Mesonephric-like adenocarcinoma harbours characteristic copy number variations and a distinct DNA methylation signature closely related to mesonephric adenocarcinoma of the cervix.
Mesonephric-like adenocarcinoma (MLA) of the female genital tract is an uncommon histotype that can arise in both the endometrium and the ovary. The exact cell of origin and histogenesis currently remain unknown. Here, we investigated whole genome DNA methylation patterns and copy number variations (CNVs) in a series of MLAs in the context of a large cohort of various gynaecological carcinoma types. CNV analysis of 19 MLAs uncovered gains of chromosomes 1q (18/19, 95%), 10 (15/19, 79%), 12 (14/19, 74%), and 2 (10/19, 53%), as well as loss of chromosome 1p (7/19, 37%). Gains of chromosomes 1q, 10, and 12 were also identified in the majority of mesonephric adenocarcinomas of the uterine cervix (MAs) as well as subsets of endometrioid carcinomas (ECs) and low-grade serous carcinomas of the ovary (LGSCs) but only in a minority of serous carcinomas of the uterine corpus (USCs), clear cell carcinomas (CCCs), and tubo-ovarian high-grade serous carcinomas (HGSCs). While losses of chromosome 1p together with gains of chromosome 1q were also identified in both MA and LGSC, gains of chromosome 2 were almost exclusively identified in MLA and MA. Unsupervised hierarchical clustering and t-SNE analysis of DNA methylation data (Illumina EPIC array) identified a co-clustering for MLAs and MAs, which was distinct from clusters of ECs, USCs, CCCs, LGSCs, and HGSCs. Group-wise comparisons confirmed a close epigenetic relationship between MLA and MA. These findings, in conjunction with the established histological and immunophenotypical overlap, suggest bona fide mesonephric differentiation, and support a more precise terminology of mesonephric-type adenocarcinoma instead of MLA in these tumours. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


A method for measuring nitrite in fresh vegetables.
A method for the measurement of nitrite in fresh vegetables is described. Interference from ascorbic acid, tannins and nitrate reductase enzyme is limited by extracting the nitrite with zinc acetate at pH 7.2-7.5 in the presence of activated carbon. Using three types of activated carbon the mean overall recovery of 40 micrograms nitrite added to samples of five types of vegetables (equivalent to 0.667 mg kg-1 nitrite fresh weight) was 35.84 micrograms (89.6%) SD 2.437, CV 6.8%. The spectrophotometric determination uses the diazotization/coupling reaction between sulphanilamide and N(1-naphthyl)ethylenediamine. The precision and sensitivity is improved by controlling the test solution to pH 1.2 +/- 0.1.


Isolation and characterization of the amyloid-related apoprotein (SAA) from human high density lipoprotein.
Two apoproteins immunologically related to the 9000-dalton abnormal tissue constituent known as amyloid protein AA were isolated from the lipoprotein density interval 1.125-1.21 g/cm3 (HDL3) of a pool of human serums by delipidation, gel filtration, and ion-exchange chromatography. Lesser amounts of the same apoproteins were isolated from the density interval 1.063-1.125 g/cm3 (HDL2). These apoproteins, designated apoSAA1 and apoSAA2, have molecular weights near 11,500, almost identical amino acid compositions, and slightly different isoelectric points. Their amino acid sequences are identical as far as determined (30 residues), except that apoSAA2 lacks the NH2-terminal arginine found in apoSAA1. The sequence is homologous with that of amyloid protein AA, which thus has residing in the plasma high density lipoproteins a potential precursor whose biological significance and function remain to be determined.


Human nonverbal courtship behavior--a brief historical review.
This article reviews research findings documenting the nature of nonverbal courtship behavior compiled through both observation and self-report methods. I briefly present the major theoretical perspectives guiding research methodologies used in the field and in the laboratory. Studies of verbal courtship, including those conducted via computer, via text messaging, or through personal advertisement, are not included in this review. The article ends by elucidating some key features of human nonverbal courtship behavior that have become apparent after scrutinizing these data.


Identification of bloodmeals in wild caught blood fed Phlebotomus argentipes (Diptera: Psychodidae) using cytochrome b PCR and reverse line blotting in Bihar, India.
Identification of the source of bloodmeals in vectors plays an important role in epidemiological studies by determining the host preferences of wild sand flies in natural habitat. The anthropophilic index is a crucial component in human leishmaniasis. Bloodmeal analysis can identify the reservoir hosts of vector borne diseases. The amplification of the mitochondrial cytochrome b gene, followed by reverse line blot analysis, helps to identify the bloodmeal ingested by the wild caught sand flies. In the current study, blood fed sand flies were collected from three different villages in Bihar, India, by using Centers for Disease Control mini traps with incandescent light. Traps were placed in five different sites in the villages. Whole genome DNA was extracted from the blood fed sand flies and was amplified for the cytochrome b region, followed by reverse line blot analysis. In total, 442 blood fed sand flies were analyzed out of which 288 (65%) were positive to cytochrome b polymerase chain reaction. Humans, cattle, buffalo, and goats were the major bloodmeals identified, followed by chickens. In some of the blood fed sand flies, multiple bloodmeals were identified. In the current study, sand flies mostly fed on humans, followed by cattle, buffalo, and goats. In this regard, it is necessary to also consider cattle, buffalo, and goats when addressing vector control in Bihar, India.


Pathological Roles of Neutrophil-Mediated Inflammation in Asthma and Its Potential for Therapy as a Target.
Asthma is a chronic inflammatory disease that undermines the airways. It is caused by dysfunction of various types of cells, as well as cellular components, and is characterized by recruitment of inflammatory cells, bronchial hyperreactivity, mucus production, and airway remodelling and narrowing. It has commonly been considered that airway inflammation is caused by the Th2 immune response, or eosinophilia, which is a hallmark of bronchial asthma pathogenesis. Some patients display a neutrophil-dominant presentation and are characterized with low (or even absent) Th2 cytokines. In recent years, increasing evidence has also suggested that neutrophils play a key role in the development of certain subtypes of asthma. This review discusses neutrophils in asthma and potentially related targeted therapies.


Mapping and characterization of a mutation in Escherichia coli that reduces the level of ribonuclease III specific for double-stranded ribonucleic acid.
Localization of a mutation affecting ribonuclease III activity (an enzyme specific for double-stranded ribonucleic acid) in Escherichia coli was attempted. By a series of matings and transduction experiments, the mutation rnc-105 was mapped near the nadB gene. In strains carrying this mutation, another mutation (ranA2074) was also found. Based on available data, their order on the E. coli chromosome appears to be tyrA, ranA, nadB, rnc, purI. Strains carrying either the ranA2074 or the rnc-105 mutation fail to grow at 45 C in enriched medium, whereas strains carrying only the rnc-105 mutation are defective in ribonuclease III activity. Strains carrying either of these mutations grow more slowly than corresponding wild-type strains in all media tested at all temperatures; the rnc-105 mutation reduces the growth rate more than the ranA2074 mutation. T4 and T7 bacteriophages form plaques with a lower efficiency on strains carrying the rnc-105 mutation than on other strains. Thus we suggest that ribonuclease III is beneficial for normal growth of E. Coli and that at higher temperatures it becomes indispensable.


Carboplatin, etoposide, and bleomycin for patients with poor-risk germ cell tumors.
A prospective study of four cycles of carboplatin (CBDCA) + etoposide + bleomycin (EBC) was conducted in 32 previously poor-risk nonseminomatous germ cell tumor (GCT) patients and the results compared with past studies. Patients with extragonadal (nine patients) and testicular nonseminomatous GCT with a probability of complete response (CR) less than 0.5 as calculated by a mathematical model using marker values and number of metastatic sites (23 patients) were included. Nineteen patients (59%) achieved a CR and 14 complete responders (43%) remain free of disease. The overall and durable CR proportions were similar to those observed in prior poor-risk studies at Memorial Sloan-Kettering Cancer Center. Myelosuppression was the major toxicity. Based on the low CR proportion, EBC is no better than other standard programs for poor-risk GCT. However, its ease of administration as an outpatient, mild renal and gastrointestinal toxicity, and efficacy comparable to cisplatin-based chemotherapy used in prior poor-risk trials at Memorial Sloan-Kettering Cancer Center warrant a Phase III trial comparing CBDCA-based and cisplatin-based chemotherapy for good-risk GCT patients.


Management of endoscopic biliary stenting for choledocholithiasis: Evaluation of stent-exchange intervals.
To evaluate the best management of plastic stents in patients with choledocholithiasis who were unfit for endoscopic stone removal or surgery. Between April 2007 and September 2017, 87 patients (median age 83.7 years) with symptomatic choledocholithiasis were treated with insertion of 7-Fr plastic stents because complete endoscopic stone retrieval was difficult, and their general condition was not suitable for surgery. Seventy of these patients agreed to regular stent management and stent exchange was carried out at every 6 mo (Group A, n = 35) or every 12 mo (Group B, n = 35). The remaining 17 patients did not accept regular stent exchange, and stents were replaced when clinical symptoms appeared (Group C). We evaluated the frequency of biliary complication and stent patency rate during follow-up periods. The patency rate of biliary plastic stents was 91.4% at 6 mo (Group A) and 88.6% at 12 mo (Group B), respectively. Acute cholangitis occurred in 2.9% of Group A patients and in 8.6% of Group B patients. In Group C, median stent patency was 16.3 mo, and stent exchange was carried out in 70.6% of cases because of acute cholangitis or obstructive jaundice. Although a high incidence of acute cholangitis occurred, there was no biliary-related mortality. Plastic stent exchange at 12-mo intervals is considered a safe procedure for patients with choledocholithiasis. Long-term biliary stenting increases biliary complications, but it can be an acceptable option for select patients who are medically unfit for further invasive procedures.


