Adverse Childhood Experiences and Symptoms of Urologic Chronic Pelvic Pain Syndrome: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Study.
Adverse Childhood Experiences (ACEs) such as sexual and physical violence, serious illness, and bereavement have been linked to number of chronic pain conditions in adulthood, and specifically to urologic chronic pelvic pain syndrome (UCPPS). We sought to characterize the prevalence of ACEs in UCPPS using a large well-characterized cohort in comparison with a group of healthy controls. We also sought to determine the association of ACE severity with psychological factors known to impact pain and to determine whether ACEs are associated with patterns of improvement or worsening of symptom over a year of naturalistic observation. For longitudinal analyses we used functional clusters identifying broad classes of (a) improved, (b) worsened, and (c) stable groups for genitourinary pain and urinary symptoms. We employed a mediation/path analysis framework to determine whether ACEs influenced 1 year outcomes directly, or indirectly through worse perceptions of physical well-being. ACE severity was elevated in UCPPS (n = 421) participants compared with healthy controls (n = 414; p < .001), and was most strongly associated with factors associated with complex chronic pain, including more diffuse pain, comorbid functional symptoms/syndromes, and worse perceived physical well-being (all p < .001). Finally, worse physical well-being mediated the relationship between ACE severity and less likelihood of painful symptom improvement (OR = .871, p = .007)) and a greater likelihood of painful symptom worsening (OR = 1.249, p = .003) at 1 year. These results confirm the association between ACEs and UCPPS symptoms, and suggest potential targets for therapeutic interventions in UCPPS. NCT01098279.


Concept for quantifying the dose from image guided radiotherapy.
Radiographic image guidance is routinely used for patient positioning in radiotherapy. All radiographic guidance techniques can give a significant radiation dose to the patient. The dose from diagnostic imaging is usually managed by using effective dose minimization. In contrast, image-guided radiotherapy adds the imaging dose to an already high level of therapeutic radiation which cannot be easily managed using effective dose. The purpose of this work is the development of a concept of IGRT dose quantification which allows a comparison of imaging dose with commonly accepted variations of therapeutic dose. It is assumed that dose variations of the treatment beam which are accepted in the spirit of the ALARA convention can also be applied to the additional imaging dose. Therefore we propose three dose categories: Category I: The imaging dose is lower than a 2% variation of the therapy dose. Category II: The imaging dose is larger than in category I, but lower than the therapy dose variations between different treatment techniques. Category III: The imaging dose is larger than in Category II. For various treatment techniques dose measurements are used to define the dose categories. The imaging devices were categorized according to the measured dose. Planar kV-kV imaging is a category I imaging procedure. kV-MV imaging is located at the edge between category I and II and is for increasing fraction size safely a category I imaging technique. MV-MV imaging is for all imaging technologies a category II procedure. MV fan beam CT for localization is a category I technology. Low dose protocols for kV CBCT are located between category I and II and are for increasing fraction size a category I imaging technique. All other investigated Pelvis-CBCT protocols are category II procedures. Fan beam CT scout views are category I technology. Live imaging modalities are category III for conventional fractionation, but category II for stereotactic treatments. Dose from radiotherapy imaging can be categorized in terms of generally accepted dose variations of therapy dose. This concept allows the quantification of daily dose from image guided radiotherapy in the spirit of the ALARA convention.


Measurement of adherence to inhaled corticosteroids by self-report and electronic medication monitoring.
Poor adherence to daily inhaled corticosteroids (ICS) is an important factor contributing to asthma morbidity. Assessing adherence in clinical settings using self-reported adherence often overestimates actual adherence. Electronic monitoring devices (EMDs) are objective means of assessing adherence, but are not routinely used in practice. Here, we aimed to establish adherence rates to ICS using EMDs in an inner-city, minority population in the Bronx, NY, and to compare two methods of self-reported adherence with EMD-measured adherence. Patients with physician-confirmed persistent asthma and daily ICS prescription were recruited. Self-reported adherence to ICS was measured by parental report for children and self-report for adults and the Medication Adherence Report Scale for Asthma (MARS-A). Two weeks after enrollment, EMD data were accessed for analysis. Daily adherence was calculated based on the number of puffs actuated per day as captured by EMD divided by the prescribed number of puffs. 41 children and 40 adults participated. Median EMD-measured ICS adherence was 41% (children) and 43% (adults). This was significantly lower than the median self-reported adherence (100% for children, p < 0.001; 100% for adults, p < 0.001). MARS-A score in children did not correlate with EMD adherence data (p = 0.18), while in adults, this correlation tended to be more consistent (p = 0.07). Adherence to daily ICS as measured using EMD is low in this population. In both adults and children, self-reported adherence was a poor indicator of true adherence. Further efforts using objective measures of medication adherence for patients with high asthma morbidity may be warranted to guide therapeutic decisions.


Corneal bee sting: improvement in the acute stage in the absence of treatment.
Bee sting injuries to the eye are relatively uncommon. The outcomes of corneal bee sting injuries are highly variable, and there is no consensus on the management at the time of initial presentation. We report a case of a 17-year-old male with a corneal bee sting injury that significantly improved in the acute stage without any treatment, which to the best of our knowledge is the first report in the literature documenting the natural history of a corneal bee sting injury in the acute stage.


Alterations in serum antibody and peripheral T-lymphocyte subsets resulting from treatment of murine immune complex glomerulonephritis with PGE2.
The effects of treatment with 16,16-dimethyl prostaglandin E2 (DMPGE2) on histologic damage, glomerular immune complex deposition, serum total IgG subclass levels, anti-apoferritin IgG levels, and peripheral blood T-lymphocyte subsets were determined in apoferritin-induced immune complex glomerulonephritis of mice. The results demonstrate that doses of DMPGE2 ranging from 2.5 to 10 micrograms twice daily significantly reduced the degree of glomerular damage in a dose-dependent manner. Similarly, these doses of DMPGE2 reduced the amount of immunoglobulin deposition along peripheral capillary loops. Total IgM, IgG1, IgG2a, and IgG2b were unaffected by DMPGE2 administration. Serum anti-apoferritin IgG levels were significantly reduced in mice receiving DMPGE2 at doses of 5 and 10 micrograms twice daily. Nephrotic mice had significantly reduced peripheral blood total T lymphocytes (Lyt-1+) and a reduction of T-suppressor (Lyt-2+) cells. Administration of DMPGE2 at doses of 5 and 10 micrograms twice daily prevented these T-lymphocyte alterations. These studies indicate that treatment of mice receiving apoferritin with DMPGE2 may prevent glomerulonephritis by altering both cellular and humoral immune responses.


Shoulder work-related musculoskeletal disorders and related factors of workers in 15 industries of China: a cross-sectional study.
Changes in modern industrial production practices can easily lead to shoulder work-related musculoskeletal disorders (WMSD). The current reports on shoulder WMSD are limited to some industries are less well studied, and the sample size is usually small. This study aimed to describe the prevalence and severity of shoulder WMSD in a large sample of Chinese workers from 15 industries, analyze the possible correlations with sociodemographic and work-related variables, and compare the differences between industries. A cross-sectional study was conducted among a sample of 55,749 participants from 252 enterprises in 15 industries throughout China. A Chinese version of the musculoskeletal disease questionnaire was used to collect the demographic factors, shoulder symptoms in past 12 months, and work-related factors including posture-related factors, repetition, vibration, work organization, job control, and environmental factors as independent variables. Descriptive statistics were used, and the binary logistic regression analysis was performed to explore the association between shoulder WMSD and potential demographic and work-related factors. Nearly 35.5% of participants reported shoulder pain and discomfort in the previous 12 months. Biopharmaceutical manufacturing (56.2%), medical services (54.4%), and aviation services (50.1%) were the three industries with the highest prevalence of shoulder WMSD. The pain score of aviation services workers was the highest. The related factors for shoulder WMSD varied among the different industries. Our study found a relatively high prevalence of shoulder WMSD in China. There were large differences in the prevalence of shoulder WMSD among industries, and the related factors were particular to each industry. Such information is useful to help occupational health practitioners and policymakers conduct preventive programs to reduce shoulder disorders in these working populations.


In-situ near infrared spectroscopy to monitor key analytes in mammalian cell cultivation.
The use of in-situ near infrared spectroscopy (NIRS) as a tool for monitoring four key analytes in a CHO-K1 animal cell culture was investigated. Previous work using on-line NIRS to monitor bioprocesses has involved its application ex-situ where the analyzer is physically outside the fermentor, or to microbial bioprocesses. This novel application of NIRS to monitor analytes within an animal cell culture using a steam sterilizable in-situ fiber optic probe is very important for furthering the use of NIRS within the bioprocessing industry. The method of calibration used to develop the models involved the use of large data sets so that all likely variation in stoichiometry was incorporated within the models. Successful models for glucose, lactate, glutamine, and ammonia were built with Standard Error of Predictions (SEP's) of 0.072 (g/L), 0.0144 (g/L), 0.308 (mM), and 0.036 (mM), respectively of the total concentration range.


Ribavirin concentration determines treatment success of first-generation DAA-based chronic HCV therapy.
Monitoring ribavirin concentrations during hepatitis C treatment with dual therapy can help optimize treatment response and minimize anaemia. A defined therapeutic range for ribavirin during direct-acting antiviral-based therapies is lacking. This analysis explores whether a therapeutic range for ribavirin concentrations can be defined in patients treated with boceprevir- or telaprevir-based triple therapies. Treatment-naive patients from ADVANCE, ILLUMINATE, OPTIMIZE and SPRINT-2, and treatment-experienced patients from RESPOND-2 were included. Multivariable logistic regression analyses were performed to evaluate whether ribavirin concentrations were an independent predictor of sustained virological response or anaemia. Optimal cutoff values and the percentage of patients within the proposed therapeutic range were determined, along with the associated chance of response. Overall, 1,502 patients were included. In both regimens, ribavirin concentrations were significantly associated with anaemia (haemoglobin level <10 g/dl) at all time points (1.75 < odds ratio [OR] <2.45) and sustained virological response was associated with ribavirin concentrations at week 8 (OR=1.43 for telaprevir and 1.78 for boceprevir). A therapeutic range for ribavirin at week 8 of 2.2-3.5 mg/l was defined for telaprevir treatment. Of the 48% of patients with a concentration within this range, 81% achieved sustained virological response and only 5.1% reported anaemia. For boceprevir treatment, the week 8 optimal range was defined as 2.2-3.6 mg/l and 50% of patients had a concentration within this range, of whom 69% achieved sustained virological response and 46% developed anaemia. We established the therapeutic range for ribavirin in boceprevir- and telaprevir-based therapy that balances safety and efficacy.


