Novel Ti-Nb alloys with improved wear resistance for biomedical implant application.
The present study involved fabrication of titanium niobium based alloys having elastic modulus close to that of human bone and subsequently determining the wear resistance of these alloys for biomedical application. In the present study three beta stabilized titanium niobium alloys having composition Ti-24Nb-4Zr-8Sn, Ti-35Nb-4Sn and Ti-29Nb-13Ta-7Zr were made by vacuum arc melting. The alloys were then aged at 1000 C for 6 hours in an argon atmosphere. Detailed microstructural characterization and phase identification was carried out using scanning electron microscopy and x-ray diffraction respectively. The hardness of the samples were measured by micro hardness measurements. The wear resistance and the friction coefficient of the samples were measured by testing in Ringer's solution (simulated body fluid). The results showed improved wear resistance of the fabricated alloys.


Yoga as an alternative intervention for promoting a healthy lifestyle among college students.
Substance use and abuse continues to plague U.S. college campuses. The literature is replete with information from various disciplines on how to identify and intervene in this public health dilemma impacting college students. Identifications, treatments, and interventions are often based on Western medicine, but there is a growing movement and evidence supporting the effectiveness, value, and usefulness of Eastern therapies to combat this problem. Yoga is one Eastern intervention that has proven beneficial for promoting quality of life and wellness relationship to several acute and chronic illnesses. As a result of advocating for the inclusion of yoga in traditional college settings, two college campuses in Central Illinois introduced yoga courses for students, faculty, and staff. The courses are reviewed, and the positive results reported by students are shared. The information and evidence of yoga's benefits collected in this study warrant consideration by college campuses to initiate this practice enhancing primary, secondary, and tertiary prevention in their populations.


A combined experimental and computational study on the transition of the calcium isopropoxide radical as a candidate for direct laser cooling.
Vibronically resolved laser-induced fluorescence/dispersed fluorescence (LIF/DF) and cavity ring-down (CRD) spectra of the electronic transition of the calcium isopropoxide [CaOCH(CH3)2] radical have been obtained under jet-cooled conditions. An essentially constant energy separation of 68 cm-1 has been observed for the vibrational ground levels and all fundamental vibrational levels accessed in the LIF measurement. To simulate the experimental spectra and assign the recorded vibronic bands, Franck-Condon (FC) factors and vibrational branching ratios (VBRs) are predicted from vibrational modes and their frequencies calculated using the complete-active-space self-consistent field (CASSCF) and equation-of-motion coupled-cluster singles and doubles (EOM-CCSD) methods. Combined with the calculated electronic transition energy, the computational results, especially those from the EOM-CCSD calculations, reproduced the experimental spectra with considerable accuracy. The experimental and computational results suggest that the FC matrix for the studied electronic transition is largely diagonal, but transitions from the vibrationless levels of the à state to the X̃-state levels of the CCC bending (ν14 and ν15), CaO stretch (ν13), and CaOC asymmetric stretch (ν9 and ν11) modes also have considerable intensities. Transitions to low-frequency in-plane [ν17(a')] and out-of-plane [ν30(a'')] CaOC bending modes were observed in the experimental LIF/DF spectra, the latter being FC-forbidden but induced by the pseudo-Jahn-Teller (pJT) effect. Both bending modes are coupled to the CaOC asymmetric stretch mode via the Duschinsky rotation, as demonstrated in the DF spectra obtained by pumping non-origin vibronic transitions. The pJT interaction also induces transitions to the ground-state vibrational level of the ν10(a') mode, which has the CaOC bending character. Our combined experimental and computational results provide critical information for future direct laser cooling of the target molecule and other alkaline earth monoalkoxide radicals.


Mycophenolate mofetil in multiple sclerosis.
To describe experience with the use of mycophenolate mofetil (MMF) in the treatment of multiple sclerosis (MS). MMF is a potent immunosuppressant that is a selective inhibitor of inosine 5'-monophosphate dehydrogenase type II, the enzyme responsible for the de novo synthesis of the purine nucleotide guanine within activated T and B lymphocytes and macrophages. A retrospective review of experience in treating 79 MS patients with MMF (61 with secondary progressive, 14 with relapsing-remitting, and 4 with primary progressive MS) in the authors' MS center. In most cases, MMF was added as adjunctive therapy in patients already being treated with either interferon-beta (n = 44) or glatiramer acetate (n = 20). Fifteen patients not able to use interferon or glatiramer acetate were treated with MMF monotherapy. Seventy percent of the patients continued MMF therapy. Eight patients discontinued therapy because of side effects, 7 patients continued to exhibit evidence of disease progression, 4 were denied insurance coverage, 2 were lost to follow-up, and 1 patient had an elevation of hepatic transaminases that resolved on discontinuation of MMF. One patient discontinued MMF therapy secondary to cytomegalovirus diarrhea. MMF was well tolerated by the majority of patients treated. While these clinical observations were uncontrolled, the clinical course of MS was either unchanged or subjectively improved in many of the treated patients. A randomized controlled trial of MMF in MS, either as monotherapy or in conjunction with interferon or glatiramer acetate, appears warranted.


Hypertensive Retinopathy and the Risk of Hemorrhagic Stroke.
Hemorrhagic stroke (HS) and hypertensive retinopathy are known end organ damage of the brain and eye respectively, with HS having deleterious consequence to the patients. This study is to correlate between hypertensive retinopathy and HS in hypertensive disease. A control group of hypertensive patients only, and an investigated group of hypertensive HS patients. Fundoscopic examination to determine the grade of retinopathy was performed and then divided into low or high severity hypertensive retinopathy. Clinical and radiological parameter included are demography, vital signs, Glasgow coma scale (GCS) on admission, clot volume, site of clot, Intracerebral hemorrhage (ICH) score and Glasgow outcome scale (GOS). Data were correlated with the severity of hypertensive retinopathy. Fifty patient in the control group and 51 patients in the investigated group were recruited. In the hypertensive HS group, 21 had low severity retinopathy (no or mild retinopathy) accounting for 41.2% and 30 patients had high severity (moderate or severe retinopathy). In the hypertensive patients 49 had low severity and one had high severity (p-value of 0.001). In HS group low severity showed better GCS score of 9-15 on admission (p-value of 0.003), clot volume less than 30 mL (p-value 0.001), and also a better 30 days mortality rate by using the ICH score (p-value 0.006), GOS score of 4 and 5 the low severity retinopathy fair better than the high severity retinopathy (p-value of 0.001), and the relative risk to develop HS in low severity and high severity retinopathy was 0.42 and 29.4, respectively. Hypertensive retinopathy screening could be used as an indicator in hypertensive patient, to evaluate the risk of developing hypertensive HS in the future.


Kinetics of inhibition of beta-amyloid aggregation by transthyretin.
Deposition of beta-amyloid (Abeta) fibrils is an early event in the neurodegenerative processes associated with Alzheimer's disease. According to the "amyloid cascade" hypothesis, Abeta aggregation, and its subsequent deposition as fibrils, is the underlying cause of disease. Abeta is a proteolytic product of amyloid precursor protein (APP); several mutations in APP have been identified that are associated with early onset of disease. Transgenic mice overexpressing APP with the Swedish mutation develop numerous plaques but, surprisingly, lack the neurofibrillary tangles and neuronal loss characteristic of Alzheimer's disease, in apparent contradiction of the amyloid cascade hypothesis. However, recent studies suggest that coproduction of sAPPalpha, an alternative proteolytic product of APP, increases synthesis of transthyretin that, in turn, interacts directly with Abeta to inhibit its toxicity. Here we report results from biophysical analysis of Abeta aggregation kinetics in the presence of transthryetin. At substoichiometric ratios, transthyretin drastically decreased the rate of aggregation without affecting the fraction of Abeta in the aggregate pool. Detailed analysis of the data using a mathematical model demonstrated that the decrease in aggregation rate was due to both a decrease in the rate of elongation relative to the rate of initiation of filaments and a decrease in lateral association of filaments to fibrils. Tryptophan quenching data indicated that transthyretin binds weakly to Abeta, with an estimated apparent KS of 2300 M-1. Taken together, the data support a hypothesis wherein transthyretin preferentially binds to aggregated rather than monomeric Abeta and arrests further growth of the aggregates.


Screening in Maternity to Ascertain Tuberculosis Status (SMATS) study.
Diagnosis of tuberculosis is difficult among pregnant women because the signs and symptoms of the disease, such as fatigue, shortness of breath, sweating, cough, and mild fever are similar to some manifestations of pregnancy. It is particularly challenging among HIV-infected women as symptoms are often masked or atypical. Currently, WHO recommends a standard four-symptom screening tool for pregnant and lactating women. There is evidence from South Africa that this screening tool (which, despite complex symptomology in this population, recommends identification of patients with weight loss, fever, current cough and night sweats), may be missing true active TB cases. However there exist several laboratory and clinical procedures that have the potential to improve the sensitivity and specificity of this screening tool. This study will evaluate the sensitivity and specificity of the current TB screening tool for pregnant and lactating women, both HIV positive and negative. We will also assess several different enhanced screening algorithm using LAM, IGRA, TST and chest radiography and clinical/laboratory procedures and tests. The study will use a cross-sectional analytical study design involving pregnant and lactating women up to six months post-delivery attending antenatal or postnatal care, respectively in one of three selected public health units in Swaziland. Participants will be consecutively enrolled and will be in one of four groups of interest: HIV infected pregnant women, non-HIV infected pregnant women, HIV infected lactating women and non-HIV infected lactating women. We expect in conducting all procedures on all participants regardless of result of the symptom screening we may experience a high refusal rate. However, this risk will be mitigated by the long data collection period of five or more months.


Safeguarding children in clinical research.
Current UK guidelines regarding clinical research on children permit research that is non-therapeutic from the perspective of that particular child. The guidelines permit research interventions that cause temporary pain, bruises or scars. It is argued here that such research conflicts with the Declaration of Helsinki according to which the interests of the research subject outweigh all other interests. Given this, in the context of clinical research, who is best placed to protect the child from this kind of exploitation? Is it the medical researcher, the child's parents or the nurse advocate? This article describes the problem, possible responses to it, and closes with a consideration of, and rejection of, a defence of current guidelines that claims moral parity between clinical research and clinical education.


