Acute pancreatitis in children: Updates in epidemiology, diagnosis and management.
Acute pancreatitis (AP), manifesting as acute onset of abdominal pain, vomiting, and nausea, is increasingly being recognized in children secondary to increased awareness, more identifiable etiologies as well as advances in diagnostic capabilities, like imaging. Despite this increased awareness and ability for more frequent diagnoses, the natural history of AP remains poorly understood leading to gaps in approach and management, especially in children. Coupled with poor epidemiologic and management awareness, there remains a lack of understanding of the long term implications of severe acute pancreatitis (SAP). Hence, the role of the primary care clinician in the early diagnosis, and management, remains critical and may affect the need for consultation with pediatric sub-specialists like gastroenterologists. This review provides guidelines regarding epidemiology, diagnosis, and management strategies to address some of these gaps.


Aseptic precautions for inserting an epidural catheter: a survey of obstetric anaesthetists.
We performed a postal survey of Fellows of the Australian and New Zealand College of Anaesthetists with a special interest in obstetric practice, about their beliefs regarding aseptic precautions for insertion of an epidural catheter in the labour ward. Of the 435 consultant anaesthetists surveyed, 367 responded (84%), revealing a wide variation in practice. It was not thought to be essential practice to remove a watch before washing hands by 51 respondents (14%), to wear a facemask by 105 (29%) or to wear a sterile gown by 45 (12%). Three anaesthetists (1%) did not believe sterile gloves were essential. However, all respondents indicated that an antiseptic skin preparation was essential. Our results raise questions regarding an acceptable standard of aseptic practice for the insertion of an epidural catheter in labour and we propose a minimal standard of essential precautions.


Expression of neuronal antigens by astrocytes derived from EGF-generated neuroprogenitor cells.
Previous studies have demonstrated that astrocytes reacting to CNS injury can express antigens normally associated with neurons. The origin of the reactive astrocytes, i.e., whether they are newly differentiated glial cells or preexisting astrocytes somehow triggered to express neuronal markers, remains difficult to determine using an in vivo model system. An in vitro model may prove more manageable. In the present study, primary brain cultures and EGF-generated neuroprogenitor cells were used to study the expression of neuronal antigens by established (primary) and nascent astrocytes, respectively. Astrocytes derived directly from dissociated mouse brains exhibited a flat morphology typical of type 1 astrocytes. These cells were nestin and GFAP positive and, in most cases, the antigens were colocalized. Primary astrocytes did not appear to express the putative neuronal markers GABA, Tau, or MAP2. Nascent astrocytes derived from EGF-generated progenitor cells showed a similar pattern of GFAP and nestin immunoreactivity. Contrary to primary astrocytes, many GFAP-intensive, stellate astrocytes exhibited Tau and MAP2. These cells also exhibited an intense nestin immunoreactivity. These data suggest that the reactive astrocytes expressing neuronal antigens in response to CNS trauma may be derived from neural progenitor cells rather than from previously differentiated astrocytes.


The mammalian gastro-intestinal tract is a NOT a major extra-pineal source of melatonin.
In 1992, a paper reported that the melatonin content of the rat duodenum was 24 000 ± 2000 pg/g tissue (range: 4000-100 000 pg/g) while the pineal melatonin content was 580 000 ± 36 000 pg/g. The data has been used for the last 30 years to infer that the gut produces 400 hundred times more melatonin than the pineal gland and that it is the source of plasma melatonin during the daytime. No-one has ever challenged the statement. In this review, evidence is summarised from the literature that pinealectomy eliminates melatonin from the circulation and that studies to the contrary have relied upon poorly validated immunoassays that overstate the levels. Similarly studies that have reported increases in plasma melatonin following tryptophan administration failed to account for cross reactivity of tryptophan and its metabolites in immunoassays. The most extraordinary observation from the literature is that in those studies that have measured melatonin in the gut since 1992, the tissue content is vastly lower than the original report, even when the methodology used could be overestimating the melatonin content due to cross reactivity. Using the more contemporary results we can calculate that rather than a 400:1 ratio of duodenum: pineal melatonin, a ratio of 0.05-0.19: 1 is likely. The gut is not a major extra-pineal source of melatonin; indeed it may well not produce any.


Photolysis study of perfluoro-2-methyl-3-pentanone under natural sunlight conditions.
The UV-vis and infrared absorption cross sections of perfluoro-2-methyl-3-pentanone (CF3CF2C(O)CF(CF3)2, 1,1,1,2,2,4,5,5,5-nonafluoro-4-(trifluoromethyl)-3-penta none), has been obtained, and a photolysis study was carried out under natural sunlight conditions in the European simulation chamber, Valencia, Spain (EUPHORE). The photolysis loss rate, J(photol), equaled (6.4 +/- 0.3) x 10(-6) s(-1) in the period of 10-14 GMT, July 14, 2003 in Valencia (0.5 W, 39.5 N) and corresponded to an effective quantum yield of photolysis of 0.043 +/- 0.011 over the wavelength range of 290-400 nm; the error limits correspond to 2sigma from the statistical analyses. The atmospheric lifetime of CF3CF2C(O)CF(CF3)2 is estimated to be around 1 week, and the global warming potential of the compound is negligible.


Expression of a protective intestinal immune response can be inhibited at three distinct sites by treatment with anti-alpha 4 integrin.
The alpha 4 integrins mediate lymphocyte adhesion to Peyer's patch high endothelial vessels and homing to Peyer's patch, as well as to mesenteric lymph nodes. In rats, immunity to infection with the nematode Trichinella spiralis is known to be mediated by CD4+ OX22- (CD45RC-) cells that home to the intestine in large numbers. These experiments were conducted to determine whether the alpha 4 integrins or LFA-1 were involved in the expression of intestinal immunity to T. spiralis. Injection of the anti-alpha 4 integrin, mAb TA-2, but not anti-LFA-1, mAb TA-3, impaired the expression of immunity. An effect of TA-2 was measured at three distinct sites along the activation pathway leading to the migration of protective CD4+ OX22- cells to the intestine. Injection of TA-2 on the same day as infection prevented normal rejection of the parasite and abrogated the characteristic appearance of blast cells in draining lymph 3 days after infection. A similar effect on the migration of blast cells at day 3 was seen when TA-2 was injected 1 day after infection, and injection 2 days after infection still reduced the number of protective cells entering TD lymph on day 3. The effect of TA-2 and TA-3 on homing of dividing cells to the gut was examined by injecting dividing cells i.v. at the same time as antibody. Under these conditions migration of dividing cells to the gut was reduced by 90 to 95% and their capacity to adoptively transfer worm rejection blocked. Furthermore, TA-2 treatment also inhibited protection when it was injected 12, 18, or 24 h after the transfer of protective cells, when these cells had already entered the gut, but not when TA-2 injection was delayed for 36 h. These results indicate the involvement of alpha 4 integrins at the following points in the generation, dissemination, and function of CD4+ OX22- effectors: 1) initial activation during the first 48 h of infection; 2) migration of protective cells to and extravasation in the gut; 3) a function after entry into gut tissues. The results suggest that entry of dividing cells into the gut is critical for the adoptive transfer of protection and that alpha 4 integrin has multiple roles in the manifestation of intestinal immunity.


Predictors of cerebral microbleeds in acute ischemic stroke and TIA patients.
Cerebral microbleeds (CMB) detected on gradient-echo T2*-weighted MRI have been associated with cognitive impairment and the potential for increased risk of intracranial hemorrhage. We evaluated risk factors for these microangiopathic lesions in a cohort of stroke and transient ischemic attack patients. Presence and number of CMB in consecutive acute stroke patients admitted to a university hospital stroke service over an 18-month period were rated. Multivariate models were generated to determine the contribution of 21 demographic and clinical variables to the frequency and number of CMB. Of 164 patients (mean age 71 years, 52% female), 57 (35%) had CMB evident on gradient-echo T2*-weighted MRI. CMB were more commonly noted among patients with small vessel disease ischemic stroke mechanism (47%) than large vessel atherothromboembolic (12%) or cardioembolic (18%, p = 0.0001). In univariate analysis, patients with CMB were older, (p = 0.008), more likely to have been on >1 antihypertensive prior to admission (p = 0.024) than those without CMB. In multivariate logistic regression analyses, presumed small vessel stroke subtype, history of atrial fibrillation, being on >1 antihypertensive prior to admission, and smoking were independent factors increasing the risk of CMB. Logistic regression analysis by number of CMB showed almost similar findings. CMB are more frequently noted in hospitalized stroke and transient ischemic attack patients with small vessel ischemia, as well as those with important modifiable vascular risk factors like atrial fibrillation and smoking.


The middle way.
Mesoscopic organization in soft, hard, and biological matter is examined in the context of our present understanding of the principles responsible for emergent organized behavior (crystallinity, ferromagnetism, superconductivity, etc.) at long wavelengths in very large aggregations of particles. Particular attention is paid to the possibility that as-yet-undiscovered organizing principles might be at work at the mesoscopic scale, intermediate between atomic and macroscopic dimensions, and the implications of their discovery for biology and the physical sciences. The search for the existence and universality of such rules, the proof or disproof of organizing principles appropriate to the mesoscopic domain, is called the middle way.


Uveitis-induced Refractory Ocular Hypotony Managed with High-dose Latanoprost.
To report a case of refractory ocular hypotony due to chronic Behcet's disease with good response to high-dose topical latanoprost. We present a 26-year-old man with a known history of Behcet's disease who developed decreasing vision and severe ocular hypotony that was refractory to multiple treatment modalities including subtenon triamcinolone acetonide, ibopamine, pars plana vitrectomy, and silicone oil injection. We decided to try high-dose topical latanoprost for the management of ocular hypotony based on recent reports. After six months, intraocular pressure (IOP) increased by 5 mm Hg, became stable at 7 mm Hg, and remained unchanged at month 24. High-dose topical latanoprost could lead to significant increase in IOP in uveitis-induced refractory ocular hypotony.


Covalent modification and exfoliation of graphene oxide using ferrocene.
Large scale preparation of single-layer graphene and graphene oxide is of great importance due to their potential applications. We report a simple room temperature method for the exfoliation of graphene oxide using covalent modification of graphene oxide with ferrocene to obtain single-layer graphene oxide sheets. The samples were characterized by FESEM, HRTEM, AFM, EDAX, FT-IR, Raman and Mössbauer spectroscopic studies. HRTEM micrograph of the covalently modified graphene oxide showed increased interlayer spacing of approximately 2.4 nm due to ferrocene intercalation. The presence of single-layer graphene oxide sheets were confirmed by AFM studies. The covalently modified ferrocene-graphene oxide composite showed interesting magnetic behavior.


