bladder. AvidinOX injected into human OSC19 tongue cancer masses orthotopically transplanted in nude mice takes up intravenously administered (90)Y-ST2210, which exerts significant antitumor activity, while preserving the integrity and functionality of the tongue. Present data confirm that AvidinOX-based radionuclide therapy is an innovative and promising approach for the local treatment of inoperable tumors.


Infection of murine macrophage cell lines by Legionella pneumophila.
Legionella pneumophila causes pneumonia by infecting alveolar macrophages. Although several model systems have been used for L. pneumophila virulence studies, no detailed comparisons have been made between them. An ideal in vitro virulence model should be cost-effective, easy to obtain in large amounts and as relevant as possible to the actual disease. We compared the MH-S cell line to human peripheral blood monocyte-derived macrophages and the J774A.1 cell line. We found that the interactions of L. pneumophila with MH-S at the cellular level resemble those of human primary monocyte-derived macrophages, suggesting that these cells provide a valuable model for this bacterial pathogen.


Screening Tools: They're So Quick! What's the Issue?
Screening tools are needed in occupational therapy practice to determine which clients require formal evaluation. Because screening tools also tell us who does not require formal evaluation, they are key to improved clinical efficiency. Screening tools are brief, easy to administer, and often freely available. These qualities also lead to misuse of screening tools, including using them to measure progress over time or to serve as a confirmatory assessment on which to base treatment planning. We present additional common missteps of screening tool use, including a lack of consideration for a tool's psychometric properties, and exemplars of these common misuses in adult and pediatric practice. Finally, we offer solutions to address these concerns.


Effects of MRP8, LPS, and lenalidomide on the expressions of TNF-α , brain-enriched, and inflammation-related microRNAs in the primary astrocyte culture.
Astrocytes are now recognized as a heterogeneous class of cells with many important and diverse functions in healthy and diseased central nervous system (CNS). MicroRNAs (miRNAs) are small, noncoding RNAs which may have key roles in astrocytes activation in response to various stimuli. We performed quantitative real-time PCR (qPCR) to detect changes in the expressions of brain-enriched miRNAs (124, 134, 9, 132, and 138), inflammation-related miRNAs (146a, 21, 181a, 221, and 222), and tumor necrosis factor alpha (TNF- α ) in the rat primary astrocyte cultures after stimulation with myeloid-related protein 8 (MRP8) and lipopolysaccharides (LPS). Further, we inhibited the expression of TNF- α in the astrocytes by using TNF- α inhibitor (lenalidomide) and tested for the first time the effect of this inhibition on the expressions of the same tested miRNAs. Stimulation of the astrocytes with MRP8 or LPS leads to significant upregulation of miRNAs (124, 134, 9, 132, 146a, 21, 181a, 221, and 222), while miRNA-138 was downregulated. TNF- α inhibition with lenalidomide leads to opposite expressions of the tested miRNAs. These miRNAs may play an important role in activation of the astrocytes and may be a novel target for cell-specific therapeutic interventions in multiple CNS diseases.


A past Haff disease outbreak associated with eating freshwater pomfret in South China.
Haff disease is unexplained rhabdomyolysis caused by consumption of fishery products in the previous 24 h. It was first identified in Europe in 1924 but the condition is extremely rare in China. Here we describe a past outbreak of acute food borne muscle poisoning that occurred in Guangdong Province (South China) in 2009. The first full outbreak of Haff disease reported in Jiangsu Province (East China) in 2010, indicated that the incidence of the disease may be increasing in China. We, therefore first retrospectively reviewed epidemiologic, trace-back, environmental studies, and laboratory analyses, including oral toxicity testing to ascertain risk and chemical analysis to identify toxin(s), from the 2009 Guangdong outbreak. Then we compared data from the 2009 outbreak with data from all other Haff disease outbreaks that were available. Clinical symptoms and laboratory findings indicated that the 2009 Guangdong outbreak disease was consistent with rhabdomyolysis. Epidemiologic, trace-back, environmental studies and laboratory analyses implied that the disease was caused by freshwater Pomfrets consumed prior to the onset of symptoms. We also identified common factors between the 2009 Guangdong outbreak and previous Haff disease outbreaks reported around the world, while as with other similar outbreaks, the exact etiological factor(s) of the disease remains unknown. The 2009 Guangdong outbreak of 'muscle poisoning' was retrospectively identified as an outbreak of Haff disease. This comprised the highest number of cases reported in China thus far. Food borne diseases emerging in this unusual form and the irregular pattern of outbreaks present an ongoing public health risk, highlighting the need for improved surveillance and diagnostic methodology.


