Improving the Well-being of Adolescents With Type 1 Diabetes During the COVID-19 Pandemic: Qualitative Study Exploring Acceptability and Clinical Usability of a Self-compassion Chatbot.
Before the COVID-19 pandemic, adolescents with type 1 diabetes (T1D) had already experienced far greater rates of psychological distress than their peers. With the pandemic further challenging mental health and increasing the barriers to maintaining optimal diabetes self-management, it is vital that this population has access to remotely deliverable, evidence-based interventions to improve psychological and diabetes outcomes. Chatbots, defined as digital conversational agents, offer these unique advantages, as well as the ability to engage in empathetic and personalized conversations 24-7. Building on previous work developing a self-compassion program for adolescents with T1D, a self-compassion chatbot (COMPASS) was developed for adolescents with T1D to address these concerns. However, the acceptability and potential clinical usability of a chatbot to deliver self-compassion coping tools to adolescents with T1D remained unknown. This qualitative study was designed to evaluate the acceptability and potential clinical utility of COMPASS among adolescents aged 12 to 16 years with T1D and diabetes health care professionals. Potential adolescent participants were recruited from previous participant lists, and on the web and in-clinic study flyers, whereas health care professionals were recruited via clinic emails and from diabetes research special interest groups. Qualitative Zoom (Zoom Video Communications, Inc) interviews exploring views on COMPASS were conducted with 19 adolescents (in 4 focus groups) and 11 diabetes health care professionals (in 2 focus groups and 6 individual interviews) from March 2022 to April 2022. Transcripts were analyzed using directed content analysis to examine the features and content of greatest importance to both groups. Adolescents were broadly representative of the youth population living with T1D in Aotearoa (11/19, 58% female; 13/19, 68% Aotearoa New Zealand European; and 2/19, 11% Māori). Health care professionals represented a range of disciplines, including diabetes nurse specialists (3/11, 27%), health psychologists (3/11, 27%), dieticians (3/11, 27%), and endocrinologists (2/11, 18%). The findings offer insight into what adolescents with T1D and their health care professionals see as the shared advantages of COMPASS and desired future additions, such as personalization (mentioned by all 19 adolescents), self-management support (mentioned by 13/19, 68% of adolescents), clinical utility (mentioned by all 11 health care professionals), and breadth and flexibility of tools (mentioned by 10/11, 91% of health care professionals). Early data suggest that COMPASS is acceptable, is relevant to common difficulties, and has clinical utility during the COVID-19 pandemic. However, shared desired features among both groups, including problem-solving and integration with diabetes technology to support self-management; creating a safe peer-to-peer sense of community; and broadening the representation of cultures, lived experience stories, and diabetes challenges, could further improve the potential of the chatbot. On the basis of these findings, COMPASS is currently being improved to be tested in a feasibility study.


Heterometallic dithiolene complexes formed by stepwise displacement of cyclopentadienyl ligands from nickelocene with CpMo(S2C2Ph2)2.
The dithiolene ligand transfer reaction between Ni(S2C2Ph2)2 (1) and CpMo(CO)3Cl (2; Cp = eta-C5H5) affords the neutral paramagnetic molybdenum bis(dithiolene) complex CpM(S2C2Ph2)2 (3), which has been structurally characterized. As found in other d1 complexes of this type, one dithiolene ligand is planar while the other is significantly folded toward the Cp ligand. An unexpected second product of the reaction is the unusual trinuclear species Ni[Mo(S2C2Ph2)2Cp]2 (4), which in the solid state contains three different dithiolene bonding modes (terminal, bridging, and semi-bridging) in the same molecule. Complex 4 can also be synthesized by displacement of the diene ligands in Ni(cod)2 with 2 equiv of 3. In contrast, the reaction of nickelocene with 3 proceeds by displacement of the Cp ligands in a stepwise manner to give initially the dinuclear species NiMo(mu-S2C2Ph2)2Cp2 5, which then reacts further with 3 to produce 4.


Colon-derived liver metastasis, colorectal carcinoma, and hepatocellular carcinoma can be discriminated by the Ca(2+)-binding proteins S100A6 and S100A11.
It is unknown, on the proteomic level, whether the protein patterns of tumors change during metastasis or whether markers are present that allow metastases to be allocated to a specific tumor entity. The latter is of clinical interest if the primary tumor is not known. In this study, tissue from colon-derived liver metastases (n = 17) were classified, laser-microdissected, and analysed by ProteinChip arrays (SELDI). The resulting spectra were compared with data for primary colorectal (CRC) and hepatocellular carcinomas (HCC) from our former studies. Of 49 signals differentially expressed in primary HCC, primary CRC, and liver metastases, two were identified by immunodepletion as S100A6 and S100A11. Both proteins were precisely localized immunohistochemically in cells. S100A6 and S100A11 can discriminate significantly between the two primary tumor entities, CRC and HCC, whereas S100A6 allows the discrimination of metastases and HCC. Both identified proteins can be used to discriminate different tumor entities. Specific markers or proteomic patterns for the metastases of different primary cancers will allow us to determine the biological characteristics of metastasis in general. It is unknown how the protein patterns of tumors change during metastasis or whether markers are present that allow metastases to be allocated to a specific tumor entity. The latter is of clinical interest if the primary tumor is not known.


Silicon-on-insulator sensors using integrated resonance-enhanced defect-mediated photodetectors.
A resonance-enhanced, defect-mediated, ring resonator photodetector has been implemented as a single unit biosensor on a silicon-on-insulator platform, providing a cost effective means of integrating ring resonator sensors with photodetectors for lab-on-chip applications. This method overcomes the challenge of integrating hybrid photodetectors on the chip. The demonstrated responsivity of the photodetector-sensor was 90 mA/W. Devices were characterized using refractive index modified solutions and showed sensitivities of 30 nm/RIU.


Contrast-Enhanced Mammography in the Diagnosis of Breast Angiosarcoma.
A 60-year-old female presented for further assessment of a new right breast lump (November 2020). She had a history of a stage I (T1bN0M0) right breast invasive mammary carcinoma, grade 2 (score 7/9) with receptors ER/PR-negative, HER2/neu-positive, diagnosed four years prior to her current presentation. At that time, she was treated with a right breast lumpectomy and local radiation. Breast assessment with contrast-enhanced mammography showed new skin thickening with associated enhancement within the palpable region. Histology of subsequent ultrasound-guided biopsy found radiation-induced breast angiosarcoma. Breast angiosarcoma is a rare entity that represents less than 1% of all breast cancers. To our knowledge, this is the first case describing the imaging findings of breast angiosarcoma on contrast-enhanced mammography.


Trans-arterial embolisation therapies for unresectable intrahepatic cholangiocarcinoma: a systematic review.
Unresectable intrahepatic cholangiocarcinoma (ICC) portends a poor prognosis despite standard systemic treatments which confer minimal survival benefits and significant adverse effects. This study aimed to assess clinical outcomes, complications and prognostic factors of TAE therapies using chemotherapeutic agents or radiation. A literature search and article acquisition was conducted on PubMed (MEDLINE), OVID (MEDLINE) and EBSCOhost (EMBASE). Original articles published after January 2000 on trans-arterial therapies for unresectable ICC were selected using strict eligibility criteria. Radiological response, overall survival, progression-free survival, safety profile, and prognostic factors for overall survival were assessed. Quality appraisal and data tabulation were performed using pre-determined forms. Results were synthesized by narrative review and quantitative analysis. Twenty articles were included (n=929 patients). Thirty three percent of patients presented with extrahepatic metastases. After treatment, the average rate of complete and partial radiological response was 10% and 22.2%, respectively. Overall median survival time was 12.4 months with a median 30-day mortality and 1-year survival rate of 0.6% and 53%, respectively. Acute treatment toxicity (within 30 days) was reported in 34.9% of patients, of which 64.3% were mild to moderate in severity. The most common clinical toxicities were abdominal pain, nausea and vomiting, and fatigue. Multiplicity, localization and vascularity of the tumor may predict worse overall survival. Trans-arterial therapies are safe and effective treatment options which should be considered routinely for unresectable ICC. Consistent and standardized methodology and data collection is required to facilitate a meta-analysis. Randomized controlled trials will be valuable in the future.


Effect of several dermatitis preventing agents on foot pad dermatitis in dwarf and normal sized single comb white Leghorn layers.
Studies were conducted to determine the effects of increased dietary levels of vitamin and trace mineral mixtures, methionine, meat and bone meal, fish meal, and safflower oil on foot pad dermatitis in dwarf and normal size Single Comb White Leghorn layers. All layers were maintained in individual wire cages throughout a 40-week experiment period. Individual birds were scored for the incidence of foot pad dermatitis and production parameters were recorded. No significant decrease in the incidence of dermatitis was observed from the following dietary supplements: a 50% increase in a vitamin or a complete trace mineral mixture; a 50% increase in an iron, copper, iodine, and cobalt or a manganese and zinc mixture; .05% methionine; 5% meat and bone meal; 3% herring fish meal; or 2% safflower oil. It was concluded that these mixtures or supplements containing such dermatitis preventative agents as pantothenic acid, zinc, and linoleic acid appeared without effect in minimizing expression of the condition in dwarfs.


Anonymous Dutch sperm donors releasing their identity.
This study examined the motivations of anonymous Dutch sperm donors to release their identity. It aimed to increase knowledge and encourage donors to become identifiable through a more informed decision, allowing more donor-conceived persons to contact their donors. Since 2010, anonymous sperm donors in the Netherlands can register in the Fiom KID-DNA Database developed by Fiom and Canisius Wilhelmina Hospital (CWZ). An online survey was sent to donors who registered in the database (May 2015-August 2017). A total of 179 male respondents participated in this study. The motives of most donors to register in the database were child-oriented: donors believe that their offspring are entitled to their physical and social details and/or they want to give their offspring the chance to contact them. Other motives are donor-oriented, such as the curiosity about the number of offspring, their well-being and the desire to establish contact. This research showed that, to encourage anonymous donors to release their identity, one should focus on providing information about the existence of DNA databases. As well as increasing the donor's awareness of problems donor-conceived persons can experience by the lack of knowledge about their descent, answering questions and concerns from donors, and exploring the curiosity about their offspring.