Risk factors for adolescent smoking: parental smoking and the mediating role of nicotine dependence.
Parental smoking and early-emerging nicotine dependence symptoms are well-documented risk factors for adolescent smoking. However, very little is known about the mediating pathways through which these risk factors may act, or whether parental smoking may cause or signal early-emerging nicotine dependence symptoms. Data were drawn from the longitudinal Social and Emotional Contexts of Adolescent Smoking Patterns Study. Adolescents who had smoked under 100 cigarettes in their lifetime (n=594; low-exposure group) and adolescents who had smoked over 100 cigarettes, but fewer than 5 cigarettes per day (n=152) were included in the analyses. Path analysis was performed on longitudinal data to investigate the association between parental smoking and smoking frequency at the 48 months follow-up, both directly and through mediating variables of smoking frequency, smoking quantity, and nicotine dependence. Father's smoking was associated with higher adolescent nicotine dependence scores at the baseline assessment wave. Structural equation modeling revealed that mother's smoking at baseline was associated with adolescent's smoking frequency at the 48-month follow-up, and its effect was partially mediated by both smoking frequency and nicotine dependence among low-exposure adolescent smokers. Parental smoking is a risk factor for future smoking in low-exposure adolescent smokers, above and beyond the risks posed by smoking behavior and nicotine dependence. Moreover, parental smoking is associated with early-onset nicotine dependence in low-exposure adolescent smokers. As an easily measureable risk factor, parent smoking status can be used to identify and intervene with novice adolescent smokers who are at high risk for chronic smoking behavior.


Drugs for cardiovascular support in anesthetized horses.
Despite the use of balanced anesthesia and fluids, drugs for cardiovascular support are often needed in anesthetized horses. Antimuscarinics can be used to treat bradycardia unrelated to hypertension. Vasopressors can be useful when hypotension is caused by vasodilation and/or when the effect of fluids and inotropes is insufficient. In most cases, however, inotropes, including sympathomimetics, calcium salts, and phosphodiesterase inhibitors, are preferred. Of the β-sympathomimetics, dobutamine remains the agent of choice. Calcium salts are mainly useful in hypocalcemic patients. Phosphodiesterase inhibitors may offer an alternative solution, but more research is needed.


Axonal transport of AAV9 in nonhuman primate brain.
A pilot study in nonhuman primates was conducted, in which two Rhesus macaques received bilateral parenchymal infusions of adeno-associated virus serotype 9 encoding green fluorescent protein (AAV9-GFP) into each putamen. The post-surgical in-life was restricted to 3 weeks in order to minimize immunotoxicity expected to arise from expression of GFP in antigen-presenting cells. Three main findings emerged from this work. First, the volume over which AAV9 expression was distributed (Ve) was substantially greater than the volume of distribution of MRI signal (Vd). This stands in contrast with Ve/Vd ratio of rAAV2, which is lower under similar conditions. Second, post-mortem analysis revealed expression of GFP in thalamic and cortical neurons as well as dopaminergic neurons projecting from substantia nigra pars compacta, indicating retrograde transport of AAV9. However, fibers in the substantia nigra pars reticulata, a region that receives projections from putamen, also stained for GFP, indicating anterograde transport of AAV9 as well. Finally, one hemisphere received a 10-fold lower dose of vector compared with the contralateral hemisphere (1.5 × 10(13) vg ml(-1)) and we observed a much stronger dose effect on anterograde-linked than on retrograde-linked structures. These data suggest that AAV9 can be axonally transported bi-directionally in the primate brain. This has obvious implications to the clinical developing of therapies for neurological disorders like Huntington's or Alzheimer's diseases.


Treponematosis eradication, with special reference to yaws eradication in Haiti.
This paper outlines the general administrative and therapeutic principles governing yaws eradication campaigns, with particular reference to the operational problems encountered in Haiti. The ways in which those problems were solved are described in the course of a relatively detailed account of the yaws eradication programme which began in that country in 1950 and which has now reached the end of the "mopping-up" phase. The author points out that lessons learnt in this mass treatment campaign can usefully be applied to eradication programmes against other diseases.


The nature of the problem: the intentional design of problems to facilitate different levels of student learning.
This paper explores the deliberate design of 'problem' situations within a 3-year problem-based nursing degree conducted at Griffith University, Nathan, Queensland, Australia. It examines problem situations within the first and third years of the course to illustrate the issues involved in designing material that enables students to achieve the curriculum aims. Although the problem situations are designed from the same health care setting, the discussion highlights how concepts and issues can be addressed in different ways depending on the desired student outcomes. The paper outlines and examines the nature of student learning and the clinical reasoning process used by students in making decisions that closely mirror those made as registered nurses in order to facilitate the achievement of clients' health goals.


A Novel Gel Thermoelectric Chemical Cell for Harvesting Low-Grade Heat Energy.
The use of gel thermoelectric chemical cells to capture low-grade heat for conversion to electricity is an attractive approach. However, there are few studies on whether the distribution of redox species in the electrolyte has an effect on the performance of cells. Herein, this concern was discussed by constructing a novel gel thermoelectric chemical cell (Cu-C-cg). Using cellulose-like rice paper as a separator, a concentration gradient of electrolyte was carefully constructed, so that the concentration of potassium ferrocyanide gradually decreased from the hot electrode to the cold electrode while the concentration of potassium ferricyanide gradually increased. Through electrochemical measurement and analysis, it was found that the thermoelectric performance of this cell outperformed the cell without electrolyte concentration gradients. Meanwhile, this performance could be enhanced by the use of asymmetric electrodes composed of copper foil and carbon electrodes. After optimizing the conditions, the open-circuit voltage, output power, and Seebeck coefficient of the Cu-C-cg cell at 12 K temperature difference were 0.450 V, 183 μW, and 7.82 mV K-1 , respectively. This work not only provides a novel idea in gel-based cell design but also an excellent thermoelectric chemical cell.


Fine-needle aspiration cytology diagnosis of tuberculosis.
Fine-needle aspiration cytology of lymph nodes and extranodal swellings in 160 cases showed granulomatous reaction with or without caseation necrosis in 83%. The material was acellular or predominantly composed of necrotic material, polymorphs, and lymphocytes in 17%. The age of the patient ranged from 1.5 to 72 yr. The male to female ratio was 1:1.3. Acid-fast bacilli (AFB) could be demonstrated in 40.6% of cases. In cases associated with cellular reaction and necrosis. AFB positivity was 50.0%, while it was 66.7% in cases with acellular necrotic material.


Probing Dynamic Processes in Lithium-Ion Batteries by In Situ NMR Spectroscopy: Application to Li1.08Mn1.92O4 Electrodes.
Mobi-Li-ty: Lithium mobility, as a function of temperature during battery cycling, can be simply monitored by using in situ T2' relaxation measurements. Since Li dynamics are strongly related to structural properties, the changes in in situ T2' can be used to detect structural changes, such as Li ordering.


Functional oxygen extraction fraction (OEF) imaging with turbo gradient spin echo QUIXOTIC (Turbo QUIXOTIC).
QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption (QUIXOTIC) is a recent technique that measures voxel-wise oxygen extraction fraction (OEF) but suffers from long scan times, limiting its application. We implemented multiecho QUIXOTIC dubbed turbo QUIXOTIC (tQUIXOTIC) that reduces scan time eightfold and then applied it in functional MRI. tQUIXOTIC utilizes a novel turbo gradient spin echo readout enabling measurement of venular blood transverse relaxation rate in a single tag-control acquisition. Using tQUIXOTIC, we estimated cortical gray matter (GM) OEF, created voxel-by-voxel GM OEF maps, and quantified changes in visual cortex OEF during a blocked design flashing checkerboard visual stimulus. Contamination from cerebrospinal fluid partial volume averaging was estimated and corrected. The average cortical GM OEF was estimated as 0.38 ± 0.06 (n = 8) using a 3.4-min acquisition. The average OEF in the visual cortex was estimated as 0.43 ± 0.04 at baseline and 0.35 ± 0.05 during activation, with an average %ΔOEF of -20%. These values are consistent with those of past studies. tQUIXOTIC successfully estimated cortical GM OEF in clinical scan times and detected changes in OEF during blocked design visual stimulation. tQUIXOTIC will be useful to monitor regional OEF clinically and in blocked design or event-related functional MRI experiments. Magn Reson Med 79:2713-2723, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


A generic solution for web-based management of pseudonymized data.
Collaborative collection and sharing of data have become a core element of biomedical research. Typical applications are multi-site registries which collect sensitive person-related data prospectively, often together with biospecimens. To secure these sensitive data, national and international data protection laws and regulations demand the separation of identifying data from biomedical data and to introduce pseudonyms. Neither the formulation in laws and regulations nor existing pseudonymization concepts, however, are precise enough to directly provide an implementation guideline. We therefore describe core requirements as well as implementation options for registries and study databases with sensitive biomedical data. We first analyze existing concepts and compile a set of fundamental requirements for pseudonymized data management. Then we derive a system architecture that fulfills these requirements. Next, we provide a comprehensive overview and a comparison of different technical options for an implementation. Finally, we develop a generic software solution for managing pseudonymized data and show its feasibility by describing how we have used it to realize two research networks. We have found that pseudonymization models are highly heterogeneous, already on a conceptual level. We have compiled a set of requirements from different pseudonymization schemes. We propose an architecture and present an overview of technical options. Based on a selection of technical elements, we suggest a generic solution. It supports the multi-site collection and management of biomedical data. Security measures are multi-tier pseudonymity and physical separation of data over independent backend servers. Integrated views are provided by a web-based user interface. Our approach has been successfully used to implement a national and an international rare disease network. We were able to identify a set of core requirements out of several pseudonymization models. Considering various implementation options, we realized a generic solution which was implemented and deployed in research networks. Still, further conceptual work on pseudonymity is needed. Specifically, it remains unclear how exactly data is to be separated into distributed subsets. Moreover, a thorough risk and threat analysis is needed.