Adipocyte apoptosis after burn injury is associated with altered fat metabolism.
Burn injury often is associated with the abnormal lipid metabolism, including hyperlipidemia, desensitization to lipolytic responses to catecholamines, and reduction in the size of the white adipose tissue. Understanding the biological mechanisms for the decrease in fat mass despite desensitization to catecholamines is important both for the study of lipid metabolism and for the study of its relationship to concomitant insulin resistance. Using epididymal adipose tissue from adult male Sprague-Dawley rats after burn injury (n = 102) or sham-burn injury (n = 102), we tested the hypothesis that a whole-body burn injury causes apoptosis in that tissue. At 1, 3, and 7 days after 40% to 50% body burn injury to the rat, epidydimal adipose tissue was harvested and studied for apoptotic changes and lipolytic properties. For apoptosis, paraformaldehyde-fixed tissue sections were analyzed by in situ TdT-mediated dUTP-X nick-end labeling (TUNEL) staining, and tissue homogenates were also analyzed for DNA fragmentation by enzyme-linked immunoassay and ligation-mediated polymerase chain reaction ladder assay. Isolated adipocytes were stimulated with isoprotenerol, and glycerol production was measured as a reflector of effectiveness of lipolysis. Epididymal adipose tissue showed increased apoptosis manifested by the positive TUNEL staining and increased DNA fragmentation by enzyme-linked immunoassay at day 3 and 7 after burn injury. The DNA fragmentation was confirmed further by the ligation-mediated polymerase chain reaction ladder assay. This elevated DNA fragmentation persisted in the burned animals from day 3 until day 7 after burn injury, the end of observation period. Increase in apoptosis was correlated with decrease in DNA content and tissue weight in the epidydimis. At the functional level, a significant decrease in isoproterenol-induced lipolytic activity (glycerol production) was observed to almost 50% of control level at day 3 and 7 but was not decreased at day 1. Apoptosis of adipocytes may play a role in the altered lipid metabolism, including hyperlipidemia observed in burned subjects.


The enemy who sealed the world: effects quarantine due to the COVID-19 on sleep quality, anxiety, and psychological distress in the Italian population.
The 2019 Coronavirus Disease (COVID-19) pandemic has become a global health emergency. The extreme actions aimed to reduce virus diffusion have profoundly changed the lifestyles of the Italian population. Moreover, fear of contracting the infection has generated high levels of anxiety. This study aimed to understand the psychological impact of the COVID-19 outbreak on sleep quality, general anxiety symptomatology, and psychological distress. An online survey collected information on socio-demographic data and additional information concerning the COVID-19 pandemic. Furthermore, sleep quality, sleep disorders, generalized anxiety symptoms, psychological distress, and post-traumatic stress disorder (PTSD) symptomatology related to COVID-19 were assessed. This study included 2291 respondents. The results revealed that 57.1% of participants reported poor sleep quality, 32.1% high anxiety, 41.8% high distress, and 7.6% reported PTSD symptomatology linked to COVID-19. Youth and women, those uncertain regarding possible COVID-19 infection, and greater fear of direct contact with those infected by COVID-19 had an increased risk of developing sleep disturbances, as well as higher levels of anxiety and distress. Finally, a significant relationship between sleep quality, generalized anxiety, and psychological distress with PTSD symptoms related to COVID-19 was evidenced. Our findings indicate that the COVID-19 pandemic appears to be a risk factor for sleep disorders and psychological diseases in the Italian population, as previously reported in China. These results should be used as a starting point for further studies aimed to develop psychological interventions to minimize the brief and long-term consequences of the COVID-19 pandemic.


Be Active or Not: the Relative Contribution of Active and Passive Tumor Targeting of Nanomaterials.
Malignant tumor (cancer) remains as one of the deadliest diseases throughout the world, despite its overall mortality drops. Nanomaterials (NMs) have been widely studied as diagnostic and/or therapeutic agents for tumors. A feature of NMs, compared to small molecules, is that NMs can be concentrated passively in tumors through enhanced permeability and retention (EPR) effect. In the meantime, NMs can be engineered to target toward tumor specific markers in an active manner, e.g., receptor-mediated targeting. The relative contribution of the EPR effect and the receptor-mediated targeting to NM accumulation in tumor tissues has not been clearly defined yet. Here, we tackle this fundamental issue by reviewing previous studies. First, we summarize the current knowledge on these two tumor targeting strategies of NMs, and on how NMs arrive to tumors from blood circulation. We then demonstrate that contribution of the active and passive effects to total accumulation of NMs in tumors varies with time. Over time, the receptor-mediated targeting contributes more than the EPR effect with a ratio of 3 in the case of urokinase-type plasminogen activator receptor (uPAR)-mediated targeting and human serum albumin (HSA)-mediated EPR effect. Therefore, this review highlights the dynamics of active and passive targeting of NMs on their accumulation at tumor sites, and is valuable for future design of NMs in cancer diagnosis and treatment.