The Metabolomic Strategy in Tuberculosis Therapy.
Tuberculosis causes around 1.4 million deaths every year remaining to be a major cause of morbidity and mortality. Mycobacterium tuberculosis is adept at surviving the assault of our immune system, which has perplexed many researchers. Not only are they difficult to treat, but also difficult to detect accurately. The current reservoir of drugs and method to diagnose them is depleting faster than we are able to replace them with newer one. The advances made in the field of metabolomic have opened up a window of opportunities such as identification of new drug and druggable site, prediction of drug toxicity and detection of new biomarkers to accurately diagnose the disease. With its short history of less than two decades, metabolomics has shown very promising future to tackle this concern. Equally important developments in analytical techniques and application of data interpretation have further facilitated the scope of this field. The present review discusses the advances in metabolomic research with an emphasis on tuberculosis diagnosis and therapeutics.


Recent advances in renal development.
Anatomical development of the kidney is achieved by the reciprocal induction of the ureteric bud and the metanephric mesenchyma. This interaction triggers the process of nephrogenesis and culminates in the formation of the mature kidney. In vivo, nephrogenesis is coordinated with renal vascularization. In fact, vascular precursors, epithelial progenitors, and mesenchymal cells communicate with one another in a highly organized fashion. As a result of this complex interaction, a mature kidney, architecturally and functionally ready for extrauterine life, is produced. This review deals with the relevant molecules and mechanisms governing nephrovascular development.


Two-Year Recurrence After First-Ever Stroke in a General Population of 1.4 Million Japanese Patients - The Shiga Stroke and Heart Attack Registry Study.
Despite many effective strategies for the prevention of recurrent stroke, individuals who survive an initial stroke have been shown to be at high risk of recurrent stroke. The aim of this study was to investigate the current status of stroke recurrence after first-ever stroke using a population-based stroke registry in Japan.Methods and Results:As part of the Shiga Stroke and Heart Attack Registry, the Shiga Stroke Registry is an ongoing population-based stroke registry study that covers approximately 1.4 million residents of Shiga Prefecture, Japan. A total of 1,883 first-ever stroke survivors at 28 days was registered in 2011 and followed-up until the end of 2013. Recurrence was defined as any type of stroke after 28 days from the onset of an index event. Two-year cumulative recurrence rates were estimated using cumulative incidence function methods. Over a mean 2.1-year follow-up period, 120 patients experienced recurrent stroke and 389 patients died without recurrence. The 2-year cumulative recurrence rate was higher in patients with index ischemic stroke (6.8%) than in those with index hemorrhagic stroke (3.8%). Two-year cumulative recurrence rate after first-ever stroke remained high, particularly among patients with ischemic stroke, in the present population-based registry study in a real-world setting in Japan. Further intensive secondary prevention strategies are required for these high-risk individuals.


A kampo medicine, Yin-Chiao-san, prevents bleomycin-induced pulmonary injury in rats.
Yin-Chiao-San (YCS), a kampo medicine, is widely used for patients with pulmonary disease and was applied for the treatment of SARS in Asia countries in 2003. For this reason, the present study investigated the preventive effect of YCS on bleomycin (BLM)-induced pulmonary fibrosis (PF) in rats. Animals were divided into four groups: (1) saline control group; (2) BLM-induced group, in which 15 mg/kg BLM was intraperitoneally injected three times per week for a period of 5 weeks; (3) BLM + vitamin E (10 mg/kg/day) as a positive group; (4) and BLM + YCS (1000 mg/kg/day). After 35 days, the rats were anesthetized, killed and then the lungs and bronchoalveolar lavage fluids (BALFs) were collected. The attenuation of pulmonary fibrosis was estimated according to the lung index, malondialdehyde (MDA), catalase (CAT), hydroxyproline (HP) and tumor necrosis factor-alpha (TNF-alpha) level in lung tissue and BALF. The serial sections of lung were stained with haematoxylin-eosin and Masson trichrome for histopathological observation of pulmonary fibrosis. The results indicated that YCS significantly reduced the lung index, MDA, HP and TNF-alpha, but YCS significantly enhanced the CAT level when compared with the BLM-induced group (p < 0.05). Additionally, the BLM group displayed severe histopathological change in the lung tissue, but YCS treatment could attenuate the BLM-induced PF. In conclusion, the results demonstrated that YCS possesses antioxidant and antiinflammatory activities and also inhibited collagen formation. Thus, YCS exhibited a preventive effect in BLM-induced PF and it is suggested that YCS may be applied to attenuate the side effects of BLM in chemotherapy.


The growth rate of metastatic nonseminomatous germ cell testicular tumours measured by marker production doubling time--II. Prognostic significance in patients treated by chemotherapy.
Tumour growth rates have been measured in metastatic non-seminomatous germ cell testicular tumours (NSGCTT) by estimating the rate of rise of tumour marker production (TMP). TMP was calculated for the time between orchidectomy and the start of chemotherapy in a group of 58 patients with metastatic NSGCTT treated with BEP combination chemotherapy (bleomycin, etoposide and cisplatin). Calculation of TMP (iu/l/day) took account of the continuing clearance of marker from the serum. TMP increased with time in 51 patients and this rise generally appeared to be exponential. The rate of this increase was expressed as the marker production doubling time (MPDT) and is a measure of the tumour growth rate. MPDT varied from 0.5 to greater than 80 days (45 cases) for AFP + ve patients and from 1.8 to greater than 80 days (34 cases) for HCG + ve patients. Patients who failed BEP first line therapy had shorter MPDTs than those who responded (AFP P = 0.08, HCG P = 0.003). It was found that patients with a MPDT less than or equal to 4 days were more likely to fail treatment than those who had a MPDT greater than 4 days (AFP P = 0.009, HCG P = 0.005). MPDTs were independent of initial serum marker concentration. Patients with small volume disease had longer MPDTs than patients with large volume disease (AFP P = 0.02, HCG P = 0.04). Rapid tumour growth rate reflected by short MPDT carries a poor prognosis in patients with NSGCTT treated by BEP chemotherapy.


Relationship of circulating CD4+ T-lymphocytes and p24 antigenemia to the risk of developing AIDS in HIV-infected subjects with oral hairy leukoplakia.
To investigate the relationship of circulating CD4+ T-lymphocytes and p24 antigenemia to the development of AIDS in HIV-infected subjects with hairy leukoplakia (HL), we have followed over eight years 173 HIV-positive patients, all asymptomatic at the start of the study, and compared those who developed HL (n=55) to those who did not (n=118). Both groups included injection drug users (IDUs), homosexual men, and hemophiliacs. At the time of their first visit, both HL+ and HL- patients had a normal value of CD4+ cells and a low frequency of p24 antigenemia. During the years of follow-up, patients in the HL+ group showed a greater reduction in CD4+ cells, a significant increase in p24 antigenemia, and a higher rate of progression to AIDS. Our study demonstrates that in HIV-positive patients, HL is associated with more compromised immunological parameters and a higher viral replication and that its appearance has a negative prognostic value in relation to AIDS progression.


Quantum-Dot Single-Photon Sources for Entanglement Enhanced Interferometry.
Multiphoton entangled states such as "N00N states" have attracted a lot of attention because of their possible application in high-precision, quantum enhanced phase determination. So far, N00N states have been generated in spontaneous parametric down-conversion processes and by mixing quantum and classical light on a beam splitter. Here, in contrast, we demonstrate superresolving phase measurements based on two-photon N00N states generated by quantum dot single-photon sources making use of the Hong-Ou-Mandel effect on a beam splitter. By means of pulsed resonance fluorescence of a charged exciton state, we achieve, in postselection, a quantum enhanced improvement of the precision in phase uncertainty, higher than prescribed by the standard quantum limit. An analytical description of the measurement scheme is provided, reflecting requirements, capability, and restraints of single-photon emitters in optical quantum metrology. Our results point toward the realization of a real-world quantum sensor in the near future.


The reduction in maize leaf growth under mild drought affects the transition between cell division and cell expansion and cannot be restored by elevated gibberellic acid levels.
Growth is characterized by the interplay between cell division and cell expansion, two processes that occur separated along the growth zone at the maize leaf. To gain further insight into the transition between cell division and cell expansion, conditions were investigated in which the position of this transition zone was positively or negatively affected. High levels of gibberellic acid (GA) in plants overexpressing the GA biosynthesis gene GA20-OXIDASE (GA20OX-1OE ) shifted the transition zone more distally, whereas mild drought, which is associated with lowered GA biosynthesis, resulted in a more basal positioning. However, the increased levels of GA in the GA20OX-1OE line were insufficient to convey tolerance to the mild drought treatment, indicating that another mechanism in addition to lowered GA levels is restricting growth during drought. Transcriptome analysis with high spatial resolution indicated that mild drought specifically induces a reprogramming of transcriptional regulation in the division zone. 'Leaf Growth Viewer' was developed as an online searchable tool containing the high-resolution data.


A comparison of review methods in tobacco prevention and control guidelines.
To compare methods and conclusions of selected guidelines evaluating youth tobacco interventions. Eight reviews were compared regarding (a) search and assessment of evidence, (b) translation into recommendations, and (c) conclusions regarding tobacco cessation among youth. Narrative and systematic review methods were employed. Five systematic reviews adopted different (a) criteria for study inclusion, (b) methods estimating summary outcome measurements, and (c) standards for concluding on the evidence of effectiveness. Evidence reviews provide useful summaries, conclusions, and recommendations. Youth Tobacco Cessation: A Guide for Making Informed Decisions provides an inital systematic review of the evidence on effectiveness of youth tobacco use.


Carotid Ultrasonography Can Identify Stroke Patients Ineligible for Intravenous Thrombolysis Therapy due to Acute Aortic Dissection.
Acute aortic dissection is the most common acute aortic condition requiring urgent surgical therapy. Due to lack of typical symptoms, it is sometimes difficult to identify acute aortic dissection causing ischemic stroke. We report a case of a patient with acute ischemic stroke who was deemed ineligible for intravenous recombinant tissue plasminogen activator treatment based on a finding of acute aortic dissection detected by carotid ultrasonography. After urgent aortic replacement surgery, the patient recovered with no neurological deficit. This case underscores the crucial role of carotid ultrasonography for the investigation of possible underlying acute aortic dissection when considering the use of intravenous recombinant tissue plasminogen activator therapy for hyperacute stroke.


