SVIoT: A Secure Visual-IoT Framework for Smart Healthcare.
The advancement of the Internet of Things (IoT) has transfigured the overlay of the physical world by superimposing digital information in various sectors, including smart cities, industry, healthcare, etc. Among the various shared information, visual data are an insensible part of smart cities, especially in healthcare. As a result, visual-IoT research is gathering momentum. In visual-IoT, visual sensors, such as cameras, collect critical multimedia information about industries, healthcare, shopping, autonomous vehicles, crowd management, etc. In healthcare, patient-related data are captured and then transmitted via insecure transmission lines. The security of this data are of paramount importance. Besides the fact that visual data requires a large bandwidth, the gap between communication and computation is an additional challenge for visual IoT system development. In this paper, we present SVIoT, a Secure Visual-IoT framework, which addresses the issues of both data security and resource constraints in IoT-based healthcare. This was achieved by proposing a novel reversible data hiding (RDH) scheme based on One Dimensional Neighborhood Mean Interpolation (ODNMI). The use of ODNMI reduces the computational complexity and storage/bandwidth requirements by 50 percent. We upscaled the original image from M × N to M ± 2N, dissimilar to conventional interpolation methods, wherein images are upscaled to 2M × 2N. We made use of an innovative mechanism, Left Data Shifting (LDS), before embedding data in the cover image. Before embedding the data, we encrypted it using an AES-128 encryption algorithm to offer additional security. The use of LDS ensures better perceptual quality at a relatively high payload. We achieved an average PSNR of 43 dB for a payload of 1.5 bpp (bits per pixel). In addition, we embedded a fragile watermark in the cover image to ensure authentication of the received content.


Feeling unsafe in the healthcare setting: patients' perspectives.
This literature review aimed to discover the factors that contribute to patients feeling unsafe in the healthcare setting. Electronic searches were undertaken using three databases to examine publications from 2002 to 2016. The design used a modified Cooper's (1982) five-stage integrative review method. Fourteen articles were identified, producing seven themes: information and communication, loss of control, staff presence, impersonal care, patients' vulnerable emotional and physical state, not being taken seriously, and the patient perception of of a lack of staff experience, knowledge, proactivity and interest. The findings suggest that, in maintaining a quality service for patients, nurses can contribute to the reduction of patients' feelings of being unsafe and vulnerable. Patients do not just feel unsafe when errors occur, but also when service quality is noticeably poor. Where lack of quality is perceived as an indication of potential threat, this lack may contribute to patients feeling unsafe within the healthcare setting.


Classifying Elite From Novice Athletes Using Simulated Wearable Sensor Data.
Movement screens are frequently used to identify differences in movement patterns such as pathological abnormalities or skill related differences in sport; however, abnormalities are often visually detected by a human assessor resulting in poor reliability. Therefore, our previous research has focused on the development of an objective movement assessment tool to classify elite and novice athletes' kinematic data using machine learning algorithms. Classifying elite and novice athletes can be beneficial to objectively detect differences in movement patterns between the athletes, which can then be used to provide higher quality feedback to athletes and their coaches. Currently, the method requires optical motion capture, which is expensive and time-consuming to use, creating a barrier for adoption within industry. Therefore, the purpose of this study was to assess whether machine learning could classify athletes as elite or novice using data that can be collected easily and inexpensively in the field using inertial measurement units (IMUs). A secondary purpose of this study was to refine the architecture of the tool to optimize classification rates. Motion capture data from 542 athletes performing seven dynamic screening movements were analyzed. A principal component analysis (PCA)-based pattern recognition technique and machine learning algorithms with the Euclidean norm of the segment linear accelerations and angular velocities as inputs were used to classify athletes based on skill level. Depending on the movement, using metrics achievable with IMUs and a linear discriminant analysis (LDA), 75.1-84.7% of athletes were accurately classified as elite or novice. We have provided evidence that suggests our objective, data-driven method can detect meaningful differences during a movement screening battery when using data that can be collected using IMUs, thus providing a large methodological advance as these can be collected in the field using sensors. This method offers an objective, inexpensive tool that can be easily implemented in the field to potentially enhance screening, assessment, and rehabilitation in sport and clinical settings.


