Astigmatism in 12-year-old Australian children: comparisons with a 6-year-old population.
To study the distributions of refractive (RA), corneal (CA), and internal astigmatism (IA) in 12-year-old Australian children and to explore differences from previous findings in 6-year-old children. Eligible year 7 students (2353/3144 [75.3%], median age, 12 years) from a random cluster sample of 21 high schools in Sydney, Australia, were examined by keratometry, cycloplegic autorefraction, and review of questionnaire data. Prevalence rates of RA, CA, and IA > or =1.0 D in right eyes were 6.7% (95% confidence interval [CI], 5.0-8.4), 26.6% (CI, 22.1-31.1), and 26.5% (CI, 22.9-30.0), respectively. RA was predominantly with-the-rule (WTR; 40.4%, CI, 32.6 to 48.2) and against-the-rule (ATR; 43.6%, CI, 35.7-51.5), CA was WTR (88.8%, CI, 86.3-91.3), and IA was ATR (90.2%, CI, 87.8-92.6). The girls had significantly greater CA and IA prevalence, with greater ATR astigmatism and lower oblique IA than did the boys. The European white-Australian children had lower CA prevalence than did the East Asian-Australian children and higher IA prevalence than did the South Asian-Australian children. Ethnic differences in RA prevalence were not significant, when adjusted for confounders. RA was more frequently ATR in European white than in other ethnic groups. Compensation between CA and IA reduced the magnitude of RA. Comparison with the data on 6-year-old children revealed minimal differences for all astigmatic components. There was a relatively low prevalence of RA, due to compensation between CA and IA. The minimal differences in all components of astigmatism between the two age cohorts suggest that astigmatism is stable between ages 6 and 12 years, although this conclusion needs to be confirmed in longitudinal studies.


"I am a fat baby, who moved to a fat child, who moved to a fat teenager, who moved to a fat adult": Women's reflections of a lifetime of body and weight concern.
The present study explored how women aged 50-65 years reflect and make meaning of a lifetime of body and weight struggles. Seven purposefully selected women with longstanding body image challenges participated in interviews and reflected on their perceptions, thoughts, and emotions around their body and weight since childhood. Findings revealed consistent and consuming concerns about the body; prevalent body-related self-conscious emotions; influential social experiences that impact physical self-perceptions; and enduring impacts of weight bias, stigma, and discrimination. Collectively, these findings provide support for the stability of body disturbances and highlight the need to explore the unique body-related narratives of women in midlife.


[Infected joint fracture. Diagnosis, treatment and results in 63 patients].
For diagnosis, treatment and prognosis of infected articular fractures special attention should be paid to the following: When conventional treatment with puncture and irrigation of the joint after a maximum of 7 days is not successful, synovectomy in the early stage of infection, before extensive cartilage destruction particularly in the knee, elbow joint and hand, is the appropriate treatment. The progressive destruction of the cartilage and bone is interrupted. As a result of the early functional after-treatment good mobility of the joint and cartilage nutrition are achieved. In patients who were treated with synovectomy the time for healing was only 4 months, after arthrectomy 7 months and arthrodesis 20 months. Taking into consideration the complaints, mobility and shortening of the leg synovectomies had better results. The overall result demonstrates that despite enormous therapeutic effort, the infection in articular fractures is a serious complication which often leads to permanently functional deficiencies. Of 55 re-examined patients 34 were free of complaints, 5 amputations were necessary as a result of severe neurovascular damage and sepsis. The best results were achieved with early synovectomy.


Estimating rice chlorophyll content and leaf nitrogen concentration with a digital still color camera under natural light.
The color of crop leaves is closely correlated with nitrogen (N) status and can be quantified easily with a digital still color camera and image processing software. The establishment of the relationship between image color indices and N status under natural light is important for crop monitoring and N diagnosis in the field. In our study, a digital still color camera was used to take pictures of the canopies of 6 rice (Oryza sativa L.) cultivars with N treatments ranging from 0 to 315 kg N ha(-1) in the field under sunny and overcast conditions in 2010 and 2011, respectively. Significant correlations were observed between SPAD readings, leaf N concentration (LNC) and 13 image color indices calculated from digital camera images using three color models: RGB, widely used additive color model; HSV, a cylindrical-coordinate similar to the human perception of colors; and the L (*) a (*) b (*) system of the International Commission on Illumination. Among these color indices, the index b (*) , which represents the visual perception of yellow-blue chroma, has the closest linear relationship with SPAD reading and LNC. However, the relationships between LNC and color indices were affected by the developmental phase. Linear regression models were used to predict LNC and SPAD from color indices and phasic development. After that, the models were validated with independent data. Generally, acceptable performance and prediction were found between the color index b (*) , SPAD reading and LNC with different cultivars and sampling dates under different natural light conditions. Our study showed that digital color image analysis could be a simple method of assessing rice N status under natural light conditions for different cultivars and different developmental stages.


[Chemiluminescence spectroscopic analysis of homogeneous charge compression ignition combustion processes].
To study the combustion reaction kinetics of homogeneous charge compression ignition (HCCI) under different port injection strategies and intake temperature conditions, the tests were carried out on a modified single-cylinder optical engine using chemiluminescence spectroscopic analysis. The experimental conditions are keeping the fuel mass constant; fueling the n-heptane; controlling speed at 600 r x min(-1) and inlet pressure at 0.1 MPa; controlling inlet temperature at 95 degrees C and 125 degrees C, respectively. The results of chemiluminescence spectrum show that the chemiluminescence is quite faint during low temperature heat release (LTHR), and these bands spectrum originates from formaldehyde (CH2O) chemiluminescence. During the phase of later LTHR-negative temperature coefficient (NTC)-early high temperature heat release (HTHR), these bands spectrum also originates from formaldehyde (CH2O) chemiluminescence. The CO--O* continuum is strong during HTHR, and radicals such as OH, HCO, CH and CH2O appear superimposed on this CO--O* continuum. After the HTHR, the chemiluminescence intensity is quite faint. In comparison to the start of injection (SOI) of -30 degrees ATDC, the chemiluminescence intensity is higher under the SOI = -300 degrees ATDC condition due to the more intense emissions of CO--O* continuum. And more radicals of HCO and OH are formed, which also indicates a more intense combustion reaction. Similarly, more intense CO--O* continuum and more radicals of HCO and OH are emitted under higher intake temperature case.


[X-ray diagnosis of Sivert-Kartagener's syndrome].
Clinico-roentgenological data of 11 patients with Sivert-Kartagener's syndrome are analysed. Five patients were operated on during childhood for chronic relapsing pulmonary pathology. The used roentgenological methods included x-ray of the thorax, bilateral bronchography, x-ray of the paranasal sinuses. Detailed roentgenological data on this syndrome are of major practical significance due to surgical methods of treatment of purulent bronchiectasia after preliminary sanation of the paranasal sinuses.


Sleep timing is associated with self-reported dietary patterns in 9- to 15-year-olds.
To examine sleep timing differences in self-reported dietary patterns of children and adolescents. Cross-sectional. Students aged 9-15 years (n=119, 11.7±1.3 years, 76% female) attending a summer program for the gifted. The upper and lower quartiles of reported midsleep time (weighted weekday-weekend average) were used to identify early (n=28) and late (n=27) sleep timing groups. Sleep patterns were assessed via self-report. Participants also rated their likelihood to consume 9 different categories of food and drinks on a 5-point scale ranging from "no likelihood" to "high likelihood." Foods were grouped as follows: (1) sugary and caffeinated beverages; (2) high-energy-dense, nutrient-poor foods (ie, sugary, salty, fatty foods); and (3) low-energy-dense, nutrient-rich foods (ie, vegetables, proteins, carbohydrates, fruits). Midsleep time was 02:11±00:25 for the early and 06:14±01:00 for the late sleep timing groups. Participants reporting later sleep timing were more likely to consume sugary/caffeinated beverages and high-energy-dense, nutrient-poor foods throughout the day compared with their early sleep timing peers. The late vs the early sleep timing group also had a higher likelihood of overall consumption of foods and drinks from all categories into the evening and nighttime hours. Our findings indicate that children and adolescents who exhibit late sleep timing are more likely to make poorer dietary choices, which may have important implications for understanding pathways to adiposity and obesity risk during this sensitive period of development.


Bone Fractures in Children With Cholestatic Liver Disease May Mimic Those Seen in Child Abuse.
Certain fractures in children are highly specific for child abuse. Metabolic bone disease frequently develops in patients with cholestatic liver disease (CLD); this can result in weakened bones and a predisposition to pathologic fractures. Fractures that occur in patients with rickets and osteopenia may mimic a bone response to inflicted injury, which in children raise the concern of child abuse. Here we report a series of 15 patients with CLD who developed pathologic fractures in the setting of metabolic bone disease. During initial evaluation, the caretakers of 5 of these 15 patients were reported to child protective services and investigated for child abuse. Pediatricians should be aware that children with CLD have an increased incidence of pathologic fractures, even after the cholestasis has resolved.


The management of old urethral injury in young girls: analysis of 44 cases.
Traumatic urethral injury in girls is rare, and there is no consensus on its management. The authors report their 22-year experience. Forty girls presented with urethrovaginal fistula. Twenty-six girls presented with cystostomy tube in place, whereas 17 girls presented with complete urinary incontinence. Incision and dilatation of the obliterated urethra was carried out in 7 patients. Vaginal repair of urethrovaginal fistula was performed in 4 patients. Transpubic reconstruction of the urethra using a modified Young-Dees-Leadbetter procedure with simultaneous repair of the urethrovaginal fistula was performed in 35 patients (once in 27, twice in 5, and 3 times in 3 patients). Follow-up in 40 girls averaged 3.5 years. Twenty-nine patients have regained normal urinary control, and 11 patients have mild stress urinary incontinence. Four patients were lost to follow-up. Simple dilation of the obliterated urethra can reestablish satisfactory urethral patency if the obliterated segment is short. The vaginal approach to urethrovaginal fistula may be successful in patients without concomitant urethral stricture or in those with stricture amenable to simple dilation. The transpubic approach remains the method of choice for repairing complete urethral disruption and severe urethral stricture, especially when associated with urethrovaginal fistula.


CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo.
Upon their recognition of antigens presented by the MHC, T cell proliferation is vital for clonal expansion and the acquisition of effector functions, which are essential for mounting adaptive immune responses. The CD98 heavy chain (CD98hc, Slc3a2) plays a crucial role in the proliferation of both CD4+ and CD8+ T cells, although it is unclear if CD98hc directly regulates the T cell effector functions that are not linked with T cell proliferation in vivo. Here, we demonstrate that CD98hc is required for both CD4+ T cell proliferation and Th1 functional differentiation. T cell-specific deletion of CD98hc did not affect T cell development in the thymus. CD98hc-deficient CD4+ T cells proliferated in vivo more slowly as compared with control T cells. C57BL/6 mice lacking CD98hc in their CD4+ T cells could not control Leishmania major infections due to lowered IFN-γ production, even with massive CD4+ T cell proliferation. CD98hc-deficient CD4+ T cells exhibited lower IFN-γ production compared with wild-type T cells, even when comparing IFN-γ expression in cells that underwent the same number of cell divisions. Therefore, these data indicate that CD98hc is required for CD4+ T cell expansion and functional Th1 differentiation in vivo, and suggest that CD98hc might be a good target for treating Th1-mediated immune disorders.


Skin tests, T cell responses and self-reported symptoms in children with allergic rhinitis and asthma due to house dust mite allergy.
In allergic responses, a distinction is made between an early-phase response, several minutes after allergen exposure, and a late-phase response after several hours. During the late phase, eosinophils and T cells infiltrate the mucosa and play an important role in inflammation. The aim of this study was to examine the relationship between allergen-induced late-phase skin responses and in vitro T cell reactivity. In addition, the relationship between allergen-induced skin or T cell responses and the severity of self-reported symptoms was studied in children with house dust mite allergy. A total of 59 house dust mite-allergic children (6-18 years) were recruited in general practice. These children or their parents rated their nasal and asthma symptoms on diary cards during 1 month. Allergen skin tests were performed and read after 15 min (early phase) and 6 h (late phase). Allergen-specific T cell proliferation was determined, and Th2 cytokine (IL-5 and IL-13) secretion was analysed. The size of the late-phase skin response correlated with in vitro T cell proliferation (r(s)=0.38, P=0.003) but not with Th2 cytokine secretion (r(s)=0.16, P=0.2 for both IL-5 and IL-13). Moreover, the late-phase skin response and T cell proliferation correlated with asthma symptoms (r(s)=0.30, P=0.02 for skin response and r(s)=0.28, P=0.03 for T cell proliferation) but not with nasal symptoms (r(s)=0.19, P=0.15 for skin response and r(s)=0.09, P=0.52 for T cell proliferation). The early-phase skin response correlated with the nasal symptom score (r(s)=0.34, P=0.01) but not with asthma symptom scores (r(s)<0.005, P=0.97). In this study, the late-phase skin test response correlated with in vitro T cell proliferation but not with Th2 cytokine secretion. We found weak or no correlations between late-phase skin responses and symptoms of asthma or rhinitis in children with house dust mite allergy. This suggests that late-phase skin responses reflect certain T cell properties but are of limited value for the evaluation of airway symptoms in atopic children.


[Comparative analysis on composition principles of traditional Chinese medicine prescriptions for osteoporosis and osteoarthritis].
This paper collected the traditional Chinese medicine (TCM) prescriptions of osteoporosis and osteoarthritis from CNKI to set up database and used TCM inheritance system to analyze the composing principles in prescriptions. We collected 103 and 106 prescriptions for osteoporosis and osteoarthritis respectively, then analyzed inherent principles between herbs in prescriptions by using the TCM inheritance system, and obtained the frequency of each herb, and drug combinations of two diseases' prescriptions. The result showed that the principles in TCM prescriptions of osteoporosis and osteoarthritis are similarities, buch as tonifying kidney and invigorating the circulation of blood, but differences of the specific drugs. That is to say, tonifying kidney is the main method of osteoporosis treatment, however, invigorating the circulation of blood is the main method of osteoarthritis treatment.


An Assessment of In Vitro Antifungal Activities of Efinaconazole and Itraconazole against Common Non-Dermatophyte Fungi Causing Onychomycosis.
Onychomycosis is a fungal nail infection which is relatively common and difficult to treat. Treatment modalities include nail avulsion, surgical debridement and combination therapy with oral and topical antifungal drugs. In spite of a host of available drugs, clinical cure rates remain discouraging. Drug toxicities, prolonged regimens, lack of patient compliance, and high keratin affinity of drugs are all contributive factors. Efinaconazole is a novel topical triazole antifungal agent that has shown excellent in vitro activity against both dermatophyte and non-dermatophyte fungi causing onychomycosis. This study presents the in vitro susceptibility profiles of 44 common non-dermatophyte fungi against efinaconazole and itraconazole, another azole drug used in the treatment of onychomycosis.


Factors associated with take-home naloxone kit usage in British Columbia: an analysis of administrative data.
The British Columbia (BC) Take-Home Naloxone (THN) program provides naloxone to people at risk of experiencing or witnessing an opioid overdose for use in reversing suspected overdose events. This study seeks to examine trends and correlates of individuals obtaining a THN kit in BC between 2017 and 2020. Records of THN kits distributed between 2017 and 2020 were the primary source of data for this analysis. Frequency tables were used to describe characteristics of people obtaining kits from THN sites. Correlates of individuals obtaining a THN kit to replace a previous kit reported as used to reverse an overdose were assessed with multivariate logistic regression. Between January 1, 2017, and December 31, 2020, 240,606 THN kits were reported distributed by registered sites to members of the public, with 90,011 records indicating that a kit was obtained to replace a previous kit that had been used to reverse an overdose. There was a significant trend in increasing kits reported used by year (p < 0.01). The kit recipient's risk of overdose was a significant predictor of having reported using a THN kit, and the strength of the association was dependent on gender (Male: Adjusted odds ratio (AOR) 5.37 [95% confidence interval (CI) 5.08 - 5.67]; Female: AOR 8.35 [95% CI 7.90 - 8.82]; Trans and gender expansive: AOR 3.68 [95% CI 2.82 - 4.79]). Between 2017 and 2020, THN kits were used to reverse tens of thousands of overdose events in BC, with people at risk of overdose (i.e. people who use drugs [PWUD]) having greater odds of using a kit to reverse an overdose than those not at risk. Thus, PWUD are responsible for reversing the vast majority of overdoses. THN kits are being distributed to the people who use them most. However, additional strategies in conjunction with community-based naloxone distribution programs are needed to address the rising number of illicit drug toxicity deaths.


Hsa_circ_001988 attenuates GC progression in vitro and in vivo via sponging miR-197-3p.
Hsa_circ_001988 has been identified as a tumor suppressor gene in several carcinomas. However, its expression pattern and role in gastric cancer (GC) have still remained elusive. This study aimed to explore the functions of hsa_circ_001988 in GC. Quantitative reverse transcription polymerase chain reaction assay was performed to assess the expressions of hsa_circ_001988, miR-197-3p, FBXW7, CCDC6, and U2AF65 in GC tissues. The correlation analysis was undertaken to find out the relationship between hsa_circ_001988 expression and clinicopathological factors. A series of cellular experiments were carried out to describe the effects of hsa_circ_001988 on GC in vivo and in vitro. Besides, RNA immunoprecipitation (RIP) assay was performed to verify the relationship among EIF4A3, U2AF65, and hsa_circ_001988. We first found that the expression of hsa_circ_001988 was decreased in 341 GC patients that was related to World Health Organization histological types, Lauren types, and tumor invasion depth (p < .05). Silencing of hsa_circ_001988 facilitated proliferation, colony formation, migration, and invasion of GC cells, while overexpression of hsa_circ_001988 reversed the effect on GC progression in vitro. Additionally, the results of subcutaneous xenotransplanted tumor model demonstrated that overexpressing hsa_circ_001988 significantly suppressed the subcutaneous tumor growth in vivo. Mechanistically, hsa_circ_001988 attenuated the miR-197-3p expression possibly due to its molecular sponge effect, and then, positively promoted FBXW7 expression. Afterwards, FBXW7 regulated the expressions of yes-associated protein 1, cyclinD1, CCDC6, and EMT-related proteins. Notably, RIP assay showed the enrichment relationship among EIF4A3, U2AF65, and hsa_circ_001988. Additionally, EIF4A3 or U2AF65 promoted cyclization of hsa_circ_001988 in GC. Hsa_circ_001988 inhibits the proliferation and metastasis of GC via modulating EIF4A3/U2AF65-mediated hsa_circ_001988/miR-197-3p/FBXW7 axis.


Changes in individual needs for care and quality of life in Assertive Community Treatment patients: an observational study.
It is largely unknown which unmet needs in the Camberwell Assessment of Need Short Appraisal Schedule (CANSAS) need to be resolved in order to improve a patients' subjective quality of life (QoL). We therefore investigated the pattern of individual unmet needs over time and its relation to QoL over time. Using data gathered from 251 patients in a Routine Outcome Monitoring procedure in Assertive Community Treatment (ACT) teams, we used paired samples tests to analyze differences in QoL total scores and the number of unmet needs between baseline and follow-up data. Ordinal regression was used to analyze the relationship between outcome in individual unmet needs and QoL. As well as small improvements in QoL over time in patients in contact with ACT, we found a small to moderate decrease in unmet needs over time. While a decreasing number of unmet needs was associated with an increase in QoL, outcomes in QoL and individual unmet needs were weakly related (r ≤ .165). Ordinal regression analysis showed that a better outcome in individual unmet needs related to accommodation and day-time activities was weakly related to a better outcome in QoL. Patients receiving ACT make small improvements in their QoL and ACT may help to solve some of their needs. QoL benefits from reducing needs for care, in particular the need for appropriate housing and meaningful daytime activities.


Predation Risk within Fishing Gear and Implications for South Australian Rock Lobster Fisheries.
Depredation of southern rock lobster (Jasus edwardsii) within fishing gear by the Maori octopus (Pinnoctopus cordiformis) has economic and ecological impacts on valuable fisheries in South Australia. In addition, depredation rates can be highly variable resulting in uncertainties for the fishery. We examined how in-pot lobster predation was influenced by factors such as lobster size and sex, season, fishing zone, and catch rate. Using mixed modelling techniques, we found that in-pot predation risk increased with lobster size and was higher for male lobsters. In addition, the effect of catch rate of lobsters on predation risk by octopus differed among fishing zones. There was both a seasonal and a spatial component to octopus predation, with an increased risk within discrete fishing grounds in South Australia at certain times of the year. Information about predation within lobster gear can assist fishery management decision-making, potentially leading to significant reduction in economic losses to the fishery.


