Ectopic pregnancy: its relationship to tubal reconstructive surgery.
Ectopic pregnancy is the shady companion of tubal surgery. Among patients with ectopic pregnancy, relatively few have a history of tubal surgery as their underlying etiologic factor when compared with other etiologies such as PID. Nevertheless, a history of tubal surgery should place the patient at a higher-risk group for ectopic pregnancy; 3% to 20% of these patients will encounter an ectopic pregnancy after the corrective surgery. The incidence of ectopic pregnancy after tubal surgery is extremely variable and is closely linked to the degree of restoration of normal functional and anatomic integrity after the surgical procedure. This depends, to a large extent, on the amount of previous damage to the tube and its potential reversibility. Major improvements in surgical technique can, therefore, have reduced, but not eliminated, the occurrence of tubal pregnancy. The incidence of ectopic pregnancy associated with any given tubal surgical procedure should be taken into consideration when surgery is contemplated. When the risk of ectopic pregnancy is unacceptably high, or when the patient is reluctant to be exposed to a high risk of ectopic pregnancy, IVF-ET could be offered as an alternative. Table 11 represents the incidence of ectopic pregnancy associated with the various surgical procedures. The figures demonstrate the wide variation in outcome for the same procedure.


Inactivation of the p53 tumor suppressor gene via a novel Alu rearrangement.
Inactivation of the p53 tumor suppressor gene is a common finding in human cancer. In most cases, inactivation is due to a point mutation in the gene, but rearrangement of the p53 gene is sometimes observed. We analyzed the inactivation of p53 in the human pancreas cancer cell line Hs766T, which harbors a structural alteration in the p53 gene. This inactivation was found to be the result of a complex deletion/insertion event involving at least two different Alu elements. The rearrangement eliminated exons 2-4 from the p53 gene, whereas a 175-bp Alu fragment was inserted between the breakpoints of the deletion. DNA sequence analysis of this Alu fragment revealed that it is identical to an Alu element in intron 1 of the p53 gene. This is the first report of p53 inactivation due to a rearrangement involving Alu elements. This type of inactivation may go unnoticed when only traditional methods to detect p53 alterations are used.


Imaging of pigmented villonodular synovitis.
Pigmented villonodular synovitis (PVNS) is a rare, benign, idiopathic proliferative disorder of the synovium that results in villous and/or nodular formation in joints, tendon sheaths, and bursae. The disease can be localized or diffuse. Patients with this condition typically present with symptoms of mild discomfort and associated stiffness of the involved joint; however, the spectrum of presentations is broad. Diagnosis of PVNS can be clinically difficult, and plain radiographs are usually nonspecific. Magnetic resonance (MR) imaging is a highly diagnostic modality in characterizing PVNS when it contains hemosiderin deposits exhibiting low signal intensity on all MR image pulse sequences. This article discusses the presentation, pathology, differential diagnosis, diagnostic modalities as well as various treatment options of PVNS.


Incorporating Bacteria as a Living Component in Supramolecular Self-Assembled Monolayers through Dynamic Nanoscale Interactions.
Supramolecular assemblies, formed through noncovalent interactions, has become particularly attractive to develop dynamic and responsive architectures to address living systems at the nanoscale. Cucurbit[8]uril (CB[8]), a pumpkin shaped macrocylic host molecule, has been successfully used to construct various self-assembled architectures for biomedical applications since it can simultaneously bind two aromatic guest molecules within its cavity. Such architectures can also be designed to respond to external stimuli. Integrating living organisms as an active component into such supramolecular architectures would add a new dimension to the capabilities of such systems. To achieve this, we have incorporated supramolecular functionality at the bacterial surface by genetically modifying a transmembrane protein to display a CB[8]-binding motif as part of a cystine-stabilized miniprotein. We were able to confirm that this supramolecular motif on the bacterial surface specifically binds CB[8] and forms multiple intercellular ternary complexes leading to aggregation of the bacterial solution. We performed various aggregation experiments to understand how CB[8] interacts with this bacterial strain and also demonstrate that it can be chemically reversed using a competitor. To confirm that this strain can be incorporated with a CB[8] based architecture, we show that the bacterial cells were able to adhere to CB[8] self-assembled monolayers (SAMs) on gold and still retain considerable motility for several hours, indicating that the system can potentially be used to develop supramolecular bacterial biomotors. The bacterial strain also has the potential to be combined with other CB[8] based architectures like nanoparticles, vesicles and hydrogels.


Familial gynecomastia with increased extraglandular aromatization of plasma carbon19-steroids.
We evaluated a family in which gynecomastia occurred in five males in two generations. In each affected subject, gynecomastia and male sexual maturation began at an early age. The ratio of the concentration of plasma estradiol-17 beta to that of plasma testosterone was elevated in each affected subject. In the three siblings with gynecomastia, the transfer constant of conversion of androstenedione to estrone (i.e., the fraction of plasma androstenedione that was converted to estrone as measured in the urine) was 10 times that of normal persons. The transfer constant of conversion of testosterone to estradiol-17 beta in the one subject studied also was 8-10 times that of normal men, whereas the transfer constants of conversion of estrone to estradiol-17 beta and of estradiol-17 beta to estrone were normal. Despite the elevation in extraglandular aromatase activity, there was a normal response of the hypothalamic-pituitary axis to provocative stimuli. This is the second documentation of gynecomastia that is associated with increased extraglandular aromatase activity, and the first time that the defect was found to be familial with a probable X-linked (or autosomal dominant, sex limited) mode of inheritance.


Impact of Environmental Indicators on the COVID-19 Pandemic in Delhi, India.
Currently, there is a massive debate on whether meteorological and air quality parameters play a crucial role in the transmission of COVID-19 across the globe. With this background, this study aims to evaluate the impact of air pollutants (PM2.5, PM10, CO, NO, NO2, and O3) and meteorological parameters (temperature, humidity, wind speed, and rainfall) on the spread and mortality due to the COVID-19 outbreak in Delhi from 14 Mar 2020 to 3 May 2021. The Spearman's rank correlation method employed on secondary data shows a significant correlation between the COVID-19 incidences and the PM2.5, PM10, CO, NO, NO2, and O3 concentrations. Amongst the four meteorological parameters, temperature is strongly correlated with COVID-19 infections and deaths during the three phases, i.e., pre-lockdown (14 March 2020 to 24 March 2020) (r = 0.79), lockdown (25 March 2020 to 31 May 2020) (r = 0.87), and unlock (1 June 2020 to 3 May 2021) (r = -0.75), explaining the variability of about 20-30% in the lockdown period and 18-19% in the unlock period. NO2 explained the maximum variability of 10% and 7% in the total confirmed cases and deaths among the air pollutants, respectively. A generalized linear model could explain 80% and 71% of the variability in confirmed cases and deaths during the lockdown and 82% and 81% variability in the unlock phase, respectively. These findings suggest that these factors may contribute to the transmission of the COVID-19 and its associated deaths. The study results would enhance the ongoing research related to the influence of environmental factors. They would be helpful for policymakers in managing the outbreak of COVID-19 in Delhi, India.


Loss of heterozygosity mapping at chromosome arm 16q in 712 breast tumors reveals factors that influence delineation of candidate regions.
Loss of heterozygosity (LOH) at the long arm of chromosome 16 occurs in at least half of all breast tumors and is considered to target one or more tumor suppressor genes. Despite extensive studies by us and by others, a clear consensus of the boundaries of the smallest region of overlap (SRO) could not be identified. To find more solid evidence for SROs, we tested a large series of 712 breast tumors for LOH at 16q using a dense map of polymorphic markers. Strict criteria for LOH and retention were applied, and results that did not meet these criteria were excluded from the analysis. We compared LOH results obtained from samples with different DNA isolation methods, ie., from microdissected tissue versus total tissue blocks. In the latter group, 16% of the cases were excluded because of noninterpretable LOH results. The selection of polymorphic markers is clearly influencing the LOH pattern because a chromosomal region seems more frequently involved in LOH when many markers from this region are used. The LOH detection method, i.e., radioactive versus fluorescence detection, has no marked effect on the results. Increasing the threshold window for retention of heterozygosity resulted in significantly more cases with complex LOH, i.e., several alternating regions of loss and retention, than seen in tumors with a small window for retention. Tumors with complex LOH do not provide evidence for clear-cut SROs that are repeatedly found in other samples. On disregarding these complex cases, we could identify three different SROs, two at band 16q24.3 and one at 16q22.1. In all three tumor series, we found cases with single LOH regions that designated the distal region at 16q24.3 and the region at 16q22.1. Comparing histological data on these tumors did not result in the identification of a particular subtype with LOH at 16q or a specific region involved in LOH. Only the rare mucinous tumors had no 16q LOH at all. Furthermore, a positive estrogen content is prevalent in tumors with 16q LOH, but not in tumors with LOH at 16q24.3 only.


Impact of Glutathione on Wines Oxidative Stability: A Combined Sensory and Metabolomic Study.
This paper is a comprehensive study regarding the role of glutathione as a natural antioxidant on white wines aging potential. It includes sensory and ultrahigh resolution mass spectrometry (FTICR-MS) metabolomics of aged chardonnay wines from 2008 to 2009 vintages, made after glutathione spiking at alcoholic fermentation or bottling. The closure effect was also considered. The sensory analysis revealed a clear vintage, closure and glutathione effect on wines oxidative character after several years of bottle aging. Spearman rank correlation was applied to link the sensory analysis and the exact mass information from FT-ICR-MS. FTICR-MS along with multivariate statistical analyses put in evidence that glutathione efficiency against wines sensory oxidative stability is related to wines antioxidant metabolome consisting of N- and S- containing compounds like amino acids, aromatic compounds and peptides. The chemical composition and origin of wines antioxidant metabolome suggests that its management since the very beginning of the vinification process is a key factor to estimate wines aging potential.


Diagnostic advances in interstitial lung disease.
In summary, the interstitial lung diseases represent a large group of diseases with similar clinical and pathophysiologic features but widely different etiologies. A definitive diagnosis usually depends on obtaining tissue; however, a clinical diagnosis may be adequate for therapeutic intervention in selected cases. A schematic approach to the evaluation of interstitial lung disease is presented in Figure 5. Currently, there is intense research in developing accurate noninvasive tests not only to enhance diagnosis but also to help monitor and modulate treatment.