Laser subtotal meniscectomy in rabbits.
This study investigates the healing potential of the peripheral rim of rabbit meniscus following laser subtotal meniscectomy. Thirty animals were operated with 23 bilateral meniscectomies and 7 sham controls. When sacrificed at intervals up to 6 months, the harvested peripheral rims demonstrated a devitalized layer of fibrocartilage averaging 17 micron in thickness, indicating an extremely superficial thermal effect of the laser energy utilizing power densities of 20 to 38 W. Viable chondrocytes and minimal alteration of collagen fibril structure and orientation were noted within 20 to 50 micron of the meniscus free margin. By 2 weeks, a proliferation of vascular buds near the free margin of the meniscus was observed with an increase in ground substance production and chondrocyte population. By 10 weeks, the free margin was completely sealed and was composed of logically oriented collagen fibers and only slightly increased numbers of chondrocytes. It was concluded that the healing potential of rabbit meniscus is unimpaired following laser resection of the central margin, and that the repair process is mediated by a proliferation of chondrocytes, supported in part by neovascularity within the substance of the meniscus.


Association of HIV infection and antiretroviral therapy with the occurrence of an unfavorable TB treatment outcome in a rural district hospital in Eastern Cape, South Africa: A retrospective cohort study.
Our objective was to assess differences in TB treatment outcomes between individuals who were HIV negative, HIV positive on anti-retroviral treatment (ART) and HIV positive not on ART, at TB treatment initiation at a rural district hospital in Eastern Cape, South Africa. This was a retrospective cohort study of individuals diagnosed with TB between January 2017 and April 2020 at a district hospital. Adults 15 years and over with reported HIV status and treatment outcome were included (N = 711). A categorical outcome with three levels was considered: unfavorable, down referral, and success. We report descriptive statistics for the association between HIV and ART status and treatment outcome using Chi-square and Fisher's exact tests. A multinomial baseline logit model was used to estimate odds ratios for treatment outcomes. Overall, 59% of included patients were HIV positive with 75% on ART. Eighty-eight patients 12% had an unfavorable outcome. Half of all patients were down referred with an additional 37% having a successful outcome. Individuals without HIV were more likely to be down referred (versus unfavorable) compared to individuals with untreated HIV (2.90 OR, 1.36, 6.17 95% CI). There was a greater likelihood for individuals without HIV having a successful TB treatment outcome compared to individuals with untreated HIV (4.98 OR, 2.07, 11.25 95% CI). The majority of individuals had positive TB treatment outcomes (down referred or success). However, people without HIV had nearly five times greater odds of having successful outcomes than those with untreated HIV.


Predicting adolescents' persistence, non-persistence, and recent onset of nonmedical use of opioids and stimulants.
This study sought to distinguish among adolescents who were persistent, non-persistent, or recent onset nonmedical users of prescription opioids and stimulants (respondents' ages ranged from 12-17 years, N=126,764). The multinomial logistic regression analyses of combined data from the 2003 through 2009 National Survey of Drug Use and Health were used to investigate the association of respondents' sex, age, family income, race, parental status, population density, and user status (persistent, non-persistent, recent onset) on common illicit substances (cigarettes, alcohol, marijuana, and inhalants) with opioid and stimulant use. The odds of nonmedical opioid and stimulant use were significantly greater for females than males, and increased with age. Results were mixed for income, race, and parental status. Population density was largely unrelated to nonmedical use. Persistent nonmedical users of common illicit substances, especially marijuana and inhalants, were at greatest risk for nonmedical opioid and stimulant use. Non-persistent use of common illicit substances was a strong predictor of both non-persistent opioid and stimulant use. Recent onset of common substance use predicted recent onset of prescription opioid and stimulant use. Results indicate that persistence may be related to polysubstance use involving prescription opioids and stimulants, supporting efforts to investigate the underlying causes of polysubstance use.


Gut microbiota and metabonomics used to explore the mechanism of Qing'e Pills in alleviating osteoporosis.
The traditional Chinese medicine Qing'e Pills (QEP) has been used to treat postmenopausal osteoporosis (PMO). We evaluated the regulatory effects of QEP on gut microbiota in osteoporosis. Eighteen female SD rats were divided into three groups: sham surgery (SHAM), ovariectomized (OVX) and ovariectomized treated with QEP (OVX + QEP). Six weeks after ovariectomy, QEP was administered to OVX + QEP rats for eight weeks (4.5 g/kg/day, i.g.). After 14 weeks, the bone microstructure was evaluated. Differences in gut microbiota were analysed via 16S rRNA gene sequencing. Changes in endogenous metabolites were studied using UHPLC-Q-TOF/MS technology. GC-MS was used to detect short-chain fatty acids. Furthermore, we measured serum inflammatory factors, such as IL-6, TNF-α and IFN-γ, which may be related to gut microbiota. OVX + QEP exhibited increased bone mineral density (0.11 ± 0.03 vs. 0.21 ± 0.02, p< 0.001) compared to that of OVX. QEP altered the composition of gut microbiota. We identified 19 potential biomarkers related to osteoporosis. QEP inhibited the elevation of TNF-α (38.86 ± 3.19 vs. 29.43 ± 3.65, p< 0.05) and IL-6 (83.38 ± 16.92 vs. 45.26 ± 3.94, p< 0.05) levels, while it increased the concentrations of acetic acid (271.95 ± 52.41 vs. 447.73 ± 46.54, p< 0.001), propionic acid (28.96 ± 5.73 vs. 53.41 ± 14.26, p< 0.01) and butyric acid (24.92 ± 18.97 vs. 67.78 ± 35.68, p< 0.05). These results indicate that QEP has potential of regulating intestinal flora and improving osteoporosis. The combination of anti-osteoporosis drugs and intestinal flora could become a new treatment for osteoporosis.


'Old wine in a new bottle': conceptualization of biodiversity offsets among environmental practitioners in Uganda.
Biodiversity offsets are increasingly adopted to mitigate the negative impacts of development activities on biodiversity. However, in practice, there are inconsistencies in how biodiversity offsets are understood and implemented. Based on interviews with environmental practitioners, the study sought to explore the conceptual understanding of biodiversity offsets among personnel involved in the design and implementation of offset schemes in Uganda. The study employed a 'technical use analysis' to seek personal interpretation and operationalization of the concept of biodiversity offsets. The results revealed that the concept tends to be simplified and adjusted to individual, project, and country contexts. The respondents had varied perceptions of biodiversity offsets in practice as compared to the theoretical concept. Biodiversity offsets were classified under five terms: trade-offs, payments, substitutes, compensations, and mitigation measures. The terms were derived from perceived inability of the measure to attain no net loss, and similarities of biodiversity components and services across impact and offset sites. Biodiversity offsets were thus considered no different from ordinary environmental conservation measures, contributing nothing unique to the conservation agenda. The study concludes that widespread implementation of biodiversity offsets under prevailing perceptions will escalate biodiversity loss. The study recommends emphasis on attaining no net loss through implementing outcome-based offsets as opposed to purpose-based offsets, that require delivering of 'no net loss' gains prior to projects being considered biodiversity offsets.


A new benzoylphloroglucinol derivative with an adamantyl skeleton and other constituents from Garcinia multiflora: effects on neutrophil pro-inflammatory responses.
A novel benzoylphloroglucinol derivative, garcimultiflorone D (1), with an unusual adamantyl-caged skeleton was isolated from the fruits of Garcinia multiflora, together with four known compounds. The structure of 1 was determined through extensive 1D/2D-NMR and mass-spectrometric analyses. Garcimultiflorone D (1) exhibited inhibitory activities with IC(50) values of 7.21±1.07 and 6.01±0.37 μg/ml against fMLP/CB-induced superoxide anion generation and elastase release, respectively.


Preliminary screening of the potential active ingredients in traditional Chinese medicines using the Ussing chamber model combined with HPLC-PDA-MS.
An in vitro intestinal absorption model combined with high-performance liquid chromatography-photo diode array-tandem mass spectrometry (HPLC-PDA-MS) was used for preliminary screening of potential active ingredients from complex multi-component traditional Chinese medicine (TCM) system. Oral administration is one of the main administration methods for TCMs. Only the ingredients that could be absorbed have the opportunity to play a role. Thus, these were defined as potential active ingredients. Studying of intestinal absorption can provide a theoretical basis for the mechanism of TCMs. The Caco-2 cell model, the everted rat gut sac model, and the Ussing chamber model were established for TCMs. The degree of anastomosis between the in vitro intestinal model and the actual intestinal absorption of TCMs were evaluated by the gavage method in rats. The Ussing chamber model was best fit for oral experiments in rats and was selected as the research means to preliminarily screen potential active ingredients from eight TCMs, including Salvia miltiorrhiza Bunge, Astragalus propinquus Schischkin, Plantago asiatica L, Fallopia multiflora (Thunb.) Harald, Epimedium brevicornu Maxim, Moutan Cortex, Citrus reticulata Blanco, and Panax notoginseng (Burkill) F. H. Chen ex C. H. Chow. A total of 44 components were absorbed and screened as the potential active ingredients from the 80 components identified in eight TCMs by HPLC-PDA-MS.


Late relapsing testicular cancer detected with 18F-FDG PET preceded by long-term alpha-fetoprotein elevation.
Late relapse (LR) of testicular cancer is often associated with chemoresistance, and thus the first choice of therapy is surgery if complete resection is possible. In some LR cases (including our patient, a 31-year-old Japanese man), elevation of alpha-fetoprotein (AFP) may precede the radiologic detection of LR. Approximately 500 days after the start of our patient's AFP elevation, 18F-fluordeoxyglucose positron emission tomography (FDG-PET) revealed strong FDG uptake in an equivocally enlarged external iliac lymph node. The lymphadenectomy as salvage surgery resulted in long-term complete remission without further treatment. Using FDG-PET made it possible to perform effective salvage surgery.


Protein engineering on enzymes of the peptide elongation cycle in Sulfolobus solfataricus.
The present article is a review of the work done on the elongation factors EF-1 alpha, EF-2 and EF-1 beta isolated from the hyperthermophilic archaeon Sulfolobus solfataricus. The molecular, physical and biochemical properties of the intact, truncated, mutant or chimeric forms are described and compared.