Cancer incidence trends among native Hawaiians and other Pacific Islanders in the United States, 1990-2008.
Lack of annual population estimates for disaggregated Native Hawaiian and Other Pacific Islander (NHOPI) populations limits the ability to examine cancer incidence rates and trends to understand the cancer burdens among NHOPIs. Utilizing 1990 and 2000 population census data, we estimated the annual populations by age and sex for Native Hawaiians, Samoans, and Guamanians/Chamorros for 1990-2008 in regions covered by 13 of the National Cancer Institute's SEER registries. Cancer diagnoses during 1990-2008 from these registries were used to calculate the age-adjusted (2000 US Standard) incidence rates by sex, calendar year/period, and cancer type for each population. The annual percentage change (APC) in incidence rates was estimated with the 95% confidence intervals (95% CIs) calculated for both the rate and APC estimates. Statistically significant declining trends were found in Native Hawaiians, in men for lung and stomach cancers (APC = -2.3%; 95% CI = -3.3 to -1.3; and APC = -3.8%; 95% CI = -6.0 to -1.6, respectively), and in women for breast cancer (APC = -4.1%; 95% CI = -5.7 to -2.5) since 1998 and lung cancer (APC = -6.4%; 95% CI = -10.7 to -1.8) since 2001. Rising incidence trends were experienced by Samoans, especially by Samoan women for breast (APC = 2.7%; 95% CI = 0.9 to 4.5) and uterus (APC = 7.3%; 95% CI = 6.2 to 8.4) cancers. With limited data, Guamanians/Chamorros demonstrated lower, but increasing, incidence rates than other NHOPIs. Population-based cancer incidence rates for disaggregated NHOPI populations help identify disparities in cancer burden and provide valuable information to improve cancer control efforts among NHOPIs.


Successful tracheoscopy-assisted reconstruction of traumatic tracheal avulsion in a cat.
To outline the clinical findings, surgical management, complications, and outcomes in a case of intrathoracic, traumatic, tracheal avulsion. A 2-year-old domestic shorthair cat presented with respiratory distress 18 days after a motor vehicle accident. A tracheal avulsion was diagnosed and treated by surgical anastomosis. The initial anastomosis failed. The subsequent tracheoscopic-assisted tracheal anastomosis was successful. The cat had no further episodes of respiratory distress following the second surgery in a 9-month follow-up period. This communication describes a complication of intrathoracic, traumatic, tracheal avulsion repair that has not previously been described and the use of tracheoscopy during the subsequent surgical procedure to ensure accurate suture placement.


Members of the receptor for advanced glycation end products axis as potential therapeutic targets in patients with lupus nephritis.
The relationship of inflammation and the expression of full-length receptor for advanced glycation end products (flRAGE) on monocytes, plasma levels of RAGE ligand high mobility group box protein 1 (HMGB1), soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) was assessed to elucidate the effect of HMGB1/DNA/RAGE-mediated innate inflammatory responses in patients with lupus nephritis. Cell surface expression of flRAGE was elevated on the monocytes of lupus patients, correlated with plasma HMGB1 levels. Plasma sRAGE level negatively correlated with systemic lupus erythematosus (SLE) disease activity index. Plasma esRAGE level was significantly lower in SLE patients with flare while esRAGE/sRAGE ratio negatively correlated with complement C3 level. HMGB1 alone could moderately induce ex vivo IL-6 production from monocytes, resulting in activation of intracellular p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase and nuclear factor (NF)-κB. Moreover, toll-like receptor-9 ligand together with HMGB1 exhibited a synergistic effect on IL-6 and IL-12p70 secretions and the phosphorylation of p38 MAPK and NF-κB. Therefore, over-expression of flRAGE in lupus may lead to the amplification of RAGE ligands-mediated inflammatory responses through the activation of p38 MAPK and NF-κB. Plasma sRAGE may serve as a potential biomarker for disease activity and a future therapeutic target in SLE.


Do behavioral responses mediate or moderate the relation between cardiovascular reactivity to stress and parental history of hypertension?
To examine whether differences in behavioral responses to stress mediated or moderated the relation between cardiovascular response to stress and parental history of hypertension, 64 healthy undergraduates-16 men with hypertensive parents (PH+), 16 men without hypertensive parents (PH-), 16 PH+ women, and 16 PH- women-participated in a mental arithmetic task, mirror tracing task, and 2 interpersonal role plays. PH+ participants exhibited higher resting heart rates than PH- participants and higher resting systolic blood pressures (SBPs) than PH- women. PH+ participants exhibited greater SBP responses to tasks and engaged in more negative verbal and nonverbal behavior across tasks than PH- counterparts. Differences in behavioral responding neither mediated nor moderated the observed relation between parental history status and SBP response to stress.


Effect of heat treatment to sweet potato flour on dough properties and characteristics of sweet potato-wheat bread.
The effect of heat treatment at 90, 100, 110 and 120 ℃ for 20 min to sweet potato flour on dough properties and characteristics of sweet potato-wheat bread was investigated. The lightness (L*) and a* of sweet potato flour samples after heat treatment were increased, while the b* were decreased significantly, as well as the particle size, volume and area mean diameter ( p < 0.05). A slight change of the microstructures of sweet potato flour was observed, where the number of irregular granules increased as the temperature increased from 90 to 120 ℃. Compared with sweet potato flour samples without heat treatment and with heat treatment at 90, 100 and 120 ℃, the gelatinization temperature and enthalpy change of sweet potato flour at 110 ℃ were the lowest, which were 77.94 ℃ and 3.67 J/g, respectively ( p < 0.05). After heat treatment, gas retention of the dough with sweet potato flour increased significantly from 1199 ml without heat treatment to 1214 ml at 90 ℃ ( p < 0.05). In addition, specific loaf volume of sweet potato-wheat bread with sweet potato flour after heat treatment increased significantly, which was the largest at 90 ℃ (2.53 cm3/g) ( p < 0.05). Thus, heat treatment at 90 ℃ to sweet potato flour could be potentially used in wheat bread production.


Myocardial infarction: cardioprotection by erythropoietin.
Extensive research during the last decade demonstrated that a single systemic administration of -erythropoietin (EPO) lead to significant attenuation of myocardial infarction (MI) induced in animals, mostly small rodents, either by a myocardial ischemia followed by reperfusion or by a permanent ligation of a coronary artery. Both methods are critically reviewed with the aim of helping the reader in appreciating key issues in the translation of experimental results to the clinic. Results of several clinical trials in patients with acute MI completed to date failed to demonstrate beneficial effects of EPO, and thus put into question the validity of results obtained in animal models. Comprehensive review of design and results of animal experiments and clinical trials presented here allowed authors to postulate that therapeutic window for EPO during developing MI is very narrow and was possibly missed in negative clinical trials. This point was illustrated by the negative outcome of experiment in the rat model of MI in which timing of EPO administration was similar to that in clinical trials. The design of future clinical trials should allow for a narrow therapeutic window of EPO. Given current standards for onset-to-door and door-to-balloon time the optimal time for EPO administration should be just prior to PCI.


The impact of obesity on drug prescribing in primary care.
Healthcare costs attributable to obesity have previously involved estimations based on costs of diseases commonly considered as having obesity as an underlying factor. To quantify the impact of obesity on total primary care drug prescribing. Review of computer generated and handwritten prescriptions to determine total prescribing volume for all drug classes. Twenty-three general practice surgeries in the UK. Stratified random selection of 1150 patients who were obese (body mass index [BMI]>30 kg/m(2)) and 1150 age and sex-matched controls of normal weight (BMI 18.5-<25 kg/m(2)). Retrospective review of medical records over an 18-month period. A higher percentage of patients who were obese, compared with those of normal weight, were prescribed at least one drug in the following disease categories: cardiovascular (36% versus 20%), central nervous system (46% versus 35%), endocrine (26% versus 18%), and musculoskeletal and joint disease (30% versus 22%). All of these categories had a P-value of <0.001. Other categories, such as gastrointestinal (24% versus 18%), infections (42% versus 35%), skin (24% versus 19%) had a P-value of <0.01, while respiratory diseases (18% versus 21%) had a P-value of <0.05. Total prescribing volume was significantly higher for the group with obesity and was increased in the region of two- to fourfold in a wide range of prescribing categories: ulcer healing drugs, lipid regulators, beta-adrenoreceptor drugs, drugs affecting the rennin angiotensin system, calcium channel blockers, antibacterial drugs, sulphonylureas, biguanides, non-steroidal anti-inflammatories (NSAIDs) (P<0.001) and fibrates, angiotensin II antagonists, and thyroid drugs (P<0.05). The main impact on prescribing volumes is from numbers of patients treated, although in some areas there is an effect from greater dosage or longer treatment in those who are obese including calcium channel blockers, antihistamines, hypnotics, drugs used in the treatment of nausea and vertigo, biguanides, and NSAIDs (P<0.05) reflected in significantly increased defined daily dose prescribing. This large study of contemporary practice indicates that obesity more than doubled prescribing in most drug categories.


Work activities of practical nurses and risk factors for the development of musculoskeletal disorders.
Musculoskeletal and emotional disorders are important causes of reported diseases, causing medical absences, and eventually earlier decrease of work ability. This paper reports the results of a study carried out among practical nurses working at the Orthopedics and Trauma Institute. The objectives of the study were: (a) to describe the routine activities performed during day and night shifts, and (b) to compare the work activities performed in different wards during these shifts. A Brazilian version of the Work Ability Index--WAI (TUOMI et al., 1994) was answered by 83 practical nurses. Forty-three of them (52%) reported pains or musculoskeletal diseases, either based on their own opinion or diagnosed by a physician. These nurses were invited to join the second phase of the study and twenty-nine accepted it. All work activities performed in 29 shifts were observed and recorded. The results showed that day shifts were far more demanding in terms of the number of activities related to patients' care than afternoon and night shifts. Also, body postures associated with day work activities demanded important physical efforts. The number of nurses in charge during night shifts was substantially lower than during day shifts. This could lead to an overload and affect the health of the nurses.


[Epidemiological and pathological features of cancer in Fez Boulemane region, Morocco].
In Fez-Boulemane, Morocco, there is no cancer registry so there is a lack of information about the incidence and characteristics of cancer in the region. In this retrospective study we examined the epidemiological and pathological features of 5532 cases of cancer collected from the Department of Pathology in Hassan II University Hospital of Fes from 2004 to 2010. The mean age of the patients was 53.5 years and 52% were male. Digestive cancers and skin cancers were the most common. Digestive cancers were predominantly colorectal and stomach. Cancers of the urinary bladder and colorectal cancers were the leading cancers in men accounting respectively for 9% and 8% of all male cancers. In women, cancers of the breast (62%) and uterine cervix (22.6%) predominated. As a first step in cancer control in our area, establishment of a regional cancer registry is recommended.


