Fibrinogen and low density lipoprotein in the development of cerebral atherosclerosis.
Cerebral arteries from 65 human subjects were examined by immunofluorescence, using antisera against human fibrinogen and low density lipoprotein (LDL). Deposition of fibrinogen and LDL was most frequent at the bifurcation of the middle cerebral arteries and least in the basilar arteries in all age groups. In general, deposition of LDL was associated with deposition of fibrinogen, and lone deposition of LDL in the absence of fibrinogen was only rarely seen. Fibrinogen was scattered in the intercellular spaces, and located in the inner layer or edges of the thickened intima of the bifurcation with increasing plaque formation. Fibrinogen was observed even in the subendothelial region of the uninvolved intima at the bifurcations. LDL was present in the cytoplasm of the endothelial cells in the earliest stage, and it increased in the extracellular stroma with increase in intimal thickening, corresponding closely to the distribution of perifibous oil-red-O-stained lipids. No LDL was detected in the uninvolved intima. The observations suggest that deposition of fibrinogen in the intima might precede LDL deposition and possibly play a more important role than LDL in the development of atherosclerotic lesions in the cerebral arteries, especially in their early stage. Severe atherosclerosis at the bifurcations may be in part due to increased permeation of these plasma proteins, possibly as a result of hemodynamic stress.


Investigation of spatial pattern of apnea disorder using geographic information system (GIS)-case study of Kermanshah metropolis.
Apnea disorder is influenced by social and environmental factors. By assessing its hot spots and geography, the foci of this disorder and its at-risk groups can be identified for health interventions. This study was conducted to investigate the spatial pattern of apnea disorder using GIS in the Kermanshah metropolis. In cross-sectional study was conducted in kermanshah, the statistical population were 119 people (73.95% male and 26.05% female) of Kermanshah residents, which referred to the sleep center from 2012 to 2018 due to apnea disorder. Information was collected from the records of patients referred to the Sleep Disorder Center of Farabi Hospital, which is the only service center in the west part of Iran. The statistical tests were the mean center, standard distance, Getis-Ord Gi * index, nearest neighbor index, and kernel density estimation test in GIS software. The spatial pattern of patients with apnea disorder has cluster formation in the Kermanshah metropolis. The age group of 50-54 had more apnea disorder than other age groups. In this age group, women were more prone to apnea than men. In terms of education, people with high education are more affected by this disorder; So that with the increase in education level, apnea disorder had also increased. Also, the findings showed that the disorder was more common in unemployed, married, overweight people with BMI (25-30), and obese people (30-40). The spatial pattern of patients with apnea disorder was clustered and does not correspond to the high population density centers located in the marginal and slum areas of the city. These can be used by stakeholders, including governmental organizations and health authorities at the national-regional level.


An optimal double-magic flip angle for performing the distance measurement REDOR experiment on a spin S=1.
Distance measurements between a half-spin and a quadrupolar S=1 spin having a small quadrupolar coupling constant can be performed using the rotational echo double resonance (REDOR) experiment. We derived an analytical expression for the probability of transitions between energy levels resulting from the application of an arbitrary pulse flip angle to the quadrupolar spin and consequently minimized the probability that populations of individual levels do not undergo a spin transition during the pulse. As a result we discovered that if the flip angle of the quadrupolar spin pulse is 109.47°, the maximal recoupling values are the largest possible and the signal reaches a maximum value of 8/9, larger than in the use of either a 90° pulse or a 180° pulse. In addition, the slope of the initial decay is higher than that of the 90° pulse. The recoupling signal can be modeled by an exact analytical formula in the ideal case and simulations show that the advantage of the 109.47° pulse is preserved when the quadrupolar coupling constant CQ has a finite value typical of (2)H and (6)Li spins (up to CQ~200kHz). Experimental results on two spin pairs, (2)H-(13)C and (6)Li-(13)C, demonstrate the validity and accuracy of this method.


Chemical Reactions of Cationic Metallofullerenes: An Alternative Route for Exohedral Functionalization.
The chemistry of cationic forms of clusterfullerenes remain less explored than that of the corresponding neutral or anionic species. In the present work, M3 N@Ih -C80 (M=Sc or Lu) cations were generated by both electrochemical and chemical oxidation methods. The as-obtained cations successfully underwent the typical Bingel-Hirsch reaction that fails with neutral Sc3 N@Ih -C80 . Two isomeric Sc3 N@Ih -C80 cation derivatives, [5,6]-open and [6,6]-open adducts, were synthesized, and the former has never been prepared by means of a Bingel-Hirsch reaction with neutral clusterfullerenes. In the case of the Lu3 N@Ih -C80 cation, however, only a [6,6]-open adduct was obtained. Density functional theory (DFT) calculations indicated that the oxidized M3 N@Ih -C80 was much more reactive than the neutral compound upon addition of the diethyl bromomalonate anion. The Bingel-Hirsch reaction of M3 N@Ih -C80 cations occurred by means of an unusual outer-sphere single-electron transfer (SET) process from the diethyl bromomalonate anion to the stable intermediate [M3 N@C80 (C2 H5 COO)2 CBr]. . Remarkably, the diethyl bromomalonate anion was found to act as both a nucleophile and an electron donor.


Potentially avoidable hospital admissions in older patients with acute myeloid leukaemia in the USA: a retrospective analysis.
Older adults (≥60 years of age) with acute myeloid leukaemia spend a substantial proportion of their life in hospital after diagnosis. We examined reasons for their hospital admissions and identified potentially avoidable hospital admissions (PAH) in this age group in the USA. In this retrospective analysis, we examined the reasons for hospital admissions in older patients diagnosed with and treated for acute myeloid leukaemia at two tertiary care hospitals in the USA. We included patients receiving intensive induction chemotherapy or non-intensive treatment. We excluded those with acute promyelocytic leukaemia, those seen only for a one-time consultation who received primary treatment elsewhere, and those who received supportive care alone. We identified the eligible cohort using the Dana-Farber Cancer Institute and Massachusetts General Hospital Leukemia Clinical Research Information Systems database. Practising oncologists used a consensus-driven medical record review process to identify the primary reason for each hospital admission and categorise it as potentially avoidable or not avoidable on the basis of an adaptation of Graham's criteria for PAH. We used multivariable logistic regression analyses to identify predictors of PAH. Between May 1, 2005, and Dec 23, 2011, we assessed 1040 hospital admissions (excluding initial admission for diagnosis) in 329 consecutively admitted patients. The most common primary reasons for hospital admissions were: fever or infection (396 [38%]), planned admission for chemotherapy or transplantation (391 [38%]), and uncontrolled symptoms (102 [10%]). We identified 172 (27%) of 649 unplanned hospital admissions as potentially avoidable; among these admissions, 82 (48%) were readmissions because of previous premature hospital discharge, 32 (19%) because of problems that could have been managed in the outpatient setting, and 26 (15%) because of failure of timely outpatient follow-up. In a mixed logistic regression model, higher education (odds ratio 1·43 [95% CI 1·01-2·00]; p=0·04) and receipt of non-intensive induction chemotherapy (1·97 [1·25-3·10]; p=0·003) were predictors of PAH. Although many hospital admissions in older patients with acute myeloid leukaemia are unavoidable and driven by the illness course and its treatment, a substantial proportion are potentially avoidable. Future interventions to reduce PAH in this population are clearly warranted. National Cancer Institute, National Palliative Care Research Center, and Cambia Health Foundation.


Reliability of pictorial Longshi Scale for informal caregivers to evaluate the functional independence and disability.
The pictorial Longshi Scale was designed to assess patients' functional ability in the Chinese context, which is gradually used by some informal caregivers. However, its reliability compared with healthcare professionals has not been examined. A multi-centre cross-sectional study conducted in 24 Chinese hospitals. We recruited patients undergoing rehabilitation treatment and informal caregiver dyads. Informal caregivers and healthcare professionals evaluated patients' functional ability using the Longshi Scale according to three levels (bedridden, domestic and community). The Kappa coefficient and McNemar-Bowker test were used to examine the consistency and accuracy between the two parallel assessments. This study involved 947 patients (mean age: 46.07 ± 11.72 years) and informal caregiver dyads (64.86 ± 12.94 years). Most patients were males (66.3%), while most caregivers were females (60.7%). Over 70% of patients and caregiver dyads had a secondary-school education and lower. Around 90% of caregivers were relatives (spouse, 42.8%; offspring, 20.7%; siblings: 13.3%; parent, 12.0%) of patients. The agreement in sub-levels of the Longshi Scale between caregivers and healthcare professionals ranges from 73%-89%, and the corresponding Kappa coefficients range from 0.504-0.786. Caregivers were more likely to assign fewer patients to the bedridden group and more to the domestic group than healthcare professionals. The subgroup analysis by education level indicated that the difference in assigning patients into three degrees of functional disability was only significant in those with primary-school education, while non-significant in those with secondary-school education and higher. The evaluation outcomes of functional ability using the Longshi Scale are similar between informal caregivers and healthcare professionals. However, informal caregivers' education level is a dominant factor in affecting the assessment accuracy compared with healthcare professionals. Informal caregivers with a secondary-school education and higher are supported to evaluate patients' functional ability independently.


Perioperative Lung Function Monitoring for Anatomic Lung Resections.
The aim of this study was to prospectively investigate the correlation between postoperative spirometry values and pulmonary complications after anatomic lung resections. In addition, we compared postoperative pulmonary function changes between open and minimally invasive approaches. Three hundred eighty-four patients who underwent an anatomic lung resection at our institution between June 2013 and June 2016 were enrolled in this prospective observational trial. Bedside spirometry was performed before surgery and postoperatively every second day until discharge. For the 250 patients who completed the trial, the following data were collected and analyzed: spirometry findings, pain management, surgical procedure, and postoperative complications. A propensity score matched analysis was performed to compare open and minimally invasive approaches. Postoperative pneumonia was significantly more frequent after open surgery (13.2% versus 4.4%, p = 0.016); furthermore, these patients showed significantly greater losses of forced expiratory volume in 1 second on postoperative day 4 compared with patients without pneumonia (loss in percent from preoperative absolute values: 43.2% versus 32,2%, p = 0.013). When focusing on patients without pneumonia, propensity matched analysis revealed a significantly faster recovery of forced expiratory volume in 1 second on postoperative day 4 in the minimally invasive group compared with the open group (p = 0.011). Daily bedside spirometry might be a helpful diagnostic adjunct for early recognition, and hence, timely treatment, of pulmonary infection after open anatomic lung resections. In addition, minimally invasive techniques not only resulted in a lower rate of pulmonary infections but also resulted in faster postoperative recovery of pulmonary function and shorter hospital stay.