[DNVF Memorandum Health Services Research in Oncology].
Health services research in oncology deals with all situations which cancer patients face. It looks at the different phases of care, i. e. prevention / early detection, prehabilitation, diagnostics, therapy, rehabilitation and palliative care as well as the various actors, including those affected, the carers and self-help. It deals with healthy people (e. g. in the context of prevention / early detection), patients and cancer survivors. Due to the nature of cancer and the existing care structures, there are a number of specific contents for health services research in oncology compared to general health services research while the methods remain essentially identical. This memorandum describes the subject, illustrates the care structures and identifies areas of health services research in oncology. This memorandum has been prepared by the Oncology Section of the German Network for Health Services Research and is the result of intensive discussions.


Distinctive malfunctions of calmodulin mutations associated with heart RyR2-mediated arrhythmic disease.
Calmodulin (CaM) is a cytoplasmic calcium sensor that interacts with the cardiac ryanodine receptor (RyR2), a large Ca(2+) channel complex that mediates Ca(2+) efflux from the sarcoplasmic reticulum (SR) to activate cardiac muscle contraction. Direct CaM association with RyR2 is an important physiological regulator of cardiac muscle excitation-contraction coupling and defective CaM-RyR2 protein interaction has been reported in cases of heart failure. Recent genetic studies have identified CaM missense mutations in patients with a history of severe cardiac arrhythmogenic disorders that present divergent clinical features, including catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS) and idiopathic ventricular fibrillation (IVF). Herein, we describe how two CPVT- (N54I & N98S) and three LQTS-associated (D96V, D130G & F142L) CaM mutations result in alteration of their biochemical and biophysical properties. Ca(2+)-binding studies indicate that the CPVT-associated CaM mutations, N54I & N98S, exhibit the same or a 3-fold reduced Ca(2+)-binding affinity, respectively, versus wild-type CaM, whereas the LQTS-associated CaM mutants, D96V, D130G & F142L, display more profoundly reduced Ca(2+)-binding affinity. In contrast, all five CaM mutations confer a disparate RyR2 interaction and modulation of [(3)H]ryanodine binding to RyR2, regardless of CPVT or LQTS association. Our findings suggest that the clinical presentation of CPVT or LQTS associated with these five CaM mutations may involve both altered intrinsic Ca(2+)-binding as well as defective interaction with RyR2.


Co-targeting AR and HSP90 suppresses prostate cancer cell growth and prevents resistance mechanisms.
Persistent androgen receptor (AR) signaling in castration resistant prostate cancer (CRPC) underpins the urgent need for therapeutic strategies that better target this pathway. Combining classes of agents that target different components of AR signaling has the potential to delay resistance and improve patient outcomes. Many oncoproteins, including the AR, rely on the molecular chaperone heat shock protein 90 (Hsp90) for functional maturation and stability. In this study, enhanced anti-proliferative activity of the Hsp90 inhibitors 17-allylamino-demethoxygeldanamycin (17-AAG) and AUY922 in androgen-sensitive and CRPC cells was achieved when the agents were used in combination with AR antagonists bicalutamide or enzalutamide. Moreover, significant caspase-dependent cell death was achieved using sub-optimal agent doses that individually have no effect. Expression profiling demonstrated regulation of a broadened set of AR target genes with combined 17-AAG and bicalutamide compared with the respective single agent treatments. This enhanced inhibition of AR signaling was accompanied by impaired chromatin binding and nuclear localization of the AR. Importantly, expression of the AR variant AR-V7 that is implicated in resistance to AR antagonists was not induced by combination treatment. Likewise, the heat shock response that is typically elicited with therapeutic doses of Hsp90 inhibitors, and is a potential mediator of resistance to these agents, was significantly reduced by combination treatment. In summary, the co-targeting strategy in this study more effectively inhibits AR signaling than targeting AR or HSP90 alone and prevents induction of key resistance mechanisms in prostate cancer cells. These findings merit further evaluation of this therapeutic strategy to prevent CRPC growth.