[Hypersensitivity reactions to ethylenediamine].
Most allergic reactions to aminophylline are caused by hypersensitivity to ethylendiamine. We present 3 asthmatic patients, 2 of whom had immediate allergic symptoms after the administration of aminophylline. The third patient presented generalized erythrodermia 24 hours after receiving aminophylline. In all three cases sensitivity to ethylendiamine was observed in skin testing. These patients can tolerate other theophylline preparations not containing ethylendiamine.


Morphometry of the canine prostate vasculature.
Morphometric data of the tissue vasculature are fundamental to the development of models for blood perfused tissue mass and heat transfer. Vascular casts of six canine prostates were made and morphometry was performed on 14 transverse sections. The region sampled was restricted to the midsection within the parenchyma. General vascular features that were observed include the radially arranged arteries and veins within the parenchyma, the axially oriented periurethral venous plexae, and the parenchymal arteries ramifying less than the veins. The arterial and venous lumen diameters (mean +/- SD) are 84 +/- 31 (N = 42) and 125 +/- 51 (N = 117), respectively. The lengths for a single vessel generation are 2147 +/- 1196 microm (N = 14) and 1265 +/- 693 microm (N = 39) for the arteries and veins, respectively. Intervessel distances are 4056 +/- 2350 microm (N = 33) between arteries, 1526 +/- 982 microm (N = 330) between veins, and 1498 +/- 874 microm (N = 108) between arteries and veins. A simple vasculature model of evenly distributed vessels imbedded in tissue for heat transfer analysis was developed. The artery-artery distance being about three times that of the vein-vein distance suggested a rete-like configuration of arteries surrounded by veins. An effective distance of 1519 microm between vessels was used. Based upon this vasculature model, the vessel density was calculated to be 5.6 arteries/cm(2) and 44.5 veins/cm(2).


The Impact of Tobacco Control Policies on Smoking Among Socioeconomic Groups in Nine European Countries, 1990-2007.
It is uncertain whether tobacco control policies have contributed to a narrowing or widening of socioeconomic inequalities in smoking in European countries during the past two decades. This paper aims to investigate the impact of price and non-price related population-wide tobacco control policies on smoking by socioeconomic group in nine European countries between 1990 and 2007. Individual-level education, occupation and smoking status were obtained from nationally representative surveys. Country-level price-related tobacco control policies were measured by the relative price of cheapest cigarettes and of cigarettes in the most popular price category. Country-level non-price policies were measured by a summary score covering four policy domains: smoking bans or restrictions in public places and workplaces, bans on advertising and promotion, health warning labels, and cessation services. The associations between policies and smoking were explored using logistic regressions, stratified by education and occupation, and adjusted for age, Gross Domestic Product, period and country fixed effects. The price of popular cigarettes and non-price policies were negatively associated with smoking among men. The price of the cheapest cigarettes was negatively associated with smoking among women. While these favorable effects were generally in the same direction for all socioeconomic groups, they were larger and statistically significant in lower socioeconomic groups only. Tobacco control policies as implemented in nine European countries, have probably helped to reduce the prevalence of smoking in the total population, particularly in lower socioeconomic groups. Widening inequalities in smoking may be explained by other factors. Policies with larger effects on lower socioeconomic groups are needed to reverse this trend. Socioeconomic inequalities in smoking widened between the 1990s and the 2000s in Europe. During the same period, there were intensified tobacco control policies in many European countries. It is uncertain whether tobacco control policies have contributed to a narrowing or widening of socioeconomic inequalities in smoking in European countries. This study shows that tobacco control policies as implemented in the available European countries have helped to reduce the prevalence of smoking in the total population, particularly in lower socioeconomic groups. Widening inequalities in smoking may be explained by other factors.


Magnetotransport Studies of Encapsulated Topological Insulator Bi2Se3 Nanoribbons.
The majority of proposed exotic applications employing 3D topological insulators require high-quality materials with reduced dimensions. Catalyst-free, PVD-grown Bi2Se3 nanoribbons are particularly promising for these applications due to the extraordinarily high mobility of their surface Dirac states, and low bulk carrier densities. However, these materials are prone to the formation of surface accumulation layers; therefore, the implementation of surface encapsulation layers and the choice of appropriate dielectrics for building gate-tunable devices are important. In this work, all-around ZnO-encapsulated nanoribbons are investigated. Gate-dependent magnetotransport measurements show improved charge transport characteristics as reduced nanoribbon/substrate interface carrier densities compared to the values obtained for the as-grown nanoribbons on SiO2 substrates.


Determination of "indeterminate score" measurements in lean nonalcoholic fatty liver disease patients from western Saudi Arabia.
Noninvasive measures to estimate liver fibrosis in lieu of biopsy in nonalcoholic liver disease (NAFLD) can broadly differentiate high vs low degrees of condition extent. However, an "indeterminate score" necessitates further clinical investigation and biopsy becomes essential, highlighting the need for identification of other noninvasive factors with accuracy for this midlevel extent and its prognosis. Lean NAFLD cases are of particular interest regarding this issue, as they present as otherwise healthy, and will benefit greatly from the less invasive assessment. To estimate the agreement of two noninvasive assessment tools in lean NAFLD patients, and assess factors related to indeterminate scores. Ultrasound-diagnosed NAFLD patients, without sign of other chronic liver disease (n = 1262), were enrolled from a tertiary private medical centre between 2016-2019. After grouping by body mass index (obese, overweight, and lean), each participant underwent FibroScan. NAFLD fibrosis score (NFS) was used for subclassification (lower, higher, and indeterminate). No patient underwent liver biopsy. The kappa statistic was used to assess inter-rater agreement between the three groups on liver fibrosis degree assessed via FibroScan and NFS. Indeterminate score among the three groups was assessed to identify factors that predict its determination. The NAFLD study cohort was composed of lean (159/1262, 12.6%), overweight (365/1262, 29%) and obese (737/1262, 58.4%) individuals. The lean patients were significantly younger (49.95 ± 15.3 years, P < 0.05), with higher serum high density lipoprotein (52.56 ± 16.27 mg/dL, P < 0.001) and lower prevalences of type 2 diabetes mellitus, hypertension and hyperlipidaemia. All groups showed a predominance of lower fibrosis degree. The lean NAFLD patients showed a significantly lower NFS (P < 0.001). Degree of agreement between FibroScan and NFS was fair between the lean and obese NAFLD categories, and moderate in the overweight category. NFS was predictive of indeterminate score. Age was a factor among all the body mass index (BMI) categories; other associated factors, but with less strength, were serum alanine aminotransferase in the overweight category and BMI in the obese category. Lean NAFLD patients showed lower degree and prevalence of liver fibrosis by NFS; however, follow-up biopsy is still needed.


Experimental preseeding of the STARFlex atrial septal occluder device with autologous cells.
Devices used in interventional cardiology are permanent implants. However, most of the devices fulfill only a temporary function. For example, atrial septal defect (ASD) occluders serve as mechanical shields until complete in- and overgrowth of the occluding device by endogenous tissue from the defect edges has occurred. Thereafter, the foreign body material of the devices is no longer needed and bears potential long-term adverse effects. The concept of "biodegradable" occluder devices that act as transient mechanical shields to close the defects and as scaffolds for overgrowth with autologous tissue is, therefore, tempting. Since rapid and complete ingrowth as well as coverage by firm tissue is a prerequisite for any such "biological" occluder devices, the feasibility and short-term in vivo response to STARFlex devices preceeded with autologous cells was studied in an experimental sheep model. The experiments demonstrated that autologous cell preceeding of cardiovascular implants is technically feasible. Cells survived the mechanical stress of device implantation. A precoating of conventional STARFlex occluders led to an increased cellular density after cell seeding of the device, an increased resistance of the precultured cytolayer against mechanical stress, and a significantly higher poststress viability of "implanted" cells. Experimental closure of ASD using autologous-cell preseeded STARFlex devices was uncomplicated. In the sheep model this led to rapid, complete, and firm ingrowth of the device into the adjacent atrial tissue. A thicker layer of young fibrous granulation tissue in organization was found on the preceeded devices compared with the unseeded control group after 4 weeks in vivo. Currently, an increased thrombogenicity limits in vivo application.


Long-term cytocompatibility of various endodontic sealers using a new root canal model.
It was the purpose of our study to determine the cytotoxicity of several types of root canal sealers in vitro over the period of 1 yr by using a new test model. Roots of extracted human teeth were filled with N2, Apexit, Roekoseal, AH Plus, Ketac Endo, Endomethasone, and one gutta-percha point. In addition, roots filled with laterally condensed gutta-percha/N2. Teeth filled with one gutta-percha point only were controls. All specimens were consecutively extracted with distilled water for a total period of 1 yr. Extracts were investigated for cytotoxicity by using immortalized 3T3 fibroblasts and primary human periodontal ligament fibroblasts. Results were statistically analyzed with Dunnett's t tests (p < 0.05). Pronounced cytotoxic effects were only caused by N2-extracts in both cell cultures (p < 0.05). Furthermore, statistically significant cytotoxic alterations were also induced by 10-week eluates of Endomethasone (p < 0.05). All other investigated materials did not significantly alter cell metabolism.


Update: Malaria, U.S. Armed Forces, 2020.
Malaria infection remains an important health threat to U.S. service members who are located in endemic areas because of long-term duty assignments, participation in shorter-term contingency operations, or personal travel. In 2020, a total of 28 service members were diagnosed with or reported to have malaria. This was the lowest number of cases in any given year during the 10-year surveillance period and represents a 15.2% decrease from the 33 cases identified in 2019. The relatively low numbers of cases during 2012-2020 mainly reflect decreases in cases acquired in Afghanistan, a reduction largely due to the progressive withdrawal of U.S. forces from that country. The number of malaria cases caused by Plasmodium falciparum in 2020 (n=8) was the second lowest observed during the surveillance period. The percentage of 2020 cases of malaria caused by Plasmodium vivax (53.6%; n=15) was the highest during any given year of the surveillance period. The remaining 5 malaria cases were labeled as associated with other/unspecified types of malaria (17.9%). Malaria was diagnosed at or reported from 13 different medical facilities in the U.S., Germany, Africa, and Korea. Providers of medical care to military members should be knowledgeable of and vigilant for clinical manifestations of malaria outside of endemic areas.