Platelet adenylate cyclase and monoamine oxidase in women with alcoholism or a family history of alcoholism.
Characteristic changes of platelet membrane monoamine oxidase and adenylate cyclase activities have been described in men with alcoholism. We studied the occurrence of these changes in abstinent alcoholic women and in nonalcoholic female control subjects with and without family histories of alcoholism. Blood samples were collected from 23 female alcoholics and 39 nonalcoholic female social drinkers. Platelet membrane assays were performed for monoamine oxidase and adenylate cyclase activities. Alcoholic women had lower basal adenylate cyclase (p < 0.01) and adenylate cyclase activities stimulated by cesium fluoride (p < 0.001), by the guanine nucleotide analog 5'-guanylylimidodiphosphate (p < 0.02), and by prostaglandin E1 (p < 0.01). Female control subjects with family histories of alcoholism also had lower basal adenylate cyclase (p < 0.01) and adenylate cyclase activities enhanced by incubation with cesium fluoride (p < 0.005) and 5'-guanylylimidodiphosphate (p < 0.001). Monoamine oxidase activity levels measured with (p < 0.001) and without ethanol (p < 0.01) were higher for alcoholic women. No significant differences were found between female control subjects with and without family histories of alcoholism for monoamine oxidase in the absence or presence of ethanol. In vitro platelet adenylate cyclase activity may facilitate a diagnosis of alcoholism in women and may be a biologic indicator of vulnerability in the offspring of alcoholics.


Vicair Academy Mattress in the prevention of pressure damage.
There are many costs associated with the development of pressure ulcers, both in terms of the patient experience and those associated with healing. If patients who are deemed to be at risk are identified and suitable preventive equipment is provided, incidence of pressure ulcer development can be reduced significantly. Pressure-reducing mattresses are primarily used to prevent pressure ulcers from occurring, in conjunction with other preventive measures, such as repositioning. The Vicair Academy Mattress, manufactured by Vicair BV and distributed by Gerald Simonds, uses Vicair's 'dry air' flotation system to offer maximum pressure and shear protection to patients who are at high risk of developing pressure ulcers.


Use of serum lipid and apolipoprotein concentrations to predict extent of diet-induced atherosclerotic lesions in aortas and coronary arteries and to demonstrate regression of lesions in individual rhesus monkeys.
In most studies, the assessment of lesion "regression" is based on comparisons of group means between the "progression" and regression groups. This comparison depends on the assumption that the extent and distribution of lesions produced by the end of the lesion-induction period in the regression animals are equal to those observed in the progression group. To determine whether significant regression of lesions occurs in an individual regression animal, it is necessary to obtain a measure of the lesions produced in these animals at the end of the lesion-induction period. We achieved this goal by developing models using multiple stepwise regression analysis that related steady-state serum cholesterol and apolipoprotein B and A-I concentrations measured during a lesion-induction period in 27 rhesus monkeys fed an atherogenic high-saturated-fat/high-cholesterol diet for 2 years. The models were developed to estimate the percent of intimal surface with lesions, the esterified cholesterol content (micrograms/cm2) for the artery segments, and three histomorphometric measures (mean intimal thickness, mean maximal intimal thickness, and mean percent stenosis) for the coronary arteries. In these models, multiple R2 ranged from 0.42 to 0.74 for the aortas and peripheral arteries, indicating that approximately one half to three fourths of the variance in lesions was accounted for. For the three histomorphometric measures in coronary arteries, however, the multiple R2 was 0.27 or 0.28, indicating that only approximately one fourth of the variance in lesions was accounted for.(ABSTRACT TRUNCATED AT 250 WORDS)


Endoscopic Transnasal Skull Base Surgery in Pediatric Patients.
Introduction In pediatric patients, endoscopic transnasal surgery (ETNS) poses challenges because of the small size of the developing skull and narrow endonasal corridors. Objective This study aimed to evaluate the efficacy of ETNS in children by assessing our experience of endoscopic skull base surgery. Materials and Methods All pediatric patients ( n = 54) who were eligible for surgery using only the endonasal endoscopic approach at our tertiary center between 2012 and 2018 were included in this study. The surgeries were performed simultaneously by an endoscopic skull base team of neurosurgeons and otolaryngologists. Hormonal analyses were conducted before and after surgery in all patients with sellar/parasellar lesions. Patients older than 8 years underwent smell and visual testing. Results In the 54 patients aged 1 to 17 years who underwent surgery, craniopharyngioma was the most common pathology (29.6%), followed by pituitary adenoma (22.2%). Gross total resection was achieved in 33 (76.7%) of 41 patients who underwent surgery because of the presence of tumors. All visual deficits improved, although one patient sustained olfactory deterioration. Sixteen (29.6%) patients presented with complications such as transient diabetes insipidus and temporary visual loss. Conclusions Despite anatomy-related challenges in children, adequate results can be achieved with high rates of success, and the functional and anatomical integrity of the developing skull and nose of children can be preserved. In pediatric patients, ETNS is a safe and effective option for addressing various lesions along the skull base.