Recalling war trauma of the Pacific War and the Japanese occupation in the oral history of Malaysia and Singapore.
The Pacific War and the Japanese Occupation were traumatic periods in the lives of people now over seventy years old in Malaysia and Singapore. This study traces why individuals interviewed for oral history of the Pacific War and the Japanese Occupation have often been able to tell stories of trauma without being overwhelmed by their reminiscences. It emphasizes that memories of traumatic experiences of the Pacific War and the Japanese Occupation in Malaysia and Singapore are mediated and eased by supportive social networks that are part of the interview subject's community. The individual's personal memories of traumatic war experiences are positioned in the context of the collective memory of the group and, thus, are made easier to recall. However, for individuals whose personal memories are at variance with the collective memory of the group they belong to, recalling traumatic experiences is more difficult and alienating as they do not have the support in their community. The act of recalling traumatic memories in the context of the collective memory of a group is particularly relevant in Malaysia and Singapore. These countries have a long history of being plural societies, where although the major ethnic groups -- the Malays, Chinese, and Indians -- have lived side by side peacefully, they have lived in culturally and socially separate worlds, not interacting much with the other groups. The self -- identity of many older people who lived through the Pacific War and the Japanese Occupation is inextricably bound up with their ethnicity. Oral history on war trauma strongly reflects these identities.


Irbesartan attenuates Ang II-induced BMP-2 expression in human umbilical vein endothelial cells.
Bone morphogenetic protein-2 (BMP-2), a transforming growth factor-beta superfamily member cytokine, plays a key role both in vascular development and in pathophysiological processes. However, the effects and mechanisms of angiotensin II (Ang II) on BMP-2 expression remain unknown in human umbilical vein endothelial cells (HUVECs). Here we show that Ang II treatment significantly increased BMP-2 expression, associated with NF-kappaB activation, which was suppressed by treatment with pyrrolidine dithiocarbamate (PDTC) or irbesartan. Furthermore, the increased levels of MDA (malondialdehyde) in conditioned media and the decrease in activities of total superoxide dismutases (SOD) caused by Ang II were reversed by irbesartan or PDTC treatment. Our findings indicate that Ang II-induced BMP-2 expression might contribute to NF-kappaB activation. BMP-2 expression induced by Ang II might involve excessive oxidative stress.


Infectious Myelopathies.
This article reviews infectious etiologies of spinal cord dysfunction, emphasizing the importance of recognizing common clinicoradiographic syndromes and interpreting them in the context of exposure risk and individual host susceptibilities. This article discusses the shifting spectrum of neurologic infectious diseases, the growing population of patients who are immunocompromised, and the emergence of effective antiretroviral therapies. In addition, it discusses new molecular and serologic tests that have the potential to enhance our ability to rapidly and accurately diagnose infectious diseases of the spine. When evaluating patients with suspected infectious myelopathies, it is imperative to narrow the range of pathogens under consideration. The geography, seasonality, and clinicoradiographic presentation and immunocompetence status of the patient define the range of potential pathogens and should guide testing and initial management.