Interaction of polymorphonuclear leukocytes with immune complexes trapped in rheumatoid articular cartilage.
When rheumatoid articular cartilage samples were incubated with normal polymorphonuclear leukocytes (PMN) in vitro, large numbers of PMN were seen attached to the articular surface. As observed by electron microscopy, significant numbers of these cells invaded the cartilage tissue and phagocytosed amorphous material which presumably contained immune complexes. In control cartilage from osteoarthritic, pyogenic, and normal subjects, only a few PMN were attached to the articular surface after incubation with PMN. These results demonstrate that immune complexes trapped in the superficial region of the rheumatoid articular cartilage may play an important role in the destruction of cartilage by the release of lysosomal enzymes from PMN.


Protective roles of nanomelatonin in cerebral ischemia-reperfusion of aged brain: Matrixmetalloproteinases as regulators.
Cerebral ischemia-reperfusion (CIR) injury occurs as a result of oxygen occlusion in the carotid artery through embolus or thrombus formation or cerebrovascular hemorrhage. The oxygen thrust during reperfusion causes the generation of reactive oxidative species (ROS) which exert a potential threat to neuronal survival. ROS may possibly be arrested by antioxidants. After CIR, extracellular matrix remodeling takes place, which is governed by matrix metalloproteinases (MMPs). Augmentation of lipid per oxidation, perturbation of antioxidant enzyme activities and the loss of pyramidal neuronal cells in rat brain were attributed to CIR injury. Melatonin can readily cross the blood-brain barrier (BBB) to exert protective effects as an antioxidant but it is quickly cleared by the circulating blood. Also melatonin is easily degraded by light and hence is found to be ineffective during daytime. Results of the present study showed that unlike free melatonin (FM), the application of nanocapsulated melatonin (NM) exhibited significantly higher potential even at much lower concentrations to rescue neuronal cells and mitochondria during CIR insult and also restored the activities of antioxidative enzymes and MMPs to their normal levels. Hence, nanoencapsulated melatonin may be considered as a suitable drug delivery system for brain to exert protection against CIR injury.


Lack of effect of metoclopramide on colonic motility after cholecystectomy.
The effect of metoclopramide on postoperative colonic ileus was evaluated in a randomised, double-blind study in 20 patients after cholecystectomy. The start of propulsive colonic motility and colonic transit time after operation were measured by radio-opaque markers and serial abdominal radiographs. Metoclopramide 20 mg given intravenously three times a day until the fourth postoperative day (n = 10) did not significantly reduce the duration of postoperative colonic paralysis compared with control patients (n = 10), nor were there any differences between the groups when the time of first postoperative passage of gas and faeces were compared. In conclusion, the use of metoclopramide in the postoperative period did not result in a quicker return of propulsive motility in the right or left colon as judged by the radio-opaque markers and serial abdominal radiographs.


Cosmetic outcomes of cesarean section scar; subcuticular suture versus intradermal buried suture.
The objective of the study was to compare cosmetic outcomes and overall satisfaction rate of cesarean section scar between conventional subcuticular suture and intradermal buried vertical mattress. Patients were enrolled to the study by chart review. A scar assessment was obtained retrospectively through a telephone survey. The patient component of the patient and observer scar assessment scale (POSAS) was utilized along with the overall satisfaction of the patient regarding their cesarean section scar and their willingness to choose the same skin closure technique when anticipating their next cesarean section. A total of 303 cases of cesarean section was recruited, 102 finished telephone surveys were calculated for the analyses. Subcuticular suture was regarded as control group (n=52) and intradermal buried suture as test group (n=50). The PSAS score of the test group (mean, 21.8) was lower than that of the control group (mean, 28), with a statistical significance (P=0.02). Overall satisfaction rate did not differ between the two groups. Two parameters of the PSAS score and the level of overall satisfaction showed significant correlation (Pearson's r, -0.63; P<0.01). We suggested the use of intradermal buried vertical mattress as a cosmetically superior skin closure method for application in cesarean sections over subcuticular stitch.


Suffering for her art: the chronic pain syndrome of pianist Clara Wieck-Schumann.
Clara Schumann was an outstanding pianist, systematically trained as a child prodigy by her father Friedrich Wieck. Married to the composer Robert Schumann she gave birth to 8 children, however, was able to continue performing regularly in public. After the mental breakdown of her husband, she had to increase her public performance activities due to the need to earn a living for her large family. In this time, the first pains in the right arm occurred, which at the beginning were of shorter duration, however increasingly required prolonged periods of rest. Later, when attempting to work on the highly demanding piano works of Johannes Brahms, especially on his first piano concerto, she developed chronic pain, which forced her to interrupt any concert activities for more than 1 year. Obviously, Brahms' modern treatment of the piano in an almost orchestral way imposed technical difficulties which Clara Schumann was not properly prepared to deal with. Finally, she underwent a multimodal pain therapy in the private sanatorium of Dr. Esmarch, which consisted of an integrated interdisciplinary approach comprising pain medication, psychotherapy, physiotherapy and modification of playing habits. She fully recovered and successfully continued her career as an internationally renowned concert pianist. The case report impressively demonstrates the stressors an outstanding female elite musician had to cope with in the 19th century. Furthermore, it is a convincing example of how the intuition and mere experience of a sensitive and understanding doctor lead to the right conclusions and to a modern multimodal pain therapy in chronic overuse injury. Furthermore the case report demonstrates the important role of prevention, including physical exercises, self-awareness, and reasonable practice schedules.


Hot weather and heat extremes: health risks.
Hot ambient conditions and associated heat stress can increase mortality and morbidity, as well as increase adverse pregnancy outcomes and negatively affect mental health. High heat stress can also reduce physical work capacity and motor-cognitive performances, with consequences for productivity, and increase the risk of occupational health problems. Almost half of the global population and more than 1 billion workers are exposed to high heat episodes and about a third of all exposed workers have negative health effects. However, excess deaths and many heat-related health risks are preventable, with appropriate heat action plans involving behavioural strategies and biophysical solutions. Extreme heat events are becoming permanent features of summer seasons worldwide, causing many excess deaths. Heat-related morbidity and mortality are projected to increase further as climate change progresses, with greater risk associated with higher degrees of global warming. Particularly in tropical regions, increased warming might mean that physiological limits related to heat tolerance (survival) will be reached regularly and more often in coming decades. Climate change is interacting with other trends, such as population growth and ageing, urbanisation, and socioeconomic development, that can either exacerbate or ameliorate heat-related hazards. Urban temperatures are further enhanced by anthropogenic heat from vehicular transport and heat waste from buildings. Although there is some evidence of adaptation to increasing temperatures in high-income countries, projections of a hotter future suggest that without investment in research and risk management actions, heat-related morbidity and mortality are likely to increase.


Antigenic analysis of testicular cytochromes c using monoclonal antibodies.
Testicular cytochrome c (cyt ct) was isolated from testes of sexually mature, rat, mouse, rabbit, and bull, among which rat testis is highly rich in cyt ct. By fusion of NS-1 myeloma cells and spleen cells of mice immunized with rat cyt ct, 11 stable mouse hybridoma cell lines were established. Using an enzyme-linked immunosorbent assay, it was determined that 4 of the 11 anti-rat cyt ct monoclonal antibodies (McAb) did not bind to somatic cyt c (cyt cs) of vertebrates nor to cyt ct of mouse, rabbit, and bull. Four other McAb showed no binding to cyt cs but showed different patterns of cross-reactivity with these four cyt ct. Therefore, these McAb appear to be very sensitive and useful probes for the discrimination or identification of extremely similar isocytochromes c. Although the primary amino acid sequences between cyt cs of rat and mouse are identical, the antigenic structure of cyt ct of rat and mouse are clearly distinct with regard to cross-reactivity with some anti-rat cyt ct McAb. Furthermore, these McAb also reveal that the primary amino acid sequences of cyt ct, which reflect differences in the surface conformation of the molecule, are probably species specific.


Amino acid oxidation of the D1 and D2 proteins by oxygen radicals during photoinhibition of Photosystem II.
The Photosystem II reaction center is vulnerable to photoinhibition. The D1 and D2 proteins, lying at the core of the photosystem, are susceptible to oxidative modification by reactive oxygen species that are formed by the photosystem during illumination. Using spin probes and EPR spectroscopy, we have determined that both O2•- and HO• are involved in the photoinhibitory process. Using tandem mass spectroscopy, we have identified a number of oxidatively modified D1 and D2 residues. Our analysis indicates that these oxidative modifications are associated with formation of HO• at both the Mn4O5Ca cluster and the nonheme iron. Additionally, O2•- appears to be formed by the reduction of O2 at either PheoD1 or QA Early oxidation of D1:332H, which is coordinated with the Mn1 of the Mn4O5Ca cluster, appears to initiate a cascade of oxidative events that lead to the oxidative modification of numerous residues in the C termini of the D1 and D2 proteins on the donor side of the photosystem. Oxidation of D2:244Y, which is a bicarbonate ligand for the nonheme iron, induces the propagation of oxidative reactions in residues of the D-de loop of the D2 protein on the electron acceptor side of the photosystem. Finally, D1:130E and D2:246M are oxidatively modified by O2•- formed by the reduction of O2 either by PheoD1•- or QA•- The identification of specific amino acid residues oxidized by reactive oxygen species provides insights into the mechanism of damage to the D1 and D2 proteins under light stress.


Analytical methods for disease association studies with immunogenetic data.
Disease association studies involving highly polymorphic immunogenetic data may involve analyses at one or many units of analysis, including amino acid, allele, genotype and haplotype levels, as well as consideration of gene-gene or gene-environment interactions. The selection of the appropriate statistical tests is critical and will be dependent on the nature of the dataset (e.g., case-control vs. family data) as well as the specific research hypotheses being tested. This paper describes the various study and analysis categories used for such analyses, including the advantages and limitations of such techniques.