Knock-down of farnesyl pyrophosphate synthase protects heart-derived H9c2 cells against hypoxia/reoxygenation-induced injury.
Farnesyl pyrophosphate synthase (FPPS) is a key enzyme in the mevalonate pathway. Our previous studies have indicated that cardiac-specific overexpression of FPPS induces cardiac hypertrophy and dysfunction in mice, and inhibition of FPPS prevents angiotensin (Ang) II-induced hypertrophy in cardiomyocytes. However, the role for FPPS in myocardial ischemia/reperfusion (MIR) injury is still not clear. The objective of this work was to investigate the effect of FPPS on MIR injury in H9c2 cells which were subjected to hypoxia/reoxygenation (HR) to mimic MIR. Prior to HR, cells were transfected with pE-mFPPS, shFPPS, or pE-GFP. Our results showed that the overexpression of FPPS reduced cell proliferation, increased cell injury and cell apoptosis, and knock-down of FPPS improved cell proliferation, decreased cell injury, and cell apoptosis after HR. Besides, overexpression of FPPS increased Rac1 activity and reactive oxygen species (ROS) generation, while FPPS silencing decreased Rac1 activity and ROS generation. Based on these findings, we propose that knock-down of FPPS reduces Rac1 activity and ROS production, and finally leads to the decrease of HR-induced injury in H9c2 cells. These findings point that FPPS might be a potential target in preventing H9c2 cells from HR-induced injury.


Comparison of Cattle Serum Antibody Responses to Five Different Mycobacterial Antigens in an ELISA System.
The presence of common zoonosis diseases caused by Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM), such as Johne's and Crohn's diseases, poses a public health threat and economic losses to Iranian livestock. Therefore, the early detection of mycobacteria is of paramount importance. In this regard, enzyme-linked immunosorbent assay (ELISA) is a new, simple to use, rapid, and useful diagnostic tool. This study was performed to evaluate different crude antigens obtained from Mycobacterium species using an indirect ELISA test to identify the mycobacterial infection in infected livestock. Five different strains of Mycobacteria including M. tuberculosis, M. phlei, M. bovis, M. aviumsubspecies paratuberculosis, and M. bovis AN5 were cultured. The crude antigens in the samples were precipitated with trichloroacetic acid 4%. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis of crude antigens isolated from different Mycobacterium species was reported. The total level of protein was determined by the Lowry protein assay. After the crude antigen preparation, the ELISA test was performed and the results were compared with the purified protein derivative skin test. Data analysis was performed using SPSS software version 25. All five strains were detected in more than 92% of healthy animals. The highest sensitivity of ELISA tests was in M. bovis AN5 antigen which was greater than 83%. The highest diagnostic specificity and efficiency of assays were in M. avium subspecies paratuberculosis which was 95.83% and over 83%, respectively. Regarding the results, M. avium subspecies paratuberculosis and M. bovis AN5 antigens were promising candidates for the design of diagnostic ELISA due to their sensitivity, specificity, and efficiency.


Time-resolved laser-induced incandescence of soot: the influence of experimental factors and microphysical mechanisms.
We present a data set for testing models of time-resolved laser-induced incandescence of soot. Measurements were made in a laminar ethene diffusion flame over a wide range of laser fluences at 532 nm. The laser was seeded to provide a smooth temporal profile, and the beam was spatially filtered and imaged into the flame to provide a homogeneous spatial profile. The particle incandescence was imaged onto a fast photodiode. The measurements are compared with the standard Melton model [Appl. Opt. 23,2201 (1984)] and with a new model that incorporates physical mechanisms not included in the Melton model.


Plant villins: versatile actin regulatory proteins.
Regulation of actin dynamics is a central theme in cell biology that is important for different aspects of cell physiology. Villin, a member of the villin/gelsolin/fragmin superfamily of proteins, is an important regulator of actin. Villins contain six gelsolin homology domains (G1-G6) and an extra headpiece domain. In contrast to their mammalian counterparts, plant villins are expressed widely, implying that plant villins play a more general role in regulating actin dynamics. Some plant villins have a defined role in modifying actin dynamics in the pollen tube; most of their in vivo activities remain to be ascertained. Recently, our understanding of the functions and mechanisms of action for plant villins has progressed rapidly, primarily due to the advent of Arabidopsis thaliana genetic approaches and imaging capabilities that can visualize actin dynamics at the single filament level in vitro and in living plant cells. In this review, we focus on discussing the biochemical activities and modes of regulation of plant villins. Here, we present current understanding of the functions of plant villins. Finally, we highlight some of the key unanswered questions regarding the functions and regulation of plant villins for future research.


Restoration of renal function in patients with newly diagnosed multiple myeloma is not associated with improved survival: a population-based study.
Renal impairment (RI) in patients with multiple myeloma (MM) is associated with poor prognosis. In this population-based cohort study, we assessed the effects of renal response, evaluated according to the IMWG-criteria, on overall survival (OS) in patients with newly diagnosed MM with RI at presentation. All included patients were diagnosed between January 2005 and January 2014 with MM and RI in Friesland, a province of the Netherlands. Of the 131 included patients, 61% achieved renal response. Using a time-varying exposure Cox model, no difference in OS between renal response and non-response was observed (HR = 1.08, 95% CI = 0.67-1.74, p = .76). In multivariable analysis, baseline eGFR <30 ml/min (HR = 1.71), age >70 yrs (HR = 1.77), hypercalcemia (HR = 2.73), lambda Bence-Jones (HR= 1.76), and initial treatment regimen (HR = 0.89 for thalidomide, HR = 1.95 in treatment regimens without novel agents and HR = 3.60 for no chemotherapy, all vs. bortezomib) were associated with decreased OS. In conclusion, achieving renal response was not associated with improved OS.


Hong Kong Liver Cancer Staging System Is Associated With Better Performance for Hepatocellular Carcinoma: Special Emphasis on Viral Etiology.
Hong Kong Liver Cancer (HKLC) staging system was developed for prognostic and treatment evaluation for hepatocellular carcinoma (HCC) but is not externally validated. We aimed to evaluate and compare HKLC system with Barcelona Clínic Liver Cancer (BCLC) staging system. The prognostic performance, discriminatory ability, and efficacy of treatment recommendations were compared between the BCLC and HKLC systems. Significant differences in survival were found across all stages of BCLC and across stages I to IV of HKLC systems (P < 0.01). HKLC system was associated with higher homogeneity in prognostic accuracy. The survival was similar between patients treated according to the HKLC or BCLC system (P = 0.07). However, more patients were treated according to HKLC recommendations than to BCLC recommendations (57% vs. 47%, P < 0.001). In a hypothetical cohort created by random sampling, patients treated according to the HKLC scheme had better survival compared with patients treated according to the BCLC system (P < 0.001).Subgroup analyses between hepatitis B virus (HBV) and hepatitis C virus (HCV)-related HCC were performed. More HCV-related HCC were at earlier BCLC or HKLC stages (both P < 0.001). The HKLC system was more informative with greater homogeneity in predicting survival in both HBV and HCV cohorts. However, HKLC treatment recommendations were associated with better long-term survival only in HBV-related HCC but not in HCV-related HCC (P < 0.001 and P = 0.79, respectively).In conclusion, we provided external validation of the HKLC system. Compared with the BCLC system, the HKLC system has better prognostic accuracy and therapeutic efficacy in the entire cohort and in HBV-related HCC but not in HCV-related HCC. Due to high heterogeneity among patients of various etiologies, staging and treatment strategies tailored to specific HCC etiology are required.


Quantitative chiral and achiral determination of ketamine and its metabolites by LC-MS/MS in human serum, urine and fecal samples.
Ketamine (KET) is a widely used anesthetic drug which is metabolized by CYP450 enzymes to norketamine (n-KET), dehydronorketamine (DHNK), hydroxynorketamine (HNK) and hydroxyketamine (HK). Ketamine is a chiral compound and S-ketamine is known to be the more potent enantiomer. Here, we present the development and validation of three LC-MS/MS assays; the first for the quantification of racemic KET, n-KET and DHNK in human serum, urine and feces; the second for the separation and quantification of the S- and R-enantiomers of KET, n-KET and DHNK, and the third for separation and quantification of 2S,6S-hydroxynorketamine (2S,6S-HNK) and 2R,6R-hydroxynorketamine (2R,6R-HNK) in serum and urine with the ability to separate and detect 10 additional hydroxylated norketamine metabolites of racemic ketamine. Sample preparation was done by liquid-liquid extraction using methyl tert-butyl ether. For achiral determination of KET and its metabolites, an isocratic elution with ammonium acetate (pH 3.8; 5mM) and acetonitrile on a C18 column was performed. For the separation of S- and R-enantiomers of KET, n-KET and DHNK, a gradient elution was applied using a mobile phase of ammonium acetate (pH 7.5; 10mM) and isopropanol on the CHIRAL-AGP® column. The enantioselective separation of the HNK metabolites was done on the chiral column Lux®-Amylose-2 with a gradient method using ammonium acetate (pH 9; 5mM) and a mixture of isopropanol and acetonitrile (4:1). The mass spectrometric detection monitored for each analyte 2-3 mass/charge transitions. D4-ketamine and D4-n-KET were used as internal standards. The assays were successfully validated according to current bioanalytical guidelines and applied to a pilot study in one healthy volunteer. Compared to previously published methods, our assays have superior analytical features such as a lower amount of required matrix, faster sample preparation, shorter analytical run time and higher sensitivity (LLOQ up to 0.1ng/ml). Moreover, our assay enables for the first time the enantioselective determination of 2R,6R- and 2S,6S-HNK which were shown to be responsible for the promising antidepressant effects of ketamine.


[Esophageal perforation after replacement of descending thoracic aorta for rupture mycotic aneurysm].
Primary mycotic aneurysm of the thoracic aorta has rarely been reported. The patient was a 61-year-old male who had a ruptured mycotic aneurysm of the descending thoracic aorta without any evidence of infectious disorders in his history. The patient developed esophageal perforation after graft replacement of the descending thoracic aorta. After continuous irrigation of the left pleural cavity and the mediastinum for one month, the thoracic esophagus was resected and reconstructed. However, the patient died of DIC following uncontrolled sepsis on the 98th postoperative day. Pathogenesis of the esophageal perforation and operative procedures that might have been effective in saving the patient were discussed.


Family and Market: Nonagricultural Employment in Rural China.
This study relies on the 2005 wave of Chinese General Social Survey (CGSS) to investigate nonagricultural employment in rural China. Given China's move away from collective agriculture, households began to act as the basic unit of production, which allows some peasants to leave the family farm, enter the wage sector or run private business. The first model runs logistic regressions to estimate the type of employment for individual men and women in a married couple, and the second model is conducted at the couple level to estimate the likelihood of four outcomes: both spouses, neither spouse, or one spouse (husband or wife) in nonagricultural jobs. Both models reveal that better educated persons are more likely to be engaged in nonagricultural work. Women's employment is more responsive to the presence of grandparents and young children in the household, yet "young" grandparents and "old" grandparents make a difference. At the market level, local geographic, economic and labor force conditions of the village also play an important role in shaping family employment patterns, and the eastern and central regions illustrate a higher likelihood of nonagricultural employment than the western region.


