[The late results of observing and treating patients with histiocytosis X and involvement of the jaw bones].
Eighty-one patients with histiocytosis X involving the jaw bones were followed up for 30 years; the patients presented with involvement of the lungs, skin, mucosa, other bones of the skeleton, and diabetes insipidus signs. In 58 of the 81 patients eosinophilic granuloma eventuated in a generalized process: chronic xanthomatosis or Hand-Schüller-Christian's disease. This fact permits a conclusion that eosinophilic granuloma is an initial stage of the same systemic disease, histiocytosis X, and that subdivision of histiocytosis X into 3 forms, accepted in literature, is undesirable, for it erroneously presents the essence of the process. Therapeutic recommendations are given.


LAG3 and Its Ligands Show Increased Expression in High-Risk Uveal Melanoma.
Uveal melanoma (UM) is a rare ocular malignancy which originates in the uveal tract, and often gives rise to metastases. Potential targets for immune checkpoint inhibition are lymphocyte-activation gene 3 (LAG3) and its ligands. We set out to analyse the distribution of these molecules in UM. The expression of mRNA was determined using an Illumina array in 64 primary UM from Leiden. The T lymphocyte fraction was determined by digital droplet PCR. In a second cohort of 15 cases from Leiden, mRNA expression was studied by Fluidigm qPCR, while a third cohort consisted of 80 UM from TCGA. In the first Leiden cohort, LAG3 expression was associated with the presence of epithelioid cells (p = 0.002), monosomy of chromosome 3 (p = 0.004), and loss of BAP1 staining (p = 0.001). In this Leiden cohort as well as in the TCGA cohort, LAG3 expression correlated positively with the expression of its ligands: LSECtin, Galectin-3, and the HLA class II molecules HLA-DR, HLA-DQ, and HLA-DP (all p < 0.001). Furthermore, ligands Galectin-3 and HLA class II were increased in monosomy 3 tumours and the expression of LAG3 correlated with the presence of an inflammatory phenotype (T cell fraction, macrophages, HLA-A and HLA-B expression: all p < 0.001). High expression levels of LAG3 (p = 0.01), Galectin-3 (p = 0.001), HLA-DRA1 (p = 0.002), HLA-DQA1 (p = 0.04), HLA-DQB2 (p = 0.03), and HLA-DPA1 (p = 0.007) were associated with bad survival. We conclude that expression of the LAG ligands Galectin-3 and HLA class II strongly correlates with LAG3 expression and all are increased in UM with Monosomy 3/BAP1 loss. The distribution suggests a potential benefit of monoclonal antibodies against LAG3 or Galectin-3 as adjuvant treatment in patients with high-risk UM.


The incidence of oropharyngeal dysphagia in infants with GERD-like symptoms.
Symptoms of infantile gastroesophageal reflux disease (GERD) may overlap with oropharyngeal dysphagia, but the evaluation and treatment of these conditions vary greatly. In this investigation, the incidence of oropharyngeal dysphagia in infants with GERD-like symptoms is determined. A retrospective chart review was performed on infants referred to a pediatric gastroenterology clinic for GERD-like symptoms. A feeding screen was performed in all infants. Standardized bedside swallow evaluation and modified barium swallow (MBS) studies were then performed when clinically indicated. A similarly aged cohort of normal participants also underwent a standard bedside swallow evaluation for group comparison. Study population included 67 infants. A swallow evaluation was recommended in 39 of 67 infants with abnormalities noted in all. Swallowing abnormalities were more frequent and clustered in infants with GERD-like symptoms vs controls. MBS was abnormal in 16 of 17 qualifying infants. Characteristics of at-risk infants included extreme prematurity, developmental delay, or symptoms refractory to antireflux medications. Oropharyngeal dysphagia is prominent in infants with GERD-like symptoms.


Interleukin-1beta but not tumor necrosis factor is involved in West Nile virus-induced Langerhans cell migration from the skin in C57BL/6 mice.
Langerhans cells are bone marrow-derived epidermal dendritic cells. They migrate out of the epidermis into the lymphatics and travel to the draining lymph nodes where they are responsible for the activation of T cells in the primary immune response. Tumor necrosis factor and interleukin-1beta, have previously been shown to be responsible for Langerhans cell migration in response to contact sensitizers in BALB/C mice; however, which cytokines are responsible for mediating Langerhans cell migration in response to a replicating cutaneously acquired virus such as the West Nile Virus, are not known. We have devised a method for identifying Langerhans cells in the draining lymph nodes using E-cadherin labeling and flow cytometry. We infected tumor necrosis factor-deficient gene knockout mice (tumor necrosis factor-/-) intradermally with West Nile Virus and found that levels of Langerhans cell emigration and accumulation in the draining lymph nodes were similar to wild-type C57BL/6 mice. This was borne out by the finding that high levels of systemic neutralizing anti-tumor necrosis factor antibody failed to inhibit the migration of Langerhans cells from the epidermis and their accumulation in the draining lymph nodes in wild-type C57BL/6 mice. In West Nile Virus-infected, tumor necrosis factor-/- mice treated with systemic neutralizing anti-interleukin-1beta antibodies, however, migration of Langerhans cells from the epidermis and their accumulation in the draining lymph nodes were significantly inhibited compared with control antibody-treated, infected animals. The results indicate that Langerhans cell migration, accumulation in the draining lymph nodes and the initiation of lymph node shut-down in response to a cutaneous West Nile Virus infection is dependent on interleukin-1beta and can occur in the absence of tumor necrosis factor.


Clotrimazole vs haloprogin treatment of tinea cruris.
A study to compare the efficacy of clotrimazole 1% solution with that of haloprogin 1% solution for the treatment of tinea cruris was conducted among military personnel on active duty in a hot, humid climate. Eighty patients with documented dermatophyte infections were treated with the topical antifungal agents. Analysis of the response to treatment for 14 days demonstrated that clotrimazole was significantly more effective clinically and mycologically than haloprogin. With no further treatment, significantly more patients treated with clotrimazole remained free of the disease four weeks later.


Revisiting the Management of Pediatric Kidney Transplants, A Multicenter Analysis
The newest Kidney Disease Improving Global Outcomes (KDIGO) guideline recommendations were investigated mainly for the care of adult kidney transplant recipients, but no guideline exists for the management of pediatric transplant recipients. This review provides update recommendations in the management of pediatric kidney transplantation. Four electronic databases, PubMed, EMBASE, Google Scholar, and Web of Science were searched systematically for the last two decades, using Mesh terms in English language. The Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach was used for grading the quality of the overall evidence and the strength of recommendations for each outcome across the studies. The overall quality of evidence categorized as high (A), moderate (B), low (C), or poor (D). The strength of a recommendation was determined as level 1 (recommended) or level 2 (suggested). The ungraded statements were determined on the basis of common sense to provide general advice. Of the 317 citations which were screened for the evidence review, 62 were included in data extraction. The included studies were randomized controlled trials, prospective cohorts and cross-sectional, descriptive, and review studies. Of the 115 statements, 56 (48.6%) were graded 1 (we recommend), 34 (29.5%) were graded 2 (we suggest), and 25 (21.7%) were ungraded statements. Altogether, only 22 (19.1%) of recommendations reached the "A" or "B" levels of quality of evidence. The pediatric kidney transplant recipients are different from adult recipients regarding the primary kidney diseases, surgical techniques, drug metabolism, adherence to medications, growth and neurocognitive development and immunization needs prior to transplantation. DOI: 10.52547/ijkd.7179.


First Report of Muskmelon Fruit Rot Caused by Fusarium nanum in China.
Muskmelon (Cucumis melo L.) is one of the most widely cultivated and economically important fruit crops in the world. However, many pathogens can cause decay of muskmelon fruit, including Fusarium asiaticum, F. equiseti, F. incarnatum and F. lateritium (Hao et al. 2021; Wang et al. 2019). Fusarium spp. are the most important pathogens affecting muskmelon fruit yield and quality (Wang et al. 2011). In August 2020, fruit rot symptoms were observed on ripening muskmelons (cv. Tianbao) in several fields in Jiyang District, Jinan City of Shandong Province, China. The incidences of infected muskmelon ranged from 15% to 30% and caused an average 20% yield loss. Symptoms appeared as pale brown, water-soaked lesions that were irregular in shape, with the lesion sizes ranging from a small spot (1 to 2 cm) to decay of the entire fruit. The core and surface of infected fruit were colonized and covered with white mycelia. Two infected muskmelons were collected from two fields, 7 km apart. Tissues removed from inside the infected fruit were surface disinfected with 75% ethanol for 30 s, and cultured on potato dextrose agar (PDA) at 25°C in the dark for 5 days. Four purified cultures were obtained using the single spore method. On carnation leaf agar (CLA), macroconidia were 1 to 5 septate, falcate, with a pronounced dorsiventral curvature with blunt to papillate apical cell, and barely to distinctly notched basal cell, measuring 12 to 35 × 3.5 to 6 μm. Microconidia and chlamydospores were not observed. These morphological characteristics were consistent with the description of Fusarium sp. Because these isolates had similar morphology, two representative isolates (XP9 and XP10) were selected for multilocus phylogenetic analyses. DNA was extracted from the representative isolates using a CTAB method. Nucleotide sequences of the internal transcribed spacers (ITS) (White et al. 1990), calmodulin (CAM), RNA polymerase II second largest subunit (RPB2), translation elongation factor 1-α gene (TEF1) (Xia et al. 2019) were amplified using specific primers, sequenced, and deposited in GenBank (ITS: MW391507 and MW391508, CAM: MW392787 and MW392788, RPB2: MW392795 and MW392796, TEF1: MW392791 and MW392792). The Fusarium MLST database pairwise alignment of ITS (546 bp), CAM (628 bp), RPB2 (902 bp) and TEF1 (718 bp) sequences from isolate XP9 showed 99.63%, 99.33%, 100.00% and 99.71% similarity with the corresponding sequences (GQ505685, GQ505508, GQ505774 and GQ505596) of the reference strain of F. nanum (NRRL 22244), respectively. The overlap of ITS, CAM, RPB2 and TEF1 sequences from XP9 and NRRL 22244 were 100.00%, 95.06%, 97.45% and 94.99%, respectively. Alignments of a combined dataset of ITS, CAM, RPB2 and TEF1 were made using MAFFT v. 7, and phylogenetic analyses were conducted in MEGA v. 7.0 using the maximum likelihood method. The muskmelon isolates (XP9 and XP10) clustered together with the F. nanum reference strain CGMCC3.19498 and NRRL 22244 (100% bootstrap) (Wang et al., 2019). To perform a pathogenicity test, 10 μl of conidial suspensions (1 × 106 conidia/ml) were injected into each muskmelon fruit using a syringe, and the control fruit was inoculated with 10 μl of sterile distilled water. There were ten replicated fruits for each treatment. The test was repeated three times. After 7 days at 25°C, the interior of the inoculated muskmelons begun to rot, and the rot lesion expanded from the core towards the surface of the fruit, then white mycelia were produced on the surface. Ten isolations were re-isolated from the infected tissues and identified by morphological and phylogenetic analyses and confirmed to fulfill Koch's postulates. No symptoms were observed on the control muskmelons. To our knowledge, this is the first report of muskmelon fruit rot caused by F. nanum in China. Considering the economic value of the muskmelon crop, correct identification can help farmers select appropriate field management measures for control of this disease.