Histone deacetylase 3 is required for development and metamorphosis in the red flour beetle, Tribolium castaneum.
Hormones are chemical communication signaling molecules released into the body fluids to stimulate target cells of multicellular organisms. We recently showed that histone deacetylase 1 (HDAC1) plays an important role in juvenile hormone (JH) suppression of metamorphosis in the red flour beetle, Tribolium castaneum. Here, we investigated the function of another class I HDAC member, HDAC3, and show that it is required for the normal development of T. castaneum. RNA interference-mediated knockdown of the HDAC3 gene affected development resulting in abnormally folded wings in pupae and adults. JH analog, hydroprene, suppressed the expression of HDAC3 in T. castaneum larvae. The knockdown of HDAC3 during the final instar larval stage resulted in an increase in the expression of genes coding for proteins involved in JH action. Sequencing of RNA isolated from larvae injected with dsRNA targeting malE (E. coli gene, control) or HDAC3 followed by differential gene expression analysis identified 148 and 741 differentially expressed genes based on the P-value < 0.01 and four-fold difference, and the P-value < 0.05 and two-fold difference, respectively. Several genes, including those coding for myosin-I heavy chain (Myosin 22), Shaven, and nuclear receptor corepressor 1 were identified as differentially expressed genes in HDAC3 knockdown larvae. An increase in histone H3 acetylation, specifically H3K9, H3K18, and H3K27, was detected in HDAC3 knockdown insects. Overall, these data suggest that HDAC3 affects the acetylation levels of histones and influences the expression of genes coding for proteins involved in the regulation of growth, development, and metamorphosis.


Influence of subjective happiness on the prefrontal brain activity: an fNIRS study.
Focusing on the relationship between subjective happiness (SH) and emotional changes, we examined influences of SH on emotion-related prefrontal activity using multichannel NIRS. The International Affective Picture System (IAPS) was used to evoke emotional changes. Subjects were a total of 18 right-handed healthy students. Frequency of picture-induced increases in oxygenated haemoglobin (oxy-Hb) was evaluated. Subjects with a high SH score had a higher frequency of increased oxy-Hb in the left prefrontal cortex (PFC) while viewing pleasant pictures, whereas they showed a lower frequency in the right PFC while viewing unpleasant pictures. It is well known that the left PFC and right PFC are engaged in different ways in the emotional processes. Although further investigations are required, the present results indicate that the SH level influences the right-left differences in emotion-related prefrontal activity.


[Medication in infectious acute diarrhea in children].
Acute infectious diarrhea in children remain still a frequent cause of morbidity. 50 % of them are due to rotavirus. Oral rehydration therapy and early realimentation have drastically reduced their mortality and morbidity. Beside oral or eventually IV rehydration therapy no medication has proven its efficacy based on the main HMO criteria (reduction of over 30 % of the stool output) except racecadotril and loperamide which is contre-indicated for the last one in children less than 2 years old. Other medications such as silicates or some probiotics have shown efficacy on diarrhea duration or stool consistency but not on stool output. They have so no formal indication in infectious diarrhea and should be considered as "comfort" treatment. Antibiotics, beside their indication in shigella, cholera and amibiasis could be used in invasive diarrhea in some debilating conditions or infants less than 3 months.


Rectus sheath haematoma in elderly patients: a diagnostic challenge.
We report three cases of rectus sheath haematoma in elderly women. This condition is commonly misdiagnosed at any age but is an even more elusive diagnosis in elderly patients. It is important to consider rectus sheath haematoma in older patients with an abdominal or pelvic mass or spontaneous abdominal ecchymoses.


Myeloma immunoglobulin rearrangement and translocation detection through targeted capture sequencing.
Multiple myeloma is a plasma cell neoplasm characterized by clonal immunoglobulin V(D)J signatures and oncogenic immunoglobulin gene translocations. Additional subclonal genomic changes are acquired with myeloma progression and therapeutic selection. PCR-based methods to detect V(D)J rearrangements can have biases introduced by highly multiplexed reactions and primers undermined by somatic hypermutation, and are not readily extended to include mutation detection. Here, we report a hybrid-capture approach (CapIG-seq) targeting the 3' and 5' ends of the V and J segments of all immunoglobulin loci that enable the efficient detection of V(D)J rearrangements. We also included baits for oncogenic translocations and mutation detection. We demonstrate complete concordance with matched whole-genome sequencing and/or PCR clonotyping of 24 cell lines and report the clonal sequences for 41 uncharacterized cell lines. We also demonstrate the application to patient specimens, including 29 bone marrow and 39 cell-free DNA samples. CapIG-seq shows concordance between bone marrow and cfDNA blood samples (both contemporaneous and follow-up) with regard to the somatic variant, V(D)J, and translocation detection. CapIG-seq is a novel, efficient approach to examining genomic alterations in myeloma.


Differential intermittent radiation therapy: a conceptual model.
Cell membranes are made up of repeating units and subunits of various chemical moieties. It is proposed that these repeating units give each type of cell membrane a natural resonant frequency characteristic of that particular cell. It is further stipulated that this natural resonance is modified by attached antigens, and that this modification is unique to each different tumor type and patient. A signal that is of the same frequency as the natural resonance of the cell membrane may then be used to excite the cell membrane to its natural or modified resonant frequency and lyse it, as well as any metastases with the same characteristic. This resonant frequency must first be determined by growing tumor cells in culture, and is likely to be unique to each patient. Possible other uses of an excitatory signal may be to break apart chemical moieties. The only requirement is that this excitatory signal be matched to the resonant frequency of the cell wall or moiety to be lysed. The excitatory signal may come from various sources-sonic, electrical, x-ray, radio frequency, laser or nuclear. But the problem which must be solved is devising a method for determining the resonant frequencies of cell membranes.


Differentiating Adolescent Suicide Attempters and Ideators: A Classification Tree Analysis of Risk Behaviors.
Although many youth consider suicide, only a subset act on suicidal thoughts and attempt suicide. The objective of this study was to identify patterns of risk factors that differentiate adolescents who experienced suicidal thoughts from those who attempted suicide. This study analyzed data from the 2013, 2015, and 2017 National Youth Risk Behavior Surveys. Classification tree analysis was used to identify combinations of health risk behaviors and demographic factors that improved the identification of past-year suicide attempts among adolescents with past-year suicide ideation or planning (overall n = 7,493). Forty percent of the past-year ideators attempted suicide in the same period. The best-performing tree included three variables and defined four subgroups. Youth characterized by heroin use and past-year physical fights were at a strikingly high risk of being attempters (78%). Youth who had experienced rape were also likely to be attempters (58%), whereas those who had endorsed none of these three variables were relatively less likely to be attempters (29%). Overall, the tree's classification accuracy was modest (area under the curve = .65). This study advances previous research by identifying notable constellations of risk behaviors that accounted for adolescents' transition from suicidal ideation to behavior. However, even with many health risk behavior variables, a large sample, and a multidimensional analytic approach, the overall classification of suicide attempters among ideators was limited. Implications for future research are discussed.


Inter observer agreement in the assessment of the motor response of the Glasgow 'coma' scale.
The motor response of the Glasgow 'coma' scale is readily learned by nurses and doctors. It can be used as a reliable indicator of changes in the state of a comatose patient, as there is a high agreement rate between different observers.


Effect of carbonation on leachability, strength and microstructural characteristics of KMP binder stabilized Zn and Pb contaminated soils.
This study presents a systematic investigation of effects of carbonation on the contaminant leachability and unconfined compressive strength of KMP stabilized contaminated soils. A field soil spiked with Zn and Pb individually and together is stabilized using a new KMP additive under standard curing conditions and also with carbonation. The KMP additive is composed of oxalic acid-activated phosphate rock, monopotassium phosphate and reactive magnesia. The stabilized soils are tested for acid neutralization capacity, toxic characteristics leaching characteristics, contaminant speciation and unconfined compression strength. X-ray diffraction, scanning electron microscope and energy dispersive spectroscopy analyses are performed to assess reaction products. The results demonstrate that carbonation increases both acid buffer capacity index and unconfined compressive strength, but decreases leachability of KMP stabilized soils. These results are interpreted based on the changes in chemical speciation of Zn and Pb and also stability and solubility of the reaction products (metal phosphates and carbonates) formed in the soils. Overall, this study demonstrates that carbonation has positive effects on leachability and strength of the KMP stabilized soils.


The EspB protein of enterohaemorrhagic Escherichia coli interacts directly with alpha-catenin.
Enterohaemorrhagic Escherichia coli (EHEC) belongs to a family of pathogens that cause attaching and effacing (A/E) lesion on target cells. The EspB protein of EHEC is translocated both to the host cell cytoplasm and to the membrane, and is essential for the signalling events leading to A/E lesion. To determine the actual role of EspB in this process, we tried to identify the EspB binding partner of the host cell protein, using a yeast two-hybrid assay, and obtained a cytoskeletal-associated protein, alpha-catenin. The alpha-catenin bound directly to the N-terminal region of EspB, both in solid (overlay assay) and solution (pull-down assay) phases, and it was recruited to the EHEC adherence site, dependent on EspB. Expression of the N-terminal region of EspB, as well as the whole EspB in host cells, inhibited F-actin accumulation on the adherence site. We conclude that EspB recruits alpha-catenin at the EHEC adherence site by direct interaction, and that the recruitment of alpha-catenin is essential for EHEC-induced A/E lesion formation.


Mast cell restricted mouse and human tryptase·heparin complexes hinder thrombin-induced coagulation of plasma and the generation of fibrin by proteolytically destroying fibrinogen.
The mouse and human TPSB2 and TPSAB1 genes encode tetramer-forming tryptases stored in the secretory granules of mast cells (MCs) ionically bound to heparin-containing serglycin proteoglycans. In mice these genes encode mouse MC protease-6 (mMCP-6) and mMCP-7. The corresponding human genes encode a family of serine proteases that collectively are called hTryptase-β. We previously showed that the α chain of fibrinogen is a preferred substrate of mMCP-7. We now show that this plasma protein also is highly susceptible to degradation by hTryptase-β· and mMCP-6·heparin complexes and that Lys(575) is a preferred cleavage site in the protein α chain. Because cutaneous mouse MCs store substantial amounts of mMCP-6·heparin complexes in their secretory granules, the passive cutaneous anaphylaxis reaction was induced in the skin of mMCP-6(+)/mMCP-7(-) and mMCP-6(-)/mMCP-7(-) C57BL/6 mice. In support of the in vitro data, fibrin deposits were markedly increased in the skin of the double-deficient mice 6 h after IgE-sensitized animals were given the relevant antigen. Fibrinogen is a major constituent of the edema fluid that accumulates in tissues when MCs degranulate. Our discovery that mouse and human tetramer-forming tryptases destroy fibrinogen before this circulating protein can be converted to fibrin changes the paradigm of how MCs hinder fibrin deposition and blood coagulation internally. Because of the adverse consequences of fibrin deposits in tissues, our data explain why mice and humans lack a circulating protease inhibitor that rapidly inactivates MC tryptases and why mammals have two genes that encode tetramer-forming serine proteases that preferentially degrade fibrinogen.