Macrophage HIF-1α Is an Independent Prognostic Indicator in Kidney Cancer.
Clear cell renal cell carcinoma (ccRCC) is frequently associated with inactivation of the von Hippel-Lindau tumor suppressor, resulting in activation of HIF-1α and HIF-2α. The current paradigm, established using mechanistic cell-based studies, supports a tumor promoting role for HIF-2α, and a tumor suppressor role for HIF-1α. However, few studies have comprehensively examined the clinical relevance of this paradigm. Furthermore, the hypoxia-associated factor (HAF), which regulates the HIFs, has not been comprehensively evaluated in ccRCC. To assess the involvement of HAF/HIFs in ccRCC, we analyzed their relationship to tumor grade/stage/outcome using tissue from 380 patients, and validated these associations using tissue from 72 additional patients and a further 57 patients treated with antiangiogenic therapy for associations with response. Further characterization was performed using single-cell mRNA sequencing (scRNA-seq), RNA-in situ hybridization (RNA-ISH), and IHC. HIF-1α was primarily expressed in tumor-associated macrophages (TAMs), whereas HIF-2α and HAF were expressed primarily in tumor cells. TAM-associated HIF-1α was significantly associated with high tumor grade and increased metastasis and was independently associated with decreased overall survival. Furthermore, elevated TAM HIF-1α was significantly associated with resistance to antiangiogenic therapy. In contrast, high HAF or HIF-2α were associated with low grade, decreased metastasis, and increased overall survival. scRNA-seq, RNA-ISH, and Western blotting confirmed the expression of HIF-1α in M2-polarized CD163-expressing TAMs. These findings highlight a potential role of TAM HIF-1α in ccRCC progression and support the reevaluation of HIF-1α as a therapeutic target and marker of disease progression.


Fetal mosaicism, should conventional karyotype always be performed?
The application of classical cytogenetic and DNA-based molecular techniques to detect cell lineages of mosaicism derived from cultured or noncultured fetal cells may result in discordant results. This retrospective study aimed to assess the inconsistent diagnostic outcomes, technical availability, and limitations of chromosomal microarray analysis (CMA) and karyotyping for mosaicism. A total of 75 fetuses diagnosed with mosaicism by karyotype analysis or CMA were selected, and the results from both the methods were compared and further analyzed. A total of 42 (56%, 42/75) CMA results were consistent with karyotypes, consisting of 22 cases of mosaic sex chromosomal abnormalities, 8 routine autosomal aneuploidy cases, 8 other autosome aneuploidy cases, 3 large cryptic genomic rearrangements, and 1 small supernumerary marker chromosome. Discrepancy between karyotype analysis and CMA was observed in 33 (44%, 33/75) mosaicisms involving 15 sex chromosomal abnormalities, 1 routine autosomal aneuploidies, 5 other autosome aneuploidy cases, 8 large cryptic genomic rearrangements, and 4 small supernumerary marker chromosomes. Considering the disparities between methods as well as the cell populations analyzed, both CMA and karyotype analysis have their own advantages and disadvantages. Therefore, CMA should ideally be used in combination with karyotyping to detect more cases of mosaicism than using either test alone.


A new way to find evidence quickly and efficiently.
Evidence coming from scientific research helps us make better decisions in relation with the care we provide to our patients. Some evidence is more reliable than other is, and systematic reviews are considered the best available evidence for answering questions that compare two or more alternatives of care, as long as they are well conducted and up-to-date. There has lately been a fast growth of the amount of available systematic reviews, so users need to choose between several possible options. Epistemonikos database is a highly efficient search resource, since it groups the larger number of systematic reviews worldwide, and allows accessing the body of evidence for a specific question in a simple and intuitive way. Additionally, it offers tools that enable the choice among different systematic reviews and for keeping the evidence for a question updated with minimal effort.


Aberrant LncRNA Expression in Leukemia.
Leukemia is a common malignant cancer of the hematopoietic system, whose pathogenesis has not been fully elucidated. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides without protein-coding function. Recent studies report their role in cellular processes such as the regulation of gene expression, as well as in the carcinogenesis, occurrence, development, and prognosis of various tumors. Evidence indicating relationships between a variety of lncRNAs and leukemia pathophysiology has increased dramatically in the previous decade, with specific lncRNAs expected to serve as diagnostic biomarkers, novel therapeutic targets, and predictors of clinical outcomes. Furthermore, these lncRNAs might offer insight into disease pathogenesis and novel treatment options. This review summarizes progress in studies on the role(s) of lncRNAs in leukemia.


Long-term survival in children with atrioventricular septal defect and common atrioventricular valvar orifice in Sweden.
The survival for patients with atrioventricular septal defect has improved markedly over the last decades and, during the same period, the survival of children with Down's syndrome has also increased. The aim of our study was to investigate long-term survival in patients having atrioventricular septal defect with common valvar orifice, but without associated significant congenital heart defects, in the setting of Down's syndrome, comparing the findings to those in chromosomally normal children with the same malformation. In a population-based retrospective study, we scrutinised the medical records from 801 liveborn children with atrioventricular septal defect born in Sweden during the period 1973 through 1997. Data on gender, presence or absence of Down's syndrome, associated congenital heart defects, date of birth, operation and death were recorded and followed up until 2001. An isolated atrioventricular septal defect with common atrioventricular valvar orifice was present in 502 children, of whom 86% had Down's syndrome. We found a significant reduc tion over time in age at operation, and in postoperative mortality at 30 days, from 28 to 1%. Using a multiple logistic regression model, we found no significant differences in mortality between genders, nor between those with or without Down's syndrome. Early corrective surgery could not be identified as a significant independent factor for survival. The 5-year postoperative survival in patients with Down's syndrome increased from 65% over the period from 1973 through 1977, to about 90% in the period 1993 through 1997, and the same trend was observed in chromosomally normal patients. Survival in uncomplicated atrioventricular septal defect with common atrioventricular valvar orifice has greatly increased, and surgical correction is now equally successful in patients with Down's syndrome and chromosomally normal patients, and for both genders. Death in connection with surgery is no longer the major threat, and focus must now be on long-term follow-up.


Tumor regression of advanced carcinomas following intra- and/or peri-tumoral inoculation with VRCTC-310 in humans: preliminary report of two cases.
The authors report their clinical experience with VRCTC-310 in two patients suffering with advanced cancer in which the skin was severely compromised. VRCTC-310 is a combination of the snake venoms crotoxin (CT) and cardiotoxin (CD). The local (peritumoral) treatment with the drug (0.O14 mg/kg/week during 6 weeks) provoked the complete disappearance of a relapsed skin squamous cell cancer in one patient. The other patient was an aged woman with local-advanced breast cancer (carcinoma en cuirasse) who was inoculated intra-and-peritumoral with VRCTC-310. After 6 weekly courses (0.014 mg/kg/week) with the drug a > 80% tumor reduction was seen. A 133 days follow-up demonstrated not only an objective complete response of the primary tumor mass, but the disappearance of supraclavicular tumor mass as well a significant reduction in lymphangitis. To our knowledge, this is the first communication about the in vivo antitumoral activity of VRCTC-310 when injected locally to humans. Further studies are now in progress.


Suppression of IgE antibody production in sensitized mice and rats by tolerogenic conjugates of synthetic hydrophilic polymers with antigen or hapten: effect on antigen-induced histamine release from peritoneal mast cells.
IgE antibodies were produced in mice and rats by immunization with ragweed pollen extract (RAG) or dinitrophenylated ovalbumin (DNP3-OA). Treatment of these animals with tolerogenic conjugates of (i) the antigen (RAG or OA) with monomethoxypolyethylene glycol (mPEG), or (ii) DNP with polyvinyl alcohol (DNP-PVA) resulted, within 7-14 days, in a fall in circulating IgE antibodies and in mast cell sensitivity, as assessed by the radioallergosorbent test (RAST) and in the in vitro antigen-induced histamine release (HR) test, respectively. The reduction in responsiveness was more marked in mice than rats; 10 days after a booster immunization, the IgE antibody titres in the RAG-mPEG-treated group of mice were approximately 10-fold lower than in the saline-treated group, with a 100-fold difference in cell sensitivity. DNP-PVA treatment of mice produced a more than 10-fold reduction in IgE anti-DNP titres with a substantial reduction in histamine release.


Head and neck carcinoma with distant metastases: a retrospective analysis of 44 cases treated with cisplatin-based chemotherapeutic regimens.
The rarity of medical reports on the chemotherapeutic management of head and neck cancer metastatic to distant organs prompted us to review the effect of cisplatin-based regimens in this clinical setting. Out of 44 eligible patients, 10 patients (23%) achieved a CR, 16 patients (36%) has a PR, 7 (16%) no change, and 11 (25%) progressed. Patients with rhinopharyngeal carcinoma showed a 69% overall response rate, while those with other head and neck carcinomas had a 54% overall response rate. No preferential site of response was detected. The difference in mean survival of responding patients between the rhinopharyngeal group and the non-rhinopharyngeal group was statistically significant (P < 0.05). Responding patients survived longer than non responders (P < 0.05 in both groups). Interestingly, 3 patients in the rhinopharyngeal cancer group survived more than 2 years from the start of chemotherapy for metastatic disease. These data strengthen the observation that rhinopharyngeal carcinoma, even with distant metastases, responds to chemotherapy better than other carcinomas arising in the head and neck region. Moreover, although survival is still dismal, cisplatin-based systemic chemotherapy seems an effective palliative treatment for metastatic head and neck cancer.


Using the Vessel Health and Preservation framework to enhance vein assessment and vascular access device selection.
There is a range of risk factors that can lead to peripheral intravenous (IV) cannula failure, and several failed cannulation attempts can result in the patient experiencing increased pain, discomfort and delays in receiving IV therapy. The Vessel Health and Preservation (VHP) framework is a tool that can be used to improve clinical decision-making and the patient experience in relation to vascular access and IV therapy. Use of the VHP framework can ensure the right vein and right vascular access device (VAD) is selected at the right time for each patient. This article describes how healthcare practitioners can use the VHP framework to support and enhance vein assessment and VAD selection. It outlines the various types of VAD available, focusing on short-term peripheral IV cannulae, which are the most commonly used devices. It also explores the potential benefits of implementing the VHP framework in clinical areas.


Vertebral osteomyelitis in an immunosuppressed patient with rheumatoid arthritis.
We report a case of spontaneous osteomyelitis of the cervical spine complicated by epidural abscess due to methicillin-resistant Staphylococcus aureus (MRSA) in a patient with rheumatoid arthritis with no obvious focus of infection or bacteraemia. The patient was on immunosuppressants and complete blood count revealed neutropaenia. He was successfully treated with intravenous antibiotics and surgery.