Identification of AHK2- and AHK3-like cytokinin receptors in Brassica napus reveals two subfamilies of AHK2 orthologues.
Cytokinin (CK) signalling is known to play key roles in the regulation of plant growth and development, crop yields, and tolerance to both abiotic stress and pathogen defences, but the mechanisms involved are poorly characterized in dicotyledonous crops. Here the identification and functional characterization of sensor histidine kinases homologous to Arabidopsis CK receptors AHK2 and AHK3 in winter oilseed rape are presented. Five CHASE-containing His kinases were identified in Brassica napus var. Tapidor (BnCHK1-BnCHK5) by heterologous hybridization of its genomic library with gene-specific probes from Arabidopsis. The identified bacterial artificial chromosome (BAC) clones were fingerprinted and representative clones in five distinct groups were sequenced. Using a bioinformatic approach and cDNA cloning, the precise gene and putative protein domain structures were determined. Based on phylogenetic analysis, four AHK2 (BnCHK1-BnCHK4) homologues and one AHK3 (BnCHK5) homologue were defined. It is further suggested that BnCHK1 and BnCHK3, and BnCHK5 are orthologues of AHK2 and AHK3, originally from the B. rapa A genome, respectively. BnCHK1, BnCHK3, and BnCHK5 displayed high affinity for trans-zeatin (1-3nM) in a live-cell competitive receptor assay, but not with other plant hormones (indole acetic acid, GA3, and abscisic acid), confirming the prediction that they are genuine CK receptors. It is shown that BnCHK1 and BnCHK3, and BnCHK5 display distinct preferences for various CK bases and metabolites, characteristic of their AHK counterparts, AHK2 and AHK3, respectively. Interestingly, the AHK2 homologues could be divided into two subfamilies (BnCHK1/BnCK2 and BnCHK3/BnCHK4) that differ in putative transmembrane domain topology and CK binding specificity, thus implying potential functional divergence.


Optimizing outcomes for neonatal ARPKD.
A retrospective analysis was conducted on 10 consecutive cases of neonatal ARPKD, 9 of whom received kidney transplants (KT). All were diagnosed antenatally (n = 6) or at birth. In the first month of life 70% required ventilatory support. Pre-emptive bilateral nephrectomy and peritoneal dialysis (PD) catheter placement were performed in 9 at a mean age of 7.8 +/- 11.9 months. The indications for nephrectomy were massive kidneys, resulting in suboptimal nutrition and respiratory compromise. All patients received assisted enteral nutrition, with significant increase in mean tolerated feeds following nephrectomy (p < 0.05), with increase in mean normalized weight and height (0.92 and 1.2 delta SDS respectively), by one year post-transplantation. KT was performed at a mean age and weight of 2.5 +/- 1.4 years and 13.3 +/- 6.1 kg. The mean creatinine clearance at one year post-KT was 91.3 +/- 38.1 mls/min/1.73 m(2), with a projected graft life expectancy of 18.4 years. Patient survival was 89% and death censored graft survival was 100%, at a mean follow-up of 6.1 +/- 4.5 years post-transplant. Six patients demonstrated evidence of hepatic fibrosis, one of which required liver transplantation. In patients with massive kidneys from ARPKD, pre-emptive bilateral nephrectomy, supportive PD and early aggressive nutrition, can minimize early infant mortality, so that subsequent KT can be performed with excellent patient and graft survival.


Six mechanisms behind carer wellbeing effects: A qualitative study of healthcare delivery.
Health and care services for patients may improve or harm the wellbeing of their family carers. Formal consideration of these effects (also known as spillovers) in decision-making is advocated, but, to date, little is known about how they occur. This paper presents the first empirical study to determine the mechanisms by which health and care services affect family carers' wellbeing. The study focused on three major health conditions: dementia, stroke, and mental health. Focus groups and interviews were conducted with 49 purposefully sampled care professionals and family carers in the UK between December 2016 and September 2017. Transcripts were coded and analysed thematically, using descriptive accounts and an explanatory account. The analysis generated six over-arching mechanisms by which health and care services affect family carers' wellbeing, through: (i) information (degree to which service delivery informs and trains family carers); (ii) management of care (shifts of responsibility for care between formal and family sectors); (iii) patient outcomes (services changing patient outcomes); (iv) alienation (feelings of alienation or inclusion created by service delivery); (v) compliance (barriers to patients complying and engaging with services); and (vi) timing or location (changes in the timing or location of services). Each mechanism was associated with sub-themes relating to both positive and negative spillovers on the family carers. The six mechanisms can be summarised with the mnemonic 'IMPACT'. The IMPACT mechanisms may be useful in designing and evaluating services to optimise the wellbeing of carers as well as patients.


Prevalence, morphologic features and proliferation indices of breast carcinoma molecular classes using immunohistochemical surrogate markers.
There is dearth of studies that provide a practical working formulation of breast cancer gene expression analysis for the surgical pathologist. ER, PR, HER2 were used as surrogate markers to classify 205 breast carcinomas into molecular classes. Ki-67 labeling index was calculated using an image analysis system. The data was analyzed for molecular class prevalence, and inter-relationships amongst morphologic parameters, Ki-67 index, and molecular classes. Of the 205 tumors, 113 (55%) were classified as luminal A (strong ER+, HER2 negative), 34 (17%) as luminal B (weak to moderate ER+, HER2 negative), 32 (15%) as triple negative (negative for ER/PR and HER2), 8 (4%) as ERBB2 (negative for ER/PR but HER2+), 10 (5%) as luminal A-HER2 hybrid (strong ER+ and HER2+), and 8 (4%) as luminal B-HER2 hybrid (weak to moderate ER+ and HER2+). The average Ki-67 index was lowest in luminal A (15.8%), intermediate for ERBB2 (27.8%) and highest for triple negative tumors (>50%). Multivariate logistic regression analyses found the following associations: ERBB2 tumors with apocrine differentiation (p=0.0031); Triple negative tumors with high Ki-67 index (p<0.0001) and CK5 positivity (p<0.0001); HER2 negative-low receptor positive tumors (luminal B) with increased lymph node involvement (p=0.0141). The immunohistologic criteria were validated on a different set of 359 cases treated with neoadjuvant chemotherapy, which showed a pathologic complete response predominantly in ERBB2 and triple negative tumors. Immunohistochemistry is a reliable surrogate tool to classify breast carcinoma according to the gene expression profile classification.


Congenital mixed giant hiatal hernia in a four-month-old infant.
Congenital hiatal hernia is a rare pathology, presenting at 28 months of age on average. Paraesophageal/mixed hernias cause recurrent respiratory infections, vomiting, anemia, and growth failure. Four-month-old infant, with irritability since birth and partial feeding intolerance in the last 24 hours. A partial intrathoracic stomach was evidenced in the esophago-gastro-duodenal contrast study. A thoraco-abdominal CT scan was carried out, with giant mixed hiatal hernia, right posterolateral diaphragmatic hernia, and congenital short esophagus being considered as potential diagnoses. A giant mixed hiatal hernia was noted during surgery. Laparoscopic herniorrhaphy and Nissen fundoplication were performed. In the pediatric population, Bochdalek's hernia and Morgagni's hernia are the most frequent congenital diaphragmatic hernias. Hiatal hernia is rare and causes gastrointestinal symptoms more frequently. Surgery is the treatment of choice, with the objective of preventing or minimizing these symptoms as well as gastric volvulus.


Across the board: Licheng Sun.
In this series of articles the board members of ChemSusChem discuss recent research articles that they consider of exceptional quality and importance for sustainability. In this entry, Prof. Licheng Sun discusses how solar fuel production (such as water splitting) can be made more efficient and economic on an industrial scale. Recommended is the work by Prof. Xuping Sun, who use non-noble metal-phosphorus-based nanostructures as efficient electrocatalysts for hydrogen generation from water.


Combinatorial patterns of graded RhoA activation and uniform F-actin depletion promote tissue curvature.
During development, gene expression regulates cell mechanics and shape to sculpt tissues. Epithelial folding proceeds through distinct cell shape changes that occur simultaneously in different regions of a tissue. Here, using quantitative imaging in Drosophila melanogaster, we investigate how patterned cell shape changes promote tissue bending during early embryogenesis. We find that the transcription factors Twist and Snail combinatorially regulate a multicellular pattern of lateral F-actin density that differs from the previously described Myosin-2 gradient. This F-actin pattern correlates with whether cells apically constrict, stretch or maintain their shape. We show that the Myosin-2 gradient and F-actin depletion do not depend on force transmission, suggesting that transcriptional activity is required to create these patterns. The Myosin-2 gradient width results from a gradient in RhoA activation that is refined through the balance between RhoGEF2 and the RhoGAP C-GAP. Our experimental results and simulations of a 3D elastic shell model show that tuning gradient width regulates tissue curvature.


The ApaH-like phosphatase TbALPH1 is the major mRNA decapping enzyme of trypanosomes.
5'-3' decay is the major mRNA decay pathway in many eukaryotes, including trypanosomes. After deadenylation, mRNAs are decapped by the nudix hydrolase DCP2 of the decapping complex and finally degraded by the 5'-3' exoribonuclease. Uniquely, trypanosomes lack homologues to all subunits of the decapping complex, while deadenylation and 5'-3' degradation are conserved. Here, I show that the parasites use an ApaH-like phosphatase (ALPH1) as their major mRNA decapping enzyme. The protein was recently identified as a novel trypanosome stress granule protein and as involved in mRNA binding. A fraction of ALPH1 co-localises exclusively with the trypanosome 5'-3' exoribonuclease XRNA to a special granule at the posterior pole of the cell, indicating a connection between the two enzymes. RNAi depletion of ALPH1 is lethal and causes a massive increase in total mRNAs that are deadenylated, but have not yet started 5'-3' decay. These data suggest that ALPH1 acts downstream of deadenylation and upstream of mRNA degradation, consistent with a function in mRNA decapping. In vitro experiments show that recombinant, N-terminally truncated ALHP1 protein, but not a catalytically inactive mutant, sensitises the capped trypanosome spliced leader RNA to yeast Xrn1, but only if an RNA 5' polyphosphatase is included. This indicates that the decapping mechanism of ALPH1 differs from the decapping mechanism of Dcp2 by leaving more than one phosphate group at the mRNA's 5' end. This is the first reported function of a eukaryotic ApaH-like phosphatase, a bacterial-derived class of enzymes present in all phylogenetic super-groups of the eukaryotic kingdom. The substrates of eukaryotic ApaH-like phosphatases are unknown. However, the substrate of the related bacterial enzyme ApaH, diadenosine tetraphosphate, is highly reminiscent of a eukaryotic mRNA cap.


