Electrocardiogram of posterior wall infarction.
The purpose of the study was to assess the frequency of infarction of the posterior wall of the left ventricle which shows a high R wave in leads V1-2 on electrocardiogram. Serial electrocardiograms of 1 452 patients with myocardial infarction were analyzed. Features of posterior wall infarction were found in 106 cases (7.3%). In 13 cases, the area of infarction was limited to the posterior wall; in 12 cases, concomitant features of lateral wall infarction were found; in 38 cases, the changes involved the inferior wall as well, and in 43 cases, the inferior and lateral walls were involved concomitantly. A high R wave in V1-2 was observed already in the first ECG obtained on the day of the onset of the disease in 32 out of 106 cases, while in 74 cases it appeared only in the subsequent days. High voltage of R wave was found in V1 exclusively in 20 cases, in V2 exclusively in 36 cases, and simultaneously in V1 and V2 in 50 cases. The analysis suggests that posterior wall infarction is fairly frequent (7.3%) but occurs in only 1% of cases as an isolated process. Knowledge of the features of posterior wall infarction is of practical importance; simultaneous detection of features of infarction of the posterior and the inferior or lateral walls is proof of a widespread myocardial necrosis and may be of prognostic significance.


[Importance of form in dental implantation].
Thirteen implantations have been made in the mandibular arches of 6 dogs. They consisted of commerical titanium blades and screws and of replicas of extracted dental roots variously shaped and made of titanium. All replicas and some of the commerical implantations were covered with pure aluminium using the plasmajet tecnique. Clinico-radiological, histopathological and microradiographical observation showed that only some of the replicas of dental roots give promising results.


Eradication of Helicobacter pylori infection might improve clinical status of patients with Parkinson's disease, especially on bradykinesia.
Previous studies have shown that Helicobacter pylori infection might make clinical status worse in patients with Parkinson's disease and Helicobacter pylori eradication might improve clinical status by modifying the pharmacokinetics of L-dopa. Here, we investigate whether Helicobacter pylori eradication could benefit idiopathic parkinsonism and Helicobacter pylori infection will effect which aspect of motor symptom significantly. A cohort study involving idiopathic Parkinson's disease patients, screened for Helicobacter status by 13C urea breath test. Clinical status was evaluated by using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn-Yahr stage. If patients had motor complications, they were quantified at the "on" time. The Helicobacter pylori positive patients could choose to receive Helicobacter pylori eradication or not by themselves. Group 1 was Helicobacter pylori negative patients. Group 2 was Helicobacter pylori positive patients who didn't receive eradication treatment. Group 3 was Helicobacter pylori positive patients who received successful eradication treatment. Repeat clinical assessments and 13C urea breath test was performed at 1year later. Numerical data were expressed as mean±standard deviation (SD) RESULTS: Ninety-four consecutive patients with Parkinson's disease were recruited and underwent the initial 13C urea breath test, but only forty-eight patients successfully completed the total study. In Group 3, the UPDRS-III scores (=Motor Examination Section Scores) were significantly lower 1year later compared to baseline (18.3±8.38 vs. 25.9±8.37, P=0.007). The differences were main in UPDRS-23 (=Finger Taps) (1.7±1.16 vs. 2.4±1.51, P=0.045), UPDRS-25 (Rapid Alternation Movements of Hands) (1.6±1.35 vs. 2.4±1.71, P=0.031) and UPDRS-26 (=Leg Agility) (1.3±1.25 vs.2.1±0.99, P=0.011). There was difference among three groups in the UPDRS-26 (P=0.040) of clinical status change of one year. The eradication of Helicobacter might improve the clinical status of idiopathic parkinsonism, especially on bradykinesia.


An epidemiological study of metagonimiasis along the upper reaches of the Namhan River.
An epidemiological study of Metagonimus infection was undertaken along the upper reaches of the Namhan River, with special consideration on the species (type) of the worms collected from humans. Eggs of Metagonimus spp. were detected from 15 (9.7%) of 154 people examined in Umsong-gun, and from each infected person (5 cases) 6,015-24,060 worms (mean 13,233) were recovered after treatment with praziquantel (10 mg/kg). Eggs were also detected from 37 (48.1%) of 77 people in Yongwol-gun, from whom (27 cases) 1-4,965 worms (means 1,215) were collected. The worm from Umsong-gun consisted of both Metagonimus Miyata type and Metagonimus takahashii, whereas those from Yongwol-gun consisted of only Metagonimus Miyata type. When the uterine eggs of the two kinds and M. yokogawai (obtained from people in Tamjin River basin) were morphologically compared, it was suggested that the egg size should be a good indicator for discrimination of the species or type. The source of human infection was proved to be fresh water fishes; 49 of 52 Zacco platypus examined, 6 of 8 Hemibarbus longirostris, 13 of 15 Pseudogobio esocinus, 4 of 6 Odontobutis obscura interrupta, and 17 of 18 Carassius carassius were found infected with Metagonimus metacercariae. From the results, it is concluded that the upper reaches of the Namhan River are endemic foci of Metagonimus Miyata type and M. takahashii.


Morning to evening changes in the electrical and mechanical properties of human soleus motor units activated by H reflex and M wave.
The aim of the present study was to compare the relative contribution of the soleus motor units (MUs) activated by H and M waves to the plantar-flexion torque in the morning and in the evening. Twelve healthy male subjects (physical education students) took part in this investigation. The electromechanical properties of the plantar flexor muscles were recorded at two different times of day: between 06:00 and 08:00 h and between 17:00 and 19:00 h. Plantar-flexion torque and concomitant electromyographic activity of soleus muscle were assessed under voluntary and evoked conditions. The results indicated a significant decrease in maximal voluntary muscle torque of triceps surae and associated soleus EMG in the evening as compared with the morning. The mean values of MVC ranged from 131.6+/-9.6 N m in the morning to 125.1+/-9.0 N m in the evening. Peak-to-peak values of soleus H (max) and M (max) potentials were comparable in the morning and in the evening (2.97 vs 3.18 mV and 7.95 vs 7.44 mV for H (max) and M (max), respectively). The H (max)/M (max) ratio was not modified between the two experimental test sessions (34.8 vs 41.3%). The peak amplitude of the twitch produced by the H (max) wave (Pt (H max)) decreased significantly. When estimating the mechanical contribution to (Pt (H max)) of the slowest and fastest-twitch MUs reflexively and directly activated, we observed that the contribution of the slowest MUs did not change while those of the fastest decreased significantly in the evening. To conclude, a weaker reflex twitch torque caused by higher fatigue state of the MUs directly activated by the M wave which accompanied H (max) in the evening may be regarded as a possible explanation of the weaker plantar-flexion torque production in the evening.


β2→1-Fructans Modulate the Immune System In Vivo in a Microbiota-Dependent and -Independent Fashion.
It has been shown in vitro that only specific dietary fibers contribute to immunity, but studies in vivo are not conclusive. Here, we investigated degree of polymerization (DP) dependent effects of β2→1-fructans on immunity via microbiota-dependent and -independent effects. To this end, conventional or germ-free mice received short- or long-chain β2→1-fructan for 5 days. Immune cell populations in the spleen, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) were analyzed with flow cytometry, genome-wide gene expression in the ileum was measured with microarray, and gut microbiota composition was analyzed with 16S rRNA sequencing of fecal samples. We found that β2→1-fructans modulated immunity by both microbiota and microbiota-independent effects. Moreover, effects were dependent on the chain-length of the β2→1-fructans type polymer. Both short- and long-chain β2→1-fructans enhanced T-helper 1 cells in PPs, whereas only short-chain β2→1-fructans increased regulatory T cells and CD11b-CD103- dendritic cells (DCs) in the MLN. A common feature after short- and long-chain β2→1-fructan treatment was enhanced 2-alpha-l-fucosyltransferase 2 expression and other IL-22-dependent genes in the ileum of conventional mice. These effects were not associated with shifts in gut microbiota composition, or altered production of short-chain fatty acids. Both short- and long-chain β2→1-fructans also induced immune effects in germ-free animals, demonstrating direct effect independent from the gut microbiota. Also, these effects were dependent on the chain-length of the β2→1-fructans. Short-chain β2→1-fructan induced lower CD80 expression by CD11b-CD103- DCs in PPs, whereas long-chain β2→1-fructan specifically modulated B cell responses in germ-free mice. In conclusion, support of immunity is determined by the chemical structure of β2→1-fructans and is partially microbiota independent.


Primary malignant melanoma of the ovary: a report of 9 definite or probable cases with emphasis on their morphologic diversity and mimicry of other primary and secondary ovarian neoplasms.
Most malignant melanomas encountered in the ovary are metastatic, and the recent literature has focused on such neoplasms. Primary tumors are rare with most reports being only of single cases. When the tumor is associated with teratomatous elements from which it arises, not only is the diagnosis of melanoma much more likely to be made but also is a primary nature proven. However, although all the primary tumors likely are of teratomatous origin, evidence of such an origin may be effaced resulting in problems both in identifying the tumor as melanoma and in determining if it is primary or not. In this report, we describe 9 primary or probably primary ovarian melanomas and explore the varied problems the cases posed. The patients ranged from 18 to 72 years. The tumors, all of which were unilateral, ranged from 4 to 23 cm; only 2 were black. In 6 cases, there was an associated dermoid cyst or monodermal teratoma (struma ovarii), 5 in the ipsilateral and 1 in the contralateral ovary. The tumors were variously composed of large epithelioid cells with eosinophilic cytoplasm, small cells, spindle-shaped cells, or a combination, and in 5 cases, melanin pigment (Masson Fontana positive) was identified. In all cases, most of the tumor cells had prominent nucleoli. All neoplasms had a predominantly diffuse growth pattern with a focal nested architecture in 3 cases. Other noteworthy morphological features were tumor giant cells with wreath-like nuclei (4 cases), signet ring cells (1 case), clear cells (1 case), intranuclear pseudoinclusions (2 cases), a focally myxoid stroma (2 cases), a pseudopapillary appearance caused by degeneration (2 cases), and follicle-like structures (3 cases). In 1 case in a 21-year-old, there was associated hypercalcemia, and focally, the neoplasm, which contained follicle-like structures, resembled small cell carcinoma of the hypercalcemic type. All cases tested by immunohistochemistry were positive with 1 or more melanocytic markers, and electron microscopy performed in 3 cases revealed intracytoplasmic melanosomes or premelanosomes. The wide differential potentially includes neoplasms within most of the categories of primary ovarian neoplasia, as well as metastatic melanoma, and is facilitated by thorough sampling to identify teratomatous elements, by awareness of the spectrum of melanoma in the ovary, and by positivity with melanocytic markers. This is an area where electron microscopy can still also contribute useful information.