[Therapeutic approach of cleft lip and palate at Caen University Hospital].
The therapeutic approach of facial cleft in Caen University Hospital depend on two teams: primary treatment by the Pediatric Plastic Unit (60 cases/year), and secondary treatment by the department of Plastic and Maxillofacial Surgery (more than 30 cases/year). The lip closure is realised before the age of one month with the Tennisson's technic. The palate closure is performed between 6 and 12 months old. Each patient is presented at a multidisciplinary consultation which include a surgeon, an orthodontist, an orthophonist, a psychologist and otologist. At about 5 years old, the orthodontic approach begins with palatal expansion with a modified quadhelix to prepare function its treatment is underwent at this age too. After the age of 9-10 years the orthodontic treatment continued on the permanent teeth. If necessary, the sequelae on maxilla, lips and nose are treated at the end of the adolescence.


Serum complement activation on heterologous platelets is associated with arterial thrombosis in patients with systemic lupus erythematosus and antiphospholipid antibodies.
Complement plays a major role in inflammation and thrombosis associated with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). A cross-sectional retrospective analysis was performed to evaluate serum complement fixation on platelets and thrombotic incidence using banked sera and clinical data from patients with SLE (n = 91), SLE with antiphospholipid antibodies (aPL) or APS (n = 78) and primary aPL (n = 57) or APS (n = 96). In-situ complement fixation was measured as C1q and C4d deposition on heterologous platelets using an enzyme-linked immunosorbent assay approach. Platelet activation by patient serum in the fluid phase was assessed via serotonin release assay. Enhanced in-situ complement fixation was associated with the presence of IgG aPL and IgG anti-beta2 glycoprotein 1 antibodies (P < 0.05) and increased platelet activation (P < 0.005). Moreover, enhanced complement fixation, especially C4d deposition on heterologous platelets, was positively associated with arterial thrombotic events in patients with SLE and aPL (P = 0.039). Sera from patients with aPL possess an enhanced capacity for in-situ complement fixation on platelets. This capacity may influence arterial thrombosis risk in patients with SLE.


Plasma retinol and alpha-tocopherol concentrations in insulin-dependent diabetes mellitus: their relationship to microvascular complications.
Plasma alpha-tocopherol and retinol, both assayed by an HPLC method, have been evaluated in a group of 60 patients affected by insulin-dependent (type 1) diabetes mellitus, stratified according to the presence of retinopathy and nephropathy diagnosed by an urinary albumin excretion rate ranging between 20 and 200 micrograms/min (microalbuminaria) or > 200 micrograms/min (macroalbuminuria), all of whom were compared with 26 healthy controls strictly matched for age and sex. Plasma lipids and age were positively correlated with plasma retinol and alpha-tocopherol in both diabetic and control subjects. Either plasma retinol or its ratio to cholesterol were significantly and independently reduced in the younger subset of diabetics, as compared to controls, independently from other confounding variables, while plasma alpha-tocopherol was unchanged in diabetic subjects and in healthy controls. Retinopathy was not associated with altered levels of both plasma alpha-tocopherol or retinol. The presence of increased urinary albumin excretion was associated with higher plasma levels of alpha-tocopherol and, only for macroalbuminuria, of retinol. However, after processing the data by a multivariate model, nephropathy was characterized by an increase only in plasma alpha-tocopherol. In conclusion, according to our findings, plasma retinol is significantly decreased in younger insulin-dependent diabetic patients while alpha-tocopherol is significantly altered in diabetic patients with nephropathy.


[Congenital perineal lipoma with accessory scrotum: a case report].
A tumor mass covered with scrotum-like skin on its tip was found on the perineal region of 3-year-old boy since his birth. The mass was diagnosed as congenital lipoma, which was resected, because of its gradual enlargement. Histopathological findings of the tumor indicated perineal lipoma, and the scrotum-like portion was diagnosed as an accessory scrotum. In the Japanese literature, 7 congenital perineal lipomas (6 males, 1 female) have been reported and all male cases except 1 case (no description about scrotum) were accompanied with an accessory scrotum. We conclude that there may be a close relationship between congenital perineal lipoma and accessory scrotum.