[Enzymatic changes in cancer].
Several enzymes were estimated in different tumors. Ceruloplasmin, lactate dehydrogenase (LDH), and phosphohexose isomerase (PHI) showed a direct correlation with tumor growth and remission. The ratio LDH/PHI was low in solid tumors and high in lymphomas, suggesting a different metabolism.


Significance of cell groups in voided urine.
To determine the significance of different types of cell groups in voided urine for diagnosing transitional cell carcinoma (TCC). We reviewed voided urine specimens, with corresponding biopsies taken within 120 days after urine collection, for cell groups. Type and number of cell groups were correlated with the histologic diagnoses. Of 5,001 voided urine specimens, 134 (3%) had corresponding biopsies. Flat sheets were significantly more common in urine specimens with corresponding negative biopsies (24%) than in those with biopsies showing TCC (6%) (chi 2 P = .0032). The incidence of collared, three-dimensional cell groups was low (0-7%) and not associated with biopsy findings. Irregular, three-dimensional cell groups were more common than collared cell groups and were most common in cases with invasive TCC on biopsy (38%). While this was statistically significantly more common than in urines associated with negative biopsies (17%) (chi 2 P = .0499), it was not specific. Requiring three or more irregular cell groups did not improve discrimination between TCC and benign cases. Cell groups of any type or number were not more common in cases associated with grade 1 papillary TCC than negative biopsies. Diagnoses associated with multiple irregular, three-dimensional cell groups and a negative biopsy included medullary sponge kidney, hemorrhagic cystitis, cystitis not otherwise specified, and urolithiasis. Irregular, three-dimensional cell groups were most common in voided urine from patients with invasive TCC, but the identification of cell groups of any type in voided urine had little diagnostic utility.


Modelling studies of water in crystalline nanoporous aluminosilicates.
The paper presents a review of molecular modelling studies of hydrated nanoporous aluminosilicates (zeolites and clays) performed during the last decade. A special emphasis is set on the calculation of the dynamical quantities and collective properties of the confined water. Some new results concerning the behaviour of water molecules in the siliceous silicalite and zeolite beta structures are presented.


Bartonella henselae in canine cavitary effusions: prevalence, identification, and clinical associations.
Previous reports suggest an association between Bartonella infection and effusions in dogs and human beings. The aims of this study were to determine the prevalence of Bartonella infection in canine effusions and to investigate historic and clinical parameters predictive of Bartonella in dogs with effusions. Canine cavitary effusions submitted for analysis and, if available, paired EDTA blood, were screened for Bartonella infection using the Bartonella α-proteobacteria growth medium enrichment culture/PCR diagnostic platform (Bartonella enrichment PCR or ePCR) at Galaxy Diagnostics, Inc. Bartonella henselaeDNA was PCR-amplified and sequenced from 15% (12/80) of sampled dogs. Enrichment culture prior to PCR testing was required for Bartonella detection in 92% (11/12) of cases. Twenty percent (4/20), 13% (8/60), and 0% (0/4) of dogs with pleural, peritoneal, and pericardial effusions, respectively, tested positive. Bartonella henselae was detected most frequently in the fall, and young and middle-aged dogs appeared to be overrepresented. Golden Retrievers and Yorkshire/Silky Terriers each comprised 25% of infected dogs (odds ratio 3.4 for Golden Retrievers). There was a weak association with hemorrhagic effusions. Fifty percent of Bartonella-positive dogs had hemorrhage as a component of their effusion compared to 37% of PCR-negative dogs (odds ratio 1.7). Viable B henselae organisms occur in pleural and peritoneal effusions of dogs; the clinical relevance of which remains unclear and may represent opportunistic infection. Associations found in this study included seasonal variation, age, breed, and site of effusion.


Associations between psychological characteristics and indicators of metabolic syndrome among Chinese adults.
Current knowledge about the relationship between psychological characteristics and metabolic syndrome (MetS) components is limited in Asian populations. The purpose of this study is to investigate linkages between physiological markers of MetS and life satisfaction, hostility, and depression in Chinese adults. Secondary analyses were conducted using cross-sectional data from parents of randomly selected middle school students participating in a pilot study in Qingdao, China. Among 440 parents who consented to participate (237 women, 203 men), 368 provided valid responses in all three categories of psychological characteristics, and only those subjects were included in these analyses. General linear models and logistic regressions were run separately by gender, controlling for covariates. Among women, life satisfaction was inversely associated with triglyceride levels (p = .04), LDL-C (p < .01), risk of hypertriglyceridemia (OR[.53], p < .01), HDL-C (OR[.78], p = .03), and MetS (OR[.52], p = .03). No associations were found between life satisfaction and any psychological characteristics among men. Among women, hostility was positively associated with triglyceride level (p = .04) and risk of hypertriglyceridemia (OR[2.12], p < .05). Among men, hostility was positively associated with waist circumference (p = .04), waist-hip ratio (p < .05), and fasting plasma insulin (p < .01). Depression was not associated with any physiological measurement in either gender. These findings indicate that relationships exist between certain psychological characteristics and physiological indicators of MetS among Chinese adults, although there may be important differences between genders.


Self-scaling of clipped photon correlations.
The estimates of photoemission rate correlations that are obtained by clipped, e.g., one-bit, correlation techniques are in general distorted by the clipping, unless scaling techniques are used. It is shown that the Pois-son statistics of photoemission processes are such that the processes are inherently self-scaling when the range of signal fluctuations is contained in the range of inherent noise fluctuations. Self-scaling occurs, for example, when the total mean emission rate is large compared with the time varying signal rate. It permits clipped correlation to be used without distortion.


Mechanism of branching in negative ionization fronts.
When a strong electric field is applied to nonconducting matter, narrow channels of plasma called streamers may form. Branchlike patterns of streamers have been observed in anode directed discharges. We explain a mechanism for branching as the result of a balance between the destabilizing effect of impact ionization and the stabilizing effect of electron diffusion on ionization fronts. The dispersion relation for transversal perturbation of a planar negative front is obtained analytically when the ratio D between the electron diffusion coefficient and the intensity of the externally imposed electric field is small. We estimate the spacing lambda between streamers and deduce a scaling law lambda approximately D(1/3).


An unusual cause of intestinal obstruction--computed tomographic findings.
Computed tomographic findings in a case of acute intestinal obstruction due to ingested heroin packages are described. Ingestion of drug packages for the purpose of contraband transportation is a well-known method employed by drug-traffickers and intestinal obstruction may be seen as a complication. Plain radiographs and history are usually adequate for diagnosis when required for medico-legal purposes.


[Study of screening nephroprotective bioactive substances based on triple-color fluorescence probes in Carthami flos].
In this study, an approach based on triple-color fluorescence probes was developed for screening potential nephro-protective bioactive substances. Three fluorescent probes (i. e. FDA, MTR and Hoechst 33342) were used to label HK-2 cells injured by doxorubicin hydrochloride, and cellular fluorescence images were subsequently acquired and analyzed by a cellular-fluorescence image microscopy platform. The established method was applied to screening 53 components of Carthami Flos, and three components C17, C18 and C19 were found to exhibit nephroprotective effects against doxorubicin hydrochloride induced injury on HK-2 cells. Eight compounds (i. e. hydroxysafflor yellow A, 6-hydroxykaempferol-3-O-rutinoside-6-O-glucoside, 6-hydroxykaempferol-3,6-di-O-gluco-side or 6-hydroxykaempferol-6, 7-di-O-glucoside, 6-hydroxykaempferol-3-O-rutinoside, 6-hydroxykaempferol-3-O-glucoside or 6-hydroxykaempferol-7-O-glucoside, rutin, isoquercetin, and kaempferol-3-O-rutinoside) in components C17, C18 and C19 were preliminarily identified by liquid chromatography-mass spectrometry (LC-MS). Isoquercetin, rutin, kaempferol-3-O-rutinoside, and hydroxysafflor yellow A were confirmed by comparing with reference substances, Further study indicated that these four compounds had moderate nephroprotective effects, while isoquercetin showed a significant nephroprotective effect in a dose-dependent manner. These results suggest that isoquercetin, rutin, kaempferol-3-O-rutinoside and hydroxysafflor yellow A might be the nephroprotective bioactive substances in Carthami Flos.


The ineligible patient: how to treat patients not included in clinical studies.
Targeted therapies are currently the standard of care for metastatic renal cell carcinoma (mRCC). Five VEGF pathway inhibitors (sorafenib, sunitinib, bevacizumab in combination with interferon-alpha, pazopanib, and axitinib) and two mTOR inhibitors (everolimus and temsirolimus) are now FDA approved for mRCC based on results from phase III randomized clinical trials (RCTs). However, several subgroups of patients are excluded from enrollment due to strict eligibility criteria. The toxicity and efficacy of targeted therapies in these populations are unknown. PubMed was searched for citations of the pivotal phase III RCTs leading to FDA approval. These publications were cross-referenced with their associated entries on www.ClinicalTrials.gov, and both were abstracted for eligibility criteria for patient enrollment. Based on this data, PubMed was searched for both prospective and retrospective studies evaluating toxicity and efficacy of targeted therapies for mRCC in these ineligible patient subgroups. We reviewed published toxicity and efficacy data in several ineligible patient subgroups, including patients with non-clear cell renal cell carcinoma, poor performance status, poor renal function, CNS metastases, significant cardiac comorbidities, and prior systemic therapy. Targeted therapies appear to be safe in most ineligible patient populations, including patients with poor renal function. However, patients with preexisting cardiac comorbidities are at greater risk of developing cardiac toxicity on sunitinib. Targeted therapies appear to have some efficacy in maintaining stable disease in these subgroups, but are limited to rare partial responses. Prospective cohort studies are needed to accurately assess the safety and efficacy of targeted therapies in ineligible patient subgroups.