Recombination Alters the Dynamics of Adaptation on Standing Variation in Laboratory Yeast Populations.
The rates and selective effects of beneficial mutations, together with population genetic factors such as population size and recombination rate, determine the outcomes of adaptation and the signatures this process leaves in patterns of genetic diversity. Previous experimental studies of microbial evolution have focused primarily on initially clonal populations, finding that adaptation is characterized by new strongly selected beneficial mutations that sweep rapidly to fixation. Here, we study evolution in diverse outcrossed yeast populations, tracking the rate and genetic basis of adaptation over time. We combine time-serial measurements of fitness and allele frequency changes in 18 populations of budding yeast evolved at different outcrossing rates to infer the drivers of adaptation on standing genetic variation. In contrast to initially clonal populations, we find that adaptation is driven by a large number of weakly selected, linked variants. Populations undergoing different rates of outcrossing make use of this selected variation differently: whereas asexual populations evolve via rapid, inefficient, and highly variable fixation of clones, sexual populations adapt continuously by gradually breaking down linkage disequilibrium between selected variants. Our results demonstrate how recombination can sustain adaptation over long timescales by inducing a transition from selection on genotypes to selection on individual alleles, and show how pervasive linked selection can affect evolutionary dynamics.


Chronic total occlusions: experience with fiber-optic guidance technology--optical coherence reflectometry.
Chronic total occlusions are difficult to treat and continue to challenge the interventional cardiologist. The primary difficulty is safely crossing the total occlusion with a guidewire before any revascularization can begin. One of the main reasons conventional and newer guidewires have not proven effective is simply the lack of visualization to safely steer the guidewire across the occlusion. This limitation can be overcome with new technology using a "forward-looking" fiber-optic guidance. The Safe-Steer TO (Total Occlusion) Crossing System is a new guidance system that uses optical coherence reflectometry to steer a guidewire through total occlusions. Optical coherence reflectometry uses algorithms to determine tissue types (plaque vs arterial wall) by measuring the intensity of the reflection of near-infrared light. The authors' clinical experience with the Safe-Steer System has met considerable success. With their initial 28 patients (7 women, 21 men) with known chronic total occlusions and confirmed ischemia, the primary success rate for the crossing the occlusion was 86% (24/28 cases). The average occluded lesion length was 41.1 +/- 30.8 mm. Our initial clinical experience demonstrates that the optical guidewire is a viable technology in the treatment of chronic total occlusions.


Visual search with color.
Three experiments were conducted to discover how rapidly people can find a particular target when they know the color of the target. The subjects searched for specific-colored three-digit numbers among other three-digit numbers on a circular display screen. Three factors had profound effects on search speed. Search time increased dramatically (and approximately linearly) as the number of display items of the target's color increased from one to all of the items on the display. Search time also increased with the number of items not of the target's color (background items), if the color of those background items was sufficiently similar to that of the target. If the color of those background items was dissimilar to that of the target, then the background items had no effect. An effect of patterned versus random placement of target-colored items was also demonstrated.


Is a flat-line a good thing? On the privatization of Israel's healthcare system.
Israel presents an intriguing conundrum: on the one hand, it provides quality healthcare in a near-universal healthcare system; on the other, it has maintained healthcare costs level at approximately 7.7% of GDP. This comes at a time when all western nations struggle with one or both sides of the equation: how to offer affordable, good quality health care to the population while curbing the sharp rise in health related costs. This paper explains both how Israel has achieved this 'flat line" effect and the social and political costs of this achievement.


