Use of ECT in the United States in 1975, 1980, and 1986.
The objective was to analyze nationally representative data from the National Institute of Mental Health (NIMH) to update trends in the use of ECT in the United States. The data are estimates from the NIMH Sample Survey Program for 1975, 1980, and 1986, which include representative samples of inpatients in psychiatric facilities in the United States. The authors' analyses use trend data from public general hospitals, private general hospitals, private psychiatric hospitals, and state and county mental hospitals. They report on 126,739 patients who received ECT in 1975, 1980, and 1986, focusing on data from 1980 and 1986. In 1986, 36,558 patients received ECT. This represents a decrease from the 1975 figure (58,667 patients) but no change from 1980 (31,514 patients). ECT was used primarily in private general hospitals (64%) and private psychiatric hospitals and much less often in public general hospitals and state and county mental hospitals. In 1986 over 90% of ECT recipients were white, and 84% had an affective disorder diagnosis. Although 71% of the patients who received ECT were women, hospital type and age were more important than gender in predicting ECT use. Individuals 65 years of age and older received ECT out of proportion to their numbers in inpatient care. The declining use of ECT in the United States ended in the 1980s. Few African Americans receive ECT, and its use is becoming more targeted toward patients with affective disorders. The amount of services research done on this modality is very small. Basic questions have yet to be answered, including who refers patients for ECT and why, and how ECT fits into the overall course of treatment.


Assessment of endpoints in pulmonary arterial hypertension associated with connective tissue disease.
Connective tissue disease-associated pulmonary arterial hypertension (PAH) is mostly related to systemic sclerosis, overlap syndromes with features of systemic sclerosis, mixed connective tissue disease, and systemic lupus erythematosus. It is an important cause of mortality in these conditions and represents up to one third of patients seen in most specialist pulmonary hypertension centers. Patients with PAH associated with connective tissue disease may have a worse outcome than those with other forms of PAH. Most randomized clinical trials of PAH therapies have included patients with connective tissue disease as part of a mixed population. Overall, analyses suggest that treatment responses parallel those seen in idiopathic PAH, though subgroup analyses must be interpreted with caution. There may also be significant comorbidity from other pulmonary complications such as interstitial fibrosis, aspiration, or chest wall restriction. In addition, the majority of clinical trials have used 6-minute walk distance as the primary endpoint; the clinical relevance of this is questionable in connective tissue disease patients, who often have multiple comorbidities, other than PAH, which adversely affect exercise tolerance.


Unmasking the molecular link between arrhythmogenic cardiomyopathy and Brugada syndrome.
The intercalated discs that connect cardiomyocytes control cell-to-cell adhesion and communication. Several macromolecular structures (desmosomes, fascia adherens junctions, gap junctions, and sodium-channel complexes) coexist in, and confer their mechanical and electrical properties to, the intercalated disc. Traditionally, each structure was assumed to have a unique function in the intercalated disc. However, growing evidence suggests that these complexes act together in intercellular communication and adhesion, forming a single structural and functional entity - the connexome. This nascent idea has provided conceptual support for the overlapping of two diseases based on disturbance of the intercalated disc - arrhythmogenic cardiomyopathy (ACM) and Brugada syndrome (BrS). In this Perspectives article, we present the latest findings about the functions of, and interactions between, the structures of the intercalated disc that support the concept of the connexome. We also summarize the genetic, molecular, and pathophysiological mechanisms underlying ACM and BrS, focusing on the overlap between these diseases.


Successful hepatitis B vaccination in patients who underwent transplantation for hepatitis B virus-related cirrhosis: preliminary results.
Long-term hepatitis B immunoglobulin (HBIg) prophylaxis prevents endogenous hepatitis B virus (HBV) reinfection in the majority of liver transplant recipients. Active hepatitis B vaccination after orthotopic liver transplantation (OLT) in these patients has produced conflicting results to date. On this study, patients who remained hepatitis B surface antigen (HBsAg) negative with passive immunization after OLT for HBV cirrhosis were actively immunized using recombinant HBV antigen (Engerix), together with a novel adjuvant system (monophosphoryl lipid A and a natural saponine molecule). This led to a sustained antibody response to HBsAg (>500 IU/L) in 5 of 10 patients. This antibody response prevented reinfection and allowed termination of prophylactic HBIg substitution for more than 12 months in these patients.


Left-sided Poland's syndrome associated with dextrocardia.
Poland's syndrome is a rare congenital anomaly accompanied by the absence of the pectoralis major, and the ipsilateral upper-limb and chest wall deformities. Hypoplasia of the breast, agenesis of the ipsilateral rib cartilage, athelia, and ipsilateral developmental finger anomalies such as syndactyly can also be seen. In the literature, only 56 cases of dextrocardia and left-sided Poland's syndrome have been described. Herein, a case of left-sided Poland's syndrome coexisting with dextrocardia and nasal hemangioma was presented.


Ethnic inequalities in involuntary admission under the Mental Health Act: an exploration of mediation effects of clinical care prior to the first admission.
Studies show ethnic inequalities in rates of involuntary admission and types of clinical care (such as psychological therapies). However, few studies have investigated if there is a relationship between clinical care practices and ethnic inequalities in involuntary admission. This study investigated the impact of ethnicity and clinical care on involuntary admission and the potential mediation effects of prior clinical care. In this retrospective cohort study, we used data from the electronic records of the South London and Maudsley NHS Foundation Trust and identified patients with a first hospital admission between January 2008 and May 2021. Logistic regression and mediation analyses were used to investigate the association between ethnicity and involuntary admission, and whether clinical care, in the 12 months preceding admission, mediates the association. Compared with White British people, higher odds of involuntary admission were observed among 10 of 14 minority ethnic groups; with more than twice the odds observed among people of Asian Chinese, of Asian Bangladeshi and of any Black background. There were some ethnic differences in clinical care prior to admission, but these had a minimal impact on the inequalities in involuntary admission. More out-patient appointments and home treatment were associated with higher odds of involuntary admission, whereas psychological therapies and having a care plan were associated with reduced odds of involuntary admission. Ethnic inequalities in involuntary admission persist after accounting for potential mediating effects of several types and frequencies of clinical care. Promoting access to psychological therapies and ensuring that care plans are in place may reduce involuntary admissions.


Continued Inpatient Care After Primary Total Knee Arthroplasty Increases 30-Day Post-Discharge Complications: A Propensity Score-Adjusted Analysis.
Discharge destination, either home or skilled care facility, after total knee arthroplasty (TKA) may be associated with significant variation in postacute care outcomes. The purpose of this study was to characterize the 30-day postdischarge outcomes after primary TKA relative to discharge destination. All primary unilateral TKAs performed for osteoarthritis from 2011-2014 were identified in the National Surgical Quality Improvement Program database. Propensity scores based on predischarge characteristics were used to adjust for selection bias in discharge destination. Propensity-adjusted multivariable logistic regressions were used to examine associations between discharge destination and postdischarge complications. Among 101,256 primary TKAs identified, 70,628 were discharged home and 30,628 to skilled care facilities. Patients discharged to facilities were more frequently were female, older, higher body mass index class, higher Charlson comorbidity index and American Society of Anesthesiologists scores, had predischarge complications, received general anesthesia, and classified as nonindependent preoperatively. Propensity adjustment accounted for this selection bias. Patients discharged to skilled care facilities after TKA had higher odds of any major complication (odds ratio = 1.25; 95% confidence interval, 1.13-1.37) and readmission (odds ratio = 1.81; 95% confidence interval, 1.50-2.18). Skilled care was associated with increased odds for respiratory, septic, thromboembolic, and urinary complications. Associations with death, cardiac, and wound complications were not significant. After controlling for predischarge characteristics, discharge to skilled care facilities vs home after primary TKA is associated with higher odds of numerous complications and unplanned readmission. These results support coordination of care pathways to facilitate home discharge after hospitalization for TKA whenever possible.


Propagation of granulocytic Ehrlichia spp. from human and equine sources in HL-60 cells induced to differentiate into functional granulocytes.
Ehrlichia spp. from human and equine sources in the northeastern Unites States were detected by PCR, isolated, and propagated in the HL-60 promyelocytic leukemia cell line. Growth of Ehrlichia from both equine and human sources was enhanced by addition of retinoic acid, which causes granulocytic differentiation of the HL-60 cells. DNA sequencing of a portion of the 16S rDNA gene supported the hypothesis that the same pathogen was responsible for both equine and human granulocytic ehrlichiosis.


[The electrophysiological phenomenon of prolonged epileptiform peak-wave activity to the slow sleep phase].
Thirty-six cases of epilepsy with the phenomenon of prolonged epileptiform peak-wave activity in slow sleep (PESS) are presented. The peculiarities of this phenomenon are singled out. Basing on the obtained results, the authors describe a modified variant of PESS pattern which is characterized by the presence of the stable regional amplitude prevalence of peak-wave discharges and/or stable regional epileptiform activity in the "classic" PESS pattern.


Testing hypotheses about sun-climate complexity linking.
We reexamine observational evidence presented in support of the hypothesis of a sun-climate complexity linking by N. Scafetta and B. J. West, Phys. Rev. Lett. 90, 248701 (2003)10.1103/PhysRevLett.90.248701, which contended that the integrated solar flare index (SFI) and the global temperature anomaly (GTA) both follow Lévy walk statistics with the same waiting-time exponent mu approximately 2.1. However, their analysis does not account for trends in the signal, cannot deal correctly with infinite variance processes (Lévy flights), and suffers from considering only the second moment. Our analysis shows that properly detrended, the integrated SFI is well described as a Lévy flight, and the integrated GTA as a persistent fractional Brownian motion. These very different stochastic properties of the solar and climate records do not support the hypothesis of a sun-climate complexity linking.


[Acute respiratory failure due to pneumocystis pneumonia successfully treated with combined use of sivelestat sodium hydrate].
A 22-year-old man was admitted to our hospital with fever, cough and dyspnea. His chest radiograph showed diffuse ground-glass attenuation in both lung fields. Arterial blood gas analysis showed hypoxemia (PaO2 28.7 Torr breathing room air) and he required mechanical ventilation within 6 hours after admission. Gomori methenamine silver (GMS) stain of the bronchoalveolar lavage (BAL) fluid smear showed round and indented organisms, and polymerase chain reaction revealed pneumocystis jirovecii in the BAL fluid. The HIV antibody was positive and peripheral blood CD4-positive lymphocytes decreased to 4.0%. Pneumocystis pneumonia complicated with acquired immunodeficiency syndrome (AIDS) was diagnosed. There was no four-fold rise in screen viral titers. We treated him with antibiotics, trimethoprim-sulfamethoxazole, ganciclovir, fos-fluconazole, steroid pulse therapy and sivelestat sodium hydrate. Respiratory failure was relieved within 5 days following treatment. The percentage of neutrophils in the BAL fluid was elevated (44.6%). Neutrophil elastase on admission was increased and improved to the normal range after treatment. Sivelestat sodium hydrate is an anti-neutrophil elastase inhibitor and may be one of the treatment options for acute respiratory failure due to pneumocystis pneumonia in AIDS patients.


