Effect of chlorhexidine gluconate on acute nonmicrobial inflammation reaction.
The effects of chlorhexidine on the appearance of leukocytes and some hydrolytic enzymes were studied in an experimental acute nonmicrobial inflammation reaction caused by implanation of viscose sponge beneath the backskin. The results showed that chlorhexidine gluconate decreased the number of leukocytes in the inflammatory exudate. The drug used had no measurable effect on the distribution of different types of leukocytes. Chlorhexidine has a clear inhibitory effect on the appearance of phosphatases, glycosidases and peptidases. On the other hand the effect on proteinases was small.


Lymphoid cell development from fetal hematopoietic progenitors and human pluripotent stem cells.
Lymphoid cells encompass the adaptive immune system, including T and B cells and Natural killer T cells (NKT), and innate immune cells (ILCs), including Natural Killer (NK) cells. During adult life, these lineages are thought to derive from the differentiation of long-term hematopoietic stem cells (HSCs) residing in the bone marrow. However, during embryogenesis and fetal development, the ontogeny of lymphoid cells is both complex and multifaceted, with a large body of evidence suggesting that lymphoid lineages arise from progenitor cell populations antedating the emergence of HSCs. Recently, the application of single cell RNA-sequencing technologies and pluripotent stem cell-based developmental models has provided new insights into lymphoid ontogeny during embryogenesis. Indeed, PSC differentiation platforms have enabled de novo generation of lymphoid immune cells independently of HSCs, supporting conclusions drawn from the study of hematopoiesis in vivo. Here, we examine lymphoid development from non-HSC progenitor cells and technological advances in the differentiation of human lymphoid cells from pluripotent stem cells for clinical translation.


A modified fluorescent sensor for reporting glucose concentration in the airway lumen.
We have modified the periplasmic Escherichia coli glucose/galactose binding protein (GBP) and labelled with environmentally sensitive fluorophores to further explore its potential as a sensor for the evaluation of glucose concentration in airway surface liquid (ASL). We identified E149C/A213R GBP labelled with N,N'-Dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)ethylenediamine (IANBD, emission wavelength maximum 536nm) with a Kd for D-glucose of 1.02mM and a fluorescence dynamic range of 5.8. This sensor was specific for D-glucose and exhibited fluorescence stability in experiments for several hours. The use of E149C/A213R GBP-IANBD in the ASL of airway cells grown at air-liquid-interface (ALI) detected an increase in glucose concentration 10 minutes after raising basolateral glucose from 5 to 15mM. This sensor also reported a greater change in ASL glucose concentration in response to increased basolateral glucose in H441 airway cells compared to human bronchial epithelial cells (HBEC) and there was less variability with HBEC data than that of H441 indicating that HBEC more effectively regulate glucose movement into the ASL. The sensor detected glucose in bronchoalveolar lavage fluid (BALf) from diabetic db/db mice but not normoglycaemic wildtype mice, indicating limited sensitivity of the sensor at glucose concentrations <50μM. Using nasal inhalation of the sensor and spectral unmixing to generate images, E149C/A213R GBP-IANBD fluorescence was detected in luminal regions of cryosections of the murine distal lung that was greater in db/db than wildtype mice. In conclusion, this sensor provides a useful tool for further development to measure luminal glucose concentration in models of lung/airway to explore how this may change in disease.


Neuropeptide Y3-36 incorporated into PVAX nanoparticle improves functional blood flow in a murine model of hind limb ischemia.
We generated a novel nanoparticle called PVAX, which has intrinsic antiapoptotic and anti-inflammatory properties. This nanoparticle was loaded with neuropeptide Y3-36 (NPY3-36), an angiogenic neurohormone that plays a central role in angiogenesis. Subsequently, we investigated whether PVAX-NPY3-36 could act as a therapeutic agent and induce angiogenesis and vascular remodeling in a murine model of hind limb ischemia. Adult C57BL/J6 mice (n = 40) were assigned to treatment groups: control, ischemia PBS, ischemia PVAX, ischemia NPY3-36, and Ischemia PVAX-NPY3-36 Ischemia was induced by ligation of the femoral artery in all groups except control and given relevant treatments (PBS, PVAX, NPY3-36, and PVAX-NPY3-36). Blood flow was quantified using laser Doppler imaging. On days 3 and 14 posttreatment, mice were euthanized to harvest gastrocnemius muscle for immunohistochemistry and immunoblotting. Blood flow was significantly improved in the PVAX-NPY3-36 group after 14 days. Western blot showed an increase in angiogenic factors VEGF-R2 and PDGF-β (P = 0.0035 and P = 0.031, respectively) and antiapoptotic marker Bcl-2 in the PVAX-NPY3-36 group compared with ischemia PBS group (P = 0.023). Proapoptotic marker Smad5 was significantly decreased in the PVAX-NPY3-36 group as compared with the ischemia PBS group (P = 0.028). Furthermore, Y2 receptors were visualized in endothelial cells of newly formed arteries in the PVAX-NPY3-36 group. In conclusion, we were able to show that PVAX-NPY3-36 can induce angiogenesis and arteriogenesis as well as improve functional blood flow in a murine model of hind limb ischemia.NEW & NOTEWORTHY Our research project proposes a novel method for drug delivery. Our patented PVAX nanoparticle can detect areas of ischemia and oxidative stress. Although there have been studies about delivering angiogenic molecules to areas of ischemic injury, there are drawbacks of nonspecific delivery as well as short half-lives. Our study is unique because it can specifically deliver NPY3-36 to ischemic tissue and appears to extend the amount of time therapy is available, despite NPY3-36's short half-life.


Microwave-assisted palladium-catalyzed direct arylation of 1,4-disubstituted 1,2,3-triazoles with aryl chlorides.
Treatment of 1,4-disubstituted 1,2,3-triazoles with aryl chlorides in the presence of potassium carbonate under palladium catalysis and microwave irradiation at 250 degrees C for 15 min leads to arylation of the triazole at the 5-position. A variety of functional groups, including ester and hydroxy groups, are compatible. The procedure is suitable for the regioselective preparation of trisubstituted triazoles. Microwave irradiation accelerates the reaction, thus allowing the rapid synthesis of trisubstituted triazoles, which are difficult to synthesize selectively.


Lessons from Cuba for Global Precision Medicine: CYP2D6 Genotype Is Not a Robust Predictor of CYP2D6 Ultrarapid Metabolism.
A long-standing question and dilemma in precision medicine is whether and to what extent genotyping or phenotyping drug metabolizing enzymes such as CYP2D6 can be used in real-life global clinical and societal settings. Although in an ideal world using both genotype and phenotype biomarkers are desirable, this is not always feasible for economic and practical reasons. Moreover, an additional barrier for clinical implementation of precision medicine is the lack of correlation between genotype and phenotype, considering that most of the current methods include only genotyping. Thus, the present study evaluated, using dextromethorphan as a phenotyping probe, the relationship between CYP2D6 phenotype and CYP2D6 genotype, especially for the ultrarapid metabolizer (UM) phenotype. We report in this study, to the best of our knowledge, the first comparative clinical pharmacogenomics study in a Cuban population sample (N = 174 healthy volunteers) and show that the CYP2D6 genotype is not a robust predictor of the CYP2D6 ultrarapid metabolizer (mUM) status in Cubans. Importantly, the ultrarapid CYP2D6 phenotype can result in a host of health outcomes, such as drug resistance associated with subtherapeutic drug concentrations, overexposure to active drug metabolites, and altered sensitivity to certain human diseases by virtue of altered metabolism of endogenous substrates of CYP2D6. Hence, phenotyping tests for CYP2D6 UMs appear to be a particular necessity for precision medicine in the Cuban population. Finally, in consideration of ethical and inclusive representation in global science, we recommend further precision medicine biomarker research and funding in support of neglected or understudied populations worldwide.


Virgins at age 26: who are they?
Background Studies on virgins remain scarce. This study explores the characteristics of virgin young adults, the reasons for remaining virgin, and its potential social and health implications. Data were drawn from the 2017 Swiss study on sexual health and behaviour among young adults. A total of 5175 participants (mean age 26 years ± 0.01) were divided into virgins and non-virgins. Virginity was defined as never having had a sexual partner, defined as a person with whom the participant has had sexual contact with or without penetration. A total of 275 (5.3% (95% CI: 4.7-6.0), 58% males) were virgins. Virgins had higher odds of being male (aOR: 2.27 (95% CI: 1.62-3.17)) and reporting poorer health (1.43 (1.07-1.92)). They had lower odds of living on their own (0.24 (0.18-0.32)), being satisfied with their social life (0.78 (0.72-0.85)), having experimented with substances (e.g. drunkenness, 0.27 (0.19-0.67)) and having used online dating (0.52 (0.26-1.12)) or pornography (0.67 (0.42-0.94)). The main reason for remaining virgin was 'I have not found the right person' for females, and 'I have not had the occasion' for males. Among young adults, 1 in 20 is a virgin. Virgins do not seem to have gone through the usual experimentations of adolescence, are less socially driven and reported more health challenges. The main reason for remaining a virgin reveals gender-stereotyped responses. Sexual inactivity among young adults should be considered by health professionals to ensure the absence of distress and open discussion for potential questions.


[Role of exogenous thyrocalcitonin in post-traumatic skin regeneration].
The character and completeness of posttraumatic skin regeneration, as well as the role of fibroblastic cells were studied under the effect of thyrocalcitonine (TCT). By means of cytological, morphological, histochemical autoradiographic, electron microscopic and some biochemical methods, stimulating effect of TCT on the cell proliferation and differentiation in the host regeneration was demonstrated. Application of TCT enhanced the main stages of collagenogenesis that, in its turn, promoted earlier transformation of granulous tissue into connective tissue and stimulated healing of experimental wounds.