Antigravitropic PIN polarization maintains non-vertical growth in lateral roots.
Lateral roots are typically maintained at non-vertical angles with respect to gravity. These gravitropic setpoint angles are intriguing because their maintenance requires that roots are able to effect growth response both with and against the gravity vector, a phenomenon previously attributed to gravitropism acting against an antigravitropic offset mechanism. Here we show how the components mediating gravitropism in the vertical primary root-PINs and phosphatases acting upon them-are reconfigured in their regulation such that lateral root growth at a range of angles can be maintained. We show that the ability of Arabidopsis lateral roots to bend both downward and upward requires the generation of auxin asymmetries and is driven by angle-dependent variation in downward gravitropic auxin flux acting against angle-independent upward, antigravitropic flux. Further, we demonstrate a symmetry in auxin distribution in lateral roots at gravitropic setpoint angle that can be traced back to a net, balanced polarization of PIN3 and PIN7 auxin transporters in the columella. These auxin fluxes are shifted by altering PIN protein phosphoregulation in the columella, either by introducing PIN3 phosphovariant versions or via manipulation of levels of the phosphatase subunit PP2A/RCN1. Finally, we show that auxin, in addition to driving lateral root directional growth, acts within the lateral root columella to induce more vertical growth by increasing RCN1 levels, causing a downward shift in PIN3 localization, thereby diminishing the magnitude of the upward, antigravitropic auxin flux.


Temporal small RNA transcriptome profiling unraveled partitioned miRNA expression in developing maize endosperms between reciprocal crosses.
In angiosperms, the endosperm nurtures the embryo and provides nutrients for seed germination. To identify the expression pattern of small interfering RNA in the developing maize endosperm, we have performed high-throughput small RNA transcriptome sequencing of kernels at 0, 3, and 5 days after pollination (DAP) and endosperms at 7, 10, and 15 DAP using B73 and Mo17 reciprocal crosses in previous study. Here, we further explored these small RNA-seq data to investigate the potential roles of miRNAs in regulating the gene expression process. In total, 57 conserved miRNAs and 18 novel miRNAs were observed highly expressed in maize endosperm. Temporal expression profiling indicated that these miRNAs exhibited dynamic and partitioned expression patterns at different developmental stages between maize reciprocal crosses, and quantitative RT-PCR results further confirmed our observation. In addition, we found a subset of distinct tandem miRNAs are generated from a single stem-loop structure in maize that might be conserved in monocots. Furthermore, a SNP variation of Zma-miR408-5p at 11th base position was characterized between B73 and Mo17 which might lead to completely different functions in repressing targets. More interestingly, Zma-miR408-5p exhibited B73-biased expression pattern in the B73 and Mo17 reciprocal hybrid endosperms at 7, 10, and 15 DAP according to the reads abundance with SNPs and CAPS experiment. Together, this study suggests that miRNA plays a crucial role in regulating endosperm development, and exhibited distinct expression patterns in developing endosperm between maize reciprocal crosses.


Ezetimbe as potential treatment for cholesterol gallstones: the need for clinical trials.
Obesity is associated with insulin resistance, non-alcoholic fatty liver disease (NAFLD) and gallstones.High fat diets (unsaturated fats) rich in cholesterol have been demonstrated to produce not only gallstones but also NAFLD and insulin resistance. Interestingly, a high incidence of gallstones is being reported in association with insulin resistance and NAFLD. Laparoscopic cholecystectomy is the best definitive therapy for symptomatic gallbladder disease. Ezetimibe is a drug that inhibits the absorption of both dietary and biliary cholesterol in the small intestine. Importantly, ezetimibe showed potential benefit not only in treating and preventing gallstones but also in insulin resistance and NAFLD. Further studies are required before the use of ezetimibe for the treatment of gallstones can be advocated.


[Sudden cerebrovascular accidents in the District of Martin. The clinical picture and epidemiologic data].
The authors investigated stroke morbidity (incidence, prevalence) and mortality, established register, and analyzed the epidemiological situation of this disease in the Martin district. Precondition for this study has been in 35 years neurological following the stroke patients at four neurological out-patients departments of the district and their hospitalization at the Neurological Clinic in Martin. During the period from 1983-1986 559 patients with an average age of 64.1 +/- 12.8 years (the range being 4-97 years) were treated at the above institutions. During four years of the study the average incidence of the stroke was 108/100.000/year. The mortality of the group 45/100.000/year is, as compared with world-wide statistics, low and is due to the care devoted to stroke patients for many years. The calculated, so-called expected prevalence, is 920 +/- 147/100.000 and can be explained by the relatively low mortality. In the Turiec region there are some 1012 +/- 162 stroke patients. This number was obtained by calculation for the number of inhabitants of the Martin District.


ERβ-mediated estradiol enhances epithelial mesenchymal transition of lung adenocarcinoma through increasing transcription of midkine.
Epithelial-mesenchymal transition (EMT) plays a specific role in the migration of tumor cells. Both estrogen and midkine (MK) have been thought to be important factors in promoting the progression of non-small-cell lung cancer (NSCLC) and can enhance EMT. Some evidence indicated the correlation between estradiol (E2) and MK, but the precise mechanism on their interreaction is unknown. Here, we try to clarify whether and how E2 regulates MK expression to promote EMT. We found that E2 increased MK mRNA expression in lung adenocarcinoma cells LTEP-a2 and A549 in a time-dependent manner. E2-induced MK expression was inhibited by the estrogen receptor (ER) antagonist ICI 182,780 and tamoxifen but not by phosphoinositide-3 kinase and MAPK inhibitors, suggesting a genomic mechanism of E2 on the regulation of MK transcription. Moreover, luciferase reporter and chromatin immunoprecipitation assays exhibited that E2 induced ERβ recruitment to the estrogen response element in the MK promoter. Small interfering RNA to ERα and ERβ revealed that ERβ mainly mediated E2-induced MK transcription. Interestingly, E2 enhanced MK expression in accordance with increase of EMT, whereas knockdown of MK could block EMT under E2 stimulation. Importantly, through analyzing lung adenocarcinoma tissues, there was indeed a correlation among levels of E2, MK, and EMT-related protein expression. Taken together, we reported a previously unrecognized mechanism on E2 in the regulation of MK expression and proved that MK plays a pivotal role in progression of E2-regulated EMT.


Sustaining an ageing population: the role of micronutrients in frailty and cognitive impairment.
Age-related frailty and cognitive decline are complex multidimensional conditions that significantly impact the ability of older adults to sustain functional capacity and independence. While underlying causes remain poorly understood, nutrition continually emerges as one associated risk element. Many studies have addressed the importance of adequate nutrition in delaying the onset of these conditions, but the specific role of micronutrients is not well established. The consideration of pre-frailty as an outcome variable is also limited in the current literature. In this review, we focus on the potential value of maintaining micronutrient sufficiency to sustaining the health of the ageing population. Using data from the Irish longitudinal study on ageing, we consider several vitamins known to have a high prevalence of low status in older adults and their impact on pre-frailty, frailty and cognitive impairment. They include vitamin B12 and folate, both of which are associated with multiple biological mechanisms involved in long-term health, in particular in cognitive function; vitamin D, which has been associated with increased risk of musculoskeletal disorders, depression and other chronic diseases; and the carotenoids, lutein and zeaxanthin, that may help mitigate the risk of frailty and cognitive decline via their antioxidant and anti-inflammatory properties. We show that low concentrations of folate and carotenoids are implicated in poorer cognitive health and that the co-occurrence of multiple nutrient deficiencies confers greatest risk for frailty and pre-frailty in the Irish longitudinal study on ageing cohort. These health associations contribute to evidence needed to optimise micronutrient status for health in the older adult population.


Stone recurrences in kidneys made stone-free by percutaneous extraction.
Of 100 renal units which were made stone-free by percutaneous stone extraction in 1985, 86 (86.0%) were re-examined radiologically up to 5 years after operation. The re-examination was performed because of symptoms or as part of a regular check-up or after calling the patient. Intrarenal calcifications were diagnosed in 27 of 86 (31.4%) of the renal units, but only in 11 (12.8%) were there stones requiring treatment.


The impact of community context on children's health and nutritional status in China.
The link between community environment and individual health outcomes has been widely documented in Western literature, but little is known about whether community context influences children's health over and above individual characteristics in developing countries. This study examines how community socioeconomic status (SES) influences children's self-rated health and nutritional status in urban and rural China and explores whether the effects of community SES vary by a child's gender and family background. Using data from the China Family Penal Studies in 2010, this study focuses on children aged 10-15 years old living in 261 urban neighborhoods and 293 rural villages in China. Multilevel regression models are estimated to examine the effect of community SES on the probability of reporting poor/fair health and nutritional status measured by height for age while controlling for individual and family characteristics. The results suggest that community SES has a positive and curvilinear effect on children's health and nutritional status in urban China, and it only positively influences children's nutrition in rural China. Community SES has a stronger effect for boys than for girls, and for children in poorer families and families with lower levels of parental involvement.


Modeling the Parasitic Filariasis Spread by Mosquito in Periodic Environment.
In this paper a mosquito-borne parasitic infection model in periodic environment is considered. Threshold parameter R0 is given by linear next infection operator, which determined the dynamic behaviors of system. We obtain that when R0 < 1, the disease-free periodic solution is globally asymptotically stable and when R0 > 1 by Poincaré map we obtain that disease is uniformly persistent. Numerical simulations support the results and sensitivity analysis shows effects of parameters on R0, which provided references to seek optimal measures to control the transmission of lymphatic filariasis.


Control of Excited-State Conformations in B,N-Acenes.
We present a new concept to control the conformations of molecules in the excited state through harvesting negative hyperconjugation. The strategy was realized with the 2,3,1,4-benzodiazadiborinane scaffold, which was prepared by a new synthetic procedure. Photochemical studies identified dual light emission, which was assigned to well-defined conformers. The emission at longer wavelength can be switched off by restricting the rotational degrees of freedom in the solid state as well as by controlling the energy levels of the excited states through adjusting the solvent polarity.


Nursing home administrator compensation: pay equity and determinants of salary.
This study evaluates the issue of gender-based pay inequality. Male NHAs earn 7 percent more than female NHAs, but factors such as education, experience, tenure, facility size, ownership, location, competition, and emphasis on private pay census account for the difference. The findings, however, indicate that racial inequalities and gender differences among married NHAs may be present, requiring further investigation. Key implications of the results are discussed.