Research evidence and delivering race equality in mental health.
Research evidence has been central to the forming and steering of the Delivering Race Equality programme in mental health in England. Evidence can be conceived of an used in many ways. Sensible fusions across evidence, values, policy and practice need to be found, an issue that has been at the heart of the DRE programme. Research evidence could not at the outset provide all of the answers for a complex and ambitious programme such as DRE. Instead the programme has taken a formative approach, continuing to learn from experience and commissioned research to seek improvement in its work to address quality improvements in care.


[Allergic contact dermatitis caused by insulin pumps and glucose monitors in children with diabetes].
Insulin pump therapy and the use of flash or continuous glucose monitoring in children is increasing. The diabetes devices are attached to the skin for several days to weeks with a strong adhesive, and recently, several cases of allergic contact dermatitis in children caused by components of the adhesive have been reported. In this review, we discuss such problems. The most frequent cause of allergic contact dermatitis is acrylates in the adhesive material, and the problem is serious and calls for rapid development of devices used in the treatment and monitoring of Type 1 diabetes without allergenic agents.


Comparison of propofol/ketamine versus propofol/alfentanil for dilatation and curettage.
The use of propofol with an analgesic agent is probably the principal technique for the induction of anesthesia for dilatation and curettage (D&C) at the present time. We designed a randomized, double-blind study to compare the clinical efficacy of ketamine and alfentanil when combined with propofol for short-lasting anesthesia during D&C. The study included 60 patients scheduled for D&C. Either alfentanil 10 microg/kg(-1) IV (Group A) or ketamine 0.5 mg/kg(-1) IV (Group K) were given to each patient with propofol 0.7 mg/kg(-1) IV for anesthesia induction. Surgeon and patient satisfaction, Aldrete score, Verbal Pain Scale rating, total propofol dose, orientation time, and adverse events such as bradycardia, hypotension, nausea, and vomiting were evaluated. In Group A orientation time was significantly shorter and propofol consumption significantly lower than in Group K. Both alfentanil/propofol and ketamine/propofol combinations provide reliable and effective hypnosis and analgesia; however, the ketamine/propofol combination leads to higher consumption of propofol and results in a longer orientation time than the alfentanil/propofol combination.


Prevention and control of schistosomiasis: a current perspective.
Schistosomiasis is a neglected tropical disease that ranks second only to malaria in terms of human suffering in the tropics and subtropics. Five species are known to infect man and there are currently over 240 million people infected worldwide. The cornerstone of control to date has been mass drug administration with 40 mg/kg of praziquantel but there are problems with this approach. Human and bovine vaccines are in various stages of development. Integrated control, targeting the life cycle, is the only approach that will lead to sustainability and future elimination.


[The role of adjuvant endocrine therapy in the management of operable breast cancer].
Since June, 1982, a chemoendocrine adjuvant clinical trial has been conducted at the Aichi Cancer Center Hospital. Women with operable breast cancer were stratified on the basis of the number of positive axillary nodes. Node negative patients received tamoxifen (TAM) for 6 months (Trial I), patients with 1-7 positive nodes received either cyclophosphamide (CPA) for 4 weeks and TAM for one year (Trial II), and patients with 8 or more positive nodes received either CPA for 8 weeks and TAM for 3 years (Trial III). Numbers of evaluable cases are 449 for Trial I, 228 for Trial II and 84 for Trial III. This is an interim report, and the median follow-up time is 3 years and 5 months. This is a prospective non-randomized trial, and control groups (observation group and chemotherapy group) are historical. 1. Premenopausal patients in Trial I yielded intermediate outcome between those of observation and chemotherapy groups. Thus, for this subgroup, adjuvant chemotherapy can be considered as a standard, and addition of TAM is recommended. 2. The benefit of TAM is apparent for postmenopausal patients in Trial I. 3. TAM is effective for both pre- and postmenopausal patients in Trial II. Addition of more aggressive chemotherapy should be considered. 4. Premenopausal patients in Trial III had a better disease-free survival compared with those of control groups. More effective combined chemotherapy may yield longer overall survival. 5. Postmenopausal patients in Trial III had a better disease-free and overall survival rate. Adjuvant TAM and combined chemotherapy can be considered as standard care for this subgroup.


Long-Term Autonomic Thermoregulating Fabrics Based on Microencapsulated Phase Change Materials.
Microcapsules loaded with n-docosane as phase change material (mPCMs) for thermal energy storage with a phase change transition temperature in the range of 36-45 °C have been employed to impregnate cotton fabrics. Fabrics impregnated with 8 wt % of mPCMs provided 11 °C of temperature buffering effect during heating. On the cooling step, impregnated fabrics demonstrated 6 °C temperature increase for over 100 cycles of switching on/off of the heating source. Similar thermoregulating performance was observed for impregnated fabrics stored for 4 years (1500 days) at room temperature. Temperature buffering effect increased to 14 °C during heating cycle and temperature increase effect reached 9 °C during cooling cycle in the aged fabric composites. Both effects remained stable in aged fabrics for more than 100 heating/cooling cycles. Our study demonstrates high potential use of the microencapsulated n-docosane for thermal management applications, including high-technical textiles, footwear materials, and building thermoregulating covers and paints with high potential for commercial applications.


Imported African Tick Bite Fever in Japan: A Literature Review and Report of Three Cases.
African tick bite fever (ATBF) is an acute febrile illness caused by Rickettsia africae. ATBF is an important differential diagnosis of acute febrile illness among returned travelers. However, little information is available on ATBF cases imported to Japan, as only seven have been reported to date. To characterize the epidemiological and clinical profiles of patients diagnosed with ATBF in Japan, we reported three new ATBF cases at our hospital between May 2015 and April 2018 and conducted a literature review.


Identification and management of fetal anemia due to hemolytic disease.
Hemolytic disease of the fetus and newborn (HDFN) is a condition caused by maternal alloantibodies against fetal red blood cells (RBCs) that can cause severe morbidity and mortality in the fetus and newborn. Adequate screening programs allow for timely prevention and intervention resulting in significant reduction of the disease over the last decades. Nevertheless, HDFN still occurs and with current treatment having reached an optimum, focus shifts toward noninvasive therapy options. This review focusses on the timely identification of high risk cases and antenatal management. Furthermore, we elaborate on future perspectives including improvement of screening, identification of high risk cases and promising treatment options. In high-income countries mortality and morbidity rates due to HDFN have drastically been reduced over the last decades, yet worldwide anti-D mediated HDFN still accounts for 160,000 perinatal deaths and 100,000 patients with disabilities every year. Much of these deaths and disabilities could have been avoided with proper identification and prophylaxis. By implementing sustainable prevention, screening, and disease treatment measures in all countries this will systemically reduce unnecessary perinatal deaths. There is a common responsibility to engage in this cause.


Association between surgical wait time and hospital length of stay in primary total knee and hip arthroplasty.
In countries with social healthcare systems, such as Canada, patients may experience long wait times and a decline in their health status prior to their operation. The aim of this study is to explore the association between long preoperative wait times (WT) and acute hospital length of stay (LoS) for primary arthroplasty of the knee and hip. The study population was obtained from the provincial Patient Access Registry Nova Scotia (PARNS) and the Canadian national hospital Discharge Access Database (DAD). We included primary total knee and hip arthroplasties (TKA, THA) between 2011 and 2017. Patients waiting longer than the recommended 180 days Canadian national standard were compared to patients waiting equal or less than the standard WT. The primary outcome measure was acute LoS postoperatively. Secondarily, patient demographics, comorbidities, and perioperative parameters were correlated with LoS with multivariate regression. A total of 11,833 TKAs and 6,627 THAs were included in the study. Mean WT for TKA was 348 days (1 to 3,605) with mean LoS of 3.6 days (1 to 98). Mean WT for THA was 267 days (1 to 2,015) with mean LoS of 4.0 days (1 to 143). There was a significant increase in mean LoS for TKA waiting longer than 180 days (2.5% (SE 1.1); p = 0.028). There was no significant association for THA. Age, sex, surgical year, admittance from home, rural residence, household income, hospital facility, the need for blood transfusion, and comorbidities were all found to influence LoS. Surgical WT longer than 180 days resulted in increased acute LoS for primary TKA. Meeting a shorter WT target may be cost-saving in a social healthcare system by having shorter LoS. Cite this article: Bone Jt Open 2021;2(8):679-684.


Effect of ionic surfactants on the hydration behavior of triblock copolymer micelles: a solvation dynamics study of coumarin 153.
Dynamic fluorescence Stokes shift measurements of coumarin 153 (C153) have been carried out to study the influence of ionic surfactants (sodium dodecyl sulfate, SDS and hexadecyltrimethylammonium chloride, CTAC) on the hydration behavior of aqueous poly(ethylene oxide)(20)-poly(propylene oxide)(70)-poly(ethylene oxide)20 (P123) block copolymer micelles. Increase in SDS or CTAC concentration at a fixed P123 concentration induces the steady-state emission spectra of C153 to shift gradually toward lower energy. This is attributed to an increase in polarity (due to enhanced hydration) experienced by the probe as a consequence of incorporation of ionic head groups in the Corona region. The observed dynamic fluorescence Stokes shift value decreases more in mixed micellar systems than in pure copolymer micelles and the trends are quite similar in the presence of SDS and CTAC. The spectral shift correlation functions were observed to be nonexponential in nature. Critical analysis of the spectral shift correlation function indicates a fast solvation component (<0.2 ns) in P123 micelles, which was absent in the presence of ionic surfactants. Due to increased hydration in the presence of ionic surfactants, the initial fast solvation event was elusive in mixed copolymer-surfactant systems, reflecting the absence of faster solvation component and reduced observed Stokes shift in mixed systems. It has been argued that in the low surfactant concentration region, increase in hydration with the incorporation of ionic head groups in the Corona region is mainly due to increase in mechanically trapped water content. However, at higher surfactant concentrations, bound water content dominates and leads to slower solvation dynamics. The present results also indicate that though CTAC alters the Corona hydration more efficiently than SDS, the overall influence of ionic surfactants on the Corona hydration is grossly similar irrespective of the cationic or anionic nature of the surfactants. Interaction of SDS and CTAC with poly(ethylene oxide)(100)-poly(propylene oxide)(70)-poly(ethylene oxide)(100) (F127) block copolymer micelles has also been studied to comprehend the effect of copolymer composition. The overall trends in dynamic fluorescence Stokes shift and solvation times are similar in both the copolymer micelles.