The effect of metal microstructure on the initial attachment of Escherichia coli to 1010 carbon steel.
Metallurgical features have been shown to play an important role in the attachment of microorganisms to metal surfaces. In the present study, the influence of the microstructure of as-received (AR) and heat-treated (HT) 1010 carbon steel on the initial attachment of bacteria was investigated. Heat treatment was carried out with the aim of increasing the grain size of the carbon steel coupons. Mirror-polished carbon steel coupons were immersed in a minimal medium inoculated with Escherichia coli (ATCC 25922) to investigate the early (15, 30 and 60 min) and relatively longer-term (4 h) stages of bacterial attachment. The results showed preferential colonisation of bacteria on the grain boundaries of the steel coupons. The bacterial attachment to AR steel coupons was relatively uniform compared to the HT steel coupons where an increased number of localised aggregates of bacteria were found. Quantitative analysis showed that the ratio of the total number of isolated (i.e., single) bacteria to the number of bacteria in aggregates was significantly higher on the AR coupons than the HT coupons. Longer-term immersion studies showed production of extracellular polymeric substances by the bacteria and corrosion at the grain boundaries on both types of steel coupon tested.


Experiences in surgical closure of atrial septal defect with anterior mini-thoracotomy approach.
Anterior mini-thoracotomy approach is a good alternative to median sternotomy in Atrial Septal Defect (ASD) repair. Our purpose is to explain the details of our technique and peresent the results. Seventy five patients with ASD (52 female and 23 male) were operated with anterior mini-thoracotomy approach in our tertiary center between March 2012 and March 2014. The mean age was 14±10 ranged from 2 to 42 years. Outcomes were defined according to cardiopulmonary and aortic cross-clump time, intensive care unit stay time, morbidity, mortality, the size of incision, the amount of post-operative bleeding, need for blood transfusion and reoperation. Mean Cardiopulmonary bypass time was 49.62 minutes (26 to 105 minutes) and mean aortic cross clamp time was 22.29±6.77 minutes (11 to 47 minutes). The mean amount of blood transfusion was 47.49± 62.22 mm (0 to 200 cc) and the mean chest tube drainage after surgery was 80.17 ±121.06 mm (0 to 600 cc). One patient re-operated for dehiscence of ASD surgical sutures and there was no reoperation for surgical bleeding or tamponade drainage in these patients. In 74 cases the defect was secundum type, in 2 patients it was sinus venosus type and in one with associated partial Anomalous repair. Anterior thoracotomy approach is safe and may be the surgical technique of choice for secundum ASD repair in all age groups and we can utilize this technique also for more complicated kinds of surgery for instance, sinus venosus type ASD with or without Partial Anomalous Defect.


The intramedullary elongation nail for femoral lengthening.
We have analysed the results of 24 femoral lengthenings in 23 patients operated on between 1993 and 2000, using a gradual elongation intramedullary nail (Albizzia). Of the 23 patients, 22 had femoral deficiency and one was of short stature. Their mean age was 16.9 years. Technical difficulties encountered during the procedure were mild or moderate in 18 femora and severe in six femora. Distraction was obtained by 15 ratchetings per day (1 mm/day). There were 18 excellent results although in two patients this was achieved after the development of a pseudarthrosis which required further surgery. There were four good and two fair results in which the lengthening obtained was at least 3 cm less than had been projected. The consolidation index was 35.2 days/cm. No patient had associated long-term stiffness of the knee. Femoral lengthening using an elongation nail gives good results and is a comfortable procedure.


Visible-Light Photosynthesis of CHF2 /CClF2 /CBrF2 -Substituted Ring-fused Quinazolinones in Dimethyl Carbonate.
With eco-friendly and sustainable CO2 -derived dimethyl carbonate as the sole solvent, the visible-light-induced cascade radical reactions have been established as a green and efficient tool for constructing various CHF2 /CClF2 /CBrF2 -substituted ring-fused quinazolinones.


Memantine - neuroprotective drug in aging brain.
Aging is the process of progressive accumulation of changes over time, which is additionally connected with increasing susceptibility to some diseases and ultimately leads to death. Aging is associated mainly with loss of permanent cells, e.g. in heart, skeletal muscle and brain. During aging neurons die mainly in the apoptotic way. Apoptosis can be divided into three phases: initiation, execution and degradation. During the execution phase activation of specific enzymes, caspases, is observed. These enzymes are responsible for initiation of the death machinery. Caspase-9 is connected with the internal pathway of apoptosis, which begins at the mitochondrium in response to apoptotic stimulants, such as free radicals, UV radiation or chemotherapeutics. Before the executive phase starts, cytochrome c leaks from the mitochondrium to the cytoplasm, where it joins to the protein Apaf-1 and procaspase-9 and forms a complex called the apoptosome. Then procaspase-9 is converted by autolysis to caspase-9, which subsequently activates procaspase-3 to the active form which ultimately leads to apoptosis. Immunohistochemical analysis demonstrated a small decrease in caspase-9 and caspase-3 activation during normal aging and an increase in this process after application of stress factors. Also increased apoptosis in the cerebrum after administration of a drug for Alzheimer disease, memantine, to aging rats was observed. Taken together, the results obtained in this study seem to confirm the neuroprotective effect of memantine on increasing levels of cells with active caspase-3 and active caspase-9. It probably improves caspase-dependent apoptosis in the aging brain.


Skin reactivity to substance P, not to neurokinin A, is increased in allergic asthmatics.
The tachykinins substance P (SP) and neurokinin A are believed to be major mediators of neurogenic inflammation. To determine whether the skin reactivity to tachykinins is increased in asthmatics, we examined the erythemas and wheals induced by intradermal injections of SP, the C-terminal peptide SP6-11, the N-terminal peptide SP1-9 and neurokinin A (10(-7)-10(-5) M) in 10 allergic asthmatics and 9 normal subjects. SP and SP1-9 induced both erythemas and wheals in a concentration-dependent manner in allergic asthmatics and in normal subjects, whereas SP6-11 and neurokinin A induced only wheals in both groups. SP induced greater erythemas and wheals in allergic asthmatics than in normal subjects. However, the wheals induced by neurokinin A were not significantly different between the two groups. SP1-9 also induced greater erythemas and wheals in allergic asthmatics than in normal subjects, whereas the wheals induced by SP6-11 were not significantly different between the two groups. Therefore, the increased skin reactivity to SP was dependent on the N-terminal peptide but not on the C-terminal peptide. We conclude that the skin reactivity to SP but not to neurokinin A is increased in allergic asthmatics.


Laparoscopic repair of morgagni's hernia with percutaneous placement of suture.
Simultaneous laparoscopic repair of Morgagni's hernia and laparoscopic cholecystectomy in a 59-year-old lady is described. In contrast to most previous reported series, in which repairs were fashioned with direct intracorporeal suturing, stapling, or mesh placement, an alternative technique of suture placement with a percutaneously inserted needle was applied. The procedure was smooth, and there was no evidence of recurrent hernia 9 months after the operation.


Tuberculosis screening among homeless persons with AIDS living in single-room-occupancy hotels.
Congregate facilities for homeless persons with the acquired immunodeficiency syndrome (AIDS) are often endemic for tuberculosis. We evaluated tuberculosis screening methods at single-room-occupancy hotels housing persons with AIDS. Residents were screened by cross matching the New York City Tuberculosis Registry, interviewing for tuberculosis history, skin testing, and chest radiography. Cases were classified as either previously or newly diagnosed. Among the 106 participants, 16 (15%) previously diagnosed tuberculosis cases were identified. Participants' tuberculosis histories were identified by the questionnaire (100%) or by registry match (69%). Eight participants (50%) were noncompliant with therapy. These findings prompted the establishment of a directly observed therapy program on site.


Congenital alveolar proteinosis.
Pulmonary alveolar proteinosis is recently described as a rare cause of lung dysfunction and respiratory distress in term neonates. In several cases, a deficiency or insufficiency of surfactant protein B SP-B has been caused by a frame shift mutation in the gene encoding SP-B. Three siblings with congenital pulmonary alveolar proteinosis showed clinical and radiological evidence. Histopathological and immunohistochemical studies in the last sibling revealed deficiency of SP-B, one of the group of 3 specific lipoproteins that reduce the surface tension between air and liquid interface within pulmonary alveoli, suggesting a gene associated illness.


[Healthy Cities projects in Europe].
The WHO Healthy Cities Project has been developed in Europe to place health high on the agenda of city decision-makers. It has promoted comprehensive local strategies for health and sustainable development. Cities endorse principles and strategies, establish project infrastructures, work on specific goals, products, changes, and outcomes, and invest in formal and informal networking and cooperation. Consistent research and development efforts are contributing towards a more evidence-based policy making and to the emergence of a framework to meet the demands of the new public health movement.


Management strategies to decrease the prevalence of mastitis caused by one strain of Staphylococcus aureus in a dairy herd.
The dairy herd at Washington State University had an outbreak of mastitis caused by a single strain of Staphylococcus aureus. The outbreak strain, termed novel, could not be controlled with routine contagious mastitis pathogen control procedures (incidence, 3.4 infections/100 cow months; peak prevalence > 22%). Our objective was to implement mastitis control measures that would decrease the incidence and prevalence of intramammary infection (IMI) caused by S aureus in the herd. The following intervention strategies were successfully implemented: strict segregation of cattle with IMI caused by S aureus, intensified culling of cattle with multiple-quarter IMI caused by S aureus, and inducing cessation of lactation of infected quarters in single-mammary-quarter infected cattle. One year after implementation of these control measures, incidence of IMI caused by S aureus was 0.35 infections/100 cow months, and prevalence had decreased from 20 to 8%.


Treatment with the anti-IL-6 receptor antibody attenuates muscular dystrophy via promoting skeletal muscle regeneration in dystrophin-/utrophin-deficient mice.
Chronic increases in the levels of the inflammatory cytokine interleukin-6 (IL-6) in serum and skeletal muscle are thought to contribute to the progression of muscular dystrophy. Dystrophin/utrophin double-knockout (dKO) mice develop a more severe and progressive muscular dystrophy than the mdx mice, the most common murine model of Duchenne muscular dystrophy (DMD). In particular, dKO mice have smaller body sizes and muscle diameters, and develop progressive kyphosis and fibrosis in skeletal and cardiac muscles. As mdx mice and DMD patients, we found that IL-6 levels in the skeletal muscle were significantly increased in dKO mice. Thus, in this study, we aimed to analyze the effects of IL-6 receptor (IL-6R) blockade on the muscle pathology of dKO mice. Male dKO mice were administered an initial injection (200 mg/kg intraperitoneally (i.p.)) of either the anti-IL-6R antibody MR16-1 or an isotype-matched control rat IgG at the age of 14 days, and were then given weekly injections (25 mg/kg i.p.) until 90 days of age. Treatment of dKO mice with the MR16-1 antibody successfully inhibited the IL-6 pathway in the skeletal muscle and resulted in a significant reduction in the expression levels of phosphorylated signal transducer and activator of transcription 3 in the skeletal muscle. Pathologically, a significant increase in the area of embryonic myosin heavy chain-positive myofibers and muscle diameter, and reduced fibrosis in the quadriceps muscle were observed. These results demonstrated the therapeutic effects of IL-6R blockade on promoting muscle regeneration. Consistently, serum creatine kinase levels were decreased. Despite these improvements observed in the limb muscles, degeneration of the diaphragm and cardiac muscles was not ameliorated by the treatment of mice with the MR16-1 antibody. As no adverse effects of treatment with the MR16-1 antibody were observed, our results indicate that the anti-IL-6R antibody is a potential therapy for muscular dystrophy particularly for promoting skeletal muscle regeneration.