Prospective randomized trial of 100u vs 200u botox in the treatment of idiopathic overactive bladder.
To evaluate the clinical outcomes of two different doses of BTX-A in patients with refractory idiopathic overactive bladder. Thirty nine patients with refractory idiopathic overactive bladder from 1/1/2008 till 30/3/2009 were evaluated in a tertiary care hospital. Patients were evaluated using urodynamic studies, voiding diary, UDI-6 and IIQ-7 questionnaires prior to being prospectively randomized (alternate randomization) to the BTX-A applications and three months after treatment. Voiding diary and residual volume were followed two weeks later. All patients received intradetrusorial injections of BTX-A (Botox, Allergan, Irvine, CA) of 100u or 200u under cystoscopic control on an outpatient basis. The primary endpoint was assessed for the improvement of urodynamic parameters and adverse events at three months after the initial treatment. Secondary end points included urinary frequency, urgency and UUI episodes as assessed by voiding diary and QoL. Eleven patients were enrolled to each arm of the study. There were no significant differences in demographic characteristics between the two groups. Urodynamic assessment at the end of the third month showed significant improvement in urodynamic variables in both groups. There was no statistically significant difference in urodynamic parameters and in the voiding diary between the two groups. QOL was significantly improved in both groups with no statistically significant difference between the different doses. Only three patients developed acute urinary retention. BTX-A at 100u and 200u appears to improve symptoms, urodynamic parameters and QoL with no statistical significance between the two groups.


Down-regulated expression of atypical PKC-binding domain deleted asip isoforms in human hepatocellular carcinomas.
Asip is a mammalian homologue of polarity protein Par-3 of Caenorhabditis elegans and Bazooka of Drosophila melanogaster. Asip/Par-3/Bazooka are PDZ-motif containing proteins that localize asymmetrically to the cell periphery and play a pivotal role in cell polarity and asymmetric cell division. In the present study, we have cloned human asip cDNA and its splicing variants by 5'-RACE and RT-PCR using candidate human EST clones which have a high homology to rat asip cDNA. The full-length cDNA of human asip encodes a 1,353 aa protein exhibiting 88% similarity to the rat one. Human asip is a single copy gene consisting of at least 26 exons and localizing in human chromosome 10, band p11.2, with some extraordinarily long introns. All exon/intron boundary nucleotides conform to the "gt-ag" rule. Three main transcripts were detected by Northern blot analysis, and at least five variants, from alternative splicing and polyadenylation, have been identified by RT-PCR and liver cDNA library screening. Exon 17b deleted asip mRNAs expressed ubiquitously in normal human tissues, including liver, on RT-PCR analysis. However, they were absent from most human liver cancer cell lines examined. More interestingly, the expression of exon 17b deleted variants was down regulated in 52.6% (10/19) clinic specimens of human hepatocellular carcinomas (HCCs), compared with the surrounding nontumorous liver tissues from the same patients. The presence of various splicing transcripts, the variation of their distribution among different tissues and cells, and their differential expressions in human HCCs suggest that human Asip isoforms may function in different context.


The impact of stress-coping strategies on perceived stress during the COVID-19 pandemic among university students an interventional study.
Coronavirus (COVID-19) pandemic is a public health emergency. During the outbreak, a broad range of psychological disorders affected people at the individual, community, and international levels. This study aimed to assess the role of stress-coping strategies in relieving perceived stress among university students during the COVID-19 pandemic. This interventional study was nested on a cross-sectional design and involved students at Faiyum University in 2022. Out of a sample of 2640 students, 2176 (82.4%) experienced moderate perceived stress, while 56 (2.1%) had more severe levels. Being female, nonmedical students, and rural inhabitants having a low socioeconomic status were associated with scores for severe and moderate levels of perceived stress. Among the interventional group, Modified Perceived Stress Scale scores significantly decreased after the implementation of the stress-coping program, with a p value < 0.001. Improvements in perceived stress levels were observed among male, medical, and high-socioeconomic-status students. Perceived stress levels were associated with being female, engaging in nonmedical study, and having low socioeconomic status and decreased after a stress-coping program was implemented. These findings assert the need to develop regular campaigns to provide psychological support and stress-coping strategies that may help students overcome different stressors.


Draft Genome Sequence of Pseudoalteromonas sp. Strain PAB 2.2 Isolated from Abrolhos Bank (Brazil).
We present here the draft genome sequence of Pseudoalteromonas sp. strain PAB 2.2, isolated from water of Parcel de Abrolhos coral reef (17°57'32.7″; 38°30'20.3″), on Abrolhos Bank, at a depth of 12 m. The assembly consists of 4,434,635 bp and contains 40 contigs, with a G+C content of 41.60%.


Structure and Energetics of the Samarium Diiodide-HMPA Complex in Tetrahydrofuran.
The role of HMPA as a ligand for SmI2 and the stoichiometry and energetics of formation for the SmI2-HMPA complex in THF were investigated employing UV-vis spectroscopy, isothermal titration calorimetry (ITC), and vapor pressure osmometry (VPO). The aggregation number for SmI2 in THF was found to be 0.98 ± 0.09 over the entire concentration range studied (6.71-84.0 mM), indicating that SmI2 is monomeric. The UV-vis data suggest that four HMPA ligands coordinate to SmI2, and this was supported by ITC experiments. The combined results are consistent with [SmI2(HMPA)4] being the reductant responsible for the unique reactivity exhibited by SmI2-HMPA cosolvent combinations.


Unilateral versus bilateral botulinum toxin injections in adductor spasmodic dysphonia.
Thyroarytenoid injection of botulinum toxin is the therapy of choice in spasmodic dysphonia. However, there is no convincing evidence as to whether unilateral or bilateral injections are to be preferred. For this reason, a prospective study was designed in which voice quality, duration of effect, and side effects were assessed. Twenty-seven patients with adductor spasmodic dysphonia were treated with percutaneous injections of botulinum toxin. The first treatment consisted of injection of 5 units in the left thyroarytenoid muscle. The second treatment, 2.5 units in both sides, took place when the effect of the first procedure had completely ceased. All patients underwent both procedures. By means of self-rating scales, effects and side effects were assessed over at least 3 months. There was no difference between the procedures in duration of voice improvement, nor in the occurrence of breathy dysphonia. After a bilateral injection, statistically more patients reported swallowing problems. However, most patients preferred the bilateral injection, in spite of more and longer-lasting side effects.


Contributed review: optical micro- and nanofiber pulling rig.
We review the method of producing adiabatic optical micro- and nanofibers using a hydrogen/oxygen flame brushing technique. The flame is scanned along the fiber, which is being simultaneously stretched by two translation stages. The tapered fiber fabrication is reproducible and yields highly adiabatic tapers with either exponential or linear profiles. Details regarding the setup of the flame brushing rig and the various parameters used are presented. Information available from the literature is compiled and further details that are necessary to have a functioning pulling rig are included. This should enable the reader to fabricate various taper profiles, while achieving adiabatic transmission of ∼99% for fundamental mode propagation. Using this rig, transmissions ranging from 85% to 95% for higher order modes in an optical nanofiber have been obtained.


Percutaneous arterial closure for inadvertent cannulation of the subclavian artery--a call for caution.
An uncommon occurrence during central venous catheterization, inadvertent arterial sheath placement can cause potentially serious complications. When the subclavian artery is inadvertently cannulated, catheter removal may be complicated by significant hemorrhage due to its noncompressible location. We report a case of inadvertent insertion of a 7 Fr central venous catheter into the subclavian artery of a patient with severe kyphoscoliosis, Duchenne muscular dystrophy and cardiomyopathy. The catheter was successfully removed, however the initial attempt at closure device deployment resulted in abrupt closure of the subclavian artery. Prompt angiography and balloon inflation via an already present sheath in the brachiocephalic artery resulted in restoration of flow and successful closure at the puncture site with the collagen-based vascular closure device was confirmed. This averted an otherwise urgent surgical sheath removal and arteriotomy repair in an extremely high-risk patient who was deemed a poor candidate for open surgical repair.


Detection of right ventricular dysfunction in acute pulmonary embolism by computed tomography or echocardiography: A systematic review and meta-analysis.
Right ventricular (RV) dysfunction predicts worse outcomes in acute pulmonary embolism (PE). Because computed tomography (CT) pulmonary angiography visualizes cardiac structures, it is a potential method for assessing RV function without the delays associated with inpatient echocardiography. We conducted a systematic review and meta-analysis to assess the diagnostic accuracy of CT scan findings for detecting RV dysfunction compared with echocardiography. We searched MEDLINE and EMBASE from inception to April 2020 for studies comparing RV dysfunction on CT scan with echocardiography standard. Study quality was assessed with the QUADAS-2 risk of bias tool. Meta-analysis was performed using a bivariate mixed effects regression framework. After screening, 26 studies (3508 patients) were included. In a pooled analysis, septal deviation (5 studies; 459 patients) had a sensitivity of 0.31 (95% CI 0.25-0.38; I2 = 0%), specificity of 0.98 (95% CI 0.90-1.00; I2 = 59.4%), and positive likelihood ratio of 13.6 (95% CI 3.1-60.4) for RV dysfunction compared with echocardiography. The pooled sensitivity of increased RV/left ventricular ratio (21 studies; 3111 patients) was 0.83 (95% CI 0.78-0.87; I2 = 81.8%), whereas the pooled specificity was 0.75 (95% CI 0.66-0.82; I2 = 94.2%) and negative likelihood ratio was 0.23 (0.18-0.29). Overall, RV dysfunction can be detected by CT imaging but the diagnostic accuracy when compared with echocardiography varies depending on specific findings. The presence of septal bowing appears to be highly specific for RV dysfunction. Our findings suggest that multiple CT findings of RV dysfunction may improve diagnostic accuracy and further studies are warranted.


REPRODUCTIVE ISOLATION AND DISTINCT POPULATION STRUCTURES IN TWO TYPES OF THE FRESHWATER SHRIMP PALAEMON PAUCIDENS.
Twenty local populations of the Japanese freshwater shrimp Palaemon paucidens were electrophoretically and morphologically surveyed. Based on the diagnostic distributions of some alleles at Gpi, Mpi, Mdh-1, and Mdh-2, these populations were largely classified into two types (A and B). The A type occurred in lakes, ponds, and rivers, while the B type was observed only in rivers. Average Nei's genetic distance (D) between the two types fell into the subspecies range (D¯=0.1186). The coefficient of gene differentiation, GST , varied considerably between the two types. In 12 populations of the A type, with a GST value of 0.281, nine pond and lake populations showed a higher GST (0.246) than the three river populations (0.151). On the other hand, GST was 0.036 for the eight local populations of the B type. The lower rostrum tooth number had a mode of two in type A and three in type B. Type-A populations largely varied in the upper rostrum tooth number and egg size but type B did not. Under laboratory conditions, mating frequently occurred within each type, but not between types. Furthermore, no embryonic development was observed in the few cases of intertype mating. These results indicate that the A and B types had experienced cladogenic separation with pre- or postmating isolation, whereafter the A type, under geographic isolation, underwent genetic and phenotypic differentiation, while the B type, under extensive gene flow, did not undergo differentiation.