The mitochondrial genome of the thermal dimorphic fungus Penicillium marneffei is more closely related to those of molds than yeasts.
We report the complete sequence of the mitochondrial genome of Penicillium marneffei, the first complete mitochondrial DNA sequence of a thermal dimorphic fungus. This 35 kb mitochondrial genome contains the genes encoding ATP synthase subunits 6, 8, and 9 (atp6, atp8, and atp9), cytochrome oxidase subunits I, II, and III (cox1, cox2, and cox3), apocytochrome b (cob), reduced nicotinamide adenine dinucleotide ubiquinone oxireductase subunits (nad1, nad2, nad3, nad4, nad4L, nad5, and nad6), ribosomal protein of the small ribosomal subunit (rps), 28 tRNAs, and small and large ribosomal RNAs. Analysis of gene contents, gene orders, and gene sequences revealed that the mitochondrial genome of P. marneffei is more closely related to those of molds than yeasts.


A new combination of mutated loxPs in a vector for construction of phage antibody libraries.
In the construction of large antibody libraries by in vivo recombination, two non-homogeneous loxP sites are required for the exchange of V genes between phagemids to create many new VH-VL combinations. The mutated loxP511 was designed not to recombine with the wild-type loxP (loxPwt) in early studies and a combination of the two has been used to construct antibody libraries. But recent reports have shown that recombination occurs between loxPwt and loxP511. This suggests that the combinational use of loxP511 and loxPwt might lead to the loss of the V gene diversity of antibody libraries. Therefore, it is necessary to find a new combination of loxPs to avoid the excision recombination in the antibody library. In this study, we found that the excision recombination between loxP511 and loxP2272, another mutated loxP sequence, was undetectable within one phagemid, while the excision recombination between loxP511 and loxPwt occurred at a frequency of 40%, higher than that reported previously. Furthermore, the in vivo recombination of different phagemids with loxP511 and loxP2272 showed that the V gene exchange was efficiently mediated to produce new VH-VL combinations. It was concluded that the loxP511 and loxP2272 combination was more favorable for reducing the excision recombination and constructing large phage antibody libraries with high diversity.


Patient Perceptions of Illness Identity in Cancer Clinical Trial Decision-Making.
When patients are diagnosed with cancer, they begin to negotiate their illness identity in relation to their past and future selves, their relationships, and their group memberships. Thus, how patients view their cancer in relation to their other identities may affect how and why they make particular decisions about treatment options. Using the Communication Theory of Identity (CTI), the current study explores: (1) how and why illness identity is framed across identity layers in relation to one particular cancer treatment: participation in a cancer clinical trial (CT); and (2) how and why patients experience identity conflicts while making their treatment decisions. Semi-structured, in-depth interviews were analyzed for 46 cancer patients who were offered a CT. Results of a grounded theory analysis indicated that patients expressed separate identity frames (e.g., personal, relational, and communal), aligned identity frames (e.g., personal and communal), and identity conflicts (e.g., personal-personal). This study theoretically shows how and why patient illness identity relates to cancer treatment decision-making as well as how and why patients relate (and conflict) with the cancer communal identity frame. Practical implications include how healthcare providers and family members can support patient decision-making through awareness of and accommodating to identity shifts.


A comparison of the suppressive effects of testosterone and a potent new gonadotropin-releasing hormone antagonist on gonadotropin and inhibin levels in normal men.
GnRH antagonists have been developed in large part because of their potential use as contraceptive agents, particularly in men. Specifically, it was hoped that GnRH antagonists combined with testosterone (T) would be a more effective contraceptive regimen than T alone. We compared the suppressive effects of a potent GnRH antagonist, Na1-Glu [AcD2NaL1,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA),+ ++DAla10-GnRH], and of T together and separately on serum and urinary gonadotropin and serum inhibin levels in normal men. Ten-day courses of Nal-Glu (75 micrograms/kg; Nal-Glu alone), 200 mg testosterone enanthate, im, on days 0 and 7 (T alone), and the combination (Na1-Glu + T) were given to nine men. Serum gonadotropin and inhibin concentrations decreased after 1-2 days of Na1-Glu administration, while gonadotropin suppression occurred more slowly after T alone. Serum T fell to 30% of baseline values during Na1-Glu administration. The combination of Na1-Glu + T was more effective in suppressing serum LH, FSH, and inhibin than was either Na1-Glu alone or T alone. All hormone levels returned to baseline levels within 2.5 weeks after the end of the three regimens. We conclude that the Na1-Glu GnRH antagonist effectively inhibits gonadotropin, inhibin, and sex steroid secretion when given daily for 10 days and that the administration of Nal-Glu + T results in more complete gonadotropin and gonadal suppression than that produced by either agent given alone. These results encourage further investigation of the combination of a GnRH antagonist and T as a male contraceptive regimen and of the antagonist alone as a treatment for hormone-dependent neoplasia.


Tick-borne relapsing fever Borreliosis, a major public health problem overlooked in Senegal.
Tick-borne relapsing fever (TBRF) is the most common vector-borne bacterial disease in humans in West Africa. It is frequently clinically confused with malaria. Our study aims to determine, on a micro-geographic scale, the conditions for the maintenance and spread of TBRF in the Niakhar district of Senegal. We conducted clinical, entomological and animal reservoir investigations. Field surveys were carried out in order to investigate the presence of Ornithodoros sonrai vector ticks and to detect Borrelia spp. by qPCR using the 16S rRNA and glpQ genes, respectively. Micromammal trapping series were carried out inside homes and Borrelia infection was detected using brain tissue qPCR. Capillary blood samples from febrile patients were also tested for Borrelia using qPCR. More than 97% (40/41) of the villages surveyed were infested with O. sonrai ticks. The prevalence of Borrelia spp. infections in ticks was 13% (116/910), and over 73% (85/116) were positively confirmed as being Borrelia crocidurae. Borreliosis cases accounted for 12% (94/800) of episodes of fever and all age groups were infected, with children and young people between the ages of 8-14 and 22-28 being the most infected by the disease (16% and 18.4%). TBRF cases occurred in all seasons, with a peak in August. In two species of small rodents that were found to be infected (Arvicanthis niloticus, Mus musculus), the proportion of Borrelia infection was 17.5% (10/57), and the highest prevalence of infection (40.9%, 9/22) was observed in A. niloticus. Our study indicates that TBRF is an endemic disease in the Niakhar district, where children and young people are the most infected. Arvicanthis niloticus and O. sonrai ticks are massively present and appear to be the main epidemiological reservoirs causing its extensive spread to humans.


Serum antibody responses to periodontal microbiota in chronic and aggressive periodontitis: a postulate revisited.
The authors revisited the 1999 International Workshop postulate of robust serum antibody responses to infecting agents in localized aggressive periodontitis (LAgP) and weak responses in generalized aggressive periodontitis (GAgP). Antibody responses were further examined in localized and generalized chronic periodontitis (LCP and GCP). The study includes 119 patients (60 males and 59 females, aged 11 to 76 years), 18 with LAgP, 37 with GAgP, 37 with LCP, and 27 with GCP. Multiple subgingival plaque samples/patient (1,057 in total) were analyzed with respect to 11 bacterial species using checkerboard DNA-DNA hybridizations, and serum immunoglobulin (Ig)G levels were measured against the same bacteria using checkerboard immunoblotting. Further, infection ratios (antibody level over the average bacterial colonization by the homologous species) were computed for each patient. Comparisons of bacterial colonization, serum IgG levels, and infection ratios were made across the diagnostic categories using multivariable linear regression models adjusting for age and race/ethnicity. There were no statistically significant differences in serum IgG levels to Aggregatibacter actinomycetemcomitans among the four diagnostic categories. IgG levels to several species, including Porphyromonas gingivalis, Treponema denticola, and Campylobacter rectus, were highest in patients with GAgP and significantly different from LCP and GCP, but not from LAgP. Comparisons based on infection ratios showed no statistically significant differences for any species between GAgP and LAgP. This study provides evidence against the 1999 Workshop's postulate of weak serum antibody responses in patients with GAgP and shows that serum IgG responses in GAgP are comparable to those in LAgP, but higher than in GCP or LCP for several species.


Geoff Cloke at 65: a pioneer in organometallic chemistry.
Professor Geoff Cloke FRS celebrates his 65th birthday in 2018. In a career spanning four decades, his research endeavours have accounted for some of the most innovative synthetic chemistry of the modern era, with his many publications describing truly exceptional compounds and experimental methods that portray a unique chemical imagination. In addition to his scientific accomplishments, Cloke can be particularly proud of his successful mentoring, a level of dedication that propelled many students and post-docs on to become research leaders in their own right. In compiling this collection of some of his research articles, a small cross-section of his friends, colleagues and collaborators, wish to pay tribute to his modesty, compassion and generous personality.


Carbon nanotubes induce oxidative DNA damage in RAW 264.7 cells.
The induction of DNA and chromosome damage following in vitro exposure to carbon nanotubes (CNT) was assessed on the murine macrophage cell line RAW 264.7 by means of the micronucleus (MN) and the comet assays. Exposures to two CNT preparations (single-walled CNT (SWCNT > 90%) and multiwalled CNT (MWCNT > 90%) were performed in increasing mass concentrations (0.01-100 microg/ml). The frequency of micronuclei was significantly increased in cells treated with SWCNT (at doses above 0.1 microg/ml), whereas MWCNT had the same effect at higher concentrations (1 microg/ml) (P < 0.05). The results of the comet assay revealed that the effects of treatment with SWCNT were detectable at all concentrations tested (1-100 microg/ml); oxidized purines increased significantly, whereas pyrimidines showed a significant increase (P < 0.001) only at the highest concentration (100 microg/ml). In cells treated with MWCNT, an increase in DNA migration due to the oxidative damage to purines was observed at a concentration of 1 and 10 microg/ml, whereas pyrimidines showed a significant increase only at the highest mass concentration tested. However, both SWCNT and MWCNT induced a statistically significant cytotoxic effect at the highest concentrations tested (P < 0.001). These findings suggest that both the MN and comet assays can reliably detect small amount of damaged DNA at both chromosome and nuclear levels in RAW 264.7 cells. Moreover, the modified version of the comet assay allows the specific detection of the induction of oxidative damage to DNA, which may be the underlying mechanism involved in the CNT-associated genotoxicity.