[Which programmable functions of pacemakers are available, and what is their clinical relevance?].
Microprocessors incorporated into cardiac pacemakers enable a substantial number of programmable functions (Table 1), the clinical relevance of which is the subject of this overview. Stimulation mode: The mode of operation can be chosen as fixed-rate, triggered and inhibited stimulation. Rate: Rate-programmability enables optimal setting with respect to electrophysiologic and hemodynamic considerations. Impulse amplitude and width: With programmable impulse amplitude and width excessive stimulation energy can be avoided and the duration of the aggregate prolonged. In some pacemakers, the output current can be chosen as "unregulated or regulated" whereby with regulated current the magnitude of the output impulse remains constant until the battery is depleted. Functional impairment of the pacemaker through threshold elevation or muscle stimulation can be eliminated by reprogramming of the impulse amplitude or width. Sensitivity: Programmability of the input sensitivity enables noninvasive counteraction of detection disturbances (as undersensing especially with low-amplitude atrial signals and oversensing of interference signals with subsequent pacemaker inhibition; Figure 1). A new option, automatic sensitivity setting, regulates the registration of cardiac activity at the atrial and/or ventricular level within a safety margin of 2:1; even though somewhat problematic, undersensing is rare. Electrode polarity: Depending on the clinical situation, the unipolar or bipolar electrode may offer advantages. The programmability of the electrode polarity accordingly represents a clinically-relevant new development which provides a favourable combination of bipolar detection and unipolar stimulation. Some modern dual-chamber systems enable separate programming of the atrial and ventricular electrode configurations. Hysteresis: For single-chamber systems and, more recently, AV-sequential pacemakers, hysteresis is optionally available, that is, a programmable prolongation of the basic interval after detection of a spontaneous cardiac event. With further refinement, the so-called search hysteresis prolongs the stimulation interval after a constant number of continuous stimulation cycles to a programmed hysteresis interval to allow spontaneous cardiac activity; if this is detected during the prolonged interval, the pacemaker is inhibited, otherwise the pacemaker stimulates at the set rate. An AV-interval hysteresis - to date only available in one pacemaker system - prolongs the duration of the AV-interval in the following cycles to a programmed interval, if, within the programmed AV-interval, spontaneous AV-conduction is detected. Additionally, after a defined number of AV-cycles an AV-interval prolongation is chosen to assess the possibility of physiologic AV-conduction. AV-interval: Modern AV-sequential pacemakers incorporate integration of the differential and rate-adaptive AV-interval.(ABSTRACT TRUNCATED AT 400 WORDS)


A solid-state (17)O NMR study of L-tyrosine in different ionization states: implications for probing tyrosine side chains in proteins.
We report experimental characterization of (17)O quadrupole coupling (QC) and chemical shift (CS) tensors for the phenolic oxygen in three l-tyrosine (l-Tyr) compounds: l-Tyr, l-Tyr.HCl, and Na(2)(l-Tyr). This is the first time that these fundamental (17)O NMR tensors are completely determined for phenolic oxygens in different ionization states. We find that, while the (17)O QC tensor changes very little upon phenol ionization, the (17)O CS tensor displays a remarkable sensitivity. In particular, the isotropic (17)O chemical shift increases by approximately 60 ppm upon phenol ionization, which is 6 times larger than the corresponding change in the isotropic (13)C chemical shift for the C(zeta) nucleus of the same phenol group. By examining the CS tensor orientation in the molecular frame of reference, we discover a "cross-over" effect between delta(11) and delta(22) components for both (17)O and (13)C CS tensors. We demonstrate that the knowledge of such "cross-over" effects is crucial for understanding the relationship between the observed CS tensor components and chemical bonding. Our results suggest that solid-state (17)O NMR can potentially be used to probe the ionization state of tyrosine side chains in proteins.


Preliminary studies of mammary secretions in the mare to assess foetal readiness for birth.
The status of the mare and foetus in relation to readiness for birth was assessed by measurement of the electrolytes sodium, potassium and calcium in mammary secretions pre-partum. Sixteen Thoroughbred mares were allowed to foal spontaneously and the ionic status of their mammary secretions was measured over three to five weeks pre-partum. From these measurements, a scoring system was developed where an ionic score of 35 points or more suggested that the mare was within 24 h of foaling. On the basis of this ionic score, 10 pony mares were induced with either oxytocin or fluprostenol and assessment of foal maturity was made by physical, behavioural and physiological criteria. Eight pony mares, induced when the ionic score was 35 points or more, delivered full term foals; two mares were induced when their scores were 30 and 20 points and delivered a full term and slightly immature foal respectively. These results suggest that foetal maturity may be related to electrolyte concentrations in mammary secretions and that an ionic score of 35 points or more may indicate that induction would be successful in terms of maturity of the newborn foal.