Qualitative research and the question of rigor.
In this article, the authors discuss the issue of rigor in relation to qualitative social research. It takes a critical focus on the inadequacy of applying a quantitative concept of rigor to evaluate qualitative research. Informed through the researchers' own experience, suggestions are made for a concept of rigor that meets the needs of qualitative research more adequately. Incorporating a notion of ethics, the authors develop a cluster of terms around which they argue that qualitative research can meaningfully speak about rigor: attentiveness, empathy, carefulness, sensitivity, respect, reflection, conscientiousness, engagement, awareness, and openness.


Yeast chromosomal engineering to improve industrially-relevant phenotypes.
Genome structural variations enable microbes to evolve quickly under environmental stress. Recent efforts in synthetic biology have shown the ability of yeast chromosomal engineering to generate a larger scale of genome structural variations, which require a high efficiency of DNA rearrangement technology. In this review, we summarize the recent development of the SCRaMbLE system, an evolutionary approach, and the CRISPR/Cas9 technology to generate yeast genome rearrangement. Both technologies exhibit the powerful applications of chromosomal engineering to accelerate phenotypic evolution. We highlight several studies where yeast genome rearrangement has successfully improved industrially-relevant phenotypes, including the production of novel medicine, nutrition supplements, anti-tumor molecules, and the tolerance of environmental stress and drug resistance.


Add-on Protective Effect of Pentoxifylline in Advanced Chronic Kidney Disease Treated with Renin-Angiotensin-Aldosterone System Blockade - A Nationwide Database Analysis.
A combination therapy of pentoxifylline with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) decreased proteinuria or glomerular filtration rate decline in early chronic kidney disease (CKD). Whether adding pentoxifylline to ACEI/ARB provides additional benefits on outcome is unclear in CKD stage 5 patients who have not yet received dialysis (CKD 5 ND). A prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database. From January 1, 2000 to June 30, 2009, we enrolled 14,117 CKD 5 ND with serum creatinine levels >6 mg/dL and hematocrit levels <28% and who have been treated with ACEI/ARB. All patients were divided into pentoxifylline users and nonusers. Patient follow-up took place until dialysis, death before initiation of dialysis or December 31, 2009. Finally, 9,867 patients (69.9%) required long-term dialysis and 2,805 (19.9%) died before dialysis. After propensity score-matching, use of pentoxifylline was associated with a lower risk for long-term dialysis or death in ACEI/ARB users (HR, 0.94; 95% CI, 0.90-0.99) or ARB users (HR, 0.91; 95% CI, 0.85-0.97). In conclusion, pentoxifylline exhibited a protective effect in reducing the risk for the composite outcome of long-term dialysis or death in ACEI/ARB treated CKD 5 ND.


Biliary cystadenoma: Case report with MRI findings and surgical confirmation.
Biliary cystadenoma is a very uncommon benign cystic neoplasm involving the liver and the biliary tract. Most common presentations include right upper quadrant pain, nausea, vomiting, obstructive jaundice, and enlarging liver size. It can mimic many more commonly occurring diseases such as hepatic cyst, hepatic abscess, hydatid disease of the liver, and hepatic tuberculosis. Hence it becomes very challenging for physicians to correctly diagnose it due to its rarity and similarity with other conditions. Furthermore, very few pieces of literature guide physicians in correctly identifying the disease. Based on his physical examination and detailed investigation, we present a case report of a 72-year-old female diagnosed with biliary cystadenoma. We hope that this case report will significantly add to the existing literature on this subject.


Accelerated induction therapy and resection for poor prognosis stage III non-small cell lung cancer.
Induction therapy and resection may improve the survival of patients with poor prognosis stage III non-small cell lung cancer, at the cost of significant treatment prolongation. The purpose of this study was to assess toxicity, response, and survival of an accelerated induction regimen and resection in poor prognosis stage III non-small cell lung cancer. Forty-two surgically staged patients with poor prognosis stage III non-small cell lung cancer received 11 days of induction treatment consisting of 96 hours of continuous chemotherapy infusions of cisplatin (20 mg.m-2.day-2), 5 fluorouracil (1,000 mg.m-2.day-2), and etoposide (75 mg.m-2.day-2) concurrent with accelerated fractionation radiation therapy (1.5 Gy twice a day, to a dose of 27 Gy). Induction was followed in 4 weeks by resection. Postoperatively, a second course of continuous chemotherapy and concurrent accelerated fractionation radiation therapy (postoperative dose 13 to 36 Gy) was given. Despite some degree of induction toxicity in all patients there was only one induction death (2.4%). A clinical partial response was seen in 24 patients (57%). Thirty-six patients (86%) underwent thoracotomy, and resection was possible in 33 (79%). Pathologic downstaging was seen in 17 patients (40%), and 2 patients (5%) had no residual carcinoma at operation. There were 11 postoperative complications (31%) and 4 postoperative deaths (11%). Thirteen patients (31%) are alive and disease-free, 24 (57%) have persistent disease or have recurred (15 distant, 5 locoregional, 4 both), and 9 patients are alive with disease. The median survival is 21 months and the 2-year Kaplan-Meier survival is 43%, with no differences identified between stages IIIA and IIIB patients (p = 0.63). We conclude that accelerated induction therapy and resection in poor prognosis stage III non-small cell lung cancer (1) is toxic, with a 12% treatment mortality; (2) is effective with a 79% resection rate and 40% pathologic downstaging rate; (3) provides excellent local control; (4) may prolong survival; and (5) is of value in stage IIIB as well as stage IIIA patients.


Neuromuscular patterns of stereotypic hindlimb behaviors in the first two postnatal months. III. Scratching and the paw-shake response in kittens.
Neuromuscular patterns of scratching and the paw-shake response were studied in normal kittens from birth to postnatal day 60. Onset of both behaviors coincided with the development of secure weight-bearing posture and occurred on postnatal day 21 for scratching and postnatal day 26 for paw shaking. At onset, cycle periods for scratching (5-6 Hz) and paw shaking (8-10 Hz) were similar to that for adult cats, and EMG patterns were adult-like. The scratch cycle consisted of reciprocal flexor and extensor bursts of equal duration, while the shake cycle consisted of coactive knee extensor and ankle flexor bursts alternately active with ankle extensor bursts. The lack of scratching and paw shaking during the first 3 postnatal weeks and the adult-like EMG patterns at onset are consistent with the hypothesis that pattern-generating circuits within lumbosacral segments are available early in development but inhibited by the rostral neuraxis until postural control is sufficient to accommodate the response. To eliminate rostral inputs, including descending input critical for postural control, kittens were spinalized at the T12 level, and onset of paw shaking was accelerated. In kittens spinalized at birth, paw-shake onset occurred on postnatal day 14, while in kittens spinalized on postnatal day 14, onset occurred 48 h after spinalization. In all spinal kittens, however, knee extensor activity was disrupted and not normal by postnatal day 60. Mature neuromuscular patterns for scratching and paw shaking are available at onset of the behavior during normal development. Spinalization hastens the onset of paw shaking but the normal neuromuscular synergy is disrupted as well as the temporal structure of the multi-cycle response. Disruptions following spinalization may be due to altered development of spinal pattern generators or aberrant feedback from atypical hindlimb motions due to a retardation of hindlimb growth and an alteration of muscle contractile properties in spinal kittens.


Posterior kV-CBCT scanning of the head and neck region minimizes doses to critical organs with sustained image quality.
We evaluated the absorbed dose to critical organs, as well as the image quality, at different partial angles in kV-CBCT (Cone Beam Computed Tomography) scanning of the head and neck region. CBCT images of phantom from a 200° rotation were performed by using three different scanning paths, anterior, posterior, and right lateral with Catphan504 and RANDO phantoms. Critical organ dose was measured using TLD 100H in the RANDO phantom. The image quality of those phantoms was evaluated, using HU uniformity, HU linearity, contrast-to-noise ratio, low contrast visibility and spatial resolution with the Catphan504 dataset; and 5-point grading scales for the RANDO phantom dataset by five radiation oncologists. The image qualities from Catphan504 and RANDO phantom of every scanning path were comparable, with no statistically significant difference (p ≥ 0.05). However, there was a significant difference in the critical organ dose in all paths (p < 0.05), depending on the critical organ location and the scanning direction. Scanning directions show no effects on the image quality. Differences in absorbed dose to critical organs should were evaluated. The posterior scanning path for the CBCT was deemed preferable due because of considerably lower doses to several critical organs of the head and neck region.


Chemical Strategies of the Beetle Metoecus Paradoxus, Social Parasite of the Wasp Vespula Vulgaris.
The parasitoid beetle Metoecus paradoxus frequently parasitizes colonies of the common wasp, Vespula vulgaris. It penetrates a host colony as a larva that attaches itself onto a foraging wasp's body and, once inside the nest, it feeds on a wasp larva inside a brood cell and then pupates. Avoiding detection by the wasp host is crucial when the beetle emerges. Here, we tested whether adult M. paradoxus beetles avoid detection by mimicking the cuticular hydrocarbon profile of their host. The beetles appear to be chemically adapted to their main host species, the common wasp, because they share more hydrocarbon compounds with it than they do with the related German wasp, V. germanica. In addition, aggression tests showed that adult beetles were attacked less by common wasp workers than by German wasp workers. Our results further indicated that the host-specific compounds were, at least partially, produced through recycling of the prey's hydrocarbons, and were not acquired through contact with the adult host. Moreover, the chemical profile of the beetles shows overproduction of the wasp queen pheromone, nonacosane (n-C29), suggesting that beetles might mimic the queen's pheromonal bouquet.


Clonal frequency analysis of B cells producing pathogenic anti-DNA antibody-associated idiotypes in systemic lupus erythematosus.
In order to identify the mechanism responsible for autoantibody production in systemic lupus erythematosus (SLE), B cell repertoires associated with anti-DNA idiotypes were explored by a limiting dilution analysis using Epstein-Barr virus (EBV) transformation methods and ELISA spot assays. The frequencies of B cell clones producing antibodies to DNA and to conventional antigens, tetanus toxoid, dinitrophenyl, or keyhole limpet hemocyanin were higher in active SLE compared to those in inactive SLE and in normal subjects. In addition, there was a disproportionate increase in anti-DNA antibody- and anti-DNA idiotype (Id)-producing clones at the precursor cell levels as well as at the mature cell level. On the other hand, numbers of anti-Id clones against anti-DNA-Id, termed 0-81 Id, were markedly increased at inactive stages of the disease but not at active stages. These were confirmed by serial studies in some patients with SLE. These results support a two-step mechanism for autoantibody production, in which initial polyclonal activation is followed by an antigen-driven process, and indicate an alteration of the precursor B cell repertoire in SLE, which may also associate with a preferential expansion of anti-DNA clones.