Operative choice for displaced proximal humeral fractures in adolescents with open visible physis: A comparative study of external fixator vs. Kirschner wire.
For adolescents with severely displaced proximal humeral fracture (PHF), surgery is a good choice yielding excellent outcomes, and Kirchner wire (KW) is a cost-effective choice for fixation. Purpose of this study is to compare the clinical outcomes of external fixator (EF) and KW for the treatment of PHF in adolescents. Patients of PHF operated at our institute, from January 2008 to January 2016, were reviewed retrospectively. Demographic data, including sex, age at the time of surgery, operated side, and hardware choice, were collected from the hospital database. Preoperative radiographs were reviewed and classified according to Neer-Horwitz classification. Shoulder function was evaluated at the last follow-up using the American Shoulder and Elbow Surgeons (ASES) score. Complications, including infection, malunion, nonunion, stiffness of the shoulder joint, and failure of fixation were also recorded. Thirty-five patients, including 23 males and 12 females, were included in the EF group, whereas 40 patients, including 25 males and 15 females, were included in the KW group (P = 0.867). The average age of patients in the EF group was 13.3 ± 1.7 years, and that of KW was 13.6 ± 1.8 years (P = 0.409). Patients in both groups were followed-up for at least 12 months. The operative time in the EF group (42.4 ± 11.2 min) was significantly shorter than those in the KW group (54 ± 13.6 min) (P < 0.001). The frequency of fluoroscopy in the EF group (12 ± 2.4 times) was significantly less than those in the KW group (17 ± 2.8 times (P < 0.001). The rate of open reduction was significantly higher in KW (35%) group than those in the EF group (0%) (P < 0.001). There was no case of nonunion and malunion in both groups. External fixator is superior to Kirschner wire in the treatment of proximal humeral fractures in adolescents with shorter operative time and lower rate of open reduction with comparable clinical outcomes.


Interconversion of carbon sites in boat-chair-boat cyclodecane; conformations of chlorocyclodecane and cyclodecyl acetate.
Interconversion of carbon sites in boat-chair-boat (BCB) cyclodecane occurs by way of the twist-boat-chair (TBC) conformation, which predicts that C-1 exchanges with C-4, etc. The previously obtained low-temperature 13C spectra could be matched by assuming (1,4) or (1,3) exchange, but not (1,2) exchange. A free-energy barrier of 5.54 kcal/mol was obtained for conversion of BCB to TBC at -137.4 degrees C. The major conformation of chlorocyclodecane and cyclodecyl acetate is assigned to the IIIe BCB.


Three Scientific Controversies to Engage Students in Reading Primary Literature.
In this review, three sets of papers are presented. Each of the sets presents a historical or active controversy in neuroscience ranging from cell biology and cell signaling, to developmental neuroscience, to cognitive neuroscience. The first set captures a historical controversy about whether the beta/gamma subunit of G-proteins can be active in opening ion channels. The second set represents a modern instantiation of the oldest debate in neuroscience: are our minds and brains the product of innate factors or environmental influences. This debate plays out in a series of papers on the development of the visual system. The third set contrasts the view that the hippocampus and surrounding structures primarily function to represent our location in space (a position for which the 2014 Nobel Prize in Physiology or Medicine was awarded to three investigators) with the perspective that the hippocampus is a general-purpose structure for declarative memories, spatial or non-spatial. The first and third controversies feature publications of virtually identical experiments that show opposing results. All three controversies are discussed in regards to the individual scientists who did the experiments and debated directly with each other. The first (beta/gamma subunits) emphasizes the value of reproducibility in scientific research, the second (visual cortex development) emphasizes the value of new techniques and updating scientific models, and the third (hippocampus) exposes students to an ongoing, albeit under discussed, debate.


[Prosthetic reconstruction of the trachea and carina].
We have performed prosthetic reconstruction of the trachea and carina in 12 patients since 1979. We used Neville's prosthesis in 7 patients and Katsura's prosthesis in 5 patients. Seven patients were operated on for lung cancer, 2 patients for adenoid cystic carcinoma of the trachea and the others for large cell carcinoma of the trachea, thyroid cancer and tuberculous granuloma, respectively. Prosthetic reconstruction of the trachea was performed in 4 patients. Carinal resection was performed in 8 patients: With right sleeve pneumonectomy in 4 patients, with right upper lobectomy in 2 patients and only carinal resection in 2 patients. Prosthetic reconstruction after the carinal resection was performed using 3 straight types, 1 curved type and 4 bifurcated types. With regard to the complications of the prosthetic reconstruction, dehiscence at the anastomotic site was seen in 5 patients, granulation in 4 patients, empyema in 3 patients, massive hemorrhage in 2 patients and migration of the prosthesis in 1 patient. Five patients survived more than 1 year. The longest survival time was 43 months. To prevent complications of the prosthetic reconstruction, we improved the anastomotic method, reinforced the anastomotic site with Marlex mesh and protected the surrounding vessels with Lyodura.


Postgraduate training in Ireland: expectations and experience.
Postgraduate medical training in Ireland has been compared unfavourably with training abroad and blamed for an "exodus" of graduates of Irish medical schools. Exploration of features of a good training environment and development of tools to measure it have been the focus of much published research. There have been no Irish studies examining training environment using such validated tools. The aim of this study was to use a validated tool, to examine the expectations and experience of training, amongst those training under the Royal College of Physicians of Ireland (RCPI). The Dutch Residency Education Climate Test (D-RECT) is a 50 item tool to measure postgraduate learning environments. D-RECT was sent to all new entrants to RCPI training programmes in July 2012 (n = 527) and completed in regard to expectations of training (response rate 80.6 %). In March 2013, D-RECT was sent to all RCPI trainees (n = 1,246) to complete in relation to the post held on 1 March (response rate 32.6 %). Data were analysed in SPSS version 18. Experience fell short of expectations for basic specialist training, however, scores for experience rose with greater seniority to match expectations. Positive aspects were teamwork, consultant willingness to discuss patients and respectful treatment of trainees. Areas of weakness were provision of feedback and time to learn new skills. Measurement of learning environment at a national level using a quantitative tool provides useful information for quality assurance and improvement of training.


Less sitting, more physical activity and higher cardiorespiratory fitness: associations with weight status among a national sample of children.
Background: Very few studies have evaluated the independent and combined associations of sedentary behavior (SB), moderate-to-vigorous physical activity (MVPA) and cardiorespiratory fitness (CRF) on obesity. Our recent work has evaluated this paradigm in the adult population,but no study has evaluated this paradigm in the child population, which was the purpose of this study. Methods: A national sample of children (N=680, 6-11 years) were evaluated via the National Youth Fitness Survey; this study was conducted in 2012, employing a nationally representative sample, occurring across 15 different geographic regions in the United States. SB and MVPA were assessed via parental recall, with CRF objectively measured via a treadmill-based aerobic test. Obesity was determined for measured body mass index. A PACS (Physical Activity Cardiorespiratory Sedentary) score was created ranging from 0-3, indicating each child's number of positive characteristics (PA, CRF, SB). Results: Meeting MVPA guidelines (OR adjusted=0.47; 95% CI: 0.29-0.77) and above-median CRF (OR adjusted=0.12; 95% CI: 0.07-0.21), but not SB (OR adjusted=0.62; 95% CI: 0.35-1.10),were associated with reduced odds of obesity. Compared to those with a PACS score of 0, the odds of obesity for PACS scores of 1-3, respectively, were: 0.31 (0.18-0.53), 0.12 (0.04-0.34), and 0.05 (0.02-0.10). Conclusion: These findings highlight the need for public health strategies to promote child MVPA and CRF, and to reduce SB.


[European medicine in the conquest of America].
The author hold up America's discovery is the most important event in mankind history, because of the transcendental changes in all aspects of the thought, culture and social development it originated. The study displays the most important aspects of the process: aboriginal medicine, invisible enemy, withholding conquest, first medical doctors, medical practice, medicine man clinical assistance and medical education.


Care for older people with a dementia in acute hospital settings.
If nurses plan and approach older people with dementia with positive values, and learn from the person's communication through their behaviour, the outcomes for all parties can be improved. The vignette has offered one example, but also demonstrates that there are no failure-proof ways of communicating, and sometimes nurses need to learn through trial and error. Only in this way can they become more skilled in their interventions to facilitate rather than manage challenging behaviours. Avoidance and ignorance do not help in either the short term or the long term. The good news is that single interventions are successful 45 per cent of the time and multiple interventions, as shown in Box 2, are more successful (Bair et al 1999).


Evaluation of a Method for Long-Term Cryopreservation of Fungal Strains.
The conservation of microorganisms is essential for their in-depth study. However, today's most widely used conservation methods, based on the use of distilled water, soil, oils, or silica, do not guarantee the stability of fungal cells, especially dermatophytes. This problem led us to evaluate the conservation capacity of a cryogenic vials system containing glass beads covered in a cryopreservant hypertonic solution as an alternative method of storage of fungal cells at -80°C. Up to 570 strains of fungi belonging to 27 different species, isolated from clinical samples, were inoculated into cryotubes containing 25 glass beads covered in a cryopreserving hypertonic solution. Suspensions were mixed vigorously and the cryopreserving solution was discarded. The tubes were frozen at -80°C for a period of 42 months and periodically, a glass bead was removed from each cryotube and inoculated onto Sabouraud dextrose agar, and incubated at 30°C for 7-14 days to evaluate the number of colonies recovered, their purity, and phenotypic characteristics. All yeast isolates were recovered, unlike 2 isolates (4.4%) of the mold group and 21 (10.7%) of the dermatophytes. Survival rates were close to 100% for yeasts and molds, with expiration times being estimated for almost indefinite stocks, and 62% for dermatophytes, with an average expiration date of 25.5 years. The phenotypic characteristics remained comparable to those of the strains before storage. Conservation at -80°C using cryogenic vials is a reliable and efficient system for the conservation of fungal collections, and although the behavior differs by groups, stratified survival data are obtained to avoid extinction.


[Crime prevention in high-functioning pervasive developmental disorders with paraphilia].
Paraphilia refers to occasional concomitant disorders of pervasive developmental disorder (PDD). When a restricted interest of PDD is focused on a sexual object, paraphilia may be develop as a problematic symptom. However, having this concomitant disorder does not always result in criminal behavior. When the social interactivity of a particular patient with PDD is severely impaired, paraphilia could lead to a sex crime. Because pedophilia targets sacrifice innocent and defenseless children, it is critical to prevent such sex crimes by understanding the psychopathology of PDD with paraphilia, especially pedophilia. Two cases of male adolescents with high-functioning PDD and pedophilia were reported; one ended up committing a serious crime, and the other controlled his sexual impulse. The psychopathology of these two cases was similar; however, the outcome turned out to be quite different. The similarity and dissimilarity of these two cases were analyzed. We came to a conclusion that early intervention could be a key to prevent the development of criminal sexual behavior in PDD with paraphilia (pedophilia). Both patients became aware of pedophilia during adolescence and developed a depressive state at the time of consulting our clinic. In the first case, the patient stabbed a woman with a knife. He could not respect other people, including women he was sexually interested in and has always been preoccupied with his own peculiar ideas. He did not listen to other people's opinions and his abnormal thoughts had never been corrected because of his lack of ability to form interpersonal relationships. The second patient could control his sexual impulse. He has an ability to sympathize with the child he is sexually interested in and has confronted his sexual impulses. He could build interpersonal relationship with others and listen to other people's opinions. He made an effort to manage his sexual impulses positively through individual psychotherapy. He was diagnosed at the age of two years and started rehabilitation training soon after. He had some experiences of consulting people when he was in trouble. In the treatment and correctional education of pedophilia, some sort of special care regarding the characteristics of PDD is indispensable; e.g., pointing-out and explaining unacceptable behavior repeatedly, teaching the correct action concretely, and changing the pathological sexual preference into a constructive one, etc. These therapeutic approaches are quite different from controlling paraphilia without PDD. PDD adolescents with impaired social interactivity could be further helper if they are diagnosed at an earlier stage of their lives and managed appropriately. A sense of being accepted by others and also experiences of mutual interaction with others are particularly important for them. Professionals should be aware that an early and proper intervention method could prevent the later development of criminal behavior in PDD adolescents who suffer from a sense of incompatibility with others because of concomitant paraphilia.