Use of plasma for immediate diagnosis of multiple sclerosis (plasma-erythrocyte unsaturated fatty acid test): comparison with the erythrocyte-unsaturated fatty acid (E-UFA) test.
A labile factor in plasma (but not serum) of MS subjects confers MS like properties vis à vis effect of linoleic acid (LA) and arachidonic acid (AA), on the electrophoretic mobility of washed red blood cells (RBC) irrespective of their provenance. Plasma from anomalous MS relatives and other neurological diseases (OND) likewise confer corresponding properties on washed RBC. The magnitude of results produced by LA and AA on plasma coated cells is equal to that produced by LA and AA directly on the original cells and approximately twice that reported with latex particles.


Bibliometric Reports for Institutions: Best Practices in a Responsible Metrics Scenario.
Carrying out bibliometric reports is one of the common tasks performed by librarians and practitioners within the framework of their professional duties. The emergence of novel data sources, the need to measure new research activities and the growing demand for fairer and more equitable evaluation within the framework of the Responsible Metrics movement has led to calls for a review of the traditional approaches to these types of reports. The main goal of this study is to outline a series of recommendations for bibliometricians, consultants and research support librarians when drafting bibliometric reports in their institutions. These best practices can significantly enhance the quality and utility of bibliometric reports, posing their practitioners as key players in the science management process.


Assessment for addiction in pain-treatment settings.
The identification of the disease of addiction is important to safe and effective clinical management of pain in persons with addictive disorders. The disease of addiction affects approximately 10% of the general population, and its prevalence may be higher in subpopulations of patients with pain. The presence of active addiction may facilitate the experience of pain. Both active and recovering addiction may complicate the use of medications, such as opioids, important to the management of pain. There is, further, persistent misunderstanding among health care providers, regulators, and the general population regarding the nature and manifestations of addiction that may result in undertreatment of pain and stigmatization of patients using opioids for pain control. The author seeks to clarify understanding of addiction, to underscore the importance of identifying addiction in the context of pain treatment, and to provide a rational approach to assessment for addiction in patients with pain. Current scientific understanding of addiction as a chronic illness is briefly reviewed. Recent definitions related to addiction are presented. The impact of addictive disorders on pain and pain treatment are explored. The roles of medical interview, physical examination, laboratory studies, and standard addiction screening tools in assessing for addiction are outlined. Differential considerations in distinguishing therapeutic use of opioids for analgesia from addictive or other nontherapeutic use of opioids are discussed. In summary, the article provides salient background and a detailed approach to assessment for addictive disorders in the context of pain treatment.


Assessing the burden of congenital rubella syndrome in China and evaluating mitigation strategies: a metapopulation modelling study.
A rubella vaccine was licensed in China in 1993 and added to the Expanded Programme on Immunization in 2008, but a national cross-sectional serological survey during 2014 indicates that many adolescents remain susceptible. Maternal infections during the first trimester often cause miscarriages, stillbirths, and, among livebirths, congenital rubella syndrome. We aimed to evaluate possible supplemental immunisation activities (SIAs) to accelerate elimination of rubella and congenital rubella syndrome. We analysed residual samples from the national serological survey done in 2014, data from monthly rubella surveillance reports from 2005 and 2016, and additional publications through a systematic review. Using an age-structured population model with provincial strata, we calculated the reproduction numbers and evaluated the gradient of the metapopulation effective reproduction number with respect to potential supplemental immunisation rates. We corroborated these analytical results and estimated times-to-elimination by simulating SIAs among adolescents (ages 10-19 years) and young adults (ages 20-29 years) using a model with regional strata. We estimated the incidence of rubella and burden of congenital rubella syndrome by simulating transmission in a relatively small population lacking only spatial structure. By 2014, childhood immunisation had reduced rubella's reproduction number from 7·6 to 1·2 and SIAs among adolescents were the optimal elimination strategy. We found that less than 10% of rubella infections were reported; that although some women with symptomatic first-trimester infections might have elected to terminate their pregnancies, 700 children could have been born with congenital rubella syndrome during 2014; and that timely SIAs would avert outbreaks that, as susceptible adolescents reached reproductive age, could greatly increase the burden of this syndrome. Our findings suggest that SIAs among adolescents would most effectively reduce congenital rubella syndrome as well as eliminate rubella, owing both to fewer infections in the immunised population and absence of infections that those immunised would otherwise have caused. Metapopulation models with realistic mixing are uniquely capable of assessing such indirect effects. WHO and National Science Foundation.


Factors affecting shoulder pain in adolescents and young adults with spina bifida.
This study was designed to determine whether factors affecting shoulder pain in adults with spinal cord injury also affected adolescent and young adult manual wheelchair users with spina bifida. Forty-one participants with spina bifida rated their pain using the Wheelchair User's Shoulder Pain Index. Results showed no significant relationship between shoulder pain and age or duration of wheelchair use but significant differences in pain between age groups. Participation in a sports program and level of lesion were not factors in pain intensity. Propelling up an incline was the activity for which the highest intensity of pain was reported. Shoulder pain in adolescents and young adults with spina bifida is not as great as previously reported in adults with spinal cord injuries but older subjects had greater pain than younger subjects.