Mates and marriage matter: genetic and environmental influences on subjective wellbeing across marital status.
Specific environments and social relationships may alter the impact of genes. Previous studies have shown marriage to moderate heritability for depressive symptoms in females, suggesting that marriage provides protection or compensation against genetic risks. Similar mechanisms may be relevant for subjective wellbeing (SWB), which is considerably influenced by genes and almost universally associated with marital status. Questionnaire data on SWB from a population-based sample of 1250 monozygotic (MZ) and 981 dizygotic (DZ) male and female twin pairs (n = 4462) were analyzed using structural equation modeling by means of Mx to investigate genetic and environmental influences on SWB across marital status. Resemblance for SWB in MZ twins exceeded that of DZ twins, but the magnitude of this difference varied across marital status. Genetic factors explained 51% and 54% of the variance in SWB among unmarried males and females, and 41% and 39% in married or cohabitating respondents. Remaining variance was attributable to the nonshared environment. The genetic influences were partly different (r(g) = 0.64) across marital status in females, but overlapping in married and single males. Our findings show that marriage moderates the magnitude of genetic influences on SWB in both males and females, with a smaller estimate of genetic influences for those with a marital or equivalent partner. The genetic influences on SWB are thus clearly contingent on the environmental context.


Neurotrophins and cortical development.
The mammalian cerebral cortex requires the proper formation of exquisitely precise circuits to function correctly. These neuronal circuits are assembled during development by the formation of synaptic connections between hundreds of thousands of differentiating neurons. Although the development of the cerebral cortex has been well described anatomically, the cellular and molecular mechanisms that guide neuronal differentiation and formation of connections are just beginning to be understood. Moreover, despite evidence that coordinated patterns of activity underlie reorganization of brain circuits during critical periods of development, the molecular signals that translate activity into structural and functional changes in connections remain unknown. Recently, the neurotrophins have emerged as attractive candidates not only for regulating neuronal differentiation in the developing brain, but also for mediating activity-dependent synaptic plasticity. The neurotrophins meet many of the criteria required for molecular signals involved in neuronal differentiation and plasticity. They are present in the cerebral cortex during development and their expression is regulated by synaptic activity. In turn, the neurotrophins themselves strongly influence both short-term synaptic plasticity and long-term potentiation and depression. In addition to their functional effects, the neurotrophins also profoundly regulate the structural changes that underlie axonal and dendritic differentiation. Finally, the neurotrophins have been implicated in mediating synaptic competition required for activity-dependent plasticity during the critical period. This chapter presents and discusses the rapidly accumulating evidence that the neurotrophins are critical for neuronal differentiation and that they may be involved in activity-dependent synaptic refinement in the developing cerebral cortex.


A proline tRNA(CGG) gene encompassing the attachment site of temperate phage 16-3 is functional and convertible to suppressor tRNA.
Several temperate bacteriophage utilize chromosomal sequences encoding putative tRNA genes for phage attachment. However, whether these sequences belong to genes which are functional as tRNA is generally not known. In this article, we demonstrate that the attachment site of temperate phage 16-3 (attB) nests within an active proline tRNA gene in Rhizobium meliloti 41. A loss-of-function mutation in this tRNA gene leads to significant delay in switching from lag to exponential growth phase. We converted the putative Rhizobium gene to an active amber suppressor gene which suppressed amber mutant alleles of genes of 16-3 phage and of Escherichia coli origin in R. meliloti 41 and in Agrobacterium tumefaciens GV2260. Upon lysogenization of R. meliloti by phage 16-3, the proline tRNA gene retained its structural and functional integrity. Aspects of the co-evolution of a temperate phage and its bacterium host is discussed. The side product of this work, i.e. construction of amber suppressor tRNA genes in Rhizobium and Agrobacterium, for the first time widens the options of genetic study.


Protein kinase Cɛ inhibition restores megakaryocytic differentiation of hematopoietic progenitors from primary myelofibrosis patients.
Among the three classic Philadelphia chromosome-negative myeloproliferative neoplasms, primary myelofibrosis (PMF) is the most severe in terms of disease biology, survival and quality of life. Abnormalities in the process of differentiation of PMF megakaryocytes (MKs) are a hallmark of the disease. Nevertheless, the molecular events that lead to aberrant megakaryocytopoiesis have yet to be clarified. Protein kinase Cɛ (PKCɛ) is a novel serine/threonine kinase that is overexpressed in a variety of cancers, promoting aggressive phenotype, invasiveness and drug resistance. Our previous findings on the role of PKCɛ in normal (erythroid and megakaryocytic commitment) and malignant (acute myeloid leukemia) hematopoiesis prompted us to investigate whether it could be involved in the pathogenesis of PMF MK-impaired differentiation. We demonstrate that PMF megakaryocytic cultures express higher levels of PKCɛ than healthy donors, which correlate with higher disease burden but not with JAK2V617F mutation. Inhibition of PKCɛ function (by a negative regulator of PKCɛ translocation) or translation (by target small hairpin RNA) leads to reduction in PMF cell growth, restoration of PMF MK differentiation and inhibition of PKCɛ-related anti-apoptotic signaling (Bcl-xL). Our data suggest that targeting PKCɛ directly affects the PMF neoplastic clone and represent a proof-of-concept for PKCɛ inhibition as a novel therapeutic strategy in PMF.


Intrapulmonary-located Castleman's disease, which was surgically resected without pulmonary resection.
Castleman's disease (CD) is a rare disease with unknown aetiology. It is characterised by benign lymph node hyperplasia that may involve all lymph nodes. The most common locations are the mediastinum and abdomen. CD arising from intrapulmonary lymph nodes has been reported in five cases, in the English language literature to date. Tumours in these patients are usually resected during lung surgery. An asymptomatic 29-year-old male patient was evaluated due to a mass lesion with a diameter of 55 mm located in the infrahilar region of the right lung with a high degree of contrast enhancement on thoracic computed tomography (CT). Vascularity of this central lesion was excluded by pulmonary angiography. Thoracotomy was performed due to the inability to obtain a diagnosis with percutaneous fine needle aspiration biopsies. A frozen section examination of the mass revealed a benign lesion, arising from the intrapulmonary lymph nodes and protruding to the lower-lobe parenchyma. The mass was then extracted from the parenchyma. After histopathological evaluation of the mass, CD involving the lymph nodes was diagnosed. CD rarely involves the intrapulmonary lymph nodes. Diagnosis is difficult in these patients, and thoracotomy may be required. After obtaining benign results by mass sampling, limited resection of these masses, while sparing the lung parenchyma, may be possible.


Influence of postshock epicardial activation patterns on initiation of ventricular fibrillation by upper limit of vulnerability shocks.
Shocks of identical strength and timing sometimes induce ventricular fibrillation (VFI) and other times do not (NoVFI). To investigate this probabilistic behavior, a shock strength near the upper limit of vulnerability, ULV(50), was delivered to yield equal numbers of VFI and NoVFI episodes. In 6 pigs, a 504-electrode sock was pulled over the ventricles. ULV(50) was determined by scanning the T wave. S(1) pacing was from the right ventricular apex. Ten S(2) shocks of approximate ULV(50) strength were delivered at the same S(1)-S(2) coupling interval. Intercycle interval (ICI) and wave front conduction time (WCT) were determined for the first 5 postshock cycles. ICI and the WCT of cycle 1 were not different for VFI versus NoVFI episodes (P=0.3). Beginning at cycle 2, ICI was shorter and WCT was longer for VFI than NoVFI episodes (P<0.05). The first cycle after shocks of the same strength (ULV(50)) delivered at the same time has the same activation pattern regardless of shock outcome. During successive cycles, however, a progressive decrease in ICI and increase in WCT occur during VFI but not NoVFI episodes. These findings suggest shock outcome is (1) deterministic but exquisitely sensitive to differences in electrophysiological state at the time of the shock that are too small to detect or (2) probabilistic and not determined until after the first postshock cycle.


Deterministic Role of Concentration Surplus of Cation Vacancy over Anion Vacancy in Bipolar Memristive NiO.
Migration of oxygen vacancies has been proposed to play an important role in the bipolar memristive behaviors because oxygen vacancies can directly determine the local conductivity in many systems. However, a recent theoretical work demonstrated that both migration of oxygen vacancies and coexistence of cation and anion vacancies are crucial to the occurrence of bipolar memristive switching, normally observed in the small-sized NiO. So far, experimental work addressing this issue is still lacking. In this work, with conductive atomic force microscopy and combined scanning transmission electron microscopy and electron energy loss spectroscopy, we reveal that concentration surplus of Ni vacancy over O vacancy determines the bipolar memristive switching of NiO films. Our work supports the dual-defects-based model, which is of fundamental importance for understanding the memristor mechanisms beyond the well-established oxygen-vacancy-based model. Moreover, this work provides a methodology to investigate the effect of dual defects on memristive behaviors.


Comorbid anxiety and depression.
Anxiety and depressive disorders often occur as comorbid illnesses and share many common symptoms. Risk factors for these disorders most likely include interactions of environmental and genetic factors. The presence of comorbid anxiety and depression adversely affects clinical and treatment outcomes. Selective serotonin reuptake inhibitors are usually considered first-line treatment for patients with these disorders, although alternative antidepressants or additional therapies are often necessary. Studies suggest that benzodiazepines, anticonvulsants, and atypical antipsychotics may be effective as augmentation therapy to optimize outcome, with buspirone and beta-blockers useful in some patients as well. Cognitive-behavioral therapy is also an effective therapeutic alternative for affected patients.


Binder-free mechanochemical metal-organic framework nanocrystal coatings.
The practical applications of metal-organic frameworks (MOFs) usually require their assembly into mechanically robust structures, usually achieved via coating onto various types of substrates. This paper describes a simple, scalable, and versatile mechanochemical technique for producing MOF nanocrystal coatings on various non-prefunctionalised substrates, including ZrO2, carbon cloth, porous polymer, nickel foam, titanium foil and fluorine-doped tin oxide glass. We revealed the detailed mechanisms that ensure the coating's stability, and identified the coating can facilitate the interfacial energy transfer, which allowed the electrocatalysis application of the MOF coating on conductive substrates. We further demonstrated that coatings can be directly generated in a one-pot fashion by ball milling MOF precursors with substrates.