Clinical application of SPECT-CT with 99mTc-Tektrotyd in bronchial and thymic neuroendocrine tumors (NETs).
Neuroendocrine tumors (NETs) of the thorax including bronchial and thymic tumors belong to foregut NETs. Limited loco-regional thoracic NETs can be resected with surgery, but in extensive metastatic disease the treatment is mainly palliative. A high incidence and density of somatostatin receptors (SSTR2, SSTR3, and SSTR5) are found in thoracic NETs. The purpose of this study was to evaluate the role of SPECT-CT somatostatin receptor scintigraphy (SRS) with 99mTc-Tektrotyd for imaging, staging and follow up of patients with bronchial and thymic neuroendocrine tumors. Forty-one patients with thoracic tumors with neuroendocrine differentiation were studied. Sixty-eight examinations including SPECT-CT studies of the neck and chest and/or abdomen and pelvis were carried out 2-4 hrs. post i.v. administration of aver-age 740 MBq activity dose of 99mTc-EDDA/HYNIC-TOC (Tektrotyd, Polatom). In all 41 investigated patients we obtained 81.25% (13/16), 88% (22/25) and 85.36% (35/41) of sensitivity, specificity and accuracy of this diagnostic approach, respectively. Somatostatin-receptor scintigraphy correctly identified all primary NETs located in the lungs and thymus. SPECT-CT studies with 99mTc-EDDA/HYNIC-TOC resulted in exact pre-surgical and pre-treatment N/M staging of bronchial and thymic NETs, except 2 cases with multiple hepatic metastases and 1 with massive suprarenal metastasis. It can be concluded that SPECT-CT with 99mTc-EDDA/HYNIC-TOC is a valuable tool for staging and follow-up of patients with thoracic NETs.


DNA barcoding revises a misidentification on mossy frog: new record and distribution extension of Theloderma corticale Boulenger, 1903 (Amphibia: Anura: Rhacophoridae).
As an endangered animal group, mossy frog (genus Theloderma) has attracted the attention of biologists and wildlife conservationists. Clarifying the taxonomic status and distribution of each species in Theloderma is important to determine the conservation status for each species, establish appropriate conservation strategies and probe the speciation process. Recently, we discovered a medium-sized species of mossy frog of the genus Theloderma in April 2015 during municipal surveys of amphibians in Dayao Mountain of Jinxiu. It was collected from the water-filled tree cavities. However, there remains some uncertainty about the species determination of the mossy frog in the Yinshan station of Dayao Mountain in Guangxi Province, China. Previously, the mossy frog in Guangxi Province was recognized as Th. kwangsiense. In order to clarify the species status of the mossy frog obtained from Guangxi, we sequenced 2414 bp of the 12S and 16S genes in the sample collected from the Dayao Mountain. Combining all the sequence in NCBI, genetic analyses from the data suggest that the sample from the Dayao Mountain is Th. corticale rather than Th. kwangsiense. It is most likely that the most previous studies had wrong species identification. And, it is the first time we use DNA barcoding to prove that the species obtained from Guangxi is a new distribution of Th. corticale.


Effect of particle aggregation on the survival of irradiated vaccinia virus.
Galasso, G. J. (University of North Carolina School of Medicine, Chapel Hill), and D. G. Sharp. Effect of particle aggregation on the survival of irradiated vaccinia virus. J. Bacteriol. 90:1138-1142. 1965.-The survival curve (plaque titer versus time) of vaccinia virus irradiated with ultraviolet light was found to be strongly dependent, in both shape and general slope, on the degree of aggregation among the virus particles. When special care was taken to produce completely dispersed virus, a straight steep line resulted. Some severely aggregated preparations produced a straight line also, but of much less slope. Thus, the straight line, often taken as evidence of complete dispersion, is not a reliable measure for vaccinia virus. None of the experimental curves resembled the classical multihit curve predicted by the Poisson function for the behavior of uniformly aggregated virus. The aggregation was observed, by electron microscopy, to be nonuniform, and of such a distribution that the survival curves can be qualitatively accounted for in terms of multiplicity reactivation of irradiated virus within cells that receive groups of two or more particles. The greatly increased survival value of aggregates of virus, which indicates multiplicity reactivation, is worthy of note.


Interleukin-1 accelerates autocrine growth of myeloma cells through interleukin-6 in human myeloma.
Recombinant interleukin 1 alpha (rIL-1 alpha) augmented proliferation of freshly isolated myeloma cells as well as B-cell stimulatory factor 2 (BSF-2)/interleukin-6 (IL-6). Recombinant IL-1 alpha-induced proliferation was partially inhibited by anti-IL-6 antibody. In the culture supernatants of rIL-1 alpha-stimulated myeloma cells, IL-6 activities, which were measured by using an IL-6-dependent murine hybridoma clone, MH60.BSF2, were increased, when compared with those in the culture supernatants of nonstimulated myeloma cells. Furthermore, IL-6 messenger RNA (mRNA) expression was also augmented in IL-1 alpha-stimulated myeloma cells. Therefore rIL-1 alpha stimulates myeloma cells to produce IL-6, which consequently augments proliferation of myeloma cells. Thus, IL-1 can accelerate autocrine growth of myeloma cells through IL-6.


[Two cases of spermatic cord leiomyosarcoma].
A 72-year-old man and a 59-year-old man presented with painless hard swelling of left scrotal content. They underwent left high orchiectomy with clinical diagnosis of spermatic cord tumor. The pathological examination revealed leiomyosarcoma. The former had adjuvant radiation therapy locally. These are the 28th and 29th cases of spermatic cord leiomyosarcoma in Japan.


The management of proximal biliary tract tumors.
Although a relatively unusual tumor, carcinoma of the proximal biliary tree merits inclusion in the differential diagnosis of all cases of obstructive jaundice. A confident preoperative diagnosis is possible, in the majority of cases, with percutaneous transhepatic cholangiography. The improved accuracy of diagnosis of the tumor has indicated that the incidence is higher than hitherto suspected. Early diagnosis and careful evaluation and selection of cases both preoperatively and intraoperatively should improve overall resectability rates as well as survival. In the past, the overall results of treatment of bile duct cancer were unsatisfactory, with the majority of patients dead within one year of liver failure and sepsis. Now, however, as well as possible cures, extended periods of effective palliation can be provided by current techniques. Transhepatic Silastic biliary stents and U tubes provide lasting palliation. New techniques in radiotherapy allow delivery of massive doses of radiation locally to the tumor site. The results of the transhepatic intubation procedures with or without curative resection, combined with radiotherapy, are encouraging and merit continued evaluation. Chemotherapy treatment using currently available regimens appears to offer very little benefit to these patients.


Lipid studies in the blood and brain in multiple sclerosis and motor neurone disease.
The lipid patterns of plasma, red blood cells, and leucocytes from normal controls and from patients with multiple sclerosis and motor neurone disease have been studied by thin-layer chromatography. The fatty acid composition of cholesterol esters and lecithin in plasma from normal subjects and from patients with multiple sclerosis are reported. The fatty acid composition of lecithin of cerebral white matter from normal control subjects, from multiple sclerosis, and from motor neurone disease as well as of cholesterol esters in multiple sclerosis are recorded and compared. No significant abnormalities were found in the blood lipid profile in multiple sclerosis, but in motor neurone disease red cell sphingomyelin was slightly reduced and white cell lecithin slightly increased. The fatty acids of plasma cholesterol esters showed a slight decrease in palmitic and stearic acid in multiple sclerosis. The fatty acids in lecithin in multiple sclerosis, both in the apparently normal white matter and in the plaques, showed a slightly increased degree of saturation, while the loss of unsaturated acids was in oleic acids.


A comparison of group A streptococci from invasive and uncomplicated infections: are virulent clones responsible for serious streptococcal infections?
From the mid-1980s, numerous reports of invasive group A streptococcal infections suggested that "highly virulent clones" were responsible. However, there have been virtually no extensive reports and comparisons of diverse temporal and geographic community isolates from uncomplicated throat infections to confirm the hypothesis. A unique collection of such "control" strains allowed in-depth assessment of association of M serotypes 1, 3, and 28 "clones" with invasive infections. Clones were defined by using small-fragment chromosomal restriction-enzyme analysis, pulsed-field gel electrophoresis, and M protein gene (emm) sequencing. After comparison with controls, no clone within these M serotypes had statistically increased association with invasive infections. The prevalence of specific virulence-associated clones appeared to essentially reflect their normal population prevalence. Although this does exclude other potential streptococcal factors, these findings suggest that host factors including individual and population-based immunity must also be significant in influencing infection potential.


Methamphetamine and psychiatry: A story of the colourless substance of abuse.
The current paper aims to provide an overview of methamphetamine in its historical context, integrated with a current understanding derived from animal studies and clinical experience. Despite over a century of clinical experience, methamphetamine remains a troublesome substance. There remains an urgent need at multiple levels from various sectors to combat this ongoing problem, and psychiatry has an essential role in this endeavour.


An intriguing case of acute myocardial ischaemia in a patient with severe respiratory failure with veno-venous extracorporeal support.
We describe a case of a young woman requiring veno-venous extracorporeal support for severe secondary respiratory failure who developed a myocardial ischaemia due to an intermittent obstruction of the right coronary sinus by a fluttering thrombus. She was medically treated with full anticoagulation regimen, needed for the veno-venous extracorporeal membrane oxygenation support, without any other ischaemic or embolic event.