Probing and controlling photothermal heat generation in plasmonic nanostructures.
In the emerging field of thermoplasmonics, Joule heating associated with optically resonant plasmonic structures is exploited to generate nanoscale thermal hotspots. In the present study, new methods for designing and thermally probing thermoplasmonic structures are reported. A general design rationale, based on Babinet's principle, is developed for understanding how the complementary version of ideal electromagnetic antennae can yield efficient nanoscale heat sources with maximized current density. Using this methodology, we show that the diabolo antenna is more suitable for heat generation compared with its more well-known complementary structure, the bow-tie antenna. We also demonstrate that highly localized and enhanced thermal hot spots can be realized by incorporating the diabolo antenna into a plasmonic lens. Using a newly developed thermal microscopy method based on the temperature-dependent photoluminescence lifetime of thin-film thermographic phosphors, we experimentally characterize the thermal response of various antenna and superstructure designs. Data from FDTD simulations and the experimental temperature measurements confirm the validity of the design rationale. The thermal microscopy technique, with its robust sensing method, could overcome some of the drawbacks of current micro/nanoscale temperature measurement schemes.


Multinucleate cell angiohistiocytoma: an uncommon mucosal tumour.
Multinucleate cell angiohistiocytoma (MCAH) is an uncommon benign soft-tissue lesion with characteristic histological and immunohistochemical features. It is unclear if it represents a benign neoplasm or a reactive/inflammatory process. The overwhelming majority of these tumors have been described on cutaneous surfaces. One case has been reported on the skin of the lip. This is the first documentation of MCAH within the oral cavity. The clinical presentation, histopathological features and immunohistochemical reactivity pattern are described. Because of the benign nature of this lesion, a conservative approach is recommended in its management. Surgical excision appears to be curative.


Numerical Simulation and Comparison of the Mechanical Behavior of Toughened Epoxy Resin by Different Nanoparticles.
Adding nanoparticles as the second phase to epoxy can achieve a good toughening effect. The aim of this paper is to simulate the toughening behavior of epoxy resin by different nanoparticles using a convenient and effective finite element method. The mechanical behaviors of epoxy resins toughened by nano core-shell polymers, liquid rubber, and nanosilica were compared by numerical simulations using the representative volume element (RVE). It is indicated that the addition of a nano core-shell polymer and liquid rubber can reduce the tensile properties of epoxy resin, while nanosilica is on the contrary. With the increase of nanoparticle content, the length of crack propagation decreases, and the toughening effect of the nano core-shell polymer is the best. The failure mode is determined by the particle/matrix interface when the modulus of the nanoparticle is much larger than that of epoxy resin. However, it is determined by the interface properties of the particle/matrix and the modulus of nanoparticles in other cases. The results provide a theoretical basis for toughening nanoparticle selection of nanoparticle-toughened epoxy resin and other similar simulations in the future.


Grapevine Wood-Degrading Activity of Fomitiporia mediterranea M. Fisch.: A Focus on the Enzymatic Pathway Regulation.
Fomitiporia mediterranea is a Basidiomycetes fungus associated with some of the Esca complex diseases and responsible for decay in grapevine wood. Its role in the onset of foliar symptoms has recently been reconsidered, mainly after evidence showing a reduction in foliar symptom expression after removal of rotten wood. The study of its degradation pathways has already been approached by other authors, and with this study much information is consolidated. A microscopic observation of degraded wood provides a first approach to the characterization of F. mediterranea modalities of wood cellular structure degradation. The decay of grapevine wood was reproduced in vitro, and the measurement of each wood-forming polymer loss highlighted characteristics of F. mediterranea common to selective white rot and showed how fungal strain and vine variety are factors determining the wood degradation. All these observations were supported by the analysis of the laccase and manganese peroxidase enzyme activity, as well as by the expression of the genes coding 6 putative laccase isoforms and 3 manganese peroxidase isoforms, thereby highlighting substantial intraspecific variability.


Trehalose dimycolate elicits eosinophilic skin hypersensitivity in mycobacteria-infected guinea pigs.
Delayed-type hypersensitivity represents high levels of protein Ag-specific adaptive immunity induced by mycobacterial infection, and can be monitored in the Ag-challenged skin. Besides protein Ags, recent evidence has suggested that a substantial immunity directed against glycolipid Ags is also elicited in response to mycobacterial infection, but skin hypersensitivity to this class of Ags has not been fully assessed. To address this issue directly, glycolipid-specific skin reactions were evaluated in guinea pigs infected with Mycobacterium avium complex (MAC). Significant skin induration was observed in MAC-infected, but not mock-infected, guinea pigs, following intradermal administration of a mixture of MAC-derived glycolipids. Surprisingly, this glycolipid-specific skin response involved up-regulated expression of IL-5 mRNA in situ and marked local infiltration of eosinophils. Challenge experiments with individual glycolipid components detected an outstanding capability for trehalose dimycolate (TDM), but not a structurally related glycolipid, glucose monomycolate, to elicit the skin response. T lymphocytes derived from the spleen of MAC-infected, but not uninfected, guinea pigs specifically responded to TDM in vitro by up-regulating IL-5 transcription, and this response was not blocked by Abs that reacted to the known guinea pig group 1 CD1 proteins. Finally, the eosinophilic skin hypersensitivity to TDM was also elicited in guinea pigs vaccinated with bacillus Calmette-Guerin, which contrasted sharply with the classical delayed-type hypersensitivity response to the purified protein derivative. Therefore, the TDM-elicited eosinophilic response defines a new form of hypersensitivity in mycobacterial infection, which may account for local infiltration of eosinophils often observed at the site of infection.


Extramural vascular invasion and response to neoadjuvant chemoradiotherapy in rectal cancer: Influence of the CpG island methylator phenotype.
To identify whether CpG island methylator phenotype (CIMP) is predictive of response to neoadjuvant chemoradiotherapy (NACRT) and outcomes in rectal cancer. Patients undergoing NACRT and surgical resection for rectal cancer in a tertiary referral centre between 2002-2011 were identified. Pre-treatment tumour biopsies were analysed for CIMP status (high, intermediate or low) using methylation specific PCR. KRAS and BRAF status were also determined using pyrosequencing analysis. Clinical information was extracted from case records and cancer services databases. Response to radiotherapy was measured by tumour regression scores determined upon histological examination of the resected specimen. The relationship between these molecular features, response to NACRT and oncological outcomes were analysed. There were 160 patients analysed with a median follow-up time of 46.4 mo. Twenty-one (13%) patients demonstrated high levels of CIMP methylation (CIMP-H) and this was significantly associated with increased risk of extramural vascular invasion (EMVI) compared with CIMP-L [8/21 (38%) vs 15/99 (15%), P = 0.028]. CIMP status was not related to tumour regression after radiotherapy or survival, however EMVI was significantly associated with adverse survival (P < 0.001). Intermediate CIMP status was significantly associated with KRAS mutation (P = 0.01). There were 14 (9%) patients with a pathological complete response (pCR) compared to 116 (73%) patients having no or minimal regression after neoadjuvant chemoradiotherapy. Those patients with pCR had median survival of 106 mo compared to 65.8 mo with minimal regression, although this was not statistically significant (P = 0.26). Binary logistic regression analysis of the relationship between EMVI and other prognostic features revealed, EMVI positivity was associated with poor overall survival, advanced "T" stage and CIMP-H but not nodal status, age, sex, KRAS mutation status and presence of local or systemic recurrence. We report a novel association of pre-treatment characterisation of CIMP-H with EMVI status which has prognostic implications and is not readily detectable on pre-treatment histological examination.


Comparison of heavy metal accumulation and cadmium phytoextraction rates among ten leading tobacco (Nicotiana tabacum L.) cultivars in China.
Cadmium (Cd) contamination is one of the most serious global environmental problems, and phytoremediation, which uses Cd-accumulator plants, is potentially one of the sustainable solutions. Pot experiments with natural and Cd-amended soils were conducted to investigate the accumulation of heavy metals in 10 leading cultivars of tobacco in China. The extraction ability and profiles of Cd accumulation among plant organs were also analyzed. The tobacco roots accumulated cobalt, nickel, and Cd, while the leaf highly bioaccumulated Cd and lowly accumulated zinc, selenium and mercury. The transport from the tobacco stem to the leaf plays a critical role in the accumulation of these elements. The ratios of Cd concentration in the leaves at lower, middle and upper positions were comparatively stable. The high Cd-extracting cultivars were "Hongda", "NC89" and "Zhongyan 100" when grown in normal soils, "CuiBi 1" and "Hongda" in moderately contaminated soils, and "YuYan 87", "LongJiang 851" and "K326" in severely contaminated soils. Tobacco leaves could accumulate about 80% of the total Cd extracted from the soil by the plant. Considering the Cd-extraction limitations exhibited by leading tobacco cultivars, screening of germplasm resources for high or low levels of Cd-accumulation is still an important target for the future.