An Experimental Study of the Kinetics of OH/OD(v = 1,2,3) + SO2: The Limiting High-Pressure Rate Coefficients as a Function of Temperature.
The kinetics of the reaction OH/OD(v = 1,2,3) + SO2 were studied using a photolysis/laser-induced fluorescence technique. The rate coefficients OH/OD(v = 1,2,3) + SO2, k1, over the temperature range of 295-810 K were used to determine the limiting high-pressure limit k1∞. This method is usually applicable if the reaction samples the potential well of the adduct HOSO2 and if intramolecular vibrational relaxation is fast. In the present case, however, the rate coefficients showed an additional fast removal contribution as evidenced by the increase in k1 with vibrational level; this behavior together with its temperature dependence is consistent with the existence of a weakly bound complex on the potential energy surface prior to adduct formation. The data were analyzed using a composite mechanism that incoporates energy-transfer mechanisms via both the adduct and the complex, and yielded a value of k1∞(295 K) equal to (7.2 ± 3.3) × 10-13 cm3 molecule-1 s-1 (errors at 1σ), a factor of between 2 and 3 smaller than the current recommended IUPAC and JPL values of (2.0-1.0+2.0) and (1.6 ± 0.4) × 10-12 cm3 molecule-1 s-1 at 298 K, respectively, although the error bars do overlap. k1∞ was observed to only depend weakly on temperature. Further evidence for a smaller k1∞ is presented in the companion paper.


Can dead man tooth do tell tales? Tooth prints in forensic identification.
We know that teeth trouble us a lot when we are alive, but they last longer for thousands of years even after we are dead. Teeth being the strongest and resistant structure are the most significant tool in forensic investigations. Patterns of enamel rod end on the tooth surface are known as tooth prints. This study is aimed to know whether these tooth prints can become a forensic tool in personal identification such as finger prints. A study has been targeted toward the same. In the present in-vivo study, acetate peel technique has been used to obtain the replica of enamel rod end patterns. Tooth prints of upper first premolars were recorded from 80 individuals after acid etching using cellulose acetate strips. Then, digital images of the tooth prints obtained at two different intervals were subjected to biometric conversion using Verifinger standard software development kit version 6.5 software followed by the use of Automated Fingerprint Identification System (AFIS) software for comparison of the tooth prints. Similarly, each individual's finger prints were also recorded and were subjected to the same software. Further, recordings of AFIS scores obtained from images were statistically analyzed using Cronbach's test. We observed that comparing two tooth prints taken from an individual at two intervals exhibited similarity in many cases, with wavy pattern tooth print being the predominant type. However, the same prints showed dissimilarity when compared with other individuals. We also found that most of the individuals with whorl pattern finger print showed wavy pattern tooth print and few loop type fingerprints showed linear pattern of tooth prints. Further more experiments on both tooth prints and finger prints are required in establishing an individual's identity.


Kβ X-ray Emission Spectroscopy of Cu(I)-Lytic Polysaccharide Monooxygenase: Direct Observation of the Frontier Molecular Orbital for H2O2 Activation.
Lytic polysaccharide monooxygenases (LPMOs) catalyze the degradation of recalcitrant carbohydrate polysaccharide substrates. These enzymes are characterized by a mononuclear Cu(I) active site with a three-coordinate T-shaped "His-brace" configuration including the N-terminal histidine and its amine group as ligands. This study explicitly investigates the electronic structure of the d10 Cu(I) active site in a LPMO using Kβ X-ray emission spectroscopy (XES). The lack of inversion symmetry in the His-brace site enables the 3d/p mixing required for intensity in the Kβ valence-to-core (VtC) XES spectrum of Cu(I)-LPMO. These Kβ XES data are correlated to density functional theory (DFT) calculations to define the bonding, and in particular, the frontier molecular orbital (FMO) of the Cu(I) site. These experimentally validated DFT calculations are used to evaluate the reaction coordinate for homolytic cleavage of the H2O2 O-O bond and understand the contribution of this FMO to the low barrier of this reaction and how the geometric and electronic structure of the Cu(I)-LPMO site is activated for rapid reactivity with H2O2.


Bilateral hydroureter and hydronephrosis causing renal failure due to a procidentia uteri: a case report.
We report a case of complete uterine prolapse that resulted in bilateral hydroureter, hydronephrosis, and renal dysfunction. The nonoperative reduction of the prolapse with a vaginal pessary reversed the obstructive uropathy and ameliorated renal function. The lower urinary tract should be imaged in patients with complete uterine prolapse. If present, obstructive uropathy should be relieved by the reduction of the prolapse before irreversible renal damage occurs.


Impacts of stable element intake on 14C and 129I dose estimates.
The purpose of this study was to evaluate and provide insights related to the influence of the intake of stable isotopes of carbon and iodine on the committed doses due to the ingestion of (14)C and (129)I. This was accomplished through the application of two different computational approaches. The first was based on the assumption that ground (drinking) water was the only source of intake of (14)C and (129)I, as well as stable carbon and stable iodine. In the second, the intake of (14)C and (129)I was still assumed to be restricted to that in the ground (drinking) water, but the intake of stable carbon and stable iodine was expanded to include that in other components of the diet. The doses were estimated using either a conversion formula or the applicable dose coefficients in Federal Guidance Reports No. 11 and No. 13. Serving as input for the analyses was the estimated maximum concentrations of (14)C or (129)I that would be present in the ground water due to potential releases from the proposed Yucca Mountain high-level radioactive waste repository during the first 10,000 y after closure. The estimated contributions of stable carbon and iodine through the consumption of ground water were based on analyses of samples collected in the Amargosa Valley, NV. The contributions through dietary intake were based on surveys conducted in the United States. Based on the accompanying analyses, it was noted that stable isotope intake has a significant effect on the estimated doses due to the intake of radioactive isotopes of the same element. While this is a well-known fact, this observation has international implications in terms of dose estimates for key radionuclides, such as (14)C and (129)I, a primary reason being the wide variations in the intakes of stable carbon and iodine in various countries. For this reason, analysts planning to apply the dose coefficients developed by the International Commission on Radiological Protection (ICRP) should either confirm that the average total intake in their country of stable isotope(s) of the radioactive isotope being evaluated is in reasonable agreement with the value assumed by the ICRP or suitably modify the ICRP dose coefficients to account for any differences. If such a procedure is to be implemented, there is a need for periodic updates of the dietary intakes of various stable elements in countries throughout the world. The importance of this is documented by recent surveys in Asia that revealed that their average total daily intake of stable iodine was less than half of the ICRP value for Reference Man. In this case, application of the ICRP dose coefficients, without modification, would underestimate the dose due to ingested (129)I by a factor of more than two. A related situation exists in the United States where the latest surveys indicate that the daily intake of stable iodine is 75% of the ICRP value.


Beyond data management: how ecoinformatics can benefit environmental monitoring programs.
We review ways in which the new discipline of ecoinformatics is changing how environmental monitoring data are managed, synthesized, and analyzed. Rapid improvements in information technology and strong interest in biodiversity and sustainable ecosystems are driving a vigorous phase of development in ecological databases. Emerging data standards and protocols enable these data to be shared in ways that have previously been difficult. We use the U.S. Environmental Protection Agency's National Coastal Assessment (NCA) as an example. The NCA has collected biological, chemical, and physical data from thousands of stations around the U.S. coasts since 1990. NCA data that were collected primarily to assess the ecological condition of the U.S. coasts can be used in innovative ways, such as biogeographical studies to analyze species invasions. NCA application of ecoinformatics tools leads to new possibilities for integrating the hundreds of thousands of NCA species records with other databases to address broad-scale and long-term questions such as environmental impacts, global climate change, and species invasions.


Assessing participants' perceptions on group-based principles for action in community-based health enhancing physical activity programmes: The APEF tool.
In community-based health enhancing physical activity (CBHEPA) programmes, group-based principles for action such as active participation, enjoyment, and fostering group processes are widely advocated. However, not much is known about participants' perceptions of these principles as there are no assessment tools available. Therefore, this article describes the development of the APEF (Active Participation, Enjoyment, and Fostering group processes) tool and reports on its implementation in a Dutch CBHEPA programme. Indicators for the principles have been identified from literature research, interviews with professionals, and secondary analysis of three group interviews with 11 practitioners. To address the identified indicators, the APEF tool was developed, pretested, and used in 10 focus groups with 76 participants. The APEF tool consists of eight statements about group-based principles for action, on which CBHEPA participants vote, followed by in-depth discussion. The voting procedure engages participants. Spider diagrams visualise participants' perceptions of group-based principles. The APEF tool addresses the challenge of relating group level outcomes to individual outcomes such as physical activity behaviour. The tool facilitates as well as evaluates group-based principles for action, it stimulates dialogue and is culturally sensitive, but it needs strong facilitating skills to manage group dynamics.


Procedural Sedation and Analgesia in Trauma Patients in an Out-of-Hospital Emergency Setting: A Prospective Multicenter Observational Study.
The quality of procedural analgesia and sedation among trauma patients has not been studied much in the prehospital setting. The main objective of this study was to characterize the quality of procedural analgesia sedation practices in prehospital settings in trauma patients. This was an open-label observational prospective multicenter study (January 01, 2012-December 31, 2013). We included all consecutive trauma victims undergoing a potentially painful procedure on the accident scene. The primary endpoint was the procedural pain intensity. Data for 210 patients aged 11 to 98 years were analyzed. The most common lesions were limb fractures or dislocations. The most common procedures were limb realignment and splinting. Overall, 25 different drug combinations [with paracetamol [acetaminophen], non-steroidal anti-inflammatory drugs, nefopam, opioids, loco-regional anesthesia, Equimolar Mixture of Oxygen/Nitrous Oxide (EMONO), sedative drugs] were used by the emergency medical services (EMS). One hundred seventeen patients (55%) received either one or two sedative drugs (among ketamine, propofol, and midazolam), 171 patients (81%) received morphine that was combined with a sedative drug in 54% of cases. During the procedure, 95 patients, 45% [95% Confidence Interval (CI) 39-52] experienced intense to severe pain. Among patients who received sedative drugs, 27% (32/117) had intense to severe pain vs. 68% (63/93) in patients who did not, that is, 40% difference [95% CI 33.8-47.0]. Seventeen patients (8%) experienced 18 adverse events of which 6 were respiratory adverse events. A deep sedation occurred in 17 patients. No center had any specific protocols for procedural sedation analgesia. Procedural sedation-analgesia was inadequate in almost half of the trauma patients in the out-of-hospital setting. The reasons of these failures were probably multiple. The non-administration of a sedative drug despite an indication or non-adapted doses, in the context of a lack of specific protocols, was certainly one of them.