Cerebrovascular disease mortality in Spain, 1955-1992: an age-period-cohort analysis.
The purpose of this study was to assess the contributions of period and birth cohort effects to changes in cerebrovascular disease (CVD) mortality in Spain over the period 1955-1992. Poisson regression models were fitted to age-and sex-specific CVD mortality rates obtained from National Vital Statistics. In the period 1955-1975, CVD mortality remained stable. In the period 1975-1992, CVD mortality declined by 54% (rate ratio, RR: 0.46; 95% confidence interval, CI: 0.43-0.49) in males and 62% (RR: 0.38; 95% CI: 0.34-0.42) in females. The cohort effect was very small up to the generation born in 1905, moving clearly downward thereafter. CVD mortality for subjects born in the period 1945-1949 was lower than for those born in the period 1905-1909 by 68% (RR: 0.32; 95% CI:0.16-0.63) in males and 82% (RR: 0.18; 95% CI: 0.07-0.45) in females. Among the possible partial explanations for these effects are the decline in ischemic heart disease and rheumatic fever mortality, the drop in salt and alcohol intake, the reduction in smoking among males and blood pressure among females, and the widespread use of antihypertensive treatments in Spain over the last 20 years.


The Effect of a Golden Hour Policy on the Morbidity and Mortality of Combat Casualties.
The term golden hour was coined to encourage urgency of trauma care. In 2009, Secretary of Defense Robert M. Gates mandated prehospital helicopter transport of critically injured combat casualties in 60 minutes or less. To compare morbidity and mortality outcomes for casualties before vs after the mandate and for those who underwent prehospital helicopter transport in 60 minutes or less vs more than 60 minutes. A retrospective descriptive analysis of battlefield data examined 21,089 US military casualties that occurred during the Afghanistan conflict from September 11, 2001, to March 31, 2014. Analysis was conducted from September 1, 2014, to January 21, 2015. Data for all casualties were analyzed according to whether they occurred before or after the mandate. Detailed data for those who underwent prehospital helicopter transport were analyzed according to whether they occurred before or after the mandate and whether they occurred in 60 minutes or less vs more than 60 minutes. Casualties with minor wounds were excluded. Mortality and morbidity outcomes and treatment capability-related variables were compared. For the total casualty population, the percentage killed in action (16.0% [386 of 2411] vs 9.9% [964 of 9755]; P < .001) and the case fatality rate ([CFR] 13.7 [469 of 3429] vs 7.6 [1344 of 17,660]; P < .001) were higher before vs after the mandate, while the percentage died of wounds (4.1% [83 of 2025] vs 4.3% [380 of 8791]; P = .71) remained unchanged. Decline in CFR after the mandate was associated with an increasing percentage of casualties transported in 60 minutes or less (regression coefficient, -0.141; P < .001), with projected vs actual CFR equating to 359 lives saved. Among 4542 casualties (mean injury severity score, 17.3; mortality, 10.1% [457 of 4542]) with detailed data, there was a decrease in median transport time after the mandate (90 min vs 43 min; P < .001) and an increase in missions achieving prehospital helicopter transport in 60 minutes or less (24.8% [181 of 731] vs 75.2% [2867 of 3811]; P < .001). When adjusted for injury severity score and time period, the percentage killed in action was lower for those critically injured who received a blood transfusion (6.8% [40 of 589] vs 51.0% [249 of 488]; P < .001) and were transported in 60 minutes or less (25.7% [205 of 799] vs 30.2% [84 of 278]; P < .01), while the percentage died of wounds was lower among those critically injured initially treated by combat support hospitals (9.1% [48 of 530] vs 15.7% [86 of 547]; P < .01). Acute morbidity was higher among those critically injured who were transported in 60 minutes or less (36.9% [295 of 799] vs 27.3% [76 of 278]; P < .01), those severely and critically injured initially treated at combat support hospitals (severely injured, 51.1% [161 of 315] vs 33.1% [104 of 314]; P < .001; and critically injured, 39.8% [211 of 530] vs 29.3% [160 of 547]; P < .001), and casualties who received a blood transfusion (50.2% [618 of 1231] vs 3.7% [121 of 3311]; P < .001), emphasizing the need for timely advanced treatment. A mandate made in 2009 by Secretary of Defense Gates reduced the time between combat injury and receiving definitive care. Prehospital transport time and treatment capability are important factors for casualty survival on the battlefield.


Intraspecific variation in estrogen receptor alpha and the expression of male sociosexual behavior in two populations of prairie voles.
Estrogen (E) regulates a variety of male sociosexual behaviors. We hypothesize that there is a relationship between the distribution of estrogen receptor alpha (ERalpha) and the degree of male social behavior. To test this hypothesis, ERalpha immunoreactivity (IR) was compared in prairie voles (Microtus ochrogaster) from Illinois (IL), which are highly social, and Kansas (KN), which are less social. The expression of androgen receptors (AR) in males also was compared between populations. The expression of ERalpha and AR were compared in brains from KN and IL males and females using immunocytochemistry (ICC). There were significant intrapopulational differences, with males expressing less ERalpha-IR than females in the medial preoptic area, ventromedial nucleus, ventrolateral portion of the hypothalamus, and bed nucleus of the stria terminalis (BST). IL males also displayed less ERalpha-IR in the medial amygdala (MeA) than IL females. While IL males expressed significantly less ERalpha-IR in the BST and MeA than KN males, there was no difference in AR-IR. Differences in the pattern of ERalpha-IR between KN and IL males were behaviorally relevant, as low levels of testosterone (T) were more effective in restoring sexual activity in castrated KN males than IL males. The lack of difference in AR combined with lower expression of ERalpha-IR in IL males suggests that behavioral differences in response to T are associated with aromatization of T to E and that reduced sensitivity to E may facilitate prosocial behavior in males.


Recombinant PTD-Cu/Zn SOD attenuates hypoxia-reoxygenation injury in cardiomyocytes.
Oxidative stress plays a pivotal role in myocardial ischemia-reperfusion injury. Increasing the protein expression of intracellular Cu/Zn SOD, which is the major endogenous antioxidant enzyme, may attenuate or prevent hypoxia-reoxygenation injury (HRI) in cultured cardiomyocytes. However, ectogenic Cu/Zn-SOD can hardly be transferred into cells to exert biological effects. In this study, we constructed PTD-Cu/Zn SOD plasmid with a kind of translocation structure-Protein transduction domain (PTD) and detected its transmembrane ability and antioxidant effects in H9c2 rat cardiomyocytes subjected to hypoxia/reoxygenation injury (HRI). We constructed the pET-PTD-Cu/Zn SOD (CDs) prokaryotic expression vectors in plasmid that were inserted into E. coli BL21 to induce the protein expression of PTD-Cu/Zn SOD. H9c2 cardiomyocyte HRI was achieved by exposing cardiomyocytes to 12 h hypoxia followed by 2 h reoxygenation. Protein expression of PTD-Cu/Zn SOD in cardiomyocytes was assayed by Western blot and their enzyme activities were investigated by immunohistochemistry and flow cytometry. In cultured cardiomyocytes hypoxia-reoxygenation injury model, exogenous PTD-Cu/Zn SOD could penetrate cell membrane to clear superoxide anion and decrease hydrogen peroxide level in H9c2 cardiomyocytes subjected to HRI. The level of mitochondrial membrane potential was restored to normal, and the cell apoptosis was reduced in cardiomyocytes with PTD-Cu/Zn SOD treatment during HRI. Recombinant PTD-Cu/Zn SOD could scavenge intracellular-free superoxide anion, protect mitochondria from damages, and attenuate the hypoxia-reoxygenation injury in cultured cardiomyocytes.


The role of the organ microenvironment in brain metastasis.
More than 40% of patients with lung cancer and breast cancer develop brain metastasis. With improved local control and therapy of metastasis to visceral organs, the morbidity and mortality due to late diagnosed brain metastasis are projected to rise. The median survival for untreated patients is 1-2 months, which may be extended to 6 months with surgery, radiotherapy, and chemotherapy. The development of a relevant mouse model for the establishment and growth of brain metastasis has advanced our understanding of the biology and therapy of this most feared consequence of cancer. Injection of murine or human tumor cells into the internal carotid artery of mice produces experimental metastases in specific regions of the brain that are not due to patterns of initial cell arrest, motility, or invasiveness, but rather to the ability of metastatic tumor cells to exploit homeostatic mechanisms and proliferate. Immunohistochemical and morphometric analyses demonstrate that the density of blood vessels within experimental metastases in brains of mice or in clinical specimen of human lung cancer brain metastases is lower than that in the adjacent tumor-free brain parenchyma. However, brain metastasis-associated blood vessels are dilated and contain numerous dividing endothelial cells. Immunohistochemical analysis also reveals that tumor cells located less than 100 μm from a blood vessel are viable, whereas more distant tumor cells undergo apoptosis. Tumor cells within brain metastasis produce VEGF which induces permeability in adjacent vessels. The BBB in metastases that are larger than 0.25 mm in diameter is leaky. Metastases in the brain are resistant to chemotherapeutic drugs. The venerable "seed and soil" hypothesis suggests that the outcome of metastasis depends on the interaction between unique tumor cells and the specific organ microenvironment. The demonstration that activated astrocytes whose physiological role is to protect neurons from toxic substances can be exploited by tumor cells for protection from chemotherapeutic drugs suggests new approaches to the treatment of this fatal disease.


Airflow resistance of heat and moisture exchange filters with and without a tracheostoma valve.
Rehabilitation of laryngectomees has been furthered by the introduction of heat and moisture exchange (HME) filters, placed over a tracheostoma or on a tracheostoma valve (TSV). The airflow resistance of HME filters is an important factor with regard to the comfort of the patient. The goal of this study was to determine the airflow resistance (defined as the pressure drop over the device divided by the squared airflow through the device) of 4 commercially available HME filters with and without a TSV. The pressure drop over and the airflow through the devices were measured in vitro. Distinct differences among the devices were found. The mean airflow resistance of the HME filters ranged from 135 to 346 Pa x s2/L2, that of TSVs was between 66 and 297 Pa x s2/L2, and that of the combination was between 263 and 454 Pa x s2/L2. The Stom-Vent 2 HME filter and the Adeva Window TSV with an Adeva filter had the lowest airflow resistance of the devices measured in this study.