Clinical and economic impact of universal varicella vaccination in Norway: A modeling study.
Norway has not implemented universal varicella vaccination, despite the considerable clinical and economic burden of varicella disease. An existing dynamic transmission model of varicella infection was calibrated to age-specific seroprevalence rates in Norway. Six two-dose vaccination strategies were considered, consisting of combinations of two formulations each of a monovalent varicella vaccine (Varivax® or Varilrix®) and a quadrivalent vaccine against measles-mumps-rubella-varicella (ProQuad® or PriorixTetra®), with the first dose given with a monovalent vaccine at age 15 months, and the second dose with either a monovalent or quadrivalent vaccine at either 18 months, 7 or 11 years. Costs were considered from the perspectives of both the health care system and society. Quality-adjusted life-years saved and incremental cost-effectiveness ratios relative to no vaccination were calculated. A one-way sensitivity analysis was conducted to assess the impact of vaccine efficacy, price, the costs of a lost workday and of inpatient and outpatient care, vaccination coverage, and discount rate. In the absence of varicella vaccination, the annual incidence of natural varicella is estimated to be 1,359 per 100,000 population, and the cumulative numbers of varicella outpatient cases, hospitalizations, and deaths over 50 years are projected to be 1.81 million, 10,161, and 61, respectively. Universal varicella vaccination is projected to reduce the natural varicella incidence rate to 48-59 per 100,000 population, depending on the vaccination strategy, and to reduce varicella outpatient cases, hospitalizations, and deaths by 75-85%, 67-79%, and 75-79%, respectively. All strategies were cost-saving, with the most cost-saving as two doses of Varivax® at 15 months and 7 years (payer perspective) and two doses of Varivax® at 15 months and 18 months (societal perspective). All modeled two-dose varicella vaccination strategies are projected to lead to substantial reductions in varicella disease and to be cost saving compared to no vaccination in Norway.


In Vitro Toxicological Assessment of Gadodiamide in Normal Brain SVG P12 Cells.
Magnetic resonance imaging (MRI) is a technique for evaluating patients with primary and metastatic tumors. The contrast agents improve the diagnostic accuracy of MRI. Large quantities of a contrast agent must be administrated into the patient to obtain useful images, which leads to cell injury. Gadolinium has been reported to cause central lobular necrosis of the liver and nephrogenic systemic fibrosis. However, the toxicity caused on brain tissue is uncertain. This study mainly aimed on the in vitro study of high concentration (2 and 5-fold of normal concentration) gadolinium-based contrast agents (GBCAs), gadodiamide (Omniscan®), on normal brain glial SVG P12 cells. MTT assay, DAPI staining, immunofluorescent staining, LysoTracker Red staining, and western blotting analysis were applied on the cells. The viability of gadodiamide (1.3, 2.6, 5.2, 13 and 26 mM)-treated SVG P12 cells was significantly reduced after 24 h of incubation. Gadodiamide caused significant autophagic flux at 2.6, 5.2 and 13.0 mM as seen by acridine orange (AO) staining, LC-3-GFP and LysoTracker Red staining. The expression levels of autophagy-related proteins such as beclin-1, ATG-5, ATG-14 and LC-3 II were up-regulated after 24 h of gadodiamide incubation. Autophagy inhibitors including 3-methyladenine (3-MA), chloroquine (CQ) and bafilomycin A1 (Baf) significantly alleviated the autophagic cell death effect of gadodiamide on normal brain glial SVG P12 cells. Gadodiamide induced significant apoptotic effects at 5.2 mM and 13.0 mM as seen by DAPI staining and the pan-caspase inhibitor significantly alleviated the apoptotic effect. Gadodiamide at 5.2 mM and 13.0 mM inhibited antiapoptotic protein expression levels of Bcl-2 and Bcl-XL, while promoted pro-apoptotic protein expression levels of Bax, BAD, cytochrome c, Apaf-1, cleaved-caspase-9 and cleaved-caspase-3. Normal brain glial SVG P12 cells treated with high concentrations of gadodiamide can undergo autophagy and apoptosis.


Gene transfer directly demonstrates a role for TCR V alpha elements in superantigen recognition.
Recent structure-function studies of ours and others indicating that regions of the TCR other than V beta are involved in the TCR-superantigen (SAg)-MHC class II trimolecular interaction were correlative; thus, while the conclusions were persuasive, they were not unequivocal. The transfection experiments described in this report show that 1) responsiveness to staphylococcal enterotoxin B in V beta6 T cells was transferred by a V alpha4- but not by V alpha8- and V alpha10-containing alpha-chain cDNA constructs, 2) responsiveness was not transferred by a chimeric alpha-chain construct containing the N and J regions from a responsive T hybrid clone and the V alpha10 V alpha region from a nonresponsive clone, and 3) responsiveness was transferred by a chimeric alpha-chain construct in which most of the V alpha region (from the N terminus to the C-terminal end of the complementarity-determining region 2) was derived from the V alpha4 alpha-chain of a responsive T hybrid and the rest (framework 3, N, and J) from the V alpha8 alpha-chain of a nonresponsive T hybrid. Thus, these data provide the first direct evidence for a specific SAg response facilitating activity in a defined V alpha segment and map this activity N-terminal of framework region 3. Furthermore, the diversity in the alpha- and beta-chain junctional regions of a panel of staphylococcal enterotoxin B-responsive V beta6 T hybrid clones excludes a stringent corequirement for a particular junctional region for the V alpha4 segment to mediate its facilitating activity. Finally, a model postulating a universal role for V alpha elements in TCR recognition of SAg is presented.


Ruthenium hydrides encapsulated in sol-gel glasses exhibit new ultrafast vibrational dynamics.
Vibrational dynamics were measured by IR pump-probe spectroscopy and two-dimensional IR spectroscopy for triruthenium dodecacarbonyl and the undecacarbonyl hydride that forms when it is encapsulated in an alumina sol-gel glass. For comparison, a triruthenium undecacarbonyl hydride salt was also synthesized and studied in neat solution to identify the potential influence of the confined solvent environment on the dynamics experienced by carbon monoxide ligands. The vibrational lifetime was found to be significantly decreased for both hydride species relative to the dodecacarbonyl compound. Conversely, spectral diffusion of the CO vibrations was measured to be faster for the parent compound. The most significant dynamic changes occurred upon transformation from the starting compound to the hydride, while only minor differences were observed between the dynamics of the freely dissolved and sol-gel encapsulated hydrides. The results suggest that the structural change to the hydride has the largest impact on the dynamics and that its improved catalytic properties likely do not originate from confined solvent effects.


Attitude similarity and satisfaction of family members of schizophrenics with services of a professional.
Examined a hypothesis that satisfaction with professionals among families of schizophrenics varies as a function of how similar the professionals' attitudes about schizophrenia are to the family members' attitudes. Twenty-eight family members of individuals diagnosed by DSM-III criteria as having schizophrenia completed a questionnaire that assessed their attitudes with regard to causes and treatments of schizophrenia. Ss then were mailed a completed questionnaire and were asked to indicate how satisfied they would be working with a person who held the attitudes expressed in the questionnaire. In the attitude-similar condition, the questionnaire was 90% in agreement with their own attitudes, and in the attitude-discrepant condition, the questionnaire was 10% in agreement. Responses were received from 21 family members. Results supported the hypothesis; family members in the attitude-similar condition reported that they would be more satisfied with the professional than did family members in the attitude-discrepant condition. Implications for work with families of schizophrenics are discussed.


Usefulness of videothoracoscopic intrapericardial examination of pulmonary vessels to identify resectable clinical T4 lung cancer.
Discrepancies in predicting resectability by imaging techniques (computed tomography and magnetic resonance imaging) compared with actual intraoperative findings have persuaded us to perform systematic exploratory videothoracoscopy (EVT) as the first step in the surgical evaluation of patients with lung cancer. Resectability of centrally located primary tumors with intrapericardial extension (clinical T4), however, can be established only by direct examination of the pericardial sac contents. Therefore, in these instances, videopericardioscopy (VPC) has been added to our protocol. From April 1993 to December 2000, members of our department used EVT to assess 620 patients with lung cancer. Of them, 27 patients, 25 men and 2 women, were seen with pericardial tumor extension. The mean age of the group was 62 years (range, 41 to 77 years). To be properly evaluated, these patients underwent VPC. We used three and, occasionally, four incisions to perform EVT. The same incisions were used to enter the pericardial cavity during VPC. In 15 of the 27 patients, hilar and vascular invasion was correctly predicted by imaging techniques. The other 12, however, were correctly staged only during EVT. The tumor was deemed unresectable by VPC in 6 patients (5 with invasion at the origin of the pulmonary artery and 1 with involvement of the left inferior pulmonary vein and left atrium), and exploratory thoracotomy was obviated. There was no morbidity or mortality in these 6 patients, and their mean length of hospital stay was 48 hours. The remaining 21 patients underwent thoracotomy and intrapericardial lung resection. Six of them had been considered to have unresectable disease on the basis of computed tomographic findings or magnetic resonance imaging studies. An average of 22 minutes (range, 16 to 33 minutes) was added to the operation when VPC was used. This study suggests that EVT is superior to imaging techniques (computed tomography or magnetic resonance imaging) in detecting tumor extension into the pericardium. In addition, short of an exploratory thoracotomy, VPC seems to be the most definitive study to establish resectability of centrally located tumors with pericardial invasion. Unnecessary exploratory thoracotomies can thus be avoided.


Low-dose ferrous bisglycinate chelate supplementation in chronic kidney disease and hemodialysis patients.
Provision of parenteral or oral iron supplementation can restore iron stores and maintain stable hemoglobin levels in chronic kidney disease (CKD) and hemodialysis (HD) patients. The route for oral or intravenous (IV) administration of iron depends on the acuity of anemia, costs, and patient tolerance. IV iron can restore iron stores rapidly but also carries higher risks for allergy and infection. Oral iron supplementation is limited by high gastrointestinal adverse effects. We conducted an open-label trial to study the efficiency of a film-coated iron supplementation tablet, which contains ferrous bisglycinate chelate, vitamin C, and folic acid, in CKD stage 3b to 4 and HD patients. Twenty-seven HD patients and 20 CKD patients participated this study. After a 16-week intervention, low-dose ferrous bisglycinate chelate improved serum iron concentration (67.8 vs 87.2 mg/dL, p = 0.04) and transferrin saturation (24.7% vs 31.3%, p = 0.03) in stage 3 to 4 CKD patients, restored iron loss, and maintained stable hemoglobin levels in HD patients. No GI upset events were reported. Ferrous bisglycinate chelate is a well-tolerated oral iron supplementation for CKD and HD patients.