[Introduction to and general remarks on molecular imaging].
Molecular imaging is a visualization of quantity and dynamics of molecules to understand the process of gene regulation and physiological function of the proteins in living tissue or cells. Examples of the research include the development and application of fluorescent proteins, quantum dots, nanoparticles for optical imaging, micro bubbles for ultrasound, ferromagnetic compounds for MRI and radiopharmaceuticals for positron emission tomography (PET). PET is most promising in this field, because of its high sensitivity of the measurement and easy applicability to humans. In this general remark, the topics will be concentrated on molecular imaging with PET for the diagnosis of Alzheimer's disease (AD) in early stage. 11C-MP4P (N-methlpiperidyl-4-propionate), is a probe for the measurement of acetylcholine esterase (AchE) activity in the human brain by PET. The AchE activities (k3) in early onset AD measured with PET was low in hippocampus, amygdale and wide spread neocortex including parietal and temporal cortex compared to those in age-matched control. The results indicated that the decrease of AchE activities is preceded by the decrease of blood flow. One of the topics in this research field is an imaging of aggregated amyloid Abeta in the AD brain. Kudo et al, screened more than 2,600 compounds and found several good probes for amyloid Abeta imaging, including BF-168 and BF-227. Okamura demonstrated that BF-168 specifically bind to the amyloid plaques in the brain of a transgenic mouse (PS1/APPsw). Furumoto et al successfully labeled BF-227 with C-11, and clinical PET studies using 11C-BF-227 is now ongoing at Tohoku University. Preliminary clinical study revealed that the compound accumulated in the tempo-parietal region of the brain in AD patient, although non-specific accumulation in the thalamus, basal ganglia and white matter was observed. The goal of this project is to detect AD at pre-clinical stage.


Atomic mass tag of bismuth-209 for increasing the immunoassay multiplexing capacity of mass cytometry.
Mass cytometry (or CyTOF) is an atomic mass spectrometry-based single-cell immunoassay technology, which has provided an increasingly systematic and sophisticated view in basic biological and clinical studies. Using elemental reporters composed of stable heavy metal isotopes, more than 50 cellular parameters are measured simultaneously. However, this current multiplexing does not meet the theoretical capability of CyTOF instrumentation with 135 detectable channels, primarily due to the limitation of available chemistries for conjugating elemental mass tags to affinity reagents. To address this issue, we develop herein additional metallic mass tag based on bismuth-209 (209 Bi) for efficient conjugation to monoclonal antibody. This enables the use of an addtional channel m/z = 209 of CyTOF for single-cell immunoassays. Bismuth has nearly the same charge-to-radius ratio as lanthanide elements; thus, bismuth(III) cations (209 Bi3+ ) could coordinate with DTPA chelators in the same geometry of O- and N-donor groups as that of lanthanide. In this report, the coordination chemistry of 209 Bi3+ with DTPA chelators and Maxpar® X8 polymers were investigated in details. Accordingly, the protocols of conjugating antibody with bismuth mass tag were provided. A method based on UV-Vis absorbance at 280 nm of 209 Bi3+ -labeling DTPA complexes was developed to evaluate the stoichiometric ratio of 209 Bi3+ cations to the conjugated antibody. Side-by-side single-cell analysis experiments with bismuth- and lanthanide-tagged antibodies were carried out to compare the analytical sensitivities. The measurement accuracy of bismuth-tagged antibody was validated within in vitro assay using primary human natural killer cells. Furthermore, bismuth-tagged antibodies were successfully employed in cell cycle measurements and high-dimensional phenotyping immunoassays. © 2017 International Society for Advancement of Cytometry.


[Modification of the thyroidectomy operation in rats].
The removal of thyroid lobes and isthmus was performed with the help of fine scissors employed in ophthalmology. The use of this instrument made it possible to considerably reduce the damage of elastic connective tissue of the trachea during operation which is of importance for the preservation of the life of experimental animals.


Left ventricular free wall rupture: A real nightmare.
Left ventricular free wall rupture (LVFWR) is a rarest but often lethal mechanical complication of acute myocardial infarction (AMI). The mortality rate for LVFWR is described from 75% to 90% and it is the cause for 20% of in-hospital deaths after AMI. Death results essentially from the limited time available for emergent intervention after onset of symptoms. Emergency surgery is indicated and normally the rupture site is easily identified, but it may not be apparent macroscopically, corresponding to transmyocardial or subepicardial dissection with an external rupture far from the infarction site, or already thrombosed and contained. Repair of the ventricular wall is usually achieved either by suturing the edges of the tear or closing it with patches of artificial material or biological tissues, usually using some kind of biological glue. However, several cases of successful conservative management have been described. In this Editorial, I comment on the metanalysis conducted by Matteucci et al, published in this issue of the Journal, including 11 nonrandomized studies and enrolling a total of 363 patients, which brings a great deal of new knowledge that can help not only in the prevention but also in the management of this dreadful complication of AMI.


Phytochemical screening and in-vitro evaluation of pharmacological activities of peels of Musa sapientum and Carica papaya fruit.
Aqueous, absolute and 80% ethanolic extract of fruit peels of Musa sapientum and Carica papaya were investigated for their antibacterial activity, measured by disc diffusion method and antioxidant activity, measured by four different methods. Papaya and banana peels were found to contain terpenoids, tannins, alkaloids, saponins steroid, phenols, fixed oils and fats. 80% ethanolic extract of banana peel was found to contain highest total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activity but in papaya peel, highest TPC and reducing activity was shown by water extract while, TFC and radical scavenging activity was given by 80% ethanolic extract. In banana, water extract showed highest antibacterial activity against tested bacteria while in case of papaya, absolute ethanolic extract showed highest antibacterial activity. The present study revealed that peels of banana and papaya fruits are potentially good source of antioxidant and antibacterial agents.


Tissue-specific repression of starvation and stress responses of the Neurospora crassa con-10 gene is mediated by RCO1.
The Neurospora crassa con-10 gene is weakly expressed in mycelia but is induced approximately 1000-fold during macroconidiation. Studies of the promoter elements and trans-acting factors that regulate con-10 expression are needed to gain a detailed understanding of developmental regulation. The rco-1 mutant displays a 10-fold elevated basal level of expression of con-10. In contrast to the wild type, con-10 expression in mycelia of the rco-1 mutant was rapidly induced to high levels by starvation for carbon or nitrogen and by heat shock. Although con-10 is developmentally induced late in conidiation, con-10 was inducible by heat shock shortly after exposure of the wild-type mycelium to air. These findings support the view that RCO1 is a cell type-specific repressor of con-10. We propose that inactivation of RCO1 allows developing conidiophores to adjust the timing of con-10 induction in response to stress.


Reversible Cerebral Vasoconstriction Syndrome in the Setting of COVID-19 and Pleomorphic Sarcoma: A Case Report.
Reversible cerebral vasonstriction syndrome (RCVS) is an increasingly recognized clinical and radiologic syndrome. However, it has been rarely reported in the setting of the novel coronavirus disease-2019 (COVID-19) infection or sarcomatous tumors. RCVS might be the initial manifestations of COVID-19 infection or noncatecholamine producing masses including sarcoma. A 44-year-old male who developed COVID-19-related symptoms followed by rapid onset of severe headaches in the setting of persistently elevated blood pressure (BP). Brain imaging showed multifocal arterial narrowing in the anterior and posterior circulation consistent with RCVS. Serial imaging demonstrated resolution of the arterial narrowing after BP control was achieved with improvement in the patient's headaches. Further investigation for secondary causes of the patient's elevated BP revealed a right renal mass, and the patient underwent right nephrectomy, and the biopsy results confirmed the diagnosis of pleomorphic sarcoma. Our case suggests a possible association between severe acute respiratory syndrome coronavirus 2 with development of RCVS, but further studies are needed to validate this observation, establish a causal relationship and define a pathophysiological mechanism. Considering tumors other than catecholamine-producing masses as a potential risk factor for developing RCVS might lead to earlier detection and treatment of any underlying malignancy in patients whom the main and sole presentation could be RCVS.


High Selectivity and Sensitivity in Chemiresistive Sensing of Co(II) Ions with Liquid-Phase Exfoliated Functionalized MoS2 : A Supramolecular Approach.
Chemical sensing of water contamination by heavy metal ions is key as it represents a most severe environmental problem. Liquid-phase exfoliated two-dimensional (2D) transition metal dichalcogenides (TMDs) are suitable candidates for chemical sensing thanks to their high surface-to-volume ratio, sensitivity, unique electrical characteristics, and scalability. However, TMDs lack selectivity due to nonspecific analyte-nanosheet interactions. To overcome this drawback, defect engineering enables controlled functionalization of 2D TMDs. Here, ultrasensitive and selective sensors of cobalt(II) ions via the covalent functionalization of defect-rich MoS2 flakes with a specific receptor, 2,2':6',2″-terpyridine-4'-thiol is developed. A continuous network is assembled by healing of MoS2 sulfur vacancies in a tailored microfluidic approach, enabling high control over the assembly of thin and large hybrid films. The Co2+ cations complexation represents a powerful gauge for low concentrations of cationic species which can be best monitored in a chemiresisitive ion sensor, featuring a 1 pm limit of detection, sensing in a broad concentration range (1 pm - 1 µm) and sensitivity as high as 0.308 ± 0.010 lg([Co2+ ])-1 combined with a high selectivity towards Co2+ over K+ , Ca2+ , Mn2+ , Cu2+ , Cr3+ , and Fe3+ cations. This supramolecular approach based on highly specific recognition can be adapted for sensing other analytes through specific ad-hoc receptors.