The Impact of motivational interviewing on illness perception in patients with stable coronary artery disease. A randomised controlled study
Background: Coronary heart disease (CHD) constitutes one of the most frequent causes of death for individuals > 60 years. Lifestyle dependent risk factors are key. Hence, cardiac rehabilitation is essential for optimal CHD treatment. However, individuals rarely comprehend their illness. Motivational interviewing promotes illness perception. Aim/Methods: A randomised-controlled study was conducted to determine the effect of motivational interviewing on illness perception. Patients with stable coronary heart disease were consecutively recruited after elective percutaneous transluminal coronary angioplasty (PTCA). The intervention group received a short motivational interview (MI) about the disease and related risk factors as an intervention. The control group had usual treatment. Illness perception was assessed (Illness Perception Questionnaire-Revised) prior to the intervention and six months afterwards. Results: A total of 312 patients (intervention group: n = 148, control group: n = 164) were recruited into the study (mean age: 66.2 years). After the intervention, a significant change was observed in the domain of emotional reactions regarding the disease. Conclusion: To improve illness perception in patients with stable CHD, one short intervention with MI may have an effect. Whether intensifying the MI-intervention is more effective, requires further research.


Annulatascus nilensis sp. nov., a new freshwater ascomycete from the River Nile, Egypt.
Annulatascus nilensis sp. nov., from freshwater habitats in Egypt, is described, illustrated and compared to other species in the genus. Phylogenetic analyses of its LSU rDNA sequence with similar fungi placed the new species in the genus Annulatascus (Annulatascaceae, Sordariomycetidae incertae sedis). Annulatascus nilensis is characterized by immersed ascomata with an ascomatal neck oriented horizontally to the substrate surface, asci with a long, narrow stalk and massive bipartite apical ring, and 5-11-septate, hyaline ascospores surrounded by a large irregular, granular sheath that is not seen in water.


[Snacking behaviors of Chinese female adults aged 18 to 49 years old in 2004-2015].
To describe shift in snacking behavior among Chinese female adults aged 18 to 49 years old in 2004-2015, and to analyze the contribution of snacks to energy and nutrients among them. The present study used data from "China Health and Nutrition Health" where a multistage stratified cluster design was employed to select a stratified probability sample. A total of 12 523 female participants aged 18-49 years old who participated in surveys conducted in 2004-2015 with completed data of demographic characteristics and dietary measurementswere selectedas subjects. There were 2376, 2149, 2142, 2844 and 3012 subjects in waves of 2004, 2006, 2009, 2011, and 2015, respectively. Multivariate Logistic regression model was used to analyze the relationship between socioeconomic factors and snack consumption. Generalized linear model was used to analyze the energy and nutrient intake of snack consumers and non-snack consumers, as well as the contribution of snacks to energy and nutrients. The consumption rate of snacking for women aged 18 to 49 years old had an increasing trend over time(P<0.05), and the rate was 14.24% in 2015, 3.5 times as high as that in 2004. Participants aged 18 to 29 years old whose snake consumption rates were relatively higher compared to those of other aged groups in general waves; also, female adults from the higher education group, the higher yearly income group, and the higher urbanicity index group, and those with the history of smoking or the alcohol use tended to consumed snacks. The change of the influential factors in relation to the consumption of the participant's snack was observed, and age, income level, education level, living area, and the behavior of smoking and drinking were all important factors of snacking. The daily energy and nutrient intake of female snack consumers aged 18 to 49 years old was higher than that of non-snack consumers. The contribution rate of snacks to energy and nutrients varies significantly between survey years; and the contribution of snacks to energy and main nutrients was more than 20% in 2011. Snacks have become an important part of the diet of Chinese women aged 18 to 49 years old. Future health promotion programs should be targeted on nutrition education and intervention to guide a reasonable diet structure.


Sinusitis in children.
Upper respiratory tract infection and allergic inflammation are recognized as the important risk factors for acute sinusitis, with upper respiratory tract infection being most common. In children with acute or chronic sinusitis, the respiratory symptoms of nasal discharge, nasal congestion and cough are usually prominent. Radiography has traditionally been used to determine the presence or absence of sinus disease. The radiographic findings most diagnostic of bacterial sinusitis are diffuse opacification, mucous membrane thickening or an air-fluid level. The predominant organisms include Streptococcus pneumoniae, Branhamella catarrhalis and nontypable Haemophilus influenzae. Several viruses including adenovirus and parainfluenzae have also been recovered. Clinical improvement is prompt in nearly all children treated with an appropriate antimicrobial agent.


Magnesium hydrogen carbonate natural mineral water enriched with K(+)-citrate and vitamin B6 improves urinary abnormalities in patients with calcium oxalate nephrolithiasis.
The influence of drinking magnesium hydrogen carbonate natural mineral water enriched with potassium citrate on urinary metabolic abnormalities was prospectively studied in 27 patients with recurrent calcium oxalate nephrolithiasis. The mean 24-hour urinary pH shifted from 6.34 to 6.93 (p < 0.01), the mean urinary magnesium/urinary creatinine ratio rose from 0.47 to 0.67 (p < 0.01), the mean urinary citrate/urinary creatinine ratio increased from 0.26 to 0.35 (p NS), and the mean 24-hour urinary calcium decreased from 7.98 to 6.05 mmol (p < 0.05). The effects of magnesium hydrogen carbonate natural mineral water enriched with potassium citrate were found to be favorable on urinary calcium, urinary magnesium/urinary creatinine ratio and urinary pH in patients with calcium oxalate nephrolithiasis.


Life cycle analysis of fuel production from fast pyrolysis of biomass.
A well-to-wheels (WTW) analysis of pyrolysis-based gasoline was conducted and compared with petroleum gasoline. To address the variation and uncertainty in the pyrolysis pathways, probability distributions for key parameters were developed with data from literature. The impacts of two different hydrogen sources for pyrolysis oil upgrading and of two bio-char co-product applications were investigated. Reforming fuel gas/natural gas for H2 reduces WTW GHG emissions by 60% (range of 55-64%) compared to the mean of petroleum fuels. Reforming pyrolysis oil for H2 increases the WTW GHG emissions reduction up to 112% (range of 97-126%), but reduces petroleum savings per unit of biomass used due to the dramatic decline in the liquid fuel yield. Thus, the hydrogen source causes a trade-off between GHG reduction per unit fuel output and petroleum displacement per unit biomass used. Soil application of biochar could provide significant carbon sequestration with large uncertainty.


[Perioperative complications of transurethral resection of bladder tumor in patients receiving antithrombotic therapy].
We examined perioperative complications of transurethral resection of bladder tumor (TURBT) in patients receiving antithrombotic therapy. We retrospectively studied 276 patients who underwent TURBT in our institute from January 2007 to March 2013. The study group consisted of 105 patients (38%) who were receiving antithrombotic agents, and the other 171 patients (62%) without antithrombotic agents were assigned to the control group. The period of discontinuation of antithrombotic agents complied with our institutional rule. The most frequently used agent was aspirin (69 patients : 66%), followed by warfarin (25 patients : 24%). Fourteen patients receiving warfarin (56%) needed heparin bridging therapy. There was no significant difference in average operative time (51 minutes versus 54 minutes), or average days to removal of urethral catheter (3.7 days versus 3.3 days) between the study and control groups. Hemorrhagic and ischemic complications were noted in 11 (10.5%) and 2 (1.9%) patients in the study group and 11 (6.4%) and none (0%) of the patients in the control group, respectively, with no significant difference between the 2 groups. However, prevalence of hemorrhagic complications in patients receiving heparin bridging therapy (21.4%) was significantly higher than that in the control group. Ischemic complications in the study group included chest pain suggestive of angina in one patient and acute myocardial infarction leading to death in another patient. We should pay attention to hemorrhagic complications in patients receiving heparin bridging therapy and keep in mind the possibility of lethal ischemic complications after discontinuation of antithrombotic agents.


A novel aspartic protease with HIV-1 reverse transcriptase inhibitory activity from fresh fruiting bodies of the wild mushroom Xylaria hypoxylon.
A novel aspartic protease with HIV-1 RT inhibitory activity was isolated and characterized from fruiting bodies of the wild mushroom Xylaria hypoxylon. The purification protocol comprised distilled water homogenization and extraction step, three ion exchange chromatographic steps (on DEAE-cellulose, Q-Sepharose, and CM-cellulose in succession), and final purification was by FPLC on Superdex 75. The protease was adsorbed on all the three ion exchangers. It was a monomeric protein with a molecular mass of 43 kDa as estimated by SDS-PAGE and FPLC. Its N-terminal amino acid sequence was HYTELLSQVV, which exhibited no sequence homology to other proteases reported. The activity of the protease was adversely affected by Pepstatin A, indicating that it is an aspartic protease. The protease activity was maximal or nearly so in the pH range 6-8 and in the temperature range 35-60°C. The purified enzyme exhibited HIV-1 RT inhibitory activity with an IC₅₀ value of 8.3 μM, but was devoid of antifungal, ribonuclease, and hemagglutinating activities.


Augmentation of unstable pertrochanteric fractures in the osteoporotic elderly patient: operative technique for 1 or 2 head screw systems.
The incidence of proximal femoral fractures has substantially risen in the elderly. This rise has been attributed to an increase in their life span and the underlying poor bone stock and osteoporosis. One of the main reasons for revision surgery, reported to be as high as 19%, is the cut-out of the fixation device at the apex of the femoral head. Augmentation, facilitated by injecting cement (PMMA) around the apex of the proximal screw of the fixation device is considered a useful method with regards to the increased purchase between the bone and implant interface. The aim of this study is the description of the cement Augmentation operative technique for unstable osteoporotic pertrochanteric fractures with 1-2 femoral head screw devices.


Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing.
Clinical presentation of central nervous system (CNS) infections caused by varicella-zoster virus (VZV) is highly sophisticated, making identification challenging. We retrospectively reported 18 cases of VZV neurologic disease confirmed by metagenomic next-generation sequencing (mNGS). The detection rate of mNGS was higher than that of PCR assay (100 vs 66.7%, p < 0.05) and serum IgM antibody (100 vs 68.8%, p < 0.05) measurement. Of the 18 cases, five patients were diagnosed with acute meningitis, three with acute meningitis combined with facial neuritis, three with acute meningitis combined with polycranial neuritis, and the remaining seven with various clinical diagnoses. Typical clinical symptoms included headache (15), fever (9), and rash (11). Cranial or spinal MRI showed abnormalities in 12 patients, and 17 patients had obvious neurological symptoms. The predominant genotype of VZV in this study was genotype J (100%, 10/10). All patients were treated with acyclovir/penciclovir and dexamethasone, 16 recovered and 2 died. Our study highlights the good performance of mNGS in diagnosing CNS infection caused by VZV. It could provide additional diagnostic evidence in patients with diverse clinical spectrum and variable manifestations.


Biomass-Derived Carbon Materials as Prospective Electrodes for High-Energy Lithium- and Sodium-Ion Capacitors.
Biomass-derived carbon materials have received special attention as efficient, low-cost, active materials for charge-storage devices, regardless of the power system, such as supercapacitors and rechargeable batteries. In this Minireview, we discuss the influence of biomass-derived carbonaceous materials as positive or negative electrodes (or both) in high-energy hybrid lithium-ion configurations with an organic electrolyte. In such hybrid configurations, the electrochemical activity is completely different to conventional electrical double-layer capacitors; that is, one of the electrodes undergoes a Faradaic reaction, whilst the counter electrode undergoes a non-Faradaic reaction, to achieve high energy density. The use of a variety of biomass precursors with different properties, such as surface functionality, the presence of inherent heteroatoms, tailored meso-/microporosity, high specific surface area, various degrees of crystallization, calcination temperature, and atmosphere, are described in detail. Sodium-ion capacitors are also discussed, because they are an important alternative to lithium-ion capacitors, owing to the low abundance and high cost of lithium. The electrochemical performance of carbonaceous electrodes in supercapacitors and rechargeable batteries are not discussed.


Thyroid-like follicular carcinoma of kidney: Case presentation and literature review.
Thyroid follicular carcinoma like renal tumour (TFCLRT) is a rare variant of primary renal epithelial tumour and was first reported in 2006. Up till now, 40 cases have been identified worldwide and alarmingly, 17 cases have been identified from China only. The condition has been included in the WHO Renal Tumours Classification 2016. We present here the first case of thyroid follicular carcinoma like renal tumour from Pakistan that was managed in our surgical unit and a literature review. Left-sided radical nephrectomy was performed through a midline incision. The left kidney was removed along with intact Gerota fascia, left adrenal gland and lymph nodes alongwith aorta.


Baculovirus surface display of SARS coronavirus (SARS-CoV) spike protein and immunogenicity of the displayed protein in mice models.
The baculovirus surface display technique has provided an ideal tool to display foreign proteins with natural conformation, functions, and immunogenicity. In this work, we explored the application of this technique on SARS-associated coronavirus (SARS-CoV) spike (S) protein, and further analyzed the immunogenicity of displayed S protein. The entire ectodomain of S protein was fused between the gp64 signal peptide and the VSV-G membrane anchor and successfully displayed on the baculovirus surface. Subcutaneous injection with purified S-displayed baculoviruses without adjuvant elicited highly effective production of specific and neutralizing antibodies against S protein in mice. These results confirmed a successful surface display of S protein on baculoviruse, and suggested a potential role of S-displayed baculoviruses as a novel live virus-based vaccine candidate for SARS-CoV.


Normative and Cataclysmic Career Transitions: A Nurse's Memoir.
Drawn from 54 years of experience as a nursing professional, this author gives a personal account of 2 types of career transitions: (1) normative transitions/stages, which include position changes, educational pursuits, and promotion; and (2) cataclysmic transitions, such as dismissal, bankruptcy, and mergers, that arise out of disruptive work situations that dramatically influence one's beliefs, actions, and perspective over time and ultimately shape a career. The importance of influencers throughout a career and lessons learned along the way are also explored.


From Simple to Sinister: Kaposi Sarcoma Masquerading as a Subconjunctival Hemorrhage.
A young male in his early 30s presented with spontaneous left eye redness for three months associated with blood-stained eye discharge. There was no history of trauma, blood dyscrasias, or anticoagulant intake. On examination, visual acuity was normal in both eyes. An anterior segment examination of the left eye showed subconjunctival hemorrhage with a fleshy bright red conjunctival mass hidden in the inferotemporal fornix. Other parts of the ocular examination including the contralateral eye were unremarkable. Upon further inquiry, the patient revealed a history of a retroviral disease diagnosed eight years ago but had not pursued treatment. Systemic examination revealed a raised non-pigmented lesion of the tongue and a painless purplish plaque at the back. Investigations showed a high viral ribonucleic acid (RNA) load and confirmed the Kaposi sarcoma of the conjunctiva, tongue, and skin; cryptococcal meningitis; smear-negative pulmonary tuberculosis; and late latent syphilis. He was comanaged by multidisciplinary teams. Highly active antiretroviral therapy (HAART) was commenced. Treatment was a challenge considering the simultaneous presence of malignancy and a serious fungal infection of the brain in an immunosuppressed patient. Fortunately, three months post treatment, he showed remarkable improvement as there was almost a complete resolution of conjunctival Kaposi sarcoma. This case revealed an unusual presentation of Kaposi sarcoma affecting the conjunctiva, which could have been mistaken for simple subconjunctival hemorrhage in a young patient without informed comorbidity.


The Nature of the Enthalpy-Entropy Compensation and "Exotic" Arrhenius Parameters in the Denaturation Kinetics of Proteins.
Protein unfolding is a ubiquitous process responsible for the loss of protein functionality (denaturation), which, in turn, can be accompanied by the death of cells and organisms. The nature of enthalpy-entropy compensation (EEC) in the kinetics of protein unfolding is a subject of debate. In order to investigate the nature of EEC, the "completely loose" transition state (TS) model has been applied to calculate the Arrhenius parameters for the unfolding of polyglycine dimers as a model process. The calculated Arrhenius parameters increase with increasing dimer length and demonstrate enthalpy-entropy compensation. It is shown that EEC results from the linear correlations of enthalpy and entropy of activation with dimer length, which are derived directly from the properties of the transition state. It is shown that EEC in solvated (hydrated, etc.) proteins is a direct consequence of EEC in proteins themselves. The suggested model allows us also to reproduce and explain "exotic" very high values of the pre-exponential factor measured for the proteins unfolding, which are drastically higher than those known for unimolecular reactions of organic molecules. A similar approach can be applied to analyzing the nature of EEC phenomena observed in other areas of chemistry.


Molecular Characterization and Genetic Diversity of Ginkgo (Ginkgo biloba L.) Based on Insertions and Deletions (InDel) Markers.
As a "living fossil", ginkgo (Ginkgo biloba L.) has significant ornamental, medicinal, and timber value. However, the breeding improvement of ginkgo was limited by the lack of enough excellent germplasms and suitable molecular markers. Here, we characterized numerous polymorphic insertion/deletion (InDel) markers using RAD-seq in 12 different ginkgo cultivars. The total of 279,534 InDels identified were unequally distributed across 12 chromosomes in the ginkgo genome. Of these, 52.56% (146,919) and 47.44% (132,615) were attributed to insertions and deletions, respectively. After random selection and validation, 26 pairs of polymorphic primers were used for molecular diversity analysis in 87 ginkgo cultivars and clones. The average values of observed heterozygosity and polymorphism information were 0.625 and 0.517, respectively. The results of population structure analyses were similar to those of neighbor-joining and principal component analyses, which divided all germplasms into two distinct groups. Moreover, 11 ginkgo core collections accounted for approximately 12.64% of the total ginkgo germplasms obtained, representing well the allelic diversity of all original germplasms. Therefore, these InDels can be used for germplasm management and genetic diversity analyses in ginkgo and the core collections will be used effectively for ginkgo genetic improvement.


Adsorptive removal of naphthalene induced by structurally different Gemini surfactants in a soil-water system.
A new generation of surfactant, Gemini surfactants, have been synthesized and have attracted the attention of various industrial and academic research groups. This study focused on the use of symmetric and dissymmetric quaternary ammonium Gemini surfactants to immobilize naphthalene onto soil particles, and is used as an example of an innovative application to remove HOC in situ using the surfactant-enhanced sorption zone. The sorption capacity of modified soils by Gemini surfactant and natural soils was compared and the naphthalene sorption efficiency, in the absence and presence of Gemini surfactants with different alkyl chain lengths, was investigated in the soil-water system. The results have shown that the increased added Gemini surfactant formed admicelles at the interface of soil/water having superior capability to retard contaminant. Symmetric and dissymmetric Gemini surfactants have opposite effect on the aspect of removing of PAH attributing to their solubilization and sorption behavior in soil-water system. Compared with the natural soil, sorption of naphthalene by Gemini-modified soil is noticeably enhanced following the order of C12-2-16 < C12-2-12 < C12-2-8. However, the symmetric Gemini surfactant C12-2-12 is the optimized one for in situ barrier remediation, which is not only has relative high retention ability but also low dosage.


The mycotoxin aflatoxin B1 stimulates Epstein-Barr virus-induced B-cell transformation in in vitro and in vivo experimental models.
Although Epstein-Barr virus (EBV) infection is widely distributed, certain EBV-driven malignancies are geographically restricted. EBV-associated Burkitt's lymphoma (eBL) is endemic in children living in sub-Saharan Africa. This population is heavily exposed to food contaminated with the mycotoxin aflatoxin B1 (AFB1). Here, we show that exposure to AFB1 in in vitro and in vivo models induces activation of the EBV lytic cycle and increases EBV load, two events that are associated with an increased risk of eBL in vivo. AFB1 treatment leads to the alteration of cellular gene expression, with consequent activations of signaling pathways, e.g. PI3K, that in turn mediate reactivation of the EBV life cycle. Finally, we show that AFB1 triggers EBV-driven cellular transformation both in primary human B cells and in a humanized animal model. In summary, our data provide evidence for a role of AFB1 as a cofactor in EBV-mediated carcinogenesis.