Development of dextran sulphate sodium-induced experimental colitis is suppressed in genetically mast cell-deficient Ws/Ws rats.
Ws/Ws rats have a small deletion of the c-kit gene, and are deficient in both mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC). In the present study we investigated the role of intestinal MMC in the development of dextran sulphate sodium (DSS)-induced experimental colitis using Ws/Ws rats. Ws/Ws and control (+/+) rats were given a 3% DSS aqueous solution orally for 10 days, and the subsequent mucosal damage was evaluated macroscopically and histologically. The mucosal myeloperoxidase (MPO) activities and histamine levels were also measured. (i) DSS induced severe oedema and hyperaemia with sporadic erosions in the control (+/+) rats, but these changes were significantly attenuated in the Ws/Ws rats (P < 0.01). (ii) The microscopic mucosal damage score was lower in the Ws/Ws rats than in the control (+/+) rats (P = 0.06). (iii) There were no significant differences in mucosal MPO activity between the Ws/Ws and control (+/+) rats (P = 0.46). (iv) The mucosal histamine levels in the colon were significantly reduced in the Ws/Ws rats compared with the control (+/+) rats (P < 0.05). (v) Significant positive correlations were observed between mucosal histamine levels and the degree of mucosal oedema (calculated as colonic wet weight/protein content) (r = 0.778, P < 0.01), and between histamine levels and the macroscopic damage (r = 0.623, P < 0.05), respectively. (vi) DSS induced a local recruitment of MMC in the colonic mucosa of Ws/Ws rats, and mucosal damage gradually increased in accordance with this MMC recruitment. These results indicate that MMC play an important role in the development of DSS colitis.


Enhanced effects of bleomycin on pulmonary function disturbances in patients with decreased renal function due to cisplatin.
We examined whether cisplatin-induced nephrotoxicity augmented bleomycin-induced pulmonary toxicity in patients with testicular cancer treated with etoposide and cisplatin with (BEP) or without bleomycin (EP). Before and at 3-week intervals during chemotherapy, creatinine clearance and lung functions were measured. In patients receiving BEP, deterioration of renal function correlated with a decrease in transfer factor of the lungs for carbon monoxide (TLCO) and vital capacity (VC), parameters known to reflect bleomycin-induced pulmonary effects. Other lung functions did not correlate with renal function. In the EP group, no relationships were observed at all. These observations suggest enhanced pulmonary effects of bleomycin when combined with cisplatin. Therefore, attention should be paid to the potential development of bleomycin-induced pulmonary toxicity in patients treated with BEP.


Serotonin in panic anxiety.
Disorders in serotonin transmission and/or metabolism are associated with various psychiatric diseases. In recent years evidence has emerged that serotonin may play a role in the pathogenesis of panic disorder. After an introduction into basic physiology, this evidence is reviewed. The possible meaning of these data is discussed in the context of some recent human experimental models of panic.


Small molecule chemokine mimetics suggest a molecular basis for the observation that CXCL10 and CXCL11 are allosteric ligands of CXCR3.
The chemokine receptor CXCR3 directs migration of T-cells in response to the ligands CXCL9/Mig, CXCL10/IP-10 and CXCL11/I-TAC. Both ligands and receptors are implicated in the pathogenesis of inflammatory disorders, including atherosclerosis and rheumatoid arthritis. Here, we describe the molecular mechanism by which two synthetic small molecule agonists activate CXCR3. As both small molecules are basic, we hypothesized that they formed electrostatic interactions with acidic residues within CXCR3. Nine point mutants of CXCR3 were generated in which an acidic residue was mutated to its amide counterpart. Following transient expression, the ability of the constructs to bind and signal in response to natural and synthetic ligands was examined. The CXCR3 mutants D112N, D195N and E196Q were efficiently expressed and responsive in chemotaxis assays to CXCL11 but not to CXCL10 or to either of the synthetic agonists, confirmed with radioligand binding assays. Molecular modelling of both CXCL10 and CXCR3 suggests that the small molecule agonists mimic a region of the '30s loop' (residues 30-40 of CXCL10) which interacts with the intrahelical CXCR3 residue D112, leading to receptor activation. D195 and E196 are located in the second extracellular loop and form putative intramolecular salt bridges required for a CXCR3 conformation that recognizes CXCL10. In contrast, CXCL11 recognition by CXCR3 is largely independent of these residues. We provide here a molecular basis for the observation that CXCL10 and CXCL11 are allosteric ligands of CXCR3. Such findings may have implications for the design of CXCR3 antagonists.


Establishing an online physical exercise program for people with hemophilia.
Hemophilia is a congenital bleeding disorder with an estimated frequency of 1:10,000 births. Repeated joint bleeding is a hallmark of the disorder and leads to painful hemophilic arthropathy. Regular exercise can help improve joint stability and function, reduce the risk of injury and bleeding and improve physical fitness and quality of life. This method paper describes an online training concept aiming to offer access to appropriate exercise instructions for people with hemophilia who are not able to attend regular training at a hemophilia center. The online exercise program is accessible through the homepage of the Department of Physical Medicine, Rehabilitation and Occupational Medicine of the Medical University Vienna as well as through scanning a QR code printed on information material using a smart phone or tablet. The program contains exercises to improve mobility, coordination, muscular strength and flexibility. A brief introduction is given by a hematologist, a pediatrician and a physiatrist. An introductory video informs about contraindications and essential precautions, such as medical attendance and sufficient factor therapy to consider before starting the training. Another video gives advice on the exercise composition. The demonstrated exercises are explained by a physician and are available for adults and children. To individualize training recommendations and offer further diagnostic tools and physical treatment options as necessary, the Department of Physical Medicine, Rehabilitation and Occupational Medicine of the Medical University of Vienna will establish consultation hours for people with hemophilia. As hemophilia is an orphan disease, patients are mainly treated in specialized centers. For patients who live far from these centers or have limited access to a training there for other reasons, the physical medicine consultation hour and the implementation of online exercise instructions offer individually adapted exercise information for a regular home-based training to benefit from increased physical fitness and joint stability.


Effects of Intratympanic Injection of Isosorbide on the Vestibular Function of Animal Models of Endolymphatic Hydrops.
The aims of this study were to investigate the effects of intratympanic injections of isosorbide on vestibular function in animal models of endolymphatic hydrops and to find a new treatment option for the acute onset of vertigo in Ménière disease (MD). Seventy male guinea pigs received intratympanic injection of isosorbide (IT-ISB). The animals were divided into three study groups: control, a chronic hydrops model, and an acute hydrops model. Intracochlear drug concentrations were measured using high-performance liquid chromatography. Vestibular function was analyzed using an animal rotator test with bidirectional sinusoidal harmonic acceleration before and after IT-ISB administration. Histological changes were also investigated. ISB successfully permeated the perilymph through the round window membrane (RWM) at all three concentrations (25%, 50%, and 100%). In the chronic hydrops model, while IT-ISB histologically induced a reduction of endolymphatic hydrops, vestibular function was unchanged. In the acute hydrops model, no endolymphatic hydrops was histologically observed, and vestibular symmetry was also preserved after IT-ISB. ISB passed through the RWM into the perilymphatic space even at lower concentrations. IT-ISB histologically reduced hydrops in the chronic model and preserved symmetrical vestibular function in the acute model. IT-ISB could be a treatment candidate for acute attacks of vertigo in MD.


Allosteric Signaling Is Bidirectional in an Outer-Membrane Transport Protein.
In BtuB, the Escherichia coli TonB-dependent transporter for vitamin B12, substrate binding to the extracellular surface unfolds a conserved energy coupling motif termed the Ton box into the periplasm. This transmembrane signaling event facilitates an interaction between BtuB and the inner-membrane protein TonB. In this study, continuous-wave and pulse electron paramagnetic resonance in a native outer-membrane preparation demonstrate that signaling also occurs from the periplasmic to the extracellular surface in BtuB. The binding of a TonB fragment to the periplasmic interface alters the configuration of the second extracellular loop and partially dissociates a spin-labeled substrate analog. Moreover, mutants in the periplasmic Ton box that are transport-defective alter the binding site for vitamin B12 in BtuB. This work demonstrates that the Ton box and the extracellular substrate binding site are allosterically coupled in BtuB, and that TonB binding may initiate a partial round of transport.


The effect of race on the CYP3A-mediated metabolism of vincristine in pediatric patients with acute lymphoblastic leukemia.
The purpose of this preliminary study was to compare racial background and CYP3A distribution in pediatric acute lymphoblastic leukemia patients as it relates to vincristine-related neurotoxicity. Patients with B-precursor acute lymphoblastic leukemia treated at Children's Hospital of Michigan were eligible to participate in this study. Determination of the CYP3A variant for each patient was done using Qiagen DNA Blood Mini Kit and polymerase chain reaction amplification. Patients were monitored during their leukemia treatment course for vincristine-related neurotoxicity. Fifty-four patients were enrolled. Twenty-nine Caucasian patients (81%) and 13 African-American patients (77%) experienced neurotoxicity. CYP3A genotyping was done for 52 patients. Two African-American and two Caucasian patients were homozygous A/A for the CYP3A5*3 polymorphism. Three of these patients (75%) experienced grade 2 neuropathy. Two Caucasian patients and one African-American patient were heterozygous A/G. Two of these patients (66.7%) experienced grade 2 or 3 neuropathy. Thirty-five patients (67.3%) were homozygous for the mutant inactive G/G allele for CYP3A5*3, eight African-American and 27 Caucasian patients. Of these, six of the African-American patients (75%) and 22 of the Caucasian patients (81.5%) experienced neuropathy. The CYP3A5*3 genotype causes very low expression of the CYP3A5 protein and hence decreased vincristine metabolism. In this study, patients who expressed CYP3A5*3 had an increased incidence of vincristine-related neurotoxicity. Overall, a greater percentage of Caucasian patients had documented incidences of neurotoxicity. A larger sample size and more detailed gene analysis are needed for future studies.