A pharmacist-managed clinic for treatment of latent tuberculosis infection in health care workers.
A pharmacist-managed clinic for treating latent tuberculosis infection (LTBI) in health care workers (HCWs) is described. The hospital-based clinic was begun in 1993 after a review showed that only 0.8% of HCWs at the institution who were prescribed isoniazid for LTBI completed it. The goals of the clinic are to improve HCWs' adherence to LTBI treatment, enhance outcomes, and minimize adverse drug reactions. The clinic is staffed by a pharmacist, a medical resident, and a nurse. If an employee is diagnosed with LTBI, he or she is referred to the clinic, where the pharmacist conducts an initial assessment and provides information on medication available for treatment. The worker is then scheduled for monthly follow-up visits with the pharmacist for the first three months of LTBI therapy, during which the pharmacist evaluates treatment adherence and potential adverse effects. Thereafter, the pharmacist interviews the patient monthly by telephone until therapy is complete. HCWs are allowed only a one-month supply of medication with each refill. From June 1993 through June 1997, of 131 employees who started treatment, 122 (93%) completed it. From June 1997 through December 2001, annual therapy completion rates ranged from 90% to 100%. No cases of active tuberculosis have been reported in treated patients, and only nine adverse drug reactions were reported for the 1997-2001 period. A pharmacist-managed clinic substantially improved rates of treatment completion among HCWs with LTBI.


Quantitative analysis of sphingolipids for lipidomics using triple quadrupole and quadrupole linear ion trap mass spectrometers.
Sphingolipids are a highly diverse category of bioactive compounds. This article describes methods that have been validated for the extraction, liquid chromatographic (LC) separation, identification and quantitation of sphingolipids by electrospray ionization, tandem mass spectrometry (ESI-MS/MS) using triple quadrupole (QQQ, API 3000) and quadrupole-linear-ion trap (API 4000 QTrap, operating in QQQ mode) mass spectrometers. Advantages of the QTrap included: greater sensitivity, similar ionization efficiencies for sphingolipids with ceramide versus dihydroceramide backbones, and the ability to identify the ceramide backbone of sphingomyelins using a pseudo-MS3 protocol. Compounds that can be readily quantified using an internal standard cocktail developed by the LIPID MAPS Consortium are: sphingoid bases and sphingoid base 1-phosphates, more complex species such as ceramides, ceramide 1-phosphates, sphingomyelins, mono- and di-hexosylceramides, and these complex sphingolipids with dihydroceramide backbones. With minor modifications, glucosylceramides and galactosylceramides can be distinguished, and more complex species such as sulfatides can also be quantified, when the internal standards are available. LC ESI-MS/MS can be utilized to quantify a large number of structural and signaling sphingolipids using commercially available internal standards. The application of these methods is illustrated with RAW264.7 cells, a mouse macrophage cell line. These methods should be useful for a wide range of focused (sphingo)lipidomic investigations.


M60-like metalloprotease domain of the Escherichia coli YghJ protein forms amyloid fibrils.
Amyloids are protein fibrils with a characteristic spatial structure. Amyloids were long perceived as the pathogens involved in a set of lethal diseases in humans and animals. In recent decades, it has become clear that amyloids represent a quaternary protein structure that is not only pathological but also functionally important and is widely used by different organisms, ranging from archaea to animals, to implement diverse biological functions. The greatest biological variety of amyloids is found in prokaryotes, where they control the formation of biofilms and cell wall sheaths, facilitate the overcoming of surface tension, and regulate the metabolism of toxins. Several amyloid proteins were identified in the important model, biotechnological and pathogenic bacterium Escherichia coli. In previous studies, using a method for the proteomic screening and identification of amyloids, we identified 61 potentially amyloidogenic proteins in the proteome of E. coli. Among these proteins, YghJ was the most enriched with bioinformatically predicted amyloidogenic regions. YghJ is a lipoprotein with a zinc metalloprotease M60-like domain that is involved in mucin degradation in the intestine as well as in proinflammatory responses. In this study, we analyzed the amyloid properties of the YghJ M60-like domain and demonstrated that it forms amyloid-like fibrils in vitro and in vivo.


Cross-linked compared with historical polyethylene in THA: an 8-year clinical study.
Wear particle-induced osteolysis is a major cause of aseptic loosening in THA. Increasing wear resistance of polyethylene (PE) occurs by increasing the cross-link density and early reports document low wear rates with such implants. To confirm longer-term reductions in wear we compared cross-linked polyethylene (irradiation in nitrogen, annealing) with historical polyethylene (irradiation in air) in a prospective, randomized clinical study involving 48 patients who underwent THAs with a minimum followup of 7 years (mean, 8 years; range, 7-9 years). The insert material was the only variable. The Harris hip score, radiographic signs of osteolysis, and polyethylene wear were recorded annually. Twenty-three historical and 17 moderately cross-linked polyethylene inserts were analyzed (five patients died, three were lost to followup). At 8 years, the wear rate was lower for cross-linked polyethylene (0.088 +/- 0.03 mm/year) than for the historical polyethylene (0.142 +/- 0.07 mm/year). This reduction (38%) did not diminish with time (33% at 5 years). Acetabular cyst formation was less frequent (39% versus 12%), affected fewer DeLee and Charnley zones (17% versus 4%), and was less severe for the cross-linked polyethylene. The only revision was for an aseptically loose cup in the historical polyethylene group. Moderately cross-linked polyethylene maintained its wear advantage with time and produced less osteolysis, showing no signs of aging at mid-term followup. Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Dose response and time course of alterations in tryptophan metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the most TCDD-susceptible and the most TCDD-resistant rat strain: relationship with TCDD lethality.
It has previously been shown that an increase in plasma free tryptophan and a consequent increase in brain serotonin (5-HT) metabolism may be associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) lethality. In the present study we have studied the dose-response and time course relationships of these phenomena in the most TCDD-susceptible Long-Evans (Turku AB [L-E]; LD50 ca. 10 micrograms/kg) and the most TCDD-resistant Han/Wistar (Kuopio [H/W], LD50 > 7200 micrograms/kg) rat strains. Six days after exposure, there was a dose-related increase in brain 5-HT turnover and plasma free tryptophan in both male and female L-E rats. Pair-fed control rats did not exhibit changes in these parameters. The increases emerged in the dose range known to elicit lethality in L-E rats. Furthermore, the increases in plasma free tryptophan correlated well with the changes in body weight caused by TCDD. In contrast, in H/W rats no such increases in brain 5-HT metabolism or plasma free tryptophan were discernible. Similarly, body weight changes were minor in H/W rats despite almost 1000-fold greater doses of TCDD. Large neutral amino acids other than tryptophan were not markedly changed in the plasma of either rat strain. In attempts to identify the mechanism by which TCDD might affect tryptophan binding to albumin, some other physiological factors known to be carried by albumin were determined. Nonesterified fatty acids (NEFA) in the plasma were dose dependently elevated in male and female L-E rats and there was a moderate or good correlation (r = 0.654 for male and r = 0.731 for female rats) between this parameter and plasma free tryptophan. A moderate increase in plasma NEFA was also seen in pair-fed control rats. Bilirubin was dose dependently increased in the plasma of female L-E rats and there was a good correlation between plasma free tryptophan and total (r = 0.779) or conjugated (r = 0.825) bilirubin. The concentration of albumin tended to be suppressed in female L-E rats. The main tryptophan metabolizing enzyme, hepatic tryptophan pyrrolase, was inhibited in female L-E rats but not in male L-E rats or H/W rats of either gender. Moreover, in female L-E rats the time course for changes in plasma free tryptophan and in body weight was remarkably similar, with both effects emerging early (1 or 2 days) after TCDD exposure and showing progressive development thereafter until the last time point of 10 days.(ABSTRACT TRUNCATED AT 400 WORDS)


[Masked hypertension during pregnancy].
Hypertension during pregnancy is one of the leading causes of maternal and foetal morbidity and mortality. Monitoring of blood pressure is therefore an essential part of prenatal care. Masked hypertension, where blood pressure levels are elevated at home despite normal blood pressure levels monitored in a clinical setting, may lead to cardiovascular and obstetric complications equal to those of sustained hypertension. This article discusses masked hypertension and the need for further investigation of blood pressure monitoring during pregnancy.


Suicide by fire in a car trunk: a case with potential pitfalls.
We present an unusual case in which an adult female committed suicide by fire while enclosed in the trunk of her vehicle. A finding of suicide was reached only because several key investigative facts were uncovered. Without these discoveries the case may still remain open as a suspicious death. Fire is rarely used as a mechanism of suicide in Western culture, and, as such, similar cases should be reported to advance our recognition of this phenomenon.


A simplified method to develop optimal gingival contours for the single implant-supported, metal-ceramic crown in the aesthetic zone.
Prosthetic replacement of the missing single maxillary central incisor with an implant-supported crown represents a profound aesthetic challenge for the restorative dentist, laboratory technician, and surgeon. In addition to the visual fidelity of color, translucency, contour, and surface texture, the proper soft tissue outline is sacrosanct to the illusion of a natural tooth. The contrast between the uniformly round shoulder of the implant and the tooth's curvilinear cementoenamel junction is particularly problematic. This clinical report demonstrates a simplified method that precisely controls the facial gingival and proximal soft tissue contours for implant-supported, metal-ceramic crowns in the aesthetic zone, using the cervical anatomy of the maxillary incisor tooth as a guide. A new role for the provisional crown that is intended to maximize the volume of keratinized tissue is also described.


Enantioselective N-heterocyclic carbene-catalyzed β-hydroxylation of enals using nitroarenes: an atom transfer reaction that proceeds via single electron transfer.
A novel oxidative N-heterocyclic carbene-catalyzed reaction pathway has been discovered. Alkyl and aryl enals undergo β-hydroxylation via oxygen atom transfer from electron-deficient nitrobenzenes, followed by trapping of the resultant acyl azolium by the solvent. The proposed mechanism involves a single electron transfer event to initiate the reaction followed by radical recombination. This represents a profound mechanistic departure from the established two-electron disconnects in NHC catalysis.