Suppression of inflammation by the rhizome of Anemarrhena asphodeloides via regulation of nuclear factor-κB and p38 signal transduction pathways in macrophages.
The rhizome of Anemarrhena asphodeloides Bunge (A. asphodeloides) has been used as a traditional East Asian medicine for the treatment of various types of inflammatory disease. However, to the best of our knowledge, there have been no systemic studies regarding the molecular mechanisms of action of the A. asphodeloides rhizome anti-inflammatory effects. The aim of the present study was to elucidate the anti-inflammatory effects and underlying mechanism of action of ethanol extracts of the rhizome of A. asphodeloides (EAA) in murine macrophages. Non-cytotoxic concentrations of EAA (10-100 µg/ml) significantly decreased the production of NO and interleukin (IL)-6 in lipopolysaccharide (LPS)-stimulated macrophages, while the production of tumor necrosis factor-α was not regulated by EAA. EAA-mediated reduction of nitric oxide (NO) was due to reduced expression levels of inducible NO synthase (iNOS). Furthermore, protein expression levels of LPS-induced cyclooxygenase-2, another inflammatory enzyme, were alleviated in the presence of EAA. EAA-mediated reduction of those proinflammatory mediators was due to inhibition of nuclear factor-κB (NF-κB) and activator protein 1 transcriptional activities followed by the stabilization of inhibitor of κ Bα and inhibition of p38, respectively. These results indicate that EAA suppresses LPS-induced inflammatory responses by negatively regulating p38 and NF-κB, indicating that EAA is a candidate treatment for alleviating inflammation.


Peripheral ossifying fibroma.
A case of peripheral ossifying fibroma (POF) in the mandibular gingiva of a 17-year-old male is described. The lesion was asymptomatic, firm, pink, and present on the lingual alveolar mucosa interdentally between 43 and 44. Radiographic investigations revealed no significant findings. Excisional biopsy was performed for the lesion. Microscopic findings confirmed the diagnosis of POF.


Prevalence of pulmonary atypical alveolar cell hyperplasia in an autopsy population: a study of 100 cases.
A precursor lesion of pulmonary adenocarcinoma has not been clearly defined. Previous studies suggested that atypical alveolar cell hyperplasia (AACH) might represent such a precursor lesion. Most previous studies showed an association between AACH and adenocarcinoma in surgical resection specimens. In this study, we searched for the prevalence of AACH and nonatypical alveolar cell hyperplasia (ACH) in a general autopsy population. Cases in which there was clinical or anatomic evidence of pulmonary neoplasia were excluded from the study. In the 100 consecutive autopsies examined, we found four cases of ACH and two cases of AACH. The two AACH lesions showed cytologic atypia and stained positively for p53 and c-erb-2. These findings suggest a possible role for AACH as a precursor lesion of adenocarcinoma of the lung.


Interface Coordination Engineering of P-Fe3O4/Fe@C Derived from an Iron-Based Metal Organic Framework for pH-Universal Water Splitting.
Developing electrocatalysts with high energy conversion efficiency is urgently needed. In this work, P-Fe3O4/Fe@C electrodes with rich under-coordinated Fe atom interfaces are constructed for efficient pH-universal water splitting. The introduction of under-coordinated Fe atoms into the P-Fe3O4/Fe@C interface can increase the local charge density and polarize the 3d orbital lone electrons, which promotes water adsorption and activation to release more H*, thus elevating electrocatalytic activity. As a donor-like catalyst, P-Fe3O4/Fe@C displays excellent electrocatalytic performance with overpotentials of 160 mV and 214 mV in acidic and alkaline electrolytes at 10 mA cm-2, in addition to pH-universal long-term stability.


Immunodeficiency-associated malignant lymphoma. Three cases showing genotypic evidence of both T- and B-cell lineages.
Dual rearrangement of both immunoglobulin and T-cell receptor (TCR) genes has been described in up to 30% of precursor lymphoid neoplasms, but this phenomenon occurs rarely in lymphomas with a mature phenotype. We describe three cases of immunodeficiency-associated lymphomas, two in patients with acquired immunodeficiency syndrome (AIDS) and one in a patient with a renal transplant, in which both immunoglobulin and TCR gene rearrangements were identified. Two cases exhibited clonal JH, clonal JK, and clonal TCR beta gene rearrangements; the other case had clonal JK and TCR beta gene rearrangements with deletion of JH. Two of these bigenotypic lesions exhibited a B-cell phenotype, and the other exhibited evidence of both a B- and T-cell phenotype, containing cytoplasmic CD3 as well as monoclonal kappa light chain. In addition, two of the cases exhibited the presence of clonal Epstein-Barr viral DNA. These observations suggest that lymphomas arising in immunodeficiency states may be more prone to disordered differentiation than those arising in an intact immune system.


Circulating Exosomal miR-96 as a Novel Biomarker for Radioresistant Non-Small-Cell Lung Cancer.
Patients with non-small-cell lung cancer (NSCLC) frequently develop radioresistance, resulting in poor response to radiation and unfavourable prognosis. Early detection of radioresistance hence can guide the adjustment of treatment regimens in time. Exosomes are lipid bilayer-enclosed vesicles with sub-micrometer size that are released by various cells. Exosomes contain a tissue-specific signature wherein a variety of proteins and nucleic acids are selectively packaged. Growing evidence shows exosomes are involved in cancer pathophysiology and exosomes as the latest addition to the liquid biopsy portfolio have been used in cancer diagnosis. Compared to cell free RNA, exosomal lipid envelope can effectively protect RNA cargo against degradation. Therefore, exosomes may hold great promise for the identification of radioresistance. Here, we report six plasma exosomal miRNAs could be used to distinguish radioresistant NSCLC patients from radiosensitive NSCLC patients and to evaluate the prognosis of NSCLC. Samples were obtained from 52 NSCLC patients with or without radioresistance and 45 age-matched healthy volunteers. Exosomes in 1 ml plasma were isolated followed by extraction of small RNA. The expression levels of miRNAs were determined by quantitative real-time PCR. Potential miRNA markers were further evaluated in additional 52 NSCLC patients. We found exosomal miR-1246 and miR-96 are significantly overexpressed in NSCLC patients. Moreover, exosomal miR-96 in patients with radioresistant NSCLC is significantly higher than that of controls. Exosomal miR-96 also demonstrates a significant correlation with vascular invasion and poor overall survival. Altogether, our results indicate that exosomal miR-96 could be a non-invasive diagnostic and prognostic marker of radioresistant NSCLC.


Disability in an eastern religious context: historical perspectives.
Disability in the past of eastern religions has attracted little formal or comparative scrutiny. A range is sketched here of historical data, viewpoints and attitudes on disability in Hinduism, Buddhism and Islam, which continue to influence the thoughts of half the world's population. Approaches for more detailed studies are suggested, moving towards such global measures for understanding, remediating and accommodating disability as would be more appropriate and acceptable to the non-western majority. Popular notions associated with disabilities in these religions are discussed.


Two objective "archivable" tests for voluntary muscle testing in ulnar and median nerve paralysis.
Two tests are proposed for assessment of ulnar and median nerve function for use under field conditions: (i) "flap flexion" of fingers for ulnar nerve, and, (ii) tip-to-tip thumb opposition to the fourth finger for median nerve. These tests, which are a part of a series of simple clinical tests proposed for rapid neurological evaluation of the function of the nerves involved in leprosy, are simple, objective and easy to do. Because these tests depend on the strength of muscles tested, they might spare its direct assessment. In fact, it is difficult to assess and grade the strength of the little muscles of the hand and that is very much dependent on the examiner's own experience. Therefore, it is rather subjective. The tests described here may also be used for evaluating the results of corrective surgery of the hand. Whenever possible, making photographic records of these two tests, to be archived in the forms where everyone can see and compare them, seems to be easier and more objective than the subjective transcription of the feelings of an examiner assessing the strength of the small muscles of the hand. These two tests seem to be most objective for a scientific prospective study with a long term follow up. So, they could be used in assessing the results of leprosy neuritis by medical treatment, or, by medical treatment completed (when necessary only and not routinely) by surgical decompression of nerves and also of corrective surgery of claw hand, or, loss of opposition of the thumb.


[A Structural Equation Model for Happiness in Mothers with Young Children].
This study aimed to develop and test a model of the happiness of mothers with young children based on the stress-coping-adaptation model of Lazarus and Folkman. The data collection period was from May to July 2016. A self-report questionnaire was used to collect data from 210 mothers with children under 5 years of age living in Seoul, Gyeonggi, and Gangwon provinces. The exogenous variable was parenting stress, and the endogenous variables were parenting alliance, depression, optimism, ways of coping, and happiness. Data from 201 questionnaires were analyzed using the SPSS 22.0 and AMOS 20.0 programs. Data analyses included descriptive statistics, factor analysis, and structural equation modeling. The final modified model showed a reasonable fit to the data, and out of 25 paths, 13 were statistically significant. This model explained 78.4% of the variance in the happiness of mothers with young children and confirmed that depression, optimism, parenting alliance, and social support-focused coping have a direct effect on the subject's happiness. Parenting stress also influenced happiness through parenting alliance, depression, and optimism. In order to bolster the happiness of mothers with young children, positive psychological interventions that can minimize psychological vulnerabilities, such as depression, and that can enhance their strengths, such as optimism, may serve as effective ways of coping with and adapting to stress.


Coagulation factors and fibrinogen in pleural effusions.
31 pleural effusions from 27 patients with varied diseases were studied for specific coagulation factors and fibrinogen. In all fluids, exudates had a higher content of factors and fibrinogen than transudates. When pleural fluid to plasma total protein ratios were compared to specific coagulation factors a positive correlation existed for all. This was not true for fibrinogen. There was a poor correlation between the molecular weights of the specific factors and fibrinogen and their appearance in the pleural fluid. The concentration of factor XII in 35% and factor XI in 11% of pleural fluid exceeded their respective plasma concentration.


Upper gastrointestinal haemorrhage in severe dengue: To scope or not to scope?
Upper gastrointestinal haemorrhage (UGIH) in severe dengue represents a clinical dilemma in term of management. The recommended treatment in dengue with UGIH involves blood product transfusion support and proton pump inhibitor (PPI) infusion. Despite being the mainstay of treatment in non-dengue UGIH, the role of endoscopic haemostatic intervention in severe dengue remains controversial. In the present report, we present a case of severe dengue complicated with upper gastrointestinal haemorrhage successfully underwent early therapeutic endoscopic intervention in a district hospital.