Cataract development in patients treated with proton beam therapy for uveal melanoma.
To evaluate the incidence, risk factors, and dosages of proton beam therapy associated with cataract development, and long-term visual outcomes after treatment of uveal melanoma. All patients receiving primary proton beam therapy for uveal melanoma between 1998 and 2008 with no signs of cataract before irradiation were included. A minimum follow-up of 12 months was determined. Exclusion criteria included all applied adjuvant therapies such as intravitreal injections, laser photocoagulation, tumor resections, or re-irradiation. For subgroup analysis, we included all patients who underwent brachytherapy between 1998 and 2008 for uveal melanoma, considering the above mentioned inclusion and exclusion criteria. Two hundred and fifty-eight patients matched our inclusion criteria. Median follow-up was 72.6 months (12.0-167.4 months). Of these 258 patients, 71 patients (66.3 %) presented with cataract after 31.3 months (0.7-142.4 months), of whom 35 (20.4 %) required surgery after 24.2 (0.7-111.1 months) to ensure funduscopic tumor control. Kaplan-Meier estimates calculated a risk for cataract of 74.3 % after 5 years. There was no increase in metastasis or local recurrence in these patients. Patient's age was the sole independent statistically significant risk factor for cataract development. The probability of cataract occurrence significantly increased with doses to lens exceeding 15-20 CGE. Neither the appearance of cataract nor cataract surgery influenced long-term visual outcome. Cataract formation is the most frequent complication after irradiation. There is no benefit vis-a-vis brachytherapy with regard to cataract development. Data indicate a dose-effect threshold of 0.5 CGE for cataractogenesis, with significantly increasing risk above a dose of 15 CGE. Furthermore, cataract surgery can be performed without an increased risk for metastasis.


Halogenated Carboxylates as Organic Anodes for Stable and Sustainable Sodium-Ion Batteries.
Organic materials are competitive as anodes for Na-ion batteries (NIBs) due to the low cost, abundance, environmental benignity, and high sustainability. Herein, we synthesized three halogenated carboxylate-based organic anode materials to exploit the impact of halogen atoms (F, Cl, and Br) on the electrochemical performance of carboxylate anodes in NIBs. The fluorinated carboxylate anode, disodium 2, 5-difluoroterephthalate (DFTP-Na), outperforms the other carboxylate anodes with H, Cl, and Br, in terms of high specific capacity (212 mA h g-1), long cycle life (300 cycles), and high rate capability (up to 5 A g-1). As evidenced by the experimental and computational results, the two F atoms in DFTP reduce the solubility, enhance the cyclic stability, and interact with Na+ during the redox reaction, resulting in a high-capacity and stable organic anode material in NIBs. Therefore, this work proves that fluorinating carboxylate compounds is an effective approach to developing high-performance organic anodes for stable and sustainable NIBs.


Changes in serum erythropoietin levels during allogeneic bone marrow transplantation.
Serial serum erythropoietin levels were measured in 10 consecutive patients undergoing allogeneic bone marrow transplantation. Observed erythropoietin levels are compared with those predicted from a large control population of anaemic patients not receiving chemotherapy. There was an initial acute rise in serum erythropoietin, peaking between days 1 and 4 after marrow transfusion, which was unrelated to changes in haemoglobin concentration. Patients maintained serum erythropoietin concentrations at around twice the predicted level for the first 2 weeks following transplantation, with a gradual fall into the expected range by wk 3. Erythropoietin levels did not change with episodes of bacterial infection or acute graft-versus-host disease. A patient with severe aplastic anaemia had initial successful engraftment with normalisation of erythropoietin levels, but showed a marked and amplified rise in erythropoietin 2 wk before falling peripheral blood counts indicated failure of the bone marrow graft.


New chemical constituents from Oryza sativa straw and their algicidal activities against blue-green algae.
Five new constituents, 5,4'-dihydroxy-7,3'-dimethoxyflavone-4'-O-β-D-xylopyranosyl-(2a→1b)-2a-O-β-D-xylopyranosyl-(2b→1c)-2b-O-β-D-xylopyranosyl-2c-octadecanoate (1), 5,4'-dihydroxy-7,3'-dimethoxyflavone-4'-O-α-D-xylopyranosyl-(2a→1b)-2a-O-α-D-xylopyranosyl-(2b→1c)-2b-O-α-D-xylopyranosyl-(2c→1d)-2c-O-α-D-xylopyranosyl-2d-octadecanoate (2), kaempferol-3-O-α-D-xylopyranosyl-(2a→1b)-2a-O-α-D-xylopyranosyl-(2b→1c)-2b-O-α-D-xylopyranosyl-(2c→1d)-2c-O-α-D-xylopyranosyl-2d-hexadecanoate (3), methyl salicylate-2-O-α-D-xylopyranosyl-(2a→1b)-2a-O-α-D-xylopyranosyl-(2b→1c)-2b-O-α-D-xylopyranosyl-(2c→1d)-2c-O-α-D-xylopyranosyl-(2d→1e)-2d-O-α-D-xylopyranosyl-(2e→1f)-2e-O-α-D-xylopyranosyl-(2f→1g)-2f-O-α-D-xylopyranosyl-(2g→1h)-2g-O-α-D-xylopyranosyl-2h-geranilan-8',10'-dioic acid-1'-oate (4), and oleioyl-β-D-arabinoside (5), along with eight known compounds, were isolated from a methanol extract of Oryza sativa straw. The structures of the new compounds were elucidated using one- and two-dimensional NMR spectroscopies in combination with IR, ESI/MS, and HR-ESI/FTMS. In bioassays with blue-green algae, the efficacies of the algicidal activities of the five new compounds (1-5) were evaluated at concentrations of 1, 10, and 100 mg/L. Compound 5 had the highest growth inhibition (92.6 ± 0.3%) for Microcystis aeruginosa UTEX 2388 at a concentration of 100 ppm (mg/L). Compound 5 has high potential for the ecofriendly control of weeds and algae harmful to water-logged rice.


[Effects of emodin on cell apoptosis of intestinal mucosa and serum leptin in rats with severe acute pancreatitis].
To explore the mechanisms of emodin in protecting intestinal mucosal barrier in rat with severe acute pancreatitis (SAP). Sixty SD rats were randomly divided into three groups: sham-operation group, untreated group, and emodin group. SAP in rats of the untreated group and the emodin group was induced by retrograde pumping of 3.0% sodium cholate to the common bile duct. Specimens were obtained 24 hours after the severe acute pancreatitis was induced. Serum level of leptin, serum activity of amylase and plasma content of endotoxin were measured. Ileum mucosa from ileocecal junction was observed by light microscopy and electron microscopy to measure pathological and ultrastructural changes. Apoptosis of ileum mucosal cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, and expression of Bax in ileum mucosal cells was measured by immunohistochemical method. Compared with the sham-operation group, there was significant increase in the levels of leptin, endotoxin, the activity of amylase, apoptosis index and Bax expression in the untreated group (P<0.01). Compared with the untreated group, the level of endotoxin, apoptotic index and Bax expression level in the emodin group were significantly reduced (P<0.01) and the leptin level was increased (P<0.05). More severe pathological changes appeared in the untreated group than in the sham-operation group under the light and electron microscopes; meanwhile less severe damage was observed in the emodin group as compared with the untreated group. Emodin can inhibit the apoptosis of intestinal mucosa cells and up-regulate the serum leptin content to protect the intestina1 barrier function and prevent the translocation of bacteria and endotoxin.


Diagnosing multiple sclerosis at a later age: more than just progressive myelopathy.
Multiple sclerosis (MS) is usually considered a 'young persons' disease', typically presenting between the ages of 20 and 40. In this study we review our experience with patients diagnosed at age 60 or over, with particular emphasis on patients who continue to have evidence of active inflammation despite a later onset. We reviewed all cases of MS diagnosed at or over age 60 in our center over a 5-year period. We identified 111 patients and recorded their clinical and imaging characteristics using prespecified variables. Analyses were performed to describe their interval to diagnosis, clinical syndromes, imaging and laboratory characteristics. At the time of diagnosis, 8% of patients had a clinically isolated syndrome, 33% were in the relapsing-remitting stage, while 23% had a secondary progressive course, and 32% were primary progressive. Eighty-eight percent of patients had a brain MRI judged 'typical for MS', and 32% of all patients receiving gadolinium had enhanced lesions. Forty-six percent of patients with relapsing-remitting MS or clinically isolated syndrome exhibited gadolinium enhancement. Myelitis was the most common initial clinical syndrome, and progressive myelopathy was a common but not exclusive clinical syndrome at the time of diagnosis. A relapsing pattern of MS is not uncommon, even in patients diagnosed over the age of 60. Active inflammation (clinical relapses and gadolinium enhancement) occurs in a significant number of patients with MS with later diagnosis. These observations have implications for evaluation and treatment of patients with MS presenting at an older age.


Spatial pattern of sonic hedgehog signaling through Gli genes during cerebellum development.
The cerebellum consists of a highly organized set of folia that are largely generated postnatally during expansion of the granule cell precursor (GCP) pool. Since the secreted factor sonic hedgehog (Shh) is expressed in Purkinje cells and functions as a GCP mitogen in vitro, it is possible that Shh influences foliation during cerebellum development by regulating the position and/or size of lobes. We studied how Shh and its transcriptional mediators, the Gli proteins, regulate GCP proliferation in vivo, and tested whether they influence foliation. We demonstrate that Shh expression correlates spatially and temporally with foliation. Expression of the Shh target gene Gli1 is also highest in the anterior medial cerebellum, but is restricted to proliferating GCPs and Bergmann glia. By contrast, Gli2 is expressed uniformly in all cells in the developing cerebellum except Purkinje cells and Gli3 is broadly expressed along the anteroposterior axis. Whereas Gli mutants have a normal cerebellum, Gli2 mutants have greatly reduced foliation at birth and a decrease in GCPs. In a complementary study using transgenic mice, we show that overexpressing Shh in the normal domain does not grossly alter the basic foliation pattern, but does lead to prolonged proliferation of GCPs and an increase in the overall size of the cerebellum. Taken together, these studies demonstrate that positive Shh signaling through Gli2 is required to generate a sufficient number of GCPs for proper lobe growth.


Eversion endarterectomy for external iliac artery occlusive disease.
The advent of effective endovascular techniques has revolutionized the treatment of iliac occlusive disease. Long-segment iliac occlusions remain technically difficult to treat, particularly in the presence of femoral disease. Iliac endarterectomy is an established procedure for the treatment of iliac occlusive disease, but it has been suggested that in the era of effective endovascular intervention, its role is limited. A review of all patients who had eversion endarterectomy of the external iliac artery from a single institution between 2000 and 2008. Twenty-one patients (18 male) underwent eversion external iliac endarterectomy, 15 for external iliac and 6 for iliofemoral disease. Mean age was 64.7 years (range: 46-78 years) and the modal American Society of Anaesthesiologists (ASA) grade was 3. The indications were critical ischemia (n = 16) and disabling claudication (n = 5). Twelve had adjunctive procedures. The mean follow-up was 25.3 months (range: 1-59 months). There were no technical failures. Seventeen patients had significant improvement in symptoms and three had moderate improvement. The cumulative primary patency at 1 year was 81%. One patient had no improvement (because of infrainguinal occlusive disease), and subsequently required femoro-popliteal bypass. There was no systemic morbidity within 30 days. There was 1 in-hospital death from sudden cardiac arrest (47 days postoperatively). Six patients died during follow-up (from unrelated illness). Eversion external iliac endarterectomy is an effective means of treating iliofemoral occlusive disease with excellent short-term outcomes and a low complication rate in a cohort with high levels of comorbidity.