Radioimmunologic method for detection of antitubular basement membrane antibodies.
A radioimmunoassay for detection of antitubular basement membrane (TBM) antibodies was set up using a human TBM antigen (mol wt, 70,000 daltons), purified after collagenase treatment of the insoluble membrane by preparative polyacrylamide electrophoresis, and labeled with iodine 125. Free labeled antigens were separated from those bound to immunoglobulins by a 20% polyethylene glycol (mol wt, 6,000 daltons) solution. In the presence of normal human or Brown Norway rat sera, less than 10% of the labeled antigens were precipitated. In the presence of sera or of kidney eluates from rats immunized with human TBM, the precipitation of the labeled TBM antigens reached 73%, but in the presence of sera from two patients presenting with an interstitial nephritis and linear deposits along the TBM only, up to 47% of the same antigens were precipitated. In these two cases, the anti-TBM antibodies were mainly directed against the heteropolysaccharide-containing glycopeptides isolated from TBM, that is, against the noncollagenous polypeptides of the TBM antigens. Anti-TBM antibodies were sought in the sera of 52 normal blood donors and of 11 patients presenting with glomerulonephritis and linear deposits of immunoglobulins. The average percentage (+/- 1 SD) of labeled TBM antigens precipitated in the serum of normal blood donors was 7.1 +/- 1.2. Of the patients presenting with glomerulonephritis and linear deposits along the GBM, 9 out of 11 exhibited anti-TBM antibodies by radioimmunoassay; among these 9 patients, 8 also displayed linear deposits of IgG along the TBM. Absorption of anti-TBM and anti-GMB antibodies with particulate TBM or GBM, with both types of glycopeptides isolated from GBM or TBM, indicated that the anti-TBM antibodies were directed against the noncollagenous polypeptides of TBM but that the anti-GBM antibodies mainly reacted with the collagenous polypeptides of TBM and GBM. Finally, it was found that the sera of 2 patients out of 15 presenting with lupus nephritis contained a significant anti-TBM-binding activity, mainly directed against the noncollagenous material of TBM.


Nutrition and development of gastric cancer.
Gastric cancerogenesis is a multistage process. Dietary studies may contribute to elucidation of that complex problem.


Graft versus host disease: clinical evaluation, diagnosis and management.
Graft versus H\host disease (GVHD) can be a devastating complication following bone marrow transplantation. Acute or chronic systemic GVHD can be lethal, and severe damage of different organs and tissues can occur with both types of GVHD. Ocular involvement, either in an acute or chronic presentation, may range from mild to severe with accompanying vision loss present in 60-90 % of patients. Chronic ocular GVHD, the most common form of GVHD, affects mainly the lacrimal gland, meibomian glands, cornea and conjunctiva, mimicking other immunologically mediated inflammatory diseases of the ocular surface without specific symptoms or signs. However, dry eye disease is the main manifestation of GVHD. The long-term treatment of ocular GVHD continues to be challenging and involves a multidisciplinary approach wherein the ophthalmologist plays a major role. Besides systemic immunosuppression and ocular lubricants, topical steroids and topical cyclosporine are commonly prescribed. Newer therapeutic interventions for moderate and severe ocular GVHD include the use of serum eye drops and scleral contact lenses. In this manuscript, we review the mechanisms, clinical findings, and treatment of ocular GVHD.


Comparison of surgical and oncological outcomes between oncoplastic breast-conserving surgery versus conventional breast-conserving surgery for treatment of breast cancer: A systematic review and meta-analysis of 31 studies.
To evaluate comparative outcomes of oncoplastic breast conserving surgery (OBCS) versus conventional breast conserving surgery (BCS) for breast cancer treatment. A systematic search of multiple electronic data sources was conducted, and all eligible studies comparing OBCS and BCS were included. Characteristics of the tumour includes preoperative size of tumour on imaging and the weight of the specimen after resection. While positive margins rate, re-excision rate, completion mastectomy rate and loco-regional recurrence were considered as oncological outcome parameters. Post-operative complications include surgical site infection (SSI), seroma, haematoma and skin/nipple necrosis. Thirty-one studies reporting a total number of 115011 patients who underwent OBCS (n = 11978) or BCS (n = 103033) were included. OBCS group showed lower risk of positive margins rate [OR 0.76, P = 0.05], re-excision rate [OR 0.72, P = 0.02], and loco-regional recurrence [OR 0.62, P = 0.03] compared to BCS group. There was no significant difference between the two groups regarding post-operative complications. Although there is a lack of level 1 evidence, the available studies clearly demonstrate superior or at least equivalent outcomes when comparing OBCS with conventional BCS. The benefits of OBCS include dealing with larger tumours, wider surgical margins and better aesthetic results for patients.


Closure of two atrial septal defects using two separate Amplatzer ASD devices.
The majority of patients with atrial septal defect require a single device for closure but a small proportion have more than one defect in the atrial septum. We report a patient who had two moderate-sized atrial septal defects in whom transcatheter closure of both the defects using two Amplatzer septal occluders was performed successfully.


Immobilized-liposome chromatographic analysis of drug partitioning into lipid bilayers.
The chromatographic retardation of drugs on a gel bed with immobilized liposomes was shown to correlate with the absorption of the drugs through epithelial cell layers, which is related to drug partitioning into the lipid bilayers of cell membranes. The capacity factors were divided by the lipid concentration (mM) in the gel bed to obtain specific capacity factors, Ks. The logarithm of the octanol-water distribution ratios showed a linear correlation with log Ks, whereas the logarithm of the apparent permeability coefficients in epithelial cell monolayers and the absorption of drugs orally administered in humans (data from other laboratories) increased over the interval 0 < log Ks < 1 and attained a saturation level in the interval 1 < log Ks < 3. Immobilized-liposome chromatography may be applicable for prediction of drug uptake through epithelial cell membranes.


Outcomes in 140 critically ill patients with status epilepticus.
Despite recent management guidelines, no recent study has evaluated outcomes in ICU patients with status epilepticus (SE). An 8-year retrospective study. Observational study in 140 ICU patients with SE, including 81 (58%) with continuous SE and 59 (42%) with intermittent SE (repeated seizures without interictal recovery). The 95 men and 45 women had a median age of 49 years (IQR 24-71). Median seizure time was 60 min (IQR 20-180), and 58 patients had seizures longer than 30 min. The SE was nonconvulsive in 16 (11%) patients and convulsive in 124 (89%), including 89 (64%) with tonic-clonic generalized seizures, 27 (19%) with partial seizures, 7 (5%) with myoclonic seizures, and 1 with tonic seizures. The most common causes of SE were cerebral insult in 53% and anticonvulsant drug withdrawal in 20% of patients. No cause was identified in 35% of patients. Median time from SE to treatment was 5 min (IQR 0-71). The SE was refractory in 35 (25%) patients. Mechanical ventilation was needed in 106 patients. Hospital mortality was 21%. By multivariate analysis, independent predictors of 30-day mortality were age (OR 1.03/year; 95% CI 1.00-1.06), GCS at scene (OR 0.84/point; 95% CI 0.72-0.98), continuous SE (OR 3.17; 95% CI 1.15-8.77), symptomatic SE (OR 4.08; 95% CI 1.49-11.10), and refractory SE (OR 2.83; 95% CI 1.06-7.54). Mortality in SE patients remains high and chiefly determined by seizure severity. Further studies are needed to evaluate the possible impact of early maximal anticonvulsant treatment on outcomes.


Impact of pretransplant minimal residual disease on the post-transplant outcome of pediatric acute lymphoblastic leukemia.
There are few reports on the clinical significance of MRD before HSCT in pediatric ALL. We retrospectively analyzed the clinical significance of FCM-based detection of MRD (FCM-MRD) before allogeneic HSCT in pediatric ALL. Of 38 pediatric patients who underwent allogeneic HSCT for the first time between 1998 and 2014, 33 patients were in CR and five patients were in non-CR. The CR group was further divided into two groups based on the pretransplant FCM-MRD level: the MRD(neg) (<0.01%; 30 patients) group and the MRD(pos) (≥0.01%; three patients) group. There were significant differences in the three-yr event-free survival rates between the CR and non-CR group, and between the MRD(neg) and MRD(pos) group. The three-yr cumulative RI in the MRD(neg) group were 27.3% ± 8.8%, whereas two of the three patients in the MRD(pos) group relapsed within one yr after HSCT. The clinical outcome of the MRD(pos) group was as poor as that of the non-CR group in pediatric ALL. Therefore, an improvement in pretransplant treatment that aims to achieve a more profound remission would contribute to reducing the risk of relapse.


Volunteer participation in feeding residents: training and supervision in a long-term care facility.
The increasing number of residents in long-term care facilities who require full and partial assistance during meals has created a need for volunteer support to enhance the quality of life for residents. The correlation between dependence in eating and the existence of swallowing disorders and the risk of aspiration in persons with swallowing disorders suggests that training must be given to volunteers who feed residents. A formalized program for volunteer training and supervision was implemented at Coler Memorial Hospital, a long-term care facility. The program's development and benefits are outlined. Implementation of this program resulted in better training of volunteers, increased socialization, communication, and safety for patients during meals.


Capsular contracture and steroid-related complications after augmentation mammaplasty. A preliminary study.
Ninety-one patients who had had augmentation mammaplasties were evaluated retrospectively. The intra-implant use of steroids appeared to reduce the incidence of breast firmness--at least over the short follow-up period--but there were complications from this which appear to be dose related (mg of Solu-Medrol/100 cc saline). A long-term evaluation of such patients is desirable. Meanwhile, our limited data strongly suggest that the intra-implant use of steroids should be used only with caution as to the dose and with a careful follow-up.


Support, sensitivity, satisfaction: Filipino, Turkish and Vietnamese women's experiences of postnatal hospital stay.
To assess Filipino, Turkish and Vietnamese women's views about their care during the postnatal hospital stay. Interviews were conducted with recent mothers in the language of the women's choice, 6-9 months after birth, by three bilingual interviewers. Three hundred and eighteen women born in the Philippines (107), Turkey (107) and Vietnam (104) who had migrated to Australia. Women were recruited from the postnatal wards of three maternity teaching hospitals in Melbourne, Australia, and interviewed at home. Overall satisfaction with care was low, and one in three women left hospital feeling that they required more support and assistance with both baby care and their own personal needs. The method of baby feeding varied between the groups, with women giving some insight into the reason for their choice. A significant minority wanted more help with feeding, irrespective of the method. The need for rest was a recurrent theme, with women stating that staff's attitudes to individual preferences, coupled with lack of assistance, made this difficult. The majority of comments women made regarding their postnatal stay focused on the attitude and behaviour of staff and about routine aspects of care. Issues related to culture and cultural practices were not of primary concern to women. Maternity services need to consider ways in which care can focus on the individual needs and preferences of women.