[Late results of Imhäuser's osteotomy for slipped capital femoral epiphysis (author's transl)].
The author has reviewed the clinical and radiological results of 55 patients 11 to 22 years following an Imhäuser three dimensional intertrochanteric osteotomy for slipped capital femoral epiphysis. 13 additional patients responded by questionnaire. Of these 68 hips 66 were painfree and functional. One patient complained of pain (due to coxarthrosis proven by x-ray). A second patient was dissatisfied with the functional range of his hip. 40 of the 55 hips which were examined clinically and radiologically had full range of motion, 10 hips showed minimal and 5 hips significant limitation of motion. Radiologically 73% of the 55 hips examined were rated excellent or good, 27% showed beginning degenerative changes (including one patient with marked coxarthrosis). The results were greatly influenced by the severity and direction of slipping, preoperative treatment and the accuracy of operative correction. This study permits the conclusion that three dimensional intertrochanteric osteotomy prevented or at least delayed the development of degenerative changes in the majority of cases. It is possible that many of these patients will not develop coxarthrosis.


Lipids from oxidized low-density lipoprotein modulate human trophoblast invasion: involvement of nuclear liver X receptors.
Human embryonic implantation involves major invasion of the uterine wall and remodeling of the uterine arteries by extravillous cytotrophoblast cells (EVCT). Abnormalities in these early steps of placental development lead to poor placentation and fetal growth defects and are frequently associated with preeclampsia, a major complication of human pregnancy. We recently showed that oxidized low-density lipoproteins (oxLDLs) are present in situ in EVCT and inhibit cell invasion in a concentration-dependent manner. The aim of the present study was to better understand the mechanisms by which oxLDL modulate trophoblast invasion. We therefore investigated the presence of oxLDL receptors in our cell culture model of human invasive primary EVCT. We found using immunocytochemistry and immunoblotting that the lectin-like oxLDL receptor-1 was the scavenger receptor mainly expressed in EVCT and was probably involved in oxLDL uptake. We next examined the effect of low-density lipoprotein oxidative state on trophoblast invasion in vitro using EVCT cultured on Matrigel-coated Transwell. We demonstrated that only oxLDL containing a high proportion of oxysterols and phosphatidylcholine hydroperoxide derivatives that provide ligands for liver X receptor (LXR) and peroxisomal proliferator-activated receptor gamma (PPARgamma), respectively, reduced trophoblast invasion. We next investigated the presence and the role of these nuclear receptors and found that in addition to PPARgamma, human invasive trophoblasts express LXRbeta, and activation of these nuclear receptors by specific synthetic or natural ligands inhibited trophoblast invasion. Finally, using a PPARgamma antagonist, we suggest that LXRbeta, rather than PPARgamma, is involved in oxLDL-mediated inhibition of human trophoblast invasion in vitro.


HIV vaccines: problems and prospects.
Several lines of evidence now argue strongly that a successful HIV vaccine does not need to block infection completely. It has to mimic what already occurs in a minority of unvaccinated individuals--namely, rapid clearance of infection or reduction of viral load to a level that does not produce symptoms or permit transmission to others. The various vaccine candidates are reviewed.


Assessment of Antibacterial Efficacy of Callistemon viminalis (Sol. ex Gaertn.) G. Don against Some Isolates Obtained from Urinary Tract Infections.
This study aimed to examine the antibacterial effects of constituents obtained from Callistemon viminalis leaves. This goal was achieved by using three organic solvents, namely Ethanol, Ethyl acetate, and Hexane to prevent the growth of the causative urinary tract infections isolates, such as Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, and Proteus sp. in Iraq. The C. viminalis fresh leaves collected from different regions of Hillah City, during March 2020, were classified according to the taxonomic features of Iraqi Flora. Extractions were completed by a method of digestion and then the stock solution of 200 mg/mL was prepared in 10% of Dimethylsulfoxide. A Millipore filter (0.22 µm) was used for the sterilization of all the extracts used in this study. Agar well diffusion method was utilized to test the antibacterial effects of the constituents separated from the dried leaves of C. viminalis against the urinary tract infection bacteria at three concentrations of 50, 100, and 200 mg/mL for each extracted constitute by the three different solvents. Dimethylsulfoxide 10% and the meropenem were utilized as the negative and positive controls. Constituents separated by ethanol solvent at 200 mg/mL exhibited significant supremacy (P≤0.05) over the meropenem against Proteus sp. isolate, and exhibited the same significant difference (P≤0.05), compared to the meropenem drug against E. coli. Constituents extracted by Ethyl acetate organic solvent at a concentration of 200 mg/mL exhibited a similarly significant effect (P≤0.05), compared to the meropenem against Proteus sp. isolate. However, the hexane extract was the least effective among the other solvents utilized in this study. The results of the current study revealed that constituents in the leaves of C. viminalis could be considered a valuable herbal remedy for controlling urinary tract infections pathogenic bacteria.


Contraceptive efficacy of the diaphragm, the sponge and the cervical cap.
A reanalysis of data from two clinical studies--in which 1,439 women were randomly assigned to use either the contraceptive sponge or the diaphragm and 1,394 women were randomly assigned to use either the cervical cap or the diaphragm--found first-year probabilities of failure during typical use of 17% for the sponge, 18% for the cervical cap and 13-17% for the diaphragm. The first-year probabilities of failure during perfect use are 11-12% for the sponge, 10-13% for the cervical cap and 4-8% for the diaphragm. The probability of failure during perfect use is significantly higher among women who have given birth than among those who have not for users of the sponge (19-21% vs. 9-10%) and users of the cervical cap (26-27% vs. 8-10%), but not for users of the diaphragm.


Isolation of a T7-Like Lytic Pasteurella Bacteriophage vB_PmuP_PHB01 and Its Potential Use in Therapy against Pasteurella multocida Infections.
A lytic bacteriophage PHB01 specific for Pasteurella multocida type D was isolated from the sewage water collected from a pig farm. This phage had the typical morphology of the family Podoviridae, order Caudovirales, presenting an isometric polyhedral head and a short noncontractile tail. PHB01 was able to infect most of the non-toxigenic P. multocida type D strains tested, but not toxigenic type D strains and those belonging to other capsular types. Phage PHB01, the first lytic phage specific for P. multocida type D sequenced thus far, presents a 37,287-bp double-stranded DNA genome with a 223-bp terminal redundancy. The PHB01 genome showed the highest homology with that of PHB02, a lytic phage specific for P. multocida type A. Phylogenetic analysis showed that PHB01 and PHB02 were composed of a genus that was close to the T7-virus genus. In vivo tests using mouse models showed that the administration of PHB01 was safe to the mice and had a good effect on treating the mice infected with different P. multocida type D strains including virulent strain HN05. These findings suggest that PHB01 has a potential use in therapy against infections caused by P. multocida type D.


The Crossmatch/Issue Ratio: Use of a Novel Quality Indicator and Results of an International Survey on RBC Crossmatching and Issuing Practices.
To understand the worldwide scope of RBC crossmatching and issuing practices and measure efficiency using a novel quality indicator, the crossmatch/issue (C/I) ratio. An electronic survey was disseminated to hospital transfusion services collecting details about RBC crossmatching and issuing practices. Respondents were asked to enumerate the number of RBCs crossmatched and issued at their institutions during the 2014 calendar year to calculate the C/I ratio. Fifty-two survey responses were received, mostly from North American transfusion services (28/52, 54%). The electronic crossmatch was the most common technique (n = 29), and most respondents performed the crossmatch at the time that an order for RBCs was received in the transfusion service (even if an order to issue the RBCs was not received). Data to calculate the C/I ratio were supplied by 22 respondents, and the mean ± SD was 1.30 ± 0.34. There was no difference in C/I ratios between services that use the electronic or serologic crossmatch techniques (P = .49). The ratio was the same at the four sites that crossmatch RBCs at the time of issue compared with the time of order receipt (mean ± SD, 1.11 ± 0.09 vs. 1.35 ± 0.36, respectively; P = .19). Electronic crossmatching is common, and the C/I ratio can be an indicator of efficiency.


MREIT experiments with 200 µA injected currents: a feasibility study using two reconstruction algorithms, SMM and harmonic B(Z).
Magnetic resonance electrical impedance tomography (MREIT) is a technique that produces images of conductivity in tissues and phantoms. In this technique, electrical currents are applied to an object and the resulting magnetic flux density is measured using magnetic resonance imaging (MRI) and the conductivity distribution is reconstructed using these MRI data. Currently, the technique is used in research environments, primarily studying phantoms and animals. In order to translate MREIT to clinical applications, strict safety standards need to be established, especially for safe current limits. However, there are currently no standards for safe current limits specific to MREIT. Until such standards are established, human MREIT applications need to conform to existing electrical safety standards in medical instrumentation, such as IEC601. This protocol limits patient auxiliary currents to 100 µA for low frequencies. However, published MREIT studies have utilized currents 10-400 times larger than this limit, bringing into question whether the clinical applications of MREIT are attainable under current standards. In this study, we investigated the feasibility of MREIT to accurately reconstruct the relative conductivity of a simple agarose phantom using 200 µA total injected current and tested the performance of two MREIT reconstruction algorithms. These reconstruction algorithms used are the iterative sensitivity matrix method (SMM) by Ider and Birgul (1998 Elektrik 6 215-25) with Tikhonov regularization and the harmonic B(Z) proposed by Oh et al (2003 Magn. Reason. Med. 50 875-8). The reconstruction techniques were tested at both 200 µA and 5 mA injected currents to investigate their noise sensitivity at low and high current conditions. It should be noted that 200 µA total injected current into a cylindrical phantom generates only 14.7 µA current in imaging slice. Similarly, 5 mA total injected current results in 367 µA in imaging slice. Total acquisition time for 200 µA and 5 mA experiments was about 1 h and 8.5 min, respectively. The results demonstrate that conductivity imaging is possible at low currents using the suggested imaging parameters and reconstructing the images using iterative SMM with Tikhonov regularization, which appears to be more tolerant to noisy data than harmonic B(Z).