[Knee osteoarthritis and SPA therapy: assessment of joint function and quality of life].
In industrialized countries the increase in life expectancy of the population has led to an increase in chronic diseases such as osteoarthritis (OA). Knee osteoarthritis for the high disability and psychological stress, not considered adequately, has negative impact on the quality of life. In this pathology SPA therapy, in particular the sulphur mud-bath therapy, can provide a stage of the therapeutic strategy. However, studies on the impact of SPA therapy on the quality of life in knee osteoarthritis are insufficient. The aim research was to evaluate the effectiveness of SPA therapy on chronic pain, joint function and psychological distress that characterize knee osteoarthritis. The study has been performed on 44 subjects affected by knee Osteoarthritis, being 27 (61%) women and 17 (39%) men (mean age: 58±8.7 years, age range: 42-76 years). The investigated subjects were treated with a cycle of a combination of daily locally applied mud-packs and bicarbonate-sulphurous mineral bath water from Terme of Telese SpA (Benevento-Italy). At the beginning and at the end of the Spa therapy was evaluated the level of pain (using VAS scale), the degree of knee flexion (using goniometer), the level of anxiety and depression (using SDS Zung Test and SAS Zung test) and the impact of sulphurous mud-bath treatment on quality of life (using the algofunctional Lequesne indice). At the end of Spa therapy the results of our study have shown a significant (p<0.05) reduction of the pain (1.8±1.6 → 0,9±1,3) and a significant (p<0.01) increase of the knee flexion (79°±22 → 91.3°±19) with an improved quality of life. The data from this investigation seem to indicate that the SPA therapy may be useful in improving joint function and quality of life in knee osteoarthritis.


Cognitive and Social Functioning Deficits after Anti-N-Methyl-D-Aspartate Receptor Encephalitis: An Exploratory Case Series.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently described life-threatening autoimmune disorder associated with a characteristic multi-stage neuropsychiatric syndrome. Although it is known that the majority of patients experience neuropsychological disturbance post-treatment, some aspects of the cognitive profile remain unclear. This study sought to investigate patterns of cognitive functioning in a sample of anti-NMDAR encephalitis patients. Seven (6F:1M; mean age, 26.4 years; range, 16-37 years) treated patients completed a comprehensive set of neurocognitive and social functioning measures. Performance was analyzed using normative data (where available), and comparison with matched controls (10F:4M; mean age, 25.8 years; range, 16-38 years). Individual cognitive profiles ranged from within normal limits to extensive dysfunction. Relative to controls, the patient group's performance was affected in the domains of verbal/ visual memory, working memory, attention, processing speed, executive functioning, and social cognition. The patient group also reported significantly higher levels of anxiety compared to controls. These results add to the accumulating evidence that neurocognitive deficits, consistent with the distribution and functions of the NMDAR system can persist during recovery from anti-NMDAR encephalitis. This is the first study to provide evidence of performance decrements on measures of social cognition, including some involving theory of mind. (JINS, 2016, 22, 828-838).


A linear multiporphyrinic
A linear multiporphyrinic [2]-rotaxane has been synthesized using the transition metal-templating method for threading a gold(III)-incorporating macrocycle onto a rodlike, phenanthroline-derived chelate bearing carboxylate end groups. Stoppering has been performed by reacting the resulting prerotaxane with the amino derivative of a zinc tetraarylporphyrin under EDC-HOBt activation. A 34% yield has been realized for this one-pot, double amide bond formation.


Otitic hydrocephalus associated with lateral sinus thrombosis and acute mastoiditis in children.
The incidence of intracranial complications of acute otitis media (AOM) has decreased and the need for operative and medical treatment is declined during the antibiotic era. To describe pathognomonic signs, evaluation management, operative findings, clinical course and outcome of otitic hydrocephalus and lateral sinus thrombosis as complications of AOM and mastoiditis in pediatric patients. Two children, 9 and 13 years old, with the diagnosis of OH and TK and MRI findings are presented. Intracranial complications in children resulted from unsuccessful treatment of AOM, which led to acute mastoiditis and lateral sinus thrombosis. Both of the presented children had thrombus in their sigmoid sinus preoperatively, demonstrated by MRI, causing decreased blood flow. Both patients underwent a mastoidectomy and delamination of sigmoid sinus with puncture of sinuses. After medical and surgical treatment, blood flow through the sinus increased significantly. In both cases signs of increased intracranial pressure ceased. The clinical presentation of otogenic lateral sinus thrombosis (LST) as a complication of acute otitis media (AOM) can be masked by antibiotic treatment. The episodes of vomiting, headache, visual impairment and a history of AOM seem to be indicative for otitic hydrocephalus. MRI scans of patients with similar symptoms should be carefully studied to facilitate the early diagnosis of dural sinus thrombosis with increased intracranial pressure. Contrast-enhanced computed tomography scan and magnetic resonance imaging play a major role in determining diagnosis and treatment plans in this intracranial complications. Management included systemic antibiotics, short-term heparin anticoagulation and surgical decompression. In our patients intensive i.v. antibiotic treatment, steroids, anticoagulants and surgery led to a significant improvement in the clinical condition.


SAMase gene of bacteriophage T3 is responsible for overcoming host restriction.
Deletion and point mutants of T3 have been isolated and used to show that the early region of T3 DNA is organized in the same way as that of T7 DNA. Homologous early RNAs and proteins of the two phages have been identified by electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate. Both phages have five early mRNA's, numbered 0.3, 0.7, 1,1.1 and 1.3 from left to right, although no T3 protein that corresponds to the 1.1 protein of T7 has yet been identified. In general, corresponding early RNAs and proteins of the two phages migrate differently on gels, indicating that they differ in molecular weight and/or conformation. In both T7 and T3, gene 0.3 is responsible for overcoming the DNA restriction system of the host, gene 0.7 specifies a protein kinase, gene 1 specifies a phage-specific RNA polymerase, and gene 1.3 specifies a polynucleotide ligase. The 0.3 protein of T3 is responsible for the S-adenosylmethionine cleaving activity (SAMase) induced after T3 (but not T7) infection. However, cleaving of S-adenosylmethionine does not appear to be the primary mechanism by which T3 overcomes host restriction, since at least one mutant of T3 has lost the SAMase activity without losing the ability to overcome host restriction.


Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection.
The clinical course of HIV-1 infection is highly variable among individuals, at least in part as a result of genetic polymorphisms in the host. Toll-like receptors (TLRs) have a key role in innate immunity and mutations in the genes encoding these receptors have been associated with increased or decreased susceptibility to infections. To determine whether single-nucleotide polymorphisms (SNPs) in TLR2-4 and TLR7-9 influenced the natural course of HIV-1 infection. Twenty-eight SNPs in TLRs were analysed in HAART-naive HIV-positive patients from the Swiss HIV Cohort Study. The SNPs were detected using Sequenom technology. Haplotypes were inferred using an expectation-maximization algorithm. The CD4 T cell decline was calculated using a least-squares regression. Patients with a rapid CD4 cell decline, less than the 15th percentile, were defined as rapid progressors. The risk of rapid progression associated with SNPs was estimated using a logistic regression model. Other candidate risk factors included age, sex and risk groups (heterosexual, homosexual and intravenous drug use). Two SNPs in TLR9 (1635A/G and +1174G/A) in linkage disequilibrium were associated with the rapid progressor phenotype: for 1635A/G, odds ratio (OR), 3.9 [95% confidence interval (CI),1.7-9.2] for GA versus AA and OR, 4.7 (95% CI,1.9-12.0) for GG versus AA (P = 0.0008). Rapid progression of HIV-1 infection was associated with TLR9 polymorphisms. Because of its potential implications for intervention strategies and vaccine developments, additional epidemiological and experimental studies are needed to confirm this association.


ACTH for epileptic spasms in Leigh syndrome with SLC19A3 mutation can induce status dystonicus.
Patients with Leigh syndrome (LS) sometimes develop epileptic spasms (ES). ACTH treatment for ES may be effective without serious adverse events in some patients with LS. Status dystonicus is a life-threatening disorder characterized by an acute exacerbation of generalized dystonia and often develops as a triggered event. The underlying pathophysiology of status dystonicus remains unclear. To our knowledge, there has been no reported case of status dystonicus associated with ACTH treatment. Here, we describe the first reported patient with LS, harbouring compound heterozygous mutations in SLC19A3 gene, who developed status dystonicus following initial intramuscular injection of a course of ACTH treatment for ES. Stressors can precipitate acute exacerbation in SLC19A3-related disorders. Interestingly, in this patient, external discomfort stimuli tended to induce transient hypertonia with opisthotonos. This report suggests that attention should be paid to acute exacerbation of generalized dystonia when ACTH treatment for ES is started in patients with LS, who have dystonia tend to exacerbate transiently by external discomfort stimuli.


Polysphondylium multicystogenum sp. nov., a new dictyostelid species from Sierra Leone, West Africa.
Polysphondylium multicystogenum, a new heterothallic species of dictyostelids, is described based on three isolates collected from soils in Sierra Leone, West Africa. This species is characterized by sorophores with a combination of clavate base and ovoid to oblong tip cell, smaller spores and abundant microcyst production under the usual culture conditions for sorocarp formation at 20 C. This is the first report of Polysphondylium producing such abundant microcysts.


Human pituitary tumor-transforming gene 1 overexpression reinforces oncogene-induced senescence through CXCR2/p21 signaling in breast cancer cells.
hPTTG1 (human pituitary tumor-transforming gene 1) is an oncogene overexpressed in breast cancer and several other types of cancer. Increased hPTTG1 expression has been shown to be associated with poor patient outcomes in breast cancer. Although hPTTG1 overexpression plays important roles in promoting the proliferation, invasion, and metastasis of cancer cells, it also has been suggested to induce cellular senescence. Deciphering the mechanism by which hPTTG1 overexpression induces these contradictory actions in breast cancer cells is critical to our understanding of the role of hPTTG1 in breast cancer development. MCF-10A and MCF-7 cells were used to identify the mechanism of hPTTG1-induced senescence. The interplay between hPTTG1 overexpression and chemokine C-X-C motif receptor 2 (CXCR2)/p21-dependent senescence in tumor growth and metastasis of MCF-7 cells was investigated by orthotopic transplantation of severe combined immunodeficiency (SCID) mice. Additionally, human invasive ductal carcinoma (IDC) tissue arrays were used to confirm the hPTTG1/CXCR2/p21 axis established in vitro. In this study, we investigated the mechanism of hPTTG1-induced senescence as well as its role in breast cancer progression and metastasis. Herein, we showed that hPTTG1 overexpression reinforced senescence through the CXCR2/p21 signaling. Furthermore, hPTTG1 overexpression activated NF-κB signaling to transactivate the expression of interleukin (IL)-8 and growth-regulated oncogene alpha (GROα) to execute CXCR2 signaling in MCF-7 cells. When CXCR2 expression was knocked down in hPTTG1-overexpressing MCF-7 cells, hPTTG1-induced senescence was abrogated by alleviating CXCR2-induced p21 expression. In a mouse model, CXCR2-mediated senescence limited hPTTG1-induced tumor growth and metastasis. Moreover, CXCR2 knockdown in hPTTG1-overexpressing MCF-7 tumors dramatically accelerated tumor growth and metastasis. Our in vitro and in vivo results demonstrated that hPTTG1 overexpression reinforces senescence through CXCR2 signaling, and the evasion of CXCR2/p21-dependent senescence was critical to hPTTG1 exerting its oncogenic potential. Interestingly, although CXCR2-dependent senescence restrained hPTTG1-induced tumor progression, when MCF-7 cells and hPTTG1-overexpressing MCF-7 cells were co-transplanted into the mammary fat pads of SCID mice, hPTTG1-overexpressing senescent cells created a metastasis-promoting microenvironment that promoted lung metastasis of the MCF-7 cells. Immunohistochemical analysis of human breast tumor samples also confirmed the importance of the hPTTG1/CXCR2 axis in promoting breast cancer metastasis. Our findings provide novel molecular insights into hPTTG1-induced senescence and identify a novel mechanism by which hPTTG1 promotes metastasis by regulating the senescence-associated microenvironment.