Molecular genetics of ependymoma.
Brain tumors are the leading cause of cancer death in children, with ependymoma being the third most common and posing a significant clinical burden. Its mechanism of pathogenesis, reliable prognostic indicators, and effective treatments other than surgical resection have all remained elusive. Until recently, ependymoma research was hindered by the small number of tumors available for study, low resolution of cytogenetic techniques, and lack of cell lines and animal models. Ependymoma heterogeneity, which manifests as variations in tumor location, patient age, histological grade, and clinical behavior, together with the observation of a balanced genomic profile in up to 50% of cases, presents additional challenges in understanding the development and progression of this disease. Despite these difficulties, we have made significant headway in the past decade in identifying the genetic alterations and pathways involved in ependymoma tumorigenesis through collaborative efforts and the application of microarray-based genetic (copy number) and transcriptome profiling platforms. Genetic characterization of ependymoma unraveled distinct mRNA-defined subclasses and led to the identification of radial glial cells as its cell type of origin. This review summarizes our current knowledge in the molecular genetics of ependymoma and proposes future research directions necessary to further advance this field.


Magnetic particle motions within living cells. Physical theory and techniques.
Body tissues are not ferromagnetic, but ferromagnetic particles can be present as contaminants or as probes in the lungs and in other organs. The magnetic domains of these particles can be aligned by momentary application of an external magnetic field; the magnitude and time course of the resultant remanent field depend on the quantity of magnetic material and the degree of particle motion. The interpretation of magnetometric data requires an understanding of particle magnetization, agglomeration, random motion, and both rotation and translation in response to magnetic fields. We present physical principles relevant to magnetometry and suggest models for intracellular particle motion driven by thermal, elastic, or cellular forces. The design principles of instrumentation for magnetizing intracellular particles and for detecting weak remanent magnetic fields are described. Such magnetic measurements can be used for noninvasive studies of particle clearance from the body or of particle motion within body tissues and cells. Assumptions inherent to this experimental approach and possible sources of artifact are considered and evaluated.


Laparoscopic adjustable gastric banded plication: a case-matched comparative study with laparoscopic sleeve gastrectomy.
Laparoscopic sleeve gastrectomy (LSG) has been accepted as stand-alone restrictive bariatric procedure; laparoscopic adjustable gastric banded plication (LAGBP) is an innovative technique combining gastric banding and plication of the stomach. This study aims to compare LAGBP with LSG in terms of percent excess weight loss (%EWL), resolution of comorbidities, and complications. This study was conducted in a university hospital. We retrospectively analyzed data of 60 patients: 30 each receiving LSG and LAGBP between May 2009 to October 2010. Demographics, operative data, complications, % EWL, and resolution of comorbidities were analyzed and compared. All the patients were followed for at least 1 year. LSG and LAGBP were matched for age, sex, body mass index and comorbidity ratio. Mean operative time was significantly longer in LAGBP: 62.45 ± 30.1 vs. 86.01 ± 21.88 (p = 0.001). Both groups had similar complication rates (6.67 %) and most of the patients achieved significant resolution of comorbidities. The mean %EWL was statistically significant for LSG till 18 months follow-up as compared to LAGBP, but there was no difference at 2 years (p = 0.971). Mean frequency of band adjustment after LAGBP in 2 years was 1.50 ± 1.51. There was no significant difference in comorbidity resolution in both groups. LAGBP is a dual restrictive bariatric procedure offering similar results with LSG at 2 years in terms of complications, % EWL, and comorbidity resolution with potential of continual weight loss due to band.


TRIM32 regulates mitochondrial mediated ROS levels and sensitizes the oxidative stress induced cell death.
Emerging evidence suggests that ubiquitin mediated post translational modification is a critical regulatory process involved in diverse cellular pathways including cell death. During ubiquitination, E3 ligases recognize target proteins and determine the topology of ubiquitin chains. Recruitment of E3 ligases to targets proteins under stress conditions including oxidative stress and their implication in cell death have not been systemically explored. In the present study, we characterized the role of TRIM32 as an E3 ligase in regulation of oxidative stress induced cell death. TRIM32 is ubiquitously expressed in cell lines of different origin and form cytoplasmic speckle like structures that transiently interact with mitochondria under oxidative stress conditions. The ectopic expression of TRIM32 sensitizes cell death induced by oxidative stress whereas TRIM32 knockdown shows a protective effect. The turnover of TRIM32 is enhanced during oxidative stress and its expression induces ROS generation, loss of mitochondrial transmembrane potential and decrease in complex-I activity. The pro-apoptotic effect was rescued by pan-caspase inhibitor or antioxidant treatment. E3 ligase activity of TRIM32 is essential for oxidative stress induced apoptotic cell death. Furthermore, TRIM32 decreases X-linked inhibitor of apoptosis (XIAP) level and overexpression of XIAP rescued cells from TRIM32 mediated oxidative stress and cell death. Overall, the results of this study provide the first evidence supporting the role of TRIM32 in regulating oxidative stress induced cell death, which has implications in numerous pathological conditions including cancer and neurodegeneration.


The heritability of human disease: estimation, uses and abuses.
Relatives provide the basic material for the study of inheritance of human disease. However, the methodologies for the estimation of heritability and the interpretation of the results have been controversial. The debate arises from the plethora of methods used, the validity of the methodological assumptions and the inconsistent and sometimes erroneous genetic interpretations made. We will discuss how to estimate disease heritability, how to interpret it, how biases in heritability estimates arise and how heritability relates to other measures of familial disease aggregation.


The development, implementation, and evaluation of a medical student peer teaching training curriculum during a high-fidelity prehospital trauma simulation.
While peer teaching has been found to be an effective technique during simulation, no peer teaching training curriculum (PTTC) has been developed for simulation-based learning. The objective of this study, therefore, was to develop, implement, and evaluate a PTTC during a high-fidelity trauma simulation. When developing the PTTC, we combined several validated learning models for teaching and learning procedural skills. We then implemented it over 6 days in two phases: instructional (learning how to teach) and experiential (practicing teaching). Our research team conducted a qualitative evaluation to evaluate the effectiveness of the PTTC. We analyzed written self-reflections from 20 second-year medical students who completed the PTTC. Using an iterative inductive approach to data analysis, our research team first individually coded the reflection papers. We then met to define and categorize the codes into themes. Finally, we compared these themes to the PTTC's objectives to evaluate the curriculum's effectiveness. The following themes emerged from the data: 1) learning through teaching; 2) self-actualization as an educator; and 3) role of physician as leader, advocate, and educator. The students described how the peer teaching experience improved their own procedural knowledge and skills. They also reported an increase in their leadership and communication skills as they effectively provided guidance and feedback to their peers, which led to their self-actualization as an educator. This self-actualization inspired the peer teachers' professional identity formation as leaders and educators in medicine. Based on these themes, we found our PTTC to be an effective curricular design. Our results reinforce previously described benefits to both peer teachers and learners in regard to medical knowledge and skills acquisition and furthers the academic emergency medicine community's understanding of how students' involvement as peer teachers in simulation-based education impacts their professional development.


Exploring the role of decision support systems in promoting healthier and more sustainable online food shopping: A card sorting study.
This study aims to identify opportunities and barriers in developing and implementing Food Shopping Support Systems (FSSS) for healthier and more sustainable choices, given the growing consumer demand and persistent societal problems related to food. The study examined the social and technical value of FSSS in an early development stage through one-on-one expert interviews (n = 20) and consumer focus groups (4 groups, n = 19). Experts were employed in the fields of behavioral sciences, digital marketing, decision aids, software development, persuasive technologies, and public health and sustainability. Consumer participants were used to shopping online. Through a card sorting task followed by semi-structured interview questions, responses were elicited. Participants were presented with 17 cards in 5 rounds, each addressing a different topic related to decision support. Results show that support is perceived useful, particularly when suggestions are personalized, transparent, and justified (using labelling or informative text). Opportunities for uptake were presenting suggestions early in the shopping trip in a visible but non-disruptive manner, allowing autonomy to choose the type of guidance (e.g., show sustainable but not healthier suggestions) and to (not) provide personal data, and educating consumers. Negative attitudes were associated with support being disruptive or steering, being of low credibility, and unclarity about what is healthy or sustainable. Consumer participants expressed concerns about too generic suggestions in relation to health and lack of knowledge about labelling. They emphasized that excessive support and required effort, such as repeatedly providing data, can be burdensome. Experts also worried about limited consumer interest and not having the required data to provide support. Results from this study reveal the potential for successful digital interventions to encourage healthier and more sustainable choices and what this means for further development.


Male reproductive health in cystic fibrosis.
The impact of cystic fibrosis (CF) on male reproductive health is profound. The vast majority of men with CF are infertile due to obstructive azoospermia. Multiple factors associated with CF contribute to an increased prevalence of testosterone deficiency, which adversely affects muscle mass, bone density, and quality of life. This article reviews the pathophysiology, diagnosis, and management of infertility and testosterone deficiency that occur in men with CF. With improving survival of CF patients, these topics are becoming more significant in their clinical care.