Infrared spectroscopy of human tissue. II. A comparative study of spectra of biopsies of cervical squamous epithelium and of exfoliated cervical cells.
A comparison of infrared absorption spectra obtained from the different layers of squamous epithelium from the human cervix, and infrared spectra obtained from exfoliated cervical cells, is presented. Infrared spectroscopy has been shown (in part I of this series) to be a sensitive tool to monitor maturation and differentiation of human cervical cells; therefore, this spectroscopic technique provides new insights into the composition and state of health of exfoliated cells.


Comparison of measured and predicted creatinine excretion is an unreliable index of compliance in PD patients.
To evaluate the use of the ratio of measured to predicted creatinine excretion as an index of compliance in peritoneal dialysis (PD) patients. A prospective analysis. Academic teaching hospital dialysis unit. Forty-three patients on PD. Creatinine excretion in daily dialysate and urine collections was measured on one occasion in 10 patients and on two occasions in 33 patients, and, after adding an estimate for extrarenal creatinine degradation, was divided by predicted creatinine excretion to give a creatinine excretion ratio, which has been proposed as an index of compliance with exchanges in PD patients. Values above 1.24 have been suggested to indicate noncompliance. Lean body mass was also estimated from creatinine excretion. The mean creatinine excretion ratio was 1.12, and 30% of patients had a value above 1.3. Only one patient admitted noncompliance. Studies on four consecutive days of guaranteed compliance in 7 patients with high ratios showed that creatinine excretion remained constant, suggesting that the patients were high creatinine producers rather than noncompliant. Creatinine excretion was stable when measured at intervals of days, but over months it tended to change markedly in many patients. Lean body mass estimations using creatinine excretion were low in most patients. Comparison of measured and predicted creatinine excretion is not a reliable indicator of noncompliance because many compliant patients consistently excrete more creatinine than predicted. The standard formulas were not validated in dialysis patients and underestimate creatinine excretion significantly in many PD patients. Existing estimates in the literature of noncompliance, using this methodology, may not be accurate. Better methods of detecting this problem are required.


Tissue strain amplification at the osteocyte lacuna: a microstructural finite element analysis.
A parametric finite element model of an osteocyte lacuna was developed to predict the microstructural response of the lacuna to imposed macroscopic strains. The model is composed of an osteocyte lacuna, a region of perilacunar tissue, canaliculi, and the surrounding bone tissue. A total of 45 different simulations were modeled with varying canalicular diameters, perilacunar tissue material moduli, and perilacunar tissue thicknesses. Maximum strain increased with a decrease in perilacunar tissue modulus and decreased with an increase in perilacunar tissue modulus, regardless of the thickness of the perilacunar region. An increase in the predicted maximum strain was observed with an increase in canalicular diameter from 0.362 to 0.421 microm. In response to the macroscopic application of strain, canalicular diameters increased 0.8% to over 1.0% depending on the perilacunar tissue modulus. Strain magnification factors of over 3 were predicted. However, varying the size of the perilacunar tissue region had no effect on the predicted perilacunar tissue strain. These results indicate that the application of average macroscopic strains similar to strain levels measured in vivo can result in significantly greater perilacunar tissue strains and canaliculi deformations. A decrease in the perilacunar tissue modulus amplifies the perilacunar tissue strain and canaliculi deformation while an increase in the local perilacunar tissue modulus attenuates this effect.


Modulation of Theta Phase Synchrony during Syllable Processing as a Function of Interactive Acoustic Experience in Infancy.
Plasticity, a prominent characteristic of the infant brain, supports formation of cortical representations as infants begin to interact with and adapt to environmental sensory events. Enhanced acoustic processing efficiency along with improved allocation of attentional resources at 7 months and establishment of well-defined phonemic maps at 9 months have been shown to be facilitated by early interactive acoustic experience (IAE). In this study, using an oddball paradigm and measures of theta phase synchrony at source level, we examined short- and long-term effects of nonspeech IAE on syllable processing. Results demonstrated that beyond maturation alone, IAE increased the efficiency of syllabic representation and discrimination, an effect that endured well beyond the immediate training period. As compared with naive controls, the IAE-trained group at 7, 9, and 18 months showed less theta phase synchrony for the standard syllable and at 7 and 18 months for the deviant syllable. The decreased theta phase synchrony exhibited by the trained group suggests more mature, efficient, acoustic processing, and thus, better cortical representation and discrimination of syllabic content. Further, the IAE modulatory effect observed on theta phase synchrony in left auditory cortex at 7 and 9 months was differentially associated with receptive and expressive language scores at 12 and 18 months of age.


Medical women of the West.
The presence in the West of women physicians with degrees from regular medical schools spans a period of approximately 130 years. Women's Medical College of Pennsylvania graduated many of these early women physicians. The first woman medical graduate of a western school was Lucy M. Field Wanzer, who finished in 1876 at the Department of Medicine, University of California in San Francisco. Soon thereafter, schools that would become Stanford University and the Oregon Health Sciences University schools of medicine, as well as the newly founded University of Southern California, were contributing to the pool of women physicians. The University of Michigan Medical School, the first coeducational state medical school, also educated some of the western women physicians, who by 1910 numbered about 155. This regional account of the progress of women physicians as they strove to become an integral part of the profession emphasizes the familiar themes of altruism, ingenuity, and perseverance that characterized their efforts.


Free radicals in L-arginine x HCl x H2O single crystals X-irradiated at 66K- EPR, ENDOR, EIE and DFT studies.
X-irradiation of L-arginine hydrochloride monohydrate crystals at 66 K led to at least five radicals detectable with K-band Electron Paramagnetic Resonance (EPR), Electron-Nuclear DOuble Resonance (ENDOR) and ENDOR-induced EPR (EIE) techniques. Radicals R1a and R1b were identified as carboxyl-centered radicals from one-electron reduction, (H(2)OOC*)CH (NH(3))(+)(CH(2))(3)NHC(NH(2))(2)(+) in two different conformations arising from the two geometrically distinct molecules of the asymmetric unit in the crystal. Density-Functional Theory (DFT) calculations on cluster models constructed separately for each molecule of the asymmetric unit support the assignments. Radical R2 was identified as the decarboxylation radical, *CH(NH(3))(+)(CH(2))(3)NHC (NH(2))(2)(+). Radical R3, with two proton couplings and one nitrogen coupling, was identified as a radical with the unpaired electron localized on the guanidyl group, (-)(OOC)CH(NH(3))(+)(CH(2))(3)NHC*(NH(2))(2)(+). R3 is a product of one-electron reduction different from radicals R1a and R1b. DFT calculations on a cluster model reproduced the experimental values very well and thus supported the assignment of R3. Geometry optimization indicated that the guanidyl group transformed from planar to pyramidal upon trapping the electron. Radical R4 was identified as a side chain dehydrogenation radical, (-)(OOC)CH(NH(3))(+)(CH(2))(2)*CH NHC(NH(2))(2)(+). It was not possible to collect sufficient data to identify radical R5, although it clearly exhibited hyperfine coupling to one nonexchangeable beta-proton.


End-stage renal disease causes an imbalance between endothelial and smooth muscle progenitor cells.
Patients with end-stage renal disease (ESRD) on hemodialysis have an increased risk of cardiovascular disease (CVD). Circulating endothelial progenitor cells (EPC) contribute to vascular regeneration and repair, thereby protecting against CVD. However, circulating smooth muscle progenitor cells (SPC) may contribute to adverse vascular remodeling. We hypothesized that an imbalance occurs between EPC and SPC in ESRD patients and sampled progenitor cells from 45 ESRD patients receiving regular treatment. Our study is the first to show reduced numbers of CD34+KDR+ hematopoietic stem cell (HSC)-derived EPC (type I EPC). Furthermore, monocyte-derived EPC cultured from mononuclear cells (type II EPC) were reduced in number and had a reduced capacity to stimulate endothelial cell angiogenesis. In contrast, SPC outgrowth was unaffected. In vitro incubation with uremic serum impaired type II EPC outgrowth from healthy donor mononuclear cells and did not influence SPC outgrowth. The hemodialysis procedure itself induced HSC apoptosis and caused an acute depletion of circulating EPC. Taken together, the decreased number and impaired function of EPC are compatible with impaired endogenous vascular repair in hemodialysis patients, whereas the unaffected SPC numbers suggest that the potential of progenitor cells to contribute to adverse remodeling is retained. This EPC-SPC imbalance may contribute to the acceleration of CVD in ESRD patients and could offer novel therapeutic targets.


INHIBITION OF OXIDATIVE PHOSPHORYLATION IN ESCHERICHIA COLI BY DIHYDROSTREPTOMYCIN.
Bragg, P. D. (University of British Columbia, Vancouver, B.C., Canada), and W. J. Polglase. Inhibition of oxidative phosphorylation in Escherichia coli by dihydrostreptomycin. J. Bacteriol. 86:1236-1240. 1963.-Dihydrostreptomycin inhibited the oxidation of succinate in extracts of antibiotic-sensitive Escherichia coli. The inhibitable reaction required both the particulate and the supernatant fractions from sonic extracts which had been centrifuged at 100,000 x g. Dihydrostreptomycin was found to inhibit phosphorylation coupled with the oxidation of reduced nicotinamide adenine dinucleotide (NADH). The inhibition of oxidative phosphorylation by dihydrostreptomycin appeared to precede the effect of the antibiotic on oxidation. The streptomycin antagonist, 2-heptyl-4-hydroxyquinoline N-oxide, inhibited the oxidation of succinate and of NADH, but showed little effect on oxidative phosphorylation. Oxidative phosphorylation was not affected by dihydrostreptomycin in strains of E. coli which were antibiotic-resistant or -dependent.