Jumping translocation of 15q24-qter resulting in partial trisomy: a case report.
We report on a jumping translocation with five different cell lines detected in four tissues in a 2-year-old patient. This rare type of chromosomal abnormality (not more than 30 cases published so far) proved to be a series of non-reciprocal translocations of the 15q24-qter donor chromosome segment to the telomeric region of chromosomes 5q, 10q, 16q and 19p, respectively. The process, in addition to a few cells without translocation, resulted in partial trisomy of 15q24-qter which was associated with somatic overdevelopment in the patient, with hemihypertrophy and minor anomalies. The phenotype of our patient was different from that of the other two patients found in the literature having the same donor chromosome segment involved in a similar rearrangement. Possibly, the difference in the phenotype lies in the various ratios of somatic mosaicism with five cell lines, in particular the presence of normal one which is extremely rare in patients with jumping translocation. Here we discuss the various ways on how the rearrangement could arise.


Editorial: Endoscopic Scoring Systems in Crohn's Disease for Evaluation of Responsiveness to Treatment: Are we Ready for the Prime Time of Endoscopic Assessment?
There are currently two validated endoscopic indices for evaluation of Crohn's disease (CD), the Crohn's disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn's disease (SES-CD). The study by Khanna et al. evaluated the responsiveness of the SES-CD and CDEIS using data from a trial of adalimumab. The study used appropriate statistical methods to quantify responsiveness of the indices as assessed by blinded central readers. The SES-CD demonstrated numerically greater responsiveness to a treatment of known efficacy, suggestive that the SES-CD is more efficient outcome measure than the CDEIS. Removal of stenosis as an index item and adjusting for observed segments did not improve responsiveness. In the future, the implementation of the SES-CD into daily clinical practice may become a practical tool used by gastroenterologists when caring for patients with Crohn's disease. Further studies analyzing the responsiveness of the indices in combination with clinical and patients' driven outcomes are expected prior to the indices' use in "prime time".


The effects of methyl tert-butyl ether (MTBE) on the male rat reproductive system.
Methyl tert-butyl ether (MTBE) is an oxygenated compound, which has been widely used in Asia, Europe and North America. Although numerous in vitro and in vivo studies have demonstrated the carcinogenicity and the toxicity of MTBE, there is still a lack of data on reproductive system exposure of MTBE in male rodent animals. We studied subacute exposure of MTBE on the reproductive systems of male Sprague-Dawley rats. MTBE was administered to rats at dose levels of 0, 400, 800 and 1600 mg/kg/day. After 2 or 4 weeks of treatments, the rats were euthanized, and their serum, epididymis and testes were collected. Significant adverse effects in their reproductive system were observed including: a significant increase in the percentage of abnormal sperm; an irregular and disordered arrangement of the seminiferous epithelium indicated by a histopathological examination; changed serum levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH); and decreased levels of mRNA and of androgen binding protein (ABP). In the oxidative stress study, results indicated an increased maleic dialdehyde (MDA) content, implying a raised peroxide level, and that the total antioxidant ability in serum was significantly increased. This finding was especially strong at 1600 mg/kg/day MTBE. In the 2-week treatment, at 1600 mg/kg/day, the mRNA level of 8-oxoguanine DNA glycosidase (OGG1) was significantly decreased, and the mRNA level of the extra-cellular form of superoxide dismutase (SOD(EX)) was significantly increased. Our experiments suggest that relatively high doses of MTBE can exert reproductive system toxicity of male rats and disturb the secretions of T, LH and FSH, possibly due to oxidative stress induced by MTBE.


Immunohistochemical localization of tonin in rat salivary glands and kidney.
Tonin has been localized in salivary glands and kidney by the indirect immunofluorescence technique of Coons and by the unlabeled antibody technique of Sternberger. Both techniques gave identical results. Immunoreactive tonin was localized in the cytoplasm of granular convoluted tubular cells and on the apical surface of striated duct cells and collecting duct cells of the submandibular gland. In the parotid and sublingual glands, which lack granular cells, tonin was only found on the apical surface of striated duct and collecting duct cells. In the kidney, immunoreactive tonin was found only associated with cells of the distal convoluted tubules. After fixation with Bouin fluid or with ethanol, tonin was found not only on the apical surface of the cells but also in the apical and perinuclear cytoplasm. This cytoplasmic staining has been attributed to artefactual diffusion since, after fixation with formol-picric acid, the enzyme could only be localized on the apical surface of the tubular cells.


New substituted tetrathiafulvalene-quinone dyads: the influences of electron accepting abilities of quinone units on the metal ion-promoted electron-transfer processes.
The metal ion-promoted electron transfer occurs to all new dyads 1, 2, 3, and 4, even one of them, dyad 4, which has a rather weak electron acceptor unit. The results also indicate that the metal ion-promoted electron transfer within the dyads is influenced by the electron accepting abilities of quinone units; dyad 2 with the strongest electron acceptor among the four dyads shows the strongest absorption and ESR signals attributed to TTF.+ in the presence of metal ions.


Examining perceived effects of same-sex marriage legalization among sexual minority women: Identifying demographic differences and factors related to alcohol use disorder, depression, and self-perceived health.
Reductions in structural stigma, such as gaining access to legalized same-sex marriage, is associated with positive psychological and physical health outcomes among sexual minorities. However, these positive outcomes may be less robust among sexual minority women (SMW). This study examined how perceptions of the impact of legalized same-sex marriage among SMW may 1) differ by demographic characteristics and 2) predict alcohol use disorder, depression, and self-perceived health. A diverse sample of SMW (N=446) completed an online survey in 2020 assessing the perceived impact of legalized same-sex marriage across six social-ecological domains: 1) personal impact, 2) stigma-related concerns, 3) couple impact, 4) family support, 5) work/school impact, and 6) local social climate towards LGBTQ people. Perceived impact across multiple domains differed by relationship status and sexual identity (e.g., lesbian compared to bisexual identity); only family support differed by race/ethnicity. Stigma-related concerns (e.g., experiencing or witnessing hostility or discrimination because of sexual identity, despite legalized same-sex marriage) were associated with greater odds of depression and lower odds of reporting excellent, very good, or good health. Odds of depression were lower among participants who reported higher personal impact, a greater number of family members supportive of same-sex marriage, and a more positive local social climate. Family support also predicted self-perceived health. However, participants who perceived increased support in work/school contexts after legalized same-sex marriage had higher odds of alcohol use disorder. Overall, findings underscore the importance of policy in improving health outcomes through reducing stigma-related concerns and improving social acceptance.


Role of raf proteins in cardiac hypertrophy and cardiomyocyte survival.
Cardiomyocyte survival and growth are regulated by the action of extracellular ligands that activate intracellular signaling cascades. The Raf family of protein serine/threonine kinases plays a critical role in the regulation of cardiomyocyte survival and growth. The three Raf family members, Raf-1, B-Raf, and A-Raf, are highly homologous, and they are all expressed in the heart. Protein kinases of the Raf family phosphorylate and activate the mitogen-activated protein kinase kinases (MKKs, also known as MEKs). MKKs, in turn, are dual-specificity threonine and tyrosine kinases that phosphorylate and activate extracellular signal-regulated kinases (ERKs). ERKs phosphorylate a variety of substrates, including nuclear transcription factors, which regulate cell physiology. Raf proteins also have antiapoptotic activity that is independent of MKK and ERK. In this review, the role of Raf family members in the regulation of cardiomyocyte survival and growth will be discussed.


Analysis of completed reproductive histories: a cautionary tale.
Recent authors have suggested that cross-sectional studies of adverse outcome of pregnancy are misleading, and that the only valid method of analysis controls for eventual number of pregnancies. The present study shows, by simple examples, that such a method produces results that cannot be interpreted in the way claimed for them.


The targeted delivery of the c-Src peptide complexed with schizophyllan to macrophages inhibits polymicrobial sepsis and ulcerative colitis in mice.
Hyper-inflammatory responses triggered by intracellular reactive oxygen species (ROS) can lead to a variety of diseases, including sepsis and colitis. However, the regulators of this process remain poorly defined. In this study, we demonstrate that c-Src is a negative regulator of cellular ROS generation through its binding to p47phox. This molecule also competitively inhibits the NADPH oxidase complex (NOX) assembly. Furthermore, we developed the schizophyllan (SPG)-c-Src SH3 peptide, which is a β-1,3-glucan conjugated c-Src SH3-derived peptide composed of amino acids 91-108 and 121-140 of c-Src. The SPG-SH3 peptide has a significant therapeutic effect on mouse ROS-mediated inflammatory disease models, cecal-ligation-puncture-induced sepsis, and dextran sodium sulfate-induced colitis. It does so by inhibiting the NOX subunit assembly and proinflammatory mediator production. Therefore, the SPG-SH3 peptide is a potential therapeutic agent for ROS-associated lethal inflammatory diseases. Our findings provide clues for the development of new peptide-base drugs that will target p47phox.


Hypofractionated accelerated radiotherapy with cytoprotection combined with trastuzumab, liposomal doxorubicine, and docetaxel in c-erbB-2-positive breast cancer.
Trastuzumab, an antic-erbB-2 monoclonal antibody, has become a standard component of chemotherapy for c-erbB-2-positive advanced breast carcinoma. Despite the experimental evidence of its radiosensitizing properties, trastuzumab has never been used in combination with radiotherapy for the treatment of patients with locally advanced disease. Twenty-two patients with c-erbB-2-positive locally advanced chemoresistant (7 patients) or with high-risk breast cancer (15 patients) were recruited in a treatment protocol combining hypofractionated/accelerated radiotherapy (hypoARC) supported with high-dose amifostine (1000 mg subcutaneous), concurrently with trastuzumab (4 mg/kg every 2 weeks). Thirteen of these patients (including all 7 inoperable cases) received concurrently chemotherapy with liposomal doxorubicin and docetaxel (25 mg/m2 and 40 mg/m2 every 2 weeks, respectively). Administration of trastuzumab together with highly accelerated amifostine-supported radiotherapy was feasible without an increase in early and late radiation toxicity. This was obtained despite the concurrent administration of aggressive chemotherapy. Complete responses were noted in 5 of 7 patients with locally, often far advanced, chemoresistant disease. None of the complete responders or the 15 high-risk breast cancer patients relapsed within the 3- to 26-month follow-up period. Inclusion of trastuzumab in the radiochemotherapy protocols for breast cancer does not increase radiation or systemic toxicity. The concurrent administration of aggressive radiotherapy with docetaxel and liposomal doxorubicin is feasible when supported with amifostine. The value of such regimens in the treatment of locally advanced or high risk c-erbB-2 positive breast cancer patients deserves further evaluation.