Albumin-templated platinum (II) sulfide nanodots for size-dependent cancer theranostics.
Transition-metal chalcogenides, such as noble metal chalcogenides, hold tremendous potential as efficient agents for photo-induced cancer theranostics due to their unique physicochemical properties. However, a critical bottleneck still lies in exploring simple and controllable methods to synthesize noble metal chalcogenides especially PtS for in vivo photo-induced cancer imaging and simultaneous therapy. Herein, we proposed the albumin-templated synthesis of size-controllable platinum (II) sulfide nanodots (PtS-NDs) for multimodal cancer imaging and potent photothermal therapy. PtS-NDs were precisely synthesized with a tunable size ranging from 2.1 nm to 4.5 nm through a thermodynamically controlled growth inside albumin nanocages. PtS-NDs yielded significant near-infrared (NIR) absorbance and outstanding photothermal conversion under NIR laser irradiation, as well as effective resistance to photobleaching, thereby generating remarkable in vivo photoacoustic signals and distinct hyperthermia at tumor site. Moreover, these nanodots possessed efficient cellular uptake and tumor targeting capabilities in a size-dependent manner, thus leading to controllable diagnostic and thermo-therapeutic efficacy. Specifically, PtS-NDs with core diameter of 4.5 nm displayed preferable in vivo photoacoustic and CT imaging with high sensitivity, spatially and anatomically enhanced imaging contrast, together with hyperthermia mediated tumor ablation. Thus, the albumin-templated biomimetic synthesis provided an insightful strategy on fabricating theranostic PtS-NDs for potential clinical applications. STATEMENT OF SIGNIFICANCE: Noble metal chalcogenides especially PtS are of particular importance in the field of precise nanomedicine to improve both accuracy of cancer diagnosis and efficiency of tumor treatment. However, the intensively preclinical investigation of PtS was limited due to the lack of simple and controllable synthetic methods. Here, we report an albumin-templated biomineralization synthesis of platinum (II) sulfide nanodots (PtS-NDs). Specifically, albumin-templated biomineralization of PtS-NDs was induced by the electrostatic interactions between albumin and Pt2+, followed by the nucleation and growth inside the albumin nanocages. The resulting PtS-NDs showed good dispersibility and biosafety, as well as size-dependent photophysical properties and biological behaviors. Therefore, albumin-based biomineralization is a promising and safe strategy to facilely fabricate Pt-based chalcogenide for tumor theranostics.


Upscaling of nanoparticle transport in porous media under unfavorable conditions: Pore scale to Darcy scale.
Transport and deposition of nanoparticles in porous media is a multi-scale problem governed by several pore-scale processes, and hence, it is critical to link the processes at pore scale to the Darcy-scale behavior. In this study, using pore network modeling, we develop correlation equations for deposition rate coefficients for nanoparticle transport under unfavorable conditions at the Darcy scale based on pore-scale mechanisms. The upscaling tool is a multi-directional pore-network model consisting of an interconnected network of pores with variable connectivities. Correlation equations describing the pore-averaged deposition rate coefficients under unfavorable conditions in a cylindrical pore, developed in our earlier studies, are employed for each pore element. Pore-network simulations are performed for a wide range of parameter values to obtain the breakthrough curves of nanoparticle concentration. The latter is fitted with macroscopic 1-D advection-dispersion equation with a two-site linear reversible deposition accounting for both equilibrium and kinetic sorption. This leads to the estimation of three Darcy-scale deposition coefficients: distribution coefficient, kinetic rate constant, and the fraction of equilibrium sites. The correlation equations for the Darcy-scale deposition coefficients, under unfavorable conditions, are provided as a function of measurable Darcy-scale parameters, including: porosity, mean pore throat radius, mean pore water velocity, nanoparticle radius, ionic strength, dielectric constant, viscosity, temperature, and surface potentials of the particle and grain surfaces. The correlation equations are found to be consistent with the available experimental results, and in qualitative agreement with Colloid Filtration Theory for all parameters, except for the mean pore water velocity and nanoparticle radius.


Prothrombin antigen levels in symptomatic and asymptomatic carriers of the 20210A prothrombin variant.
A recently discovered variant in the prothrombin gene (20210A) has been found in approximately 5-10% of patients with venous thromboembolism. It has been shown that patients with this variant present with high levels of prothrombin in plasma and this is maintained to be the most likely mechanism by which the risk of thrombosis is increased. We have evaluated prothrombin antigen levels in 50 carriers of the 20210A allele and compared with non-carriers. 327 subjects were subdivided according to deficiency status and previous thrombosis. 30 symptomatic and 20 asymptomatic carriers had increased mean prothrombin levels as compared to symptomatic (n=178) or asymptomatic (n=99) non-carriers. The percentage of subjects with prothrombin levels above cut-off values of 1.15u/ml or 1.30u/ml was significantly higher in carriers of the prothrombin variant as compared to non-carriers, regardless of a previous thrombosis. However, among non-carriers the percentage of those with prothrombin levels above cut-off values was significantly higher in the group of symptomatic as compared to asymptomatic individuals. In conclusion, increased prothrombin antigen levels, as detected by a specific ELISA, were found among 50 symptomatic and asymptomatic carriers of the 20210A prothrombin variant as well as among a large group of symptomatic non-carriers. The data are in agreement with those found by using functional tests for the determination of prothrombin levels in these patients.


Inhibition of cell division and stimulation of progesterone receptor synthesis in rat oestrogen target tissues by non-steroidal antioestrogens.
Recent studies from this laboratory have demonstrated oestradiol-oestrogen receptors associated with the nuclear compartment of the rat uterine cell will initiate protein synthesis, as evidenced by a rise in progesterone receptor concentrations, and cell division whereas the anti-oestrogen - oestrogen receptor complex causes protein synthesis and cellular hypertrophy rather than hyperplasia. It is probable that this separation of biological activities resides in the intrinsic activity of the respective receptor complexes. We have demonstrated that caution should be exercised in the interpretation of low affinity ligand-hormone receptor interactions undertaken in vitro. Simple tests for ligand specificity for a binding protein are clearly insufficient evidence to characterise a hormone receptor complex using a conventional 15 hr technique of sucrose density gradient analysis. Oestrogens and anti-oestrogens do not seem to disrupt the subunit integrity of the cytoplasmic oestrogen receptor and it appears likely that the ligand plays a fundamental role in confering the correct biological properties to the hormone receptor complex.


A review of parenting and adolescent sexual behavior: the moderating role of gender.
In spite of the established link between parenting and adolescent sexual risk behavior, less is known about the role of adolescent gender as a potential moderator of this association. This literature review integrates findings from 24 studies to examine gender as a moderator of the link between parenting and youth sexual risk behavior. Despite the wide variability in methodology across the reviewed studies, findings suggest that monitoring may be more protective against sexual risk behavior for boys than girls, whereas parental warmth and emotional connection may be an especially salient factor for girls. The results of this review support further research on gender as an important factor in better understanding the role of parenting in the development of adolescent sexual behavior. Furthermore, the findings highlight the potential role of gender-specific, tailored family-focused prevention programs targeting sexual behavior.


Hypotension from spinal anesthesia in patients aged greater than 80 years is due to a decrease in systemic vascular resistance.
To determine the exact mechanism underlying spinal anesthesia-induced hypotension in the elderly patient. Retrospective case-control study. Operating room (OR) in a general hospital. Records from 60 consecutive patients over 80 years of age, who underwent hip fracture repair (intramedullary nail or compression hip screw) during spinal anesthesia were studied. After injection of isobaric 0.5% bupivacaine in the L(3)-L(4) intervertebral space in the lateral decubitus position, patients were turned supine. Acetate Ringer's solution (300 mL) was infused over 30 minutes after subarachnoid puncture. A decrease in systolic arterial pressure to less than 100 mmHg was treated with an intravenous injection of 5 mg ephedrine. The hypotension group (n=18) comprised patients who required ephedrine during the 30 minutes after the puncture, and the nonhypotension group (n=42) consisted of patients who maintained stable arterial pressure with crystalloid infusion only. Cardiac output (CO) and stroke volume variation (SVV) every 20 seconds using the Vigileo-FloTrac system continuously from arrival in the operating room (OR) to 30 minutes after the subarachnoid puncture were recorded. Serial changes in systemic vascular resistance (SVR), CO, and SVV from baseline after puncture were compared between the two groups. The decrease in SVR over 20 minutes after the puncture was significantly greater in the hypotension group than the nonhypotension group (P = 0.047). Cardiac output was stable in the two groups. Stroke volume variation in the first 10 minutes after the puncture increased to similar levels in the two groups, then decreased gradually to baseline. No significant differences were noted in circulatory parameters on arrival at the OR. A decrease in SVR, not CO, is the main mechanism of hypotension seen during spinal anesthesia in elderly patients.


Clinical profile, viral load, management and outcome of neonates born to COVID 19 positive mothers: a tertiary care centre experience from India.
Despite rapidly evolving knowledge about COVID 19 infection, routes of perinatal COVID 19 transmission and viral load in mother neonate dyad remain uncertain. Data were analysed to describe the clinicodemographic profile and viral load in neonates born to COVID 19 positive mothers. Of 2947 deliveries, 69 mothers were COVID 19 positive (2.3%), with 1 abortion, 2 macerated stillbirths and 2 fresh stillbirths as pregnancy outcomes. Of 65 tested neonates, 10.7% (7) were confirmed COVID 19 positive by RTPCR (reverse transcriptase-polymerase chain reaction). Viral load (cycle threshold, Ct of E, RDRp) in neonates was comparable with the Ct reported from adults; however, neonates had milder clinical manifestations. All 7 neonates who tested positive for COVID 19 were subsequently discharged. Six of the 7 neonates were asymptomatic and 1 neonate needed respiratory support (indication being prematurity) which resolved after 48 h. Maternal and neonatal comparison of Ct of E and RdRp gene was statistically non-significant (25.97 vs 19.68, p = 0.34 and 26.5 vs 25.0, p = 0.84). Viral loads of mothers with COVID 19 positive neonates compared with mothers with COVID 19 negative neonates for E and RdRp gene were also statistically non-significant (25 vs 27.19, p = 0.63 and 19.6 vs 27.6, p = 0.08). The majority (93%) of neonates tested later than 48 h (roomed in with mother and breastfed) tested negative.Conclusion: The study supports milder manifestation in COVID 19 positive neonates. Risk of transmission from COVID 19 positive mother to neonate by rooming-in and breastfeeding is low. In this study on a limited number of neonates, maternal viral load was not found to be associated with the positivity status or severity of the illness of neonate. What is Known: • Neonates born to COVID 19 positive mothers are at risk of COVID 19 infection. What is New: • Risk of transmission of COVID 19 from mother to neonate, with rooming-in and breastfeeding, appears low. • In this study on a limited number of neonates, maternal viral load of COVID 19 (E and RdRp cycle thresholds) was not associated with severity of illness or COVID 19 positivity in neonates.


Double stent retriever technique for rescue recanalization in refractory large vessel occlusions.
Acute ischemic stroke patients with large vessel occlusion (LVO) involving bifurcation usually have a difficult and high clot burden. By using conventional technique often resulting in a reduction in the possibility of successful recanalization. The double stent retriever technique can be considered for rescue recanalization. We reported a case of refractory terminal left internal carotid occlusion that was treated using double stent retriever technique. Two microcatheter were advanced across the occlusion were one to the superior branch of middle cerebral artery and another was on inferior branch. Both stent retrievers were pulled back together and complete recanalization was achieved. This technique were reported in some case series to be effective and based on our initial experience using this technique it seems the expansion improved after deployment of the second stent retriever and it traps the clot within its stent struts, to facilitate clot retrieval. Therefore, double stent retriever technique can be one of the choices for rescue recanalization in refractory clot occlusion and it may potentially help other clinicians in similar situations.