A Review of Proposed Mechanisms in Rheumatoid Arthritis and Therapeutic Strategies for the Disease.
Rheumatoid arthritis (RA) is characterized by synovial edema, inflammation, bone and cartilage loss, and joint degradation. Patients experience swelling, stiffness, pain, limited joint movement, and decreased mobility as the condition worsens. RA treatment regimens often come with various side effects, including an increased risk of developing cancer and organ failure, potentially leading to mortality. However, researchers have proposed mechanistic hy-potheses to explain the underlying causes of synovitis and joint damage in RA patients. This review article focuses on the role of synoviocytes and synoviocytes resembling fibroblasts in the RA synovium. Additionally, it explores the involvement of epigenetic regulatory systems, such as microRNA pathways, silent information regulator 1 (SIRT1), Peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α), and protein phosphatase 1A (PPM1A)/high mobility group box 1 (HMGB1) regulators. These mechanisms are believed to modulate the function of receptors, cytokines, and growth factors associated with RA. The review article includes data from preclinical and clinical trials that provide insights into potential treatment options for RA.


Elastic properties of functionalized carbon nanotubes.
We study the effects of covalent functionalization of single wall carbon nanotubes (CNT) on their elastic properties. We consider simple organic molecules -NH, -NH2, -CH2, -CH3, -OH attached to CNTs' surface at various densities. The studies are based on the first principles calculations in the framework of density functional theory. We have determined the changes in the geometry and the elastic moduli of the functionalized CNTs as a function of the density of adsorbed molecules. It turns out that elastic moduli diminish with increasing concentration of adsorbents, however, the functionalized CNTs remain strong enough to be suitable for reinforcement of composites. The strongest effect is observed for CNTs functionalized with -CH2 radical, where the Young's modulus of the functionalized system is 30% smaller than in the pristine CNTs.


Slow vibrations in transport through molecules.
We show how one can measure the signal from slow jumps of a single molecule between metastable positions using a setup where the molecule is fixed to one lead and one of the coupling strengths is controlled externally. Such a measurement yields information about slow processes deforming the molecule in times much longer than the characteristic time scales for the electron transport process.


HIV seroprevalence in emergency department patients: Lagos University Teaching Hospital, Lagos, 1999.
The emergency department patients represent a cross-section of the entire population and values of HIV seroprevalence in them have been used to assess the general trends of HIV surveillance in other countries. The objectives of this study is to determine 1. Whether seroprevalence of HIV antibodies in patients attending emergency departments could serve as a marker of prevalence of HIV antibody in the general population. 2. The degree of clinical suspicion or knowledge of the medical personnel to the status o the HIV seropositive patients is also evaluated. A total of 312 emergency department patients of Lagos University Teaching Hospital (LUTH) had their blood samples screened for antibodies against Human Immunodeficiency Virus (HIV) types I and II by ELISA based techniques: Immunocomb II HIV I & II Bispot Kits. Repeatedly reactive samples were confirmed by another ELISA based technique using Immunocomb I & II Combfirm kits. The attending medical doctor was asked whether there was any suspicion or knowledge that the patient being attended to, was HIV seropositive. The seroprevalence of HIV antibodies was 5.77% with no significant difference in sex incidence. The age groups 20-29 and 30-39 years were most affected. The seropositive nature of affected patients was unsuspected by medical personnel in 55.56% of the HIV antibodies seropositive patients. The Federal Ministry of Health in 2000, estimated the National prevalence rate of HIV to have been 5.4% in 1998. This figure is comparable to that obtained in this study and revalidates the fact that emergency department patients may be used for disease surveillance in the population. The seropositive status of majority of the HIV positive patients was unsuspected by the attending medical personnel. Thus, strict adherence to universal safety precautions is essential for all medical personnel. Post exposure prophylaxis should be made readily accessible to all medical personnel.


Entecavir monotherapy for lamivudine-refractory chronic hepatitis B.
EVALUATION OF: Sherman M, Yurdaidin C, Simsek H et al. Entecavir therapy for lamivudine-refractory chronic hepatitis B: improved virologic, biochemical and serology outcomes through 96 weeks. Hepatology 48, 99-108 (2008). This article evaluates the efficacy, safety and resistance profile of entecavir treatment in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B lamivudine-refractory patients. A total of 286 patients were randomized and treated with entecavir 1 mg (n = 141) or continued lamivudine 100 mg (n = 145). At week 52, 77 entecavir-treated patients with a protocol-defined virologic response continued blinded therapy for up to 96 weeks. Cumulative proportions of all treated patients who achieved confirmed efficacy end points were also analyzed. It was shown that with 2 years of treatment, 30% of all entecavir-treated patients achieved HBV DNA of less than 300 copies/ml by PCR and 85% had alanine aminotransferase normalization (vs 1 and 29% of lamivudine-treated patients; p < 0.0001). HBeAg seroconversion was achieved by 17% of all entecavir-treated patients (24 out of 141) versus 6% of all lamivudine-treated patients (8 out of 1450; p < 0.0011) and was sustained in 11 patients (7.8%) 6 months after treatment discontinuation. However, entecavir treatment was associated with an increasing rate of drug resistance. Therefore, entecavir monotherapy does not appear to be the treatment of choice for lamivudine-refractory HBV patients and either a combination of potent antivirals with nonoverlapping resistance patterns or the use of newer nucleotides as monotherapy (e.g., tenofovir) could be helpful in the management of this difficult population.


Phosphorus acquisition strategy of Vallisneria natans in sediment based on in situ imaging techniques.
Phosphorus (P) availability is closely related to the distributions of pH, O2 and phosphatase activities in the rhizosphere of plants growing in soils and sediments. In this study, the P uptake processes and mechanisms of Vallisneria natans (V. natans) during two vegetation periods (i.e., week three and six) were revealed using three noninvasive 2D imaging techniques: planar optode (PO), diffusive gradients in thin films (DGT) and zymography. The results showed that increased phosphatase activity, O2 concentration and root-induced acidification were observed together in the rhizosphere of root segments and tips. In week three, when V. natans was young, the flux of DGT-labile P accumulated more in the rhizosphere in comparison with the bulk sediment. This was because increased phosphatase activity (of up to 35%) and root-induced acidification (with pH decreasing by up to 0.25) enhanced P acquisition of V. natans by the third week. However, the flux of DGT-labile P turned to depletion during weeks three to six of V. natans growth, after Fe plaque formed at the matured stage. The constant hydrolysis of phosphatase and acidification could not compensate for the P demand of the roots by the sixth week. At this stage, Fe plaque become the P pool, due to P fixation with solid Fe(III) hydroxides. Subsequently, V. natans roots acquired P from Fe plaque via organic acid complexation of Fe(III).


Bone volume, mineral density, and fracture risk after kidney transplantation.
Disordered mineral metabolism reverses incompletely after kidney transplantation in numerous patients. Post-transplantation bone disease is a combination of pre-existing chronic kidney disease and mineral disorder and often evolving osteoporosis. These two frequently overlapping conditions increase the risk of post-transplantation fractures. We studied the prevalence of low bone volume in bone biopsies obtained from kidney transplant recipients who were biopsied primarily due to the clinical suspicion of persistent hyperparathyroidism between 2000 and 2015 at the Hospital District of Helsinki and Uusimaa. Parameters of mineral metabolism, results of dual-energy x-ray absorptiometry scans, and the history of fractures were obtained concurrently. One hundred nine bone biopsies taken at a median of 31 (interquartile range, IQR, 18-70) months after transplantation were included in statistical analysis. Bone turnover was classified as high in 78 (72%) and normal/low in 31 (28%) patients. The prevalence of low bone volume (n = 47, 43%) was higher among patients with low/normal turnover compared to patients with high turnover [18 (58%) vs. 29 (37%), P = 0.05]. Thirty-seven fragility fractures in 23 (21%) transplant recipients corresponding to fracture incidence 15 per 1000 person-years occurred during a median follow-up 9.1 (IQR, 6.3-12.1) years. Trabecular bone volume did not correlate with incident fractures. Accordingly, low bone mineral density at the lumbar spine correlated with low trabecular bone volume, but not with incident fractures. The cumulative corticosteroid dose was an important determinant of low bone volume, but not of incident fractures. Despite the high prevalence of trabecular bone loss among kidney transplant recipients, the number of fractures was limited. The lack of association between trabecular bone volume and fractures suggests that the bone cortical compartment and quality are important determinants of bone strength and post-transplantation fracture.


Differences of plasma IL-1 and TNF-α in healthy Chinese Population.
Pleiotropic proinflammatory cytokines, interleukin- 1 (IL-1) and tumor necrosis factor-α (TNF-α), involved in the regulations of various immune responses, inflammatory processes and hematopoiesis. In the present study, the expression levels of IL-1 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). Following the cytokine blockade as a successful clinical therapy for autoimmune diseases such as rheumatoid arthritis, the patients are more susceptible to a variety of opportunistic infections. IL-1 and TNF-α may be useful predictive biomarkers of diseases and offer potential targets for therapeutic intervention of inflammatory diseases. However, our results showed that the plasma IL-1 level was significantly higher in women compared to men (69.5 ± 19.8 pg/ml in men and 80.1 ± 19.5 pg/ml in women, respectively); the plasma levels of TNF-α were higher in men than women (20.8 ± 4.9 pg/ml and 18.7 ± 7.1 pg/ml, respectively). The significant gender difference of plasma interleukin-1 (IL-1) and TNF-α levels present in healthy adults in Jiangsu Province, China (P=0.002 and P=0.015, respectively), and may be as a hint for sex differences of susceptibility to many diseases and elementary immune response.


Internalization of atrial natriuretic factor by AtT-20 corticotropin-secreting cells.
Because extended exposure of AtT-20 corticotropin-secreting cells to atrial natriuretic factor (ANF) results in a desensitization of ANF-induced cGMP synthesis, we sought to establish whether pretreatment of AtT-20 cells with the atrial peptide also led to an internalization process. In fact, by coupling an ultrastructural approach to cryoultramicrotomy, ANF-immunoreactivity was detected at both the plasma membrane level and at intracellular sites in AtT-20 cells. Internalization was observed within 5 min at which time labelling was observed in the plasma membrane level, in vacuole-like structures in close proximity to the plasma membrane, in cytoplasmic matrix and sometimes in mitochondria. After 30 min exposure Golgi apparatus, mitochondria and nuclear euchromatin were also labelled. Following 1-4 hr, labelling in other cell compartments, e.g. lysosomal, was increased, while it was reduced in plasma membranes and vacuole-like structures. Secretory granules and endoplasmic reticulum were not labelled throughout the time course. Extraction of a intracellular [125I] ANF from AtT-20 cells following 4 hr incubation suggested that about 90% of the peptide was intact. The data suggest that internalization of ANF may serve to terminate the biological response associated with ANF receptor activation; subcellular distribution of internalized, intact ANF suggests that the peptide may have other, as yet unidentified, intracellular actions.