Chloroquine affects biosynthesis of Ia molecules by inhibiting dissociation of invariant (gamma) chains from alpha-beta dimers in B cells.
Biosynthetic conversion of Ia oligomers from three chains (alpha, beta, gamma) to two (alpha, beta) before surface expression was inhibited in B lymphoid cells by treatment with chloroquine, resulting in the accumulation of Ia complexes composed of mature alpha and beta chains, and gamma chains at various states of sialylation. Other stages of Ia biosynthesis and processing appeared unaffected, indicating that chloroquine selectively interfered with the gamma chain dissociating mechanism itself. Similar effects were also observed with ammonium chloride. Because of the nature of such lysosomotropic agents, these results suggest that an intracellular acidic compartment may be involved in processing Ia oligomers to accomplish dissociation from gamma chains. Since chloroquine is known to inhibit Ia-restricted antigen presentation in accessory cells, our results raise the possibility that the pathways of antigen processing and Ia biosynthesis may use some common intracellular compartments.


Patient decision-making regarding left ventricular assist devices : A multiple case study.
To understand how patients make decisions regarding a left ventricular assist device (LVAD). A qualitative multiple case study design was used to explore the context and influence of individuals regarding patients' decision-making processes through: 1) detailed, in-depth interviews of those mostly involved in the patient's decision and 2) pertinent data including observations, medical records, educational information and physical artifacts. Data clusters and patterns of co-occurring codes were examined using thematic analysis. Themes were extrapolated from individual case summaries to provide an in-depth analysis of each case and a cross-case analysis across the multiple cases. The predominant theme, consistent with other studies, was the salience of survival. This case study approach revealed new themes beyond those of prior studies. Patients considered: 1) self-care management for patients without a caregiver, 2) acceptability and future expectations of the LVAD and 3) the role of nurses in eliciting patients' fears, values and preferences. The patients' decision-making processes regarding an LVAD involve a cost-benefit analysis of the anticipated needs and consequences of the LVAD. Acceptability of the device is relevant to clinical practice and public policy. Nurses have a unique role in seeking patients' concerns, an essential component of shared decision-making.


Reaction modes and mechanism in indolizine photooxygenation reactions.
Photooxygenations of 1,2-, 1,3-, and 2,3-di- and 1,2,3-trisubstituted indolizines 1a-1f under different reaction conditions in methanol and acetonitrile have been investigated to establish the general reaction pattern and mechanism in indolizine photooxygenation in view of the influence of the ring substituents and substitution pattern. Photooxygenations of 1-acyl-2-phenylindolizines 1a and 1b and 1,3-dibenzoyl-2-phenylindolizine (1d) are self-sensitized, while those of 1-(p-nitrobenzoyl)-2-phenylindolizine (1c) and 2-phenyl-3-(p-chlorobenzoyl)indolizine (1e) need to be sensitized by rose bengal (RB) or methylene blue (MB). These reactions proceed via a singlet oxygen mechanism yet follow different pathways in methanol and in acetonitrile, with peroxidic zwitterion D (in methanol) and dioxetane E across the indolizine C2-C3 bond (in acetonitrile) as the intervening intermediates. Methanol trapping of the peroxidic zwitterion results in C3-N bond cleavage and pyrrole ring opening to give the corresponding (E)- and (Z)-3-(2-pyridinyl)-3-benzoylpropenoic acid methyl esters (2 and 3) and 4-(2-pyridinyl)-3-phenyl-5-aryl-5-hydroxyfuran-2-one (4) as products in methanol, while O-O bond homolysis of the dioxetane furnishes 3-(2-pyridinyl)-3-benzoyl-2-phenyloxirane-2-carboxaldehyde (6) and 1-(6-methyl-2-pyridinyl)-2-phenylethanedione (5) as products in acetonitrile. 3-Benzoyl-1-indolizinecarboxylic acid methyl ester (1f) is unreactive toward singlet oxygen; however, it could be photooxygenated under electron transfer conditions with 9,10-dicyanoanthracene (DCA) as a sensitizer. This reaction takes place by the combination of the indolizine cation radical with the superoxide anion radical (or molecular oxygen) to give the pyridine ring oxidized methyl 3-benzoyl-5-methoxy-8-hydroxy-1-indolizinecarboxylate (9f), dimethyl 2-(2-pyridinyl)fumarate (8f), and dimethyl 2-(2-pyridinyl)maleate (7f) as products.


Measuring Receptive ASL Skills in Novice Signers and Nonsigners.
We tested the utility of two standardized measures of receptive skills in American Sign Language (ASL) in hearing adults who are novice signers: the ASL Comprehension Test (ASL-CT; Hauser, P. C., Paludneviciene, R., Riddle, W., Kurz, K. B., Emmorey, K., & Contreras, J. (2016). American Sign Language Comprehension Test: A tool for sign language researchers. Journal of Deaf Studies and Deaf Education, 21(1), 64-69. https://doi.org/10.1093/deafed/env051) and the ASL Receptive Skills Test (ASL-RST; Allen, T. E., & Enns, C. (2013). A psychometric study of the ASL Receptive Skills Test when administered to deaf 3-, 4-, and 5-year-old children. Sign Language Studies, 14(1), 58-79. https://doi.org/10.1353/sls.2015.0006; Enns, C. J., & Herman, R. C. (2011). Adapting the Assessing British Sign Language Development: Receptive Skills Test into American Sign Language. Journal of Deaf Studies and Deaf Education, 16(3), 362-374. https://doi.org/10.1093/deafed/enr004). We also administered these tests to hearing nonsigners, with the goal of identifying items where the correct answer can be readily deduced through iconicity and/or test-taking skills, even by people with no prior ASL knowledge. We predicted that removing such items would strengthen the correlation between test score and ASL experience (as measured by semesters of instruction). We found that this relationship was stronger for the ASL-CT than the ASL-RST in this population, but still weaker than previously reported, and not substantially improved by any item selection strategy that we employed.


Differences in the Vulnerability of Waterbird Species to Botulism Outbreaks in Mediterranean Wetlands: an Assessment of Ecological and Physiological Factors.
Avian botulism kills thousands of waterbirds every year, including endangered species, but information about the differences between species in vulnerability to botulism outbreaks and the capacity to act as carriers of Clostridium botulinum is still poorly known. Here, we estimated the vulnerability to botulism of 11 waterbird species from Mediterranean wetlands by comparing the number of affected birds with the census of individuals at risk. The capacity of different species to act as carriers was studied by detecting the presence of the C. botulinum type C/D botulinum neurotoxin (BoNT) gene in fecal samples and prey items of waterbirds in the wild and by the serial sampling of cloacal swabs of birds affected by botulism. We found differences among species in their vulnerabilities to botulism, probably related to feeding habits, season of arrival, turnover, and, possibly, phylogenetic resilience. The globally endangered white-headed duck (Oxyura leucocephala) showed mortality rates in the studied outbreaks of 7% and 17% of the maximum census, which highlights botulism as a risk factor for the conservation of the species. Invasive water snails, such as Physa acuta, may be important drivers in botulism epidemiology, because 30% of samples tested positive for the BoNT gene during outbreaks. Finally, our results show that birds may excrete the pathogen for up to 7 days, and some individuals can do it for longer periods. Rails and ducks excreted C. botulinum more often and for longer times than gulls, which could be related to their digestive physiology (i.e., cecum development). Botulism is an important cause of mortality in waterbirds, including some endangered species. The global climate change may have consequences in the ecology of wetlands that favor the occurrence of botulism outbreaks. Here, we offer some information to understand the ecology of this disease that can be useful to cope with these global changes in the future. We have found that some species (i.e., coots and dabbling ducks) are more vulnerable to botulism and have a more relevant role in the onset and amplification of the outbreaks than other species (i.e., flamingos and grebes). Feeding habits can explain these differences in part; in addition to the well-known role of necrophagous fly maggots, we found here that water snails are frequent carriers of Clostridium botulinum This is relevant, because these water snails can thrive in eutrophic and polluted wetlands, exacerbating other changes driven by climate change in wetlands.


Macrophages escape Klotho gene silencing in the mdx mouse model of Duchenne muscular dystrophy and promote muscle growth and increase satellite cell numbers through a Klotho-mediated pathway.
Duchenne muscular dystrophy (DMD) is a muscle wasting disease in which inflammation influences the severity of pathology. We found that the onset of muscle inflammation in the mdx mouse model of DMD coincides with large increases in expression of pro-inflammatory cytokines [tumor necrosis factor-α (TNFα); interferon gamma (IFNγ)] and dramatic reductions of the pro-myogenic protein Klotho in muscle cells and large increases of Klotho in pro-regenerative, CD206+ macrophages. Furthermore, TNFα and IFNγ treatments reduced Klotho in muscle cells and increased Klotho in macrophages. Because CD206+/Klotho+ macrophages were concentrated at sites of muscle regeneration, we tested whether macrophage-derived Klotho promotes myogenesis. Klotho transgenic macrophages had a pro-proliferative influence on muscle cells that was ablated by neutralizing antibodies to Klotho and conditioned media from Klotho mutant macrophages did not increase muscle cell proliferation in vitro. In addition, transplantation of bone marrow cells from Klotho transgenic mice into mdx recipients increased numbers of myogenic cells and increased the size of muscle fibers. Klotho also acted directly on macrophages, stimulating their secretion of TNFα. Because TNFα is a muscle mitogen, we tested whether the pro-proliferative effects of Klotho on muscle cells were mediated by TNFα and found that increased proliferation caused by Klotho was reduced by anti-TNFα. Collectively, these data show that pro-inflammatory cytokines contribute to silencing of Klotho in dystrophic muscle, but increase Klotho expression by macrophages. Our findings also show that macrophage-derived Klotho can promote muscle regeneration by expanding populations of muscle stem cells and increasing muscle fiber growth in dystrophic muscle.