Remembering the object you fear: brain potentials during recognition of spiders in spider-fearful individuals.
In the present study we investigated long-term memory for unpleasant, neutral and spider pictures in 15 spider-fearful and 15 non-fearful control individuals using behavioral and electrophysiological measures. During the initial (incidental) encoding, pictures were passively viewed in three separate blocks and were subsequently rated for valence and arousal. A recognition memory task was performed one week later in which old and new unpleasant, neutral and spider pictures were presented. Replicating previous results, we found enhanced memory performance and higher confidence ratings for unpleasant when compared to neutral materials in both animal fearful individuals and controls. When compared to controls high animal fearful individuals also showed a tendency towards better memory accuracy and significantly higher confidence during recognition of spider pictures, suggesting that memory of objects prompting specific fear is also facilitated in fearful individuals. In line, spider-fearful but not control participants responded with larger ERP positivity for correctly recognized old when compared to correctly rejected new spider pictures, thus showing the same effects in the neural signature of emotional memory for feared objects that were already discovered for other emotional materials. The increased fear memory for phobic materials observed in the present study in spider-fearful individuals might result in an enhanced fear response and reinforce negative beliefs aggravating anxiety symptomatology and hindering recovery.


[Upper mesenteric venous thrombosis revealing familial resistance to activated protein C].
Mesenteric venous thrombosis is a rare disease but potentially severe because of the prognosis of intestinal infarction with high mortality rate (60%). We report the case of a 55 year-old man who presented with an upper mesenteric venous thrombosis related to a familial resistance to C reactive protein through factor V Leiden mutation. The discovery of a mesenteric venous thrombosis requires aetiological research that is usually multifactorial. Among the most frequent genetic coagulation abnormalities observed resistance to C reactive protein due to G202110A prothrombin gene mutation is the most common. Although factor V Leiden mutation is less frequent, it requires anticoagulation therapy for life in the case of the appearance of a thrombosis.


Global bioethics.
Because there is a large agenda of work that needs to be done to help ethicists to be better able to address ethical questions in healthcare from an environmentally conscious and globally coherent point of view, Cambridge Quarterly of Healthcare Ethics is initiating this occasional column on global bioethics to provide a space to publish and discuss environmental issues in healthcare. We are initiating this section with a paper of my own outlining some broad concerns about healthcare ethics in a global context ["Casuist or Cassandra? Two conceptions of the bioethicist's role," p. 451-466] and are inviting readers to submit philosophical and multidisciplinary papers taking a global perspective on ethical issues in healthcare....


A qualitative and quantitative analysis of tertiary amines in restorative resins.
Previous investigations have shown that the type and the quantity of tertiary amine influence the properties of restorative resins. It was the purpose of the present work to analyze qualitatively and quantitatively the amines in commercial restorative resins. The amines were extracted with hydrochloric acid from chloroform solutions of the monomers. For the qualitative analysis the acid amine solution was made alkaline, the amine extracted with methylenechloride and isolated. The method of analysis was NMR-spectroscopy. The quantitative determination was performed by means of UV-spectra of the acid amine solutions. Sixteen brands were investigated, and three species of amine were identified. The amount of amine varied between 0.3% and 4% by weight of the monomer. Iit is probable that the information obtained will lead to a better understanding of the nature of restorative resins.


Synthesizing learning in a workshop or conference.
With an increased emphasis on elevating the level of learning in all settings, continuing educators have the opportunity to facilitate learners achieving more from workshops. Using the recommended assessment strategy of The Big Point/Big Question allows educators to respond to pending questions, clarify major learning points, and help learners actively engage in processing information presented in workshops or conferences.


Modified McKenzie procedure for the treatment of fixed painful torticollis.
Spasmodic torticollis is characterized by involuntary movements of the neck muscles. In this video, the authors present the case of a 48-year-old man with painful right-sided rotational torticollis with contributions from both the suboccipital and the left sternocleidomastoid (SCM) muscles. He underwent a suboccipital craniectomy and C1-2 laminectomy with selective denervation of bilateral suboccipital and left-sided SCM muscles (modified McKenzie procedure). At the 2-week follow-up, he showed significant improvement and was able to rotate his neck about 70° toward the midline. Surgical treatment of spasmodic torticollis focuses on interrupting the motor pathway responsible for head turning. The modified McKenzie procedure is valuable, especially when other therapies fail. The video can be found here: https://youtu.be/TK-WybKnGJM.


A specialized rehabilitation approach improves mobility in children with osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a rare disease leading to recurrent fractures, hyperlaxicity of ligaments, short stature and muscular weakness. Physiotherapy is one important treatment approach. The objective of our analysis was to evaluate the effect of a new physiotherapy approach including side alternating whole body vibration on motor function in children with OI. In a retrospective analysis data of 53 children were analyzed. The 12 months approach included 6 months of side alternating whole body vibration training, concomitant physiotherapy, resistance training, treadmill training and 6 months follow up. Primary outcome parameter was the Gross Motor Function Measure after 12 months (M12). 53 children (male: 32; age (mean±SEM): 9.1±0.61, range 2.54-24.81 years) participated in the treatment approach. A significant increase of motor function (GMFM-66 score 55.47±2.45 to 58.67±2.83; p=0.001) and walking distance (47.04 m±6.52 to 63.36±8.25 m (p<0.01) between M0 and M12 was seen. Total body without head bone mineral density increased significantly at M12 (p=0.0189). In the cohort of OI children which participated in the specialized treatment approach improvements of motor function were observed. Therefore this program should be considered as additional therapeutic approach for children with severe OI.


The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers.
Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). Registry-based cohort study including only people with rare head and neck cancers. to help describe the natural history of rare head and neck cancers;to evaluate factors that influence prognosis;to assess treatment effectiveness;to measure indicators of quality of care. Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present. The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed.


Synthesis of a new insulin-mimetic anti-diabetic drug containing vitamin A and vanadium(IV) salt: Chemico-biological characterizations.
Diabetes patients suffer from chronic disorders in the metabolism due to high blood sugar caused by anomalies in insulin excretion. Recently, vanadium compounds have been prepared and functionalized to decrease the level of hyperglycemia. Vitamin A boosts beta cell activity; therefore, the lack of this vitamin plays a role in the development of type 2 diabetes. The aim of this article focused on the synthesis of a new anti-diabetic drug formed from the complexation of a vanadium(IV) salt with vitamin A. Vitamin A acts as a unidentate chelate through the oxygen of its -OH group. The vanadium(IV) compound is surrounded by two vitamin A molecules. The [VO(vitamin A)2(H2O)2] compound was synthesized in a binary solvent system consisting of MeOH/H2O (1:1 ratio) in alkaline media at pH = 8. This compound was characterized using Fourier transform infrared spectra (FT-IR), electronic spectra (UV-vis), effective magnetic moment, electron spin resonance (ESR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermal analysis (thermogravimetry (TG)-differential thermal analysis (DTA)). Anti-diabetic efficiency for the vanadium(IV) compound was assessed in streptozotocin (STZ)-induced diabetic mice. The results of the animal studies demonstrate the ability of the vanadium(IV) complex to act as an anti-diabetic agent, as measured by improvements of lipid profile, antioxidant activity (superoxide dismutase), malondialdehyde (MDA), glutathione, methionine synthase, and kidney and liver functions.


Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer?
We investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer. The data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure), history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded. In total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2%) patients and PCa+NIH IV prostatitis in 23 (22.7%) patients. The median total PSA level was 7.4 (3.5-20.0) ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6-20.0) ng/mL in the PCa group (p=0.67). The PSA level was≤10ng/mL in 60 (76.9%) patients in the PCa group and in 16 (69.6%) patients in the PCa+NIH IV prostatitis group (p=0.32). Our study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa.


Do imaging findings modify the effect of non-surgical treatment in patients with knee and hip osteoarthritis? A systematic literature review.
To review the available evidence on diagnostic imaging findings in knee and hip osteoarthritis (OA) as treatment effect modifiers in non-surgical OA interventions. MEDLINE, Embase and The Cochrane Central Register of Controlled Trials were searched from the earliest records published to 22 March 2022. Studies in knee and hip OA reporting subgroup analyses in randomised controlled trials with imaging findings as potential treatment effect modifiers were included. Studies were critically appraised using the Cochrane risk of bias tool and a subgroup analysis quality assessment. Of 10 014 titles and abstracts screened, eight studies met the inclusion criteria, six on knee OA and two on hip OA. The studies investigated effect modifiers in exercise therapy, intra-articular injections and unloading shoes. Imaging findings assessed as potential treatment effect modifiers were radiographic OA severity, hip effusion (ultrasound), bone marrow lesions and meniscal pathology (MRI). Two studies fulfilled the methodological quality criteria for assessing effect modification. One reported that radiographic knee OA severity modified the effect of unloading shoes on walking pain. Those with more severe radiographic knee OA had a greater response to shoe inserts. One reported no interaction between radiographic OA severity or joint effusion and the effect of intraarticular injections of corticosteroid or hyaluronic acid in hip OA, indicating no difference in response in people with greater hip joint effusion or radiographic OA severity compared with those with less severe joint disease. Overall, methodological limitations and very few studies do not permit conclusions on diagnostic imaging findings as effect modifiers in non-surgical interventions in knee and hip OA.Radiographic severity of knee OA potentially modifies the effect of unloading shoes. CRD42020181934.


A method for generating precise temporal patterns of retinal spiking using prosthetic stimulation.
The goal of retinal prosthetic devices is to generate meaningful visual information in patients that have lost outer retinal function. To accomplish this, these devices should generate patterns of ganglion cell activity that closely resemble the spatial and temporal components of those patterns that are normally elicited by light. Here, we developed a stimulus paradigm that generates precise temporal patterns of activity in retinal ganglion cells, including those patterns normally generated by light. Electrical stimulus pulses (> or =1-ms duration) elicited activity in neurons distal to the ganglion cells; this resulted in ganglion cell spiking that could last as long as 100 ms. However, short pulses, <0.15 ms, elicited only a single spike within 0.7 ms of the leading edge of the pulse. Trains of these short pulses elicited one spike per pulse at frequencies < or =250 Hz. Patterns of short electrical pulses (derived from normal light elicited spike patterns) were delivered to ganglion cells and generated spike patterns that replicated the normal light patterns. Finally, we found that one spike per pulse was elicited over almost a 2.5:1 range of stimulus amplitudes. Thus a common stimulus amplitude could accommodate a 2.5:1 range of activation thresholds, e.g., caused by differences arising from cell biophysical properties or from variations in electrode-to-cell distance arising when a multielectrode array is placed on the retina. This stimulus paradigm can generate the temporal resolution required for a prosthetic device.