Regulation of the Pacemaker Activity of Colonic Interstitial Cells of Cajal by Protease-Activated Receptors: Involvement of Hyperpolarization-Activated Cyclic Nucleotide Channels.
The exact mechanism of protease-activated receptors (PARs) on pacemaker activity of interstitial cells of Cajal (ICCs) has not been reported. We investigated the effects on pacemaker activity by the activation of PARs and its signal mechanisms in colonic ICCs. The whole-cell patch-clamp technique, RT-PCR and Ca2+ imaging were used in cultured ICCs from mouse colon. PAR-1 and PAR-2 were expressed in Ano-1 positive ICCs. TFLLR-NH2 (a PAR-1 agonist) and trypsin (a PAR-2 agonist) depolarized the membrane and increased the pacemaker potential frequency. U-73122 (a phospholipase C (PLC) inhibitor) and thapsigargin (a Ca2+ ATPase inhibitor) suppressed the TFLLR-NH2- and trypsin-induced effects on pacemaker potential. TFLLR-NH2 and trypsin also increased intracellular Ca2+ ([Ca2+]i) intensity with increasing of Ca2+ oscillations. Genistein (a tyrosine kinase inhibitor), SP600125 (a JNK inhibitor), CsCl, ZD7288, clonidine (hyperpolarization-activated cyclic nucleotide (HCN) channel blockers), SQ-22536 and dideoxyadenosine (adenylate cyclase inhibitors) suppressed the increased pacemaker potential frequency without effects on depolarization of the membrane induced by TFLLR-NH2 and trypsin. These results suggest that activation of PAR-1 and PAR-2 modulates the pacemaker activity of colonic ICCs through the PLC-dependent [Ca2+]i release pathway. The increased pacemaker potential frequency by PAR-1 and PAR-2 was also dependent on tyrosine kinase, JNK, and HCN activation.


Quantifying Clinically Meaningful Point-of-Care Ultrasound Interpretation Discrepancies Using an Emergency Department Quality Assurance Program.
Emergency medicine professional associations recommend that quality assurance (QA) programs be implemented wherever emergency department (ED) point-of-care ultrasound (POCUS) is in use. The purpose of this study is to identify the rate of clinically meaningful interpretation discrepancies between initial ED POCUS interpretation and a gold standard using a QA program in a Canadian academic ED. All POCUS examinations completed in our ED are subject to a QA process. The results of all POCUS examinations undergoing this process from July 1, 2014, to June 30, 2015, were retrospectively reviewed. Four blinded abstractors collected data with a standardized tool after a training session. Information regarding patient demographics, POCUS indication, emergency physician initial POCUS interpretation, physician POCUS expertise, the presence of an interpretation discrepancy, and whether the discrepancy was clinically meaningful was abstracted. The proportion of interpretation discrepancies, clinically meaningful discrepancies, discrepancies requiring remedial action, and differences in discrepancy rates between non-expert and expert sonographers were analyzed. A total of 2,869 POCUS studies were included for review, with 2,668 in the final data set after exclusions. In total, only 1.4% of all scans contained an interpretation discrepancy. The rate of clinically meaningful discrepancies was 0.5%, and the rate of scans requiring remedial action was 0.1%. Overall, 85.5% of all scans were performed by four POCUS expert physicians, with the remainder by a non-expert. Scans performed by non-expert sonographers were significantly more prone to discrepancies than those performed by experts. No single scan indication was more prone to discrepancy. The overall ED POCUS interpretation discrepancy rate and clinically meaningful discrepancy rate identified using our QA process were very low. The findings are limited by the small group of expert sonographers completing most scans.


Sequential assessment of the intrahepatic expression of epidermal growth factor and transforming growth factor-beta1 in hepatofibrogenesis of a rat cirrhosis model.
Responses of the liver to chronic injury include inflammation, regeneration and fibrosis, which finally lead to cirrhosis. The cause of liver cirrhosis appears to be impaired proliferative capability of hepatocytes caused by continuous hepatic damage, and subsequent accumulation of extracellular matrix produced by hepatic stellate cells (HSCs). Epidermal growth factor (EGF) and transforming growth factor-beta1 (TGF-beta1) play a crucial role in hepatocyte proliferation and hepatofibrogenesis, respectively. However, sequential analyses of the intrahepatic expression of EGF and TGF-beta1 in the course of cirrhosis development have not been examined fully. In the present study, liver cirrhosis was produced in rats by intraperitoneal administration of dimethylnitrosamine (DMN), and intrahepatic mRNA expression levels of proliferating cell nuclear antigen (PCNA), EGF and TGF-beta1 were quantitatively estimated by a real-time reverse transcription-polymerase chain reaction method. Histological and semiquantitative densitometric examination of liver sections revealed that the accumulation of extracellular matrix components was increased according to the period of DMN treatment. Histological examination of liver sections of rats treated with DMN for 4 and 6 weeks revealed pre-cirrhosis and cirrhosis, respectively. Intrahepatic mRNA expression levels of PCNA and EGF correlated well. Expression levels of both molecules were increased significantly during the course of cirrhosis development, but decreased significantly at the time of complete cirrhosis manifestation. In contrast, intrahepatic TGF-beta1 expression was increased significantly according to the period of DMN treatment, and reached a peak at the time of cirrhosis manifestation. These results suggest that proliferative capability of hepatocytes was impaired by continuous liver damage due, in part, to the decrease of a hepatocyte mitogen EGF, and that increased intrahepatic TGF-beta1 activated HSCs to retrieve space lost by hepatocyte destruction, resulting in complete cirrhosis manifestation.


Ultrasonography in acute flank pain.
In 58 patients with acute recurrent or persistent flank pain, straight x-ray (kidney, ureter, bladder region) detected stones in the urinary tract in 50 cases (86.2%), whereas ultrasonography detected stones in the urinary tract in 55 patients (94.8%). Ultrasound also detected unilateral hydronephrosis in 20 patients (34.48%). The presence of calculus was subsequently proved by intravenous urography/surgery or spontaneous passage. Ultrasonography is safe, quick, reliable and most effective diagnostic tool in such cases in rural areas. Intravenous urogram should be reserved for cases which need surgical intervention.


The transcripts of zeta-crystallin, a lens protein related to the alcohol dehydrogenase family, are altered in a guinea-pig hereditary cataract.
Zeta-Crystallin, a major component of the guinea-pig lens proteins, is distantly related to the enzymes of the zinc-containing alcohol dehydrogenase family (ADH). Analysis of the structural similarities between zeta-crystallin and ADH reveals that while characteristics important in maintaining the tertiary structure of the molecule appear conserved, the amino acids binding the catalytic zinc atom are absent in zeta-crystallin. Significantly, zeta-crystallin does not have ADH activity. Previous studies showed that the zeta-crystallin protein is modified in the lens of guinea-pigs affected with an autosomal dominant hereditary cataract. We have further investigated the molecular origin of the lens defect by examining the steady-state levels of zeta-crystallin transcripts in normal and mutant eyes. Our data indicate that no normal zeta-crystallin mRNA is present in the lens of the homozygous animals; instead, a cross-hybridizing lower molecular weight mRNA is detected at significantly reduced concentrations. Heterozygous lenses exhibit both mRNA species.


Co-delivery of doxorubicin and Bmi1 siRNA by folate receptor targeted liposomes exhibits enhanced anti-tumor effects in vitro and in vivo.
Bmi1 gene overexpression is found in various human tumors and has been shown as a potential target for gene treatment. However, siRNA-based treatments targeting Bmi1 gene have been restricted to limited delivery, low bioavailability and hence relatively reduced efficacy. To overcome these barriers, we developed a folate receptor targeted co-delivery system folate-doxorubicin/Bmi1 siRNA liposome (FA-DOX/siRNA-L). The FA-DOX/siRNA-L was prepared through electrostatic interaction between folate doxorubicin liposome (FA-DOX-L) and Bmi1 siRNA. In vitro and in vivo studies showed that FA-DOX/siRNA-L inhibited tumor growth by combinatory role of Bmi1 siRNA and doxorubicin (DOX). Co-delivery of Bmi1 siRNA and DOX by FA-DOX/siRNA-L showed significantly higher efficacy than sole delivery of either DOX or Bmi1 siRNA. Real-time PCR and western blot analysis showed that FA-DOX/siRNA-L silenced the expression of Bmi1 gene. In addition, higher accumulation of the siRNA and DOX in tumor cells indicated that folate ligand displayed tumor targeting effect. These results suggest that Bmi1 is an effective therapeutic target for siRNA based cancer treatment that can be further improved by co-delivery of DOX through targeted liposomes.


Cloned polynucleotide and synthetic oligonucleotide probes used in colony hybridization are equally efficient in the identification of enterotoxigenic Escherichia coli.
Restriction endonuclease-generated polynucleotide and synthetically produced oligonucleotide gene probes used in colony hybridization assays proved to be efficient for the detection and differentiation of enterotoxigenic Escherichia coli. To compare their relative efficiencies, these two sets of probes were radiolabeled with 32P and were applied to 74 strains of E. coli with known enterotoxin profiles and to 156 previously unexamined E. coli isolates. The enterotoxigenic bacteria Vibrio cholerae O1, Vibrio cholerae non-O1 (NAG), Yersinia enterocolitica, and E. coli harboring the plasmid vectors of the polynucleotide gene probes were examined for further evaluation of probe specificity. The two classes of probes showed a perfect concordance in their specific detection and differentiation of enterotoxigenic E. coli. In the analysis of six strains, the signal strength on autoradiography after hybridization with oligonucleotides was weaker than that obtained after hybridization with polynucleotide probes. The probes did not hybridize with DNA from V. cholerae O1, V. cholerae non-O1 (NAG), or Y. enterocolitica. The strains of E. coli harboring the plasmid vectors of the polynucleotide gene probes were, likewise, negative in the hybridization assays.


Organizational culture assessment before and after implementing patient-focused care.
Administration of a baseline multidisciplinary cultural assessment survey prior to any change effort (to evaluate as well as redesign units) is essential to success in any work redesign effort. Training efforts can then be directed toward effecting the desired changes in perceived norms and values. All involved groups should be surveyed using the same survey tool to elicit potential differences in perceptions of values among various work groups. Proactive values which are seen as predictive of greater change readiness include high teamwork (clan) values, flexibility, as shown by comfort with adhocracy, and recognition of external or market driven realities. Values and norms which are found to be problematic in change efforts include: a reactive orientation marked by strong hierarchical values, a command and control orientation, and strong reliance on rules. Predictors of success include a history of shared governance, while greater difficulties could be anticipated in both unionized and academic health care settings.