Antenatal corticosteroid prescribing: setting standards of care.
Despite widespread recognition that prenatal administration of corticosteroids dramatically reduces perinatal mortality and morbidity, clinical practice in this area remains less than ideal. We therefore reviewed our practice to identify reasons for this and to determine attainable standards of care. Retrospective case record review. Level three maternity unit in Edinburgh, UK. All women admitted at gestations of 24 to 34 weeks and 6 days inclusive, and all women receiving corticosteroids in one institution, over a 10-month period. The number and clinical features of women delivering before and after 35 weeks of pregnancy who had received corticosteroids. Seven hundred and two women were admitted during the study period; case records were available for 688 of these. One hundred and ninety-two women (28%) delivered before 35 weeks of gestation, of whom 123 (64%) had received dexamethasone. Of 69 women who received no steroids 30 (43%) were in hospital for more than 24 hours before delivery. Overall, 29% of women receiving dexamethasone delivered after 35 weeks of gestation and 42 (24%) women treated with dexamethasone received more than one course. While the grade of admitting doctor did not affect prescribing, there were other significant differences that may help guide future practice. This study provides some guidance for optimising corticosteroid prescribing and for the development of clinical practice guidelines. Approximately 80% of women should be able to receive at least some corticosteroids prior to delivery before 35 completed weeks of pregnancy.


Folate and DNA methylation during in utero development and aging.
DNA methylation is one of several epigenetic mechanisms that play a regulatory role in genome programming and imprinting during embryogenesis. Aberrant DNA methylation has been implicated in the pathogenesis of a number of diseases associated with aging, including cancer and cardiovascular and neurological diseases. Evidence is accumulating that dietary factors in utero modulate disease risk in later life. Although folic acid is a key component of DNA methylation, the impact of folic acid availability in utero on DNA methylation patterns and disease risk in adulthood is at present poorly characterized. This review describes the relationship between folic acid and DNA methylation, and the association between DNA methylation during in utero development and aging.


The Intervention of Data Mining in the Allocation Efficiency of Multiple Intelligent Devices in Intelligent Pharmacy.
With the wide application of artificial intelligence and big data technology in the medical field, the problems of high cost and low efficiency of traditional pharmacy management were becoming more and more obvious. Therefore, this paper proposed to use data mining technology to design and develop the dispensing process and equipment of intelligent pharmacy. Firstly, it summarized the existing data mining technology and association rule methods and expounded its application value in the related fields. Secondly, the data standard and integration platform of dispensing in intelligent pharmacy were established. Web service technology was used to design the interactive interface and call it to the intelligent device of pharmacy. Finally, an intelligent pharmacy management system based on association rule mining was constructed through the data mining of intelligent pharmacy equipment, in order to improve the intelligence and informatization of modern pharmacy management. For the emergency dispensing process of intelligent equipment failure, data mining was used to optimize the intelligent pharmacy equipment and dispensing process and change the pharmacy management from traditional prescription to patient drug treatment, so as to improve the dispensing efficiency of intelligent pharmacy equipment. Through the systematic test and analysis, the results showed that through the real-time risk prevention and control, the formula accuracy and operation speed of the intelligent dispensing machine were improved and the dispensing time was shortened. Through intelligent drug delivery, the unreasonable drug use of patients was reduced, the safety and effectiveness of clinical drug use were ensured, and the contradiction between doctors and patients was reduced. This study can not only optimize the medical experience of patients and provide patients with more high-quality and humanized pharmaceutical technical services but also provide some support for the intelligent management of modern hospitals.


Effect of tobacco on periodontal disease and oral cancer.
Periodontal disease and oral cancer are common health hazards. Epidemiological investigations show that smoking, periodontal disease and oral cancer are closely related. Tobacco is one of the major risk factors for periodontitis and oral cancer. A systematic literature review was performed. To identify relevant studies, the following online databases were searched using specific keywords: PubMed, Web of Science and CNKI. Tobacco not only possesses an addictive effect, but it aggravates periodontal disease by promoting the invasion of pathogenic bacteria, inhibiting autoimmune defense, aggravating the inflammatory reaction, and aggravating the loss of alveolar bone. According to current evidence, tobacco significantly aggravates the development and progression of periodontal disease and oral cancer, and periodontal disease may be related to the prevalence of oral cancer. Clinicians should strongly recommend that smokers undertake a strategy to stop smoking to avoid the exacerbation of nicotine-related periodontal disease and to reduce the incidence of oral cancer.