G protein-coupled estrogen receptor 1 (GPER 1) mediates estrogen-induced, proliferation of leiomyoma cells.
G protein-coupled estrogen receptor 1 (GPER-1, formerly known as GPR30) has been proposed as the receptor for estrogen-induced, growth of leiomyomas though its precise mechanisms of action are not clear. We obtained leiomyoma cells (LC) and normal smooth muscle cells from 28 women (n = 28, median age 38 years, median parity 1.0). We incubated them with 17-β estradiol (E(2)), after blocking, or upregulating, expression of GPER-1 with ICI182,780 (a GPER-1 agonist) and siGPR30, respectively. We evaluated the role of GPER-1 in the mitogen-activated protein kinase (MAPK) signaling pathway using Western blot analysis. We studied cell proliferation with 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide, and, mitotic activity with phosphohistone H3 (PPH3) expression in leiomyoma, and, matched, normal, smooth muscle tissues using standard immunohistochemistry. Downregulation of GPER-1 expression with siGPR30 partially attenuated the E(2)-activated MAPK signaling pathway (p < 0.01). Upregulation of GPER-1 with ICI182,780 enhanced the E(2)-activated MAPK signaling pathway (p < 0.01). ICI182,780 enhanced E(2)-induced proliferation of LC (p < 0.01), while knock down of the GPER-1 gene with GPER-1 small interfering RNA partially inhibited E(2)-induced cell proliferation (p < 0.01). There were no significant differences in PPH3 expression between LCs and normal smooth muscle tissues (p > 0.05). Neither ICI182,780 nor siGPR30 increased mitosis in LCs (p > 0.05). Our results indicate that GPER-1 mediates proliferation of estrogen-induced, LC by activating the MAPK pathway, and, not by promoting mitosis.


Predictive role of thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase expression in colorectal cancer patients receiving adjuvant 5-fluorouracil.
The combined assessment of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) gene expressions in metastatic colorectal cancer has been reported to be able to predict the efficacy of fluoropyrimidine-based chemotherapy. In order to evaluate the prognostic role in the adjuvant setting, we investigated the TS, DPD and TP expression in primary tumors of colorectal cancer patients treated with 5-fluorouracil (5-FU). TS, DPD and TP expression levels were determined by immunohistochemistry in paraffin-embedded primary tumor tissues from 62 patients with Dukes' stage B and C colorectal cancers who underwent surgery and received adjuvant systemic chemotherapy with 5-FU. The median follow-up was 90 months (range 17-127). Dukes' stage C cancer and high TS expression were independent markers of poor prognosis for disease-free survival (DFS; p = 0.0009 and p = 0.007, respectively) and overall survival (OS; p = 0.0005 and p = 0.011, respectively). By multivariate analysis, patients with high DPD expression had significantly shorter DFS (p = 0.007) and OS (p = 0.005) compared to patients with low DPD expression. In the combined analysis of 2 markers, patients with low TS and low DPD had the best outcome in terms of DFS (p = 0.007) and OS (p = 0.03). The analysis of all 3 proteins showed that the patients with low expression of all 3 markers had significantly longer DFS (p = 0.04) and OS (p = 0.01) than patients with a high value of any one of the protein expressions. However, the joint analysis of 3 markers (group with TS-/DPD-/TP-) could not identify a subgroup of patients with a better prognosis compared to the analysis of 2 markers (group with TS-/DPD-). The analysis of Dukes' stage C cancer patients confirmed a significant benefit in terms of DFS and OS (p = 0.001 and p = 0.006, respectively) when all 3 markers had low expression. We also found a positive significant correlation between TS and TP protein expression (p = 0.033). This retrospective investigation suggests that the combined assessment of TS and DPD may be useful to evaluate the prognosis of patients with Dukes' B and C colon carcinoma receiving 5-FU adjuvant chemotherapy. The role of TP as a predictor for 5-FU-based therapy needs further investigations.


Implication of vibration induced nystagmus in Meniere's disease.
The incidence of ipsilesional beating vibration induced nystagmus (VIN) is significantly higher in Meniere's disease (MD) with lower canal paresis (CP) group on caloric test and the intensity of VIN shows significant positive correlation with CP. Considering previous reports showing predominant loss of type II hair cells in MD and discrepancy of the results between caloric test and head thrust test in MD patients, VIN may provide valuable information regarding the functional reservoir of vestibular type II hair cells in MD. Clinical presentation of MD is dynamic and nystagmus changes phase to phase, which is attributed to the recovery process in addition to central compensation after active vertigo attack of MD. VIN has been shown to reflect the side difference of peripheral vestibular excitability and is well correlated with the severity of caloric weakness in vestibular neuritis. Aim of this study was to compare the intensity and the direction of VIN with CP in unilateral MD. 52 patients with unilateral definite MD on AAO-HNS guideline (1995) were included. Auditory and vestibular function tests including caloric test, post-head shaking nystagmus (HSN) and VIN were evaluated during symptom free period and cases with spontaneous nystagmus were excluded. Vibratory stimuli (100 Hz) were applied to either mastoid alternatively. Eye movement was recorded using video nystagmography system. The horizontal component of VIN was compared with HSN and caloric test. 37 patients (71%) showed VIN. VIN to ipsilesional side was in 10 and to contralesional side in 27. In patients with CP over 43% (N =23), 2 beated to ipsilesional side, 17 to contralesional side and 4 showed no VIN. In patients with CP of less than 43% (N =29), 8 beated to ipsilesional side, 10 to contralesional side and 11 showed no VIN (p<0.05). 33 patients (63%) showed HSN and 24 patients of them (72%) showed contralesional nystagmus. The intensity of VIN shows significant positive correlation with the degree of CP on caloric test (Spearman's rho =0.340, p<0.05).


Arginines in the first transmembrane segment promote maturation of a P-glycoprotein processing mutant by hydrogen bond interactions with tyrosines in transmembrane segment 11.
A key goal is to correct defective folding of mutant ATP binding cassette (ABC) transporters, as they cause diseases such as cystic fibrosis. P-glycoprotein (ABCB1) is a useful model system because introduction of an arginine at position 65 of the first transmembrane (TM) segment could repair folding defects. To determine the mechanism of arginine rescue, we first tested the effects of introducing arginines at other positions in TM1 (residues 52-72) of a P-glycoprotein processing mutant (G251V) that is defective in folding and trafficking to the cell surface (20% maturation efficiency). We found that arginines introduced into one face of the TM1 helix (positions 52, 55, 56, 59, 60, 62, 63, 66, and 67) inhibited maturation, whereas arginines on the opposite face of the helix promoted (positions 64, 65, 68, and 71) or had little effect (positions 61, and 69) on maturation. Arginines at positions 61, 64, 65, and 68 appeared to lie close to the drug binding sites as they reduced the apparent affinity for drug substrates such as vinblastine and verapamil. Therefore, arginines that promoted maturation may face an aqueous drug translocation pathway, whereas those that inhibited maturation may face the lipid bilayer. The highest maturation efficiencies (60-85%) were observed with the Arg-65 and Arg-68 mutants. Mutations that removed hydrogen bond acceptors (Y950F/Y950A or Y953F/Y953A) in TM11 predicted to lie close to Arg-65 or Arg-68 inhibited maturation but did not affect maturation of the G251V parent. Therefore, arginine may rescue defective folding by promoting packing of the TM segments through hydrogen bond interactions.


Preclinical evaluation of McN-5707 as a potential antidepressant.
Based on its activity in a variety of tests in vivo and in vitro McN-5707 [trans-6-(2-chlorophenyl)-1,2,3,5,6,10b-hexahydropyrrolo- (2,1-a)isoquinoline] is a novel potential antidepressant. McN-5707 blocked tetrabenazine-induced sedation and ptosis in mice and rats, and potently inhibited the uptake of norepinephrine by synaptosomes from rat hypothalamus (Ki approximately 2 nM), and the uptake of serotonin by synaptosomes from rat cerebral cortex (Ki approximately 10 nM). McN-5707 also inhibited the uptake of dopamine by synaptosomes from rat striatum (Ki approximately 40 nM); however, the stereotypic behavior often caused by dopamine uptake inhibitors was not evident in rats at doses of 300 mg/kg (p.o.) or less. In receptor binding assays, McN-5707 potently inhibited ketanserin binding to serotonin 5-HT2 receptors in synaptic membranes from rat cerebral cortex (apparent Ki approximately 8 nM). In mice, McN-5707 antagonized 5-hydroxytryptophan-induced head twitches. Spiperone binding to dopamine D2 receptors in synaptic membranes from rat striatum was weakly inhibited by McN-5707 (apparent Ki approximately 400 nM), as was the binding of WB4101 to alpha-1 adrenergic receptors (apparent Ki approximately 150 nM). McN-5707 was essentially inactive as an inhibitor of [3H]clonidine binding to alpha-2 adrenergic receptors and of [3H]quinuclidinyl benzilate binding to muscarinic receptors. In experiments with guinea pig ileum, McN-5707 weakly antagonized histamine-induced contractions and exhibited virtually no cholinergic or anticholinergic activity. Our observations indicate McN-5707 possesses attributes of both tricyclic and newer atypical antidepressants because it inhibits the uptake of both norepinephrine and serotonin, and blocks 5-HT2 receptors, but lacks some of the anticholinergic and behavioral properties often associated with them.


Fracture and retrosternal dislocation of the clavicle.
A case of posterior fracture-dislocation of the sternoclavicular joint is described. This injury was successfully treated by open reduction and internal fixation. This rare injury is discussed and an alternative method of treatment is described.