Membrane thickness and molecular ordering in Acholeplasma laidlawii strain A studied by 2H NMR spectroscopy.
Since Acholeplasma laidlawii can be restricted to incorporating fatty acids from the growth medium into its membrane lipids, it is possible to study the effects of the length of the acyl chains on the properties of the membrane of the organism. A. laidlawii strain A-EF22 was grown with mixtures of one perdeuterated saturated fatty acid and one monounsaturated fatty acid. The average length (<Cn>) of the acyl chains in the membrane lipids varied from 14.6 to 19.9, and the degree of unsaturation ranged from 21 to 79 mol %. 2H nuclear magnetic resonance (NMR) spectra were recorded on whole cells, on intact membranes, and on lipids extracted from these membranes. It was found that the NMR spectra for all three cases were very similar, yielding deuterium quadrupolar splittings typical for the lamellar liquid-crystalline phase (L alpha) found in model membrane systems. The use of a perdeuterated acyl chain as a reporter molecule allowed for the calculation of order parameters averaged over the entire system. These measurements yielded a wide range of average order parameters varying from 0.136 to 0.186 for the membranes and from 0.137 to 0.181 for the extracted lipids. From the order parameters the average acyl chain length can be calculated, which is related to the average membrane thickness. This value ranged from 23.2 to 30.6 A. When either the order or the membrane thickness of the intact membranes was compared to that of the extracted lipids, only slight or even undetectable differences were found. This implies that the proteins associated with the membranes do not have any large effect on the overall packing of the membrane lipids, even though the membrane thickness varied by approximately 8 A over the series studied. A decrease in the ordering of the acyl chains was observed when the length of the acyl chains incorporated from the growth medium was increased in either the membranes or the extracted lipids. This decrease correlated with the decrease in the fraction of monoglucosyldiacylglycerol (MGlcDAG) found in the membrane. Since both the average order and the membrane thickness varied, it is proposed that by changing the mole fraction of MGlcDAG the organism regulates either the membrane curvature energy or the permeability, both of which are related to lipid packing in the bilayer.


Comparison of approaches to transcriptomic analysis in multi-sampled tumors.
Intratumoral heterogeneity is a well-documented feature of human cancers and is associated with outcome and treatment resistance. However, a heterogeneous tumor transcriptome contributes an unknown level of variability to analyses of differentially expressed genes (DEGs) that may contribute to phenotypes of interest, including treatment response. Although current clinical practice and the vast majority of research studies use a single sample from each patient, decreasing costs of sequencing technologies and computing power have made repeated-measures analyses increasingly economical. Repeatedly sampling the same tumor increases the statistical power of DEG analysis, which is indispensable toward downstream analysis and also increases one's understanding of within-tumor variance, which may affect conclusions. Here, we compared five different methods for analyzing gene expression profiles derived from repeated sampling of human prostate tumors in two separate cohorts of patients. We also benchmarked the sensitivity of generalized linear models to linear mixed models for identifying DEGs contributing to relevant prostate cancer pathways based on a ground-truth model.


A stapling instrument for placement of right atrial pursestrings.
The right atrial pursestring was placed in 12 patients undergoing cardiac operations utilizing a commercially available stapling instrument. Our initial experience indicates that this device can be used for rapid, simple, and safe application of the right atrial pursestring.


Long-term renal sympathetic denervation ameliorates renal fibrosis and delays the onset of hypertension in spontaneously hypertensive rats.
This study was designed to explore the effects of long-term renal denervation (RDN) on blood pressure and renal function in spontaneously hypertensive rats (SHR). RDN was performed in bilateral renal arteries with 10% phenol in absolute ethanol in SHR and Wistar-Kyoto rats (WKY) at 13 weeks. Age-matched SHR and WKY served as controls. Blood pressure was measured. Plasma, urine and kidneys were collected 8 months after the RDN operation. Plasma renin activity (PRA), aldosterone levels, reactive oxidative stress, renal function and structural remodeling were assessed. RDN-treated SHR demonstrated a lower spontaneous rise in systolic blood pressure than rats in the SHR-Sham group (P < 0.01, at 20, 27, 34 and 41 weeks), except at 48 weeks (198.2 ± 12.9 vs 209.4 ± 11.9 mmHg, P = 0.145). WKY were not affected by RDN. Renal tissue norepinephrine was decreased by RDN in both SHR and WKY. Plasma PRA activity, aldosterone levels, and NAD(P)H oxidase activity were reduced by the RDN in SHR. Plasma eNOS and NO were increased by RDN only in SHR. The renal nerve was destroyed by RDN with no regeneration after 8 months. The progression of renal dysfunction associated with urinary protein excretion, glomerular sclerosis, and tubulointerstitial fibrosis was attenuated by RDN only in SHR through downregulation of the ACE/Ang II/AT1R axis and upregulation of the ACE2/Ang-(1-7)/MasR axis in the kidney. Thus, RDN delays the onset of hypertension and ameliorates glomerular sclerosis and tubulointerstitial fibrosis in SHR.


X-linked sideroblastic anemia: identification of the mutation in the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) in the original family described by Cooley.
In 1945, Thomas Cooley described the first cases of X-linked sideroblastic anemia (XLSA) in two brothers from a large family in which the inheritance of the disease was documented through six generations. Almost 40 years later the enzymatic defect in XLSA was identified as the deficient activity of the erythroid-specific form of delta-aminolevulinate synthase (ALAS2), the first enzyme in the heme biosynthetic pathway. To determine the nature of the mutation in the ALAS2 gene causing XLSA in Cooley's original family, genomic DNAs were isolated from two affected hemizygotes, and each ALAS2 exon was PCR amplified and sequenced. A single transversion (A to C) was identified in exon 5. The mutation predicted the substitution of leucine for phenylalanine at residue 165 (F165L) in the first highly conserved domain of the ALAS2 catalytic core shared by all species. No other nucleotide changes were found by sequencing each of the 11 exons, including intron/exon boundaries, 1 kb of 5'-flanking and 350 nucleotides of 3'-flanking sequence. The mutation introduced an Mse I site and restriction analysis of PCR-amplified genomic DNA confirmed the presence of the lesion in the two affected brothers and in three obligate heterozygotes from three generations of this family. Carrier diagnosis of additional family members identified the mutation in one of the proband's sisters. After prokaryotic expression and affinity purification of both mutant and normal ALAS2 fusion proteins, the specific activity of the F165L mutant enzyme was about 26% of normal. The cofactor, pyridoxal 5'-phosphate, activated and/or stabilized the purified mutant recombinant enzyme in vitro, consistent with the pyridoxine-responsive anemia in affected hemizygotes from this family.


Assessment of portal venous system patency in the liver transplant candidate: a prospective study comparing ultrasound, microbubble-enhanced colour Doppler ultrasound, with arteriography and surgery.
To determine the role of microbubble-enhanced colour Doppler ultrasound (CDUS) in assessing portal venous patency prior to liver transplantation. Over a 2-year period, all patients with chronic liver disease undergoing routine pre-transplant CDUS examination in whom the portal venous system was inadequately demonstrated were recruited to the study. CDUS was performed in 368 patients and 33 patients (9%) were recruited. A repeat CDUS examination following an intravenous bolus injection of the microbubble contrast agent Levovist (Schering Healthcare AG, Berlin, Germany) was performed. Diagnostic confidence was recorded on a free linear analogue scale for both examinations. Findings were compared with indirect portography and surgery. Of the 33 patients with sub-optimal baseline examinations, improvement in portal vein visualization was achieved in 31 patients (94%). Median diagnostic confidence increased from 50% (interquartile range 30-60) to 90% (interquartile range 75-98) (P < 0.001) following administration of Levovist. Overall accuracy of portal vein assessment using microbubble-enhanced CDUS in 15 patients in whom a definitive diagnosis was made within 2 months was 87%. Microbubble-enhanced CDUS is a simple, inexpensive adjunct to standard pre liver transplant screening of the portal vein. It is particularly helpful in patients with end-stage cirrhosis who are at high risk of portal vein thrombosis and in whom the conventional examination is sub-optimal.


Interactions between pairs of DNA-binding dyes: results and implications of chromosome analysis.
A number of DNA-binding dyes, with spectral properties making them suitable as components of energy donor-acceptor pairs, are described. If such pairs are used to stain metaphase chromosomes, and if the energy acceptor (e.g., actinomycin D or methyl green) has a binding specificity opposite to the binding or fluorescence specificity of the donor (e.g., 33258 Hoechst, quinacrine or chromomycin A3), contrast in donor fluorescence can be enhanced, leading to patterns selectively highlighting standard or reverse chromosome bands or particular polymorphic regions. Such results presumably reflect chromosomal regions enriched in 10-20 base pair clusters to which the donor binds and fluoresces but to which the acceptor cannot bind. For other pairs, involving counterstains such as netropsin or echinomycin, which are not suitable as energy acceptors, specific changes observed in polymorphic region fluorescence are most likely due to binding competition between dyes. Dye pairs producing contrast by either method can be used to differentiate between homologous chromosomes or to facilitate detection of specific chromosomal rearrangements. Preliminary data indicate that contrast enhancement generated in fixed metaphase chromosomes spread on microscopic slides can also be observed in suspensions of unfixed metaphase chromosomes, reinforcing the expectation that the methodology described will be of use in flow cytometry.


The Hob proteins are novel and conserved lipid-binding proteins at ER-PM contact sites.
Membrane contact sites are critical junctures for organelle signaling and communication. Endoplasmic reticulum-plasma membrane (ER-PM) contact sites were the first membrane contact sites to be described; however, the protein composition and molecular function of these sites is still emerging. Here, we leverage yeast and Drosophila model systems to uncover a novel role for the Hobbit (Hob) proteins at ER-PM contact sites. We find that Hobbit localizes to ER-PM contact sites in both yeast cells and the Drosophila larval salivary glands, and this localization is mediated by an N-terminal ER membrane anchor and conserved C-terminal sequences. The C-terminus of Hobbit binds to plasma membrane phosphatidylinositols, and the distribution of these lipids is altered in hobbit mutant cells. Notably, the Hobbit protein is essential for viability in Drosophila, providing one of the first examples of a membrane contact site-localized lipid binding protein that is required for development.


[Oxidation by nitrite of azurin and cytochrome c-551 from Pseudomonas aeruginosa].
The nitrite oxidizes reduced azurin and cytochrome c-551 from Pseudomonas aeruginosa. The effects of pH, ionic strength and concentrations of nitrite, EDTA and the protein on the oxidation were investigated. The results obtained indicate that nitrite interacts not only with the terminal electron carrier of the nitrite reducing chain (nitrite reductase, cytochrome cd1) but also with the intermediate electron carrier components of the chain (azurin and cytochrome c-551).