Workplace health promotion for older workers: a systematic literature review.
Aging of the workforce is a growing problem. As workers age, their physical, physiological and psychosocial capabilities change. Keeping older workers healthy and productive is a key goal of European labor policy and health promotion is a key to achieve this result. Previous studies about workplace health promotion (WHP) programs are usually focused on the entire workforce or to a specific topic. Within the framework of the EU-CHAFEA ProHealth65+ project, this paper aims to systematically review the literature on WHP interventions specifically targeted to older workers (OWs). This systematic review was conducted by making a comprehensive search of MEDLINE, ISI Web of Science, SCOPUS, The Cochrane Library, CINAHL and PsychINFO databases. Search terms included ageing (and synonyms), worker (and synonyms), intervention (and synonyms), and health (and synonyms). The search was limited to papers in English or Italian published between January, 1(st) 2000 and May, 31(st) 2015. Relevant references in the selected articles were also analyzed. Of the 299 articles initially identified as relating to the topic, 18 articles met the inclusion criteria. The type, methods and outcome of interventions in the WHP programs retrieved were heterogenous, as was the definition of the age at which a worker is considered to be 'older'. Most of the available studies had been conducted on small samples for a limited period of time. Our review shows that, although this issue is of great importance, studies addressing WHP actions for OWs are few and generally of poor quality. Current evidence fails to show that WHP programs improve the work ability, productivity or job retention of older workers. In addition, there is limited evidence that WHP programs are effective in improving lifestyles and concur to maintain the health and well-being of older workers. There is a need for future WHP programs to be well-designed so that the effectiveness and cost-benefit of workplace interventions can be properly investigated.


Efficacy of Quantitative Susceptibility Mapping with Brain Surface Correction and Vein Removal for Detecting Increase Magnetic Susceptibility in Patients with Alzheimer's Disease.
Studies on quantitative susceptibility mapping (QSM) have reported an increase in magnetic susceptibilities in patients with Alzheimer's disease (AD). Despite the pathological importance of the brain surface areas, they are sometimes excluded in QSM analysis. This study aimed to reveal the efficacy of QSM analysis with brain surface correction (BSC) and/or vein removal (VR) procedures. Thirty-seven AD patients and 37 age- and sex-matched, cognitively normal (CN) subjects were included. A 3D-gradient echo sequence at 3T MRI was used to obtain QSM. QSM images were created with regularization enabled sophisticated harmonic artifact reduction for phase data (RESHARP) and constrained RESHARP with BSC and/or VR. We conducted ROI analysis between AD patients and CN subjects who did or did not undergo BSC and/or VR using a t-test, to compare the susceptibility values after gray matter weighting. The susceptibility values in RESHARP without BSC were significantly larger in AD patients than in CN subjects in one region (precentral gyrus, 8.1 ± 2.9 vs. 6.5 ± 2.1 ppb) without VR and one region with VR (precentral gyrus, 7.5 ± 2.8 vs. 5.9 ± 2.0 ppb). Three regions in RESHARP with BSC had significantly larger susceptibilities without VR (precentral gyrus, 7.1 ± 2.0 vs. 5.9 ± 2.0 ppb; superior medial frontal gyrus, 5.7 ± 2.6 vs. 4.2 ± 3.1 ppb; putamen, 47,8 ± 16.5 vs. 40.0 ± 15.9 ppb). In contrast, six regions showed significantly larger susceptibilities with VR in AD patients than in CN subjects (precentral gyrus, 6.4 ± 1.9 vs. 4.9 ± 2.7 ppb; superior medial frontal gyrus, 5.3 ± 2.7 vs. 3.7 ± 3.3 ppb; orbitofrontal cortex, -2.1 ± 2.7 vs. -3.6 ± 3.2 ppb; parahippocampal gyrus, 0.1 ± 3.6 vs. -1.7 ± 3.7 ppb; putamen, 45.0 ± 14.9 vs. 37.6 ± 14.6 ppb; inferior temporal gyrus, -3.4 ± 1.5 vs. -4.4 ± 1.5 ppb). RESHARP with BSC and VR showed more regions of increased susceptibility in AD patients than in CN subjects. This study highlights the efficacy of this method in facilitating the diagnosis of AD.