[Fournier's gangrene as a delayed complication of closed hemorrhoidectomy].
Fournier's gangrene is recognized as a synergistic necrotizing fasciitis of the perineum and abdominal wall along with the scrotum and penis in men and the vulva in women. The major sources of Fournier's Gangrene are dermatologic, anorectal and genitourinary infections. Although anorectum is remarkably rich in bacterial flora, transanal procedures are generally free of infectious or septic complications. Nevertheless, five cases of Fournier's gangrene post hemorrhoidectomy have been published. To report a case of Fournier's gangrene as a delayed complication of closed hemorrhoidectomy and to demonstrate the management of such complication. A sixty-six years old male who had undergone an uncomplicated closed hemorrhoidectomy was readmitted to the hospital on postoperative day 7 for fever, perirectal erythema and tenderness accompanied by a dirty brown discharge from the wound. The patient was treated with fluid resuscitation and broad-spectrum antibiotics. Radical debridement of the perianal and scrotal region was performed accompanied by diverting colostomy. Four months later a reconstruction of the perianal area was performed by meshed split thickness skin graft and the colostomy was closed. Fournier's gangrene is a rare immediate or delayed complication of hemorrhoidectomy. A review of the limited available literature suggests that neither the surgical technique nor the medical history of the patient have an influence on the development of such a rare and fatal complication.


Pregnancy desire and dual method contraceptive use among people living with HIV attending clinical care in Kenya, Namibia and Tanzania.
To describe factors associated with pregnancy desire and dual method use among people living with HIV in clinical care in sub-Saharan Africa. Sexually active HIV-positive adults were enrolled in 18 HIV clinics in Kenya, Namibia and Tanzania. Demographic, clinical and reproductive health data were captured by interview and medical record abstraction. Correlates of desiring a pregnancy within the next 6 months, and dual method use [defined as consistent condom use together with a highly effective method of contraception (hormonal, intrauterine device (IUD), permanent)], among those not desiring pregnancy, were identified using logistic regression. Among 3375 participants (median age 37 years, 42% male, 64% on antiretroviral treatment), 565 (17%) desired a pregnancy within the next 6 months. Of those with no short-term fertility desire (n=2542), 686 (27%) reported dual method use, 250 (10%) highly effective contraceptive use only, 1332 (52%) condom use only, and 274 (11%) no protection. Respondents were more likely to desire a pregnancy if they were from Namibia and Tanzania, male, had a primary education, were married/cohabitating, and had fewer children. Factors associated with increased likelihood of dual method use included being female, being comfortable asking a partner to use a condom, and communication with a health care provider about family planning. Participants who perceived that their partner wanted a pregnancy were less likely to report dual method use. There was low dual method use and low use of highly effective contraception. Contraceptive protection was predominantly through condom-only use. These findings demonstrate the importance of integrating reproductive health services into routine HIV care.


Variation of Musca domestica L. acetylcholinesterase in Danish housefly populations.
Anti-cholinesterase resistance is in many cases caused by modified acetylcholinesterase (MACE). A comparison was made of toxicological data and AChE activity gathered from 21 field populations and nine laboratory strains of houseflies, Musca domestica L., to elucidate the best way of generating data to provide advice for management strategies and gathering information for resistance risk assessment on the organophosphates azamethiphos and dimethoate and the carbamate methomyl, which have been the primary insecticides used against adult houseflies in Denmark. Cluster analysis was performed and > 2000 houseflies were assigned to one of three phenotypes based on total acetylcholinesterase activity as well as inhibition by azamethiphos, methomyl or omethoate. A cluster, i.e. a phenotype, with high total AChE activity and high sensitivity to azamethiphos and less sensitivity to inhibition by methomyl and omethoate was shown to be linked to methomyl resistance. It was not possible to define any clusters that could be linked to azamethiphos or dimethoate resistance. The five mutations V180L, G262A, G262V, F327Y and G365A causing anticholinesterase resistance in houseflies were all identified in the Danish housefly strains. The data are very heterogeneous, and a correlation of molecular genetic background and resistance of phenotypes is not obvious with the available data.


DNA from lake sediments reveals long-term ecosystem changes after a biological invasion.
What are the long-term consequences of invasive species? After invasion, how long do ecosystems require to reach a new equilibrium? Answering these questions requires long-term, high-resolution data that are vanishingly rare. We combined the analysis of environmental DNA extracted from a lake sediment core, coprophilous fungi, and sedimentological analyses to reconstruct 600 years of ecosystem dynamics on a sub-Antarctic island and to identify the impact of invasive rabbits. Plant communities remained stable from AD 1400 until the 1940s, when the DNA of invasive rabbits was detected in sediments. Rabbit detection corresponded to abrupt changes of plant communities, with a continuous decline of a dominant plant species. Furthermore, erosion rate abruptly increased with rabbit abundance. Rabbit impacts were very fast and were stronger than the effects of climate change during the 20th century. Lake sediments can allow an integrated temporal analysis of ecosystems, revealing the impact of invasive species over time and improving our understanding of underlying mechanisms.


Evaluating the impact of transient shear stress on platelet activation, adhesion, and aggregation with microfluidic chip technique.
When nonphysiological stenosis occurs, the transient high shear stress formed in vessels increases the risk of thrombosis and is a potential factor for cardiovascular diseases. But the platelet adhesion and aggregation behavior at nonphysiological post-stenosis and its affecting factors are not fully understood yet. In this experiment, platelet aggregation on collagen and fibrinogen at different shear stresses and different hematocrits were observed by microfluidic technology. Platelet activation (P-selectin, glycoprotein IIb/IIIa) and monocyte-platelet aggregate (MPA) levels under different shear stresses were analyzed by flow cytometry. On fibrinogen, platelets aggregate more at higher shear stress conditions. While on collagen, it becomes more difficult for platelets to form stable aggregation at higher shear stress conditions. If platelets adhere initially at low shear stress, stable platelet aggregation can be formed at subsequent high shear stress. Moreover, when the shear stress increases, platelet activity markers (P-selectin, glycoprotein IIb/IIIa and MPAs) increase significantly. Hematocrit affects the degree of platelet aggregation, and the influence of hematocrit is obvious at high shear stress. Transient high shear stress (46 ms) can effectively activate platelets. Platelet aggregation behavior was different for coated fibrinogen and collagen protein. Stable platelet adhesion at post-stenosis is more dependent on fibrinogen and platelet aggregation is stable on both fibrinogen and collagen. Hematocrit can significantly affect the formation of platelet aggregation.


A naturalistic study of ambulatory asthma severity and reported avoidant coping styles.
To examine how the use of dispositional avoidant coping traits prospectively predicts ambulatory asthma severity in daily life. An ecological momentary assessment (EMA) design enabled examination of stable coping styles across dynamic daily changes of ambulatory peak expiratory flow rate (PEFR), asthma symptoms and stress in the natural environment of patients with asthma. A community sample of 61 adults with asthma reported their typical use of avoidant coping styles and carried palmtop computers that alerted them to record their stress and symptoms five times per day for 1 week. Some aspects of dispositional avoidant coping predicted more asthma symptoms and worse PEFR. Denial and behavioural disengagement as typical coping styles predicted more symptoms and worse PEFR. Mental disengagement was unrelated to symptoms and PEFR. These data suggest that individuals with asthma who report typically utilizing avoidant coping may have worse health parameters in momentary reports when examined in their natural environments. Differences between avoidant coping styles emerged, suggesting the existence of moderating factors of coping effectiveness.


Procalcitonin as a marker of severe bacterial infection in children in the emergency department.
Procalcitonin, the prohormone of calcitonin, is a relatively new and innovative marker of bacterial infection that has multiple potential applications in the pediatric emergency department. In healthy individuals, circulating levels of procalcitonin are generally very low (<0.05 ng/mL), but in the setting of severe bacterial infection and sepsis, levels can increase by hundreds to thousands of fold within 4 to 6 hours. Although the exact physiologic function of procalcitonin has not been determined, the consistent response and rapid rise of this protein in the setting of severe bacterial infection make procalcitonin a very useful biomarker for invasive bacterial disease. In Europe, serum procalcitonin measurements are frequently used in the diagnosis and the management of patients in a variety of clinical settings. To date, the use of procalcitonin has been limited in the United States, but this valuable biomarker has many potential applications in both the pediatric emergency department and the intensive care unit. The intent of this article is to review the history of procalcitonin, describe the kinetics of the molecule in response to bacterial infection, describe the laboratory methods available for measuring procalcitonin, examine the main causes of procalcitonin elevation, and evaluate the potential applications of procalcitonin measurements in pediatric patients.


Effect of retinoic acid on proliferation of estrogen-responsive transformed murine Leydig cells in serum-free culture.
B-1 F cells, one of the sublines established from mouse Leydig cell tumor, have been found to be maintained as an estrogen-responsive cell line under the serum-free culture conditions. Reported results that retinoids have action mechanisms similar to those of estrogen prompted us to examine the effect of retinoids on the proliferation of B-1 F cells. Stimulation of B-1 F cell growth by retinoic acid in a dose-dependent manner was observed, whereas retinoic acid did not promote but inhibited the proliferation of MCF-7 cells (estrogen- and retinoic acid receptor-positive human breast cancer cells). To elucidate the mechanism of retinoic acid-dependent cell growth, simultaneous treatment with retinoic acid and estradiol was carried out. The result did not show the additive effect on B-1 F cell growth. Hydroxytamoxifen, a potent antiestrogen, inhibited not only estradiol-dependent but also retinoic acid-dependent cell growth. However, retinoic acid failed to be associated with estrogen receptor, suggesting that retinoic acid induced enhancement of B-1 cell growth through its interaction with retinoic acid receptor. Northern blot analyses of polyadenylated RNA with complementary DNA probes for human retinoic acid receptor alpha, beta, and gamma revealed the presence of transcripts encoded by retinoic acid receptor alpha gene in B-1 F cells. These results would suggest that enhancement of the B-1 F cell growth is mediated through interaction of retinoic acid with retinoic acid receptor alpha. This stimulatory activity is inhibited by estrogen receptor complexed with hydroxytamoxifen.


Evaluation of intestinal villus height in rats after ischemia and reperfusion by administration of superoxide dismutase, polyethylene glycol-conjugated superoxide dismutase, and two 21-aminosteroids.
Intestinal ischemia was induced and maintained for 60 minutes in male Sprague-Dawley rats weighing 175 to 225 g. Prior to reperfusion, the following drugs were administered via the caudal vena cava: 0.9% NaCl (0.5 ml), superoxide dismutase (SOD; 1,000 IU/kg of body weight), polyethylene glycol-conjugated SOD (PEG-SOD; 1,000 IU/kg), or the 21-aminosteroids, U74006F (3 mg/kg) or U78715G (3 mg/kg). A sham-operated control group was included. Animals from each group were euthanatized at 5 periods of reperfusion: 5 minutes, 30 minutes, 18 hours, 3 days, and 7 days after reperfusion. Fixed tissues were embedded in paraffin, sectioned at 5 microns, and stained with H&E. Villi profiled in cross section were measured from the crypt villus junction to the tip of the villus. The mean villus height for each rat was calculated and compared by two-way ANOVA to determine the effects of time and treatment. Villus height was maintained after 30 minutes of reperfusion in rats of the sham- and U74006F-treated groups; U78715G and SOD treatment attenuated the loss in villus height, and villus height was not maintained in the PEG-SOD- and 0.9% NaCl-treated rats. In all rats, villus height was comparable to, or was greater than villus height in sham-operated controls by 18 hours after reperfusion in all animals and remained constant through 7 days. Administration of the 21-aminosteroids maintained villus height after ischemia and reperfusion. Treatment with PEG-SOD did not maintain villus height to the degree observed in rats treated with SOD.