Limitations and Challenges in Modeling Diseases Involving Spinal Motor Neuron Degeneration in Vitro.
Pathogenic conditions involving degeneration of spinal motor neurons (MNs), such as amyotrophic lateral sclerosis, sarcopenia, and spinal cord injury, mostly occur in individuals whose spinal MNs are fully mature. There is currently no effective treatment to prevent death or promote axonal regeneration of the spinal MNs affected in these patients. To increase our understanding and find a cure for such conditions, easily controllable and monitorable cell culture models allow for a better dissection of certain molecular and cellular events that cannot be teased apart in whole organism models. To date, various types of spinal MN cultures have been described. Yet these models are all based on the use of immature neurons or neurons uncharacterized for their degree of maturity after being isolated and cultured. Additionally, studying only MNs cannot give a comprehensive and complete view of the neurodegenerative processes usually involving other cell types. To date, there is no confirmed in vitro model faithfully emulating disease or injury of the mature spinal MNs. In this review, we summarize the different limitations of currently available culture models, and discuss the challenges that have to be overcome for developing more reliable and translational platforms for the in vitro study of spinal MN degeneration.


A Highly Photostable Hyperbranched Polyglycerol-Based NIR Fluorescence Nanoplatform for Mitochondria-Specific Cell Imaging.
Considering the critical role of mitochondria in the life and death of cells, non-invasive long-term tracking of mitochondria has attracted considerable interest. However, a high-performance mitochondria-specific labeling probe with high photostability is still lacking. Herein a highly photostable hyperbranched polyglycerol (hPG)-based near-infrared (NIR) quantum dots (QDs) nanoplatform is reported for mitochondria-specific cell imaging. Comprising NIR Zn-Cu-In-S/ZnS QDs as extremely photostable fluorescent labels and alkyl chain (C12 )/triphenylphosphonium (TPP)-functionalized hPG derivatives as protective shell, the tailored QDs@hPG-C12 /TPP nanoprobe with a hydrodynamic diameter of about 65 nm exhibits NIR fluorescence, excellent biocompatibility, good stability, and mitochondria-targeted ability. Cell uptake experiments demonstrate that QDs@hPG-C12 /TPP displays a significantly enhanced uptake in HeLa cells compared to nontargeted QDs@hPG-C12 . Further co-localization study indicates that the probe selectively targets mitochondria. Importantly, compared with commercial deep-red mitochondria dyes, QDs@hPG-C12 /TPP possesses superior photostability under continuous laser irradiation, indicating great potential for long-term mitochondria labeling and tracking. Moreover, drug-loaded QDs@hPG-C12 /TPP display an enhanced tumor cell killing efficacy compared to nontargeted drugs. This work could open the door to the construction of organelle-targeted multifunctional nanoplatforms for precise diagnosis and high-efficient tumor therapy.


The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major.
The promastigote surface antigen-2 (PSA-2) is a Leishmania parasite antigen, which can induce Th1-mediated protection against murine leishmaniasis when used as a vaccine. To evaluate PSA-2 as a human vaccine candidate the specific T-cell response to PSA-2 was characterised in individuals immune to cutaneous leishmaniasis. Peripheral blood mononuclear cells from Sudanese individuals with a past history of self-healing cutaneous leishmaniasis proliferated vigorously in response to PSA-2 isolated from Leishmania major, whereas the antigen did not activate cells from presumably unexposed Danes. Peripheral blood mononuclear cells from individuals with previous L. major infection had varying proliferative responses to PSA-2 derived from L. donovani promastigotes. Peripheral blood mononuclear cells activated by PSA-2 from L. major produced high amounts of interferon-gamma and tumour necrosis factor-beta, and little interleukin-4, thereby showing a Th1 cytokine pattern. Parallel cultures showed clear Th1 and Th2 response patterns to purified protein derivative of tuberculin or tetanus toxoid, respectively. Flow cytometric analysis revealed that PSA-2 induced blastogenesis in the CD3 positive population and that these cells were the major source of interferon-gamma. The results show that Th1-like cells recognising PSA-2 are expanded during infection by L. major and that they maintain their Th1-like cytokine profile upon reactivation in vitro. Since immunity to cutaneous leishmaniasis is mediated by antigen-specific Th1-like cells, PSA-2 might be considered a vaccine candidate for human leishmaniasis.


Evaluation of Dietary Choices, Preferences, Knowledge and Related Practices Among Pregnant Women Living in An Indian Setting.
Healthy and nutritious diet is very essential component of Antenatal care along with clinical advice. The objective of this study was to understand the dietary choices, preferences, knowledge and related practices among pregnant women living in an Indian setting. Hundred pregnant women were enrolled in this cross-sectional study. Information about Socio-demographic profile, food item price and approach during inflation, nutrition related knowledge, attitude and practices and 24 hour dietary recall was acquired. Majority of the participants (87%) reported regular antenatal care visits and intake of iron and folic acid tablets. Eighty two percent of the participants were acquainted with standardized marks on food items and 64% of them reported checking of these marks before purchasing. Thirty two percent of the participants did not know about balanced diet. Fifty eight percent of the participants felled in fair category of dietary recall final scores. There is still vast room for improvement of the nutritional status of pregnant women as none of the participants were able to achieve excellent status on 24 hour food record scoring sheet.


Nox4 Knockout Does Not Prevent Diaphragm Atrophy, Contractile Dysfunction, or Mitochondrial Maladaptation in the Early Phase Post-Myocardial Infarction in Mice.
Diaphragm dysfunction with increased reactive oxygen species (ROS) occurs within 72 hrs post-myocardial infarction (MI) in mice and may contribute to loss of inspiratory maximal pressure and endurance in patients. We used wild-type (WT) and whole-body Nox4 knockout (Nox4KO) mice to measure diaphragm bundle force in vitro with a force transducer, mitochondrial respiration in isolated fiber bundles with an O2 sensor, mitochondrial ROS by fluorescence, mRNA (RT-PCR) and protein (immunoblot), and fiber size by histology 72 hrs post-MI. MI decreased diaphragm fiber cross-sectional area (CSA) (~15%, p = 0.015) and maximal specific force (10%, p = 0.005), and increased actin carbonylation (5-10%, p = 0.007) in both WT and Nox4KO. Interestingly, MI did not affect diaphragm mRNA abundance of MAFbx/atrogin-1 and MuRF-1 but Nox4KO decreased it by 20-50% (p < 0.01). Regarding the mitochondria, MI and Nox4KO decreased the protein abundance of citrate synthase and subunits of electron transport system (ETS) complexes and increased mitochondrial O2 flux (JO2) and H2O2 emission (JH2O2) normalized to citrate synthase. Mitochondrial electron leak (JH2O2/JO2) in the presence of ADP was lower in Nox4KO and not changed by MI. Our study shows that the early phase post-MI causes diaphragm atrophy, contractile dysfunction, sarcomeric actin oxidation, and decreases citrate synthase and subunits of mitochondrial ETS complexes. These factors are potential causes of loss of inspiratory muscle strength and endurance in patients, which likely contribute to the pathophysiology in the early phase post-MI. Whole-body Nox4KO did not prevent the diaphragm abnormalities induced 72 hrs post-MI, suggesting that systemic pharmacological inhibition of Nox4 will not benefit patients in the early phase post-MI.


Vitex negundo L. derived specialized molecules unveil the multi-targeted therapeutic avenues against COPD: a systems pharmacology approach.
Chronic obstructive pulmonary disease (COPD) is an inflammatory disease caused by increasing breathing passage obstruction which completely disrupts human homeostasis. Some patients require lung transplantation or long-term oxygen therapy. COPD is one of the noxious diseases and its fourth leading cause of death around the globe. There is an immediate need for potential drug development to tackle this serious disease. Folk medicines are used to combat complex diseases that have shown effectiveness in the treatment of breathing diseases. Vitex negundo L. is an ethnobotanically important medicinal plant used for various ailments and modulates human cellular events. This shrub has diverse specialized metabolites and is being used as complementary medicine in various countries. Though systems-level understanding is there on the mode of action, the multi-target treatment strategy for COPD is still a bottleneck. In this investigation, systems pharmacology, cheminformatics, and molecular docking analyses were performed to unravel the multi-targeted mechanisms of V. negundo L. potential bioactives to combat COPD. Cheminformatics analysis combined with the target mining process identified 86 specialized metabolites and their corresponding 1300 direct human receptors, which were further imputed and validated systematically. Furthermore, molecular docking approaches were employed to evaluate the potential activity of identified potential compounds. In addition, pharmacological features of these bioactives were compared with available COPD drugs to recognize potential compounds that were found to be more efficacious with higher bioactive scores. The present study unravels the druggable targets and identifies the bioactive compounds present in V. negundo L., that may be utilized for potential treatment against COPD. However, further in vivo analyses and clinical trials of these molecules are essential to deciphering their efficacy.


Intravenous tecovirimat treatment of oral monkeypox lesions in a patient with HIV-1.
A man in his mid-30s presented with 1 week of painful, progressive, and confluent tongue and chin ulcerations. Swabs of the lesions were detected positive for monkeypox (mpox) DNA by polymerase chain reaction. During hospitalization, he received a diagnosis of human immunodeficiency virus-1. Due to severe oral pain, the patient was treated with intravenous tecovirimat 200 mg every 12 h for 4 days with remarkable improvement in lingual lesions. He completed a total 14-day course with oral tecovirimat. Our patient's clinical progress contributes to the data available for the potential efficacy of intravenous tecovirimat for mpox infection in humans.


Intestinal fatty acid-binding protein levels in patients with chronic renal failure.
Intestinal fatty acid-binding protein (I-FABP), a biomarker of enterocyte injury, has been reported to be a diagnostic marker of intestinal ischemia and a prognostic marker in critically ill patients. However, the kinetics of I-FABP in renal failure patients is unknown. We sought to identify I-FABP levels in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) on hemodialysis (HD) and to identify the manner in which the I-FABP levels change. Adult patients who were admitted for elective cardiac surgery with either normal renal function (NRF), CKD, or ESKD on HD were enrolled. Serum I-FABP levels in NRF and CKD patients and in ESKD patients before and after HD were determined. A total of 124 patients were evaluated: 47 NRF, 53 CKD, and 24 ESKD. The I-FABP levels of the CKD patients and pre-HD ESKD patients were significantly higher than those of the NRF patients (P = 0.018 and P <0.001, respectively). I-FABP levels were significantly negatively correlated with the estimated glomerular filtration rate in NRF and CKD patients (Spearman's ρ = -0.313, P = 0.002). In addition, I-FABP levels in ESKD patients were significantly lower after HD than those before HD (P <0.001). I-FABP levels in CKD and pre-HD ESKD patients were significantly higher than those in NRF patients. In addition, I-FABP was significantly eliminated by HD in patients with ESKD. Clinicians and researchers should consider this aspect of I-FABP when using it as a diagnostic and prognostic marker in patients with renal insufficiency.