Surface Functionalization of Ti3C2Tx MXene with Highly Reliable Superhydrophobic Protection for Volatile Organic Compounds Sensing.
Two-dimensional (2D) transition-metal carbides (Ti3C2Tx MXene) have received a great deal of attention for potential use in gas sensing showing the highest sensitivity among 2D materials and good gas selectivity. However, one of the long-standing challenges of the MXenes is their poor stability against hydration and oxidation in a humid environment, limiting their long-term storage and applications. Integration of an effective protection layer with MXenes shows promise for overcoming this major drawback. Herein, we demonstrate a surface functionalization strategy for Ti3C2Tx with fluoroalkylsilane (FOTS) molecules through surface treatment, providing not only a superhydrophobic surface, mechanical/environmental stability but also enhanced sensing performance. The experimental results show that high sensitivity, good repeatability, long-term stability, and selectivity and faster response/recovery property were achieved by the FOTS-functionalized when Ti3C2Tx was integrated into chemoresistive sensors sensitive to oxygen-containing volatile organic compounds (ethanol, acetone). FOTS functionalization provided protection to sensing response when the dynamic response of the Ti3C2Tx-F sensor to 30 ppm of ethanol was measured over in the 5 to 80% relative humidity range. Density functional theory simulations suggested that the strong adsorption energy of ethanol on Ti3C2Tx-F and the local structure deformation induced by ethanol adsorption, contributing to the gas-sensing enhancement. This study offers a facile and practical solution for developing highly reliable MXene based gas-sensing devices with response that is stable in air and in the presence of water.


Are viruses associated with human breast cancer? Scrutinizing the molecular evidence.
The three viruses most studied as possible causes of human breast cancer are mouse mammary tumor virus-like sequences (MMTV-LS), Epstein-Barr virus (EBV), and oncogenic (high risk) types of human papilloma virus (HPV). The first step in fulfilling traditional criteria for inferring that a cancer is caused by a virus is to demonstrate the virus in the affected tissue. Molecular techniques, compared to host antibody assessment and immunohistochemistry, are the most definitive in establishing viral presence. Results of 85 original molecular research investigations to detect one or more of the three viruses have been extremely divergent with no consensus reached. We evaluated the methodology of these studies for the following: type of molecular assay, DNA/RNA quality control, positive and negative assay controls, type of fixation, genome targets, methods for preventing and detecting molecular contamination, pathology of specimens processed, sample size, and proportion of specimens positive for the viral genome region targeted. Only seven of the studies convincingly demonstrated the presence of an oncogenic virus biomarker (EBV: 4/30 studies (13%); HPV 3/29 studies (10%), whereas 25 convincingly demonstrated absence of the virus studied (MMTV-LS: 4/25 (16%); EBV: 15/30 (50%); 6/29 (21%). The remainder of the studies suffered shortcomings, which, in our opinion, prevented a definitive conclusion. Only one of the studies compared frequency of the virus in breast tissue of breast cancer patients versus appropriate normal control subjects with no history of breast cancer. None of the studies were designed as epidemiologic studies to determine if the presence of the virus was significantly associated with breast cancer. Based on our evaluation, the data in the publications reviewed here remain preliminary, and do not justify a conclusion that MMTV-LS, HPV, or EBV are causally associated with breast cancer. However, they form a valuable basis for redirecting future studies.


Predictors of relapse into major depressive disorder in a nonclinical population.
This study sought to describe, the natural history of major depressive disorder in a large group of nonclinical subjects. In particular, the analysis determined demographic and clinical risk factors for the recurrence of major depressive disorder. Relatives, comparison subjects (matched to relatives for age and sex), and spouses of affectively ill probands underwent structured clinical assessments before and after a 6-year interval. Of 396 individuals who had had only major depressive disorder that ended before the initial evaluation, 33.8% (N = 134) developed a new episode during the 6-year follow-up period. Youth, but not sex, was an important demographic risk factor. The presence of minor depression at the time of initial evaluation and the number of symptoms recalled from the worst previous episode were additional clinical risk factors. At the initial evaluation, 200 other subjects had described a previous history of both major depressive disorder and a nonaffective mental disorder. When compared to the subjects who recalled only a history of major depressive disorder, these subjects were more likely to have been in an episode of chronic intermittent depression at the initial evaluation and to recall a greater number of episodes as well as a greater number of symptoms in the worst episode. A history of a nonaffective mental disorder significantly increased the risk of relapse into major depressive disorder. These findings agree well with a recent review of clinically based follow-up studies. Thus, youth and a history of nonaffective illness are important risk factors for the recurrence of major affective disorder in a broad variety of settings.


Efficacy and safety of rufinamide in pediatric epilepsy.
Rufinamide is a novel anticonvulsant medication approved by the US Food and Drug Administration (FDA) in 2008 for the treatment of seizures associated with Lennox-Gastaut syndrome in patients 4 years of age and older, based upon clinical trials demonstrating clinical efficacy and tolerability. Rufinamide is especially effective for tonic-atonic seizures in Lennox-Gastaut syndrome, but is subsequently proving to be safe and effective in clinical practice for a broad patient population with refractory epilepsy. Although further research and clinical experience is needed, rufinamide holds the promise to positively impact the care of children with epilepsy. In this review, we review the use of rufinamide in pediatric epilepsy, with a focus on efficacy and safety.