Studies on DNA damage: discordant responses of rate of DNA disentanglement (viscosimetrically evaluated) and alkaline elution rate, obtained for several compounds. Possible explanations of the discrepancies.
Alkaline elution is a well-known method for detecting DNA damage. Recently we have developed a viscosimetric method that is even more sensitive than alkaline elution. Here we report that the two methods, although apparently both revealing alkaline DNA fragmentation, can give dramatically different results for a significant series of compounds. We suspect that alkaline elution might reveal not only DNA fragmentation but also the extent of disentanglement of chromatin structure, whereas this DNA disentanglement rate, when evaluated viscosimetrically , is more strictly correlated with the initiation of DNA unwinding.


Characterization of an Unusual α-Oxoamine Synthase Off-Loading Domain from a Cyanobacterial Type I Fatty Acid Synthase.
Type I fatty acid synthases (FASs) are known from higher eukaryotes and fungi. We report the discovery of FasT, a rare type I FAS from the cyanobacterium Chlorogloea sp. CCALA695. FasT possesses an unusual off-loading domain, which was heterologously expressed in E. coli and found to act as an α-oxoamine synthase (AOS) in vitro. Similar to serine palmitoyltransferases from sphingolipid biosynthesis, the AOS off-loading domain catalyzes a decarboxylative Claisen condensation between l-serine and a fatty acyl thioester. While the AOS domain was strictly specific for l-serine, thioesters with saturated fatty acyl chains of six carbon atoms and longer were tolerated, with the highest activity observed for stearoyl-coenzyme A (C18 ). Our findings suggest a novel route to α-amino ketones via the direct condensation of iteratively produced long-chain fatty acids with l-serine by a FAS with a cis-acting AOS off-loading domain.


Binding of the peptide deformylase on the ribosome surface modulates the exit tunnel interior.
Proteosynthesis on ribosomes is regulated at many levels. Conformational changes of the ribosome, possibly induced by external factors, may transfer over large distances and contribute to the regulation. The molecular principles of this long-distance allostery within the ribosome remain poorly understood. Here, we use structural analysis and atomistic molecular dynamics simulations to investigate peptide deformylase (PDF), an enzyme that binds to the ribosome surface near the ribosomal protein uL22 during translation and chemically modifies the emerging nascent peptide. Our simulations of the entire ribosome-PDF complex reveal that the PDF undergoes a swaying motion on the ribosome surface at the submicrosecond timescale. We show that the PDF affects the conformational dynamics of parts of the ribosome over distances of more than 5 nm. Using a supervised-learning algorithm, we demonstrate that the exit tunnel is influenced by the presence or absence of PDF. Our findings suggest a possible effect of the PDF on the nascent peptide translocation through the ribosome exit tunnel.


Cow's milk allergic children can present sensitisation to probiotics.
To evaluate sensitivity to different probiotics in children with cow's milk allergy. Eighty-five patients (age range: 4 months -12 years) presenting atopic dermatitis (AD) were enrolled. Skin prick test (SPT) responses to three different probiotics preparations (Fiorilac, Dicoflor and Reuterin) were evaluated in addition to relevant food allergens. Thirty-nine patients out of 85 (45.8%) had a positive skin response to prick test for cow's milk (3 with reaction <3 mm). Of the thirty-six patients with a cow's milk weal reaction >3 mm, twenty-eight (77.8%) had a skin response to Fiorilac, four patients (11%) to Dicoflor and four (11%) to Reuterin. The proportion of SPT reaction to all the investigated probiotics preparations was significantly lower than cow's milk (r = 9.406; p = 0.002). A significantly higher sensitization was observed for Fiorilac versus Dicoflor (r = 30.916; p < 0.001) and versus Reuterin (r = 34.133; p < 0.001). Probiotic use in patients with cow's milk allergy has to be limited to products that do not contain milk. This should be clearly reported in the label. In selected patients, it is advisable to perform a screening SPT with the product to evaluate its potential contamination with milk.


Cervical Myelopathy Caused by Intracranial Dural Arteriovenous Fistula with Acute Worsening After Steroid Administration.
Intracranial dural arteriovenous fistulas (DAVFs) draining into the perimedullary venous system are rare and potentially life-threatening lesions often presenting as a myelopathy. The early and proper diagnosis of this rare disease is challenging because the symptoms are nonspecific. Acute clinical deterioration in patients with spinal DAVFs treated with steroid administration has been described. Here we report a case of cervical myelopathy caused by intracranial DAVF with acute worsening after steroid administration. The lesion was successfully treated with endovascular Onyx embolization.


Initial experience and lessons learned with implementing Lutetium-177-dotatate radiopharmaceutical therapy in a radiation oncology-based program.
To assist radiation oncology centers in implementing Lutetium-177-dotatate (177Lu) radiopharmaceutical therapy for midgut neuroendocrine tumors. Here we describe our workflow and how it was revised based on our initial experience on an expanded access protocol (EAP). A treatment team/area was identified. An IV-pump-based infusion technique was implemented. Exposure-based techniques were implemented to determine completion of administration, administered activity, and patient releasability. Acute toxicities were assessed at each fraction. A workflow failure modes and effects analysis (FMEA) was performed. A total of 22 patients were treated: 11 patients during EAP (36 administrations) and 11 patients after EAP (44 administrations). Mean 177Lu infusion time was 37 min (range 26-65 min). Mean administered activity was 97% (range 90-99%). Mean patient exposures at 1 m were 1.9 mR/h (range 1.0-4.1 mR/h) post-177Lu and 0.9 mR/h (range 0.4-1.8 mR/h) at discharge, rendering patients releasable with instructions. Treatment area was decontaminated and released same day. All patients in the EAP experienced nausea, and nearly half experienced emesis despite premedication with antiemetics. Peripheral IV-line complications occurred in six treatments (16.7%), halting administration in 2 cases (5.6%). We transitioned to peripherally inserted central catheter (PICC)-lines and revised amino acid formulary after the EAP. The second cohort of 11 patients after EAP were analyzed for PICC-line complications and acute toxicity. Nausea and emesis rates decreased (nausea G1+ 61%-27%; emesis G1+ 23%-7%), and no PICC complications were observed. FMEA revealed that a failure in amino acid preparation was the highest risk. 177Lu-dotatate can be administered safely in an outpatient radiation oncology department.


Morphology and Phase Controlled Construction of Pt-Ni Nanostructures for Efficient Electrocatalysis.
Highly open metallic nanoframes represent an emerging class of new nanostructures for advanced catalytic applications due to their fancy outline and largely increased accessible surface area. However, to date, the creation of bimetallic nanoframes with tunable structure remains a challenge. Herein, we develop a simple yet efficient chemical method that allows the preparation of highly composition segregated Pt-Ni nanocrystals with controllable shape and high yield. The selective use of dodecyltrimethylammonium chloride (DTAC) and control of oleylamine (OM)/oleic acid (OA) ratio are critical to the controllable creation of highly composition segregated Pt-Ni nanocrystals. While DTAC mediates the compositional anisotropic growth, the OM/OA ratio controls the shapes of the obtained highly composition segregated Pt-Ni nanocrystals. To the best of our knowledge, this is the first report on composition segregated tetrahexahedral Pt-Ni NCs. Importantly, by simply treating the highly composition segregated Pt-Ni nanocrystals with acetic acid overnight, those solid Pt-Ni nanocrystals can be readily transformed into highly open Pt-Ni nanoframes with hardly changed shape and size. The resulting highly open Pt-Ni nanoframes are high-performance electrocatalysts for both oxygen reduction reaction and alcohol oxidations, which are far better than those of commercial Pt/C catalyst. Our results reported herein suggest that enhanced catalysts can be developed by engineering the structure/composition of the nanocrystals.


Do exercise motives predict obligatory exercise?
Few studies have examined whether factors predicting obligatory exercise differ by gender. 303 participants completed the Obligatory Exercise Questionnaire and the Reason for Exercise Inventory. All variables correlated significantly. However, the correlation between exercising for fitness and obligatory exercise was significantly stronger in women than men. In women, obligatory exercise was predicted by exercising to improve body tone, fitness, and to enhance mood; in men, obligatory exercise was predicted by exercising to improve body tone, enjoyment, and perceived attractiveness. Implications for treatment are discussed.


Germ-free mice are not protected against diet-induced obesity and metabolic dysfunction.
Studies in the past 15 years have highlighted the role of the gut microbiota in modulation of host metabolism. The observation that germ-free (GF) mice are leaner than conventionally raised (CONV) mice and their apparent resistance to diet-induced obesity (DIO), sparked the interest in dissecting the possible causative role of the gut microbiota in obesity and metabolic diseases. However, discordant results among studies leave such relationship elusive. In this study, we compared the effects of chronic Western diet (WD) intake on body weight and metabolic function of GF and CONV mice. We fed GF and CONV mice a WD for 16 weeks and monitored body weight weekly. At the end of the dietary challenge, the metabolic phenotype of the animals was assessed. Muscle carnitine palmitoyltransferase I (CPT1) and liver AMPK activation were investigated. Both GF and CONV mice gained weight and developed glucose intolerance when fed a WD. Moreover, WD feeding was associated with increased adipose tissue inflammation, repressed hepatic AMPK activity, fatty liver and elevated hepatic triglycerides in both groups of mice. Enhanced fatty acid oxidation in the GF mouse is one of the proposed mechanisms for their resistance to DIO. The GF mice in this study showed higher CPT1 activity as compared to their CONV counterparts, despite not being protected from obesity. We provide evidence that the microbiota is not an indispensable factor in the onset of obesity and metabolic dysfunction, suggesting that the relationship between gut bacteria and metabolic diseases needs further exploration.


Seric and local antibodies against a synthetic peptide of HPV16.
An ELISA method was used to detect IgG and IgA directed against a synthetic peptide derived from the E2 ORF of the human papillomavirus (HPV) 16 in sera and in cervico-vaginal secretions from 20 women without evidence of HPV infection and from 41 women with histological diagnosis of HPV infection. The proportion of IgA positive sera (63.4% in the case-group vs. 20.0% in the control-group) and secretions (48.8% in the case-group vs. 15.0% in the control-group) was significantly higher in women with HPV infection and seemed to increase with the severity of the cervical lesion. Such a difference was not found for specific IgG. Comparing, for each patient, the antibody level in the serum and in the secretions, we found that the amount of IgA was at mean 2.4 times higher in the sera than in the secretions.