Origins of GABA(B) receptor-like immunoreactive terminals in the rat spinal dorsal horn.
By means of immunohistochemistry for gamma-aminobutyric acid receptor B subtype (GABA(B)R), the origins of GABA(B)R-like immunoreactive (GABA(B)R-LI) terminals in the rat spinal dorsal horn were investigated. After dorsal root rhizotomy and/or spinal cord hemisection, the densities of GABA(B)R-LI terminals were remarkably depleted in the ipsilateral superficial dorsal horn of relevant segments, whereas GABA(B)R-LI neurons and sparsely distributed GABA(B)R-LI terminals remained. After injection of Fluoro-Gold (FG) into the left side of superficial lumbar dorsal horn, FG retrograde-labeled neurons were mainly observed in the ipsilateral rostral ventromedial medulla (RVM) and brainstem raphe nuclei. Some of the FG-labeled neurons, especially in the RVM, exhibited GABA(B)R-like immunoreactivity. Additionally, immunofluorescence histochemical double-staining revealed that the majority of GABA(B)R-LI neurons in the periaqueductal gray (PAG), RVM and brainstem raphe nuclei showed 5-hydroxytryptamine (5-HT)-like immunoreactivity. The present study morphologically proves that GABA(B)R-LI terminals in the spinal dorsal horn originate from peripheral afferents, intrinsic neurons and supraspinal structures; GABA(B)R and 5-HT co-exist in many neurons in the PAG, RVM and brainstem raphe nuclei. Considering that PAG, RVM, brainstem raphe nuclei and spinal dorsal horn are important structures involved in the pain modulation, we suggest that the descending pain modulation system might be mediated, at least in part, by GABA(B)R.


Low-affinity hemoglobin increases tissue PO2 and decreases arteriolar diameter and flow in the rat cremaster muscle.
The hypothesis that tissue oxygen delivery in excess of metabolic demand results in vasoconstriction and reduced blood flow was tested in the cremaster muscle of anesthetized Sprague-Dawley rats by studying the effects of an intravenous infusion of RSR-13, an allosteric effector of hemoglobin. RSR-13 reduces the affinity of hemoglobin for oxygen, causing a right shift in the oxygen dissociation curve. Thus, oxygen delivery to the tissues was increased without elevations in blood flow or blood pressure. Tissue PO2, arteriolar diameter, and RBC velocity were measured and volume flow was calculated from diameter and RBC velocity in third-order arterioles. In rats receiving RSR-13 at a rate of 200 mg kg-1 in 15 min (n = 18) P50 (the PO2 at which hemoglobin is 50% saturated) increased from 36 +/- 1 to 52 +/- 3 mm Hg, and tissue PO2 increased to a maximum of 146 +/- 12% above its control value. P50 and tissue PO2 did not change in the control group (n = 8) receiving vehicle at a rate equivalent to that in the experimental group. In a separate group of rats receiving RSR-13 (n = 7), P50 increased from 38 +/- 1 to 51 +/- 3 mm Hg, calculated arteriolar flow decreased from 9 +/- 3 to a minimum of 1.4 +/- 1 nl sec-1, and arteriolar diameter decreased from 27 +/- 3 to a minimum of 13 +/- 3 micrograms P50, volume flow, and arteriolar diameter did not change in the control group (n = 10). These results suggest that an increased tissue oxygen delivery, caused by a right shift in the oxygen dissociation curve, may cause an increase in vascular resistance independent of an elevated blood flow.


Pyomyositis of the Piriformis Muscle-A Case of Piriformis Syndrome.
Piriformis syndrome is a rare cause of sciatica, which results in low backache due to sciatic nerve compression. This syndrome is associated with abnormalities in the piriformis muscle, which cause sciatic nerve entrapment, like anatomical variations, muscle hypertrophy, and inflammation. It can also result from the abnormal course of sciatic nerve itself through normal piriformis muscle. Piriformis syndrome due to pyomyositis of the piriformis muscle is extremely rare and only 23 cases are reported in literature. Herein, we report one such rare case of a patient, with pyomyositis of piriformis muscle, who presented with piriformis syndrome.


NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice.
Pancreatic adenocarcinoma is an aggressive disease with poor prognosis. In a randomized phase III trial, combination of Nab-paclitaxel (Nab-P) plus gemcitabine showed superior activity and efficacy in first-line treatment compared with gemcitabine alone. Nab-P is not dispensed in Italy; however, we obtained this drug from our Ethics Committee for compassionate use. The aim of this study was to evaluate the efficacy and safety profile of this Nab-P and gemcitabine combination in a cohort of patients treated outside clinical trials. From January 2012 to May 2014, we included 41 patients with advanced pancreatic adenocarcinoma receiving combination of 125 mg/m(2) Nab-P and 1 g/m(2) gemcitabine on days 1, 8 and 15 of a 28-day cycle, as first-line treatment. Median age of patients was 67 (range 41-77) years, and 11 patients were aged ≥70 years. Eastern Co-operative Oncology Group performance status was 0 or 1 in 32 patients (78 %) and 2 in nine patients (22 %). Primary tumor was located in the pancreatic head or body/tail in 24 (58.5 %) and 17 (41.5 %) patients, respectively, and nine patients had received biliary stent implantation before starting chemotherapy. Median carbohydrate antigen 19-9 level was 469 U/l (range 17.4-61546 U/l) and 29 patients (70.7 %) had referred pain at the time of diagnosis. Patients received a median six cycles (range 1-14) of treatment. Overall response rate was 36.6 %; median progression-free survival was 6.7 months [(95 % confidence interval (CI) 5.966-8.034), and median overall survival was 10 months (95 % CI 7.864-12.136). Treatment was well tolerated. No grade 4 toxicity was reported. Grade 3 toxicity included neutropenia in 10 patients (24.3 %), thrombocytopenia in five (12 %), anemia in three (7.3 %), diarrhea in four (9.7 %), nausea and vomiting in two (4.9 %), and fatigue in six (14.6 %). Finally, pain control was achieved in 24 of 29 patients (82.3 %) with a performance status improvement of 10 % according to the Karnofsky scale. Our results confirm that combination of gemcitabine plus Nab-P is effective both in terms of overall response rate, progression-free survival and overall survival, with a good safety profile.


Interpretive versus didactic learning approach towards oral biology: a student's perspective.
This study analyzed the preference of dental students for oral biology questions that require either an interpretive or a descriptive approach to answer and to compare the preferences with their final examination result retrospectively. A questionnaire requiring student academic number and containing two questions (one asked with an interpretive approach/the other asked with a descriptive approach) from random topics of oral biology course was distributed among students who have already appeared in the final examination. Majority of the students who had achieved good grades (A+, A, B+, B) preferred interpretive questions whereas majority of the students with average grades (C+, C, D+, D) selected descriptive questions. Common reason for picking interpretive question was that it enhances critical thinking. The descriptive questions were argued to provide students with a chance to explain more. Hence, students should be encouraged to learn interpretively to promote enquiry based learning (EBL) and critical thinking.


Monitoring sleep hours using a sleep diary and errors in rotating shiftworkers.
The sleep hours of male workers on rotating shift schedules were measured using a sleep diary. The mean age of workers was 40.3 years. Work shifts were rotated on a weekly basis and fell into three periods: morning, evening, and night. One working week consisted of 5 days. Errors that occurred during the work were also evaluated. A significant difference in the mean length of sleep was observed for each of the three shifts. Compared with the morning shift, the length of sleep for workers working evening and night shifts were significantly longer. The error of workers was not recognized in three rotating shift schedules in the survey period. Rotating shiftwork affects the amount of sleep, but not the event of error.