Youth smoking, cigarette prices, and anti-smoking sentiment.
In this paper, we develop a new direct measure of state anti-smoking sentiment and merge it with micro-data on youth smoking in 1992 and 2000. The empirical results from the cross-sectional models show two consistent patterns: after controlling for differences in state anti-smoking sentiment, the price of cigarettes has a weak and statistically, insignificant influence on smoking participation, and state anti-smoking sentiment appears to have a potentially important influence on youth smoking participation. The cross-sectional results are corroborated by results from the discrete time hazard models of smoking initiation that include state-fixed effects. However, there is evidence of price-responsiveness in the conditional cigarette demand by youth and young adult smokers.


[Hyperalphalipoproteinemia: causes of therapeutic errors in primary care].
To consider using request for cholesterol together with high density lipoproteins (cHDL) before any hypolipemic treatment. Three clinical observations. General medicine surgery of the La Orden Health Centre in Huelva. Patients diagnosed with hyperalphalipoproteinemia in whom the total cholesterol (Ct) rate did not lower after treatment with hypolipemic drugs and diet. In all patients, the Ct, triglyceride (TG), cHDL, cholesterol together with low density lipoproteins (cLDL), very low density lipoproteins (cVLDL) and apoprotein A1 (Apo A1) were determined using enzymatic, ultracentrifuge and immunonephelometric methods. The cHDL reference value was 30-70 and 30-85 mg/dl in males and females respectively. The results obtained in the three observations were: Ct (288, 292 and 284 mg/dl) cHDL (118, 122 and 114 mg/dl) Apo A1 (2.44, 2.36 and 2.02 milligrams) which were all high, whereas cLDL and cVLDL and the TG obtained normal results. We consider it necessary to carry out a cHDL and cLDL study before starting any type of hypolipemic treatment. The clinical importance of correct diagnosis of hyperalphalipoproteinemia is obvious, as hypercholesterolemia can be treated with hypolipemic drugs in spite of cLDL being normal. The cases described underline the importance of basing decisions on the treatment of hypercholesterolemia in cLDL figures and not in Ct figures.


Down, but Not Out: A Role for SMARCB1 in Synovial Sarcoma.
Reduced protein expression of the BAF complex (also known as SWI/SNF) tumor suppressor SMARCB1 is frequently observed in human synovial sarcoma, a soft-tissue malignancy driven by the oncogenic SS18-SSX fusion, which competes with wild-type SS18 for BAF complex incorporation. In this issue of Cancer Discovery, Li and Mulvihill reveal that low-expressed SMARCB1 has a functional role in synovial sarcomagenesis in mouse models expressing the SS18-SSX2 fusion and present evidence that SMARCB1 reduction in synovial sarcoma is due to wholesale degradation of canonical BAF complexes.See related article by Li et al., p. 2620.


Rac1 induces the clustering of AMPA receptors during spinogenesis.
Glutamatergic synapses switch from nonspiny synapses to become dendritic spines during early neuronal development. Here, we report that the lack of sufficient Rac1, a small RhoGTPase, contributes to the absence of spinogenesis in immature neurons. The overexpression of green fluorescence protein-tagged wild-type Rac1 initiated the formation of dendritic spines in cultured dissociated hippocampal neurons younger than 11 d in vitro, indicating that Rac1 is likely one of the missing pieces responsible for the lack of spines in immature neurons. The overexpression of wild-type Rac1 also induced the clustering of AMPA receptors (AMPARs) and increased the amplitude of miniature EPSCs (mEPSCs). The expression of constitutively active Rac1 induced the formation of unusually large synapses with large amounts of AMPAR clusters. Also, our live imaging experiments revealed that the contact of an axon induced the clustering of Rac1, and subsequent morphological changes led to spinogenesis. Additionally, the overexpression of wild-type Rac1 and constitutively active Rac1 increased the size of preexisting spines and the amplitude of mEPSCs in mature neurons (>21 d in vitro) within 24 h after transfection. Together, these results indicate that activation of Rac1 enhances excitatory synaptic transmission by recruiting AMPARs to synapses during spinogenesis, thus providing a mechanistic link between presynaptic and postsynaptic developmental changes. Furthermore, we show that Rac1 has two distinct roles at different stages of neuronal development. The activation of Rac1 initiates spinogenesis at an early stage and regulates the function and morphology of preexisting spines at a later stage.


Sex-related differences in outcome after left atrial appendage occlusion: Insights from Europe and the EWOLUTION registry.
Women with atrial fibrillation (AF) generally experience worse symptoms, poorer quality of life, and have a higher risk of stroke and death. There is limited availability of sex-related differences regarding left atrial appendage occlusion (LAAO). The aim of this study was to evaluate the sex-related differences in patients undergoing LAAO in EWOLUTION. A total of 1025 patients scheduled for elective LAAO therapy employing the WATCHMAN Gen 2.5 prospectively consented for participation; 1005 patients received a successful implant and were followed for 2 years. As we detected sex-related differences in baseline data we performed a propensity score matching. The primary endpoint is a combined endpoint of survival free from mortality, major bleeding, ischemic stroke, transitory ischemic attack (TIA) and systemic embolization (SE) up to 2-year clinical follow-up. Secondary Endpoints were periprocedural data and overall 2-year survival. Women were older but had less often vascular disease and hemorrhagic stroke. There was no sex-related significant difference after LAAO at 2 years in the combined endpoint of survival free from mortality, major bleeding, ischemic stroke, TIA, and SE (female vs. male: 79% vs.76%, p = 0.24) or in overall survival (female vs. male: 85% vs. 82%, p = 0.16). Procedural data showed a higher sealing rate after the implantation in women (complete sealing female 94% vs. male 90%, p = 0.033), significantly more pericardial effusions (female 1.2% vs. male 0.2%, p = 0.031) and a similar periprocedural risk profile. Females undergoing LAAO differ in various baseline variables, but after adjustment, we observed similar safety and efficacy of LAAO with no significant difference in long-term outcomes between women and men.


Colonization and internalization of Salmonella enterica in tomato plants.
The consumption of fresh tomatoes has been linked to numerous food-borne outbreaks involving various serovars of Salmonella enterica. Recent advances in our understanding of plant-microbe interactions have shown that human enteric pathogenic bacteria, including S. enterica, are adapted to survive in the plant environment. In this study, tomato plants (Solanum lycopersicum cv. Micro-Tom) grown in sandy loam soil from Virginia's eastern shore (VES) were inoculated with S. enterica serovars to evaluate plausible internalization routes and to determine if there is any niche fitness for certain serovars. Both infested soil and contaminated blossoms can lead to low internal levels of fruit contamination with Salmonella. Salmonella serovars demonstrated a great ability to survive in environments under tomato cultivation, not only in soil but also on different parts of the tomato plant. Of the five serovars investigated, Salmonella enterica serovars Newport and Javiana were dominant in sandy loam soil, while Salmonella enterica serovars Montevideo and Newport were more prevalent on leaves and blossoms. It was also observed that Salmonella enterica serovar Typhimurium had a poor rate of survival in all the plant parts examined here, suggesting that postharvest contamination routes are more likely in S. Typhimurium contamination of tomato fruit. Conversely, S. Newport was the most prevalent serovar recovered in both the tomato rhizosphere and phyllosphere. Plants that were recently transplanted (within 3 days) had an increase in observable internalized bacteria, suggesting that plants were more susceptible to internalization right after transplant. These findings suggest that the particular Salmonella serovar and the growth stage of the plant were important factors for internalization through the root system.


Novel BRICHOS-Related Antimicrobial Peptides from the Marine Worm Heteromastus filiformis: Transcriptome Mining, Synthesis, Biological Activities, and Therapeutic Potential.
Marine polychaetes represent an extremely rich and underexplored source of novel families of antimicrobial peptides (AMPs). The rapid development of next generation sequencing technologies and modern bioinformatics approaches allows us to apply them for characterization of AMP-derived genes and the identification of encoded immune-related peptides with the aid of genome and transcriptome mining. Here, we describe a universal bioinformatic approach based on the conserved BRICHOS domain as a search query for the identification of novel structurally unique AMP families in annelids. In this paper, we report the discovery of 13 novel BRICHOS-related peptides, ranging from 18 to 91 amino acid residues in length, in the cosmopolitan marine worm Heteromastus filiformis with the assistance of transcriptome mining. Two characteristic peptides with a low homology in relation to known AMPs-the α-helical amphiphilic linear peptide, consisting of 28 amino acid residues and designated as HfBRI-28, and the 25-mer β-hairpin peptide, specified as HfBRI-25 and having a unique structure stabilized by two disulfide bonds-were obtained and analyzed as potential antimicrobials. Interestingly, both peptides showed the ability to kill bacteria via membrane damage, but mechanisms of their action and spectra of their activity differed significantly. Being non-cytotoxic towards mammalian cells and stable to proteolysis in the blood serum, HfBRI-25 was selected for further in vivo studies in a lethal murine model of the Escherichia coli infection, where the peptide contributed to the 100% survival rate in animals. A high activity against uropathogenic strains of E. coli (UPEC) as well as a strong ability to kill bacteria within biofilms allow us to consider the novel peptide HfBRI-25 as a promising candidate for the clinical therapy of urinary tract infections (UTI) associated with UPEC.


Planning ensures local and referral care for remote rural area.
Remote, rural populations need at least some inpatient services to be provided within their communities. Replacement of an obsolete small, rural hospital in Alaska shows how planning can ensure provision of hospital services locally and through referral.