Salvage chemoradiotherapy with cisplatin and vinorelbine for postoperative locoregional recurrence of non-small cell lung cancer.
Although a few investigators have demonstrated the effect of concurrent chemoradiotherapy (CRT) for postoperative recurrent non-small cell lung cancer (NSCLC), the outcome of this treatment remains unclear. The aim of this study was to elucidate the efficacy and tolerability of concurrent CRT with cisplatin (CDDP) and vinorelbine (VNR) in patients with postoperative locoregional recurrent NSCLC. A total of 40 patients who had received concurrent CRT with CDDP and VNR between January 1999 and December 2014 were retrospectively analyzed. Patients were treated with CDDP (80 mg/m on day 1) and VNR (20 mg/m on days 1 and 8) every 4 weeks. Radiotherapy was administered concurrently during cycle 1. The delivered x-ray radiation dose was 60 Gy in all 37 patients who received x-ray radiotherapy; 3 patients received proton beam radiation (66 Gy [RBE] in 1 patient and 60 Gy [RBE] in 2 patients). The objective response rate was 85% (95% confidence interval [CI], 70.9%-92.9%). The median progression-free survival was 20.3 months (95% CI, 12.9 months-not reached). The 2-year survival rate was 78.9% (95% CI, 63.0%-89.1%). The most common grade ≥3 toxicity was neutropenia (18%). No grade ≥3 radiation pneumonitis and no treatment-related deaths were observed.Our study revealed that concurrent CRT with CDDP and VNR was active and safe for patients with postoperative locoregional recurrent NSCLC. Salvage CRT for postoperative locoregional recurrent NSCLC might be a promising treatment for selected patients.


Membrane proteins of arterivirus particles: structure, topology, processing and function.
Arteriviruses, such as equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV), are important pathogens in veterinary medicine. Despite their limited genome size, arterivirus particles contain a multitude of membrane proteins, the Gp5/M and the Gp2/3/4 complex, the small and hydrophobic E protein and the ORF5a protein. Their function during virus entry and budding is understood only incompletely. We summarize current knowledge of their primary structure, membrane topology, (co-translational) processing and intracellular targeting to membranes of the exocytic pathway, which are the budding site. We profoundly describe experimental data that led to widely believed conceptions about the function of these proteins and also report new results about processing steps for each glycoprotein. Further, we depict the location and characteristics of epitopes in the membrane proteins since the late appearance of neutralizing antibodies may lead to persistence, a characteristic hallmark of arterivirus infection. Some molecular features of the arteriviral proteins are rare or even unique from a cell biological point of view, particularly the prevention of signal peptide cleavage by co-translational glycosylation, discovered in EAV-Gp3, and the efficient use of overlapping sequons for glycosylation. This article reviews the molecular mechanisms of these cellular processes. Based on this, we present hypotheses on the structure and variability of arteriviral membrane proteins and their role during virus entry and budding.


Effects of an aerobic fitness test on short- and long-term memory in elementary-aged children.
Meta-analytic evidence supports that exercise has benefits for short-term memory (STM) and long-term memory (LTM). However, only three studies with children have tested the differential effects of exercise on STM and LTM. The purpose of this study was to examine the effects of an aerobic fitness test on STM and LTM and to consider the moderating effects of grade level. Children (7-13 years of age) were randomly assigned to either perform an aerobic fitness test before (exercise prior) or after (exercise post) performing the Rey Auditory Verbal Learning Test (RAVLT) to assess memory. Memory was tested again after approximately 24 hours. There were significant differences in memory performance as a function of grade with 4th and 6th graders consistently outperforming 2nd graders. For learning, Day 1 Retention, 24-hr recall, and Day 2 Retention, the exercise prior group performed better than the exercise post group. It is concluded that an aerobic fitness test performed prior to a declarative memory test benefits LTM as compared to when the aerobic fitness test is performed after the memory test.


Differential collagenolytic activity of Candida albicans isolated from oral mucosa and dentinal carious lesions of HIV-infected children.
The aim of this study was to compare type I collagen degradation by Candida albicans isolated from oral mucosa (M) and cavitated active dentinal caries (CAD) of HIV-infected children. To verify the proteolytic activity, the specimens were cultivated in brain-heart infusion medium and the supernatants were incubated in the presence or absence of type I collagen at 37°C for 12 hours and analyzed using 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Intensity of the bands on the gels was assessed by densitometric analysis using a scanner and images analyzed with software from Kodak Digital Science EDAS 120. Supernatants of all the C. albicans degraded type I collagen: that from M, on average, by 38.3% (SD 21.67) and that from CAD by 54% (SD 25.94; Wilcoxon test: P < .05). Predisposing factors had no association with the percentage of type I collagen degradation (Mann-Whitney test: P > .05). Candida albicans from different sites of the oral cavity of HIV-infected children has proteolytic activity for type I collagen.


Disordered biopyriboles, amphibole, and talc in the Allende meteorite: products of nebular or parent body aqueous alteration?
Transmission electron microscope observations of the Allende carbonaceous chondrite provided evidence of widespread hydrous phases replacing enstatite in chondrules. Calcic amphibole and talc occur in thin (less than 0.3 micrometer) crosscutting veins and as alteration products of primary chondrule glass in contraction cracks within the enstatite. In addition, talc and disordered biopyriboles were found replacing enstatite grains along cracks and fractures. Although rare hydrous phases have been reported in calcium- and aluminum-rich inclusions in the Allende meteorite, these observations suggest that aqueous fluids played a much more significant role in the mineralogical and geochemical evolution of Allende than has previously been thought.


Factors influencing knowledge, attitudes, and compliance of hypertensive patients.
Using a factorial design, four aspects of an educational program for 160 hypertensive patients were manipulated: number of meetings, patient responsibility and participation, directiveness of the intervention, and emphasis on negative consequences of uncontrolled hypertension. Validity checks on the manipulations included content analysis of the nurse-patient interaction and interview-based measures of the patient's responsibility, participation, and awareness of dangers. Outcome variables included repeated measures of patient knowledge, assessment by the nurse of patient attainment of identified goals, and reduction of the patient's mean arterial blood pressure. High indirect interventions tended to lead to higher goal attainment, particularly in the psychosocial area. Emphasis on negative consequences tended to promote learning for patients with long standing diagnoses, but to retard learning for recently diagnosed patients. Additional meetings and emphasis on patient responsibility were not helpful alone, but in combination they tended to lead to greater learning. Although as a whole, patients in the program tended to reduce their blood pressures, there were no statistically significant main effects or interaction effects of the educational approach variables on blood pressure reduction.


Managing hypertension among veterans in an outpatient screening program.
This report describes the outcomes of a hypertension screening and management program in an outpatient clinic for veterans (pharmacologic/nonpharmacologic subjects, N = 207) located in the Southeastern United States using a retrospective descriptive research approach. Health care was provided in the clinic by nurse practitioners and physicians in conjunction with classes that emphasize lifestyle changes. Weight was a major risk factor on admission and at subsequent visits. Quetelet Index values indicated pharmacologic patients were significantly more overweight (> 30% over ideal weight) than nonpharmacologic patients (> 20% over ideal weight). Significant reductions in blood pressure were obtained for both groups between admission readings and readings taken at 12 and 24 months (p = .0001). No significant differences in blood pressure were noted between the nonpharmacologic and pharmacologic groups. Reported lifestyle behavior changes incorporating exercise from first to last visit were more significant for the nonpharmacologic group; however, this group also reported increased alcohol consumption during this time. The pharmacologic group reported overall beneficial improvement in both exercise and decreased use of alcohol. The nonpharmacologic group on average required fewer clinic visits. Interventions targeted toward lifestyle behaviors, a common element in the treatment plans for both groups, appear to have therapeutic benefit.


[Treatment of depression in the elderly].
Depression is the most common mental health problem of later life. There is effective treatments for depression in primary care. Recommendation based on current evidence are: in primary care treatment there is no evidence that one class of antidepressant is anymore effective than others; although newer antidepressants are not more effective than older ones, they are better tolerated in healthy older people and in patients with medical co-morbidity and are safer especially in overdose. Lower dose antidepressant treatment is not recommended for older depressed patients.


Using mobile & personal sensing technologies to support health behavior change in everyday life: lessons learned.
Lifestyle modification is a key facet of the prevention and management of chronic diseases. Mobile devices that people already carry provide a promising platform for facilitating these lifestyle changes. This paper describes key lessons learned from the development and evaluation of two mobile systems for encouraging physical activity. We argue that by supporting persistent cognitive activation of health goals, encouraging an extensive range of relevant healthy behaviors, focusing on long-term patterns of activity, and facilitating social support as an optional but not primary motivator, systems can be developed that effectively motivate behavior change and provide support when and where people make decisions that affect their health.


TGF-beta's delay skeletal muscle progenitor cell differentiation in an isoform-independent manner.
Satellite cells are a quiescent heterogeneous population of mononuclear stem and progenitor cells which, once activated, differentiate into myotubes and facilitate skeletal muscle repair or growth. The Transforming Growth Factor-beta (TGF-beta) superfamily members are elevated post-injury and their importance in the regulation of myogenesis and wound healing has been demonstrated both in vitro and in vivo. Most studies suggest a negative role for TGF-beta on satellite cell differentiation. However, none have compared the effect of these three isoforms on myogenesis in vitro. This is despite known isoform-specific effects of TGF-beta1, -beta2 and -beta3 on wound repair in other tissues. In the current study we compared the effect of TGF-beta1, -beta2 and -beta3 on proliferation and differentiation of the C2C12 myoblast cell-line. We found that, irrespective of the isoform, TGF-beta increased proliferation of C2C12 cells by changing the cellular localisation of PCNA to promote cell division and prevent cell cycle exit. Concomitantly, TGF-beta1, -beta2 and -beta3 delayed myogenic commitment by increasing MyoD degradation and decreasing myogenin expression. Terminal differentiation, as measured by a decrease in myosin heavy chain (MHC) expression, was also delayed. These results demonstrate that TGF-beta promotes proliferation and delays differentiation of C2C12 myoblasts in an isoform-independent manner.