Postoperative quality of life in patients with progressive neuromuscular scoliosis and their parents.
The functional level of children with progressive neuromuscular disease is a major factor that affects the quality of life (QOL) of parents. However, only a few publications have reported changes in the QOL of parents after correctional spinal surgery. The purpose was to compare changes in QOL for both patients and parents after spinal correctional surgery for better sitting balance and to analyze correlation among radiographic parameters, functional outcome, and QOL questionnaires. Finally, the QOL of patients and parents was compared with the population norm. This study is a retrospective analysis of prospectively gathered data. From 2008 to 2011, 58 patients who underwent correctional surgery for progressive neuromuscular scoliosis and their parents were enrolled. A Muscular Dystrophy Spine Questionnaire (MDSQ) and short-form questionnaire 36 (SF-36) were used. The gathered functional outcome and QOL data using MDSQ and SF-36 for both enrolled patients and parents were compared preoperatively, postoperatively at 3 months, and at 1-year follow-up. Mean age was 15.0±4.1 years. Forty male and 18 female patients were enrolled. Mean follow-up was 38.4±13.7 months. Cobb angle was 61.5°±23.5° preoperatively, 39.0°±20.1° immediately postoperative, and 40.0°±20.2° at the final follow-up. Cobb angle, pelvic obliquity, and lumbar lordosis were significantly improved after surgery (p<.001). Among sitting-related questions, answers to questions 15 (sitting comfortably), 16 (change weight in wheelchair), 22 (sit all day), 24 (sit at table for meal), 26 (keep balance while sitting in wheelchair), and 27 (look good while sitting in wheelchair) were significantly improved after correctional surgery (p<.001). Regarding the SF-36 scales for patients, bodily pain and social functioning significantly improved postoperatively (p<.001). Muscular Dystrophy Spine Questionnaire results indicated that patients had significantly improved sitting balance-related outcomes, whereas the SF-36 indicated improvements only in bodily pain and social functioning scales. For parents, no SF-36 scales improved significantly postoperatively. Accordingly, improved sitting balance and QOL for neuromuscular scoliosis patients after surgery do not necessarily increase parent QOL.


How vessels narrow.
Vascular narrowing, the clinical dilatation of narrowed vessels, and the restenosis of those vessels are central topics in modern cardiology. This review discusses the cellular basis both for the spontaneous narrowing of vessels and for the restenotic process that occurs after angioplasty. The central issue, as discussed in this review, is likely to be remodeling of the vessel wall rather than simple accretion of lipid mass in atherosclerosis or simple physical dilatation following angioplasty. While it is true that the atherosclerotic lesion grows by accretion of lipid mass, this by itself does not narrow vessels. As we will discuss, the vessel has a phenomenal ability to accommodate changes of this sort. Narrowing must occur, at least in part, because of a failure of this normal ability to accommodate. In a similar manner, one might expect the restonotic vessel to simply remodel itself down to its preangioplasty size. The issue for cell and molecular biologists is what "remodeling" means. Until recently, the assertion has been that remodeling occurred as the result of the formation of new intimal mass; that is, the atherosclerotic vessel was seen as returning to its original dimensions following angioplasty as a result of forming a new intimal mass that filled in the dilated space. Recent studies using cell kinetic methods as well as intravascular ultrasound, however, have cast doubt upon this hypothesis. It now appears that the loss of gain following angioplasty is likely to be due to the formation of new tissues which remodel the vessel wall without necessarily adding mass to it. This is the same sort of process that is well described in wound healing. The nature of this new tissue is of great interest. Studies in this laboratory and others have identified genes which may be unique to this tissue and explain the remodeling response.


[Right-sided hemihepatectomy in the closed hepatic trauma (clinical observation and review of the literature)].
A case observation of a severe closed hepatic injury, treated using right-sided hemihepatectomy after primary suturing with tamponade performance and angiographic embolization of right hepatic artery, is presented. The literature review for this problem is presented with special attention to modern approaches in the treatment of the injured persons, suffering hepatic trauma. Various methods of treatment of hepatic injuries are analyzed as well as indications for their usage and efficacy. The tactics of conservative treatment in trauma of IV-V severity grade in the injured persons in conditions of a stable hemodynamics state presence was elaborated. The interventional radiology methods are more widely used in the patients, to whom conservative therapy is conducted or while their stable state is achieved, using a tamponade performance. While unstable state presence during the surgical treatment conduction a tendency is observed to use a "damage control" tactics.


European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack.
The aim of the present European Stroke Organisation Transient Ischaemic Attack (TIA) management guideline document is to provide clinically useful evidence-based recommendations on approaches to triage, investigation and secondary prevention, particularly in the acute phase following TIA. The guidelines were prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined TIA clinically and pragmatically for generalisability as transient neurological symptoms, likely to be due to focal cerebral or ocular ischaemia, which last less than 24 hours. High risk TIA was defined based on clinical features in patients seen early after their event or having other features suggesting a high early risk of stroke (e.g. ABCD2 score of 4 or greater, or weakness or speech disturbance for greater than five minutes, or recurrent events, or significant ipsilateral large artery disease e.g. carotid stenosis, intracranial stenosis). Overall, we strongly recommend using dual antiplatelet treatment with clopidogrel and aspirin short term, in high-risk non-cardioembolic TIA patients, with an ABCD2 score of 4 or greater, as defined in randomised controlled trials (RCTs). We further recommend specialist review within 24 hours after the onset of TIA symptoms. We suggest review in a specialist TIA clinic rather than conventional outpatients, if managed in an outpatient setting. We make a recommendation to use either MRA or CTA in TIA patients for additional confirmation of large artery stenosis of 50% or greater, in order to guide further management, such as clarifying degree of carotid stenosis detected with carotid duplex ultrasound. We make a recommendation against using prediction tools (eg ABCD2 score) alone to identify high risk patients or to make triage and treatment decisions in suspected TIA patients as due to limited sensitivity of the scores, those with score value of 3 or less may include significant numbers of individual patients at risk of recurrent stroke, who require early assessment and treatment. These recommendations aim to emphasise the importance of prompt acute assessment and relevant secondary prevention. There are no data from randomised controlled trials on prediction tool use and optimal imaging strategies in suspected TIA.


Dose of psychotherapy and long-term recovery outcomes: An examination of attendance patterns in alcohol use disorder treatment.
The purpose of this study was to examine associations between psychotherapy session attendance, alcohol treatment outcomes, and Alcoholics Anonymous (AA) attendance. Using data from Project MATCH, repeated measures latent class analyses of psychotherapy session attendance were conducted among participants in the outpatient arm who were randomly assigned to complete 12-session cognitive-behavioral therapy (CBT; n = 301), 12-session twelve-step facilitation (TSF; n = 335), or 4-session motivational enhancement therapy (MET; n = 316). Associations between psychotherapy attendance classes, heavy drinking, alcohol-related consequences, psychosocial functioning, and AA attendance were examined at posttreatment (97% retention), 1-year posttreatment (92% retention), and 3-years posttreatment (85% retention). In general, participants who attended all 12 CBT/TSF sessions had significantly fewer heavy drinking days and alcohol-related consequences at all posttreatment time points than participants who attended 0-2 CBT/TSF sessions. Participants who attended all four MET sessions generally had significantly fewer heavy drinking days and alcohol-related consequences at posttreatment and 1-year posttreatment than participants who attended 0-1 MET sessions. Participants who attended more TSF and MET sessions generally attended more AA meetings, and participants who attended less CBT sessions generally attended fewer AA meetings. With some exceptions, attending all sessions in CBT, TSF, and MET was related to the most favorable heavy drinking and alcohol-related consequences outcomes. Alcoholics' Anonymous and other mutual help groups may be attended differently based on the form and dose of psychotherapy (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Xeroradiography in the diagnosis of the Haglund syndrome.
Xeroradiography is the radiographic method of choice for assessment of soft tissues and calcaneal detail in patients suffering from a painful swelling localized in the heel. The radiographic triad of retrocalcaneal bursitis, superficial tendo Achillis bursitis, and Achilles tendon thickening, in the presence of an intact posterior superior calcaneal margin, are readily evaluated with xeroradiography. The Haglund syndrome is a painful inflammation involving the two bursae which surround the Achilles tendon. It is associated with a prominent posterior superior calcaneal margin. Of the two objective measurements devised to assess this prominence, neither the posterior calcaneal angle of Philip and Fowler of greater than 75 degrees nor the parallel pitch line (PPL) has proved to be a reliable index. In the present study, we evaluated four patients with heel pain and swelling as well as 100 control patients. The findings suggest that the prominence of the posterior calcaneal angle should be assessed relative to the known normal range rather than by comparison to a single fixed angulation which is arbitrarily designated as being abnormal.


Acetylcholine modulates gamma frequency oscillations in the hippocampus by activation of muscarinic M1 receptors.
Modulation of gamma oscillations is important for the processing of information and the disruption of gamma oscillations is a prominent feature of schizophrenia and Alzheimer's disease. Gamma oscillations are generated by the interaction of excitatory and inhibitory neurons where their precise frequency and amplitude are controlled by the balance of excitation and inhibition. Acetylcholine enhances the intrinsic excitability of pyramidal neurons and suppresses both excitatory and inhibitory synaptic transmission, but the net modulatory effect on gamma oscillations is not known. Here, we find that the power, but not frequency, of optogenetically induced gamma oscillations in the CA3 region of mouse hippocampal slices is enhanced by low concentrations of the broad-spectrum cholinergic agonist carbachol but reduced at higher concentrations. This bidirectional modulation of gamma oscillations is replicated within a mathematical model by neuronal depolarisation, but not by reducing synaptic conductances, mimicking the effects of muscarinic M1 receptor activation. The predicted role for M1 receptors was supported experimentally; bidirectional modulation of gamma oscillations by acetylcholine was replicated by a selective M1 receptor agonist and prevented by genetic deletion of M1 receptors. These results reveal that acetylcholine release in CA3 of the hippocampus modulates gamma oscillation power but not frequency in a bidirectional and dose-dependent manner by acting primarily through muscarinic M1 receptors.


Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging.
Previous studies have suggested that calcium/calmodulin-dependent protein kinase IV (CaMKIV) functions as a positive regulator for memory formation and that age-related memory deficits are the result of dysfunctional signaling pathways mediated by cAMP response element-binding protein (CREB), the downstream transcription factor of CaMKIV. Little is known, however, about the effects of increased CaMKIV levels on the ability to form memory in adult and aged stages. We generated a transgenic mouse overexpressing CaMKIV in the forebrain and showed that the upregulation of CaMKIV led to an increase in learning-induced CREB activity, increased learning-related hippocampal potentiation, and enhanced consolidation of contextual fear and social memories. Importantly, we also observed reduced hippocampal CaMKIV expression with aging and a correlation between CaMKIV expression level and memory performance in aged mice. Genetic overexpression of CaMKIV was able to rescue associated memory deficits in aged mice. Our findings suggest that the level of CaMKIV expression correlates positively with the ability to form long-term memory and implicate the decline of CaMKIV signaling mechanisms in age-related memory deficits.


Defining the role of tyrosine and rational tuning of oxidase activity by genetic incorporation of unnatural tyrosine analogs.
While a conserved tyrosine (Tyr) is found in oxidases, the roles of phenol ring pKa and reduction potential in O2 reduction have not been defined despite many years of research on numerous oxidases and their models. These issues represent major challenges in our understanding of O2 reduction mechanism in bioenergetics. Through genetic incorporation of unnatural amino acid analogs of Tyr, with progressively decreasing pKa of the phenol ring and increasing reduction potential, in the active site of a functional model of oxidase in myoglobin, a linear dependence of both the O2 reduction activity and the fraction of H2O formation with the pKa of the phenol ring has been established. By using these unnatural amino acids as spectroscopic probe, we have provided conclusive evidence for the location of a Tyr radical generated during reaction with H2O2, by the distinctive hyperfine splitting patterns of the halogenated tyrosines and one of its deuterated derivatives incorporated at the 33 position of the protein. These results demonstrate for the first time that enhancing the proton donation ability of the Tyr enhances the oxidase activity, allowing the Tyr analogs to augment enzymatic activity beyond that of natural Tyr.


Cyclosporin A inhibits IL 2-driven proliferation of human alloactivated T cells.
The influence of cyclosporin A (CsA) on the interleukin 2 (IL 2)-driven proliferation of allo-activated human T lymphocytes has been studied. CsA (50, 100, and 250 ng/ml) appeared to affect the IL 2-driven proliferation. The impaired proliferation could not be reversed with exogenous interferon-gamma. The doubling time of the cell populations appeared to increase with higher CsA doses. The cytotoxic capacity of the cells was also strongly inhibited by CsA. The cells regained proliferative and cytotoxic properties after CsA has been removed and cells were additionally cultured in normal medium. The data strongly suggest that CsA has an inhibitory influence on essential basic processes in T cells.


Use of high throughput sequencing and light microscopy show contrasting results in a study of phytoplankton occurrence in a freshwater environment.
Assessing phytoplankton diversity is of primary importance for both basic and applied ecological studies. Following the advances in molecular methods, phytoplankton studies are switching from using classical microscopy to high throughput sequencing approaches. However, methodological comparisons of these approaches have rarely been reported. In this study, we compared the two methods, using a unique dataset of multiple water samples taken from a natural freshwater environment. Environmental DNA was extracted from 300 water samples collected weekly during 20 years, followed by high throughput sequencing of amplicons from the 16S and 18S rRNA hypervariable regions. For each water sample, phytoplankton diversity was also estimated using light microscopy. Our study indicates that species compositions detected by light microscopy and 454 high throughput sequencing do not always match. High throughput sequencing detected more rare species and picoplankton than light microscopy, and thus gave a better assessment of phytoplankton diversity. However, when compared to light microscopy, high throughput sequencing of 16S and 18S rRNA amplicons did not adequately identify phytoplankton at the species level. In summary, our study recommends a combined strategy using both morphological and molecular techniques.


Challenges to Differentiate Hepatitis C Genotype 1 and 6: Results from A Field-Study in Cambodia.
We aim to report on results and challenges of different methods used for hepatitis C (HCV) genotyping in a Cambodian HCV/HIV coinfection project. Samples of 106 patients were available. HCV genotyping was initially (63 samples) done by the LightPower Taqman real-time PCR method (Viet A Corp.) and quality controlled using the Versant 2.0 line probe assay (Siemens Healthcare). Next, following interim quality control results, all 106 samples were (re)genotyped with Versant 2.0, complemented with 5'UTR/core sequencing for uninterpretable/incomplete Versant results. Using Versant, 103 (97.2%) of the 106 HCV-coinfected patients had an interpretable genotype result: 1b (50.5%), 6 non-a/non-b (30.1%), 1a (6.8%), 6a or b (4.9%), 2 (3.9%), 1 (2.9%) and 3 (1.0%). For 16 samples that were interpreted as genotype 1 or 1b per Versant's current instructions, it could not be excluded that it concerned a genotype 6 infection as the core region line patterns on the Versant test strip were unavailable, inconclusive or atypical. Upon sequencing, seven of these were genotyped as 1b and nine as genotype 6. Combining Versant and sequencing results, a definitive genotype was assigned in 104 patients: 1b (44.2%), 6 non-a/non-b (39.4%), 1a (6.7%), 6a or b (4.8%), 2 (3.8%) and 3 (1.0%). Genotyping by LightPower and Versant was discordant for 23 (of 63) samples. The LightPower assay misclassified all genotype 6 non-a/non-b samples as genotype 1, which indicates that this assay is only using 5'UTR information. HCV genotype 1b and genotype 6 non-a/non-b were most common. With Versant 2.0 (using 5'UTR and core information), genotype classification (1 or 6) remained inconclusive in 15% of samples. The locally available method (LightPower assay) failed to identify genotype 6 non-a/non-b, which highlights that methods using 5'UTR information only should not be used in Cambodia. Regional/national guidelines should be explicit about this. This study was performed as part of a larger cross-sectional study on the burden of hepatitis C coinfection in HIV patients in Cambodia (Clinical.trials.gov: HCV-Epi NCT02361541).


An automated dry-slide enzymatic method evaluated for measurement of creatinine in serum.
We evaluated an automated dry-slide enzymatic method involving creatinine iminohydrolase for measurement of creatinine in serum with the Kodak Ektachem analyzer. The means (and SD) for three commercially available quality-control sera, analyzed during eight weeks, were 9.7 (1.0), 16.6 (0.9), and 61 (2.1) mg/L. The regression equation for 105 samples measured with the Technicon SMAC (x) and Ektachem Analyzers (y) was: y = (0.89 +/- 0.007)x + (1.7 +/- 0.3) mg/L and for 170 samples measured with the Beckman Astra (x) and Ektachem analyzers (y): y = (1.00 +/- 0.005)x - (1.9 +/- 0.16) mg/L. Sixty-one samples from renal-transplant patients showed nearly the same agreement. The enzymatic method had no interference from substances that interfere with many Jaffé methods for creatinine, including acetoacetate. The drugs cephalothin and cephoxitin did not interfere, but 5-fluorocytosine interfered significantly with creatinine in the Ektachem method. Values for several ketone-positive sera were 5 to 10 mg/L higher by the Astra relative to the Ektachem. Grossly hemolyzed or lipemic samples were analyzed without difficulty. We conclude that this enzymatic method for creatinine in serum has the speed and precision necessary for routine clinical laboratory use and, except for one drug, the method appears to be specific for creatinine.


The Clinical Center's blood glucose management service: a story in quality integrated care.
Blood glucose management in the inpatient setting has been shown to be crucial to patient outcomes. As the evidence develops to determine best clinical practices for achieving inpatient glycemic goals, the Clinical Center at the National Institutes of Health has implemented a streamlined multidisciplinary approach to managing blood glucose levels for hospitalized patients. The purpose of this article is to describe the blood glucose management service at the Clinical Center. The blood glucose management service has established a consistent plan of care for diabetes management that has gained acceptance among staff and patients and improved safety and patient outcomes. This plan of care has been applied across various nursing units that serve patient populations on clinical research trials investigating common and rare diseases and treating patients from the United States and around the world.


Hemodialysis patient outcomes: provider characteristics.
Physician characteristics are associated with differential performance on quality measures and patient outcomes in several medical fields. We aimed to determine whether characteristics of physicians who provide care to dialysis patients were associated with patient outcomes. This cohort study used United States Renal Data System data for patients who initiated in-center hemodialysis between October 1, 2003, and September 30, 2006 (n = 91,276). Patient characteristics were defined and physicians identified from Part B Medicare claims for outpatient dialysis services submitted during months 4-6 of hemodialysis. Physician characteristics were obtained from the American Medical Association Physician Master File. Associations of physician characteristics with 1-year patient mortality and first hospitalization were determined using Cox proportional hazards analysis; associations with quality of care (defined by influenza vaccination and waitlisting for kidney transplant) were determined using logistic regression. Physician characteristics were not associated with patient mortality. After adjustment for patient and other provider characteristics, patients whose physicians had practiced longer or were in administrative, research, or teaching practices were more likely to be hospitalized; patients whose providers practiced in smaller metropolitan statistical areas (MSAs) were less likely. More years since training was associated with greater chance of waitlisting, and practicing in smaller MSAs with less chance. Graduation from a foreign medical school, practicing in smaller MSAs, and travelling farther from office to dialysis unit were associated with greater odds of influenza vaccination. Several characteristics of physicians seeing incident outpatient hemodialysis patients were associated with hospitalization and quality of care, but none with mortality.


Comprehensive Investigation of the Influence of High-Altitude Hypoxia on Clopidogrel Metabolism and Gut Microbiota.
The amount of metabolites converted into active metabolites is correspondingly reduced since only more than 50% of clopidogrel is absorbed. Exploring the effect of gut microbiota altered by altitude hypoxia on the pre-absorption metabolism of clopidogrel. In vitro and in vivo experiments were conducted to analyze the metabolism of clopidogrel through LCMS/MS, while 16S rRNA analysis was used to investigate the changes in the gut microbiota of high-altitude animals. We demonstrated that the intestinal flora is involved in the metabolism of clopidogrel through in vivo and in vitro experiments. In addition, the plateau environment caused changes in the number and composition of intestinal microbes. Intriguingly, alterations in the microbial population could lead to an increase in the pre-absorption metabolism of clopidogrel after rapid entry into the plateau, the amount of absorbed blood is thus reduced, which may affect the bioavailability and therapeutic effect of clopidogrel. Our results not only as a first clinical reference for dose adjustment of clopidogrel in high-altitude environments but also would be helpful to provide a statement on the broader significance within the field of pharmacokinetics or personalized medicine.