Antiproliferative effects of two amides, piperine and piplartine, from Piper species.
The present work evaluated the cytotoxicity of piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-trans-2-propenyl]-2(1H)pyridinone} and piperine {1-[5-(1,3)-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine}, components obtained from Piper species. The substances were tested for their cytotoxicity on the brine shrimp lethality assay, sea urchin eggs development, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay using tumor cell lines and lytic activity on mouse erythrocytes. Piperine showed higher toxicity in brine shrimp (DL50 = 2.8 +/- 0.3 microg/ml) than piplartine (DL50 = 32.3 +/- 3.4 microg/ml). Both piplartine and piperine inhibited the sea urchin eggs development during all phases examined, first and third cleavage and blastulae, but in this assay piplartine was more potent than piperine. In the MTT assay, piplartine was the most active with IC50 values in the range of 0.7 to 1.7 microg/ml. None of the tested substances induced hemolysis of mouse erythrocytes, suggesting that the cytotoxicity of piplartine and piperine was not related to membrane damage.


Journeys of adjustment: the experiences of adolescents living with juvenile idiopathic arthritis.
Juvenile idiopathic arthritis (JIA) is one of the most common diseases of childhood causing pain, swelling of joints and reduced mobility. Previous research has focused on the challenges and psychosocial impact of JIA, but there has been limited attention given to how young people adjust and adapt to living with a long-term condition such as JIA. The aim of this qualitative study was therefore to explore adolescents' experiences of living with JIA, with particular focus on the process of adjustment. Ten adolescents (7 female, 3 male) aged 13-17 years with good treatment adherence were recruited from an adolescent arthritis clinic. In-depth interviews were conducted, and data were analysed by two researchers independently using interpretative phenomenological analysis. These adolescents described the physical and psychosocial 'burden of living with JIA' and the challenges faced by an underlying preoccupation 'to be a normal teenager'. However, their accounts also revealed ways in which they regained agency and developed 'resilience through taking control' over their lives. This resilience helped the adolescents re-establish a sense of well-being through an ongoing process of 'acceptance and self-growth'. Although much research has adopted a deficit model that focuses on adjustment problems, the current study highlights the resourcefulness of young people in managing the challenges of living with a long-term condition. These experiences of successful adjustment can be used as the basis of positive, strength-based intervention approaches for adolescents with arthritis to enhance resilience and well-being.


Fear of COVID-19 and related factors affecting mothers' breastfeeding self-efficacy during the pandemic.
This study aimed to determine the breastfeeding self-efficacy levels of mothers during the pandemic period, to compare them according to various characteristics, and to examine the relationship between the fear of COVID-19 and breastfeeding self-efficacy. The data of this descriptive and cross-sectional were collected through a web-based survey of 392 mothers between June and August 2021. The data collection tools were the Introductory Data Form, the Breast-feeding Self-Efficacy Scale-Short Form, and the Fear of COVID-19 Scale. The mean score for breastfeeding self-efficacy was found to be 56.18 ± 8.24, while the mean score for the Fear of COVID-19 scale was 21.77 ± 6.14. Having a high fear of COVID-19, breastfeeding more frequently in this period, and suspecting that they had COVID-19 affected the breastfeeding self-efficacy scores positively, whereas graduating from primary school had a negative effect on self-efficacy. The breastfeeding self-efficacy of mothers who were fearful of COVID-19, who breastfed more frequently during the pandemic, and who had a higher education level were positively affected.


An internal amplification control system based on primer-dimer formation for PCR product detection by DNA hybridization.
The detection of PCR products by DNA hybridization techniques can suffer from inhibition of the amplification process by sample matrix components. We have designed a simple internal control system for PCR based on the incorporation of a primer pair with complementary 3' ends, resulting in the generation of a unique "primer-dimer" detectable by hybridization with a specific capture probe immobilized on polyester cloth as part of an array of amplicon-specific probes. The inclusion of this primer pair did not adversely affect the amplification and subsequent detection of target gene sequences by hybridization with immobilized probes in either single gene amplification or multiplex PCR systems. The failure to amplify target gene sequences because of the presence of inhibitors was mirrored by a failure to amplify the internal control primer-dimer, demonstrating the efficacy of this system in identifying the presence of DNA amplification inhibitors.


In vitro cytotoxicity and genotoxicity of chlorinated drinking waters sampled along the distribution system of two municipal networks.
When chlorine is used as a disinfectant for drinking water it may react with organic materials present in or released by the water pipes and thus form by-products that may represent a genotoxic hazard. The aim of this study was to assess the potential genotoxicity and cytotoxicity of extracts of chlorinated drinking water supplied by local aquifers of two Italian towns, Plants 1 and 2, located in the sub-Alpine area and on the Po plain, respectively. The raw water fell within the legal limits with regards to its chemical and physical properties. Water from Plant 2 contained higher levels of total organics (TOC) and nitrate than water from Plant 1. Water was sampled at different points along the distribution networks to evaluate the influence of the system on the amount and quality of the by-products. Cytotoxic and genotoxic damage was assessed in freshly isolated human white blood cells (WBC) and Hep-G2 cells by use of the micronucleus (MN) test and the Comet assay to measure primary DNA damage. While they did not show significant cytotoxicity, all Plant 1 water concentrates induced short-time genotoxic effects on leukocytes at concentrations > or =1 Lequiv./mL. Plant 2 samples were able to induce cytotoxic effects in both Hep-G2 cells and leukocytes. Furthermore, although there was no significant increase in MN frequency, DNA migration was strongly increased both in human leukocytes (> or =0.5 Lequiv./mL, 1h treatment, water samples collected from all points) and in Hep-G2 cells (> or =0.75 Lequiv./mL, 24 h treatment, tap water sampled at the nearest distribution point). The current use of these in vitro cytotoxicity/genotoxicity tests together with the normal chemical analyses could provide information to help water-works managers and health authorities evaluate drinking water quality and adopt strategies to reduce genotoxic compounds in tap water and prevent human exposure to these compounds.


Modeling DNA methylation in a population of cancer cells.
Little is known about how human cancers grow because direct observations are impractical. Cancers are clonal populations and the billions of cancer cells present in a visible tumor are progeny of a single transformed cell. Therefore, human cancers can be represented by somatic cell ancestral trees that start from a single transformed cell and end with billions of present day cancer cells. We use a genealogical approach to infer tumor growth from somatic trees, employing haplotype DNA methylation pattern variation, or differences between specific CpG sites or "tags," in the cancer genome. DNA methylation is an epigenetic mark that is copied, with error, during genome replication. At our tags, neutral copy errors in DNA methylation appear to occur at random, and much more frequently than sequence copy errors. To reconstruct a cancer tree, we sample and compare human colorectal genomes within small geographic regions (a cancer fragment), between fragments on the same side of the tumor, and between fragments from opposite tumor halves. The combined information on both physical distance and epigenetic distance informs our model for tumor ancestry. We use approximate Bayesian computation, a simulation-based method, to model tumor growth under a variety of evolutionary scenarios, estimating parameters that fit observed DNA methylation patterns. We conclude that methylation patterns sampled from human cancers are consistent with replication errors and certain simple cancer growth models. The inferred cancer trees are consistent with Gompertzian growth, a well-known cancer growth pattern.


Phosphodiesterase 5 inhibitor, zaprinast, selectively increases cerebral blood flow in the ischemic penumbra in the rat brain.
Guanosine 3', 5'-cyclic monophosphate (cGMP) acts as a relaxant second messenger in the cerebral vessels. cGMP-specific phosphodiesterase type 5 (PDE5) inhibitor increases intracellular cGMP levels. This study investigated the effect of the PDE5 inhibitor on the ischemic brain. Regional cerebral blood flow (rCBF), cGMP concentration, and infarction volume were measured in the rat middle cerebral artery occlusion model. Ten minutes after ischemia, the animals received an intravenous (i.v.) infusion of vehicle (phosphate-buffered saline), PDE5 inhibitor, zaprinast (10 mg/kg), or nitric oxide donor, S-nitroso-N-acetyl-penicillamine (SNAP, 100 microg/kg). rCBF was measured continuously by laser-Doppler flowmetry in the ischemic penumbra of the ischemic and contralateral sides under continuous blood pressure monitoring. cGMP concentrations were determined using the enzyme immunoassay and infarct volumes were estimated by 2,3,5-triphenyltetrazolium chloride staining. The administration of zaprinast significantly increased rCBF in the ischemic brain compared with the pre-drug control value despite the decreased mean blood pressure, whereas it did not affect rCBF in the contralateral side. The cGMP concentration was significantly higher in the ischemic cortex compared with the contralateral side. SNAP infusion increased the cGMP concentration in the bilateral cortices to a similar extent. The volume of cerebral infarction was significantly decreased by zaprinast administration. The PDE5 inhibitor zaprinast may selectively increase CBF in the ischemic brain via increased cGMP levels, thus providing a new strategy against acute cerebral infarction.


Context specificity of conflict frequency-dependent control.
Interference in the Eriksen flanker task has been shown to be reduced when the (relative) frequency of conflicting stimuli is increased, a modulation thought to reflect a higher degree of processing selectivity under conditions of frequent conflict (Botvinick, Braver, Barch, Carter, & Cohen, 2001). Previous studies suggest that stimulus location acts as a contextual cue, resulting in location-specific adjustment of processing selectivity when different locations are associated with differential conflict frequencies (Corballis & Gratton, 2003; Wendt, Kluwe, & Vietze, 2008). In the current study we extend these findings by showing that not only stimulus location but also stimulus colour can be used for context-specific adjustments. These findings suggest that processing selectivity is adjusted in parallel with current stimulus processing, potentially serving to resolve a current conflict rather than to prepare for an upcoming new conflict.


The mammalian microRNA response to bacterial infections.
MicroRNAs are small RNAs that post-transcriptionally regulate eukaryotic gene expression. In addition to their involvement in a wide range of physiological and pathological processes, including viral infections, microRNAs are increasingly implicated in the eukaryotic response to bacterial pathogens. Recent studies have characterized changes in host microRNA expression following infection with exclusively extracellular (Helicobacter pylori) or intracellular (Salmonella enterica) Gram-negative bacteria, as well as in the response to Gram-positive (Listeria monocytogenes) and other pathogens (Mycobacterium and Francisella species). In this review, we discuss the emerging roles of microRNAs in mammalian host signaling and defense against bacterial pathogens.