Does methyl jasmonate modify the oxidative stress response in Phaseolus coccineus treated with Cu?
The contribution of methyl jasmonate (MJ) as a signal molecule able to take part in the defense mechanism against copper (Cu)-imposed oxidative stress was studied in the leaves and roots of runner bean (Phaseolus coccineus) plants. Roots of plants cultivated hydroponically were preincubated in MJ (10µM) for 1h or 24h and subsequently exposed to Cu (50µM) for 5h (short-term experiment) or 5 days (long-term experiment). Enzymatic (activity of superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX; guaiacol peroxidase, POX) and non-enzymatic (accumulation of malondialdehyde, MDA; homoglutathione, hGSH; proline; anthocyanins; low molecular weight organic acids, LMWOAs) responses were determined in the leaves and roots. The antioxidative defense mechanism was significantly activated after Cu supplementation. In most cases, activities of ROS (reactive oxygen species) scavenging enzymes like SOD, CAT, APX, POX, as well as MDA, hGSH and proline concentrations increased following Cu exposure. MJ showed a time-dependent effect on antioxidative enzymes activity. In the short-term experiment, MJ elevated CAT, APX and POX activities in the roots, and POX activity in the leaves of non-Cu-treated plants. In the long-term experiment, MJ not only decreased POX and partially CAT activity in the roots, but also increased the MDA level and partially CAT activity in the leaves of the control plants. In Cu-treated plants, MJ reduced APX, but elevated POX activity in the leaves after 5-h exposure. After 5-day-Cu treatment, MJ inhibited POX activity in the leaves and mainly reduced SOD and CAT activities in the roots. Moreover, in the long-term experiment, MJ reduced tartrate and pyruvate in the leaves of Cu-stressed plants, but mostly elevated tartrate and malate in the roots comparing with Cu alone treatment. MJ alone and under Cu excess did not alter accumulation of MDA, hGSH and proline comparing with Cu alone, but partially elevated anthocyanin concentration. The results indicated that MJ was both partially potent in modifying the antioxidative enzymes activity and metabolites accumulation in non-stress and Cu-stress conditions.


Theoretical and experimental spectroscopic studies and analysis for wave function on N-phenylmorpholine-4-carboxamide benzene-1,2-diamine with computational techniques.
The present study focuses on structural and chemical analyses of N-phenylmorpholine-4-carboxamide benzene-1,2-diamine (PMCBD) using quantum computational methods. The calculated bond angle, length, and dihedral angle between atoms were compared with measured values. The observed and stimulated FT-IR (Fourier Transform Infrared Spectroscopy) spectra parameters for vibrational wavenumbers and their associated PED (Potential Energy Distribution) values in percentage have been obtained from VEDA4 software. The electronic transitions of PMCBD were discussed by TD-SCF/DFT/B3LYP based on the 6-311++G(d,p) basis set with solvents such as chloroform, ethanol, and dimethyl sulfoxide (DMSO) and gas. Density functional computations were used to study the band energy between HOMO and LUMO using the B3LYP/6-311++G(d,p) level. Mulliken analysis and natural population analysis were used for a better understanding of charge levels on different atoms such as N, H and O. The natural bonding orbital (NBO) analysis proved helpful in studying molecular and bond strengths. (NBO). The ESP acquired data on the molecule's size, shape, charge density distribution, and chemical reactivity site. This was done by mapping electron density on the surface with electrostatic potential. Non-linear optical detection of PMCBD was also discussed. Aside from the electron localization function map, state densities are also mapped using Multiwfn software, a wave function analyzer.


Which is the most ergonomic mop? A comparison of three domestic mopping systems.
To assess musculoskeletal risk factors (repetitions, posture, forces) of the upper limb during domestic floor mopping tasks. Two hundred women were surveyed to determine the most common mopping system, mopping patterns and type of flooring used in their homes. The biomechanical demands of the three most common mopping systems were then evaluated in the laboratory. Participants were also asked to rate their perceived levels of exertion and cleanliness of each mopping system. The use of wet wipes had the highest repetition count and exertion rates during mopping and scrubbing tasks. Higher peak scrubbing forces were noted for the plunge mop. All participants found the cotton fibre mop to be the cleanest. All 3 mops had medium postural risk. The advantages and disadvantages of each mopping system were outlined and may be used by occupational therapists when providing ergonomic advice to patients with upper limb musculoskeletal conditions.


The impact of a nationwide effort to reduce airbag-related deaths among children: an examination of fatality trends among younger and older age groups.
The purpose of this study was to examine the impact of a nationwide response to emerging airbag-related deaths among children. This response, implemented in 1996, focused on moving children to a rear seat and increasing proper restraint usage. Fatality trends from 1992 through 1996 and from 1996 through 2003 were examined for younger children (ages 0-3) and for older children (ages 4-12). Prior to 1997, a steady reduction in unrestrained deaths (among younger children) was offset by increases in restrained deaths (among younger and older children), increases in rear-seat deaths (among younger children), and increases in front-seat deaths (among older children). After 1996, there were significant decreases in fatalities in both age groups, with larger and more immediate reductions among the younger children. The largest reductions were immediately after 1996, when younger-child deaths declined by 16%, and after 1999, when deaths among both age groups declined by about 16%. The immediate reduction in front-seat deaths among younger children, particularly infants, appears to have been closely associated with the nationwide public information efforts implemented in 1996. Later reductions in front-seat and unrestrained deaths, among both younger and older children, were likely associated with the combination of legislative, enforcement, and public information programs, which increased after 1999. The findings suggest that a large expenditure of resources by public and private-sector organizations after 1996 resulted in the prevention of hundreds of deaths among young children. In addition, the results provide insights with regard to the categories of deaths most affected by such programs and issues that deserve additional attention.


TGFβ1 mimetic peptide modulates immune response to grass pollen allergens in mice.
Transforming growth factor β1 (TGFβ1) is a cytokine that exerts immunosuppressive functions, as reflected by its ability to induce regulatory T (Treg) cell differentiation and inhibit Th1 and Th2 responses. Hence, peptides that mimic the active core domain of TGFβ1 may be promising candidates for modulation of the allergic response. This study aimed to investigate a synthetic TGFβ1 mimetic peptide (TGFβ1-mim) for its ability to modulate the immune response during allergic sensitization to grass pollen allergens. The in vitro action of TGFβ1-mim was evaluated in human lung epithelial cells, Jurkat cells, and rat basophilic leukemia cells. The in vivo action was evaluated in a murine model of Phl p 5 allergic sensitization. Additionally, the Th2 modulatory response was evaluated in IL-4 reporter mice. In vitro, TGFβ1-mim downregulated TNF-α production, IL-8 gene expression, and cytokine secretion, upregulated IL-10 secretion, and inhibited Phl p 5-induced basophil degranulation. During Phl p 5 sensitization in mice, TGFβ1-mim downregulated IL-2, IL-4, IL-5, IL-13, and IFN-γ, upregulated IL-10, and induced Treg cell production. Furthermore, mice treated with TGFβ1-mim had lower levels of IgE, IgG1, IgG2a and higher levels of IgA antibodies than control mice. In a reporter mouse, the mimetic inhibited Th2 polarization. The TGFβ1-mim efficiently modulated various important events that exacerbate the allergic microenvironment, including the production of main cytokines that promote Th1 and Th2 differentiation, and the induction of allergen-specific regulatory T cells, highlighting its potential use in therapeutic approaches to modulate the immune response toward environmental allergens.


Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125.
Malignant ascites is a common clinical problem in ovarian cancer. NK cells are present in the ascites, but their antitumor activity is inhibited. The underlying mechanisms of the inhibition have yet to be fully elucidated. Using an Fcγ receptor-mediated NK cell activation assay, we show that ascites from ovarian cancer patients potently inhibits NK cell activation. Part of the inhibitory activity is mediated by CA125, a mucin 16 fragment shed from ovarian cancer tumors. Moreover, transcriptional analyses by RNA sequencing reveal upregulation of genes involved in multiple metabolic pathways but downregulation of genes involved in cytotoxicity and signaling pathways in NK cells purified from ovarian cancer patient ascites. Transcription of genes involved in cytotoxicity pathways are also downregulated in NK cells from healthy donors after in vitro treatment with ascites or with a CA125-enriched protein fraction. These results show that ascites and CA125 inhibit antitumor activity of NK cells at transcriptional levels by suppressing expression of genes involved in NK cell activation and cytotoxicity. Our findings shed light on the molecular mechanisms by which ascites inhibits the activity of NK cells and suggest possible approaches to reactivate NK cells for ovarian cancer immunotherapy.


Primary IgG4-related lymphadenopathy with prominent granulomatous inflammation and reactivation of Epstein-Barr virus.
We report a unique case of primary IgG4-related lymphadenopathy showing prominent granulomatous inflammation and Epstein-Barr virus (EBV) reactivation. Involved lymph nodes showed an expanded interfollicular zone with prominent granulomatous inflammation, including a predominance of epithelioid macrophages and occasional Langhans multinucleated giant cells. Bundles of spindle cells were also observed. Intermingled with the granulomatous inflammation were numerous mature plasma cells, eosinophils, and neutrophils. The percentage of IgG4+/IgG+ plasma cells was markedly elevated (70%), along with raised serum IgG4 levels. The plasma cells did not show immunoglobulin light-chain restriction. EBV-positive lymphocytes were scattered throughout the paracortical areas. Corticosteroid treatment was very effective. IgG4-related lymphadenopathy has a broad histological spectrum and might be misdiagnosed due to other conditions which morphologically closely resemble it. The correct diagnosis is important in view of the remarkable response to steroid therapy.