[Calculating emissions of exhaust particulate matter from motor vehicles with PART5 model].
PART5, a vehicle particulate emission factor model developed by USEPA, was modified and then used to obtain the emission factors of exhaust PM10 and PM2.5 from on-road automobiles, trucks and motorcycles in Beijing. The total exhaust PM10 and PM2.5 emissions from motor vehicles in 1995 and 1998 were calculated separately. The contribution ratios of different types of vehicles to the total vehicular emissions, and the share of different exhaust particulate components including Pb, direct SO4(2-), soluble organic fraction (SOF) and remaining carbon portion (RCP), were also estimated. It was shown that the emission factors of exhaust PM10 and PM2.5 from gasoline motor vehicles, motorcycles and heavy-duty diesel vehicles in Beijing were 1.7-8.6 times, 2.1-3.5 times and 1.3-1.5 times, respectively, of the USA average emission levels during the same period. The total exhaust PM10 and PM2.5 from vehicles were 2445 tons and 1890 tons in 1995 in Beijing, and increased to 3359 tons and 2694 tons in 1998, which increase by 37.4% and 42.5%, respectively.


Absorption Spectroscopy of Single Optically Trapped Gold Nanorods.
Extinction spectra of single gold nanorods optically trapped in water were measured by spatial modulation spectroscopy. Comparison of the extinction cross sections and resonance frequencies to finite element calculations allows us to determine the dimensions of the nanorod and estimate the contribution of radiation damping to the LSPR line width. Subtracting the radiation damping and bulk contributions from the measured line widths yields the electron-surface scattering contribution. The results show that the surfactant coating for the nanorods causes large electron-surface scattering effects with significant particle-to-particle variations. These effects are more pronounced than those seen for substrate-supported particles in previous single particle studies. Indeed, the measured line widths are only slightly narrower than that of the ensemble spectrum. These results show the importance of removing surfactant for sensing applications of these materials.


POPULATION GENETIC CONSEQUENCES OF DEVELOPMENTAL EVOLUTION IN SEA URCHINS (GENUS HELIOCIDARIS).
Within the sea urchin genus Heliocidaris, changes in early embryonic and larval development have resulted in dramatic differences in the length of time larvae spend in the plankton before settling. The larvae of one species, H. tuberculata, spend several weeks feeding in the plankton before settling and metamorphosing into juveniles. The other species, H. erythrogramma, has modified this extended planktonic larval stage and develops into a juvenile within 3-4 days after fertilization. We used restriction site polymorphisms in mitochondrial DNA to examine the population genetic consequences of these developmental changes. Ten restriction enzymes were used to assay the mitochondrial genome of 29 individuals from 2 localities for H. tuberculata and 62 individuals from 5 localities for H. erythrogramma. Within H. tuberculata, 11 mitochondrial genotypes were identified. A GST analysis showed high levels of genetic exchange between populations separated by 1,000 kilometers of open ocean. In contrast, in H. erythrogramma, 13 mitochondrial genotypes differing by up to 2.33% were geographically partitioned over spatial scales ranging from 800 to 3,400 kilometers. Between distant localities, there was complete mitochondrial lineage sorting and large sequence divergence between resulting clades. Over much smaller spatial scales (< 1,000 km), genetic differentiation was due to the differential sorting of very similar genotypes. This pattern of mitochondrial variation suggests that these population differences have arisen recently and may reflect the historical interplay between the restricted dispersal capabilities of H. erythrogramma and the climatic and geological changes associated with Pleistocene Ice Ages.


Economic impact of surgical intervention in the treatment of benign prostatic hyperplasia.
The economic burden of benign prostatic hyperplasia (BPH) on our health care system is significant and likely to continue to grow given the burgeoning elderly population. Coincident with the rising number of annual physician office visits and expenditures for BPH has been a dramatic shift in the disease's management, from surgical to medical care. However, long-term cost data call into question the appropriateness of medical therapy as the initial treatment approach for all men with BPH, particularly those with moderate to severe symptoms. Although there has been a paradigm shift away from traditional BPH surgery, there has been renewed interest in the treatment of BPH with novel surgical techniques and minimally invasive surgeries. The economics of surgical interventions for BPH are discussed.


Maximum standardized uptake value on FDG-PET predicts survival in stage I non-small cell lung cancer following carbon ion radiotherapy.
The present study (University Hospital Medical Information Network study no. UMIN000003797) aimed to evaluate whether the maximum standardized uptake value (SUVmax) of pretreatment 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is prognostic factor for stage I non-small cell lung cancer (NSCLC) treated with carbon ion radiotherapy (C-ion RT). Patients treated between June 2010 and June 2013 at Gunma University Heavy Ion Medical Center (Maebashi, Japan) on a prospective protocol were included in the present study. Patients with T1a-b and T2a NSCLC were treated with C-ion RT at a dose of 52.8 Gy [relative biological effectiveness (RBE)] and 60.0 Gy (RBE), respectively, in four fractions. Prior to treatment, all patients underwent FDG-PET, in which the SUVmax of primary tumors was evaluated. Local control, progression-free survival (PFS), and overall survival (OS) were calculated. A total of 45 patients were analyzed and the median follow-up period was 28.9 months. The 2-year local control, PFS and OS rates for all patients were 93, 78 and 89%, respectively. The mean SUVmax of primary tumors was 5.5, and patients were divided into higher (≥5.5) and lower (<5.5) SUVmax groups. The 2-year PFS rates were 61 and 89% for the higher and lower SUVmax groups, respectively (P=0.01), and the 2-year OS rates for the higher and lower SUVmax groups were 76 and 96%, respectively (P=0.01). The higher SUVmax group exhibited a significantly worse PFS and OS compared with the lower SUVmax group; however, the SUVmax was not associated with the local control rate. In total, 2 patients (4%) experienced grade 2 or 3 radiation pneumonitis, with their symptoms improved through conservative treatment. No patients experienced any grade 4 or 5 toxicities. The results of the present study indicate that pretreatment SUVmax is a prognostic indicator for outcomes in patients with stage I NSCLC treated with C-ion RT.


The boomerang effect in electron-hydrogen molecule scattering as determined by time-dependent calculations.
The appearance of oscillations in the energy-dependent cross sections of the vibrational excitation ν=0→ν≥3 of the hydrogen molecule in its electronic ground state as predicted by Mündel, Berman, and Domcke [Phys. Rev. A 32, 181 (1985)] was confirmed in the electron scattering experiments by Allan [J. Phys. B: At. Mol. Phys. 18, L451 (1985)]. These unusual structures were obtained in spite of the extremely short lifetime of H2- in its ro-vibrational states. Based on the standard (Hermitian) time-independent scattering calculations, Horáček et al. [Phys. Rev. A 73, 022701 (2006)] associated these oscillations with the boomerang effect. Here, we show the boomerang effect as developed in time, based on our time-dependent nuclear wavepacket (WP) calculations. The nuclear WP dynamics of H2- is determined using the non-Hermitian quantum mechanics (NH-QM) which enables the use of the Born-Oppenheimer approximation with complex potential energy surfaces. This NH-QM approach, which enables us the association of the nuclear WP dynamics as obtained from the complex potential energy curve of H2- with the evolution of cross section in time, can enlighten the dynamics in other scattering experiments.


Ovine Forestomach Matrix in the Surgical Management of Complex Lower-Extremity Soft-Tissue Defects.
Chronic lower-extremity defects may lead to major amputations and have severe consequences on patient quality of life and mortality. Dermal matrices have become part of the reconstructive ladder and are often deployed in these scenarios to quickly build neodermis, especially in volumetric defects over exposed bone and tendon initially, to allow for subsequent closure by means of split-thickness skin grafting (STSG) or secondary intention. Ovine forestomach matrix (OFM) is a decellularized extracellular matrix (ECM) bioscaffold available in both sheet and particulate forms that can be used as a dermal matrix in various soft-tissue reconstruction procedures. This retrospective case series evaluated the use of OFM products in the surgical reconstruction of 50 cases (n = 50) comprised of challenging lower-extremity defects from seven healthcare centers. Patient records were reviewed to identify comorbidities, defect cause, defect size, presence of exposed structures, Centers for Disease Control and Prevention contamination score, Wagner grade, OFM graft use, time to 100% granulation tissue, STSG use, overall time to heal, and postoperative complications. The primary study outcomes were time (days) to 100% granulation tissue formation, with secondary outcomes including overall time to wound closure (weeks), STSG take at 1 week, and complications. The results of this case series demonstrate OFM as a clinically effective treatment in the surgical management of complex lower-extremity soft-tissue defects with exposed structures in patients with multiple comorbidities. One application of OFM products was effective in regenerating well-vascularized neodermis, often in the presence of exposed structures, with a mean time to 100% granulation of 26.0 ± 22.2 days. These data support the use of OFM as a safe, cost-effective, and clinically effective treatment option for coverage in complex soft-tissue wounds, including exposed vital structures, and to shorten the time to definitive wound closure in complicated patient populations.


The impact of external innovation on new drug approvals: A retrospective analysis.
Pharmaceutical companies are relying more often on external sources of innovation to boost their discovery research productivity. However, more in-depth knowledge about how external innovation may translate to successful product launches is still required in order to better understand how to best leverage the innovation ecosystem. We analyzed the pre-approval publication histories for FDA-approved new molecular entities (NMEs) and new biologic entities (NBEs) launched by 13 top research pharma companies during the last decade (2006-2016). We found that academic institutions contributed the majority of pre-approval publications and that publication subject matter is closely aligned with the strengths of the respective innovator. We found this to also be true for candidate drugs terminated in Phase 3, but the volume of literature on these molecules is substantially less than for approved drugs. This may suggest that approved drugs are often associated with a more robust dataset provided by a large number of institutes. Collectively, the results of our analysis support the hypothesis that a collaborative research innovation environment spanning across academia, industry and government is highly conducive to successful drug approvals.


pH-Responsive Fluorescent Metal-Organic Framework as a Functional Nanofiller for Smart Coatings.
A zirconium-based UiO-type UiO-66-(OH)2 metal-organic framework@carbon dot composite (Zr-MOF@CD) is synthesized through a facile solvent-free thermal method. The Zr-MOF@CD exhibits pH-responsive fluorescence behavior, which emits blue fluorescence for pH < 9 at an emission wavelength of 470 nm. At pH > 9, the fluorescence color turns from blue to yellow, with the emission behavior at 535 nm. Zr-MOF@CDs can serve as functional nanofillers in the epoxy coating for the fabrication of a smart coating, which can realize coating damage warning and metal corrosion reporting. The blue fluorescence can be observed in the area of coating damage with just a minor scratch. Once the scratch is severe enough to expose the metal substrate, the cathodic reaction of oxygen reduction in the corrosion galvanic cell causes an increased pH, where the emission of yellow fluorescence can be identified. The stable fluorescence response is free from the influence of concentration, time, temperature, and the interfering substance. Zr-MOF@CDs can also serve as nanocontainers for loading with the corrosion inhibitor and realizing the repairing of metal corrosion. The development of the smart coating with dual functions of autonomous reporting and repairing holds great potential to improve the lifetime of metals in various industrial applications.