Touchpoints: A Business Strategy to Retain New Graduate Nurses.
The aim of this study was to reduce the turnover of new RNs (NRNs) completing a 1-year nurse residency program. Businesses use touchpoints to retain both internal and external customers, yet no evidence was found in retaining NRNs. Touchpoints, distinct points in the company-customer experience, play a vital role in the customer's experience with the company. Employees are one of a company's many customer types. This quality-improvement project implemented touchpoints to improve NRN retention rates. Retention rates and job-satisfaction scores were significantly higher among the touchpoint-intervention cohort compared with the nonintervention cohort. Implementation costs were far less than those associated with NRN turnover. Touchpoints are a practical management approach for NRN retention.


Evaluation of the human becoming theory in practice in an acute care psychiatric setting.
Using a descriptive evaluation research method, this study evaluated Parse's theory of human becoming in practice in the psychiatric setting. A pre- mid- post-implementation design served to generate qualitative data from nurses, patients, unit nurse managers, hospital nurse supervisors, and nurse documentation that illuminated changes in the quality of nursing care on three diverse pilot units. Major themes of change supported by all data sources were shifting views of human beings, altered ways of listening, altered foci of nurse-person discussions, and personal transformations. Identified themes surfaced strikingly different qualities of change for each pilot unit. Recommendations related to the successful implementation of Parse theory-based practice are presented.


Novel high voltage polymer insulators using computational and data-driven techniques.
One of the key bottlenecks in the development of high voltage electrical systems is the identification of suitable insulating materials capable of supporting high voltages. Under high voltage scenarios, conventional polymer based insulators, which are one of the popular choices of insulators, suffer from the drawback of space charge accumulation, which leads to degradation in desirable electronic properties and facilitates dielectric breakdown. In this work, we aid the development of novel polymers for high voltage insulation applications by enabling the rapid prediction of properties that are correlated with dielectric breakdown, i.e.,the bandgap (Egap) of the polymer and electron injection barrier (Φe) at the electrode-insulator interface. To accomplish this, density functional theory based methods are used to develop large, chemically diverse datasets of Φe and Egap. The deviation of the computed properties from experimental observations is addressed using a statistical technique called Bayesian calibration. Furthermore, to enable rapid estimation of these properties for a large set of polymers, machine learning models are developed using the created dataset. These models are further used to predict Egap and Φe for a set of 13k previously known polymers. Polymers with high values of these properties are selected as potential high voltage insulators and are recommended for synthesis. Finally, the models developed here are deployed at www.polymergenome.org to enable the community use.


Regeneration of the mandibular condyle after unilateral condylectomy and myotomy of the masseter in lambs.
We investigated the degree of regeneration of the mandibular condyle after unilateral condylectomy and myotomy of the masseter in growing lambs. Four 10-week-old lambs had unilateral condylectomy and myotomy of the superficial layer of the masseter on the right side, and were killed 3 months later. The joints were examined radiologically and histologically. All joints showed poor regeneration of the condylar head. In the medial plane there was partial condylar and articular cartilage reformation, but in the lateral plane there was neither condylar nor cartilaginous reformation. The articular cartilage of the temporal bone was thicker in the medial plane and the disc was thicker in the central plane, than in unoperated joints. We conclude that unilateral condylectomy and myotomy of the masseter in the growing period results in poor regeneration of the condyle.


Screw driver: an unusual cause of cervical spinal cord injury.
Non-missile penetrating spinal injuries are rare. Screw driver injury, more especially to the cervical spine, represents an even rarer subset. To our knowledge, this is the first reported case from West Africa of cervical spinal cord injury from a screw driver. A middle-aged man was stabbed from the back with a screw driver. He presented with right-sided C4 Brown-Sequard syndrome with the impaling object in situ. Cervical spine x-rays showed the screw driver to have gone into the spine between the spinous processes of C4 and C5, traversing the spinal canal and lodged in the anterior part of the C4/5 intervertebral disc space. C4 and C5 laminectomies were performed and the screw driver removed under vision. The object was found to have traversed the right side of the cervical spinal cord. The dural tear was repaired. He had some neurologic improvement initially, but later declined. He died from severe pulmonary complications 2 weeks postinjury. Screw driver represents an unusual cause of non-missile penetrating cervical spinal injury. Its neurological effects and complications of the cord injury lead to significant morbidity and mortality.


Case series of medication-related osteonecrosis of the jaw (MRONJ) patients prescribed a drug holiday.
The role of a drug holiday in the management of medication-related osteonecrosis of the jaw (MRONJ) remains controversial. Current UK guidance does not recommend this practice given the lack of conclusive evidence, and potential risk of skeletal-related events or cancer metastasis. This paper aims to describe a series of fifty patients with confirmed MRONJ who were prescribed a drug holiday as part of their management. Data were collected on exposures including: anti-resorptive and/or anti-angiogenic drug history, duration of drug, method of administration, concurrent therapy, MRONJ stage, management of MRONJ and duration of drug holiday. The primary outcome was complete healing as documented in the clinical notes. Multivariate Cox regression analysis was performed to evaluate the association between exposures and primary MRONJ outcome. Models were adjusted for age, sex, and index of multiple deprivation. Survival analysis was performed using a log-rank test, censoring any patients with no primary outcome recorded (p < 0.05). A total of 44% of patients stopped their medication for >36 months. Over half of all MRONJ cases presented in the posterior mandible and dental extraction was the most common precipitating factor (76%). Almost three-quarters (72%) of patients achieved complete healing. MRONJ recurrence (new site) was reported at 30%, mainly in those with incomplete healing of the initial area. There was a lack of evidence for an association between all recorded exposures and the primary MRONJ outcome using multivariate Cox regression. Similarly, we did not demonstrate evidence for an association between the duration of the drug holiday and MRONJ outcome. Our results support published guidelines, which do not recommend the discontinuation of bone modifying drugs for the prevention of MRONJ, or as part of treatment for established MRONJ.


Role of Th17-cell related cytokines in geriatric asthma.
This study aimed to investigate the pathogenesis of geriatric asthma through immunoglobulin E (IgE), interleukin-17A (IL-17A), IL-17F, and glucocorticoid receptor-β (GR-β) expression. We studied 51 geriatric male patients with asthma and 50 young male patients with asthma. We also included 21 normal geriatric males and 21 normal young males. All geriatric and young patients were divided into groups according to pulmonary function. Levels of cytokines, such as IgE, IL-17A, IL-17F, and GR-β, were measured. Pulmonary function was assessed. The results from patients were compared with those from the 42 healthy subjects. Serum IgE, IL-17A, IL-17F, and GR-β levels in geriatric patients with moderate or severe asthma were significantly higher than those in young patients with moderate asthma and in the normal population. Geriatric patients with asthma had higher asthma control test scores than did young patients with asthma. Hormone resistance in geriatric male patients with asthma is more serious than that in young male patients with asthma. Airway inflammation and airway remodeling in geriatric male patients with asthma may be more serious than those in young male patients with asthma, even when there is similar pulmonary function.


The role of second trimester ultrasound in the diagnosis of placental hypoechoic lesions leading to poor pregnancy outcome.
The purpose of the study was to quantify placental hypoechoic areas without blood flow by means of second trimester high-resolution ultrasound with power color Doppler and to evaluate its relationship to pregnancy outcome. Patients referred for second trimester ultrasound from January 2001 to December 2003 were eligible for the study. Patients with placental parenchymal hypoechoic areas without blood flow constituted the study group (N = 65). The control group was comprised of 65 patients who had normal placental parenchyma. The groups were similar with regards to maternal age, gestational age, parity, race, and smoking. The mean of the two largest lesion diameters was used for severity classification. Fifty-two patients (80%) had aggregate lesions of <or=5 cm and 13 (20%) had lesions >5 cm. Mean +/- standard deviation (SD) gestational age at delivery was 39.1 +/- 1.8 weeks for the control group, 37.9 +/- 2.8 weeks for those with lesions of <or=5 cm, and 35.2 +/-5.8 weeks for those with lesions >5 cm (p < 0.0001). Mean birth weight +/- SD was 3348 +/- 492 g for the controls, 3134 +/- 657 g for those with lesions of <or=5 cm, and 2524 +/- 1339 g for those with lesions >5 cm (p = 0.0005). The incidence of intrauterine growth restriction was 9.6% in the group with lesions of <or=5 cm and 38.4% in the group with lesions >5 cm, compared to 3.1% in the control group (p = 0.0003; odds ratio (OR) = 5.7, p = 0.015). The incidence of preeclampsia in the control group was 0.0%, in the group with lesions of <or=5 cm was 7.7%, and in the group with lesions >5 cm was 15.4% (p < 0.0214; OR = 14.3, p = 0.014). Increased size of hypoechoic placental lesions is associated with increased risk for adverse perinatal outcome. Such lesions might be the result of intervillous space thrombosis, and ultrasound may be a useful tool in the identification of patients with pro-thrombotic abnormalities. The capability to identify patients with placental thrombosis will help us to identify those patients who will benefit most from anti-thrombotic treatment


Adolescent brain development and animal models.
Research examining brain development during adolescence is escalating rapidly along multiple dimensions, as illustrated by the remarkable diversity of trans-disciplinary work shown in this symposium. Ontogenetic transitions characteristics of adolescence are common among mammalian species. Although no other species demonstrates the full complexity of brain and behavioral function seen in human adolescents, adolescence appears to be a highly conserved developmental stage, its characteristics sculpted to meet common evolutionary pressures that include the avoidance of inbreeding at this time of sexual emergence. Numerous similarities are found between human adolescents and adolescents of other species in terms of developmental history and genetic constraints, as well as neurobehavioral and physiological characteristics. These similarities provide face and construct validity to support use of animal models as tools for the study of adolescence and the unique opportunities and vulnerabilities afforded by this developmental transition.