Evaluation of the protective effect of ascorbic acid on nitrite- and nitrosamine-induced cytotoxicity and genotoxicity in human hepatoma line.
Nitrites are ubiquitous environmental contaminants present in drinking water and foods. Nitrosamines can be formed endogenously from nitrate and nitrite and secondary amines or may be present in food, tobacco smoke, and drinking water. The major goal of this work was to evaluate the cytotoxic, reactive oxygen species (ROS)-producing and genotoxic effects of nitrite and nitrosamines and the possible protection by ascorbic acid in HepG2 cells. It was found that nitrite, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and N-nitrosomorpholine (NMOR) decreased cell viability, increased intracellular ROS production, and caused genotoxicity. Compared to untreated cells as determined by alkaline Comet assay, nitrite, NDMA, NDEA, and NMOR raised the tail intensity up to 1.18-, 3.79-, 4.24-, and 4.16-fold, respectively. Ascorbic acid (AA, 10 microM) increased cell viability and reduced ROS production significantly (p < 0.05). Additionally, AA treatment decreased the tail intensity caused by nitrite, NDMA, NDEA, and NMOR to 33.74%, 58.6%, 44.32%, and 43.97%, respectively. It can be concluded that ascorbic acid was able to reduce both tail intensity and tail moment in all of the nitrosamine treatments, particularly in NDMA. AA protected HepG2 cells against genotoxic effects caused by nitrosamines. This protection might be through different mechanisms, some of which are not still understood in depth. The future interest will be to understand which pathways are influenced by antioxidants, particularly by AA, and the outcomes of this prevention in other cell line types.


Glycerol is not an inhibitor of mitochondrial citrate oxidation by Aspergillus niger.
We have re-assessed the hypothesis that an accumulation of intracellular glycerol triggers the accumulation of citric acid by Aspergillus niger by inhibiting the activity of the mitochondrial NADP-dependent isocitrate dehydrogenase isoenzyme. To this end, we have incubated mycelia of A. niger with 0.5 M glycerol, which resulted in a maximal intracellular glycerol pool level of 0.92 M, comparable to that determined during the early phase of citrate accumulation. This addition affected neither the uptake of [1,5-14C] citrate from the medium nor the rate of the subsequent release of 14CO2 by the mycelia, indicating no effect on citrate oxidation. Mitochondria isolated from mycelia previously loaded with 0.5 M glycerol contained 8% of the total mycelial glycerol. They released 14CO2 from exogenously added [1,5-14C]citrate at the same rate as mitochondria isolated from mycelia not loaded with 0.5 M glycerol. The addition of glycerol had no effect on the activity of the purified NADP-specific isocitrate dehydrogenase, but appeared to inhibit the activity in crude cell-free extracts of A. niger. We conclude that the intracellular accumulation of glycerol does not affect the rate of mitochondrial citrate oxidation and is therefore, in contrast to previous claims, not a trigger of citrate accumulation.


Salt and peroxide compared with conventional oral hygiene. III. Patient compliance and acceptance.
This study was undertaken to evaluate patient compliance with, and acceptance of, a salt and peroxide oral hygiene regimen compared with conventional oral hygiene regimens without or with the use of phase-contrast microscope viewing of subgingival plaque over a period of 2 years. A total of 231 subjects with early to moderate periodontitis were randomly divided into four groups. All groups were repeatedly instructed and motivated in their respective regimens. Subjects also received scaling and root planing using clinical and microbial criteria. Compliance with, and acceptance of, the two oral hygiene regimens were determined at the end of the study using a structured self-administered questionnaire. Results indicated that 74% and 58% (P less than or equal to 0.01) of subjects in the conventional and salt/peroxide groups, respectively, used their assigned regimen 4 to 7 days a week during the entire study. More than half of the subjects (54%) using each of the oral hygiene regimens indicated that they flossed once daily. Inconvenience was cited by 23% of the conventional and 43% of the salt/peroxide groups (P less than or equal to 0.01) as the main reason for not using their regimens. Twenty-three per cent of conventional group and 14% of salt/peroxide group indicated that shared their oral hygiene supplies with others. Eighty per cent and 57% (P less than or equal to 0.01) of the conventional and salt/peroxide groups, respectively, stated that they liked their regimens. Ninety-six per cent of all subjects felt that their regimen helped their periodontal status.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of preoperative chronic hypoxemia on geriatrics outcomes after hip arthroplasty: A hospital-based retrospective analysis study.
The partial pressure of oxygen decreases as altitude increases, the preoperative chronic hypoxemia (CH) may have a plausible clinical impact. Risk factors for postoperative serious adverse events (pSAEs) in patients living in high altitudes during primary hip arthroplasty (HA) are not clear.This is an observational study embracing patients from January 1, 2011 to December 31, 2015 at Yan'an Hospital of Kunming City, a 1338-bed municipal teaching hospital of Kunming Medical University. Univariate analysis revealed that significant differences between patients with and without preoperative CH occurred in intraoperative hypotension (77 [33%] vs 34 [47%], P = .040) and that significant differences between patients with and without pSAEs occurred in following variables: preoperative CH (32 [57%] vs 199 [80%], P < .001), intraoperative hypotension (37 [66%] vs 74 [30%], P < .001), highest noradrenaline support (.09 [.01-.21] vs .03 [.01-.05] μg/kg/min, P < .001), higher application of general anesthesia (15 [27%] vs 29 [12%], P = .004), and lower of combined-spinal epidural anesthesia (CSEA) (21 [37%] vs 165 [66%], P < .001). The general anesthesia and intraoperative hypotension remained the independent risk factors for pSAEs (P < .05), while the preoperative CH presented by decreasing its risk (P < .05).This study suggests that various intraoperative events including general anesthesia, hypotension were risk factors for the development of pSAEs. Preoperative CH, presenting with decreased incidence of intensive care unit (ICU) admission and pSAEs, may mimic hypoxic preconditioning in organic protection, for which further study is needed to uncover the underlying mechanisms.


The ALERT-B questionnaire: A screening tool for the detection of gastroenterological late effects after radiotherapy for prostate cancer.
There is an increasing need to measure treatment-related side effects in normal tissues following cancer therapy. The ALERT-B (Assessment of Late Effects of RadioTherapy - Bowel) questionnaire is a screening tool that is composed of four items related specifically to bowel symptoms. Those patients that respond with a "yes" to any of these items are referred on to gastroenterologist in order to improve the long-term consequences of these side effects of radiological treatment. Here we wish to test the ability of this questionnaire to identify these subsequent gastroenterological complications by tracking prostate cancer patients that were positive with respect to ALERT-B. We also carry out receiver-operator curve (ROC) analysis for baseline data for an overall ALERT-B questionnaire score with respect to subscale data for the Gastrointestinal Symptom Rating Scale (GSRS) and the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. 84.4% and 95.7% of patients identified by the ALERT-B questionnaire demonstrated complications diagnosed at 6 and 12 months post-treatment, respectively. ROC curve analysis of baseline data showed that ALERT-B detected clinically relevant levels of side effects established at baseline by the GSRS diarrhoea subscale (AUC = 0.867, 95% CI = 0.795 to 0.926) and at the minimally important level of side effects for the EPIC bowel subscale (AUC = 0.765, 95% CI = 0.617 to 0.913). These results show that ALERT-B provides a simple and effective screening tool for identifying gastroenterological complications after treatment for prostate cancer.


AgroEcoList 1.0: A checklist to improve reporting standards in ecological research in agriculture.
Many publications lack sufficient background information (e.g. location) to be interpreted, replicated, or reused for synthesis. This impedes scientific progress and the application of science to practice. Reporting guidelines (e.g. checklists) improve reporting standards. They have been widely taken up in the medical sciences, but not in ecological and agricultural research. Here, we use a community-centred approach to develop a reporting checklist (AgroEcoList 1.0) through surveys and workshops with 23 experts and the wider agroecological community. To put AgroEcoList in context, we also assessed the agroecological community's perception of reporting standards in agroecology. A total of 345 researchers, reviewers, and editors, responded to our survey. Although only 32% of respondents had prior knowledge of reporting guidelines, 76% of those that had said guidelines improved reporting standards. Overall, respondents agreed on the need of AgroEcolist 1.0; only 24% of respondents had used reporting guidelines before, but 78% indicated they would use AgroEcoList 1.0. We updated AgroecoList 1.0 based on respondents' feedback and user-testing. AgroecoList 1.0 consists of 42 variables in seven groups: experimental/sampling set-up, study site, soil, livestock management, crop and grassland management, outputs, and finances. It is presented here, and is also available on github (https://github.com/AgroecoList/Agroecolist). AgroEcoList 1.0 can serve as a guide for authors, reviewers, and editors to improve reporting standards in agricultural ecology. Our community-centred approach is a replicable method that could be adapted to develop reporting checklists in other fields. Reporting guidelines such as AgroEcoList can improve reporting standards and therefore the application of research to practice, and we recommend that they are adopted more widely in agriculture and ecology.


Development and validation of the Sociocultural Attitudes Towards Appearance Questionnaire-4 (SATAQ-4).
The Sociocultural Attitudes Towards Appearance Questionnaire-3 (SATAQ-3) and its earlier versions are measures designed to assess societal and interpersonal aspects of appearance ideals. Correlational, structural equation modeling, and prospective studies of the SATAQ-3 have shown consistent and significant associations with measures of body image disturbance and eating pathology. In the current investigation, the SATAQ-3 was revised to improve upon some conceptual limitations and was evaluated in 4 U.S. and 3 international female samples, as well as a U.S. male sample. In Study 1, exploratory and confirmatory factor analyses for a sample of women from the Southeastern United States (N = 859) indicated a 22-item scale with 5 factors: Internalization: Thin/Low Body Fat, Internalization: Muscular/Athletic, Pressures: Family, Pressures: Media, Pressures: Peers. This scale structure was confirmed in 3 independent and geographically diverse samples of women from the United States (East Coast N = 440, West Coast N = 304, and North/Midwest N = 349). SATAQ-4 scale scores demonstrated excellent reliability and good convergent validity with measures of body image, eating disturbance, and self-esteem. Study 2 replicated the factorial validity, reliability, and convergent validity of the SATAQ-4 in an international sample of women drawn from Italy, England, and Australia (N = 362). Study 3 examined a sample of college males from the United States (N = 271); the 5-factor solution was largely replicated, yet there was some evidence of an underlying structure unique to men. Future research avenues include additional item testing and modification of the scale for men, as well as adaptation of the measure for children and adolescents.