The Role of the Small Bowel in Unintentional Weight Loss after Treatment of Upper Gastrointestinal Cancers.
Upper gastrointestinal (GI) cancers are responsible for significant mortality and morbidity worldwide. To date, most of the studies focused on the treatments' efficacy and post-treatment survival rate. As treatments improve, more patients survive long term, and thus the accompanying complications including unintentional weight loss are becoming more important. Unintentional weight loss is defined as >5% of body weight loss within 6-12 months. Malignancies, particularly GI cancers, are diagnosed in approximately 25% of patients who present with unintentional weight loss. Whereas some recent studies discuss pathophysiological mechanisms and new promising therapies of cancer cachexia, there is a lack of studies regarding the underlying mechanism of unintentional weight loss in patients who are tumor free and where cancer cachexia has been excluded. The small bowel is a central hub in metabolic regulation, energy homeostasis, and body weight control throughout the microbiota-gut-brain axis. In this narrative review article, the authors discussed the impacts of upper GI cancers' treatment modalities on the small bowel which may lead to unintentional weight loss and some new promising therapeutic agents to treat unintentional weight loss in long term survivors after upper GI operations with curative intent.


Photoluminescence and raman studies of Y2O3:Eu(3+) nanotubes under high pressure.
In this work, the cubic compound Y2O3:Eu(3+) nanotubes with diameter of 70-90 nm and length of 2-3 microm are synthesized by a hydrothermal method. Photoluminescence and Raman spectra of Y2O3:Eu(3+) nanotubes in a diamond anvil cell under high pressure are measured at room temperature. The 5D0 --> 7F(0,1,2) transitions of the Eu(3+) ions exhibit red shifts to higher wavelength with pressure increasing. Above 13.4 GPa, all the Raman active modes disappear. When the pressure is released from 25.6 GPa to ambient pressure, these Raman peaks are not retrieved; this fact indicates that the nanotubes are transformed into amorphous from cubic phase at about 13.4 GPa. It may be related to the collapse of nanotube form under high pressure condition.


Graves' disease.
Graves' disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism and occurs at all ages but especially in women of reproductive age. Graves' hyperthyroidism is caused by autoantibodies to the thyroid-stimulating hormone receptor (TSHR) that act as agonists and induce excessive thyroid hormone secretion, releasing the thyroid gland from pituitary control. TSHR autoantibodies also underlie Graves' orbitopathy (GO) and pretibial myxoedema. Additionally, the pathophysiology of GO (and likely pretibial myxoedema) involves the synergism of insulin-like growth factor 1 receptor (IGF1R) with TSHR autoantibodies, causing retro-orbital tissue expansion and inflammation. Although the aetiology of GD remains unknown, evidence indicates a strong genetic component combined with random potential environmental insults in an immunologically susceptible individual. The treatment of GD has not changed substantially for many years and remains a choice between antithyroid drugs, radioiodine or surgery. However, antithyroid drug use can cause drug-induced embryopathy in pregnancy, radioiodine therapy can exacerbate GO and surgery can result in hypoparathyroidism or laryngeal nerve damage. Therefore, future studies should focus on improved drug management, and a number of important advances are on the horizon.


Schistosomiasis and the molecular biology of the male-female interaction of S. mansoni.
Parasitic helminths of the genus Schistosoma are the causative agents of schistosomiasis, an infectious disease affecting humans and animals. For humans, it is one of the most prevalent parasitemias in the world, second behind malaria. Estimates of the World Health Organisation (WHO) indicate that more than 200 million people live in endemic areas (WHO, Fact Sheet No 115). With respect to animals, a number of 530 million cattle is estimated to live in endemic territories of Africa and Asia. In the last two decades ambitious efforts have been made to develop an effective vaccine against schistosomes, but without resounding success. In addition, there is a pressing need to develop new anthelmintics due to the potential emerging resistance against the commonly used drug praziquantel. Therefore, the understanding of essential physiological or developmental processes of schistosome biology and attempts to intervene in these processes may open new ways to control the parasite. Towards this end, one possibility is to study the unusual biology of schistosomes. These digenean parasites differ from other parasitic flukes by living in the blood vessels. Furthermore, schistosomatids are the only bisexual family of the class trematoda. A nearly unique phenomenon in nature is that a continuous pairing-contact is essential for the development of the reproductive organs of the female, an aspect for the possible design of novel control strategies.


Binaural model for artificial spatial sound localization based on interaural time delays and movements of the interaural axis.
This paper presents a mathematical model for sound localization in space using two-microphone devices that possess at least two degrees of freedom. It proves a series of theorems and lemmas that are based on time difference of arrival measurements and movements of the interaural axis, forming a powerful instrument for practical robot applications. For instance, it shows that a single determined rotation of the interaural axis is sufficient to exactly yield the azimuth or the elevation of an immobile sound source in the far field, independently of microphone spacing and the speed of sound and hence of the surrounding medium. It proves that at any moment the knowledge of one value determines the magnitude of the other, with the restriction that the sign of the second value is undefined, which means that, depending on the rotation, either the back-front or the up-down ambiguity is kept unsolved. This paper also shows that parallax motion unlocks essential information about the distance and the Cartesian coordinates of the sound source. Shifting the microphone system sideways fixes the distance and the coordinate on the interaural axis. Combining rotation and translation movements completely solves the localization problem. In order to illustrate the efficacy of the model, this paper presents experiments with a low cost robot developer kit during which the azimuth, the elevation, and the distance of continuous sound sources are determined at a precision of 10 degrees and 0.5 m, respectively. Achieving this performance with low power material demonstrates how easily the model can be implemented into any robotic system.


Induction of specific cell-mediated cytoxicity in vitro by means of RNA isolated from allografted mice.
Ribonucleic acid extracts were isolated by cold phenol extraction procedure from lymphoid organs of mice immunized with allogeneic skin grafts. Cultivation of lymphocytes from normal mice with these RNA extracts in vitro led to the induction of specific immunological reactivity which was determined by microcytotoxicity assay. Pretreatment of the RNA extracts with DNase enhanced their ability to induce cytotoxicity, while pronase had no effect, and RNase completely inhibited the ability of extracts to sensitize lymphocytes. The results show that specific cell-mediated cytotoxicity can be induced in vitro in lymphocytes from normal animals by a transfer of "immune" RNA.


Family and youth factors associated with health beliefs and health outcomes in youth with type 1 diabetes.
To examine the association of family organization with metabolic control in adolescents with type 1 diabetes through the mechanisms of family self-efficacy for diabetes and disease management. Data from the baseline assessment of a longitudinal RCT were used, wherein 257 adolescent-parent dyads (adolescents aged 11-14) each completed the family organization subscale of the Family Environment Scale, the self-efficacy for Diabetes Self-Management Scale, the Diabetes Behavior Rating Scale, and 2 24-hr diabetes interviews. Structural equation modeling showed greater family organization was associated indirectly with better disease management behaviors via greater family self-efficacy (β = .38, p < .001). Greater self-efficacy was indirectly associated with better metabolic control via better disease management both concurrently (β = -.37, p < .001) and prospectively (β = -.26, p < .001). The full model indicates more family organization is indirectly associated with better metabolic control concurrently and prospectively through greater self-efficacy and better disease management (β = -.13, p < .001). Understanding the mechanisms by which family organization is associated with metabolic control provides insight into possible avenues of prevention/intervention for better diabetes management.


Association of patient autonomy with increased transplantation and survival among new dialysis patients in the United States.
It is unclear whether patients with chronic kidney disease who are more autonomous in medical decision making have better outcomes than those who are not. We examined the contribution of patient autonomy to treatment selection (peritoneal dialysis versus hemodialysis) and subsequent association with transplantation and survival. Data were obtained from the Dialysis Morbidity and Mortality Study Wave 2, a national random sample of 4,025 new dialysis patients enrolled during 1996 and 1997 and followed up until October 31, 2001. Responders were asked to quantify their contribution to treatment selection and were grouped based on perceived degree of participation as patient led, team led, or patient and team led. Groups were compared and subsequent outcomes were evaluated by using Cox regression. Six hundred thirty-six patients (26.3%) reported a patient-led decision, 860 patients (35.6%) reported a team-led decision, and 922 patients (38.1%) reported a patient-and-team-led decision in treatment assignment. Unadjusted death rates were significantly lower (127 versus 159 versus 207 deaths/1,000 patient-years at risk; P < 0.0001), and transplantation rates were significantly higher (103 versus 88 versus 41 transplantations/1,000 patient-years at risk; P < 0.0001) for patients reporting the greatest contribution to modality selection. With adjustment for case mix, mortality risks were lowest (relative risk [RR], 0.84; 95% confidence interval [CI], 0.71 to 0.99) and transplantation rates were highest (RR, 1.44; 95% CI, 1.07 to 1.93) for the patient-led group. Although the contribution of patient selection factors cannot be completely ignored, this analysis supports an association of patient autonomy with transplantation and survival. Greater efforts to empower patients with chronic kidney disease during the period before end-stage renal disease may improve clinical outcomes.


A cluster of 25B-NBOH poisonings following exposure to powder sold as lysergic acid diethylamide (LSD).
25B-NBOH is a synthetic hallucinogen closely related to the "NBOMe" family of N-substituted 2C phenethylamine derivatives. There have been no published reports documenting the clinical toxicity of NBOH derivatives. Five patients presented to the Emergency Department (ED) with altered conscious state following exposure to powder sold as "powdered LSD" at a party. A 24-year-old male who ingested the powder developed mydriasis, tachycardia, hypertension, and severe agitation requiring parenteral sedation. A 22-year-old male who insufflated the powder developed status epilepticus requiring intubation. Both patients developed acute kidney injury and one had rhabdomyolysis. In both cases, blood analysis detected 25-NBOH and no other illicit/licit drugs. Three other patients developed mild hallucinations. Hyperthermia was not documented in any case. Exposure to 25B-NBOH in a powdered form produced sympathomimetic toxicity, including hallucinations. Insufflation of 25B-NBOH led to rapid onset of status epilepticus in one case. Toxicity in all cases resolved within 12 h. Despite in vitro evidence of 5-HT2A receptor agonism, hyperthermia was not observed. Potent hallucinogens are often delivered via blotter paper to avoid excessive dosing. The severe clinical toxicity documented in these cases highlights the potential for development of adverse health effects with exposure to apparent small volumes of potent sympathomimetics.