Murine bone marrow-derived DCs activated by porcine rotavirus stimulate the Th1 subtype response in vitro.
Rotavirus (RV) infection causes acute, watery dehydrating diarrhea and even death in infants and other young animals, resulting in a severe economic burden; however, little is known about the innate immune mechanisms associated with RV infection. Dendritic cells (DCs), which are professional antigen-presenting cells (APCs), serve as a bridge connecting the innate and adaptive immune system. In this study, the interaction between murine bone marrow-derived DCs (BMDCs) and porcine rotavirus (PRV) was investigated in vitro. Upon stimulation, the expression levels of MHC-II, CD40, CD80, CD86 and CD83 in BMDCs increased in a time-dependent manner, indicating activation and maturation by PRV. In addition, up-regulated Toll-like receptor 2 (TLR2), TLR3 and NF-κB increased the production of interleukin-12 and interferon-γ. The PRV-stimulated BMDCs also showed increased stimulatory capacity in mixed lymphocyte reactions and promoted the Th1 subtype response.


Can pre-operative duplex scanning replace pre-operative short saphenous venography as an aid to localizing the sapheno-popliteal junction?
The accuracy of Duplex ultrasound scanning in locating the sepheno-popliteal junction (SPJ) was assessed by comparison with clinical examination and short saphenous venography. Twenty-three legs with varicosities of the short saphenous system had their SPJ located by Duplex scanning and marked pre-operatively. Varicography was performed on all patients. Clinical examination localised the junction to within 2 cm in 8/23 (37%) compared to 16/23 (74%) for Duplex ultrasonography and 21/23 (93%) venography. Ihis study shows that Duplex ultrasonography while more accurate than clinical evaluation, should not replace venography in the pre-operative localisation of the SPJ.


Microorganism capable of decomposing N-acetylglucosaminyl ribitol teichoic acid of Staphylococcus aureus.
Enzyme(s) capable of decomposing N-acetylglucosaminyl ribitol teichoic acid prepared from the cell wall of Staphylococcus aureus FDA 209 P was obtained from the culture supernatant of a gram-negative, rod-shaped, spore-forming soil bacterium. Properties of the bacterium were very similar to those of Bacillus circulans.


A new cycloartane nortriterpenoid from stem and leaf of Quercus variabilis.
A new compound 3-acetyloxy-epicycloeucalenol-24-one (1), with 11 known compounds 3α-acetyloxy-4α,14α-dimethyl-9β,19-cycloergost-24-oic acid (2), 3-epicycloeucalenol (3), 3-epicycloeucalenyl-24-one (4), 3-epicycloeucalenyl acetate (5), 4β,14α-dimethyl-5α-ergosta-9β,19-cyclo-24(31)-en-3β-hydroxy-4α-carboxylic acid (6), cycloeucalenone (7), friedelin (8), epifriedelanol (9), lup-20 (29)-en-3β,30-diol (10), betulin (11), lupeol (12), was isolated from the stems and leaves of Quercus variabilis Blume. Seven compounds (1-7) showed anti-inflammatory activity.


The conserved basic residues and the charged amino acid residues at the α-helix of the zinc finger motif regulate the nuclear transport activity of triple C2H2 zinc finger proteins.
Zinc finger (ZF) motifs on proteins are frequently recognized as a structure for DNA binding. Accumulated reports indicate that ZF motifs contain nuclear localization signal (NLS) to facilitate the transport of ZF proteins into nucleus. We investigated the critical factors that facilitate the nuclear transport of triple C2H2 ZF proteins. Three conserved basic residues (hot spots) were identified among the ZF sequences of triple C2H2 ZF proteins that reportedly have NLS function. Additional basic residues can be found on the α-helix of the ZFs. Using the ZF domain (ZFD) of Egr-1 as a template, various mutants were constructed and expressed in cells. The nuclear transport activity of various mutants was estimated by analyzing the proportion of protein localized in the nucleus. Mutation at any hot spot of the Egr-1 ZFs reduced the nuclear transport activity. Changes of the basic residues at the α-helical region of the second ZF (ZF2) of the Egr-1 ZFD abolished the NLS activity. However, this activity can be restored by substituting the acidic residues at the homologous positions of ZF1 or ZF3 with basic residues. The restored activity dropped again when the hot spots at ZF1 or the basic residues in the α-helix of ZF3 were mutated. The variations in nuclear transport activity are linked directly to the binding activity of the ZF proteins with importins. This study was extended to other triple C2H2 ZF proteins. SP1 and KLF families, similar to Egr-1, have charged amino acid residues at the second (α2) and the third (α3) positions of the α-helix. Replacing the amino acids at α2 and α3 with acidic residues reduced the NLS activity of the SP1 and KLF6 ZFD. The reduced activity can be restored by substituting the α3 with histidine at any SP1 and KLF6 ZFD. The results show again the interchangeable role of ZFs and charge residues in the α-helix in regulating the NLS activity of triple C2H2 ZF proteins.


Prediction of Preterm Labor from the Electrohysterogram Signals Based on Different Gestational Weeks.
Timely preterm labor prediction plays an important role for increasing the chance of neonate survival, the mother's mental health, and reducing financial burdens imposed on the family. The objective of this study is to propose a method for the reliable prediction of preterm labor from the electrohysterogram (EHG) signals based on different pregnancy weeks. In this paper, EHG signals recorded from 300 subjects were split into 2 groups: (I) those with preterm and term labor EHG data that were recorded prior to the 26th week of pregnancy (referred to as the PE-TE group), and (II) those with preterm and term labor EHG data that were recorded after the 26th week of pregnancy (referred to as the PL-TL group). After decomposing each EHG signal into four intrinsic mode functions (IMFs) by empirical mode decomposition (EMD), several linear and nonlinear features were extracted. Then, a self-adaptive synthetic over-sampling method was used to balance the feature vector for each group. Finally, a feature selection method was performed and the prominent ones were fed to different classifiers for discriminating between term and preterm labor. For both groups, the AdaBoost classifier achieved the best results with a mean accuracy, sensitivity, specificity, and area under the curve (AUC) of 95%, 92%, 97%, and 0.99 for the PE-TE group and a mean accuracy, sensitivity, specificity, and AUC of 93%, 90%, 94%, and 0.98 for the PL-TL group. The similarity between the obtained results indicates the feasibility of the proposed method for the prediction of preterm labor based on different pregnancy weeks.


Effect of ethanol on the visual-evoked potential in rat: dynamics of ON and OFF responses.
The effect of acute ethanol administration on the flash visual-evoked potential (VEP) was investigated in numerous studies. However, it is still unclear which brain structures are responsible for the differences observed in stimulus onset (ON) and offset (OFF) responses and how these responses are modulated by ethanol. The aim of our study was to investigate the pattern of ON and OFF responses in the visual system, measured as amplitude and latency of each VEP component following acute administration of ethanol. VEPs were recorded at the onset and offset of a 500 ms visual stimulus in anesthetized male Wistar rats. The effect of alcohol on VEP latency and amplitude was measured for one hour after injection of 2 g/kg ethanol dose. Three VEP components - N63, P89 and N143 - were analyzed. Our results showed that, except for component N143, ethanol increased the latency of both ON and OFF responses in a similar manner. The latency of N143 during OFF response was not affected by ethanol but its amplitude was reduced. Our study demonstrated that the activation of the visual system during the ON response to a 500 ms visual stimulus is qualitatively different from that during the OFF response. Ethanol interfered with processing of the stimulus duration at the level of the visual cortex and reduced the activation of cortical regions.


Hydrothermal synthesis of phosphate-functionalized carbon nanotube-containing carbon composites for supercapacitors with highly stable performance.
Phosphate-functionalized carbon nanotube (CNT)-containing carbon composites with hierarchical porous structure have been synthesized by a simple soft-template hydrothermal method followed by heat treatment. The resulting carbon composites are characterized by FE-SEM, TEM, TGA, FTIR microspectroscopy, and nitrogen sorption techniques. The electrochemical performance of the carbon composites as electrode materials for supercapacitors is also investigated. The results show that CNTs can be uniformly embedded in the carbon matrix, and the phosphate groups are introduced into the carbon composites successfully. The addition of CNTs with suitable content significantly improves the rate capability of carbon composites in 6 M KOH aqueous solution. Cell voltage window can be extended to 1.2 V when increasing the heat treatment temperature of carbon composites to 800 °C, and the resulting composites exhibit highly stable performance in supercapacitors at high current load of 5 A g(-1) and wide cell voltage of 1.2 V.


RORα, a potential tumor suppressor and therapeutic target of breast cancer.
The function of the nuclear receptor (NR) in breast cancer progression has been investigated for decades. The majority of the nuclear receptors have well characterized natural ligands, but a few of them are orphan receptors for which no ligand has been identified. RORα, one member of the retinoid orphan nuclear receptor (ROR) subfamily of orphan receptors, regulates various cellular and pathological activities. RORα is commonly down-regulated and/or hypoactivated in breast cancer compared to normal mammary tissue. Expression of RORα suppresses malignant phenotypes in breast cancer cells, in vitro and in vivo. Activity of RORα can be categorized into the canonical and non-canonical nuclear receptor pathways, which in turn regulate various breast cancer cellular function, including cell proliferation, apoptosis and invasion. This information suggests that RORα is a potent tumor suppressor and a potential therapeutic target for breast cancer.


A Strategy for Risk-adjusted Ranking of Surgeons and Practices Based on Patient-reported Outcomes After Elective Lumbar Surgery.
This study retrospectively analyzes prospectively collected data. The primary aim of this study is to present a scheme for patient-reported outcome (PRO)-based, risk-adjusted rankings of spine surgeons and sites that perform elective lumbar surgery, using the Quality and Outcomes Database (QOD). There is currently no means of determining which spine surgeons or centers are positive or negative outliers with respect to PROs for elective lumbar surgery. This is a critical gap as we move toward a value-based model of health care in which providers assume more accountability for the effectiveness of their treatments. Random effects regression models were fit for the following outcomes, with QOD site as a fixed effect but surgeon ID as a random effect: Oswestry Disability Index, EQ-5D, back pain and leg pain, and satisfaction. Hierarchical Bayesian models were also fit for each outcome, with QOD site as a random effect and surgeon as a nested random effect. Our study cohort consists of 8834 patients who underwent surgery by 124 QOD surgeons, for the degenerative lumbar diseases. Nonoverlapping Bayesian credible intervals demonstrate that the variance attributed to QOD site was greater than the nested variance attributed to surgeon ID for the included PROs. This study presents a novel strategy for the risk-adjusted, PRO-based ranking of spine surgeons and practices. This can help identify positive and negative outliers, thereby forming the basis for large-scale quality improvement. Assuming adequate coverage of baseline risk adjustment, the choice of surgeon matters when considering PROs after lumbar surgery; however, the choice of site appears to matter more. 3.