Built environment influences on healthy transportation choices: bicycling versus driving.
A growing body of evidence links the built environment to physical activity levels, health outcomes, and transportation behaviors. However, little of this research has focused on cycling, a sustainable transportation option with great potential for growth in North America. This study examines associations between decisions to bicycle (versus drive) and the built environment, with explicit consideration of three different spatial zones that may be relevant in travel behavior: trip origins, trip destinations, and along the route between. We analyzed 3,280 utilitarian bicycle and car trips in Metro Vancouver, Canada made by 1,902 adults, including both current and potential cyclists. Objective measures were developed for built environment characteristics related to the physical environment, land use patterns, the road network, and bicycle-specific facilities. Multilevel logistic regression was used to model the likelihood that a trip was made by bicycle, adjusting for trip distance and personal demographics. Separate models were constructed for each spatial zone, and a global model examined the relative influence of the three zones. In total, 31% (1,023 out of 3,280) of trips were made by bicycle. Increased odds of bicycling were associated with less hilliness; higher intersection density; less highways and arterials; presence of bicycle signage, traffic calming, and cyclist-activated traffic lights; more neighborhood commercial, educational, and industrial land uses; greater land use mix; and higher population density. Different factors were important within each spatial zone. Overall, the characteristics of routes were more influential than origin or destination characteristics. These findings indicate that the built environment has a significant influence on healthy travel decisions, and spatial context is important. Future research should explicitly consider relevant spatial zones when investigating the relationship between physical activity and urban form.


Effects of pulsed magnetic stimulation of GFAP levels in cultured astrocytes.
The present study evaluates the physiological effects of magnetic stimulation on astrocyte cultures. Cell cultures were exposed to pulsed magnetic stimulation (10 Hz, 10 sec) at the following levels: 0.10 tesla (T; Group A); 0.21 T (Group B); 0.42 T (Group C); and 0.63 T (Group D). Glial fibrillary acidic protein (GFAP) levels from immunoblots, total protein concentrations, and cellular morphology were analyzed at 0, 1, 3, 5, 7, 13, and 20 days poststimulation. Significantly higher GFAP levels were observed in Group D at day 3 (P = 0.0114). The change was transient as the GFAP levels quickly returned to control levels by day 5. No other significant changes in GFAP levels were observed. In comparison to control protein levels at day 0, concentrations from Groups B, C, and D were significantly lower (P < 0.006), whereas at day 3, Groups C and D were significantly higher (P < 0.02). Differences in astrocyte morphology due to magnetic stimulation were not observed. This study demonstrated that high intensity magnetic stimulation for only 10 sec induced a transient biological response.


Sclerosing nevus with pseudomelanomatous features: dermoscopic and confocal aspects.
Sclerosing nevus with pseudomelanomatous features (SNPFs) is a clinical and pathologic entity that mimics melanoma both clinically and histologically. The lesion is a melanocytic nevus, histologically characterized by fibrosis and a pseudomelanomatous proliferation. It is typically seen in young to middle-aged individuals, mainly on the back, where microtrauma or inflammatory changes are more frequent. Dermoscopic description of SNPF has been reported so far in one case series. The aim of our study was to describe the dermoscopic and confocal features of SNPF. Histopathologically confirmed cases of SNPF were retrospectively collected from three referral centres in Italy. Only lesions with available clinical, dermoscopic and histopathological data were included; confocal images were also retrieved, when available. Lesions were evaluated for the presence of 12 dermoscopic and five confocal criteria previously described. The study population included 93 lesions in as many patients (71 men and 22 women; median age: 38 years). Dermoscopically, we found a predominance of dark colours, in particular brown and blue, which were found in all lesions and the vast majority of the lesions (86/93; 92.5%) displayed at least one structureless area. By the combination of colours and structures, we observed that the majority of the lesions (67/92; 72%) were characterized by more than one structure and more than one colour. Confocal evaluation was performed on a subset of 24/93 lesions showing a regular architecture pattern (19/24 cases, 79%), with a predominance of the ringed pattern. The presence of focal cytologic atypia at the dermal-epidermal junction was present in 12/24 cases (50%) with a prevalent dendritic-shaped cell proliferation. The current study demonstrated that SNPF was frequently characterized, on dermoscopic examination, by more than one structure and more than one colour and on confocal microscopy by a regular ringed pattern with focal dendritic atypical cells.


Theory of health insurance.
The conventional explanation for purchasing insurance is to transfer risk. Psychologists, however, have shown that this explanation does not match actual behavior. They find that people generally prefer the risk of no loss at all to the certainty of a smaller actuarially equivalent loss, a situation exactly opposite to the one represented by the purchase of insurance. Nevertheless, people do purchase insurance, so there must be an explanation other than risk transfer for purchasing it. Of the explanations so far advanced, however, none have yet developed a wide acceptance. Regardless of risk issues, people will be more likely to purchase insurance when the premium is low compared to the value of the coverage to the consumer. Moral hazard raises the premium, as does adverse selection. The presence of either makes the purchase of insurance less likely. With health insurance, the tax subsidy can reduce the effective premium to less than the actuarially fair cost of insurance. This would increase the likelihood that health insurance is purchased. Finally, because of the value we place on our health, we desire access to a full range of health care. Health insurance is often the only affordable way of gaining access to this care, given the high costs of many of these procedures.


Why the home health care classification is a recognized nursing nomenclature.
The Home Health Care Classification (HHCC) is a standardized nomenclature designed for home health and/or ambulatory care. The HHCC was developed not only to code, index, and classify care, but also to document and track the nursing care process over time, and across settings and geographic locations. Five major reasons why the HHCC nomenclature should be used in computer-based home health and ambulatory care systems are discussed. The advantages outweigh the disadvantages and demonstrate why it is the preferred nursing classification vocabulary available today.


Have the Samaritans lowered the suicide rate? A controlled study.
Suicide rates in towns with a Samaritan branch were compared with rates in matched control towns without a branch. Four methods of choosing controls are described, all of which have advantages over those used by Bagley (1968). No statistically significant differences between Samaritan and control towns were found. The scientific case for the effectiveness of the Samaritans in reducing the suicide rate is therefore seriously weakened.


The population dynamics in mosquitoes and humans of two Plasmodium vivax polymorphs distinguished by different circumsporozoite protein repeat regions.
The population dynamics of two Plasmodium vivax polymorphs were studied over a two-year period in a village in a hyperendemic area of Papua New Guinea in both the mosquito and human populations. Strains of P. vivax were distinguished by different circumsporozoite (CS) protein repeats, the VK210 (classic) and the VK247 (variant) polymorphs. In 1986, 34% of P. vivax CS protein-positive mosquitoes were of the VK247 type. Although the proportion of P. vivax sporozoite antigen-positive mosquitoes compared with all sporozoite-positive mosquitoes did not change from 1986 to 1987, the proportion of P. vivax-positive mosquitoes of the VK247 polymorph decreased significantly from 34% to 11% (5 of 45) in 1987. In 1986, 61% (47 of 77) of humans tested had IgGs that recognized the VK247 CS repeat, while only 26% (22 of 84) had IgGs that recognized the VK210 CS repeat. The observed fluctuation in the proportion of the two P. vivax CS protein polymorphs recorded in the mosquito population from 1986 to 1987 is consistent with a hypothesis of selection by humoral immune pressure on the VK247 strain.


Single mothering as experienced by Burundian refugees in Australia: a qualitative inquiry.
Refugee mothers have fled from their homeland to escape persecutions with their children only to find other threats to their well-being in the new country. Building on previous research, it is known that being a new immigrant is challenging and requires adaptation. The adaptation process, known as acculturation, may not be successful leading to psychological distress. It is also known that a generation gap can occur when children acculturate faster than their parents. What was lacking was understanding about the experiences of single refugee mothers. Interpretative phenomenological study was undertaken to explore the lived experiences of eight Burundian refugee single mothers in Australia. Data were collected by in-depth interviews. Each interviews were transcribed and analyzed using thematic analysis. Findings revealed three themes. First theme 'Traditional mothering practices of Burundian culture' illustrated mothering strategies as practiced prior to their arrival in Australia including mothering with sufficient social support, strong position of parents, and regular use of physical disciplining. Second theme 'Challenges identified after arrival to new country' revealed that mothers felt their children acculturated faster than themselves which led to intergenerational gap. This has also led participants to live in a continuous dilemma, experiencing inner conflicts and struggles associated with their mothering practices, especially when mothers had arrived with a lack of knowledge relating to acceptable mothering practices in a new culture. Final theme, 'Reforming family life in Australia' highlighted the decisions made by single refugee mothers which is to embrace both new and original cultures, leading to successful acculturation. However, lack of appropriate knowledge of acceptable mothering practices led to involvement of legal authorities who threatening to remove children from the mother's care. This has led mothers feeling change of power from 'mother to child, 'to child to mother', raises concerns for family wellbeing. A need for parenting information when entering a new country including education about any legal obligations for parents such as a Child Protection Act will assist successful acculturation. As nurses are likely to encounter refugee single mothers, they are well placed to provide support and education to new refugee single mothers.


Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects.
The goal of this review is to summarize the evidence for non-targeted and delayed effects of exposure to ionizing radiation in vivo. Currently, human health risks associated with radiation exposures are based primarily on the assumption that the detrimental effects of radiation occur in irradiated cells. Over the years a number of non-targeted effects of radiation exposure in vivo have been described that challenge this concept. These include radiation-induced genomic instability, bystander effects, clastogenic factors produced in plasma from irradiated individuals that can cause chromosomal damage when cultured with nonirradiated cells, and transgenerational effects of parental irradiation that can manifest in the progeny. These effects pose new challenges to evaluating the risk(s) associated with radiation exposure and understanding radiation-induced carcinogenesis.


Expression of protein tyrosine kinases in islet cells: possible role of the Flk-1 receptor for beta-cell maturation from duct cells.
To elucidate the expression of genes of importance for beta-cell replication and the production of insulin, single-stranded cDNAs from different preparations of insulin producing cells were used as template for the polymerase chain reaction (PCR) using primers specific for protein tyrosine kinases (PTKs). In RINm5F cells, as well as in fetal rat islets, the receptor PTK fetal liver kinase-1 (Flk-1) was expressed among other receptor and cytoplasmic tyrosine kinases. To elucidate the putative effects of stimulation of the Flk-1 receptor, fetal rat islet-like structures were cultured in the presence of the ligand for this receptor, vascular endothelial growth factor (VEGF). VEGF was found to stimulate both the insulin content/islet DNA ratio and the accumulation of insulin in the culture medium without affecting the rates of beta-cell replication. To investigate the localization of expression of the Flk-1 receptor in the pancreas, serial sections of fetal pancreata were immunostained for Flk-1 and insulin. Expression of Flk-1 was detected in endothelial-like cells and cells lining pancreatic ducts. The latter are considered to contain precursor cells for the endocrine pancreas. In conclusion, specific protein tyrosine kinases are expressed in islet cells, and are presumably participating in the regulation of islet function. Specifically, the receptor PTK Flk-1 may play a role of beta-cell maturation from pancreatic duct cells.