Probiotics to adolescents with obesity: effects on inflammation and metabolic syndrome.
The connections between gut microbiota, energy homeostasis, and inflammation and its role in the pathogenesis of obesity-related disorders are increasingly recognized. We aimed to investigate the effect of the probiotic strain Lactobacillus salivarius Ls-33 on a series of biomarkers related to inflammation and the metabolic syndrome (MS) in adolescents with obesity. The study was a double-blind placebo-controlled trial including 50 adolescents with obesity randomized to Ls-33 (10 CFU) or placebo daily for 12 weeks. The average body mass index-for-age z-score was 2.6 ± 0.5. There were no differences in biomarkers of inflammation and parameters related to the MS at baseline between the probiotic and placebo groups. Furthermore, there were no differences in changes from baseline to 12-week intervention with regard to any anthropometric measures, blood pressure (systolic and diastolic), fasting glucose and insulin, homeostasis model assessment of insulin resistance, C-peptide, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, free fatty acids, C-reactive protein, interleukin-6, tumor necrosis factor alpha, or fecal calprotectin, despite the increased values of biomarkers of inflammation and of several parameters related to the MS at baseline when compared with normal-weight adolescents. The levels of L salivarius in fecal samples from the probiotic group in the present study were comparable with the levels reported for the other probiotic lactobacilli and bifidobacteria using quantitative polymerase chain reaction. It was not possible to detect any beneficial effect of the probiotic intervention with Ls-33 on inflammatory markers or parameters related to the MS in adolescents with obesity being in a state of low-grade systemic inflammation.


The shift in seasonality of legionellosis in the USA.
According to the Centers for Disease Control and Prevention (CDC), from 2000 to 2014, reported cases of legionellosis per 100 000 population increased by 300% in the USA, although reports on disease seasonality are inconsistent. Using two national databases, we assessed seasonal patterns of legionellosis in the USA. We created a monthly time series from 1993 to 2015 of reported cases of legionellosis from the CDC, and from 1997 to 2006 of medical claims of legionellosis-related hospitalisation in older adults from the Centers for Medicaid and Medicare Services (CMS). We split the study time interval into two segments (before and after 2003), and applied a Poisson harmonic regression model to each dataset and each segment. The time series of monthly counts exhibited a significant shift of seasonal peaks from mid-September (9.676 ± 0.164 months) before 2003 to mid-August (8.452 ± 0.042 months) after 2003, along with an alarming increase in the amplitude of seasonal peaks in both CDC and CMS data. The lowest monthly reported cases of legionellosis in 2015 (281) exceed the maximum value reported before 2003 (206). We also observed a discrepancy between CDC and CMS data, suggesting that not all cases of legionellosis diagnosed by hospital-based laboratories were reported to the CDC. Improved reporting of legionellosis is required to better inform the public and organise disease prevention.


Characterization of bacterial community associated with phytoplankton bloom in a eutrophic lake in South Norway using 16S rRNA gene amplicon sequence analysis.
Interactions between different phytoplankton taxa and heterotrophic bacterial communities within aquatic environments can differentially support growth of various heterotrophic bacterial species. In this study, phytoplankton diversity was studied using traditional microscopic techniques and the bacterial communities associated with phytoplankton bloom were studied using High Throughput Sequencing (HTS) analysis of 16S rRNA gene amplicons from the V1-V3 and V3-V4 hypervariable regions. Samples were collected from Lake Akersvannet, a eutrophic lake in South Norway, during the growth season from June to August 2013. Microscopic examination revealed that the phytoplankton community was mostly represented by Cyanobacteria and the dinoflagellate Ceratium hirundinella. The HTS results revealed that Proteobacteria (Alpha, Beta, and Gamma), Bacteriodetes, Cyanobacteria, Actinobacteria and Verrucomicrobia dominated the bacterial community, with varying relative abundances throughout the sampling season. Species level identification of Cyanobacteria showed a mixed population of Aphanizomenon flos-aquae, Microcystis aeruginosa and Woronichinia naegeliana. A significant proportion of the microbial community was composed of unclassified taxa which might represent locally adapted freshwater bacterial groups. Comparison of cyanobacterial species composition from HTS and microscopy revealed quantitative discrepancies, indicating a need for cross validation of results. To our knowledge, this is the first study that uses HTS methods for studying the bacterial community associated with phytoplankton blooms in a Norwegian lake. The study demonstrates the value of considering results from multiple methods when studying bacterial communities.


Diagnosis and laparoscopic management of a rudimentary uterine horn in a teenage girl, presenting with haematometra and severe endometriosis: our experience and review of literature.
A unicornuate uterus is a rare congenital malformation of the female genital tract, which appears in about 1/1000 women and is characterized by significant anatomic variability. In the most common type, a noncommunicating rudimentary horn coexists with the unicornuate uterus. The diagnosis of this anomaly is usually delayed, as it remains asymptomatic until adolescence and its initial symptoms are atypical. As a result, it is often diagnosed after the appearance of severe complications, such as haematometra, endometriosis, infertility and ectopic pregnancy. We report a case of a teenage girl presenting with dysmenorrhoea, endometriosis and haematometra secondary to a noncommunicating rudimentary horn. The diagnosis of the anomaly was based on magnetic resonance imaging (MRI) and laparoscopy. The excision of the symptomatic rudimentary horn and the ipsilateral fallopian tube was also performed laparoscopically. A review of the literature follows, focusing mainly on the diagnosis and laparoscopic management of a unicornuate uterus and its complications in adolescence. Laparoscopy is an accurate diagnostic tool, which also carries significant advantages in effective surgical management of congenital uterine anomalies, especially in young women.


Female Family Physicians May Earn $1.8 Million Less Than Male Peers Over a Lifetime.
The average salaries of female physicians are lower than those of their male peers. Previous studies demonstrate that female family physicians earn approximately 16% less than their male counterparts.1 However, multiple studies have demonstrated benefits of having a female physician, including quality of care and relationships.2,3 After controlling for multiple variables, the wage gap persists, making gender biases the most likely explanation.


Analysis of nurse-doctorates; data collected for the International Directory of Nurses with Doctoral Degrees.
In an American Nurses' Foundation survey of the 1973 population of nurses with doctoral degrees (N = 1,020) general trends in doctoral education of nurses were elicited. Specific unique characteristics were highlighted, including: a continuing trend for nurses to earn the Ph.D. rather than the Ed.D., a divergence between field of doctoral study and the current field of research interest, and a slight number of these qualified nurses actually participating in research of any kind. The majority of subjects were single; most were employed in a university or college where they held either full or associate professorships; most considered themselves still to be in the field of nursing, although their doctoral studies frequently took them out of the discipline; their work responsibilities were heavily loaded with administrative duties. As compared with the holders of doctoral degrees in other fields, nurses earned their degrees later, but took no longer to complete them. While universities in the Mid-Atlantic states were the largest producers of nurse-doctorates, universities in the Midwest were found to be the most frequent employers. Questions regarding the future direction of nurse-doctorates were raised.


Barriers and Facilitators of Adverse Event Reporting by Adolescent Patients and Their Families.
The objectives were (1) to describe barriers and facilitators of adverse event reporting by adolescent patients and parents in a pediatric hospital and (2) to identify characteristics the participants wished to have in a formal reporting system of adverse events. We used a qualitative design in which 6 focus groups, 3 with parents and 3 with adolescents, were conducted. The transcripts of audio recordings, notes of team debriefings, and written field notes of group behaviors were analyzed using NVivo software for qualitative data analysis. Participants reported that the quality of the experience with the health care system, type of communication with health care providers, and degree of personal self-confidence in communication within the health care system were 3 interacting factors influencing willingness to report adverse events. Preferred reporting mechanisms were different for different participants and included face-to-face meetings with hospital representatives, Web sites, smart phone capability, phone calls from a human, and paper mail. Reporting systems should be easy to use, ensure confidentiality, and provide user feedback. Experience, communication, and confidence are 3 factors that can engage an adolescent patient and parents in their health care. Confident adolescent patients and parents in turn have a possibility of reporting an adverse safety event given an opportunity.


Endocytosis of cholera toxin into neuronal GERL.
Cholera toxin linked covalently by glutaraldehyde to horseradish peroxidase was incubated with cultured chicken sympathetic neurons at 4 degrees. Cells were washed and brought to 37 degrees to permit endocytosis of bound toxin on plasma membranes. Massive internalization of the ligand into vesicles and cisterns of the Golgi--endoplasmic reticulum--lysosome (GERL) system was demonstrated by the cytochemical reaction for the enzyme. Surface binding and subsequent endocytosis of the cholera toxin--enzyme conjugate was inhibited when conjugate and monosialoganglioside (GM1) were simultaneously applied to cells at 4 degrees. Cholera toxin is not toxic to neurons at the levels used. These results indicate that GERL is the primary site of endocytosis of presumed complexes of cholera toxin with its plasma membrane receptor (GM1 ganglioside-containing moieties). It is suggested that, in neurons, plasma-membrane bound ligands are taken up primarily into GERL.


Neurological presentation and long-term outcome following operative intervention in patients with meningocele manqué.
We review and describe the neurological presentation and long-term outcome of patients with meningocele manqué, and describe the dysraphic features associated with this entity. Our series of patients was collected over a 25-year period with a mean follow-up of 11.5 years. The mean age of presentation was 10.4 years and 72% of the patients presented with an abnormal neurological examination. At most recent follow-up, symptoms were stable, improved, and progressed in 47, 37 and 16%, respectively. Meningocele manqué was associated with focal hirsutism in 37% of the cases. These bands were primarily found in the lumbar spine and involved two sequential vertebral levels in 42% of cases. Sectioning of meningocele manqué has good long-term results in the majority of patients. These bands should be sought in the evaluation of patients with spinal dysraphism and surgically transected.


Charcot arthropathy of the spine in spinal cord injured individuals with sacral deafferentation and anterior root stimulator implantation.
To investigate the occurrence of Charcot spinal arthropathy (CSA) after sacral deafferentation (SDAF) and sacral anterior root stimulation (SARS) of the bladder in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD) as a result of spinal cord injury (SCI). Retrospective evaluation of patients who had undergone SDAF/SARS at a single SCI rehabilitation centre. The occurrence rate of stimulation dysfunction was determined, and the medical records and radiological images of the included patients were examined for CSA. The diagnosis of CSA was based on radiological criteria. The occurrence rate of CSA was estimated for all SARS patients and for those with SARS dysfunction, and the odds ratios (OR) for the occurrence of CSA were calculated. In 11/130 SARS patients (8%), CSA was observed a median 8 years (95% CI 5-16 years) after SDAF/SARS or a median 21 years (95% CI 9-41 years) after SCI had occurred. The median follow-up time was 14 years (range 6-25 years). The proportion of patients with CSA was significantly (P = 0.036) greater in patients with SARS dysfunction (7/41) than in patients without SARS dysfunction (4/89). The odds of CSA were four times greater (OR 4.3, 95% CI 1.0-21.5) in patients with SARS dysfunction compared to those without. Furthermore, the odds of CSA were 20 times greater (OR 20.2, 95% CI 8.4-47.0) in patients with SARS compared to those without. Charcot spinal arthropathy should be considered a potential long-term complication of SDAF/SARS, and spinal instability is a possible reason for SARS dysfunction.