Endoscopic management of uterine fibroids.
Uterine fibroids are very common, but their relationship to fertility is still controversial. Data in relation to fibroids and fertility mainly come from retrospective case series and prospective uncontrolled trials. Although some authors advocate prospective controlled studies, it is unlikely that an easy answer will be found due to considerable variations in location, size and number of fibroids, presence of additional infertility factors and variation of surgical techniques. Submucosal fibroids are more likely to be associated with menstrual disorders and subfertility, and hysteroscopic myomectomy has been accepted as the standard treatment for them. Treatment of submucosal fibroids may be associated with better reproductive outcomes. There is bigger controversy over the impact of intramural and subserosal fibroids on fertility. Laparoscopic myomectomy is now used by a large number of groups for removal of these fibroids in selected cases, but still remains a challenging procedure which requires advanced laparoscopic skills. Its advantages over open myomectomy include reduced postoperative pain, shorter hospitalization, quicker recovery, reduced febrile morbidity and blood loss. It may also reduce the risk of postoperative adhesion formation. There are now large numbers of pregnancies following laparoscopic myomectomy and the risk of uterine rupture in future pregnancies seems to be very low with good surgical technique.


PTBP1 promotes tumorigenesis by regulating apoptosis and cell cycle in colon cancer.
Increased expression of polypyrimidine tract-binding protein 1 (PTBP1) has been observed in human ovarian tumors, glioblastomas, and breast cancer, but its biological roles in tumorigenesis is not fully clear. In the present research, we investigated the biological role of PTBP1 in colon cancer. We found that PTBP1 was overexpressed both in colon cancer cell lines and tissues. Tissue microarray analysis (TMA) indicated that low PTBP1 expression predicted a favorable overall survival for colon cancer patients. Using small interfering RNA technology, we found that down-regulation of PTBP1 significantly inhibited colon cancer cell growth/proliferation, and induced cell cycle arrest as well as apoptosis in vitro. Western blot analysis showed that siRNA PTBP1 could up-regulate the expression of cytoC, p53 and Bax as well as down-regulated p85, p-AKT, cyclinD1, CDK4 and Bcl2 compared to the control. Furthermore, Caspase-3 and PARP1 were activated when PTBP1 is knockdown. This study implies that PTBP1 plays an important role in tumorigenesis of colon cancer.


Zinc deficiency in exclusively breast-fed infants.
Zinc deficiency in breast-fed infants is an important disorder. Unlike acrodermatitis enteropathica, it is transient and stops when nursing ends. We report two cases of premature infants, breast-fed only, who showed skin lesions resembling acrodermatitis enteropathica. Results of laboratory investigations revealed a lowered zinc level in the infants' serum and in the mothers' milk and a normal level of zinc in the mothers' serum. After the infants were given zinc supplements and their diets diversified, the skin lesions regressed and their serum zinc levels became normal.


Airway Remodeling and Hyperreactivity in a Model of Bronchopulmonary Dysplasia and Their Modulation by IL-1 Receptor Antagonist.
Bronchopulmonary dysplasia (BPD) is a chronic disease of extreme prematurity that has serious long-term consequences including increased asthma risk. We earlier identified IL-1 receptor antagonist (IL-1Ra) as a potent inhibitor of murine BPD induced by combining perinatal inflammation (intraperitoneal LPS to pregnant dams) and exposure of pups to hyperoxia (fraction of inspired oxygen = 0.65). In this study, we determined whether airway remodeling and hyperresponsiveness similar to asthma are evident in this model, and whether IL-1Ra is protective. During 28-day exposure to air or hyperoxia, pups received vehicle or 10 mg/kg IL-1Ra by daily subcutaneous injection. Lungs were then prepared for histology and morphometry of alveoli and airways, or for real-time PCR, or inflated with agarose to prepare precision-cut lung slices to visualize ex vivo intrapulmonary airway contraction and relaxation by phase-contrast microscopy. In pups reared under normoxic conditions, IL-1Ra treatment did not affect alveolar or airway structure or airway responses. Pups reared in hyperoxia developed a severe BPD-like lung disease, with fewer, larger alveoli, increased subepithelial collagen, and increased expression of α-smooth muscle actin and cyclin D1. After hyperoxia, methacholine elicited contraction with similar potency but with an increased maximum reduction in lumen area (air, 44%; hyperoxia, 89%), whereas dilator responses to salbutamol were maintained. IL-1Ra treatment prevented hyperoxia-induced alveolar disruption and airway fibrosis but, surprisingly, not the increase in methacholine-induced airway contraction. The current study is the first to demonstrate ex vivo airway hyperreactivity caused by systemic maternal inflammation and postnatal hyperoxia, and it reveals further preclinical mechanistic insights into IL-1Ra as a treatment targeting key pathophysiological features of BPD.


Myelographic appearance of meningo-vascular lymphoma involving cauda equina.
The myelographic pattern of diffuse meningo-vascular infiltration of the cauda equina is presented as characterized by marked enlargement of the nerve root shadows and occasional nodulation. This appearance, when coupled with appropriate clinical and laboratory findings, allows a specific diagnosis to be made.


Selective delamination by milling as a first step in the recycling of photovoltaic modules.
The recycling of photovoltaic modules has been a topic of increasing interest over the last years. At industrial scale, delamination of the module structure, which represents the first step in the recycling process, is currently achieved by multi-stage crushing. However, the quality of the outputs obtained through subsequent processing is low and offers room for improvement. Milling was investigated as an alternative physical delamination method. Lab-scale experiments were conducted to evaluate the applicability of the technology in general, as well as comparing a process by which all non-glass layers are removed at the same time (one-step) with one where the backsheet is removed as a separate fraction (two-step). Furthermore, a qualitative and quantitative analysis of the resulting outputs in each case was performed. Results show effective delamination by the milling process. Advantages in comparison to the currently used delamination techniques are identified in regard to the quality of the recovered glass, which is separated directly during delamination as well as the fact that the subsequent processing can therefore be focused on the polymers, metals and silicon contained within the removed materials. Some possibly problematic aspects in regard to upscaling have also been identified and discussed. While the two-step process enables the recovery of more homogenous outputs, it is also associated with a higher effort regarding input characterization and the milling process itself. In order to reach a conclusion about which process option is more feasible, additional investigations concerning the milling process, the input material and the output fractions are needed.


Ultrastructural changes accompanying development of fatigue in frog twitch skeletal muscle fibres.
The aim of the present study was to characterise and compare alterations in the ultrastructure of the functionally identified isolated twitch skeletal muscle fibres of the frog after repeated tetanic stimulation and under experimental conditions which modified their fatigability. Single isolated twitch muscle fibres of m. iliofibularis of adult frogs Rana temporaria were subjected to intermittent tetanic stimulation. Fibres at specified degree of fatigue were processed for electron microscopic observation and ultrastructural examination. The fatigue-resistant (FR) fibres that developed 90% of the control tetanic tension after 10 min stimulation in ordinary Ringer's solution showed regions with dilated intermyofibrillar spaces containing small vesicles and swollen mitochondria. In addition to the changes observed in FR fibres, the easily fatigued (EF) fibres that produced 50% of the original tension after 3 min stimulation showed small vacuoles in the sarcoplasm. In EF fibres that preserved 10% of the control tension after 10 min stimulation and showed swelling of the longitudinal sarcoplasmic reticulum, the central element of triads and mitochondria, large vacuoles were present. FR fibres exposed to low Ca2+ medium containing 0.02 mmol/l verapamil, lost their resistance to fatigue. Their contractile responses fell down to 20 % within 0.5 min of stimulation. Those fibres displayed large vacuoles and changes in mitochondria as observed in EF fibres after 10 min stimulation. These results suggest that morphological changes accompanying reduction of the contractile force (i) appear earlier than the reduction of the contractile ability, (ii) correlate with the degree of reduction of the contractile capacity but not with the duration of contractile activity, (iii) are not specific for the fatigue fibre type.


The impact of a quality improvement intervention to reduce nosocomial infections in a PICU.
To evaluate whether a quality improvement intervention could reduce nosocomial infection rates in a PICU and improve patient outcomes. Prospective interventional cohort study conducted during three periods: preintervention period, intervention period, and long-term follow-up. A 14-bed medical and surgical PICU in a university hospital for children. The quality improvement intervention consisted of the creation of an infection control team, a program targeting hand hygiene, and quality practices focused on preventing nosocomial infections. We included 851 patients in the preintervention period, 822 in the intervention period, and 940 in the long-term follow-up period. Compared with the preintervention period, in the intervention period, the rates of central line-associated bloodstream infection decreased from 8.1 to 6/1,000 central venous catheter-days (p = 0.640), ventilator-associated pneumonia decreased from 28.3 to 10.6/1,000 days' ventilation (p = 0.005), and catheter-associated urinary tract infection decreased from 23.3 to 5.8/1,000 urinary catheter-days (p < 0.001). Furthermore, hospital length of stay decreased from 18.56 to 14.57 days (p = 0.035) and mortality decreased from 5.1% to 3.3% (p = 0.056). Multivariable logistic regression found that nosocomial infections was independently associated with increased mortality (odds ratio, 2.35 [95% CI, 1.02-5.55]; p = 0.046). Compared with the preintervention period, in the long-term follow-up period, central line-associated bloodstream infection decreased to 4.6/1,000 central venous catheter-days (p = 0.205); ventilator-associated pneumonia decreased to 9.1/1,000 ventilation-days (p = 0.001), and catheter-associated urinary tract infection decreased to 5.2/1,000 urinary catheter-days (p < 0.001). Hospital length of stay (14.45 days; p = 0.048) and mortality (3.2%; p = 0.058) also decreased. A multifaceted quality improvement intervention reduced nosocomial infection rates, hospital length of stay, and mortality in our PICU. The effects of the intervention were sustained over time.