Girls with generalized joint hypermobility display changed muscle activity and postural sway during static balance tasks.
To study knee muscle activity and static postural sway in girls with generalized joint hypermobility (GJH). Sixteen girls with GJH and 11 girls with non-GJH (NGJH) aged 14 years, randomly recruited among schoolchildren, participated in this study. GJH inclusion criteria were: Beighton score minimum 6/9 and one hypermobile knee; for NGJH: Beighton score maximum 5/9 and no knees with hypermobility. The participants performed a static two-legged balance test with eyes open (2EO) and eyes closed (2EC) and a one-legged stance test with eyes open (1EO). Postural sway (centre of pressure path length, COPL) was calculated, along with rambling and trembling components. Surface electromyography (sEMG) from the quadriceps (Q), hamstrings (H), and gastrocnemius (G) muscles was recorded, expressed as a percentage of the maximum voluntary EMG (%MVE), and the co-contraction index (CCI) of Q, H, and G muscle activity was calculated. Knee function was self-reported using the Knee Injury and Osteoarthritis Outcome Score for children (KOOS-Child). GJH had a significantly lower lateral HQ CCI and a higher medial/lateral HQ CCI ratio in all balance tasks. Group mean EMG varied from 1.3%MVE in Q (during 2EO) to 15.7%MVE in G (during 1EO). GJH had larger postural sway length than NGJH during 2EC (COPL 1.64 vs. 1.37 m/min, p < 0.001). Rambling and trembling components did not differ between groups. Girls with GJH and at least one hypermobile knee performed, compared with NGJH, static balance tasks with higher medial knee muscle activity relative to the lateral activity, and larger postural sway when vision was eliminated. The short- and long-term consequences should be studied further.


Expression of G protein-coupled receptor-30, a G protein-coupled membrane estrogen receptor, in oxytocin neurons of the rat paraventricular and supraoptic nuclei.
The regulatory actions of estrogens on magnocellular oxytocin (OT) neurons of the paraventricular and supraoptic nuclei are well documented. Although the expression and distribution of nuclear estrogen receptor-beta, but not estrogen receptor-alpha, in the OT neuron has been described, the nuclear receptors may not explain all aspects of estrogen function in the hypothalamic OT neuron. Recently a G protein-coupled receptor (GPR) for estrogens, GPR30, has been identified as a membrane-localized estrogen receptor in several cancer cell lines. In this study, we therefore investigated the expression and localization of GPR30 in magnocellular OT neurons to understand the mode of rapid estrogen actions within these neurons. Here we show that, in the paraventricular nucleus and supraoptic nucleus, GPR30 is expressed in magnocellular OT neurons at both mRNA and protein levels but is not expressed in vasopressin neurons. Specific markers for intracellular organelles and immunoelectron microscopy revealed that GPR30 was localized mainly in the Golgi apparatus of the neurons but could not be detected at the cell surface. In addition, the expression of GPR30 is also detected in the neurohypophysis. These results suggest that GPR30 may serve primarily as a nongenomic transducer of estrogen actions in the hypothalamo-neurohypophyseal system.


Glutaraldehyde fixative tonicity for scanning electron microscopy of delicate chick embryos.
Fresh pullet eggs (White Leghorn strain) were incubated from 19-2ldium-gold and observed in a Cambridge S4 scanning electron microscope. Shrunken cells with intracellular yolk granules embossed on the surface are produced by the strongly hypertonic Karnovsky's fixer (Final: 2010 mOsm). Embryos fixed with modified Karnovsky's fixer (Final: 373 mOsm) possess surfaces with irregular microappendages. Swollen cells with few microappendages are observed when embryos are fixed in a hypotonic environment (Final: 250 mOsm or less). Ideal fixatives preserve a relatively flat surface, with cells bordered by smoothsurface microappendages. For adequate SEM fixation, fixative vehicle should be approximately isotonic for tissue, with aldehyde (2% or less) added to vehicle.


Screening for economic hardship for child welfare-involved families during the COVID-19 pandemic: A rapid partnership response.
Pandemics have a wide range of economic, health and social consequences related to both the spread of a disease and efforts made by government leaders to contain it which may be particularly detrimental for the child welfare-involved population. This is because child welfare agencies serve some of the highest needs children and families. A significant proportion of these families face economic hardship, and as a result of containment measures for COVID-19, more families inevitably will. Given the range of negative consequences related to the pandemic and the evolving supports available to families, child protection workers needed a clinical tool to guide and support work with families informed by an understanding of economic hardship. The objective of this paper is to report on the development and implementation strategy of a tool to be used for practice intervention during the pandemic. Action research methodology was utilized in the creation of the clinical tool. The tool's development and implementation occurred through an academic/child welfare sector partnership involving child welfare agencies representing diverse regions and populations in Ontario, Canada. Factor analysis of representative child welfare data from the Ontario Incidence Study of Reported Child Abuse and Neglect 2018 (OIS-2018) on economic hardship was used to inform the development of questions on the clinical tool. The development and implementation strategy of the clinical tool are described, including the results from analyses of the OIS-2018. Future directions for the project are discussed, including considerations for using this tool beyond the pandemic.


Sterile tuberculous granuloma in a patient with XDR-TB treated with bedaquiline, pretomanid and linezolid.
Drug-resistant tuberculosis (DR-TB) continues to pose a threat to the global eradication of TB. Regimens for extensively drug-resistant (XDR) TB are lengthy and poorly tolerated, often with unsuccessful outcomes. The TB Alliance Nix-TB trial investigated the safety and efficacy of a 26-week regimen of bedaquiline, pretomanid and linezolid (BPaL) in participants with XDR-TB, multidrug-resistant (MDR) TB treatment failure or intolerance. In this trial 9 out of 10 participants were cured. We describe a trial participant with XDR-TB who presented with new-onset seizures soon after BPaL treatment completion. Imaging showed a right temporal ring-enhancing lesion, and a sterile tuberculous granuloma was confirmed after a diagnostic, excisional biopsy. Learning points include management of a participant with a tuberculoma after BPaL completion, efficacy of new medications for central nervous system (CNS) TB and a review of their CNS penetration. This is the first case of pretomanid use in CNS TB.


Accessing Sentence Participants: The Advantage of First Mention.
We investigate the following finding concerning the order in which participants are mentioned in sentences: In a probe recognition task, probe words are responded to considerably more rapidly when they are the names of the first- as opposed to the second-mentioned participants. Seven experiments demonstrated that this advantage is not attributable to the tendency in English for first-mentioned participants to be semantic agents; neither is it due to the fact that in many of our experiments, the first-mentioned participants were also the initial words of their stimulus sentences. Furthermore, the advantage is not attenuated when the first- and second-mentioned participants share syntactic subjecthood, or even when the first-mentioned participants are not the syntactic subjects. In sum, the effect does not appear to be attributable to linguistic factors. We suggest instead that it is the result of cognitive processes: Building a coherent mental representation requires first laying a foundation and then mapping subsequent information onto the developing representation. First-mentioned participants are more accessible because they form the foundations for their sentence. Level representations and because it is through them that subsequent information gets mapped onto the developing representations.


Clear cell sarcoma of the kidney misdiagnosed as mesoblastic nephroma: a case report and review of the literature.
Clear cell sarcoma of the kidney (CCSK) is a rare renal neoplasm of paediatrics, making up about 3% of all renal tumours in paediatrics, with a high tendency for developing bone metastasis. A seven year-old boy was referred to our clinic with two firm, large masses over the manubrium of the sternum and right frontal area, which pathologically were confirmed as a metastatic CCSK. The patient had a history of a renal mass three years earlier, for which radical nephrectomy had been performed, and histopathologic diagnosis was compatible with mesoblastic nephroma. Thus, no further investigation and therapy had been applied for the patient. CCSK is a rare but malignant and aggressive paediatric renal tumour, with a high tendency for developing distant bone metastases, leading to its poor prognosis. CCSK could be misdiagnosed as several other renal tumours such as mesoblastic nephroma, and thus CCSK should be taken carefully into consideration in the diagnosis of renal tumours.


In vitro genotoxicity testing of the furylethylene derivative UC-245 in human cells.
The possible genotoxic potential of the 2-furylethylene derivative UC-245 has been evaluated in vitro using human cells as a test system. This compound was synthesized at the Centro de Bioactivos Químicos, Universidad Central de Las Villas (Cuba) and it appears to be effective against leishmaniosis. The induced genetic damage was determined by scoring the frequency of micronuclei (MN) and the frequency of sister chromatid exchanges (SCE) in primary lymphocyte cultures set up from two different donors. The DNA breakage level was also evaluated by the Comet assay, using an established human lymphoblastoid cell line (TK6). For the MN and SCE studies, to detect eventual metabolic modification in the genotoxicity of this compound, the cultures were treated with S9 microsomal fraction. The results obtained indicate that, under the experimental conditions used, the test agent does not induce significant increases in the frequency of micronucleated cells, irrespective of presence/absence of the metabolic fraction, which would indicate a lack of clastogenic and/or aneugenic potential. Nevertheless, a clear and significant increase in the SCE frequency was observed in the treatments without S9. This would support the 2-furylethylene derivative UC-245 inducing DNA primary damage. In addition, the results obtained in the Comet assay also show that UC-245 induces a significant increase in the level of DNA breakage, which would confirm its genotoxicity.


Early CT signs of hypoxia in patients with subarachnoid hemorrhage presenting with cardiac arrest: early CT signs in SAH patients presenting with CA.
For cardiac arrest (CA) victims, brain computed tomography (CT) may serve as a prognosticator. Loss of gray-white matter discrimination (GWMD) and sulcal edema/effacement are reliable CT signs of hypoxia, and a time window may exist for development of these signs. Most data are derived from CA victims of cardiac etiology, however, and CT signs have rarely been evaluated in victims of CA secondary to subarachnoid hemorrhage (SAH). A retrospective study was conducted to clarify the incidence, temporal profile, and prognostic significance of early CT signs in resuscitated SAH-CA patients. During a 6-year period, 35 SAH-CA patients were identified. CT signs were observed in 94 %: loss of GWMD was observed in 94 %, whereas sulcal edema/effacement was observed in 77 %. In 29 patients, the interval between CA and the return of spontaneous circulation (ROSC) was estimated. CT signs developed almost invariably when the CA-ROSC interval exceeded 10 min. Loss of GWMD always preceded sulcal edema/effacement. None of the 35 patients achieved long-term survival, regardless of the presence of the CT signs. CT signs may develop earlier in patients with SAH-CA than CA of cardiac origin. Because of a poor prognosis, early CT signs are not useful prognosticators in that population.