Combining CAT with cognitive diagnosis: a weighted item selection approach.
Computerized adaptive testing (CAT) was originally proposed to measure θ, usually a latent trait, with greater precision by sequentially selecting items according to the student's responses to previously administered items. Although the application of CAT is promising for many educational testing programs, most of the current CAT systems were not designed to provide diagnostic information. This article discusses item selection strategies specifically tailored for cognitive diagnostic tests. Our goal is to identify an effective item selection algorithm that not only estimates θ efficiently, but also classifies the student's knowledge status α accurately. A single-stage item selection method with a dual purpose will be introduced. The main idea is to treat diagnostic criteria as constraints: Using the maximum priority index method to meet these constraints, the CAT system is able to generate cognitive diagnostic feedback in a fairly straightforward fashion. Different priority functions are proposed. Some of them are based on certain information measures, such as Kullback-Leibler information, and others utilize only the information provided by the Q-matrix. An extensive simulation study is conducted, and the results indicate that the information-based method not only yields higher classification rates for cognitive diagnosis, but also achieves more accurate θ estimation. Other constraint controls, such as item exposure rates, are also considered for all the competing methods.


The impact of a family-centered intervention on the ecology of adolescent antisocial behavior: modeling developmental sequelae and trajectories during adolescence.
This study used an experimental, longitudinal field trial involving random assignment to the Family Check-Up (FCU) to explore the social ecology of adolescent antisocial behavior. A sample of 998 youths and their families was followed from early to late adolescence (age 12 to 18-19). In the intervention condition, 115 families (23%) elected to receive the FCU. In general, random assignment to the FCU in middle school was associated with reductions in late adolescence antisocial behavior (age 18-19). Variable-centered analyses revealed that the effects were mediated by reductions in family conflict from early to middle adolescence (age 12-15). The link between family conflict and antisocial behavior in turn was mediated by association with deviant peers at age 17; parental monitoring at age 17 was also influential but did not attain the status of a mediator. Person-oriented analyses suggested that the FCU was associated with declining trajectories of family conflict and rising trajectories of parental monitoring but was not associated with trajectories of deviant peer association. A dual-trajectory analysis indicated that the pathways to adolescent antisocial behavior were myriad and varied, suggesting new directions for developmental and intervention research.


NMR structure of the complex between the zinc finger protein NCp10 of Moloney murine leukemia virus and the single-stranded pentanucleotide d(ACGCC): comparison with HIV-NCp7 complexes.
The structure of the 56 amino acid nucleocapsid protein NCp10 of retrovirus MoMuLV, which contains a single CX(2)CX(4)HX(4)C-type zinc finger, has been determined previously by NMR. The important role of NCp10 (or NCp7 for HIV-1) in the retroviral life cycle seems mainly related to their preferential binding to single-stranded nucleic acids. We report here the structure of the complex formed between the biologically active (14-53)NCp10 and the oligonucleotide d(ACGCC) in aqueous solution determined by 2D (1)H NMR based methods. The aromatic residue Trp(35) of NCp10 directs nucleic acid complexation as shown by its complete fluorescence quenching upon addition of d(ACGCC). (1)H and (31)P NMR studies support the insertion of Trp(35) between the G(3) and C(4) bases. A total of 577 NOE distance restraints, of which 40 were intermolecular, were used for the structure determination. The zinc finger provides a well-defined surface for the binding of d(ACGCC) through hydrophobic interactions and tryptophan stacking on the guanine. This latter interaction was also observed in the NMR-derived structures of the complexes between NCp7, which contains two successive zinc fingers, and single-stranded DNA and RNA, supporting the proposal for a major role played by aromatic residues of NCp proteins in nucleic acid recognition. Upon binding to the nucleotide a new loop in NCp10 that participates in the intermolecular interaction is formed. Additional interactions provided by positively charged residues surrounding the zinc finger appear necessary for tight binding. The structure of the complex NCp10-d(ACGCC) gives a structural explanation for the loss of virus infectivity following point mutations in the finger domain.


Bridging the Bridging Imidazolate in the Bimetallic Center of the Cu/Zn SOD1 and ALS.
Metallation status of human Cu/Zn superoxide dismutase 1 (SOD1) plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis (ALS). All of the amino acids found in the bimetallic center have been associated with ALS except for two positions. H63 which forms the bridging imidazolate ion in the bimetallic center and K136 which is not directly involved in coordination but located in the bimetallic center were not reported to be mutated in any of the identified ALS cases. In this study, we investigated the structure and flexibility of five SOD1 variants by using classical molecular dynamics simulations. These variants include three substitutions on the non-ALS-linked positions; H63A, H63R, K136A and ALS-linked positions; G37R, H46R/H48D. We have generated four systems for each variant differing in metallation and presence of the intramolecular disulfide bond. Overall, a total of 24 different dimers including the wild-type were generated and simulated at two temperatures, 298 and 400 K. We have monitored backbone mobility, fluctuations and compactness of the dimer structures to assess whether the hypothetical mutations would behave similar to the ALS-linked variants. Results showed that particularly two mutants, H63R and K136A, drastically affected the dimer dynamics by increasing the fluctuations of the metal binding loops compared with the control mutations. Further, these variants resulted in demetallation of the dimers, highlighting probable ALS toxicity that could be elicited by the SOD1 variants of H63R and K136A. Overall, this study bridges two putative SOD1 positions in the metallic center and ALS, underlining the potential use of atomistic simulations for studying disease variants.


Monitoring the modifications of the vitreous humor metabolite profile after death: an animal model.
We applied a metabolomic approach to monitor the modifications occurring in goat vitreous humor (VH) metabolite composition at different times (0, 6, 12, 18, and 24 hours) after death. The (1)H-NMR analysis of the VH samples was performed for the simultaneous determination of several metabolites (i.e., the metabolite profile) representative of the VH status at different times. Spectral data were analyzed by Principal Component Analysis (PCA) and by Orthogonal Projection to Latent Structures (OPLS) regression technique. PCA and OPLS suggested that different spectral regions were involved in time-related changes. The major time-related compositional changes, here detected, were the increase of lactate, hypoxanthine, alanine, total glutathione, choline/phosphocholine, creatine, and myo-inositol and the decrease of glucose and 3-hydroxybutyrate. We attempted a speculative interpretation of the biological mechanisms underlying these changes. These results show that multivariate statistical approach, based on (1)H NMR metabolite profiling, is a powerful tool for detecting ongoing differences in VH composition and may be applied to investigate several physiological and pathological conditions.


Yamadazyma insecticola f.a., sp. nov. and Yamadazyma epiphylla f.a., sp. nov., two novel yeast species.
Two yeast strains representing two novel yeast species were isolated from frass of an unidentified insect (ST-78(T)) and the external surfaces of rice leaves (YE170(T)) collected in Thailand. The two strains were genetically, morphologically and phenotypically distinct from recognized species and were found to represent two novel species of the genus Yamadazyma although formation of ascospores was not observed. In terms of pairwise sequence similarity of the D1/D2 region of the large subunit rRNA gene, the closest relative of strain ST-78(T) was Candida lessepsii CBS 9941(T) but with 3.8% nucleotide substitutions, while the closest relative of strain YE170(T) was strain ST-78(T) but with 4.3% nucleotide substitutions. Analysis of the sequences of the internal transcribed spacer 1 and 2 (ITS1-2) regions revealed that strain ST-78 differed from C. lessepsii CBS 9941(T) by 8.8% nucleotide substitutions and from strain YE170(T) by 9.4% nucleotide substitutions. The result of pairwise sequence similarity of the D1/D2 and ITS1-2 regions together with phylogenetic analysis indicated that strains ST-78(T) and YE170(T) represented two novel species within the Yamadazyma clade. The names Yamadazyma insecticola f.a., sp. nov. (type strain ST-78(T) = BCC 8314(T) = NBRC 110421(T) = CBS 13382(T); MycoBank no. MB810546) and Yamadazyma epiphylla f.a., sp. nov. (type strain YE170(T) = BCC 63466(T) = NBRC 110423(T) = CBS 13384(T); MycoBank no. MB810547) are proposed for the two novel yeast species.


Pilomyxoid astrocytoma in cerebellum.
Pilomyxoid astrocytoma is a new identified variant type of pilocytic astrocytoma, and typically locates in the hypothalamic and chiasmatic region. Herein, we reported a nine-year-old boy with pilomyxoid astrocytoma in the cerebellum. MRI scanning showed a tumor involved the cerebellar vermis, tonsil, the forth ventricle and brainstem. It was homogeneous isointensity on T1WI, relative hyper-intensity on T2WI, hyper-intensity on fluid attenuated inversion recovery (FLAIR) images, and uniform enhancement on contrast T1WI. The tumor was sub-totally removed and was proved histologically to be pilomyxoid astrocytoma. Follow-up at the 5th month, MRI showed the residual tumor enlarged at the brainstem. The patient survived 10 months after the operation, and finally died of respiration failure resulting from brainstem dysfunction.


Targeting host deoxycytidine kinase mitigates Staphylococcus aureus abscess formation.
Host-directed therapy (HDT) is an emerging approach to overcome antimicrobial resistance in pathogenic microorganisms. Specifically, HDT targets host-encoded factors required for pathogen replication and survival without interfering with microbial growth or metabolism, thereby eliminating the risk of resistance development. By applying HDT and a drug repurposing approach, we demonstrate that ( R )-DI-87, a clinical-stage anti-cancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), mitigates Staphylococcus aureus abscess formation in organ tissues upon invasive bloodstream infection. Mechanistically, ( R )-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, ( R )-DI-87-mediated protection of immune cells amplifies macrophage infiltration into deep-seated abscesses, a phenomenon coupled with enhanced pathogen control, ameliorated immunopathology, and reduced disease severity. Thus, pharmaceutical blockade of dCK represents an advanced anti-infective intervention strategy against which staphylococci cannot develop resistance and may help to fight fatal infectious diseases in hospitalized patients.