Neuroprotection and antioxidants.
Ischemia as a serious neurodegenerative disorder causes together with reperfusion injury many changes in nervous tissue. Most of the neuronal damage is caused by complex of biochemical reactions and substantial processes, such as protein agregation, reactions of free radicals, insufficient blood supply, glutamate excitotoxicity, and oxidative stress. The result of these processes can be apoptotic or necrotic cell death and it can lead to an irreversible damage. Therefore, neuroprotection and prevention of the neurodegeneration are highly important topics to study. There are several approaches to prevent the ischemic damage. Use of many modern therapeutical methods and the incorporation of several substances into the diet of patients is possible to stimulate the endogenous protective mechanisms and improve the life quality.


A Severe, Refractory Case of Mucous Membrane Pemphigoid After Treatment With Pembrolizumab: Brief Communication.
Pembrolizumab is a humanized antibody that targets the programmed death-1 receptor expressed in T cells with high selectivity. This therapeutic is of great importance in cancer immunotherapy yet managing the potential immune-related adverse events remains a concern. Here, we report a rare case of mucous membrane pemphigoid in the oral mucosa, upper respiratory tract, and conjunctiva of a patient with ovarian adenocarcinoma without cutaneous manifestation, which persisted even after pembrolizumab discontinuation. A brief review of pembrolizumab-related bullous pemphigoid cases is presented and possible mechanisms underlying these lesions are discussed.


Migration of mineral hydrocarbons into foods. 5. Miscellaneous applications of mineral hydrocarbons in food contact materials.
Polystyrene and acrylonitrile/butadiene/styrenes (ABS) containers for individual serving portions (80 samples of milk, cream, butter, margarine and spreads) used in the catering industry were found to contain 1-4% mineral oil. Levels of mineral oil migrating into the foods were generally low (< 5-15 mg/kg) except in one instance where levels of 45-85 mg/kg were detected in a low fat spread, and this was attributed to mineral hydrocarbon transfer from an adhesive used in the lidding. Analysis of wine bottle corks (105 samples from 11 different countries) indicated that 50% had been treated with mineral wax or mineral oil, although in all cases mineral hydrocarbon contamination of the wine was < 0.2 mg/l. Waxed paper discs sold for home-use for covering the surface of jams and preserves were found to be coated with 100 mg/dm2 of mineral hydrocarbons. However, in experiments with a variety of jams and preserves levels of migration were not significant, ranging from 0.15 to 1.2 mg/kg.


Discovery and Characterisation of Highly Cooperative FAK-Degrading PROTACs.
Focal adhesion kinase (FAK) is a key mediator of tumour progression and metastasis. To date, clinical trials of FAK inhibitors have reported disappointing efficacy for oncology indications. We report the design and characterisation of GSK215, a potent, selective, FAK-degrading Proteolysis Targeting Chimera (PROTAC) based on a binder for the VHL E3 ligase and the known FAK inhibitor VS-4718. X-ray crystallography revealed the molecular basis of the highly cooperative FAK-GSK215-VHL ternary complex, and GSK215 showed differentiated in-vitro pharmacology compared to VS-4718. In mice, a single dose of GSK215 induced rapid and prolonged FAK degradation, giving a long-lasting effect on FAK levels (≈96 h) and a marked PK/PD disconnect. This tool PROTAC molecule is expected to be useful for the study of FAK-degradation biology in vivo, and our results indicate that FAK degradation may be a differentiated clinical strategy versus FAK inhibition for the treatment of cancer.


The Abl and Arg kinases mediate distinct modes of phagocytosis and are required for maximal Leishmania infection.
Leishmania, an obligate intracellular parasite, binds several receptors to trigger engulfment by phagocytes, leading to cutaneous or visceral disease. These receptors include complement receptor 3 (CR3), used by promastigotes, and the Fc receptor (FcR), used by amastigotes. The mechanisms mediating uptake are not well understood. Here we show that Abl family kinases mediate both phagocytosis and the uptake of Leishmania amazonensis by macrophages (Ms). Imatinib, an Abl/Arg kinase inhibitor, decreases opsonized polystyrene bead phagocytosis and Leishmania uptake. Interestingly, phagocytosis of IgG-coated beads is decreased in Arg-deficient Ms, while that of C3bi-coated beads is unaffected. Conversely, uptake of C3bi-coated beads is decreased in Abl-deficient Ms, but that of IgG-coated beads is unaffected. Consistent with these results, Abl-deficient Ms are inefficient at C3bi-opsonized promastigote uptake, and Arg-deficient Ms are defective in IgG1-opsonized amastigote uptake. Finally, genetic loss of Abl or Arg reduces infection severity in murine cutaneous leishmaniasis, and imatinib treatment results in smaller lesions with fewer parasites than in controls. Our studies are the first to demonstrate that efficient phagocytosis and maximal Leishmania infection require Abl family kinases. These results highlight Abl family kinase-mediated signaling pathways as potential therapeutic targets for leishmaniasis.


Chemical Characterization, Antileishmanial Activity, and Cytotoxicity Effects of the Essential Oil from Leaves of Pluchea carolinensis (Jacq.) G. Don. (Asteraceae).
Current strategies to control leishmaniasis are mainly based on chemotherapy. However, none of the available drugs can be considered to be ideal to treat this disease. Because of the hydrophobic nature and bioactivities of their components, essential oils (EOs) can be considered as important sources for developing agents against intracellular pathogens, such as Leishmania parasites. In this study, we report the chemical characterization, antileishmanial activities, and cytotoxicity effect of the EO from Pluchea carolinensis (Jacq.) G. Don. (Asteraceae). Chemical analysis revealed that EO from aerial part from P. carolinensis is composed of 44 compounds. The main component was selin-11-en-4α-ol, which made up 51.0%. In vitro antileishmanial studies showed that P. carolinensis EO inhibited the growth of promastigotes (IC50 = 24.7 ± 7.1 μg/mL) and amastigotes (IC50 = 6.2 ± 0.1 μg/mL) of Leishmania amazonensis, while cytotoxicity evaluation revealed fivefold higher values than those for the parasites. In a model of experimental cutaneous leishmaniasis in BALB/c mice, five doses of EO at 30 mg/kg by intralesional route demonstrated smaller lesion size and parasite burden (p < 0.05) compared with animals treated with Glucantime® and untreated mice. In conclusion, in vitro and in vivo results showed the potentialities of EO from P. carolinensis with the future possibility of a new alternative in the treatment for leishmaniasis. Copyright © 2017 John Wiley & Sons, Ltd.


Arthropod Deterrents from Artemisia pallens (Davana Oil) Components.
Davanone, a key sesquiterpene component of davana oil, has been synthesized in five convenient steps. Oxygenated sesquiterpenes have been linked to insect deterrent properties. Based on initial screening of davana oil, davanone and its hydroxy precursors have been generated and are being evaluated as arthropod deterrents against disease vectors.


Incidence, Risk Factors, and Outcome of Acute Kidney Injury in Neurocritical Care.
Acute kidney injury (AKI) is a severe complication in medical and surgical intensive care units accounting for a high morbidity and mortality. Incidence, risk factors, and prognostic impact of this deleterious condition are well established in this setting. Data concerning the neurocritically ill patients is scarce. Therefore, aim of this study was to determine the incidence of AKI and elucidate risk factors in this special population. Patients admitted to a specialized neurocritical care unit between 2005 and 2011 with a length of stay above 48 hours were analyzed retrospectively for incidence, cause, and outcome of AKI (AKI Network-stage ≥2). The study population comprised 681 neurocritically ill patients from a mixed neurosurgical and neurological intensive care unit. The prevalence of chronic kidney disease (CKD) was 8.4% (57/681). Overall incidence of AKI was 11.6% with 36 (45.6%) patients developing dialysis-requiring AKI. Sepsis was the main cause of AKI in nearly 50% of patients. Acute kidney injury and renal replacement therapy are independent predictors of worse outcome (hazard ratio [HR]: 3.704; 95% confidence interval [CI]: 1.867-7.350; P < .001; and HR: 2.848; CI: 1.301-6.325; P = .009). Chronic kidney disease was the strongest independent risk factor (odds ratio: 12.473; CI: 5.944-26.172; P < .001), whereas surgical intervention or contrast agents were not associated with AKI. Acute kidney injury in neurocritical care has a high incidence and is a crucial risk factor for mortality independently of the underlying neurocritical condition. Sepsis is the main cause of AKI in this setting. Therefore, careful prevention of infectious complications and considering CKD in treatment decisions may lower the incidence of AKI and hereby improve outcome in neurocritical care.


Clinical and Microbiological Profile of HIV/AIDS Cases with Diarrhea in North India.
Intestinal infections are a significant cause of morbidity and mortality in people living with HIV/AIDS (PLWHA) especially in developing countries. The present study was conducted to assess the clinical and microbiological spectrum in HIV/AIDS cases with diarrhea and to correlate the occurrence of such pathogens with stool characters, HIV seropositivity status, and CD4 counts. Stools from 154 HIV seropositive subjects and 50 HIV negative controls were examined by direct microscopy, fecal cultures, and serological tests (Clostridium difficile Toxin A, Cryptosporidium antigen, and Entamoeba histolytica antigen ELISA). CD4 T cell enumeration was done using FACS count (Becton Dickinson). The study showed a male preponderance (112 males and 42 females). Weakness, abdominal pain, and anorexia were the most common symptoms. Coccidian parasites were the most common cause of diarrhea in HIV seropositive cases. C. parvum was seen in 60.42% while Isospora belli in 9.03%. Amongst the bacterial pathogens C. difficile was detected in 18.06%, diarrheagenic Escherichia coli in 11.11%, and Shigella spp. in 2.78%. Pathogen isolation rates were more in HIV seropositive cases and subjects with low CD4 T lymphocyte counts. Regular monitoring of CD4 T lymphocyte counts and screening for enteric pathogens will help improve the quality of life for PLWHA.


Infrared spectroscopy of tunable Dirac terahertz magneto-plasmons in graphene.
We present infrared spectroscopy study of plasmon excitations in graphene in high magnetic fields. The plasmon resonance in patterned graphene disks splits into edge and bulk plasmon modes in magnetic fields. Remarkably, the edge plasmons develop increasingly longer lifetimes in high fields due to the suppression of backscattering. Moreover, due to the linear band structure of graphene, the splitting of the edge and bulk plasmon modes develops a strong doping dependence, which differs from the behavior of conventional semiconductor two-dimensional electron gas (2DEG) systems. We also observe the appearance of a higher order mode indicating an anharmonic confinement potential even in these well-defined circular disks. Our work not only opens an avenue for the investigation of the properties of Dirac magnetoplasmons but also supports the great potential of graphene for tunable terahertz magneto-optical devices.