Anti-inflammatory and analgesic activity of protocatechuic acid in rats and mice.
Anti-inflammatory and analgesic activity of protocatechuic acid (PCA), a natural product, was evaluated in different rat models (viz., carrageenan-induced paw oedema, cotton pellet-induced granuloma and Freund's adjuvant arthritis) of inflammation and chemical and heat induced mouse models of pain. Treatment with PCA inhibited significantly different biological parameters like hind paw oedema, granuloma exudates formation and arthritis index in carrageenan oedema, cotton pellet granuloma and Freund's adjuvant arthritis, respectively. The biochemical changes viz., glutathione, superoxide dismutase, catalase, lipid peroxidation and NO in oedematous or in liver tissues and serum alanine aminotransferase and lactic dehydrogenase occurred during different types of inflammation were either significantly restored or inhibited with PCA pretreatment. Present experimental findings demonstrate promising anti-inflammatory and analgesic activity of PCA which is comparable with that of standard drugs used.


A randomised study of tailored toxicity-based dosage of fluorouracil-epirubicin-cyclophosphamide chemotherapy for early breast cancer (SBG 2000-1).
Retrospective studies have demonstrated a worse outcome in breast cancer patients not developing leukopenia during adjuvant chemotherapy. The SBG 2000-1 is the first randomised trial designed to compare individually dosed chemotherapy without G-CSF support based on grade of toxicity to standard-dosed chemotherapy based on body surface area (BSA). Patients with early breast cancer were included and received the first cycle of standard FEC (fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2). Patients with nadir leukopenia grade 0-2 after first cycle were randomised between either 6 additional courses of tailored FEC with increased doses (E 75-90 mg/m2, C 900-1200 mg/m2) or fixed treatment with 6 standard FEC. Patients with grade 3-4 leukopenia were registered and treated with 6 standard FEC. Primary end-point was distant disease-free survival (DDFS). The study enrolled 1535 patients, of which 1052 patients were randomised to tailored FEC (N = 524) or standard FEC (N = 528), whereas 401 patients with leukopenia grade 3-4 continued standard FEC and formed the registered cohort. Dose escalation did not statistically significantly improve 10-year DDFS (79% and 77%, HR 0.87, CI 0.67-1.14, P = 0.32) or OS (82% and 78%, respectively, HR 0.89, CI 0.57-1.16, P = 0.38). Corresponding estimates for the registered group of patients were DDFS 79% and OS 82%, respectively. The SBG 2000-1 study failed to show a statistically significant improvement of escalated and tailored-dosed chemotherapy compared with standard BSA-based chemotherapy in patients with low haematological toxicity, although all efficacy parameters showed a numerical advantage for tailored treatment.


A Case of Superior Mesenteric Artery Syndrome in a Healthy Active Duty Marine.
Superior mesenteric artery (SMA) syndrome is an uncommon disorder that can lead to small bowel obstructions or perforations. Typical populations include young females with anorexia. However, there have been a few reports of healthy males with acute vomiting reported to have SMA syndrome. Our case report highlights an active duty Marine who developed SMA syndrome and the importance of recognizing this disease given the severity in delay of diagnosis in population of young healthy active duty members.


Spectra of Husimi cacti: exact results and applications.
Starting from exact relations for finite Husimi cacti we determine their complete spectra to very high accuracy. The Husimi cacti are dual structures to the dendrimers but, distinct from these, contain loops. Our solution makes use of a judicious analysis of the normal modes. Although close to those of dendrimers, the spectra of Husimi cacti differ. From the wealth of applications for measurable quantities which depend only on the spectra, we display for Husimi cacti the behavior of the fluorescence depolarization under quasiresonant Forster energy transfer.


Antimicrobial and antibiofilm effects of essential fatty acids against clinically isolated vancomycin-resistant Enterococcus faecium.
Enterococcus faecium is a leading cause of hospital-acquired infections, which has become a serious public health concern. The increasing incidence of vancomycin-resistant E. faecium (VRE-fm) raises an urgent need to find new antimicrobial agents as a complement to traditional antibiotics. The study aimed to evaluate the antimicrobial and antibiofilm activity of essential fatty acids (EFAs) against VRE-fm, and further explore the molecular mechanism of the antibiofilm activity of EFAs. The microdilution broth method was used for antimicrobial susceptibility testing with traditional antibiotics and EFAs, including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LOA), γ-linolenic acid (GLA), and arachidonic acid (AA). The effect of EFAs on cell morphology of VRE-fm was investigated by scanning electron microscopy. The crystal violet method was used to evaluate the antibiofilm activities of EFAs against VRE-fm. Furthermore, the expression of biofilm-related genes (acm, atlA, esp, and sagA) of VRE-fm isolates under the action of GLA was analyzed using quantitative reverse transcription PCR (qRT-PCR) assay. VRE-fm isolates were highly resistant to most traditional antibiotics, only highly susceptible to quinupristin-dalfopristin (90.0%), tigecycline (100%), and linezolid (100%). EPA, DHA, and GLA exhibited excellent antimicrobial activity. The MIC50/90 of EPA, DHA, and GLA were 0.5/1, 0.25/0.5, and 0.5/1 mM, respectively. SEM imaging showed that strain V27 adsorbed a large number of DHA molecules. Furthermore, all EFAs exhibited excellent inhibition and eradication activities against VRE-fm biofilms. The biofilm inhibition rates of EFAs ranged from 45.3% to 58.0%, and eradication rates ranged from 54.1% to 63.4%, against 6 VRE-fm isolates with moderate biofilm formation ability. GLA exhibited remarkable antibiofilm activity against VRE-fm isolates. The qRT-PCR analysis showed that GLA could significantly down-regulate the expression of the atlA gene (P < 0.01) of VRE-fm. DHA showed the strongest antibacterial activity, while GLA showed the strongest antibiofilm effect among the EFAs with antibacterial activity. Our novel findings indicate that the antibiofilm activity of GLA may be through down-regulating the atlA gene expression in VRE-fm. Therefore, DHA and GLA had the potential to be developed as therapeutic agents to treat infections related to multiple antimicrobial-resistant E. faecium.


[The appropriateness of using the essential laboratory tests in a daily primary medical care].
The primary purpose of this study was to evaluate the clinical value on chemistry tests when we could eliminate panel of tests to be ordered. We adopted the questionnaire assessment method for getting feedback how attending physicians of the national university hospital were using the multiple laboratory tests for their daily primary medical care. Five kind of commonly ordered serum chemistry tests; total profile (1), 8 test items, total profile (2), 16 test items; pre-operation panel, 21 test items, revised total profile menus, 10 items and revised pre-operation panel, 14 items were reviewed by 134 physicians. Revised total profile menus which includes test items basically proposed by "the Essential Laboratory Tests in a daily primary medical care, The Japan Society of Clinical Pathology", has been found to be a useful disease-finding tool with acceptable costs in a national university hospital budget setting. However, it was suggested that the spectrum of detectable disorders could be broaden by adding few more test items such as CRP, glucose, Na, Cl and potassium in the proposed test menus.


Tandem mass spectrometry: the tool of choice for diagnosing inborn errors of metabolism?
The early diagnosis of inborn errors of metabolism (IEM) by laboratory-based mass screening is a prime example of preventive medicine. However, several factors restrict the range of IEM that can be screened for, and the numbers of people to whom it can be made available. Mass screening in the United Kingdom is limited primarily to that for phenylketonuria and congenital hypothyroidism. Ideally, extension of mass screening of neonates for additional clinically significant IEM is a desirable strategy. Tandem mass spectrometry (TMS) is a powerful and effective diagnostic technique and has been proposed as a means to realise this aim. Its main advantages are improved accuracy, sensitivity and specificity over existing methods, and its suitability for cost-effective multidisease IEM mass screening. The evolution, principles and applications of TMS are described, and the practical and clinical implications of extending diagnostic services for IEM using TMS are discussed.


Determinants of initial bone graft volume loss in posterolateral lumbar fusion.
Bone graft volume decreases postoperatively without known etiology. We sought to determine the bone graft volume over time in 15 consecutive patients undergoing a single-level, instrumented, posterolateral lumbar fusion for degeneration causing mechanical pain or spondylolisthesis, and to identify factors associated with bone graft resorption. Following Institutional Review Board approval, a retrospective analysis was performed. Immediate and 3-month postoperative lumbar spine CT scans were imported into imaging software for volumetric analysis. We found that the 15 patients averaged approximately 11% graft volume loss at 3 months postoperatively. All patients exhibited volumetric graft loss on each side (range, 0.3-45%). A paired t-test revealed that immediate postoperative graft volume on a patient's left or right did not reflect graft volume on that side 3 months postoperatively (p=0.0008). Gender, age, history of prior operation, history of regular exercise, body mass index, level fused, operative time, initial graft volume, and laterality did not influence percentage volumetric loss (p=0.1-0.5). Interestingly, people who smoked cigarettes (range, 10-40 pack-years) exhibited 27% graft loss, compared to 7% in those who did not (Spearman p=0.009 graft loss versus pack-years smoked). We concluded that bone graft exhibited resorption 3 months postoperatively on both sides of all patients in this series, and that smoking was significantly associated with increased bone graft resorption.


Prenatal Developmental Toxicity and Histopathological Changes of the Placenta Induced by Syzygium guineense Leaf Extract in Rats.
Many of the traditional herbal products are served to the consumer without proper efficacy and safety investigations. A laboratory-based experimental study was employed to investigate the toxic effects of Syzygium guineense leaf extract on the fetal development and histopathology of the placenta in rats. Fifty pregnant Wistar albino rats were randomly allocated into five groups, each consisting of 10 rats. S. guineense leaf extract, at doses of 250, 500, and 1000 mg/kg of body weight, was respectively administered to groups I-III rats. Groups four and five were control and ad libitum control, respectively. The number of resorptions, implantation sites, and live or dead fetuses was counted. The weight and crown-rump length of the fetuses were measured. The histopathological investigation of the placenta was conducted. Administration of 70% ethanol extract of S. guineense leaves reduced weight gain and food intake of pregnant rats at p value <0.05. The crown-rump length of the near-term rat fetus was significantly reduced in rats treated with 1000 mg/kg body weight of S. guineense extract (p value <0.05). The plant extract did not affect the number of implantations, fetal resorptions, live births, and stillbirths. The weight of the fetuses and the placentae also decreased dose-dependently. Decidual cystic degeneration was the most prevalent histopathological change observed in a rat's placenta treated with 1000 mg/kg body weight of S. guineense extract. Consumption of S. guineense leaves, especially at a high dose, may affect fetal development. Therefore, liberal use of S. guineense leaves during pregnancy should be avoided.