Evaluation of the psychometric properties of the Italian Internet Addiction Test.
Since the diffusion of Internet addiction has emerged in several cultural contexts, it seems relevant to study the properties of the Internet Addiction Test (IAT)-the most widely used screening instrument-across various cultures. In Italy, only one study has examined the IAT factor validity, and a comprehensive investigation of its psychometric characteristics is so far lacking. The purpose of this study was to perform a psychometric analysis of the Italian IAT. A total of 840 students (Mage=18.65 years, SD=3.85 years; 59% female) were recruited. Pertaining to scale dimensionality, the best-fit measurement model includes two factors: "Emotional and cognitive preoccupations with the Internet and social consequences" and "Loss of control and interference with daily duties" (χ(2)/df=3.38; comparative fit index=0.88; Tucker-Lewis Index=0.87; root mean square error of approximation=0.07), which together explained 45.59% of the variance. Internal consistency Cronbach's alpha values ranged from 0.83 to 0.86. Convergent validity was demonstrated, with significant correlations between IAT and Generalized Problematic Internet Use Scale 2 scores. The Italian version of the IAT was found to have good psychometric properties and a two-factorial structure. Identification of the IAT dimensions may help to define the construct better and develop intervention strategies.


Rash in a foreign worker.
Hookworm-related cutaneous larva migrans (HrCLM) is a zoonosis which is endemic in many sub-tropic and tropical countries including Malaysia. We report a case of a 40-year old plantation worker who presented with a pruritic rash on his abdomen. It is important for clinicians to diagnose and treat HrCLM promptly as this condition results in considerable morbidity when treatment is delayed.


The effect of rehabilitation of northern elephant seals (Mirounga angustirostris) on antimicrobial resistance of commensal Escherichia coli.
The aim of this study was to determine if antimicrobial drug use increases resistance of commensal gastrointensinal Escherichia coli of wild northern elephant seals (Mirounga angustirostris) treated in rehabilitation, and, if so, identify the risk factors involved. Minimum inhibitory concentration (MIC) levels of twelve antimicrobial drugs were determined for 289 E. coli isolates from 99 seals sampled at admission and 277 isolates obtained at release from rehabilitation using broth microdilution. Prevalence of E. coli antimicrobial resistance, MIC(50), MIC(90), and clustering of MIC values were determined for seals and the data were analyzed using Fisher's exact test, ordinal logistic regression and negative binomial regression. At release from rehabilitation 77.8% of the seals had antimicrobial resistant E. coli compared to 38.4% of the seals at admission. The MIC(90) for amoxicillin-clavulanic acid, chloramphenicol, enrofloxacin, ticarcillin-clavulanic acid, and trimethoprim-saulfamethoxazole were at levels considered to be sensitive at admission but they increased to levels of resistance at release. E. coli were grouped into four clusters by their MIC values, with increasing levels of resistance going from Cluster 1 to 4. A primary risk factor associated with the probability of a seal having E. coli in Clusters 3 and 4 was time in rehabilitation, regardless of whether the animal received treatment with antimicrobial drugs, suggesting nosocomial infection. The results of this study provide evidence that increased levels of hygiene and appropriate use of antimicrobial therapy might be important in the rehabilitation of wild animals to prevent rise in the prevalence of antimicrobial resistant bacteria.


Calvarial bone graft donor site: a histological study in a rabbit model.
Recently the calvarium has become a popular site for harvesting bone grafts because of its low incidence of morbidity, its proximity to the operative site, and the decreased amount of resorption as a result of its membranous nature. However, information regarding the phenomenon of repair at the donor site itself remains lacking. This investigation was initiated in 40 adult white New Zealand rabbits as an experimental model to study the process of repair at the donor site and to examine the possible use of hydroxyapatite to reconstruct the residual donor site deformity. Our experimental protocol closely followed our clinical procedure for the harvesting of split calvarial bone grafts. Our conclusions in the rabbit model were: (1) each of the commonly used hemostatic agents (bone wax and gelfoam) inhibit osteoneogenesis to varying degrees, (2) hydroxyapatite shows promise in the reconstruction of the donor site defect, and (3) if the periosteum comes in direct contact the defect repairs itself.


Visceral leishmaniasis diagnosis and reporting delays as an obstacle to timely response actions in Nepal and India.
To eliminate visceral leishmaniasis (VL) in India and Nepal, challenges of VL diagnosis, treatment and reporting need to be identified. Recent data indicate that VL is underreported and patients face delays when seeking treatment. Moreover, VL surveillance data might not reach health authorities on time. This study quantifies delays for VL diagnosis and treatment, and analyses the duration of VL reporting from district to central health authorities in India and Nepal. A cross-sectional study conducted in 12 districts of Terai region, Nepal, and 9 districts of Bihar State, India, in 2012. Patients were interviewed in hospitals or at home using a structured questionnaire, health managers were interviewed at their work place using a semi-structured questionnaire and in-depth interviews were conducted with central level health managers. Reporting formats were evaluated. Data was analyzed using two-tailed Mann-Whitney U or Fisher's exact test. 92 VL patients having experienced 103 VL episodes and 49 district health managers were interviewed. Patients waited in Nepal 30 days (CI 18-42) before seeking health care, 3.75 times longer than in Bihar (8d; CI 4-12). Conversely, the lag time from seeking health care to receiving a VL diagnosis was 3.6x longer in Bihar (90d; CI 68-113) compared to Nepal (25d; CI 13-38). The time span between diagnosis and treatment was short in both countries. VL reporting time was in Nepal 19 days for sentinel sites and 76 days for "District Public Health Offices (DPHOs)". In Bihar it was 28 days for "District Malaria Offices". In Nepal, 73% of health managers entered data into computers compared to 16% in Bihar. In both countries reporting was mainly paper based and standardized formats were rarely used. To decrease the delay between onset of symptoms and getting a proper diagnosis and treatment the approaches in the two countries vary: In Nepal health education for seeking early treatment are needed while in Bihar the use of private and non-formal practitioners has to be discouraged. Reinforcement of VL sentinel reporting in Bihar, reorganization of DPHOs in Nepal, introduction of standardized reporting formats and electronic reporting should be conducted in both countries.


Psychological Impact of Living Kidney Donation: A Systematic Review by the EAU-YAU Kidney Transplant Working Group.
We performed a systematic literature review of the psychological impact on donors of living kidney donation. We conducted a literature review in PubMed/Medline according to PRISMA guidelines which included both qualitative (based on interviews) and quantitative studies (based on standardized questionnaire). There were 15 quantitative studies and 8 qualitative studies with 2,732 donors. Given that the methodologies of qualitative and quantitative studies are fundamentally different, we narratively synthetized results of studies according to four axes: quality of life, anxiety/depression, consequences of donation on the donor/recipient relationship, overall satisfaction and regret. The quantitative studies reported that donor quality of life remained unchanged or improved. Donor regret rates were very low and donor-recipient relationships also remained unchanged or improved. Qualitative studies reported more complex donation experiences: one can regret donation and still decide to recommend it as in a social desirability bias. In both study types, donor-recipient relationships were closer but qualitative studies reported that post-donation rebonding was required. The qualitative studies therefore highlighted the psychological complexity of donation for donors, showing that living donation impacts the donor's life whether it is successful or not. A better understanding of the impact of donation on donors could provide better care for donors.


Radiomics and its emerging role in lung cancer research, imaging biomarkers and clinical management: State of the art.
With the development of functional imaging modalities we now have the ability to study the microenvironment of lung cancer and its genomic instability. Radiomics is defined as the use of automated or semi-automated post-processing and analysis of large amounts of quantitative imaging features that can be derived from medical images. The automated generation of these analytical features helps to quantify a number of variables in the imaging assessment of lung malignancy. These imaging features include: tumor spatial complexity, elucidation of the tumor genomic heterogeneity and composition, subregional identification in terms of tumor viability or aggressiveness, and response to chemotherapy and/or radiation. Therefore, a radiomic approach can help to reveal unique information about tumor behavior. Currently available radiomic features can be divided into four major classes: (a) morphological, (b) statistical, (c) regional, and (d) model-based. Each category yields quantitative parameters that reflect specific aspects of a tumor. The major challenge is to integrate radiomic data with clinical, pathological, and genomic information to decode the different types of tissue biology. There are many currently available radiomic studies on lung cancer for which there is a need to summarize the current state of the art.


Functional ultrasound imaging of the brain: theory and basic principles.
Hemodynamic changes in the brain are often used as surrogates of neuronal activity to infer the loci of brain activity. A major limitation of conventional Doppler ultrasound for the imaging of these changes is that it is not sensitive enough to detect the blood flow in small vessels where the major part of the hemodynamic response occurs. Here, we present a μDoppler ultrasound method able to detect and map the cerebral blood volume (CBV) over the entire brain with an important increase in sensitivity. This method is based on imaging the brain at an ultrafast frame rate (1 kHz) using compounded plane wave emissions. A theoretical model demonstrates that the gain in sensitivity of the μDoppler method is due to the combination of 1) the high signal-to-noise ratio of the gray scale images, resulting from the synthetic compounding of backscattered echoes; and 2) the extensive signal averaging enabled by the high temporal sampling of ultrafast frame rates. This μDoppler imaging is performed in vivo on trepanned rats without the use of contrast agents. The resulting images reveal detailed maps of the rat brain vascularization with an acquisition time as short as 320 ms per slice. This new method is the basis for a real-time functional ultrasound (fUS) imaging of the brain.


Ureteral occlusion decreases phospholipid and cholesterol of renal tubular membranes.
Unilateral ureteral obstruction of 24 h duration in the dog results in a 20% decrease in the amount of total phospholipids present in basolateral membranes of renal tubular cells obtained from the experimental kidney as compared with the amount of phospholipid in basolateral membranes prepared from the contralateral kidney of the same dogs or from the kidneys of normal sham-operated dogs. There was also a decrease in the content of cholesterol and cholesterol esters of the basolateral membranes from the experimental kidney. By contrast, no significant change in lipid content was observed in brush border membranes obtained from the experimental kidney of dogs with unilateral ureteral obstruction. The decrease in phospholipid content of basolateral membranes was accompanied by a 40% fall in the content of phosphatidylcholine and a 12% fall in sphingomyelin. There was a small (12%) but significant increase in the content of phosphatidylethanolamine in basolateral membranes. The mechanisms responsible for the selective decrease in phospholipid content of basolateral membranes remain to be established. It is postulated that changes in solute transport and altered response to hormones observed in the postobstructed kidney of animals with unilateral ureteral obstruction may be explained, at least in part, by changes in the lipid composition of basolateral membranes.