Reference conditions for ion-chamber based HDR brachytherapy dosimetry and for the calibration of high-resolution solid detectors.
The aim of this study has been to develop a two-step method of in-phantom dosimetry around a brachytherapy 192Ir photon source. The first step is to measure the absorbed dose rate to water with a calibrated ionization chamber under reference conditions, the second to cross-calibrate, under these conditions, small solid-state detectors such as silicon diodes, synthetic diamond or scintillation detectors suited for spatially resolved dose rate measurements at other, particularly at smaller source axis distances in the water phantom. This two-step approach constitutes a method for in-phantom dosimetry in brachytherapy, analogous to the "small calibration field" commonly used in teletherapy to provide the reference conditions for the cross-calibration of high-resolution detectors. Under reference conditions, all known corrections for radiation quality, volume averaging and position of the chamber's effective point of measurement (EPOM) have to be applied. The study is therefore particularly devoted to (1) the experimental determination of the position of the source axis, (2) a general formulation for the volume averaging correction factor of small ionization chambers and (3) the experimental determination of the EPOM positions for the PinPoint chamber 31014 and the 3D-PinPoint chamber PTW 31022 (both PTW Freiburg, Germany). The distance of 30mm from the source axis was chosen as the reference condition for cross calibrations. This concept is realized with the instrumentation available in a hospital, a scanning-type water phantom, a software package for small field dosimetry and detectors typically used in clinical routine dosimetry. The present development of a method of in-phantom dose measurement under 192Ir brachytherapy conditions was performed in recognition of the primary role of dose calculations, e.g. according to the AAPM TG43 recommendations. But in addition, the methodology tested here is paving a practicable way for the experimental check of typical dose values under clinical conditions, should the need arise.


Central nervous system involvement in early syphilis. Part II. Correlation between auditory brain stem responses (ABR) and cerebrospinal fluid abnormalities.
Twenty-six consecutive patients with secondary or early latent syphilis, all with normal neurological findings, were studied with auditory brainstem responses (ABR), cerebrospinal fluid (CSF) analysis and an assay for immune complexes in serum and CSF. Seven of the 26 patients studied had a pathological ABR pattern and 14 had one or more pathological CSF tests. Fifteen patients had circulating immune complexes in serum. No patient had demonstrable immune complexes in CSF. A significant correlation was found between an abnormal ABR pattern and pathological CSF findings--but not between pathological ABR and presence of immune complexes. ABR seems to be a sensitive method for detection of early asymptomatic CNS involvement in syphilis.


Long-term prognostic utility of pentraxin 3 and D-dimer as compared to high-sensitivity C-reactive protein and B-type natriuretic peptide in suspected acute coronary syndrome.
Vascular inflammation plays a key role in the development of atherosclerosis and acute coronary syndrome (ACS), and pentraxin 3 (PTX3) is one of several novel, promising markers of inflammation. In addition, D-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. The present study assesses the prognostic utility of these two biomarkers as compared to high-sensitivity C-reactive protein (hsCRP) and B-type natriuretic peptide (BNP), in addition to conventional clinical risk factors for coronary heart disease in patients with suspected ACS. Chest pain patients with suspected ACS (n = 871) were consecutively included in a prospective, observational study with a follow-up time of 84 months. At 7-year follow-up, 332 patients had died and 203 had suffered an adverse troponin T-positive, non-fatal cardiac event. In the multivariate analysis, levels of PTX3 above 5.88 ng/mL (median) and D-dimer above 436 µg/L (lower limit upper quartile) independently predicted mortality (HR 1.60 [95% CI 1.10-2.33]; p = 0.014 and HR 1.83 [95% CI 1.20-2.78]; p = 0.005, respectively). Also, BNP levels above 310.75 pg/mL (lower limit upper quartile) (HR 2.16 [95% CI 1.37-3.42]; p = 0.001), but not hsCRP, independently predicted mortality. Only hsCRP and BNP also predicted future myocardial infarction (HR 1.59 [95% CI 1.05-2.40]; p = 0.029 and HR 1.91 [95% CI 1.10-3.31]; p = 0.021, respectively). High levels of PTX3, D-dimer and BNP were found to be independent, long-term predictors of all-cause mortality in chest pain patients with a suspected ACS. hsCRP and BNP also predicted future myocardial infarction.


Serotype specificity of monoclonal antibodies to cucumber mosaic virus.
Ten monoclonal antibodies (McAbs) against cucumber mosaic virus (CMV) have been raised from fusion experiments performed after immunizing mice with different CMV antigens. Their reactivities with members of the three CMV serotypes, CMV-DTL, CMV-ToRS, and CMV-Co were tested in a double antibody sandwich format of enzyme immunosorbent assay (ELISA). Several of the McAbs were specific for different members of the CMV-DTL and CMV-ToRS groups while two allowed the detection of CMV-Co. By using a mixture of two McAbs, any member of the three major CMV serotypes could be detected in infected plant sap. One of the antibodies made it possible to discriminate between subunits and whole virions of CMV-D when it was used in ELISA simultaneously as coating antibody and as biotin-conjugate. McAbs were shown to be useful for quantifying the amount of CMV present in plant sap.


Eukaryotic elongation factor 2 kinase inhibitor, A484954 lowered blood pressure in spontaneously hypertensive rats via inducing vasorelaxation.
Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) suppresses protein translation. We previously reported eEF2K expression was upregulated in mesenteric arteries (MA) from spontaneously hypertensive rats (SHR). We have recently revealed A484954, an eEF2K inhibitor, acutely suppressed vasopressor agonists-induced increase of blood pressure (BP) in normal Wistar rats. In this study, we examined the acute effects of A484954 on BP in SHR and explored underlying mechanisms. BP was measured by a carotid cannulation method in SHR. Isometric contraction in MA from SHR was measured. Endothelial nitric oxide synthase (eNOS) dimerization was measured by low-temperature sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. A484954 lowered BP in 15-week-old SHR. A484954 induced relaxation in MA from both 4- and 7-9-week-old SHR. In MA from 4-week-old SHR, A484954-induced relaxation was inhibited almost completely by a NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME) and significantly by a β blocker, propranolol. In MA from 7-9-week-old SHR, on the other hand, A484954-induced relaxation was inhibited partly either by l-NAME, indomethacin, a cyclooxygenase inhibitor, or l-NAME + indomethacin. A484954 promoted the dimerization of eNOS in human endothelial cells. In summary, we have revealed A484954 lowers BP in SHR perhaps through the vasorelaxation via the production of endothelium-derived relaxing factors.


Comparative morphometric study on the depth of invasion in vulvar carcinoma.
Various studies assess the significance of depth of invasion as an important prognostic factor in squamous cell carcinoma of the vulva. However, methodologic problems exist with regard to the measurement points. While the deepest point of invasion can be measured accurately, the upper reference point is arbitrarily chosen. The goal of the present study was to identify the method of measurement and the threshold value, allowing the clearest prognostic differentiation between groups of patients with vulvar carcinoma. The study involved 124 patients treated between 1971 and 1980, who had received identical treatment (simple vulvectomy followed by local and inguinal irradiation) and identical histopathologic workup (large-scale sections). Beginning with the deepest point of tumor invasion, comparative measurement was carried out with three different points of reference: to the basement of the most superficial dermal papilla (method A), to the surface of the tumor (method B), and to the basement membrane of the deepest rete ridge (method C). The data were used to determine differences in specified end points. The results and conclusions are as follows: (1) The morphometrically determined degree of tumor invasion had prognostic significance. (2) Measurement of tumor thickness (method B) prognostically differentiates patient groups better than measurement of invasion from the most superficially lying epithelial papilla (method A), if classified into tumors up to and over 0.5 cm. (3) Patients with superficial invasive vulvar carcinomas up to 0.5 cm can be further prognostically differentiated into two groups, when measuring depth of invasion from the deepest rete ridge (method C), and classifying into tumors up to and over 0.3 cm.


Crystallization patterns in anterior vaginal fluid from bitches in oestrus.
Bitches exhibited a characteristic arborization pattern of the fluid from the anterior vagina during pro-oestrus and oestrus. These changes were monitored together with conventional vaginal cytology and plasma oestrogen and progestagen concentrations. A classical ferning pattern, similar to that seen in bovine cervical mucus at oestrus, occurred after the peak in plasma oestrogen concentrations. Ferning was most intense after the second peak of cornification of vaginal epithelial cells. It is suggested that a 'Ferning Index', when combined with conventional vaginal cytology, can be of use in determining the optimum mating time in the bitch.


Levels of aflatoxin B1, bacteria and fungi in feed and food in 1971 - 1987.
Totally 39% out of 8371 feed and their component samples were contaminated by aflatoxin B1. Mean contamination was 36μg/kg with maximum yield 10100 μg/kg. Contamination of samples by total count of organisms, mean contamination and maximum yield, respectively was: 1) bacteria 99%, 2.2×10(6), 2.4×10(8); 2) proteolytic bacteria 94%, 1.2×10(5), 3.0×10(6);3) moulds 98%, 1.3×10(5), 9.0×10(6); 4) yeasts 44 %, 3.3×10(4), 3.6×10(6). The samples were contaminated in 92 % byAspergillus spp, in 71% byAspergillus flavus, in 83% byPenicillium spp, and in 20% byFusarium spp with mean contamination 8.3×104, 1.1×10(3), 4.2×10(4), 5.0×10(3) , and maximum yield 6.8×10(6), 1.0×10(5), 5.0×10(6), 1.5×10(6), respectively. Totally 8.5% of strains were aflatoxinogenic and 4.4% of the strains were isolated from feed and 21 % of the strains from grain/nut.


Bone marrow adiposity modulation after long duration spaceflight in astronauts.
Space travel requires metabolic adaptations from multiple systems. While vital to bone and blood production, human bone marrow adipose (BMA) tissue modulation in space is unknown. Here we show significant downregulation of the lumbar vertebrae BMA in 14 astronauts, 41 days after landing from six months' missions on the International Space Station. Spectral analyses indicated depletion of marrow adipose reserves. We then demonstrate enhanced erythropoiesis temporally related to low BMA. Next, we demonstrated systemic and then, local lumbar vertebrae bone anabolism temporally related to low BMA. These support the hypothesis that BMA is a preferential local energy source supplying the hypermetabolic bone marrow postflight, leading to its downregulation. A late postflight upregulation abolished the lower BMA of female astronauts and BMA modulation amplitude was higher in younger astronauts. The study design in the extreme environment of space can limit these conclusions. BMA modulation in astronauts can help explain observations on Earth.