CC Chemokine 2 Promotes Ovarian Cancer Progression through the MEK/ERK/MAP3K19 Signaling Pathway.
Ovarian cancer is a gynecological tumor with an incidence rate lower than those of other gynecological tumor types and the second-highest death rate. CC chemokine 2 (CCL2) is a multifunctional factor associated with the progression of numerous cancers. However, the effect of CCL2 on ovarian cancer progression is unclear. Here, we found that exogenous CCL2 and the overexpression of CCL2 promoted the proliferation and metastasis of ovarian cancer cells. On the other hand, CCL2 knockdown via CRISPR/Cas9 inhibited ovarian cancer cell proliferation, migration, and invasion. The present study demonstrated that mitogen-activated protein three kinase 19 (MAP3K19) was the key CCL2 target for regulating ovarian cancer progression through transcriptome sequencing. Additionally, MAP3K19 knockout inhibited ovarian cancer cell proliferation, migration, and invasion. Furthermore, CCL2 increased MAP3K19 expression by activating the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. The present study showed the correlation between CCL2 and ovarian cancer, suggesting that CCL2 may be a novel target for ovarian cancer therapy.


NRSF regulates the developmental and hypertrophic changes of HCN4 transcription in rat cardiac myocytes.
The HCN4 channel shows differential expression patterns during the embryonic development and hypertrophy of hearts. Briefly, HCN4 expression is maximally activated in embryonic hearts and quickly diminishes after birth. However, it is reactivated during cardiac hypertrophy. The sequence analysis of HCN4 gene revealed the presence of a conserved NRSE motif, which is known to bind the transcriptional factor neuron-restrictive silencing factor (NRSF). A promoter analysis of HCN4 with rat cardiac myocytes identified the region inducing a basal transcriptional activity. This region drove a high activity in embryonic myocytes, but not in neonatal myocytes treated with hypertrophic agents. After confirming that NRSF protein binds to the NRSE, HCN4 promoter activities modified by NRSE were evaluated. With wild-type NRSE, the promoter activity correlated well with the developmental and hypertrophic changes of HCN4 expression, whereas mutant NRSE constructs failed. We conclude that the NRSE-NRSF system was implicated in HCN4 expression in cardiac myocytes.


Leukotriene C4 disposition and metabolism in the anesthetized and endotoxemic dog.
The metabolism and disposition of tritiated leukotriene C4, [3H]-LTC4, were studied in control dogs and endotoxin-treated dogs. Radioactivity was monitored in plasma, bile, and urine for 4.5 hr after an IV bolus of [3H]-LTC4. A decreased recovery of radioactivity in bile and urine was observed in the endotoxin-treated dogs. Cumulative [3H]-LTC4 metabolic patterns in bile and urine were determined by reverse-phase high-performance liquid chromatography (RP-HPLC) separation. Three primary metabolites, [3H]-LTD4, [3H]-LTE4, and a polar metabolite, (0.15-0.19)LT, accounted for most of the total bile radioactivity. The same primary metabolites were found for endotoxin-treated dogs and in similar relative amounts. [3H]-LTE4 and the polar metabolite (0.15-0.21)LT were the primary metabolites found in urine, but no N-acetyl LTE4 was found in bile or urine for either group. Plasma incubation of [3H]-LTC4 revealed heat-sensitive dipeptidase and glutamyl transpeptidase activity with significant production of [3H]-LTD4 and [3H]-LTE4 after 5- and 30-min incubation. Pharmacokinetic analysis using the two-compartment open model revealed an increased distribution phase rate constant (alpha) and distribution phase half-life [t1/2(alpha)], and decreased clearance (ClB), volume of distribution [Vd(ss) and Vd(area)] and elimination rate microconstant (Kel) of tritiated leukotrienes for endotoxin-treated dogs. This analysis along with the maintained higher plasma levels of tritiated leukotrienes, [3H]-LTs, in endotoxin-treated dogs suggests that endotoxin caused a decreased body clearance and less peripheral tissue penetration of [3H]-LTs. Collectively, these results indicate that the metabolism of LTC4 to LTD4 and LTE4, but not N-acetyl LTE4, in dogs was similar to that reported for man, pig, and monkey but dissimilar to rat. Endotoxin did not affect the types or relative amounts of metabolites found in bile or urine but appears to affect the disposition of [3H]-LTs by decreasing clearance and distribution.


Application of the FACE-Q rhinoplasty module in a mixed reconstructive and corrective rhinoplasty population in Finland.
The FACE-Q Rhinoplasty module is a patient-reported outcome instrument developed for the assessment of primarily aesthetic outcomes of rhinoplasty. The aim of our study was to produce a Finnish version of the instrument and validate it for use in patients undergoing nasal reconstruction as well as those treated with a rhinoplasty. Finnish versions of the FACE-Q scales Satisfaction with Nose, Satisfaction with Nostrils and Adverse Effects: Nose, were translated following established guidelines. Patients undergoing nasal resection, reconstruction or rhinoplasty in Helsinki University Hospital plastic surgery department in 2009-2019 were identified using theatre records. A total of 240 Finnish-speaking patients 18-85 years old were approached with a postal survey questionnaire. The questionnaire included the translated FACE-Q modules and those for Satisfaction with Facial Appearance, Appearance-Related Psychosocial Distress and Satisfaction with Outcome, as well as the general health-related quality of life instrument 15 D. The FACE-Q scales translated readily to Finnish. Eighty-three patients (35%) responded to the survey. Most FACE-Q scales performed well with high internal consistency (Cronbach's alphas 0.87-0.92) and repeatability. Only the Adverse Effects: Nose scale displayed poor consistency and a floor effect with 18% of the patients reporting no adverse outcomes. Answers to the Appearance-Related Psychosocial Distress scale were skewed towards no experienced stress. Answers to the other scales were normally distributed with weak correlation with 15 D dimensions. The Finnish translations of the FACE-Q Rhinoplasty scales perform well at assessing a diverse group of patients including those undergoing nasal reconstruction as well as those undergoing rhinoplasty.


The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50-100 years?
The recent SARS-CoV-2 pandemic, which is causing COVID-19 disease, has taught us unexpected lessons about the dangers of human suffering through highly contagious and lethal diseases. As the COVID-19 pandemic is now being partially controlled by various isolation measures, therapeutics, and vaccines, it became clear that our current lifestyle and societal functions may not be sustainable in the long term. We now have to start thinking and planning on how to face the next dangerous pandemic, not just overcoming the one that is upon us now. Is there any evidence that even worse pandemics could strike us in the near future and threaten the existence of the human race? The answer is unequivocally yes. It is not necessary to get infected by viruses found in bats, pangolins, and other exotic animals that live in remote forests to be in danger. Creditable scientific evidence indicates that the human gut microbiota harbor billions of viruses that are capable of affecting the function of vital human organs such as the immune system, lung, brain, liver, kidney, or heart. It is remotely possible that the development of pathogenic variants in the gut can lead to contagious viruses, which can cause pandemics, leading to the destruction of vital organs, causing death or various debilitating diseases such as blindness, respiratory, liver, heart, and kidney failures. These diseases could result in the complete shutdown of our civilization and probably the gradual extinction of the human race. This essay will comment on a few independent pieces of scientific facts, and then combine this information to come up with some (but certainly not all) hypothetical scenarios that could cause human race misery, even extinction, in the hope that these hypothetical scenarios will trigger preventative measures that could reverse or delay the projected adverse outcomes.


Docosahexaenoic Acid Incorporation Is Not Affected by Doxorubicin Chemotherapy in either Whole Cell or Lipid Raft Phospholipids of Breast Cancer Cells in vitro and Tumor Phospholipids in vivo.
To better understand how docosahexaenoic acid (DHA) improves the effects of doxorubicin (DOX), we examined DHA ± DOX on changes in whole cell and lipid raft phospholipids (PL) of MDA-MB-231 and MCF-7 breast cancer cells. We sought to confirm whether the relative changes in PL DHA content of MDA-MB-231 cells could be extended to PL from MDA-MB-231 tumors grown in mice fed a DHA supplemented diet ±DOX. Treatment with DHA did not change PL composition yet DOX increased the proportion of phosphatidylserine in MCF-7 cell lipid rafts by two-fold (p < 0.001). Regardless of DOX, the relative percent incorporation of DHA was higher in MDA-MB-231 cells compared to MCF-7 cells in phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine (whole cell and lipid rafts); and higher in phosphatidylethanolamine vs. phosphatidylcholine (4.4-fold in MCF-7 and 6-fold in MDA-MB-231 cells respectively). DHA treatment increased eicosapentaenoic acid and docosapentaenoic acid in MDA-MB-231 cells but not MCF-7 cells. Increased DHA content in MDA-MB-231 cells, MCF-7 cells, and MDA-MB-231 tumors in all PL moieties (except sphingomyelin) corresponded with reduced arachidonic acid (p < 0.05). Feeding mice 2.8% (w/w of fat) DHA ± DOX increased tumor necrotic regions (p < 0.05). This study established differential incorporation of DHA into whole cell and lipid rafts between human breast cancer cell lines. However, within each cell line, this incorporation was not altered by DOX confirming that DOX does not change membrane lipid composition. Furthermore, our findings indicate that membrane changes observed in vitro are translatable to in vivo changes and that DHA + DOX could contribute to the anticancer effects through increased necrosis.


Impaired baroreflex control of heart rate in high-renin renal hypertension.
The reflex responses of heart rate (HR) to bolus injection and infusion of phenylephrine and nitroglycerine were studied in rats with one-kidney, one clip (1-K, 1C) hypertension and hypertension produced by aortic ligation. Rats with mild 1-K, 1C hypertension (147 +/- 4 mmHg) and a normal renin-angiotensin system (RAS) activity had normal bradycardic and tachycardic responses, whereas rats with severe hypertension (208 +/- 3 mmHg) and over-active RAS showed impairment (70-80%) of the responses. After 12 days of aortic ligation rats with mild (146 +/- 2 mmHg) and severe (175 +/- 3 mmHg) hypertension exhibited overactivity of the RAS and marked impairment of the baroreflex control of HR. Normalization of RAS activity in rats with mild hypertension 60 days after aortic ligation, coincided with normalization of the bradycardic responses, whereas the abnormality persisted in those rats with severe hypertension in which hyperactivity of RAS also persisted. The response to 20-s carotid occlusion and the HR responses to electrical stimulation of the vagus nerve were normal in rats with renal hypertension, 12 days after aortic ligation. An ether inhalation test produced a marked reduction of 60% in the HR of control awake rats accompanied by a 46 +/- 5 mmHg increase in blood pressure. Reflex pathways other than those through the baroreceptors were largely responsible for the bradycardia since responses remained unchanged in rats with sino-aortic denervation (SAD) or when the pressure increase was prevented by phenoxybenzamine administration.(ABSTRACT TRUNCATED AT 250 WORDS)


Self-assembled films of a biferrocenyl-containing hemicyanine derivative with SiW12O40(4-): preparation, UV-visible spectroscopy and electrochemical properties.
Electrostatic self-assembled films were successfully prepared by alternating deposition of SiW12O40(4-) and a biferrocenyl-containing hemicyanine derivative on quartz or indium-tin-oxide coated glass substrates. The films were characterized by UV-visible absorption spectroscopy and cyclic voltammetry.