Endoscopic lung volume reduction with endobronchial valves in patients with severe emphysema and established pulmonary hypertension.
One of the most common forms of pulmonary hypertension (PH) is that associated with chronic obstructive pulmonary disease (COPD). So far, patients with severe emphysema and established PH have been excluded from endoscopic lung volume reduction (ELVR) therapy due to the risk of right heart decompensation. The aim of this pilot study was to evaluate the feasibility and efficacy of ELVR using one-way endobronchial valves (EBV) in this specific group of patients. We prospectively included 6 patients with COPD, severe heterogeneous emphysema, and established PH who underwent right heart catheterization and clinical assessments before and 90 days after ELVR with unilateral EBV placement. This study was not powered to measure any statistical differences in endpoints. Ninety days after ELVR, the symptoms, lung function, and hemodynamics improved in 5 out of 6 patients (1 patient normalized and 1 slightly worsened). The mean hemodynamics improved from baseline to 90 days after ELVR as follows: mean pulmonary artery pressure, -2.5 ± 3.5 mm Hg; pulmonary arterial wedge pressure, -4.3 ± 8.3 mm Hg; cardiac index, +0.3 ± 0.6 l/min/m(2), and 6-min walk distance, +59 ± 99 m. ELVR was performed without PH-related complications in all patients. To our knowledge, this is the first prospective, single-center pilot study to evaluate the feasibility and efficacy of ELVR in patients with established PH. ELVR was feasible and resulted in an improvement of clinical and hemodynamic parameters in 5 out of 6 patients. These results have to be further confirmed in larger-scale controlled studies.


Two different nucleotide substitutions of APC gene in a family with familial adenomatous polyposis.
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome leading to colorectal cancer. This disease appears as a result of germline mutation in adenomatous polyposis coli (APC) gene. The aim of the present study is to report the association between two different nucleotide substitutions detected in a family with FAP. In the proband, p.His1172Gln (c.3516delT) was detected in exon 15 of the APC gene. Furthermore, p.His1172Gln (c.3516delT) and, in addition to this mutation, p.Met1413Val (c.4237 A > G) were detected in exon 15 in both daughters of the proband. However, we believe that single nucleotide change in codon 1413 may be a polymorphic variant and deletion T in codon 1172 of APC gene is associated with FAP, attenuated FAP and extracolonic FAP involvement. Along with common use of genetic tests in the clinical practice, genotype-phenotype correlation may be recognized better and useful for early diagnosis and prevention of familial cancer syndromes.


Social Media Guidelines for Young Plastic Surgeons and Plastic Surgery Training Programs.
Social media are a powerful tool that creates a unique opportunity for the young plastic surgeon and trainee to share content, brand oneself, educate the public, and develop one's own professional voice early. The majority of all plastic surgery programs and particularly those that are highly ranked have social media opportunities for their residents, yet clear rules to guide implementation of social media programming in residency have remained unspecified. These guidelines and pitfalls can be used to inform a productive and professional entry into plastic surgery social media use for the resident and young plastic surgeon. Details regarding specific platform use to maximize exposure are provided. The core principles of patient safety and privacy, authentic photography, plastic surgery education and advocacy, and professionalism inform these guidelines. Pitfalls include establishment of an online physician-patient relationship, engaging in debate by means of online reviews, providing medical entertainment, and engaging in non-plastic surgery politics. Use of these guidelines will allow the young plastic surgeon and trainee to succeed by means of social media platforms in an ethical and professional manner.


High genetic diversity revealed by variable-number tandem repeat genotyping and analysis of hsp65 gene polymorphism in a large collection of "Mycobacterium canettii" strains indicates that the M. tuberculosis complex is a recently emerged clone of "M. canettii".
We have analyzed, using complementary molecular methods, the diversity of 43 strains of "Mycobacterium canettii" originating from the Republic of Djibouti, on the Horn of Africa, from 1998 to 2003. Genotyping by multiple-locus variable-number tandem repeat analysis shows that all the strains belong to a single but very distant group when compared to strains of the Mycobacterium tuberculosis complex (MTBC). Thirty-one strains cluster into one large group with little variability and five strains form another group, whereas the other seven are more diverged. In total, 14 genotypes are observed. The DR locus analysis reveals additional variability, some strains being devoid of a direct repeat locus and others having unique spacers. The hsp65 gene polymorphism was investigated by restriction enzyme analysis and sequencing of PCR amplicons. Four new single nucleotide polymorphisms were discovered. One strain was characterized by three nucleotide changes in 441 bp, creating new restriction enzyme polymorphisms. As no sequence variability was found for hsp65 in the whole MTBC, and as a single point mutation separates M. tuberculosis from the closest "M. canettii" strains, this diversity within "M. canettii" subspecies strongly suggests that it is the most probable source species of the MTBC rather than just another branch of the MTBC.


Multi-site voxel-based morphometry: methods and a feasibility demonstration with childhood absence epilepsy.
Voxel-based morphometry analysis of neurological disorders would benefit if it could use data acquired from different scanners, but scanner based contrast variation could interfere with the detection of disease-specific structural abnormalities. In this study we examine MRI data from three different sites to investigate structural differences between childhood absence epilepsy (CAE) subjects and controls. T1-weighted structural MRI scans were acquired from: Site A. 10 CAE, 213 controls; Site B. 15 CAE, 33 controls; and Site C. 19 CAE, 11 controls. The images were processed using the optimised VBM protocol. Three statistical analyses were undertaken: (1) Comparisons of CAE subjects and controls stratified by site. (2) Between-site comparison of controls from each site. (3) Factorial analysis of all data with site and disease status as factors. Consistent regions of structural change, located in the thalamic nuclei, were observed in the within-site analysis of CAE vs controls. Analysis of control scans, however, indicated site-specific differences between controls, which required that we adjust for site in combined analyses. Analysis of all data with adjustment for site confirmed the finding of thalamic atrophy in CAE cases. Combined VBM analysis of structural MRI scans acquired from different sites yield consistent patterns of structural change in CAE when site is included as a factor in the statistical analysis of the processed images. In MRI studies of diseases where only a limited number of subjects can be imaged at each site, our study supports the possibility of effective multi-site studies as long as both disease subjects and healthy controls are acquired from each site.


Differentiation state determines neural effects on microvascular endothelial cells.
Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells.


Blind binary masking for reverberation suppression in cochlear implants.
A monaural binary time-frequency (T-F) masking technique is proposed for suppressing reverberation. The mask is estimated for each T-F unit by extracting a variance-based feature from the reverberant signal and comparing it against an adaptive threshold. Performance of the estimated binary mask is evaluated in three moderate to relatively high reverberant conditions (T60 = 0.3, 0.6, and 0.8 s) using intelligibility listening tests with cochlear implant users. Results indicate that the proposed T-F masking technique yields significant improvements in intelligibility of reverberant speech even in relatively high reverberant conditions (T60 = 0.8 s). The improvement is hypothesized to result from the recovery of the vowel/consonant boundaries, which are severely smeared in reverberation.


The interaction between personality, offspring fitness and food abundance in North American red squirrels.
Animal personality is now frequently reported in wild and captive populations. It has been shown to be moderately heritable and to have potentially important fitness consequences. Variation in personality within a population may be maintained by balancing selection if different values of personality traits are favoured under different conditions. We measured personality in 98 female North American red squirrels (Tamiasciurus hudsonicus Erxleben), and examined whether its variation could be maintained by changing selection pressures acting via reproductive traits and yearly variation in food abundance. There was no effect of personality on parturition date or litter size, but a female's activity was correlated to the growth rate of her offspring in the nest, and her aggressiveness was correlated to their survival in the nest and overwinter. The magnitude and direction of the effects changed among life history stages and years, possibly in association with food supply in some cases, and may indicate a role for balancing selection in the maintenance of personality.


Human cytidine deaminase: understanding the catalytic mechanism.
In the absence of an experimentally elucidated three-dimensional structure of the human CDA, we built an homology model of this enzyme starting from the crystal structure of its E. coli homologous. Furthermore, we docked in the active site alternatively the substrate, the intermediate or the product. By means of molecular dynamics simulations, we determined the topology of the active site, identifying the amino acids involved in the catalytic mechanism, and outlining the central role played by E67.


[4 + 1] Cycloaddition Reaction of α,β-Alkynic Hydrazones and KSCN under Transition-Metal-Free Conditions: Synthesis of N-Iminoisothiazolium Ylides.
A novel heteroannulation reaction between α,β-alkynic hydrazones and potassium thiocyanate has been developed for the synthesis of N-iminoisothiazolium ylides. The transformation features wide substrate scope, functional tolerance, and easy operation. This investigation involves a [4 + 1]-type cycloaddition reaction and C-S/S-N bond formation under transition-metal-free conditions. The application of this transformation to the gram-scale preparation of the N-imide ylide is also accomplished.


Tear fluid content of electrochemically active components including water soluble antioxidants.
To describe the content of water-soluble antioxidants in tear fluid. We collected tear fluid from healthy subjects, either into borosilicate glass tubing or by absorption onto Schirmer strips. High pressure liquid chromatography with electrochemical detection provided data on several components in a single assay. The system was sufficiently sensitive to provide reliable values for components present in tear fluid collected at normal (basal) or stimulated rates of secretion. Tear fluid at basal secretion was found to contain four compounds often considered to function in biology as antioxidants. Ascorbic acid (AA) is found at 665 microM, tyrosine at 45 microM and glutathione (GSH) at 107 microM. Cysteine (48 microM) and uric acid (328 microM) are reported for the first time; the latter is somewhat controversial as a physiologically active antioxidant. One peak on the chromatogram was consistently present but has not been identified. During stimulation of flow by brief inhalation of ammonium hydroxide fumes, the concentration of each compound was lower. This work demonstrates the presence of electro-chemically active components that might function as antioxidants at the anterior surface of the cornea against potential damage from radiation, oxygen toxicity, abrasion and environmental chemicals.