Pathophysiology of retinopathy of prematurity.
Retinopathy of prematurity (ROP) is a vasoproliferative disease occurring in premature infants that affects the blood vessels of the developing retina. ROP results in the development of vascular shunts, neovascularization, and in its most severe form tractional retinal detachment. The development of retinal vascular shunts and neovascularization in ROP is related to local ischemia in the immature and incompletely vascularized retina. Understanding the pathophysiology of ROP helps physicians both in the prevention and treatment of ROP and will be discussed in this review article. The role of oxygen in the pathophysiology of ROP will be reviewed with recent studies discussed.


Stroma targeting nuclear imaging and radiopharmaceuticals.
Malignant transformation of tumor accompanies profound changes in the normal neighboring tissue, called tumor stroma. The tumor stroma provides an environment favoring local tumor growth, invasion, and metastatic spreading. Nuclear imaging (PET/SPECT) measures biochemical and physiologic functions in the human body. In oncology, PET/SPECT is particularly useful for differentiating tumors from postsurgical changes or radiation necrosis, distinguishing benign from malignant lesions, identifying the optimal site for biopsy, staging cancers, and monitoring the response to therapy. Indeed, PET/SPECT is a powerful, proven diagnostic imaging modality that displays information unobtainable through other anatomical imaging, such as CT or MRI. When combined with coregistered CT data, [(18)F]fluorodeoxyglucose ([(18)F]FDG)-PET is particularly useful. However, [(18)F]FDG is not a target-specific PET tracer. This paper will review the tumor microenvironment targeting oncologic imaging such as angiogenesis, invasion, hypoxia, growth, and homing, and also therapeutic radiopharmaceuticals to provide a roadmap for additional applications of tumor imaging and therapy.


Early detection of bleomycin-induced lung injury in rat using indium-111-labeled antibody directed against intercellular adhesion molecule-1.
We have investigated whether an (111)In-labeled mouse monoclonal antibody to rat intercellular adhesion molecule-1 ((111)In*aICAM-1) could detect lung injury early in rats treated with bleomycin. Rats received an intravenous injection of either (111)In*aICAM-1 or (111)In-labeled normal mouse IgG ((111)In*nmIgG) and were imaged and killed 24 hr later. Lung injury was induced by an intratracheal injection of bleomycin 4 or 24 hr before the rats were killed. After death, tissue was removed and activity was measured, lungs were cryostat-sectioned to detect the presence of ICAM-1 by immunofluorescence, and the up-regulation of LFA-1alpha was examined on blood polymorphonuclear leukocytes (PMNs) using fluorescence-activated cell-sorter (FACS) analysis. In rats injected with (111)In*aICAM-1, the percent injected dose/organ in lungs both at 4 and 24 hr postbleomycin increased significantly compared to the values in either uninjured rats or rats that received (111)In*nmIgG. At 4 and 24 hr postinjury, the target-to-blood (T/B) ratio was 8/1 and 6/1, respectively. For (111)In*nmIgG, the T/B ratio at 4 hr was 0.5/1 and 0.4/1 at 24 hr. In (111)In*aICAM-1 rats injured at 4 or 24 hr, images could easily be distinguished from uninjured rats. All images of (111)In*nmIgG rats showed only cardiac blood-pool and liver activity with little lung activity. Lung ICAM-1 immunofluorescence intensity increased in the bleomycin-treated samples compared to uninjured lungs. Expression of LFA-1alpha on PMNs increased 19% and 210% at 4 hr and 24 hr postinjury, respectively, compared to control values. Biodistribution and imaging data demonstrate that (111)In*aICAM-1 can detect early acute bleomycin-induced lung injury. Immunofluorescence and FACS data suggest that (111)In*ICAM-1 uptake is a specific process. This antibody has potential as an early radionuclide detector of acute inflammations.


Infection and inflammation and the coagulation system.
Severe infection and inflammation almost invariably lead to hemostatic abnormalities, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). Systemic inflammation results in activation of coagulation, due to tissue factor-mediated thrombin generation, downregulation of physiological anticoagulant mechanisms, and inhibition of fibrinolysis. Pro-inflammatory cytokines play a central role in the differential effects on the coagulation and fibrinolysis pathways. Vice-versa, activation of the coagulation system may importantly affect inflammatory responses by direct and indirect mechanisms. Apart from the general coagulation response to inflammation associated with severe infection, specific infections may cause distinct features, such as hemorrhagic fever or thrombotic microangiopathy. The relevance of the cross-talk between inflammation and coagulation is underlined by the promising results in the treatment of severe systemic infection with modulators of coagulation and inflammation.


Thyroid hormone preconditioning: protection against ischemia-reperfusion liver injury in the rat.
Recently, we reported that oxidative stress due to 3,3',5-triiodothyronine (T(3))-induced calorigenesis up-regulates the hepatic expression of mediators promoting cell protection. In this study, T(3) administration in rats (single dose of 0.1 mg/kg intraperitoneally) induced significant depletion of reduced liver glutathione (GSH), with higher protein oxidation, O(2) consumption, and Kupffer cell function (carbon phagocytosis and carbon-induced O(2) uptake). These changes occurred within a period of 36 hours of T(3) treatment in animals showing normal liver histology and lack of alteration in serum AST and ALT levels. Partial hepatic ischemia-reperfusion (IR) (1 h of ischemia via vascular clamping and 20 h reperfusion) led to 11-fold and 42-fold increases in serum AST and ALT levels, respectively, and significant changes in liver histology, with a 36% decrease in liver GSH content and a 133% increase in that of protein carbonyls. T(3) administration in a time window of 48 hours was substantially protective against hepatic IR injury, with a net 60% and 90% reduction in liver GSH depletion and protein oxidation induced by IR, respectively. Liver IR led to decreased DNA binding of nuclear factor-kappaB (NF-kappaB) (54%) and signal transducer and activator of transcription 3 (STAT3) (53%) (electromobility shift assay), with 50% diminution in the protein expression of haptoglobin (Western blot), changes that were normalized by T(3) preconditioning. T(3) administration involving transient oxidative stress in the liver exerts significant protection against IR injury, a novel preconditioning maneuver that is associated with NF-kappaB and STAT3 activation and acute-phase response.


Influence of gender in the psychoneuroimmunological response to therapeutic interval exercise.
Interval exercise has been used as an alternative modality to continuous exercise in patients with various conditions. Although interval exercise can improve health status, it may also exert deleterious effects. Few data are available on differences in psychoneuroimmunological response to high-intensity interval exercise, and it is not known whether males and females differ in their responses to a similar physical stress task. The aim of this study was to evaluate the differences between the psychoneuroimmunological responses of healthy active males and females to a high-intensity interval exercise protocol. Fifty healthy active subjects (25 females) underwent 2 exercise protocol sessions at least 2 weeks apart and at the same time of the day. The first session familiarized participants with the protocol. In the second, after a baseline measurement, subjects performed an exercise protocol with a standardized warm-up followed by three 30-s Wingate tests and an active recovery period. Baseline and postintervention data were gathered on the following: Holter electrocardiogram recordings (standard deviation of normal-to-normal interval [SDNN], square root of mean squared differences of successive NN intervals [RMSSD]); heart rate variability (HRV) index; salivary total protein and immunoglobulin A levels; pressure pain thresholds in masseter and upper trapezius muscles; and profile of mood states. After the exercise protocol, mood disturbance was significantly greater in the males than in the females, while the salivary immunoglobulin A level relative to total proteins was significantly lower in the males. These results suggest that high-intensity interval exercise induces a worse psychoneuroimmunological state in males than in females.


[Thyroid microcarcinoma].
The WHO classification of thyroid tumors defines papillary microcarcinoma as papillary carcinoma, 1 cm or less in diameter. Many Russian and foreign authors include follicular and medullary types. The limiting size which permits a tumor to be considered microcarcinoma if it measures either 1 cm or 1.5 cm. A number of investigators terminologically use the data of a clinical observation of patients. In this connection, there is a great variety of terms used to define thyroid microcarcinoma. This tumor is a common random finding in the gland removed for various disease or examined at autopsy. According to autopsies, the incidence of thyroid microcarcinoma ranges from 1 to 36%. A great deal of papers and studies are dedicated to the etiology and pathogenesis of thyroid microcarcinoma and the potentialities of its early diagnosis and adequate treatment. However, little attention is given to the histological structure and proliferative activity of this tumor and their impact on prognosis and data are at times slightly contradictory or inadequately complete.


Determination of Neutral Monosaccharides as Per-O-methylated Derivatives Directly from a Drop of Whole Blood by Gas Chromatography-Mass Spectrometry.
A new analytical procedure was developed for the simultaneous quantification of neutral monosaccharides from a drop of whole blood using gas chromatography-mass spectrometry analysis (GC-MS) of their per-O-methylated derivatives. The per-O-methylation reaction with methyl iodide and solid sodium hydroxide in methyl sulfoxide was used for the first time for analysis of blood monosaccharides. A blood drop volume of 0.6 μL was used without special purification. The elimination of the undesirable components was carried out during methylation in the presence of a strong base and by liquid extraction of the per-O-methylated monosaccharides. The neutral monosaccharides with an anomeric center gave four per-O-methylated isomers, which were well-separated using a capillary column. Identification was done by electron impact mass spectrometry fragmentation, retention times, and library searching. The limits of detection were determined for standards and varied from 2.0 to 2.3 ng mL(-1). Recoveries for human blood samples varied from 99.22% to 99.65%. The RSD values ranged from 1.92 to 2.37. The method is fast, sensitive, reproducible, and an alternative to current methods for quantitative analysis of blood monosaccharides.


Erythrocyte antioxidative enzyme activities and lipid peroxidation levels in patients with cutaneous leishmaniasis.
Although cutaneous leishmaniasis (CL) is a local infection, the cellular immune response against the disease is systemic, and reactive oxygen intermediates (ROIs) are an important part of cellular immune response involved in killing the parasite. However, whether these intermediates cause oxidative damage in host is unknown. In this study, the metabolism of ROIs were investigated in patients with CL, and compared with healthy subjects. Erythrocyte lipid peroxidation was determined, as an index of oxidative damage, by measurement of malondialdehyde (MDA) levels. Erythrocyte MDA levels and SOD activities were found to be significantly higher in CL patients than in control subjects (p < 0.01 and p < 0.01, respectively). However, CAT and GSH-Px activities were significantly lower in the CL group (p < 0.05 and p < 0.01, respectively). There was a tendency to decreased hemoglobin (Hb) levels, but values did not reach statistical significance. These findings suggest that changes in antioxidant enzyme activities may amplify the leishmanicidal effect in patients with CL. However, these changes may not only cause the killing of parasite but also may cause oxidative damage in the other cells or tissues.