[Echographic, MRI and CT features in a case of bladder endometriosis].
Endometriosis is relatively frequent in females of menstrual age and consists in the appearance of active endometrial tissue at site other than uterine cavity. Endometrial tissue has been described to colonise the urinary system, particularly the urinary bladder. The most common clinical features of vesical endometriosis are urgency and frequency, hypogastric pain and hematuria. We report on a case of vesical endometriosis whose presenting features were dysmenorrhea, stranguria and pelvic pain. MRI and CT did not provide different or more precise information than ultrasound scan: these findings were indistinguishable from an intrauterine lesion. On the contrary endovaginal sonography was more sensitivity than MRI and CT. Cystoscopy was negative. Nondiagnostic laparoscopy was performed. Patient underwent laparotomy and partial cystectomy. Histopatological findings demonstrated an endometriosis of the muscle layer of the bladder. The rarity of this condition prompted us to report on the problems encountered in making the differential diagnosis.


Negative coefficient of normal restitution.
This paper shows that negative coefficients of normal restitution occur inevitably when the interaction force between colliding particles is finite. We derive an explicit criterion showing that for any set of material properties there is always a collision geometry leading to negative restitution coefficients. While from a phenomenological point of view, negative coefficients of normal restitution appear rather artificial, this phenomenon is generic and implies an important overlooked limitation of the widely used hard sphere model. The criterion is explicitly applied to two paradigmatic situations: for the linear dashpot model and for viscoelastic particles. In addition, we show that for frictional particles the phenomenon is less pronounced than for smooth spheres.


Antifungal susceptibility profile of yeasts isolated from the oral cavity of cats.
Microorganisms living in the oral cavity play an important role in health and disease of the host. Cats are susceptible to oral infections, and it is documented that fungi in the oral cavity could impact these infections. Antifungal resistance has been increasing in recent years. This study was designed to identify yeast isolates from the oral cavity of healthy cats and to evaluate their antifungal susceptibility pattern. Oral specimens were collected from 60 cats and cultured at 37°C for 10 days. Yeasts were isolated and identified. Their antifungal susceptibility pattern was determined according to CLSI M44-A. Three yeast genera were isolated, including Candida spp (55.5%), Rhodotorula spp (33.3%) and Hanseniaspora spp (11.1%). Antifungal susceptibility profiling showed that, apart from a dose-dependent effect of itraconazole, Hanseniaspora spp was susceptible to all seven drugs studied. The Candida species were susceptible to all drugs except ketoconazole (sensitivity 80%) and caspofungin (sensitivity 40%). In R. glutinis and R. minuta, 100% sensitivity was observed for amphotericin B, posaconazole, ketoconazole and voriconazole. The results suggest that, in comparison with humans and other animals, cats have a different oral mycoflora in terms of species, number and diversity. However, these isolates have similar susceptibility patterns to those seen in isolates from other animals and humans. More studies should be done to further characterize the oral mycobiota of cats and its role in oral infections.


Agents that promote protein phosphorylation inhibit the activity of the Na+/Ca2+ exchanger and prolong Ca2+ transients in bovine chromaffin cells.
The Na+/Ca2+ exchanger is an important element in the maintenance of calcium homeostasis in bovine chromaffin cells. The Na+/Ca2+ exchanger from other cell types has been extensively studied, but little is known about its regulation in the cell. We have investigated the role of reversible protein phosphorylation in the activity of the Na+/Ca2+ exchanger of these cells. Cells treated with 1 mM dibutyryl cyclic AMP (dbcAMP), 1 microM phorbol 12,13-dibutyrate, 1 microM okadaic acid, or 100 nM calyculin A showed lowered Na+/Ca2+ exchange activity and prolonged cytosolic Ca2+ transients caused by depolarization. A combination of 10 nM okadaic acid and 1 microM dbcAMP synergistically inhibited Na+/Ca2+ exchange activity. Conversely, 50 microM 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine, a protein kinase inhibitor, enhanced Na+/Ca2+ exchange activity. Moreover, we used cyclic AMP-dependent protein kinase and calcium phospholipid-dependent protein kinase catalytic subunits to phosphorylate isolated membrane vesicles and found that the Na+/Ca2+ exchange activity was inhibited by this treatment. These results indicate that reversible protein phosphorylation modulates the activity of the Na+/Ca2+ exchanger and suggest that modulation of the exchanger may play a role in the regulation of secretion.


In treatment of active duodenal ulcer and Helicobacter pylori eradication.
To compare the efficacy of lansoprazole and pantoprazole in treatment of active duodenal ulcer and Helicobacterpylori eradication. A total of 50 patients, with a positive rapid urease test and endoscopically diagnosed active duodenal ulcer, were randomly assigned to one of two treatment groups after endoscopic examinations. Patients in the first group received lansoprazole 30 mg b.d., amoxycillin 1000mg b.d., clarithromycin 500 mg b.d.; patients in the second group received pantoprazole 40 mg b.d., amoxycillin 1000 mg b.d., clarithromycin 500 mg b.d for two weeks. Patients were scheduled for repeat endoscopic examination; repeat rapid urease test, and histological examination 4 weeks after the end of the therapy. Hp was eradicated in 84.2% of the patients received lansoprazole and in 83.3% of the patients received pantoprazole. The difference was not significant (P>0.05). In the lansoprazole group 90.5%, and in the pantoprazole group 83.3% of the patients experienced complete duodenal ulcer healing at the time of follow-up endoscopic examination. We found no statistical significant difference between the two groups. Lansoprazole and pantoprazole both have similar effect in eradication of Hp, and in terms of ulcer healing. Comparative studies in larger trials are needed to compare the efficacy of lansoprazole and pantoprazole in treatment of active duodenal ulcers.


Number and orientation of beams in inversely planned intensity-modulated radiotherapy of the female breast and the parasternal lymph nodes.
Intensity-modulated radiotherapy (IMRT) provides better sparing of normal tissue. We evaluated the optimum beam configuration for IMRT based on inverse treatment planning in adjuvant radiotherapy for breast cancer in a case of left-sided tumor. In addition to radiotherapy planning with the conventional technique of tangential wedged 6-MV photon beams and an oblique 15-MeV electron beam, we performed inversely planned IMRT with the step-and-shoot-technique. Dose calculation was carried out using the treatment planning system Virtuos with the inverse optimization module KonRad adapted to it. IMRT plans were generated for 2 to 16 beams. The results were compared with conventional techniques. For a maximum treatment time of 20 minutes, it is shown that IMRT with 12 modulated photon beams and 7 intensity steps is best suited for treatment in the presented case. Compared with a conventional technique with photons combined with electrons, dose conformality and homogeneity of the planning target volume was increased. The mean heart dose was reduced from 9.1 Gy to 6.1 Gy. The volume of heart irradiated with a dose higher than 30 Gy was reduced from 7.6% to 1.9%, and the volume of the left lung from 13.6% to 11.5% as well. Inverse optimization for IMRT with multiple beams is feasible in the adjuvant treatment of breast cancer. Because of the reduction of the high-dose area of a substantial cardiac volume, it is superior to conventional techniques in cases where the parasternal lymph nodes should be integrated into the target volume. Here, a clinical advantage might be detectable.


Myelitis and ascending flaccid paralysis due to congenital toxoplasmosis.
A 4-week-old female newborn developed ascending flaccid paralysis and radiologic evidence of myelitis; the diagnosis of congenital toxoplasmosis was confirmed by the presence of Toxoplasma gondii-specific immunoglobulins in both mother and infant, and detection of Toxoplasma sequences in the infant's cerebrospinal fluid by polymerase chain reaction analysis. Treatment with pyrimethamine, sulfadiazine, and methylprednisolone resulted in improvement.


Protein Carbonyl as a Biomarker of Oxidative Stress in Severe Leptospirosis, and Its Usefulness in Differentiating Leptospirosis from Dengue Infections.
Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p<0.02). Serum PC and LP levels were significantly higher in leptospirosis patients compared to critical phase dengue infections (p<0.005). Moreover, high serum PC levels appear to differentiate SL from DC [area under the curve (AUC) = 0.96; p<0.001]. Serum PC may be a reliable biomarker of oxidative damage to serum proteins to identify severe leptospirosis patients (AUC = 0.99) and also to differentiate severe leptospirosis from mild cases (AUC = 0.78; p<0.005) indicating its contribution to pathogenesis. Use of serum PC as an indicator of leptospirosis severity and as an oxidative stress biomarker in differentiating leptospirosis from dengue would provide the opportunity to save lives via prompt patient management.


An outbreak of ornithosis in Norway in 1981.
During 1981 there were 508 laboratory confirmed cases of ornithosis in Norway. This represents a 7-fold increase compared with previous years. Among 370 patients examined by the National Institute of Public Health, Oslo, 148 stated some contact with birds. There were also small family outbreaks and cases of ornithosis in school friends etc. where no bird exposure had occurred, suggesting that interhuman transmission might be involved. The clinical picture was that of a respiratory disease with pneumonia in more than half the cases. The clinical course was mild to moderately severe. At present we have no explanation for this change in the epidemiologic pattern of ornithosis in Norway.


Intractable rheumatoid arthritis. Treatment with combined cyclophosphamide, azathioprine, and hydroxychloroquine.
Seventeen patients (15 women, two men) with progressive, erosive seropositive rheumatoid arthritis (RA) refractory to conventional therapy were treated with cyclophosphamide, azathioprine, and hydroxychloroquine sulfate for an average of 27 +/- 19 months (mean +/- SD throughout) (range, five to 60 months). Disease suppression began in 14 patients within three to 16 months (mean, seven months). Five patients achieved complete remission, two had activity in a single joint only, seven had partial disease suppression, and three showed no response. Prednisone dosage was decreased or administration discontinued in nine of ten patients (5.8 +/- 1.2 to 2.7 +/- 3 mg/day). Serial hand roentgenograms showed recortication of erosions in nine patients, with "filling in" of some erosions in three of these. No change was seen in the roentgenograms of five patients, while progressive disease occurred in three instances. Combined therapy with small doses of three drugs, each with proved antirheumatic activity when used separately in larger doses, may provide satisfactory long-term disease control in patients with intractable RA. This regimen is experimental. Proof of efficacy requires a controlled study. Until such data are obtained, this drug combination is not recommended for general use.