[Differences in contraceptive practice in the city of São Paulo, Brazil: results of the Ouvindo Mulheres population survey].
Contraception is essential for women to be able to regulate their fertility, exercising a key dimension of reproductive rights. However, little is known about how women deal with this challenge in Brazil's largest city, São Paulo. To fill this gap, the population survey Ouvindo Mulheres: Contracepção no Município de São Paulo was conducted with a probabilistic sample of 4,000 women 15 to 44 years of age living in this city in 2015. This article presents the prevalence of contraceptive practice and analyzes factors associated with lack of contraception use and with types of contraceptives. Prevalence of contraception was estimated for women with at least one heterosexual relation in the 12 months prior to the interview and who were not pregnant. Logistic regression was used to verify factors associated with lack of contraception use, and the CHAID model was used to identify associations with the types of contraceptives used. Prevalence of contraception was 84.8% (95%CI: 83.2-86.3). The most prevalent contraceptives were the pill and condoms. Factors associated with lack of contraceptive use were religion (Pentecostal), number of children (fewer than 3), not having used contraceptives in the first sexual relation, not having a partner, and not having had sex in the previous month. Number of children and woman's age were the first two levels of discrimination of the types of contraceptives used. Prevalence of contraception was high, but maintaining a concentration in two methods: historically, female sterilization and the pill prevailed, nowadays, the pill and condoms do. New hormonal contraceptives should be incorporated by the Brazilian Unified National Health System (SUS), besides promoting the use of long-acting methods such as IUDs.


Anti-tumor effects of CIK combined with oxaliplatin in human oxaliplatin-resistant gastric cancer cells in vivo and in vitro.
Drug resistance remains a great challenge in the treatment of gastric cancer. The goal of this study was to explore the anti-tumor effects and mechanism of cytokine-induced killer (CIK) cell combined with oxaliplatin (L-OHP) in human oxaliplatin-resistant gastric cancer cells. After producing oxaliplatin-resistant gastric cancer cells, cell morphology, growth and doubling time were observed, followed by detection of cell cycle distribution and apoptosis, drug sensitivity (e.g., L-OHP) and expression of P-gp and livin. MTT assay, in vivo pharmacodynamics and pathomorphology experiments were used to detect killing activities of CIK combined with L-OHP. Compared with parental gastric cancer cells, oxaliplatin-resistant gastric cancer cells in S phase were reduced and cell apoptosis rate was increased (P < 0.05), the inhibition rate of 10 chemotherapeutics on oxaliplatin-resistant gastric cancer cells was significantly lower and the expression of P-gp was significantly higher (P < 0.05). However, there was no significant difference in livin expression between parental gastric cancer cells and oxaliplatin-resistant gastric cancer cells (P > 0.05). The in vitro killing activity of CIK combined with L-OHP on parental cells and oxaliplatin-resistant cells were significantly enhanced compared with L-OHP or CIK alone. And it showed greater synergetic effects against oxaliplatin-resistant cells compared with parental cells (P < 0.05). In addition, survival rate, abdominal circumference and pathomorphology results revealed stronger in vivo anti-tumor effects when the two therapies were combined. The mechanism of oxaliplatin-resistant cell secondary multidrug resistance was correlated with the variation of cell cycle distribution, extension of doubling time and upregulation of P-gp expression. The synergistic effect of CIK in combination with L-OHP on killing activity against oxaliplatin-resistant cells was shown in vivo and in vitro.


Flexural-Phonon Scattering Induced by Electrostatic Gating in Graphene.
Graphene has an extremely high carrier mobility partly due to its planar mirror symmetry inhibiting scattering by the highly occupied acoustic flexural phonons. Electrostatic gating of a graphene device can break the planar mirror symmetry, yielding a coupling mechanism to the flexural phonons. We examine the effect of the gate-induced one-phonon scattering on the mobility for several gate geometries and dielectric environments using first-principles calculations based on density functional theory and the Boltzmann equation. We demonstrate that this scattering mechanism can be a mobility-limiting factor, and show how the carrier density and temperature scaling of the mobility depends on the electrostatic environment. Our findings may explain the high deformation potential for in-plane acoustic phonons extracted from experiments and, furthermore, suggest a direct relation between device symmetry and resulting mobility.


Comparative analysis of CD8 expressed on mature CD4+ CD8+ T cell clones cultured with IL-4 and that on CD8+ T cell clones: implication for functional significance of CD8 beta.
Interleukin (IL-4) can induce CD8 expression on mature CD4+ T cells. To study this phenomenon in more detail, we characterized CD8 expressed on IL-4-induced CD4+ CD8+ (double positive) T cell clones in comparison with that on CD8+ T cell clones. Using 2ST8-5H7 mAb that detects CD8 beta expression, we found that double positive T cell clones isolated with IL-4 express CD8 alpha but not beta, in contrast to CD8+ CTL cell clones, which express both chains of CD8. Northern blot analysis revealed that these double positive clones expressed CD8 alpha but not beta mRNA, indicating that CD8 alpha and beta are independently regulated at the pre-translational level. Immunoprecipitation experiments showed that CD8 expressed on a representative IL-4-induced double positive T cell clone consists mainly of homodimers of a single 34 kd protein of CD8 alpha. The amount of multimers detected from this clone was much less than that from a CD8+ CTL clone. These results suggest that persistent expression of CD8 beta is specific for the CD8+ lineage and may be involved in polymerization and stabilization of CD8 which enhances the efficiency of class I-restricted antigen recognition.


Quality of life in recipients before and after liver transplantation in Turkey.
Liver transplantation has become the treatment of choice for patients with end-stage liver disease. Most studies show a positive effect on quality of life after liver transplantation, but most studies are based on data from Western countries and little is known about quality of life in liver transplant recipients in Turkey or other developing countries. To investigate liver transplant recipients' quality of life and factors affecting it, before and 3 months after transplantation in western Turkey. Descriptive and comparative, with data collected prospectively. Two medical centers in Western Turkey. Sixty-five adult recipients of a liver transplant between May 15 and December 31,2007. Quality of life was measured by using the Nottingham Health Profile Turkish version, and sociodemographic and clinical data were collected from patients' records. Scores on all subscales of the Nottingham Health Profile differed significantly from before to after liver transplantation. The differences between the mean scores for quality of life before and after transplantation varied significantly with the patients' sex and disease severity.


BIS-GMA--based resins in dentistry: are they safe?
The authors critically surveyed research dealing with the release of resin components from dental composites and the potential of these agents to mimic or disrupt estrogenic cell responses. The studies reviewed included those on synthetic methods used to make bisphenol A glycidyl methacrylate, or BIS-GMA, and the biological effects of this resin in cell culture and animals. The estrogenic effect of bisphenol A was targeted because bisphenol A is present as an impurity in some resins (BIS-GMA) and as a degradation product from other resins (bisphenol A dimethacrylate, or BIS-DMA). The outcomes of this review revealed that short-term administration of BIS-GMA and/or bisphenol A in animals or cell cultures can induce changes in estrogen-sensitive organs or cells. However, considering the dosages and routes of administration and the modest response of estrogen-sensitive target organs, the authors conclude that the short-term risk of estrogenic effects from treatments using bisphenol A-based resins is insignificant. Long-term effects need to be investigated further. Commonly used dental resins should not be of concern to the general public; however, pharmacological evaluation of dental materials is needed to ensure biologically safe and therapeutically effective substances.


Novel estrogens and their radical scavenging effects, iron-chelating, and total antioxidative activities: 17 alpha-substituted analogs of delta 9(11)-dehydro-17 beta-estradiol.
Antioxidant effects of N,N-dimethyl-p-toluidine, p-cresol, and p-(hydroxy)thioanisol 17 alpha-substituted analogs of 17 beta-estradiol and their delta 9(11)-dehydro homologs were investigated using four different in vitro models: rat synaptosomal lipid peroxidation induced by Fenton's reagent, Fe(II)-chelating activities, the formation of superoxide anion radicals, and total antioxidative activity. Whereas the classical estrogen 17 beta-estradiol as well as selected phenolic compounds was only moderately inhibiting iron-dependent lipid peroxidation and stimulating total antioxidative activity, besides delta 9(11)-dehydro-17 beta-estradiol (J 1213), novel estrogens such as C-17-oriented side chain analogs of 17 beta-estradiol (J 843, J 872, and J 897) and delta 9(11)-dehydro homologs (J 844, J 864, and J 898) directly altered the iron redox chemistry and diminished the formation of superoxide anion radicals generated by a xanthine/xanthine oxidase-dependent luminescence reaction to a great extent. These results suggest that definite modifications in the chemical structure of 17 beta-estradiol, e.g., the introduction of a delta 9(11)-double bond and/or p-cresol as well as p-(hydroxy)thioanisol C-17 substitution, may result in substantial changes in their antioxidant behavior. These compounds may be drug candidates for treating pathologies related to free radical formation.


Periodontal microflora of HIV positive subjects with gingivitis or adult periodontitis.
The subgingival microflora of 39 HIV+ subjects with gingivitis or adult periodontitis was cultured quantitatively anaerobically for bacteria, spirochetes, and mycoplasma and aerobically for yeasts. Isolates were characterized by conventional biochemical tests, polyacrylamide gel electrophoresis of soluble proteins, cellular fatty acid profiles, immunofluorescence, and immunodiffusion. In general, the same types of bacteria were isolated from the subgingival crevice of HIV+ subjects as we previously had isolated from the subgingival crevice of non-HIV subjects. A statistically significant difference was found between the composition of the flora of HIV+ subjects with adult periodontitis (AP) and concurrent studies of a non-HIV+ AP population. Mycoplasma salivarium was significantly elevated in the HIV+ subjects examined. Yeasts were isolated from only 10% of the samples and from 13% of the HIV-positive subjects at 0.05 to 0.0002% of the total cultivable count when present.


Clinical findings with nimodipine in dementia: test of the calcium hypothesis.
Calcium toxicity seems to be involved in ischemic brain lesions like in vascular dementia and possibly in primary degenerative dementia of Alzheimer's type. The calcium channel blocker nimodipine readily passes the blood-brain barrier and may thus serve as a pharmacologic probe to test the hypothesis of calcium toxicity. Although nimodipine proved to be superior to placebo in a considerable amount of studies in dementia the concept of calcium toxicity cannot be accepted as established. This is due to some methodological flaws in the clinical trials as well as the limited effect size. Moreover, bridging to other findings especially in Alzheimer-type dementia like amyloid deposition and the relationship to apolipoprotein-E isotypes is still far from complete.