You have to be there to enjoy it? Neighbourhood social capital and health.
Several studies have shown the positive effect of neighbourhood social capital on health. Existing research, however, has hitherto not studied whether the duration and intensity of exposure to neighbourhood social capital conditions and its effect on health. The aim of this study was to examine whether neighbourhood social capital affects individual's health immediately and equally. We used two waves of the Dutch cross-sectional 'Housing and Living Survey'. One (from 2009) as individual data (n = 65,990), and the other (from 2006) to estimate with ecometric measurements a social capital measure for 3001 Dutch neighbourhoods. We assessed by means of multilevel regression models the combined effect of exposure and amount of neighbourhood social capital on self-rated health. Duration of exposure, measured by the length of stay in the same neighbourhood is not linearly associated with individual health. Health of people who live up to 6 years or >22 years in the same neighbourhood is not affected by neighbourhood social capital. People with young children in the household or elderly were assumed to be more intensively exposed. However, exposure intensity was only found to have an effect for households with young children. Duration and intensity of exposure to neighbourhood social capital, a social aspect of the environment, matters for people's health. Interventions focusing on the health of people with young children may want to stimulate the creation of neighbourhood social capital.


Hemoptysis due to aspirin treatment alternative to warfarin therapy in a patient with atrial fibrillation.
An 80-year-old female with a history of hypertension and atrial fibrillation had been receiving warfarin anticoagulant therapy and had stably maintained an international normalized ratio (INR) within the 2.0-3.0 range. Due to dental extractions, she was prescribed aspirin (100 mg/day) as an alternative therapy to warfarin. Three days later, the patient complained of hemoptysis without obvious inducement and the INR was 3.51. The aspirin was immediately discontinued and intravenous vitamin K was administered. Hemoptysis did not reappear and the INR returned to the normal limits. According to the Drug Interaction Probability Scale, a causal relationship between aspirin and warfarin and an increased INR value is possible.


Efficacy and tolerability of febuxostat in hyperuricemic patients with or without gout: a systematic review and meta-analysis.
Febuxostat has been approved for the treatment of hyperuricemia in patients with/without gout. This meta-analysis and systematic review assessed the efficacy and tolerability of febuxostat in hyperuricemic patients with/without gout. Major electronic databases were searched for articles of all publication years (up to February 2012), as were the Web sites of the American College of Rheumatology, the European League Against Rheumatism, and the Chinese State Food and Drug Administration, and clinicaltrials.gov for unpublished studies. Only randomized, controlled trials (RCTs) were included. Ten trials were included. A significantly greater proportion of patients achieved the target serum urate level (sUA ≤6.0 mg/dL) at the final visit in the febuxostat group compared with the placebo (OR = 235.73; P < 0.01) and allopurinol groups (OR = 3.14; P < 0.01). In subgroup analysis, the proportion of patients who achieved target sUA at the final visit was significantly greater in the febuxostat-treated group (40 mg/d) compared with the allopurinol-treated group (100-300 mg/d) (50.9% vs 45.6%; OR = 1.25; 95% CI, 1.05-1.49; P = 0.01). As the dosage was increased (40, 80, 120 mg/d), the proportion of patients who achieved target sUA in the febuxostat-treated group increased gradually (50.9%, 71.4%, 82%, respectively). There was no significant difference in the occurrence of adverse events (AEs) between the febuxostat- and allopurinol-treated groups. Febuxostat was effective in reducing serum urate in hyperuricemic patients with/without gout, and febuxostat (40-120 mg/d) was more efficacious compared with allopurinol (100-300 mg/d). The doses of allopurinol to which febuxostat has been compared, although commonly prescribed, are low in the range of approved doses of allopurinol. The tolerability of febuxostat for the treatment of hyperuricemia with/without gout is similar to that of allopurinol.


Effect of Pressure on Valence and Structural Properties of YbFe2Ge2 Heavy Fermion Compound--A Combined Inelastic X-ray Spectroscopy, X-ray Diffraction, and Theoretical Investigation.
The crystal structure and the Yb valence of the YbFe2Ge2 heavy fermion compound was measured at room temperature and under high pressures using high-pressure powder X-ray diffraction and X-ray absorption spectroscopy via both partial fluorescence yield and resonant inelastic X-ray emission techniques. The measurements are complemented by first-principles density functional theoretical calculations using the self-interaction corrected local spin density approximation investigating in particular the magnetic structure and the Yb valence. While the ThCr2Si2-type tetragonal (I4/mmm) structure is stable up to 53 GPa, the X-ray emission results show an increase of the Yb valence from v = 2.72(2) at ambient pressure to v = 2.93(3) at ∼9 GPa, where at low temperature a pressure-induced quantum critical state was reported.


Incidence of salmonella meningitis in Ludhiana (Punjab).
A retrospective study was carried out at Dayanand Medical College & Hospital, Ludhiana (Pb.) during the period from January 1985 to December 1990 to know the incidence of Salmonella meningitis. Salmonella etiology was established in 8 (3.43%) cases out of 233 cases of bacterial meningitis. Out of 8 cases, 7 were children under the age of 2 years. 4 Patients yielded S. typhimurium, 3, S. typhi and 1 S. senftenberg from cerebrospinal fluid samples. No Salmonella organism was isolated from blood cultures except one in which S. typhi was isolated. S. typhimurium was the predominant isolate showing multi drug resistance to commonly used drugs such as ampicillin, chloramphenicol, streptomycin, tetracycline and kanamycin. S. senftenberg also showed similar drug resistance pattern. S. typhi, on the other hand was sensitive to above antibiotics.


Correlation between characteristics of intracranial atherosclerotic plaques and ischemic stroke in high-resolution vascular wall MRI.
Intracranial atherosclerotic stenosis is a major cause of ischemic stroke, accounting for 30% of ischemic strokes in Asian populations. To investigate the relationship between the degree of arterial stenosis and enhancement grade of intracranial atherosclerotic disease (ICAD), the plaque characteristics in different remodeling patterns, and its potential impact. A total of 210 patients diagnosed with ICAD were enrolled in this retrospective study. Patients were divided into the middle cerebral artery (MCA) group (101 cases), posterior cerebral artery (PCA) group (14 cases), basilar artery (BA) group (71 cases), and intracranial segment of vertebral artery (VA) group (90 cases) according to the difference of diseased vessels. Data on presence or absence of ischemic infarction, intracranial vascular position of lesions, plaque characteristics, ICAD enhancement grade, remodeling index, and degree of arterial stenosis were collected for analysis. The incidence of ischemic infarction in enhancement grade 2 was significantly higher than that in enhancement grade 1 in MCA group (P = 0.019). Enhancement grade 2 of ICAD was an independent risk factor for the development of ischemic infarction (odds ratio = 4.60; 95% confidence interval: 1.91-11.03; P = 0.001). There was no significant statistical difference in infarct rate between different remodeling modalities (P>0.05). Enhancement grade of ICAD is significantly associated with the degree of stenosis and the occurrence of ischemic stroke, which varies in different intracranial vessels. The pattern of vascular remodeling varies among different intracranial vessels, and the pattern of vascular remodeling has a significant impact on plaque characteristics.


Co-existence of Pseudomonas-derived cephalosporinase among plasmid encoded CMY-2 harbouring isolates of Pseudomonas aeruginosa in north India.
In Pseudomonas aeruginosa, AmpC β-lactamases are often responsible for high-level resistance to β-lactam antibiotics. The co-production of plasmid-mediated AmpC along with chromosomal Pseudomonas-derived cephalosporinases thus remain a serious clinical concern owing to high resistance spectrum towards antibiotics. The present study was performed to investigate the co-existence of both chromosomally-encoded and plasmid-mediated AmpC β-lactamase among clinical isolates of P. aeruginosa. It is a cross-sectional study carried out in the Department of Microbiology in a tertiary referral hospital of northern India. A total of 329 consecutive, non-duplicate clinical isolates of P. aeruginosa, were selected for the detection of AmpC β-lactamases and confirmed for AmpC production by modified three dimensional (M3D) test. Ceftazidime -imipenem antagonism test was used to detect inducible AmpC producers. Molecular characterisation of chromosomally-encoded blaPDC and plasmid-mediated AmpC gene was studied by performing polymerase chain reaction (PCR). A total of 214 (65%) isolates were confirmed for AmpC production by M3D test. On performing multiplex PCR, 27 isolates were detected posessing blaCMY type of plasmid-mediated AmpC gene. While 48 isolates were found to harbour chromosomally-encoded blaPDC gene co-production of both chromosomal and plasmid-encoded AmpC was reported in eleven isolates. Although these chromosomally-encoded cephalosporinases might spread more slowly than mobilised AmpC, but it is likely that in the present scenario of intense antibiotic pressure, this will become an increasing problem and may further limit our antibiotic choices.


Retention test Homburg to monitor the adhesive properties of von Willebrand factor after substitution or desmopressin therapy.
To diagnose von Willebrand disease (vWD) and to monitor drug efficacy, several tests have been established that are not, however, focused on the platelet adhesion properties of von Willebrand factor (vWF). The new platelet retention test Homburg (RTH) is characterized by a nonthrombogenic filter that retains platelets from blood when it is pressed through this filter. It was the aim of this study to examine the capability of this test to monitor the adhesive properties of vWF after its substitution in vWD or its release by desmopressin infusion. The RTH demonstrated a striking sensitivity for vWF after its release from endogenous storage sites or its supplementation in vivo as well as in vitro, whereas it did not detect an inhibition of platelet aggregability due to aspirin. Desmopressin infusions led to an immediate and highly significant increase of RTH platelet retention, followed by a gradual decline to initial values during the next 4 hours. The transfusion of a vWF concentrate also resulted in RTH data that demonstrated different kinetics than established parameters such as vWF:antigen, vWF:RiCoF, or the PFA-100 in vitro bleeding analysis. Additional in vitro experiments confirmed the correlation of RTH values with vWF concentrations. In conclusion, the RTH may be efficient to complement presently used measures to monitor vWD therapy with desmopressin or vWF concentrates.