The treatment of end-stage liver disease in childhood.
With the availability of orthotopic liver transplantation as a definitive treatment option for most cases of end-stage liver disease in children, there is renewed interest in this hitherto universally fatal condition. The potential for long-term survival after liver transplantation without disability is a realistic prospect for the majority, although the surgery is one of the most difficult surgical procedures available and represents a daunting prospect. The success of liver transplantation (80% one year and approximately 70% five year survival) has required virtually a re-definition of the diagnosis of end-stage liver disease with a view to predicted outcome and timely intervention. This includes a more aggressive approach to supportive treatment in order to maintain (if not improve) the patient's clinical status, if the treatment option of transplantation is decided upon. Preferably this treatment option should be considered and offered immediately the condition of end-stage liver disease is realised, in order to allow time for full and frank discussion of treatment options, to optimize supportive therapy, to evaluate suitability for liver transplantation and to maximize prospects of obtaining a donor organ. In Australia, particularly in children, liver transplantation is limited by the scarcity of suitable donor organs, although the development of reduction hepatectomy of an adult organ has allowed access to a much larger donor pool. This development has particular advantages in Australia, allowing organs from 80 kg adults to be transplanted successfully into 5 kg or 6 kg infants and has, at the time of writing, virtually eliminated potential paediatric recipient deaths while awaiting a suitable donor.


The Angelman or "happy puppet" syndrome. Clinical and electroencephalographic features and cerebral blood flow.
Two cases of happy puppet or Angelman syndrome are presented. They have the typical clinical features and represent the first Swedish cases. One of the patients is a man of 75 years of age, which shows that this form of severe mental retardation is well compatible with long life. Extended EEG monitoring may identify the typical EEG abnormality when this is difficult to demonstrate in routine EEG records. The typical laughter has no specific correlate in the EEG and thus is probably not an epileptic manifestation. Regional cerebral blood flow studies were normal in the young patient (11 years of age) but in the older patient showed a reduced cerebral circulation, compatible with organic dementia.


Occupational stress, safety, and health: conceptual framework and principles for effective prevention interventions.
The authors present an overarching conceptual model of occupational stress, safety, and health, incorporating multiple factors from diverse disciplines. They examine specific implications of the model for the development of prevention interventions (e.g., context-specific interventions and primary, secondary, and tertiary prevention). They review prevention interventions and describe and analyze 4 case studies that address exposure to environmental, ergonomic, and psychosocial stressors and a combination of physical-environmental and psychosocial stressors. The authors examine lessons learned from these interventions in light of the conceptual model (e.g., role of top management and integrating research and intervention).


Ectopic callose deposition into woody biomass modulates the nano-architecture of macrofibrils.
Plant biomass plays an increasingly important role in the circular bioeconomy, replacing non-renewable fossil resources. Genetic engineering of this lignocellulosic biomass could benefit biorefinery transformation chains by lowering economic and technological barriers to industrial processing. However, previous efforts have mostly targeted the major constituents of woody biomass: cellulose, hemicellulose and lignin. Here we report the engineering of wood structure through the introduction of callose, a polysaccharide novel to most secondary cell walls. Our multiscale analysis of genetically engineered poplar trees shows that callose deposition modulates cell wall porosity, water and lignin contents and increases the lignin-cellulose distance, ultimately resulting in substantially decreased biomass recalcitrance. We provide a model of the wood cell wall nano-architecture engineered to accommodate the hydrated callose inclusions. Ectopic polymer introduction into biomass manifests in new physico-chemical properties and offers new avenues when considering lignocellulose engineering.


Evidence-Based Pain Management and Palliative Care in Issue Two for 2006 of The Cochrane Library.
The Cochrane Library of Systematic Reviews is published quarterly. It now contains 2674 complete reviews, 1686 protocols for reviews in production and 6019 one page summaries of systematic reviews published in the general medical literature. In addition there are citations of 473,442 randomized controlled trials, 22 methodology reviews and 8255 cited papers in the Cochrane methodology register. The health technology assessment database contains 5648 citations. This edition of the Library contains 66 new reviews of which 4 have potential relevance for practitioners in pain and palliative medicine.


Extending the multicultural orientation (MCO) framework to group psychotherapy: A clinical illustration.
Multicultural group work has received growing attention over the past two decades; however, there is a lack of conceptual frameworks to guide therapists' cultural processes within group therapy at present. As such, we extend the multicultural orientation (MCO) to group therapy in an effort to provide a conceptual framework for group therapists to effectively engage multicultural group work. The MCO framework was developed in an effort to operationalize therapists' cultural processes of cultural humility, cultural comfort, and cultural opportunity. Although the MCO framework has been empirically tested within an individual psychotherapy context, application to alternative therapeutic modalities is needed. Given the inherent multicultural nature of group therapy and calls for group therapist to be culturally competent in the delivery of group-based services, we extend the MCO framework to the practice of group therapy. In this article, we provide a rationale for the application of the MCO framework to the practice of group therapy, and illustrate how group therapists' cultural humility, comfort, and opportunities can assist in establishing a multicultural group orientation throughout the development of the group. (PsycINFO Database Record


Hereditary Fibrinogen Aα-Chain Amyloidosis in Asia: Clinical and Molecular Characteristics.
Hereditary fibrinogen Aα-chain amyloidosis (Aα-chain amyloidosis) is a type of autosomal dominant systemic amyloidosis caused by mutations in fibrinogen Aα-chain gene (FGA). Patients with Aα-chain amyloidosis have been mainly reported in Western countries but have been rarely reported in Asia, with only five patients with Aα-chain amyloidosis being reported in Korea, China, and Japan. Clinically, the most prominent manifestation in Asian patients with Aα-chain amyloidosis is progressive nephropathy caused by excessive amyloid deposition in the glomeruli, which is similar to that observed in patients with Aα-chain amyloidosis in Western countries. In molecular features in Asian Aα-chain amyloidosis, the most common variant, E526V, was found in only one Chinese kindred, and other four kindred each had a different variant, which have not been identified in other countries. These variants are located in the C-terminal region (amino acid residues 517-555) of mature Aα-chain, which was similar to that observed in patients with Aα-chain amyloidosis in other countries. The precise number of Asian patients with Aα-chain amyloidosis is unclear. However, patients with Aα-chain amyloidosis do exist in Asian countries, and the majority of these patients may be diagnosed with other types of systemic amyloidosis.


Study of intrinsic flow properties at the normal pregnancy second trimester.
During normal pregnancy the cardiovascular system undergoes extensive changes. In a previous work we demonstrated the role of the haemorheological profile as predictor of hypertensive gestational disorders through a retrospective study. In an attempt to clarify the rheological characteristics during normal gestation, blood and plasma viscosity, erythrocyte deformability and aggregation, and plasma fibrinogen levels were measured at second trimester of pregnancy. The interrelationships of different haemorheologic parameters, were analysed by Pearson correlation coefficient. The results showed decreased erythrocyte deformability, and increased plasma viscosity and erythrocyte aggregation due to increased fibrinogen in pregnant women. Despite these modifications blood viscosity did not increase, but there was a decrease in relative blood viscosity, therefore, a profile in accordance, from the haemorheological point of view, with the classical concept stating that haemodilution is of the utmost importance to maintain an adequate microcirculation in the uteroplacental unit during normal gestation.


Diagnostic imaging of the diabetic foot.
Diagnostic imaging plays a major role in the osteoarticular disease of the foot in diabetics, allowing the diagnosis and evaluation of alterations for therapy planning. To-date conventional radiology is still of first choice in the study of the diabetic foot with the evaluation of osteoarticular damage caused by neuropathy and vascular disease. Major radiographic patterns are neuroarthropathy and osteomyelitis. Main locations are at the level of forefoot and less frequently of tarsus and tibiotarsal joint. Second choice procedures as US, CT and MRI are useful for a more accurate evaluation of soft tissue lesions and articular structures. US is the first choice procedure in soft tissue evaluation to rule out the presence of abscesses which require surgery. MRI with some limitations represents the gold standard for the study of joints and medullary disease. Spiral CT though less specific and sensitive than MRI for soft tissue and bone marrow study is still the exam of reference for the study of bone structures with three-dimensional reconstructions useful to plan orthopedic surgery.


Multicellular dosimetric chain for molecular radiotherapy exemplified with dose simulations on 3D cell spheroids.
Absorbed radiation dose-response relationships are not clear in molecular radiotherapy (MRT). Here, we propose a voxel-based dose calculation system for multicellular dosimetry in MRT. We applied confocal microscope images of a spherical cell aggregate i.e. a spheroid, to examine the computation of dose distribution within a tissue from the distribution of radiopharmaceuticals. A confocal microscope Z-stack of a human hepatocellular carcinoma HepG2 spheroid was segmented using a support-vector machine algorithm and a watershed function. Heterogeneity in activity uptake was simulated by selecting a varying amount of the cell nuclei to contain 111In, 125I, or 177Lu. Absorbed dose simulations were carried out using vxlPen, a software application based on the Monte Carlo code PENELOPE. We developed a schema for radiopharmaceutical dosimetry. The schema utilizes a partially supervised segmentation method for cell-level image data together with a novel main program for voxel-based radiation dose simulations. We observed that for 177Lu, radiation cross-fire enabled full dose coverage even if the radiopharmaceutical had accumulated to only 60% of the spheroid cells. This effect was not found with 111In and 125I. Using these Auger/internal conversion electron emitters seemed to guarantee that only the cells with a high enough activity uptake will accumulate a lethal amount of dose, while neighboring cells are spared. We computed absorbed radiation dose distributions in a 3D-cultured cell spheroid with a novel multicellular dosimetric chain. Combined with pharmacological studies in different tissue models, our cell-level dosimetric calculation method can clarify dose-response relationships for radiopharmaceuticals used in MRT.


Associations between adolescents' use of sexually explicit material and risky sexual behavior: A longitudinal assessment.
The unprecedented accessibility and affordability of online sexually explicit material (SEM) has facilitated widespread use among adolescents and growing concerns over adverse reproductive health outcomes. Although SEM-induced risky sexual behavior is among key concerns, there is a paucity of longitudinal research addressing this issue. This study aimed to assess the longitudinal association between frequency of SEM use and risky sexual behavior among adolescents in two independent 5-wave panel samples of Croatian adolescents (n = 368; n = 247). The indicators of risky sexual behavior were: (1) not using a condom at most recent sexual intercourse, and (2) reporting two or more sexual partners. Multilevel logistic regression analysis with a lagged component was used to explore the associations of interest. Controlling for sociodemographic characteristics, pubertal timing and sensation seeking, frequency of SEM use was not associated with the two indicators of sexual risk taking. This study's findings are relevant for health and educational experts, but also for concerned parents.