Unusual hemodynamic response during exercise-induced angina pectoris.
A patient with coronary artery disease exhibited reduction in systemic arterial pressure and striking changes in pulmonary artery wedge pressure and pulse contour during an episode of exercise-associated angina pectoris. There is suggestive evidence that these phenomena were secondary to marked but reversible exacerbation of mitral regurgitation.


ERRβ splice variants differentially regulate cell cycle progression.
Orphan receptors comprise nearly half of all members of the nuclear receptor superfamily. Despite having broad structural similarities to the classical estrogen receptors, estrogen-related receptors (ERRs) have their own unique DNA response elements and functions. In this study, we focus on 2 ERRβ splice variants, short form ERRβ (ERRβsf) and ERRβ2, and identify their differing roles in cell cycle regulation. Using DY131 (a synthetic agonist of ERRβ), splice-variant selective shRNA, and exogenous ERRβsf and ERRβ2 cDNAs, we demonstrate the role of ERRβsf in mediating the G1 checkpoint through p21. We also show ERRβsf is required for DY131-induced cellular senescence. A key novel finding of this study is that ERRβ2 can mediate a G2/M arrest in response to DY131. In the absence of ERRβ2, the DY131-induced G2/M arrest is reversed, and this is accompanied by p21 induction and a G1 arrest. This study illustrates novel functions for ERRβ splice variants and provides evidence for splice variant interaction.


MicroRNA-153 affects nasopharyngeal cancer cell viability by targeting TGF-β2.
The aim of the present study was to determine the function of microRNA-153 (miR-153) in the viability of nasopharyngeal cancer (NPC) cells and determine the underlying molecular mechanism. The expression of miR-153 in patients with NPC was markedly decreased compared with that in paracarcinoma tissue. miR-153 upregulation observably decreased cell viability, induced apoptosis, increased caspase-3 and -9 activity, and increased the B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 protein expression ratio in 13-9B cells. miR-153 upregulation also suppressed transforming growth factor-β2 (TGF-β2) and Smad2 protein expression in 13-9B cells. TGF-β2 inhibitor enhanced the effect of miR-153 upregulation on the inhibition of cell viability, induction of apoptosis, increase in caspase-3 and -9 activity, and increase in Bax/Bcl-2 protein expression ratio in 13-9B cells. The results of the present study indicate that miR-153 affects the progression of NPC by targeting the TGF-β2/Smad2 signaling pathway.


A situation analysis of psychiatrists in South Africa's rural primary healthcare settings.
South Africa (SA) has been facing serious challenges in providing human resources for the delivery of essential mental health (MH) services. The majority of its prescribing MH specialists, psychiatrists, practise in private, urban and peri-urban areas. The findings of a situation analysis audit of psychiatrist human resources in the public rural primary healthcare (PRPHC) sector are presented in this paper. This audit was based on both primary and secondary data. The primary data were obtained from key informant interviews with the clinical heads of 160 PRPHC facilities, while the secondary data comprised a literature review. The results indicate that psychiatrists are severely underrepresented, employed at a rate of 0.03 per 100 000 population in SA's PRPHC settings. Because of a lack of MH nurses and medical officers dedicated to MH in PRPHC facilities, recommendations are made that the current task shifting strategy be revisited to include more cadres of MH professionals with specialised psychopharmacological training, as non-medical prescribers at PRPHC level. It is advised that visiting psychiatrists and family physicians be involved in the construction of training and supervision programmes for non-medical prescribers at the primary healthcare level.


B-1 B cell subset composition of DBA/2J mice.
Studies of B cell subpopulations have focused upon BALB/c mice and related strains. The B cell subset composition of DBA/2J mice, a prototype strain for BALB/c mice, has been investigated less thoroughly. This report provides the results of a study of the B-1 B cells of DBA/2J mice. In contrast to C.B-17 mice, in which B-1 B cells expressed both the CD5 and CD11b antigens, CD11b expression was most characteristic of DBA/2J B-1 B cells. This was particularly evident in the peritoneal cavity where CD5-CD11b+ B cells were the predominant B cell subpopulation. The number of B-1 B cells increased with age in both the spleen and peritoneal cavity. Strain-specific differences in B cell subset composition may be significant when considering B cell lymphomagenesis with aging.


Multi-component lanthanide hybrids based on zeolite A/L and zeolite A/L-polymers for tunable luminescence.
Some multi-component hybrids based on zeolite L/A are prepared. Firstly, zeolite A/L is loaded with lanthanide complexes (Eu-DBM or Tb-AA (acetylacetone = AA, dibenzoylmethane = DBM)) into its channels. Secondly, 3-methacryloyloxypropyltrimethoxysilane (γ-MPS) is used to covalently graft onto the surface of functionalized zeolite A/L (Si-[ZA/L⊃Eu-DBM(Tb-AA)]). Thirdly, lanthanide ions (Eu(3+)/Tb(3+)) are coordinated to the functionalized zeolite A/L and ligands (phen(1,10-phenanthroline) or bipy (2,2'-bipyridyl)) are introduced by a ship-in-bottle method. The inside-outside double modifications of ZA/L with lanthanide complexes afford the final hybrids and these are characterized by means of XRD, FT-IR, UV-vis DRS, SEM and luminescence spectroscopy, some of which display white or near-white light emission. Furthermore, selected above-mentioned hybrids are incorporated into PEMA/PMMA (poly ethyl methylacryate/poly methyl methacrylate) hosts to prepare luminescent polymer films. These results provide abundant data that these hybrid materials can be expected to have potential application in various practical fields.


Arcticibacter eurypsychrophilus sp. nov., isolated from ice core.
A Gram-stain-negative, rod-shaped, non-flagellated bacterium, strain MJ9-5(T), was isolated from ice core of Muji Glacier. Colonies of strain MJ9-5(T) were pink, convex and round on R2A agar. Strain MJ9-5(T) grew between -1 to 25 °C with an optimum growth temperature of 10-15 °C. The strain tolerated 0-1.2 % (w/v) NaCl with an optimum of 1 %. The major cellular fatty acids of strain MJ9-5(T) were iso-C15 : 0, summed feature 3 (C16 : 1ω6c and/or C1 6 : 1ω7c). The G+C content of the genomic DNA was 38.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain MJ9-5(T) was related to members of the genus Arcticibacter. On the basis of the phenotypic characteristics and phylogenetic analysis, a novel species of this genus, Arcticibacter eurypsychrophilus sp. nov., is proposed. The type strain is MJ9-5(T) ( = KCTC 42008(T) = JCM 19862(T)).


Trivalent uranium phenylchalcogenide complexes: exploring the bonding and reactivity with CS2 in the Tp*2UEPh series (E = O, S, Se, Te).
The trivalent uranium phenylchalcogenide series, Tp*2UEPh (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate, E = O (1), S (2), Se (3), Te (4)), has been synthesized to investigate the nature of the U-E bond. All compounds have been characterized by (1)H NMR, infrared and electronic absorption spectroscopies, and in the case of 4, X-ray crystallography. Compound 4 was also studied by SQUID magnetometry. Computational studies establish Mulliken spin densities for the uranium centers ranging from 3.005 to 3.027 (B3LYP), consistent for uranium-chalcogenide bonds that are primarily ionic in nature, with a small covalent contribution. The reactivity of 2-4 toward carbon disulfide was also investigated and showed reversible CS2 insertion into the U(III)-E bond, forming Tp*2U(κ(2)-S2CEPh) (E = S (5), Se (6), Te (7)). Compound 5 was characterized crystallographically.


Complications in skin grafts when continuing antithrombotic therapy prior to cutaneous surgery requiring skin grafting: A systematic review.
The risk of postoperative bleeding and wound healing complications in skin grafts among anticoagulated patients undergoing cutaneous surgery has not been firmly established. The objective was to examine the literature and assess the risk of postoperative bleeding or wound healing complications in skin grafts among anticoagulated patients, compared with patients who discontinue or patients who are not receiving antithrombotic therapy prior to cutaneous surgery requiring skin grafting. A systematic review examining the effect of antithrombotic therapy on cutaneous surgery was performed according to the PRISMA-guidelines. PubMed and Embase databases were primarily searched for relevant literature in the period from the start date of each database to 2014. A total of eight studies representing 443 patients met criteria for inclusion. No randomised controlled trials were found; the included studies were of prospective and retrospective design. Most of the reviewed studies suggest that the use of antithrombotic therapy can increase the risk of bleeding complications in skin grafts. These complications are only wound threatening and not life threatening. Therefore, this is of concern mostly in terms of hemostasis by the surgeon and good pressure dressings. Care should be taken when operating on anticoagulated patients undergoing cutaneous surgery requiring skin grafting. However, graft failure is rare and, given the risk of thrombotic events, the reviewed studies recommend continuing all medically necessary antithrombotic therapy. The limitations of this study are the small sample sizes and the level of evidence; hence, more research is needed to substantiate these preliminary findings.


Depolymerization of chromophoric natural organic matter.
Although the importance of natural organic matter (NOM) in the environment and in drinking water treatment is well-known, its structure is still ill-defined. The fragmentation patterns of NOM treated by irradiation (various wavelengths--185-400 nm), hydroxyl radicals, chlorine, ozone, and breakdown by a white rot fungus were studied to investigate the structure of chromophoric NOM molecules. Size exclusion chromatography was used to monitor the size distributions of NOM in two natural water waters and two NOM isolates. Three distinct fragmentation patterns were observed: ozone attack appeared to be nonsize specific, UV (> or = 254 nm) irradiation preferentially removed higher molecular weight chromophores, while processes involving hydroxyl radical showed intermediate size specificity. For the samples studied, the UV (> or = 254 nm) irradiation-induced fragmentation of NOM followed the patterns suggested by a simple trimer depolymerization model, supporting the viewpoint that NOM has repeating structural units joined by photolabile chemical bonds. The largest molecules reacted most rapidly, progressively fragmenting into slower reacting smaller molecules, which initially accumulated before breaking down to become nonchromophoric. This dependency of rate on molecular size appears to follow from the law of photochemistry which states the rate of reaction is proportional to the rate of light absorption: larger chromophores had higher molar absorptivities, absorbed more photons, and hence reacted faster than smaller chromophores.