Imipenem resistance in Klebsiella pneumoniae is associated to the combination of plasmid-mediated CMY-4 AmpC β-lactamase and loss of an outer membrane protein.
This study was conducted to identify the molecular mechanisms of imipenem resistance in a Klebsiella pneumoniae (Kp16137) isolate recovered in August 2008 at the University Hospital Sahloul, Sousse, Tunisia. The strain was identified with the API 20E system; antibiotic-containing disks were used for detection of antibiotic susceptibility by a disk diffusion assay. We investigated the presence of β-lactamases by PCR, using specific primers for bla(TEM), bla(SHV), bla(CTX-M), bla(OXA), bla(CMY), bla(ACC), bla(FOX), bla(IMP), bla(KPC), bla(VIM), and by sequencing. Extraction of plasmid DNA from Kp16137 and the transconjugant was performed by the method of Kado. Southern transfer was performed on nylon. The membrane was hybridized with a specific probe for the bla(CMY-2) gene. Outer membrane proteins were isolated and were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis on 12% polyacrylamide gel. K. pneumoniae Kp16137 was resistant to all available β-lactams, including third generation cephalosporins and carbapenems. The screening of β-lactamases showed the presence of three β-lactamases: TEM-1, SHV-61, and CMY-4. The CMY-4 β-lactamase was located on an 80-kb plasmid. An analysis of the outer membrane proteins of this isolate revealed that it lacked a porin of 42 kDa. The loss of this outer membrane protein band correlated with imipenem resistance in this strain. In K. pneumoniae 16137, synthesis of a plasmid-mediated β-lactamase: AmpC CMY-4, together with alteration in permeability led to resistance to all available β-lactams and carbapenems.


Detection of Non-Alcoholic Fatty Liver Disease with Non-invasive Tools in Turkish People Living with HIV and with Apparently Normal Liver Function.
Non-alcoholic fatty liver disease (NAFLD) has become a significant cause of mortality and morbidity in people living with HIV. We aimed to investigate NAFLD presence by magnetic resonance imaging (MRI) methods, including MRI-derived proton density fat fraction (MRI-PDFF) and MRE, and ultrasound elastography among Turkish people living with HIV (PLWH), and identify factors correlated with fatty liver. We included 57 PLWH attending outpatient clinics on antiretroviral therapy (ART) for more than six months, without HBV/HCV co-infection, significant alcohol consumption, active opportunistic infection, previously diagnosed hepatobiliary disease, T2DM, and hyperlipidemia. We performed MRI, MRE, and US elastography on all participants. The mean age of the participants (M/F, 47/10) was 41.7± 12 years. The median duration of HIV infection was 3 (0.5-19 years) years. The mean MRI-PDFF was 4.4 ± 3.8 %, and 11 had fatty liver. The mean MRE value was 2.27 ± 0.6 kPa, inflammation was present in 16, and 4 participants had values consistent with fibrosis. The mean US elastography of the study population was 4.1±2.4 kPa. The mean right and left CCA intima-media of the study population was 0.65± 0.23 mm and 0.66± 0.25 mm; 16 had increased intima-media thickness. In patients with fatty liver, a significant positive correlation was present between MRE and CCA intima-media thickness (rs=0.82, p:0.006 for MRE-left CCA; r=0.68, p=0.042 for MRE-right CCA). We demonstrated that even a significant proportion of PLWH individuals with normal transaminase levels have fatty liver. Future prospective trials are warranted to understand and mitigate the risk factors, course of NAFLD, and accurate non-invasive tests, predicting fibrosis in people living with HIV.


[Evaluation of dose output according to the objects using organ-based tube-current modulation in thoracic computed tomography].
The purpose of this study was to evaluate the dose output according to the object using organ-based tube-current modulation in thoracic CT. The output doses with elliptical and circular shaped phantoms were measured using an ionizing CT chamber. The image noise was quantitatively measured in images obtained from the elliptical phantom. Although total dose outputs with and without the modulation were almost the same, dose outputs at a frontal angle of 120° decreased and those at another angle of 240° increased with the modulation. When the same-shaped phantoms were used, the differences in variation of dose outputs due to the difference in phantom size were small and those due to the difference in the percentage ratio of long- to short-axis diameter of the cross-section were large. There was no significant difference in the amount of noise with and without the dose modulation except for the case of overdose to the small phantom. Therefore, organ-based tube current modulation does not change the total dose output and it maintains the amount of noise by controlling the dose output for each projection angle. Additionally, this dose control is independent of the object size.


Synthesis and upconversion luminescence of YF3:Yb3+ Tm3+ and TiO2-coated YF3:Yb3+, Tm3+ microcrystals.
YF3:Yb3+, Tm3+ microcrystals were prepared by a microemulsion method. The microcrystals were coated with TiO2 by hydrolysis of titanium n-butoxide (TBOT). Transform electron microscopy and X-ray diffraction were used to characterize the core/shell materials. The results indicated that the low TBOT/YF3 molar ratio was favorable to preparing the uniform TiO2 coatings. The upconversion luminescence properties of YF3:Yb3+, Tm3+ and TiO2-coated YF3:Yb3+, Tm3+ microcrystals were studied under 980-nm excitation. The 1I6 --> 3H6, 1I6 --> 3F4, 1D2 --> 3H6, 1D2 --> 3F4, 1G4 --> 3H6, and 1G4 --> 3F4 emissions were observed. The upconversion mechanisms were discussed in detail.


Correlation between duration of edentulism and severity of obstructive sleep apnea in elderly edentulous patients.
To investigate the correlation between duration of edentulism and severity of obstructive sleep apnea in elderly edentulous patients. 1,017 patients aged 55-65 years, with a history of edentulism of 12-60 months were screened. Detailed history of tooth loss and period of edentulism was recorded for the 414 patients who tested positive for OSA (obstructive sleep apnea). Complete dentures were prepared for each patient and they were trained to use the dentures as a mandibular advancement device (MAD) during sleep at night. Apnea-hypopnea index (AHI) data at pre-treatment, six months and one-year post-treatment time intervals was recorded. A correlation between the period of untreated edentulism and severity of OSA and improvement post-treatment was derived in this study. Mean duration of edentulism was 12.14±2.57 months and mean AHI was 16.62±13.24. For every three month increase in the duration of edentulism (after initial 6 months of total tooth loss), there was a statistically significant increase in severity of OSA. Patients who are edentulous for more than 15 months are increasingly vulnerable to OSA. Severity of OSA in afflicted long-term edentulous patients was in direct relation to the period of untreated edentulism and regressed likewise with concomitant denture wear and mandibular advancement during sleep at night. Early prosthetic rehabilitation of edentulous patients is imperative to obviate morbidity of OSA.


Effect of hypothermia on microglial reaction in ischemic brain.
Intra-ischemic hypothermia is known to protect neurons against ischemic injury. Microglial cells have been shown to become activated following ischemia and are speculated to play significant roles in the evolution of ischemic neuronal injury. In this study, we examined the effect of intra-ischemic hypothermia on the microglial reaction in the hippocampus following transient forebrain ischemia produced in gerbils by 10 min bilateral carotid occlusion at 30 degrees C or at 37 degrees C, followed by normothermic reperfusion for 1-7 days. Microglial cells were visualized by histochemical staining with isolectin-B4 from Griffonia simplicifolia. Brains subjected to normothermic ischemia showed activation of microglia at 1 day post-ischemia; this increased with further recirculation, becoming intense by 3 days and diminished by 7 days. Ischemia under hypothermic conditions was not associated with activation of microglia, and these brains showed no significant neuronal damage, whereas the brains subjected to normothermic ischemia showed extensive neuronal necrosis in the CA1 region after 1 and 7 days reperfusion. The presence of activated microglial cells in the CA1 region prior to and in parallel with evolution of ischemic neuronal damage, the lack of such activation in brains subjected to the neuroprotective action of intra-ischemic hypothermia, together with the known potential capability of microglial cells to release cytotoxic substances appear to indicate that these cells could contribute significantly to ischemic neuronal necrosis.


Effects of resistance training on performance in previously trained endurance runners: A systematic review.
The aim of this work was to identify, synthesize and evaluate the results of randomized controlled trials examining the effects of resistance training on performance indicators in previously trained endurance runners. A database search was carried out in PubMed, Science Direct, OvidSPMedLine, Wiley, Web of Science, ProQuest and Google Scholar. In accordance with the PRISMA checklist, 18 published articles dated prior to May 2016 involving 321 endurance runners were reviewed using the PEDro scale. Resistance training led to general improvements in muscular strength, running economy, muscle power factors, and direct performance in distances between 1,500 and 10,000 m. Such improvements were not accompanied by a significant increase in body mass or signs of overtraining. However, improvements did not occur in all cases, suggesting that they might depend on the specific characteristics of the resistance training applied. Although current evidence supports the effectiveness of resistance training to improve performance in already trained endurance runners, the methodological inconsistencies identified suggest that the results should be interpreted with caution. Future studies ought to investigate the benefits of resistance training in endurance runners while considering the existence of possible differentiated effects based on the specific characteristics of the resistance training carried out.


Discovering how urban poverty and violence affect health: development and validation of a Neighborhood Stress Index.
Health problems of the urban poor have been attributed to psychosocial effects of environmental stress. Testing such models requires an ability to measure neighborhood characteristics that make life stressful. The City Stress Inventory (CSI) uses self-report to assess perceived neighborhood disorder and exposure to violence. Data from an interracial sample of urban adolescents show the CSI to be internally consistent, stable, and correlated with census indices of social disadvantage. Validity for stress research is indicated by correlations with trait depression, anger, hostility, self-esteem, and mood changes during a debate with an unfamiliar peer. The CSI can be completed by persons with an 8th-grade education.


Neuroborreliosis in a horse with common variable immunodeficiency.
Common variable immunodeficiency (CVID) is a rare condition in adult horses characterized by hypogammaglobulinemia and increased susceptibility to parasitic and bacterial infections, including recurrent respiratory diseases, septicemia, and meningitis. Lyme disease is often included as a differential diagnosis in CVID horses with signs of meningitis; however, the Borrelia burgdorferi organism has not been demonstrated previously within central nervous system tissues of CVID horses with neurologic disease, to our knowledge. We report herein a case of neuroborreliosis in a CVID horse, confirmed by combined immunologic testing, histopathology, real-time PCR assay, fluorescent in situ hybridization, and immunohistochemical staining. Implications of these findings include heightened monitoring of CVID horses for Lyme disease in endemic areas and appropriate therapy in the case of neurologic disease.