Significant Misuse of Sildenafil in London Nightclubs.
There is anecdotal evidence of misuse of erectile dysfunction medication, particularly to counteract some of the unwanted effects of recreational drugs on erectile function. However, there is little data from the United Kingdom (UK). To evaluate the prevalence of sildenafil misuse in a UK population that has previously been shown to have high recreational drug use. Questionnaire survey. Individuals attending nightclubs catering for the men who have sex with men (MSM) community in South London were asked about lifetime and last year use of recreational drugs and sildenafil. 313 individuals were surveyed over four nights in 2013: 282 (90.1%) were males and 248 (79.2%) were MSM. Last year use of recreational drugs was high: mephedrone (74.1%), cocaine (61.3%), MDMA/Ecstasy (59.2%), GHB/GBL (52.8%), cannabis (51.8%), and ketamine (50%). 136 (49.1%) MSM versus 6 (18.8%) non-MSM clubbers had misused sildenafil in the last year (p < .001). Amongst the MSM clubbers, 232 (93.5%) had heard of sildenafil, 161 (64.9%) reported misuse of sildenafil in their lifetime and 133 (53.6%) had misused sildenafil in the last year. This study demonstrates a high prevalence of sildenafil misuse in a population who are heavy users of recreational drugs; it is not likely that this young population have underlying erectile dysfunction as a reason for legitimate sildenafil use. There is the potential for interaction with other recreational drugs used including cocaine and volatile nitrites. Further work is required in to determine the extent and reason for the misuse.


Priorities and Progress in Diagnostic Research by the Antibacterial Resistance Leadership Group.
The advancement of infectious disease diagnostics, along with studies devoted to infections caused by gram-negative and gram-positive bacteria, is a top scientific priority of the Antibacterial Resistance Leadership Group (ARLG). Diagnostic tests for infectious diseases are rapidly evolving and improving. However, the availability of rapid tests designed to determine antibacterial resistance or susceptibility directly in clinical specimens remains limited, especially for gram-negative organisms. Additionally, the clinical impact of many new tests, including an understanding of how best to use them to inform optimal antibiotic prescribing, remains to be defined. This review summarizes the recent work of the ARLG toward addressing these unmet needs in the diagnostics field and describes future directions for clinical research aimed at curbing the threat of antibiotic-resistant bacterial infections.


Pigment tests evaluated by a model of chromatic discrimination.
Clinical color-vision tests are evaluated within the framework of a model of chromatic discrimination in terms of cone excitation. The motivation for this study was to derive a method for evaluation of test design, test sensitivity, and observer performance. The discrimination model is based on the assumption that chromatic discrimination is mediated in two independent channels, one for short-wavelength cones and one for long- and middle-wavelength cones. Luminance-dependent templates are derived for each channel, and they describe chromatic-discrimination behavior of the young color-normal observer. The templates incorporate receptor- and opponent-level gain controls. We show how the chromaticities of clinical tests can be calculated in cone-excitation units and how discrimination behavior on the tests can be plotted on the templates. The tests include the Farnsworth-Munsell 100-hue, the Farnsworth Panel D-15, the Farnsworth Panel D-15 desaturated, the American Optical Hardy-Rand-Rittler, the Farnsworth F2 plate, the Standard Pseudoisochromatic Plates, Part II, the Ishihara, and the Minimalist tests. Clinical-test data collected on young color-normal observers at different illumination levels show the validity of the techniques.


Promoting coping in children facing pediatric surgery.
Surgery is challenging for children and their families, calling upon them to cope with an invasive procedure, deal with the uncertainty of the surgical outcome, and manage the stress of hospitalization. Contributors to children's distress when facing pediatric surgery include their coping style, interactions with their parents, developmental level, and temperament. A pragmatic approach is outlined that can help surgeons promote successful coping in their patients while at the same time fostering successful working relationships with parents.


A syndrome of transient left ventricular apical wall motion abnormality in the absence of coronary disease: a perspective from the United States.
The syndrome of chest pain associated with characteristic anterior electrocardiographic changes, moderate increases in cardiac enzymes, and a reversible apical wall motion abnormality in the absence of coronary artery disease has been documented in Japan, but has received relatively little attention in other countries. The clinical and echocardiographic data of 12 patients (11 women, mean age 64 +/-14 years) who presented with chest symptoms, electrocardiographic (ECG) changes indicative of an acute anteroapical myocardial infarction, abnormal cardiac enzyme levels and echocardiography showing an apical wall motion abnormality were collected. Coronary angiography was performed in 10 patients. A follow-up echocardiogram was obtained within 2 weeks of the initial diagnosis in most cases. An identifiable, precipitating ("trigger") event could be identified in all 12 individuals. Respiratory distress was present in 7, the death of a relative in 3, in 4 a surgical or medical procedure had been performed, and in 1 a panic disorder was diagnosed. The echocardiograms showed a characteristic wall motion pattern of significant apical dysfunction. All of the patients who underwent coronary arteriography had noncritical coronary artery disease. Follow-up echocardiography showed normalization of the LV dysfunction in all instances. We identified a syndrome of chest pain, dyspnea, ECG and enzyme changes mimicking acute myocardial infarction, similar to the "Takotsubo" syndrome described in Japan. It is likely that the widespread use of echocardiography, coupled with increased recognition of this syndrome, will result in this diagnosis being made more commonly.


Epidermal growth factor content of submandibular glands is increased in rats with experimentally induced gastric lesions.
Occurrence and growth-promoting effect suggest that epidermal growth factor (EGF) is involved in the maintenance of the gastrointestinal mucosa. The aim of this study was to ascertain whether rats with gastric lesions, induced by cold-water stress, ethanol, or indomethacin, have altered EGF levels in their gastrointestinal tract compared with controls. For this purpose we established a solid-phase enzyme immunoassay and measured the amount of immunoreactive EGF (IR-EGF) in extracts of the submandibular gland, stomach, duodenum, jejunum, ileum, and colon. In the submandibular glands of control rats the IR-EGF content was 100-400 times higher than in the gastrointestinal tract. In animals with experimentally induced ulcer the IR-EGF content was increased in the submandibular glands (1480 versus 423 ng/g), duodenum (11.4 versus 5.8 ng/g), and colon (4.1 versus 1 ng/g), whereas no change was observed in the stomach and jejunum. When the formation of lesions was prevented by omeprazole (stress) or prostaglandin E2 (ethanol and indomethacin), the IR-EGF increase in submandibular glands and duodenum was abolished. This indicates that mechanisms regulating the synthesis and secretion of submandibular EGF might be of importance in the development of gastric and duodenal ulcers.


Association of p16 as Prognostic Factors for Oropharyngeal Cancer: Evaluation of p16 in 1470 Patients for a 16 Year Study in Northeast China.
Human papillomavirus (HPV) is an etiological risk factor for oropharyngeal squamous cell carcinomas (OPSCC). Our study investigates the prevalence, prognostic, and clinicopathologic features of HPV-related oropharyngeal cancer in Northeast China and elucidates the involvement of p16 in the tumorigenesis and progression of OPSCC. Specimens from 1470 OPSCC patients collected from 2000 to 2016 were analyzed using the status of HPV by polymerase chain reaction (PCR) and p16 immunohistochemistry. Overexpression of p16 was observed in 81 (5.51%) of the 1470 cases, and HPV positive was present in 78 cases (5.31%) of the 1470 cases. HPV positive and p16 overexpression have a good concordance. However, we found that the etiological fraction of HPV in cancers of the OPSCCs was obviously lower in Northeast China than other cohorts previously reported. Interestingly, nearly 89% of patients with p16 expression were smokers, and nearly 70% of patients with p16 expression had a history of alcohol. Our study also demonstrates that p16 expression is significantly associated with early stage primary OPSCCs and the patients with p16 expression tend to show better survival following surgery and radiotherapy.


Clustering of fMRI data: the elusive optimal number of clusters.
Model-free methods are widely used for the processing of brain fMRI data collected under natural stimulations, sleep, or rest. Among them is the popular fuzzy c-mean algorithm, commonly combined with cluster validity (CV) indices to identify the 'true' number of clusters (components), in an unsupervised way. CV indices may however reveal different optimal c-partitions for the same fMRI data, and their effectiveness can be hindered by the high data dimensionality, the limited signal-to-noise ratio, the small proportion of relevant voxels, and the presence of artefacts or outliers. Here, the author investigated the behaviour of seven robust CV indices. A new CV index that incorporates both compactness and separation measures is also introduced. Using both artificial and real fMRI data, the findings highlight the importance of looking at the behavior of different compactness and separation measures, defined here as building blocks of CV indices, to depict a full description of the data structure, in particular when no agreement is found between CV indices. Overall, for fMRI, it makes sense to relax the assumption that only one unique c-partition exists, and appreciate that different c-partitions (with different optimal numbers of clusters) can be useful explanations of the data, given the hierarchical organization of many brain networks.


The dynamic relationship between insight and suicidal behavior in first episode psychosis patients over 3-year follow-up.
Studies have established the high risk of suicide in first episode psychosis (FEP). Between 15% and 26% of FEP patients attempt suicide at least once before their first contact with psychiatric services and 2-5% die from suicide. Also, many patients with schizophrenia spectrum disorders lack insight into having a mental disorder. However, the relationship between insight changes and suicidal behavior in FEP remains poorly understood. In the present study information about suicidal behavior over a 3 years period was available on a cohort of 397 FEP patients, of whom 270 were assessed in the three dimensions of insight (into mental illness, the need for treatment, and the social consequences) at baseline, 1 and 3 years after treatment initiation. Survival analyses examined time to suicidal behavior in relation to (i) insight at baseline, (ii) the closest insight measure to the suicide attempt, and (iii) changes in insight during the follow-up. No associations were found between baseline insight dimensions and time to suicidal behavior. However, poor insight at the evaluation closest to the suicide attempt was associated with an increased risk of suicide. Stability of insight did not affect the risk of suicidal behavior, while changes in either direction were linked with an increased risk of suicidal behavior, particularly worsening insight. Insight in psychosis is a dynamic concept and we demonstrated the relationship between insight and suicide risk to be equally dynamic. Poor insight seems to increase the risk, especially when insight levels change. Repeated insight assessment to detect change from early psychosis may play a role in suicide prevention.