Fertility decision-making during the Zika virus epidemic in Brazil: Where is the decision?
In 2016, a Public Health Emergency of International Concern (PHEIC) was declared in response to the rise of microcephaly cases among newborns in Northeastern Brazil. A common reactionary measure by public health authorities was to recommend women postpone pregnancy to avoid the possible perinatal transmission of Zika virus (ZIKV). The purpose of this study was to assess how women in Fortaleza, Brazil conceptualize pregnancy; experience facilitators and barriers to pregnancy avoidance; perceive the authorities' recommendation to postpone pregnancy due to the ZIKV outbreak; and recall their experiences during the ZIKV epidemic. Qualitative methods, specifically a Rapid Anthropological Assessment (RAA), were utilized in this study. Data collection included semi-structured interviews, triangulated with observations and informal interviews with community members. The sample included 35 women (18-39 years old) who exclusively utilized the national public health care system. Findings indicated that all participants perceived the ZIKV pregnancy-postponement recommendation to be counter-cultural to Brazilian social norms. Overall women's self-perceived agency to prevent pregnancy was low due to social expectations and lack of trust for contraceptives. ZIKV prevention was not seen as a reason to utilize contraceptives. Interestingly, only women who self-perceived as more affluent were willing to attempt pregnancy prevention for educational, occupational, or financial opportunity. Pregnancy postponement as a response to a ZIKV epidemic ignores gaps in reproductive agency and defies social norms, making it unrealistic and counter-cultural. Future ZIKV health recommendations must be culturally aligned with the population, and address barriers and motivators for family planning.


A case of spontaneous thoracolumbar epidural hematoma in Covid-19 pneumonia.
Covid-19 is an important disease that still occupies our agenda, and as time passes, we have been observing its extrapulmonary manifestations. In this study, we presented a case of spontaneous thoracolumbar epidural hematoma, which we could not attribute to any cause other than Covid-19. We presented a 55-year-old female patient whose etiology could not be found to be compatible with the literature. In the formation of this disease, we did not have any positive findings except for Covid-19, which she had 20 days ago. The patient had no history of anticoagulant or antiaggregant drug use. He had no history of trauma and no signs. Hematological tests were normal. We evacuated the hematoma in the T12-L1 vertebral canal after laminectomy and the pathology result was compatible with hematoma. Although spontaneous spinal epidural hematoma is rare, many factors are blamed for its etiology. Many extrapulmonary complications of Covid-19 stand out in the literature. The fact that the patient had Covid-19 did not affect the neurosurgical approach, but we think that it is useful to examine the complaints of patients with Covid-19 more systematically. Spontaneous spinal epidural hematomas are rare. Making the correct diagnosis often takes time and is difficult. Decompression surgery is at the forefront as a treatment option. However, conservative treatment can be performed in suitable patients. As we saw in this case, we should consider Covid-19 among the etiological causes.


Methods and clinical significance of studying chemical drives.
Studying chemical control of ventilation implies evaluation of both chemoreceptor functions taken into account however the mechanical factors influencing the effector organs. The role of abnormal chemical drives has been demonstrated in COPD patients. More recently the role of abnormal chemical drives was studied during sleep. Absent or severely depressed drives may facilitate the development of central apneas and hypoventilation. High drives may lead to periodic breathing eventually with central apneas as well. Most intriguing therefore is the role of chemical drives in the pathogenesis of the obstructive and central sleep apnea syndrome. There is accumulating evidence that fluctuations in the drive to breathe may adversely affect the upper airway patency and facilitate upper airway closure and obstructive apneas. Interaction with chemical drives (eg by administration of acetazolamide) has been shown to improve central (and eventually also obstructive) sleep apnea. Studying chemical drives will probably be clinically useful in solving the complex mechanisms controlling ventilation during sleep in patients with and without underlying airway or lung disease.


A two-motif isoform of the major calcium channel subunit in skeletal muscle.
Evidence is presented that two isoforms of the voltage-dependent, dihydropyridine-sensitive calcium channel alpha 1 subunit are present in newborn and adult skeletal muscle and that expression of these isoforms is developmentally regulated. A voltage-dependent calcium channel alpha 1 cDNA from newborn muscle was cloned and found to be identical to that published from the adult, except that it was 2 kb shorter owing to an internal deletion. Nucleotide sequences, Northern blots, reverse-transcriptase PCR experiments, and sequencing of the PCR product confirmed that a segment corresponding to the inner two repeats of the structural prototype four homologous motifs is missing from the immature isoform. Immunological studies using antisera raised against synthetic peptides that correspond to sequences in the two isoforms show that the abbreviated transcript is predominant in newborn muscle, whereas the four-repeat isoform is the major species in the adult.


Cytology interpretation after a change to HPV testing in primary cervical screening: Observational study from the English pilot.
Overcalling of abnormalities has been a concern for using cytology triage after positive high-risk human papillomavirus (HPV) tests in cervical screening. The authors studied the detection of cytological and histological abnormalities at age 24 to 64 years, using data from the English HPV pilot. The pilot compared routine implementation of primary cervical screening based on cytology (N = 931,539), where HPV test results were not available before cytology reporting, with that based on HPV testing (N = 403,269), where cytology was only required after positive HPV tests. Revealed HPV positivity was associated with a higher direct referral to colposcopy after any abnormality (adjusted odds ratio [ORadj ], 1.16; 95% confidence interval [CI], 1.14-1.18). Laboratories with higher direct referral referred fewer persistently HPV-positive women after early recall. The detection of high-grade cervical intraepithelial neoplasia (CIN2+) after direct referral increased with an ORadj of 1.17 (95% CI, 1.13-1.20) for informed versus uninformed cytology. Generally, the positive predictive value (PPV) of colposcopy for CIN2+ remained comparable under both conditions of interpreting cytology. In women 50 to 64 years old with high-grade dyskaryosis, however, the PPV increased from 71% to 83% after revealing HPV positivity (ORadj , 2.05; 95% CI, 1.43-2.93). Quality-controlled cervical screening programs can avoid inappropriate overgrading of HPV-positive cytology.


TGF-β1 Neutralization Improves Pregnancy Outcomes by Restoring Endometrial Receptivity in Mice with Adenomyosis.
The objective of this research is to study the effects of TGF-β1 inhibition on endometrial receptivity and pregnancy outcomes in mice with adenomyosis. Experiments were done using a mouse model of adenomyosis which took place in a hospital-affiliated laboratory. The mouse model used for this research is ICR mouse. Adenomyosis was induced by oral gavage of tamoxifen (TAM) from postnatal days (PNDs) 1 to 4 in ICR mice. Bilateral intrauterine injection of anti-TGF-β1-neutralizing antibody or isotype IgG or PBS was performed at PND42. The mice were then either sacrificed or mated at PND64 followed by sacrificing at gestational day (GD) 4 or proceeding to delivery. Implantation numbers, rate of dams with live birth, live birth numbers, survival at 1 week old, and pup mortality rate after weaning were recorded. Collagen was demonstrated by Masson's trichrome and Van Gieson's stains. Uterine expression of a receptivity marker, leukemia inhibitory factor (LIF), was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry (IHC). Anti-TGF-β1 treatment increased the mean implantation numbers, fecundity rate, the rate of dams with live birth, pup survival rate at 1 week old, and pup mortality rate after weaning. Collagen expression in uteri with adenomyosis was attenuated by anti-TGF-β1 treatment. Increased LIF expression by anti-TGF-β1 treatment was detected by qRT-PCR, Western blot, and IHC. The results suggest that inhibition of TGF-β1 improves pregnancy outcomes by restoring endometrial receptivity in mice with adenomyosis.


Association between inhaled nitric oxide treatment and long-term pulmonary function in survivors of acute respiratory distress syndrome.
Assessment of treatments for acute respiratory distress syndrome (ARDS) has focused on short-term outcomes (for example, mortality); little information exists regarding long-term effects of ARDS treatment. Survivors of ARDS episodes may have long-term obstructive/restrictive pulmonary abnormalities and pulmonary gas exchange impairment. A 2004 prospective randomized placebo-controlled trial assessed the efficacy and safety of inhaled nitric oxide (iNO) in patients with non-septic ARDS; the primary endpoint was days alive and off assisted breathing. This analysis examined potential effects of iNO or placebo on pulmonary function six months post-treatment in ARDS survivors from that original study. ARDS survivors (N = 92) from a large-scale randomized, placebo-controlled study evaluating mortality after either 5 ppm iNO or placebo for up to 28 days were assessed six months post-treatment. Pulmonary function testing across seven parameters was conducted. At 6 months post-treatment, results indicated significantly better absolute values for iNO versus placebo for mean ± SD total lung capacity (TLC, 5.54 ± 1.42 vs. 4.81 ± 1.00; P = 0.026). There were also significantly better values for mean ± SD percent predicted values for a) forced expiratory volume in 1 second (FEV1, 80.23 ± 21.21 vs. 69.51 ± 28.97; P = 0.042), b) forced vital capacity (FVC, 83.78 ± 19.37 vs. 69.84 ± 27.40; P = 0.019), c) FEV1/FVC (96.14 ± 13.79 vs. 87.92 ± 19.77; P = 0.033), and d) TLC (93.33 ± 18.21 vs. 76.10 ± 21.84; P < 0.001). Nonsignificant differences were found in absolute FEV1, FEV1/FVC, FVC, forced expiratory flow from 25% to 75% of FVC, functional residual capacity, and CO diffusion. ARDS patients surviving after treatment with low-dose iNO had significantly better values for select pulmonary function tests at six months post-treatment than placebo-treated patients. Further trials are warranted to determine the effects of iNO on chronic lung function in ARDS survivors, a factor in long-term morbidity and quality of life in this population. A Double-blind, Randomized, Placebo-controlled, Dose-response Study of Inhaled Nitric Oxide in the Treatment of Acute Respiratory Distress Syndrome. NCT number: ISRCTN53268296.


Leiomyomatosis peritonealis disseminata: A case report and meticulous review of the literature.
Leiomyomatosis peritonealis disseminata (LPD) is a peculiar benign clinical disorder characterized by proliferation of peritoneal and subperitoneal nodules. LPD is a difficultly diagnosed benign disease that rarely degenerates into malignancy. A 40-year-old Caucasian female with vaginal bleeding proceeded to our institution for elective excision of abdominal and pelvic masses which were firstly considered as leiomyosarcomas. The histologic diagnosis of the mass lesions revealed smooth muscle benign cells. This is the first case of LPD reported in Greece. A meticulous review of the literature was conducted as well. The differential diagnosis of LPD is difficult due to its clinical resemblance with peritoneal carcinomatosis or metastatic lesions and with benign metastasizing leiomyoma (BML) as well. Etiological factors, pathophysiology and clinical manifestations which lead to a safe diagnosis of LPD are adequately described. Surgeons' thorough knowledge concerning this rare clinical condition is fundamental and crucial in order to establish a correct diagnosis and assert the appropriate treatment and the minimization of the probability of malignant transformation of LPD.