A generation apart? Gender-related experiences and health in women in early and late mid-life.
There have been a number of critiques in the last few years of the prevailing paradigm of research on gender and health, which dominated in the latter part of the 20th century. One such criticism has centred on the a historic and decontextualised way in which much evidence for gender differences has been used. In this paper we aim to show that, even within a relatively confined geographical locale over a relatively short period of time, there have been substantial changes in gender relations which are likely to have affected the experience, opportunities, and attitudes of women born in the early 1930s and early 1950s. We illustrate this using data from a study of inequalities in health in Scotland, which includes unusually rich longitudinal data on gender, including occupancy and experience of gender-related roles, attitudinal data on gender equality, and measures of gender role orientation (GRO). These are related to various dimensions of health and health behaviour. The data show substantial differences in the experiences of two generations of women, who are just 20 years apart in age, and a lack of consistency between measures of GRO and health. Whilst on the one hand these data suggest the importance of taking more account of the broader (social, historical or political) context, the analysis also highlights the methodological problems posed.


The Bordetella Bps Polysaccharide Is Required for Biofilm Formation and Enhances Survival in the Lower Respiratory Tract of Swine.
Bordetella bronchiseptica is pervasive in swine populations and plays multiple roles in respiratory disease. Additionally, B. bronchiseptica is capable of establishing long-term or chronic infections in swine. Bacterial biofilms are increasingly recognized as important contributors to chronic bacterial infections. Recently the polysaccharide locus bpsABCD has been demonstrated to serve a critical role in the development of mature biofilms formed by the sequenced laboratory strain of B. bronchiseptica We hypothesized that swine isolates would also have the ability to form mature biofilms and the bpsABCD locus would serve a key role in this process. A mutant containing an in-frame deletion of the bpsABCD structural genes was constructed in a wild-type swine isolate and found to be negative for poly-N-acetylglucosamine (PNAG)-like material by immunoblot assay. Further, the bpsABCD locus was found to be required for the development and maintenance of the three-dimensional structures under continuous-flow conditions. To investigate the contribution of the bpsABCD locus to the pathogenesis of B. bronchiseptica in swine, the KM22Δbps mutant was compared to the wild-type swine isolate for the ability to colonize and cause disease in pigs. The bpsABCD locus was found to not be required for persistence in the upper respiratory tract of swine. Additionally, the bpsABCD locus did not affect the development of anti-Bordetella humoral immunity, did not contribute to disease severity, and did not mediate protection from complement-mediated killing. However, the bpsABCD locus was found to enhance survival in the lower respiratory tract of swine.


An iridium abundance anomaly at the palynological cretaceous-tertiary boundary in northern new Mexico.
An iridium abundance anomaly, with concentrations up to 5000 parts per trillion over a background level of 4 to 20 parts per trillion, has been located in sedimentary rocks laid down under freshwater swamp conditions in the Raton Basin of northeastern New Mexico. The anomaly occurs at the base of a coal bed, at the same stratigraphic position at which several well-known species of Cretaceous-age pollen became extinct.


Maspin: the new frontier.
Maspin (mammary serine protease inhibitor) was identified in 1994 by subtractive hybridization analysis of normal mammary tissue and breast cancer cell lines. Subsequently, emerging evidence portrays maspin as a multifaceted protein, interacting with diverse group of intercellular and extracellular proteins, regulating cell adhesion, motility, apoptosis, and angiogenesis and critically involved in mammary gland development. The tissue-specific expression of maspin is epigenetically controlled, and aberrant methylation of maspin promoter is closely associated with maspin gene silencing. Identification of new tissue sites expressing maspin and novel maspin-binding partners has expanded the horizon for maspin research and promises maspin-based therapeutic approaches for combating cancer. This perspective briefly outlines the past and present strides in deciphering this unique molecule and speculates on new frontiers in maspin research and prospects of maspin as a diagnostic/prognostic indicator in cancer.


Alteration in 5-HT₂C, NMDA receptor and IP3 in cerebral cortex of epileptic rats: restorative role of Bacopa monnieri.
Bacopa monnieri is effective in stress management, brain function and a balanced mood. 5-HT2C receptors have been implicated in stress whereas NMDA receptors and mGlu5 play crucial role in memory and cognition. In the present study, we investigated the role of B. monnieri extract in ameliorating pilocarpine induced temporal lobe epilepsy through regulation of 5-HT2C and NMDA receptors in cerebral cortex. Our studies confirmed an increased 5-HT2C receptor function during epilepsy thereby facilitating IP3 release. We also observed an decreased NMDA receptor function with an elevated mGlu5 and GLAST gene expression in epileptic condition indicating the possibility for glutamate mediated excitotoxicity. These alterations lead to impaired behavioural functions as indicated by the Elevated Plus maze test. Carbamazepine and B. monnieri treatments to epileptic rats reversed the alterations in 5-HT2C, NMDA receptor functions and IP3 content thereby effectively managing the neurotransmitter balance in the cerebral cortex.


alpha-Fetoprotein and albumin genes are in tandem in the mouse genome.
The urine alpha-fetoprotein (AFP) and serum albumin genes most probably arose in evolution as the consequence of a duplication of a common ancestral gene. They have both been previously mapped to chromosome 5 in the mouse. We now have evidence that these genes are closely linked. By using a unique copy DNA probe derived from previously cloned AFP 5' flanking DNA, a recombinant DNA phage has been isolated, from a bacteriophage DNA library, that contains sequences flanking the 5' end of the AFP gene and the 3' end of the albumin gene. Restriction endonuclease mapping and DNA sequence determination of the recombinant phage and comparison to total genomic DNA confirmed that the genes are in tandem, 13.5 kilobase pairs apart, with the albumin gene to the 5' side of the AFP gene. Thus, they are transcribed from the same strand of DNA.


Hemin inhibits cyclin D1 and IGF-1 expression via STAT5b under hypoxia in ERalpha-negative MDA-MB 231 breast cancer cells.
Cyclin D1 and insulin-like growth factor 1 receptor (IGF-1R) are key regulators of cell proliferation that are overexpressed in most breast cancers. The purpose of the present study was to investigate the molecular mechanism by which hemin exerts its inhibitory effects on aggressive breast cancer cells. We found that hemin regulates cyclin D1 and IGF-1R proteins and insulin-like growth factor-1 gene expression through STAT5b in breast cancer cells. We confirmed that STAT5b, cyclin D1, and IGF-1R is up-regulated by hypoxia, and the increased STAT5b binds strongly to the STAT5-binding sites contained within the distal 5'-flanking region of IGF-1 gene in breast cancer cells. EMSA studies showed that STAT5 binding activity to the IGF-1 and cyclin D1 promoter was distinctly decreased by hemin in STAT5b-transfected COS-7 or MDA-MB 231 cells. IGF-1 gene expression was also decreased by hemin in mammary epithelial cells. STAT5b expression was inhibited in siRNA experiments and by hemin, leading to decreased levels of IGF-1. These results provide a basis for molecular targets in cancer treatment via the STAT5b/IGF-1 or /cyclin D1 pathway in solid tumor cells. These data indicate that hemin inhibits the cyclin D1 and IGF-1 expression via STAT5b under hypoxia in ERalpha-negative breast cancer cells. These findings are valuable toward understanding the role of hemin-induced inhibition of cyclin D1 and IGF-1 expression under hypoxia in invasive and metastatic breast cancer.


Highly specific and broadly potent inhibitors of mammalian secreted phospholipases A2.
We report a series of inhibitors of secreted phospholipases A2 (sPLA2s) based on substituted indoles, 6,7-benzoindoles, and indolizines derived from LY315920, a well-known indole-based sPLA2 inhibitor. Using the human group X sPLA2 crystal structure, we prepared a highly potent and selective indole-based inhibitor of this enzyme. Also, we report human and mouse group IIA and IIE specific inhibitors and a substituted 6,7-benzoindole that inhibits nearly all human and mouse sPLA2s in the low nanomolar range.


Crystal structure of a superstable mutant of human p53 core domain. Insights into the mechanism of rescuing oncogenic mutations.
Most of the cancer-associated mutations in the tumor suppressor p53 map to its DNA-binding core domain. Many of them inactivate p53 by decreasing its thermodynamic stability. We have previously designed the superstable quadruple mutant M133L/V203A/N239Y/N268D containing the second-site suppressor mutations N239Y and N268D, which specifically restore activity and stability in several oncogenic mutants. Here we present the x-ray structure of this quadruple mutant at 1.9 A resolution, which was solved in a new crystal form in the absence of DNA. This structure reveals that the four point mutations cause only small local structural changes, whereas the overall structure of the central beta-sandwich and the DNA-binding surface is conserved. The suppressor mutation N268D results in an altered hydrogen bond pattern connecting strands S1 and S10, thus bridging the two sheets of the beta-sandwich scaffold in an energetically more favorable way. The second suppressor mutation N239Y, which is located in close proximity to the DNA-binding surface in loop L3, seems to reduce the plasticity of the structure in large parts of loop L3 as indicated by decreased crystallographic temperature factors. The same is observed for residues in the vicinity of the N268D substitution. This increase in rigidity provides the structural basis for the increase in thermostability and an understanding how N268D and N239Y rescue some of the common cancer mutants.


Enhanced luminescence of SiO2:Eu3+ by energy transfer from ZnO nanoparticles.
ZnO nanoparticles embedded into SiO(2) by an ex situ method were shown to result in stable green emission with a peak at 510 nm compared to the normal peak at 495 nm from micron-sized ZnO powders. Green emission from ZnO nanoparticles was completely suppressed when they were embedded in SiO2 doped with Eu3+. Instead, the f-f emissions from Eu3+ were enhanced 5-10 times by energy transfer from the embedded ZnO nanoparticles to Eu3+. The Eu3+ luminescence increased as the Eu3+ concentration increased from 1 vs 5 mole % (for 10 mole % ZnO). In addition, the intensity increased as the embedded ZnO nanoparticles concentration increased up to 10 mole % (for 5 mole % Eu3+). The effects of phonon mediated energy transfer, quenching by activator interactions between Eu3+ ions, and energy back-transfer from Eu3+ ions to ZnO nanoparticles were discussed.


["Pediatric" forms of Creutzfeldt-Jakob disease (nvCJD)].
The authors propose the name of pediatric CJD disease (nvCJD) for those forms of this pathology which appear in childhood and adolescence (about twenty cases have been reported in Europe: 1996). The "pediatric form" differs both in terms of age ("teenagers" and also 16-year-old), but also owing to its long course (mean of 14 to 35 months) and the early onset of psychiatric and sensory symptoms. Until a few years ago, discussion of a new pediatric-adolescent form of the disease (new variant of CJD) would have been laughable.