Phosphoglucose isomerase (PGI) variants in the Netherlands.
Six hundred individuals of pure Dutch ancestry have been typed for their erythrocyte phosphoglucose isomerase phenotypes by starch gel and cellulose acetate electrophoresis. In two individuals a variant phenotype was discovered. One phenotype was found to be indistinguishable from PGI-Phillips. The other variant would appear to be a new phenotype and has been designated PGI-Jager.


Transcriptomic analyses of the HPG axis-related tissues reveals potential candidate genes and regulatory pathways associated with egg production in ducks.
Egg production is one of the most important economic traits in the poultry industry. The hypothalamic-pituitary-gonadal (HPG) axis plays an essential role in regulating reproductive activities. However, the key genes and regulatory pathways within the HPG axis dominating egg production performance remain largely unknown in ducks. In this study, we compared the transcriptomic profiles of the HPG-related tissues between ducks with high egg production (HEP) and low egg production (LEP) to reveal candidate genes and regulatory pathways dominating egg production. We identified 543, 759, 670, and 181 differentially expressed genes (DEGs) in the hypothalamus, pituitary, ovary stroma, and F5 follicle membrane, respectively. Gene Ontology (GO) analysis revealed that DEGs from four HPG axis-related tissues were enriched in the "cellular component" category. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the neuroactive ligand-receptor interaction pathway was significantly enriched based on DEGs commonly identified in all four HPG axis-related tissues. Gene expression profiles and Protein-Protein Interaction (PPI) network were performed to show the regulatory relationships of the DEGs identified. Five DEGs encoding secreted proteins in the hypothalamus and pituitary have interaction with DEGs encoding targeted proteins in the ovary stroma and F5 follicle membrane, implying that they were these DEGs might play similar roles in the regulation of egg production. Our results revealed that neuroactive ligand-receptor interaction pathway and five key genes(VEGFC, SPARC, BMP2, THBS1, and ADAMTS15) were identified as the key signaling pathways and candidate genes within the HPG axis responsible for different egg production performance between HEP and LEP. This is the first study comparing the transcriptomic profiles of all HPG axis-related tissues in HEP and LEP using RNA-seq in ducks to the best of our knowledge. These data are helpful to enrich our understanding of the classical HPG axis regulating the egg production performance and identify candidate genes that can be used for genetic selection in ducks.


Effect of subconvulsive doses of bicuculline on the incorporation of radioactive precursors into glycerolipids in rat brain areas.
Bicuculline (either 25 mumol or 12.5 mumol/kg body wt) was administered to rats by intraperitoneal route. Animals treated with 25 mumol/kg experienced convulsions, whereas those receiving 12.5 mumol/kg did not. Controls received saline instead of the drug. Radioactive precursors [2-3H] glycerol and/or [1,2 14C] ethanolamine were injected into cerebral ventriculi simultaneously with bicuculline and the rats were killed 12 min afterwards. Their brains were dissected by hand into four parts (cerebellum, brain stem, hippocampus, cerebral cortex) and the labeling of lipid classes determined after extraction and separation. Although glycerol was incorporated into lipid better than ethanolamine in all areas, the fate of the injected radioactive precursors varied according both to area and treatment. The lowest uptake of radioactivity was in the cerebral cortex and the highest in the brain stem and hippocampus. Moreover, the administration of bicuculline influenced the distribution of radioactivity among lipid classes; these variations, however, were not dependent on the administered doses of bicuculline. We conclude that the effects on glycerolipid metabolism observed in convulsing animals are due to several causes including alterations of systemic parameters (hypertension, hypoxia, etc.). The distribution of glycerol label between phospholipid and neutral lipid is proposed as a biochemical model for the study of convulsive and subconvulsive states.


Early post-hatch fasting induces satellite cell self-renewal.
Early post-hatch satellite cell kinetics are an important aspect of muscle development, and understanding the interplay between fasting and muscle development will lead to improvements in muscle mass following an illness, and optimal meat production. The objective of this experiment was to test the influence of immediate post-hatch fasting on satellite cells in the poult. Male Nicholas poults (Meleagris gallopavo) were placed into two treatments: a fed treatment with immediate access to feed and water upon placement and a fasted treatment without access to feed and water for the first three days post-hatch. 5-bromo-2'-deoxyuridine (BrdU) was injected intra-abdominally in all poults to label mitotically active satellite cells. The pectoralis thoracicus muscle was harvested two hours following the BrdU injection. Immunohistochemistry for BrdU, Pax7, Bcl-2, Pax7 with BrdU, and determining myofiber cross-sectional area along with computer-based image analysis was used to study muscle development. Fed poults had higher body masses throughout the experiment (P< or =0.01), and they had higher pectoralis thoracicus muscle mass (P< or =0.01) at ten days of age than the fasted poults. Fed poults had higher satellite cell mitotic activity at three days and four days of age (P< or =0.01) compared to the fasted poults. However, Pax7 labeling index was higher in the fasted poults (P< or =0.01) at three days, four days, and five days post-hatch than the fed group. Similarly Bcl-2 labeling was higher in the fasted than in the fed group at three days post-hatch. Therefore, fasting depleted proliferating satellite cells indicated by the lower BrdU labeling in the fasted poults compared to the fed poults, and conserved the satellite cell proliferative reserve indicated by the higher level of Pax7 labeling for the fasted poults compared to the fed poults.


Stereotactic body radiotherapy in patients with hepatocellular carcinoma in a multimodal treatment setting.
Retrospective evaluation of stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC). We retrospectively analyzed 36 patients (45 lesions) treated between 2011 and 2017. Twenty-seven had previous treatments. Current treatment consisted of SBRT alone (n = 15) or selective transarterial chemoembolization (TACE) followed by SBRT to the same lesions (n = 21). Eight patients received additional local treatments to different lesions. Liver function was predominantly moderately restricted (Child A: 29, Child B: 6, Child C: 1). Treatment planning was based on 4D-computed tomography, dose/fractionation varied depending on location and size, most commonly 3 fractions of 12.5 Gy (65% isodose) and 5 fractions of 8 Gy (80% isodose). Median follow-up was 15 months. Local recurrence was observed in 3 lesions (7%), resulting in 1‑and 2‑year local control rates of 93%. The only significantly predicting factor was the use of abdominal compression. New hepatic lesions occurred in 19 patients (52%), 1‑ and 2‑year freedom-from-hepatic-failure (FFHF) was 39% and 32%, respectively. Only the number of treated lesions was predictive for FFHF. Sixteen patients have died, resulting in 1‑ and 2‑year overall survival (OS) of 64% and 41%, respectively, significantly impacted by the number of treated lesions and Child-Pugh class. Severe acute and late toxicity (≥grade 3) was observed in 3% and 8%, respectively. 6 patients (17%) received liver transplantation (OLT) after SBRT, of whom 5 showed pathological complete remission. SBRT (±TACE) in highly pretreated HCC is effective and associated with excellent LC and low toxicity. SBRT may be used as definitive or bridging treatment prior to OLT. Patients with multifocal lesions have significantly decreased 1‑ and 2‑year FFHF and OS.


Self-reference and coronary heart disease incidence in the Western Collaborative Group Study.
Previous research has indicated that the spoken frequency of the self-references "I," "me," and "my" in a structured interview was prospectively related to coronary heart disease (CHD). To assess whether the findings would replicate in another population, we conducted a case-control analysis of 750 structured interviews from the Western Collaborative Group Study. To measure self-references, auditors counted all first person pronouns (I, me, my) and clauses spoken in the audiotaped baseline structured interviews. Matched multiple logistic regression analyses, with or without adjustment for major CHD risk variables, indicated that those who incurred CHD did not self-reference more frequently or densely than the CHD-free control subjects. Type As spoke more clauses and more total self-references but did not have a higher density of self-references than Type Bs. The results question both the method for measuring self-references and the hypothesis that self-referencing are associated with CHD.


Eruptive pseudoangiomatosis: a unique childhood exanthem?
We describe three children with an acute onset and spontaneous resolution of angioma-like papules during an apparent viral illness. A biopsy specimen from one patient revealed a unique histologic appearance that consisted of dilated dermal blood vessels with plump hobnail-shaped endothelial cells. On the basis of the natural history and histopathologic features of this exanthem, we suggest the name eruptive pseudoangiomatosis.


Perivascular deposits of serum proteins in cerebral cortex in vascular dementia.
Immunocytochemical techniques were used to study the histopathologic changes in vascular dementia, i. e., both multi-infarct dementia (MID) and MID combined with Alzheimer changes (MID/SDAT). In eight of 13 of the dementia cases strongly immunostained deposits of plasma proteins were observed around numerous capillaries of layers I-IV of frontal grey matter. Each of these deposits contained albumin, prealbumin, IgG, C1q, C3c, and fibrinogen. No such deposits were found in any of the seven non-demented aged controls. In contrast, in white matter in both demented and normal aged control cases only weak immunostaining of serum proteins was observed which gradually decreased with the distance from the vessels. The presence of heavy deposits of serum proteins exclusively around the capillaries of the gray matter in cases with vascular dementia may indicate a defect of the cortical capillary system which might play a role in the clinical symptoms seen in vascular dementia. The enrichment of C1q within the deposits is intriguing as this might occur because of the binding of C1 through its subunit C1q to the antibody-antigen complex and thereby support a possible immunologic involvement in the formation of these deposits.


Specific antibody response in porcine respiratory tract secretion following intraperitoneal immunization.
Experiments were conducted to determine whether intraperitoneal (IP) immunization and subsequent intratracheal (IT) challenge were able to augment the specific antibody response in secretions of the porcine respiratory tract. Following IP immunization and two IT challenges within a period of 18 days the specific IgG and IgA antibody response was elevated in respiratory tract secretions and serum. While a portion of the anti-ovalbumin (OVA) IgG in respiratory tract secretions was generated locally, it would appear that the bulk of anti-OVA IgA was derived from serum.