Functional consequences of cartilage degeneration in the equine metacarpophalangeal joint: quantitative assessment of cartilage stiffness.
No quantitative data currently exist on the relationship of the occurrence of cartilage degeneration and changes in site-specific biomechanical properties in the metacarpophalangeal (MCP) joint in the horse. To gain insight into the biomechanical consequences of cartilage deterioration at 2 differently loaded sites on the proximal articular surface of the proximal phalanx (P1). Static and dynamic stiffness of articular cartilage decreases significantly in degenerated cartilage. Cartilage degeneration index (CDI) values were measured at the lateral dorsal margin (Site 1), lateral central fovea (Site 2) and entire joint surface of P1 (CDIP1) in 30 horses. Group 1 contained joints without (CDIP1 values <25 %, n = 22) and Group 2 joints with (CDIP1 values >25 %, n = 8) signs of cartilage degeneration. Cartilage thickness at Sites 1 and 2 was measured using ultrasonic and needle-probe techniques. Osteochondral plugs were drilled out from Sites 1 and 2 and subsequently tested biomechanically in indentation geometry. Young's modulus at equilibrium and dynamic modulus were determined. Cartilage thickness values were not significantly different between the 2 groups and sites. Young's modulus at Site 1 was significantly higher in Group 1 than in Group 2; at Site 2, the difference was not significant. Dynamic modulus values were significantly higher in Group 1 than in Group 2 at both sites. Degenerative cartilage changes are clearly related to loss of stiffness of the tissue. Absolute changes in cartilage integrity in terms of CDI are greatest at the joint margin, but concomitant changes are also present at the centre, with a comparable decrease of the biomechanical moduli at the 2 sites. Therefore, significant cartilage degradation at the joint margin not only reflects local deterioration of biomechanical properties, but is also indicative of the functional quality in the centre. These findings may be important for improving prognostication and developing preventative measures.


Targeted disruption of the Epm2a gene causes formation of Lafora inclusion bodies, neurodegeneration, ataxia, myoclonus epilepsy and impaired behavioral response in mice.
Mutations in the EPM2A gene encoding a dual-specificity phosphatase (laforin) cause Lafora disease (LD), a progressive and invariably fatal epilepsy with periodic acid-Schiff-positive (PAS+) cytoplasmic inclusions (Lafora bodies) in the central nervous system. To study the pathology of LD and the functions of laforin, we disrupted the Epm2a gene in mice. At two months of age, homozygous null mutants developed widespread degeneration of neurons, most of which occurred in the absence of Lafora bodies. Dying neurons characteristically exhibit swelling in the endoplasmic reticulum, Golgi networks and mitochondria in the absence of apoptotic bodies or fragmentation of DNA. As Lafora bodies become more prominent at 4-12 months, organelles and nuclei are disrupted. The Lafora bodies, present both in neuronal and non-neural tissues, are positive for ubiquitin and advanced glycation end-products only in neurons, suggesting different pathological consequence for Lafora inclusions in neuronal tissues. Neuronal degeneration and Lafora inclusion bodies predate the onset of impaired behavioral responses, ataxia, spontaneous myoclonic seizures and EEG epileptiform activity. Our results suggest that LD is a primary neurodegenerative disorder that may utilize a non-apoptotic mechanism of cell death.


Mitochondrial Tethers and Their Impact on Lifespan in Budding Yeast.
Tethers that link mitochondria to other organelles are critical for lipid and calcium transport as well as mitochondrial genome replication and fission of the organelle. Here, we review recent advances in the characterization of interorganellar mitochondrial tethers in the budding yeast, Saccharomyces cerevisiae. We specifically focus on evidence for a role for mitochondrial tethers that anchor mitochondria to specific regions within yeast cells. These tethering events contribute to two processes that are critical for normal replicative lifespan: inheritance of fitter mitochondria by daughter cells, and retention of a small pool of higher-functioning mitochondria in mother cells. Since asymmetric inheritance of mitochondria also occurs in human mammary stem-like cells, it is possible that mechanisms underlying mitochondrial segregation in yeast also operate in other cell types.


3β-Acet-oxy-12-oxoolean-28-oic acid benzyl ester.
The mol-ecule of title compound, C(39)H(56)O(5), contains five fused six-membered rings, four of which (rings A, B, D and E) adopt a chair conformation, while the other (ring C) has a half chair conformation. The acet-oxy and carb-oxy-benzyl groups occupy equatorial positions.


Larger lacertid lizard species produce higher than expected iliotibialis muscle power output: the evolution of muscle contractile mechanics with body size.
Increases in body size can lead to alterations in morphology, physiology, locomotor performance and behaviour of animals. Most studies considering the effects of scaling on muscle performance have studied within-species effects, with few studies considering differences between species. A previous review of published data indicates that maximum muscle-shortening velocity decreases, but that maximum isometric stress does not change, with increased body mass across species of terrestrial animals. However, such previous analyses do not account for the phylogenetic relatedness of the species studied. Our aim was to use phylogenetically informed analysis to determine the effects of body size on isolated iliotibialis muscle performance across 17 species of lacertid lizards. Between one and five individuals were used to obtain mean performance values for each species. We analysed the relationship between each variable and body size, as estimated by snout-vent length (SVL), whilst taking into account the phylogenetic relationships between species. We found that isometric tetanus relaxation time, maximal tetanus stress (force per muscle cross-sectional area) and maximal work loop power output (normalised to muscle mass) all significantly increased with greater SVL. In contrast, fatigue resistance during repeated work loops significantly decreased with SVL and there was no effect of size on tetanus activation time. When we compare our findings with those that would be predicted by dynamic similarity, then as these lacertid species become bigger, there is a greater than expected increase in the normalised muscle power output, probably to counter the larger than expected increase in body mass.


Selection of Potential Probiotic Lactobacillus with Inhibitory Activity Against Salmonella and Fecal Coliform Bacteria.
Three hundred and sixty presumptive lactic acid bacteria (LAB) isolated from pregnant sows, newborn, suckling, and weaned piglets were preliminarily screened for anti-Salmonella activity. Fifty-eight isolates consisting of Lactobacillus reuteri (n = 32), Lactobacillus salivarius (n = 10), Lactobacillus mucosae (n = 8), Lactobacillus johnsonii (n = 5), and Lactobacillus crispatus (n = 3) were selected and further characterized for probiotic properties including production of antimicrobial substances, acid and bile tolerance, and cell adherence to Caco-2 cells. Eight isolates including Lact. johnsonii LJ202 and Lact. reuteri LR108 were identified as potential probiotics. LJ202 was selected for further use in co-culture studies of two-bacterial and multiple-bacterial species to examine its inhibitory activity against Salmonella enterica serovar Enteritidis DMST7106 (SE7106). Co-culture of LJ202 and SE7106 showed that LJ202 could completely inhibit the growth of SE7106 in 10 h of co-culture. In co-culture of multiple-bacterial species, culturable fecal bacteria from pig feces were used as representative of multiple-bacterial species. The study was performed to examine whether interactions among multiple-bacterial species would influence antagonistic activity of LJ202 against SE7106 and fecal coliform bacteria. Co-culture of SE7106 with different combinations of fecal bacteria and probiotic (LJ202 and LR108) or non-probiotic (Lact. mucosae LM303) strains revealed that the growth of SE7106 was completely inhibited either in the presence or in the absence of probiotic strains. Intriguingly, LJ202 exhibited notable inhibitory activity against fecal coliform bacteria while LR108 did not. Taken together, the results of co-culture studies suggested that LJ202 is a good probiotic candidate for further study its inhibitory effects against pathogen infections in pigs.


Nanovesicular-Mediated Intranasal Drug Therapy for Neurodegenerative Disease.
Numerous neurodegenerative conditions, such as Alzheimer's, Huntington's, Parkinson's, amyotrophic lateral sclerosis, and glioblastoma multiform are now becoming significant concerns of global health. Formulation-related issues, physiological and anatomical barriers, post-administration obstacles, physical challenges, regulatory limitations, environmental hurdles, and health and safety issues have all hindered successful delivery and effective outcomes despite a variety of treatment options. In the current review, we covered the intranasal route, an alternative strategic route targeting brain for improved delivery across the BBB. The trans-nasal pathway is non-invasive, directing therapeutics directly towards brain, circumventing the barrier and reducing peripheral exposure. The delivery of nanosized vesicles loaded with drugs was also covered in the review. Nanovesicle systems are organised in concentric bilayered lipid membranes separated with aqueous layers. These carriers surmount the disadvantages posed by intranasal delivery of rapid mucociliary clearance and enzymatic degradation, and enhance retention of drug to reach the site of target. In conclusion, the review covers in-depth conclusions on numerous aspects of formulation of drug-loaded vesicular system delivery across BBB, current marketed nasal devices, significant jeopardies, potential therapeutic aids, and current advancements followed by future perspectives.


Combination intraventricular chemotherapy for meningeal neoplasia.
Twenty two patients with meningeal neoplasia were treated with biweekly combination intraventricular chemotherapy using methotrexate, cytosine arabinoside, and thiotepa. Patients with the following malignancies were included: breast cancer, ten patients; lung cancer, seven; non-Hodgkin's lymphoma, two; malignant melanoma, one; transitional cell carcinoma of the bladder, one; and malignant glioma, one. Eight of 22 patients (36%) had a Karnofsky performance status of less than 50%. Eleven of 22 patients received radiotherapy to symptomatic areas, and seven received systemic chemotherapy in addition to combination intraventricular therapy. Patients were evaluated for both toxicity and response to therapy. Myelosuppression was the major toxic condition and occurred in 17 of 22 patients (77%). Ten patients (45%) had a nadir WBC count of less than 1000/microL or a platelet count of less than 25,000/microL. No patient achieved a complete response (CR), although nine patients (41%) had partial responses (PRs) lasting 4 to 24 + weeks. Median survival for the entire group was 10 weeks (range, 6 to 24+ weeks). In this small group of patients, simultaneous triple-drug intraventricular chemotherapy caused unacceptable myelosuppression without increasing the response rate, response duration, or survival when compared with single-agent methotrexate and radiotherapy.


Congenital osteogenesis imperfecta in Charollais cattle.
An outbreak of an apparently new hereditary bone disease--congenital osteogenesis imperfecta--in six newborn half-sib Charollais calves is described. In many respects the clinical, pathological, radiological and genetical findings resemble the congenital osteogenesis imperfecta seen in man and sheep.


Nano-sized domains related to dielectric anomaly in YFe2O4-delta.
We examined microstructures related to the charge ordering in YFe2O4-delta, by transmission electron microscopy. It is found that two types of characteristic diffuse scatterings appear at room temperature. One is characteristic diffuse streaks elongated along the [0001] direction through the (1/3 1/3 2/3 0)-type reciprocal positions and the other is diffuse spots at (1/3 - eta 1/3 - eta 2/3 + 2eta 0)-type incommensurate positions (eta approximately 0.066). Real-space images revealed that the former diffuse scattering is related to nano-domains due to the charge ordering and the latter one is related to those due to vacancy ordering. The presence of the nano-sized domains should be strongly related to the dielectric anomalies found in YFe2O4-delta.