Muscle damage, fluid ingestion, and energy supplementation during recreational alpine skiing.
This study examined energy and fluid supplementation on indices of muscle damage during alpine skiing. Skiers were assigned to a carbohydrate-protein (CP), placebo (PL), or no fluid (NF) group. CP and PL ingested 1.62 L during and after skiing. Myoglobin did not change from pre-skiing (PS) to 2 h post-skiing (2PS) for CP (24.8 +/- 1.4 and 25.6 +/- 1.6 ng/mL), but rose significantly from 26.4 +/- 1.3 to 40.0 +/- 2.8 ng/mL for PL and from 29.0 +/- 1.3 to 82.9 +/- 3.6 ng/mL for NF. Creatine kinase was maintained from PRE to 2 PS for CP, but increased significantly from 117 +/- 7.2 to 174 +/- 43.4 U/L for PL and from 126 +/- 23.2 to 243 +/- 34.3 U/L for NF. This study demonstrates that ingestion of a CP beverage minimized muscle damage indices during skiing compared to PL and NF and that ingesting fluids may also minimize muscle damage compared to a NF condition.


Direct visual internal urethrotomy for isolated, post-urethroplasty strictures: a retrospective analysis.
Urethroplasty is often successful for the treatment of male urethral stricture disease, but limited data exists on recurrence management. Our goal was to evaluate direct visual internal urethrotomy (DVIU) as a treatment option for isolated, recurrent strictures after urethroplasty. We retrospectively identified male patients who underwent urethroplasty from 1999 to 2013 and developed an isolated, recurrent stricture at the urethroplasty site treated with DVIU. Success was defined as lack of symptomatology and no subsequent intervention. Comparative analysis identified characteristics and stricture properties associated with success. A total of 436 urethroplasties were performed in 401 patients at our institution between 1999 and 2013. Stricture recurrence was noted in 64 (16%) patients. Of these, 47 (73%) underwent a DVIU. A total of 37 patients met inclusion criteria and underwent 50 DVIU procedures at the urethroplasty site. A single DVIU was successful in 13 of 37 patients (35%). A total of 4 of 6 patients required a second DVIU (67%). Overall, 17 of 43 (40%) of the total DVIUs were successful after urethroplasty. Success did not differ by age, stricture length or location, surgical technique, radiation history, prior urethroplasty or DVIU, time to failure, or etiology. Post-urethroplasty DVIU for isolated, recurrent strictures may be offered as a minimally invasive treatment option. Approximately 40% of patients were spared further intervention.


Plasma interleukin-18 levels in patients with psychiatric disorders.
There are an increasing number of reports on an association between the alteration of circulating cytokine levels and pathophysiology of psychiatric disorders. Plasma concentrations of interleukin (IL)-18 were measured in 13 nonmedicated patients with psychiatric disorders. There was a significant elevation of IL-18 levels in patients with major depression (n = 8) and panic disorder (n = 5), compared with normal controls. The mean IL-18 value of our psychiatric patients was comparable with that of various somatic disorders reported. We suggest that the elevation of plasma IL-18 levels reflects the increased production and release of IL-18 in the central nervous system under stressful settings. We propose that the measurement of IL-18 plasma levels may provide a useful index for the involvement of immune system in psychiatric disorders.


[Papillary renal cell carcinoma surrounded by unusual fibrotic reaction resembling inflammatory pseudotumour--a case report].
Authors report clinicopathological features of an unusual case of composite renal lesion occuring in 32-year-old Caucasian male. The patient was followed for cystic lesion of retroperitoneal-renal region for 5 years. He was indicated for resection of the cystic lesion because of changes of the retroperitoneal mass on CT scan. A cyst was located on upper renal pole. A huge cystic mass filled mainly by necrotic material was resected and submitted for histological examination. The wall of the cyst was composed of fibrous tissue, indistinguishable from inflammatory pseudotumor on histological level. The vital intracystic tissue was formed by well-differentiated papillary renal cell carcinoma. The most important step within differential diagnosis is distinguishing of sarcomatoid differentiation in renal cell carcinoma. This very rare case demonstrates the importance of careful examination of all spindle cell lesions of the kidney.


Contractility and endothelium-dependent relaxation of resistance vessels in polycystic kidney disease rats.
Hypertension and vascular disease are common complications in autosomal-dominant polycystic kidney disease (ADPKD). The role of changes in morphology and reactivity of resistance vessels in this disease have not previously been studied. Mesenteric resistance arteries were dissected from 8- to 14-week-old heterozygous Han:SPRD polycystic kidney disease (PKD) rats, homozygous normal Han:SPRD littermates (HSPRD) and Sprague-Dawley rats (SD). The morphology, noradrenaline (NA) contractility, endothelium-dependent acetylcholine (ACh) relaxation before and after incubation with L(G)-nitro-L-arginine methyl ester (L-NAME), and endothelium-independent 3-morphollino-sydnonimine (SIN-1) relaxation were studied with the Mulvany-Halpern myograph. Blood pressure and morphology of vessels were the same in all groups of rats, apart from a slightly higher media/lumen ratio in heterozygous PKD rats (p < 0.05). Active wall tension and contractile sensitivity to NA were higher in both heterozygous PKD rats and HSPRD than SD rats (p < 0. 05). The maximum endothelium-dependent relaxation rate was markedly decreased in heterozygous PKD (19 +/- 9%) and HSPRD (34 +/- 12%) compared to SD rats (75 +/- 11%) (p < 0.05). After incubation with L-NAME, ACh-induced relaxation was significantly attenuated in SD rats, less attenuated in HSPRD, and not significantly changed in heterozygous PKD rats. SIN-1-induced endothelium-independent relaxation was similar in all three groups. In conclusion, hyperreactivity to NA and impaired endothelium-dependent relaxation were present in resistance vessels from Han:SPRD rats, especially in animals with PKD. These abnormalities in resistance vessels from PKD rats may be important for the development of hypertension and vascular disease.


Aequorivita iocasae sp. nov., a halophilic bacterium isolated from sediment collected at a cold seep field in the South China Sea.
A moderately halophilic bacterium, designated strain KX20305T, was isolated from sediment collected from a cold seep field in the South China Sea. Cells of strain KX20305T were Gram-stain-negative, rod-shaped, non-motile, facultatively anaerobic, oxidase- and catalase-positive, and grew optimally at 25-30 °C, pH 6.0-8.0 and with 3-6 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain KX20305T grouped with members of the genus Aequorivita, including Aequorivita aquimaris D-24T (98.3 % sequence similarity), Aequorivita vladivostokensis KMM 3516T (98.1 %) and Aequorivita echinoideorum CC-CZW007T (97.5 %). Genome sequencing of strain KX20305T revealed a genome size of 3.35 Mb and a DNA G+C content of 38.71 mol%. Genomic average nucleotide identity (orthoANI) values of strain KX20305T with A. aquimaris D-24T, A. vladivostokensis KMM 3516T and A. echinoideorum JCM 30378T were 83.8, 81.7 and 75.4 %, respectively, while in silico DNA-DNA hybridization (GGDC) values for strain KX20305T with these strains were 27.2, 25.0 and 19.6 %, respectively. The major fatty acids of strain KX20305T were iso-C15 : 0, iso-C17 : 0 3-OH and 10-methyl C16 : 0/iso-C17 : 1 ω9c. The predominant respiratory quinone was menaquinone-6 (MK-6). The polar lipids mainly comprised phosphatidylethanolamine, two unidentified aminolipids and two unidentified lipids. Based on comparative analysis of phylogenetic, phylogenomic, phenotypic and chemotaxonomic characteristics, strain KX20305T represents a novel species of the genus Aequorivita, for which the name Aequorivita iocasae sp. nov. is proposed. The type strain is KX20305T (=KCTC 82699T=MCCC 1K06238T=JCM 34635T).


Application of new targeted drugs in relapsed/refractory primary central nervous system lymphoma.
The prognosis of patients with relapsed and refractory primary central nervous system diffuse large B cell lymphoma (PCNSL) is poor and there is no standard salvage treatment currently available. Gene expression profiling and next-generation sequencing have provided massive amounts of data, revealing the pathogenic mechanism of PCNSL and identifying potential mechanisms for therapeutic exploration. Here, we review targeted drugs that may change the current treatment model of PCNSL.


[Comparison on energy values of matching food items in food compositon table of four northeast Asian countries or region].
To evaluate the consistency and compatibility of the energy values in present applied Food Composition Tables or Databases (FCTs or FCDs) of NeasiaFoods members. A total 101 matching food items (N = 101 x 4) were selected from the FCTs or FCD of Japan, Korea, Taiwan and China. Statistical comparisons were conducted before and after water adjustment. Data profile plots, means and relative differences were provided. The significance of differences were examined by the block designed ANOVA (alpha = 0.05). The population mean of Chinese food items is significantly low than that of other three. Relative difference (mean and 95% CI) of water adjusted estimation indicate that energy of China is totally less 7.7% (-0.6% - 15.9%), 11.7% (3.5 % - 20.1 %) and 2.6% (-5.2% - 10.3%) than that of Japan, Taiwan, and Korea respectively. Major bias occurred in Nuts & seeds and Fungi & Algae, Japan and Taiwan higher 22% to 68% than China. The energy values in FCTs of these NEASIAFOODS members lack consistency, especially between China and other three members. Differences of food energy conversion systems are the main effect that producing discrepancies. The effect of bias in energy contributing nutrients (e.g. fat) are considerable; analytical errors, sampling errors, food processing effects, different of food species, and accumulation of them only can be estimated through interlaboratory comparison studies on the basis of totally same food samples.


Fleece-Bound Tissue Sealing in Microvascular Decompression.
Cerebrospinal fluid (CSF) leakage is a feared complication after microvascular decompression (MVD). In this study, we present our experience of fleece-bound tissue sealing in MVD with an aim to minimize the rate of postoperative CSF leakage. We treated 50 patients (female/male: 26/24) with neurovascular compression (NVC) syndromes (trigeminal neuralgia, hemifacial spasm and glossopharyngeal neuralgia) by MVD from 2003 to 2006. All patients underwent retromastoid craniectomy and duraplasty by fleece-bound tissue sealing using the so-called "sandwich technique" by a three-layer reconstruction and cranioplasty. In 49 (98%) of 50 patients, we did not observe postoperative CSF leakage. One patient (2%) suffered postoperative CSF leakage and required surgical revision. Fleece-bound tissue sealing by a three-layer reconstruction is effective and safe in the prevention of cerebrospinal fluid leakage in microvascular decompression.