Parkinson's Disease Stigma Questionnaire (PDStigmaQuest): Development and Pilot Study of a Questionnaire for Stigma in Patients with Idiopathic Parkinson's Disease.
Stigma is significant in Parkinson's disease (PD). However, no specific tool is available to assess stigma in PD comprehensively. This pilot study aimed to develop and test a stigma questionnaire specific to PD patients (PDStigmaQuest). Based on a literature review, clinical experience, expert consensus, and patients' feedback, we developed the preliminary, patient-completed PDStigmaQuest in German language. It included 28 items covering five stigma domains: uncomfortableness, anticipated stigma, hiding, experienced stigma, and internalized stigma. In this pilot study, 81 participants (PD patients, healthy controls, caregivers, and health professionals) were included to investigate the acceptability, feasibility, comprehensibility, and psychometric properties of the PDStigmaQuest. The PDStigmaQuest showed 0.3% missing data points for PD patients and 0.4% for controls, suggesting high data quality. Moderate floor effects, but no ceiling effects were found. In the item analysis, most items met the standard criteria of item difficulty, item variance, and item-total correlation. Cronbach's alpha was > 0.7 for four of five domains. PD patients' domain scores were significantly higher than healthy controls' for uncomfortableness, anticipated stigma, and internalized stigma. Feedback to the questionnaire was predominantly positive. Our results indicate that the PDStigmaQuest is a feasible, comprehensive, and relevant tool to assess stigma in PD and helps to understand the construct of stigma in PD further. Based on our results, the preliminary version of the PDStigmaQuest was modified and is currently validated in a larger population of PD patients for use in clinical and research settings.


Serum lysophosphatidylcholines to phosphatidylcholines ratio is associated with symptomatic responders to symptomatic drugs in knee osteoarthritis patients.
Identification of the optimal treatment for a given patient is of paramount importance. This is of particular relevance in osteoarthritis (OA) because of the high prevalence of the disease, extensive heterogeneity of the disease, and need for long-term treatment. The aim of the study was to examine whether serum lysophosphatidylcholines (lysoPCs) to phosphatidylcholines (PCs) ratio can predict clinical response to licofelone and naproxen treatments in symptomatic knee OA patients. One hundred fifty-eight OA patients who completed the study according to protocol (ATP) of a previous 24-month clinical trial cohort comparing the effect of licofelone vs. naproxen in symptomatic knee OA patients were included. Symptomatic responses to either treatments were classified according to the OARSI-OMERACT criteria based on the WOMAC scores at 24 months. Total concentrations of PCs and lysoPCs were measured in the serum samples collected before the initiation of the treatments, and the lysoPCs to PCs ratio was calculated. Student's t test was utilized to compare the difference in the ratio of lysoPCs to PCs between the symptomatic responders and non-responders. Logistic regression was utilized to adjust for the potential confounders. Receiver operating characteristic (ROC) analysis was performed to identify the optimal cutoff of the ratio for prediction. Data showed that 61.4% of the patients symptomatically responded to licofelone and naproxen and 38.6% were deemed as therapeutic failures (non-responders). There was no difference in responders between licofelone and naproxen (p = 0.87). Responders had a significantly higher lysoPCs to PCs ratio than non-responders (0.097 ± 0.003 vs. 0.085 ± 0.003; p = 0.006). Patients with a ratio greater than the optimal cutoff of 0.088 had 2.93 times more likely to respond to licofelone and naproxen (p = 0.002). Serum lysoPCs to PCs ratio is a marker for response to licofelone and naproxen and may aid in the personalized treatment to knee OA.


Replantation of the upper extremity in children.
Since Malt and McKhann performed the first successful replantation of a traumatically amputated extremity in 1962, there has been a flurry of case reports and articles debating the pros and cons of the various technical aspects of replantation. There have been three case reports of children, under the age of 15, who have successfully undergone replantation of the upper extremity transected throught the humerus. The first case report in this article is the fourth. The factors involved in selecting replantation or amputation, and the technical aspects of the operation which are felt to be important, are briefly reviewed. Because the mechanics of limb replantation are rather straightforward, we feel that the pediatric surgeon should be familar with the preoperative and intraoperative factors to be weight, and that this alternative to stump closure be carefully considered when one is presented with an upper extremity transection.


A hyperalgesic effect of intracerebroventricular cytokine-induced neutrophil chemoattractant-1 in the rat paw pressure test.
Cytokine-induced neutrophil chemoattractant-1 (CINC-1) is a member of the chemokine superfamily. The effect of intracerebroventricular (i.c.v) injection of CINC-1 on the mechanical nociceptive threshold in the rat was examined using the paw-pressure test. An i.c.v. injection of CINC-1 at doses of 1 and 10 pg/rat tended to decrease the nociceptive threshold for mechanical stimuli at 15 min after the injection, and significantly lowered the threshold at 30 min. The threshold stayed at these lowered level over 180 min after the injection. Lower (100 fg/rat) and higher (30 and 100 pg/rat, and 1 and 10 ng/rat) doses of CINC-1 had no effect on the mechanical nociceptive threshold. The present results suggest that CINC-1 facilitates mechanical nociception in the central nervous system (CNS).


Single-strand DNA-scaffolded copper nanoclusters for the determination of inorganic pyrophosphatase activity and screening of its inhibitor.
A fluorescence method for the determination of inorganic pyrophosphatase (PPase) activity has been established based on copper nanoclusters (CuNCs). The polythymine of 40 mer (T40) acts as a template for the reduction reaction from Cu2+ to Cu0 by ascorbic acid (AA). This reaction leads to the formation of fluorescent CuNCs with excitation/emission peaks at 340/640 nm. However, the higher binding affinity between inorganic pyrophosphate (PPi) and Cu2+ hinders the effective formation of CuNCs. This shows low fluorescence intensity. PPase catalyzes the hydrolysis of PPi into Pi during which free Cu2+ ions are produced. This facilitates the formation of fluorescent CuNCs. Thus, the fluorescence intensity was restored. The fluorescence enhancement of the system has a linear relationship with PPase activity in the range 0.3 to 20 mU·mL-1, and the detection limit is0.2 mU·mL-1. The relative intensity (I/I0) at 640 nm for the analytical solution versus system is also employed to screen the inhibitor for PPase with high efficiency. Graphical abstract Schematic representation of a fluorescent assay for the determination of inorganic pyrophosphatase activity and screening its inhibitor based on single-strand polythymine-scaffolded copper nanoclusters.


Synthesis and Modification of Tetrahedron Li10.35Si1.35P1.65S12 via Elemental Doping for All-Solid-State Lithium Batteries.
Solid-state electrolyte (SSE), as the core component of solid-state batteries, plays a critical role in the performance of the batteries. Currently, the development of SSE is still hindered by its high price, low ionic conductivity, and poor interface stability. In this work, we report the tailored synthesis of a high ionic conductive and low cost sulfide SSE for all-solid-state lithium batteries. The Li10.35Si1.35P1.65S12 with favorable tetragonal structure was synthesis by increasing the concentration of Si4+, which shows an ionic conductivity of 4.28 × 10-3 S cm-1 and a wide electrochemical stability window of up to 5 V. By further modifying the composition of the electrolyte via ionic doping, the ionic conductivity of Li10.35Si1.35P1.65S12 can be further enhanced. Among them, the 1% Co4+-doped Li10.35Si1.35P1.65S12 shows the highest ionic conductivity of 6.91 × 10-3 S cm-1, 40% higher than the undoped one. This can be attributed to the broadened MS4 - tetrahedrons and increased Li+ concentration. As a demonstration, an all-solid-state Li metal battery was assembled using TiS2 as the cathode and 1% Co4+-doped Li10.35Si1.35P1.65S12 as the electrolyte, showing capacity retention of 72% at the 110th cycle. This strategy is simple and can be easily extended for the construction of other high-performance sulfide SSEs.


Debunking material induction.
In this paper, we present an explanatory objection to Norton's material theory of induction, as applied to predictive inferences. According to the objection we present, there is an explanatory disconnect between our beliefs about the future and the relevant future facts. We argue that if we recognize such a disconnect, we are no longer rationally entitled to our future beliefs.


Management of penetrating lung injuries in civilian practice.
Recent reports of military thoracic injuries have advocated early thoracotomy and aggressive management of pulmonary injuries with resection as opposed to the more conservative and traditional treatment with chest tube thoracostomy. A retrospective study was therefore performed to determine the incidence of thoracotomy and lung resection in civilian injuries and to evaluate the effectiveness of treatment of these injuries. Between 1973 and 1985, in a series of 1,168 patients, there were 384 gunshot wounds and 784 stab wounds to the thorax. Two hundred eighty-three patients with a gunshot wound (74%) and 602 with a stab wound (77%) were treated with chest tubes alone. Sixty-eight patients (6% of the total) required operative repair of pulmonary hilar or parenchymal injury. Pulmonary resection was necessary in only 18 patients (nine with a gunshot wound and nine with a stab wound), and 10 patients had repair of hilar injuries (nine with a gunshot wound and one with a stab wound). Of patients requiring pulmonary resection, nine required wedge or segmental resection, six required lobectomy, and three patients required pneumonectomy. Mortality for all thoracic injuries was 2.3%: for those treated with chest tube alone, 0.7%; for pulmonary hilar injuries, 30%; for pulmonary parenchymal injuries, 8.6%; and for injuries necessitating lung resection, 28%. Most civilian lung injuries can be treated by tube thoracostomy alone. Although relatively few patients with primary pulmonary injury require thoracotomy, those that do are at significant risk and may require lung resection to control bleeding or hemoptysis or to remove destroyed or devitalized lung tissue.


Behavioral and neurological comparisons of neonates born to mothers of differing social environments.
Sixty newborn infants, 30 born to parents of middle to upper-middle socioeconomic status and 30 born to parents of limited personal-social resources, were assessed on the Neonatal Behavioral Assessment Scale. Although no difference between groups was found in motor and neurological status, data from this study did indicate that the prenatal factors, having no obvious physiological base, associated with the parental social environment, may affect the newborn's behavioral outcome.


A semiquantitative PCR technique for detecting chimerism in hamster-to-rat bone marrow xenotransplantation.
Although bone marrow transplantation has been used to induce donor-specific tolerance in many allogeneic models, similar effort in xenogeneic transplantation is met with obstacles like more severe graft versus host disease (GVHD). We are currently engaged in developing a GVHD-free hamster-to-rat xenotransplantation model using splenectomy, total body irradiation, and donor bone marrow transplantation. To test donor cell chimerism, particularly in the solid tissues, we developed a semiquantitative polymerase chain reaction (PCR) method using primers specific for hamster beta-actin and mitochondrial cytochrome C oxidase I and II (MCO I and II) genes and rat sex determination region on the Y chromosome (SRY) gene. Using this method, we estimated the level of hamster cells chimerism in rats subjected to splenectomy, total body irradiation (10 Gy), and hamster bone marrow transplantation (3 x 10(8) cell/recipient) and observed high levels of donor cells in all recipient tissues tested.