A nurse-led intervention improves detection and management of AKI in Malawi.
Acute kidney injury is common and has significant impact on mortality and morbidity. There is a global drive to improve the lack of knowledge and understanding surrounding the recognition, diagnosis and management of patients with AKI in resource poor healthcare systems. We propose a nurse-led education programme to medical and nursing staff of the Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi, will improve the overall care and understanding of patients with AKI that will still be effective 3 months later. This was a three phase, prospective interventional pilot study which evaluated base line knowledge and clinical practice amongst healthcare workers, provided a comprehensive combination nurse-led class room and ward based teaching programme and evaluated the change in knowledge and clinical management of patients in the high dependency areas of the hospital immediately, and 3 months, after the teaching intervention. The nurse-led intervention significantly improved the healthcare workers attitudes towards detecting or managing patients with suspected AKI (p < 0.0001). There were also significant improvements in the completion of fluid charts and recording of urine output (p < 0.0001), corner stones of AKI management. Knowledge and clinical intervention was still present three months later. There was however little change in the understanding that AKI could be a significant clinical problem in QECH and that it may have a major impact on mortality and working practice and this needs to be addressed in future teaching programmes. A low cost, nurse-led AKI educational intervention improved the knowledge and management of AKI at QECH, which was still evident 3 months later.


Precise chromosome segregation is vital for speciation and hybrid formation. The aim of the work was to study the chromosomes behaviour and inheritance of maternal and paternal genomes in Arabidopsis regenerants de-rived from in vitro cultured cells on the medium with PFFA. The Arabidopsis thaliana model hybrid between Columbia and Landsberg erecta ecotypes was developed, which chromosomes were easy to distinguish using the 12 SSLP selected markers. Also, the influence of PFFA on the callus formation and regeneration of plants was analysed. 20 regenerated plants cultured with PFFA were derived, three of which were shown to loss the heterozygosity in six loci by DNA markers analysis. Different models are certainly required to understand how and when the mechanisms leading to proper chromosome segregation are established in species and hybrids.


Comparative study of biological properties of proteins synthetised in vitro by murine decidua and deciduoma.
Supernatants from short-term in vitro cultures of murine decidual tissue obtained from the uteri of pregnant mice on day 8 postcoïtum (decidua, in the presence of paternal antigens) or from pseudopregnant mice (deciduoma, without any histocompatibility antigens were assessed for their regulatory activity; both statuses (physiological and experimental) can only be developed under hormonal conditions. All these supernatants possess no complement inhibitory activity, but they markedly impair the generation of cytotoxic T cells (CTL) and suppress anti-sheep red blood cell antibody response. These effects seem essentially located in a single AcA 22 fraction of 60 KD that inhibits CTL, while the plaque-forming cell response is strongly stimulated. Electrophoretic and gel filtration profiles of supernatants from cultures of decidua and deciduoma seem similar. The results suggest that the factors synthetised by decidua or deciduoma are the same and are not induced by exposure to foreign histocompatibility antigens of the fetus. According to these results, it seems likely that decidualization represents a localized general mechanism that can be induced, under a particular hormonal background, by different stimuli (trauma) rather than being a specific response to a particular signal (blastocyst).


[Features of emotional stability in volunteers of gerontology programs].
The paper presents an analysis of the characteristics of emotional stability in volunteers of gerontology programs (among the students of the Faculty of Psychology), depending on the structure of their life meaning and values, personal factors and professional important qualities. It is shown that the emotional stability of volunteers determines the main directions to explore the potential of the psyche of volunteers; modeling appropriate professiogram; organization of volunteer work in a particular program.


Rotaxane-type resorcinarene tetramers as histone-sensing fluorescent receptors.
Rotaxane-type receptors, which were composed of anionic cyclophane-based resorcinarene tetramers as the wheel and a 2,6-disubstituted naphthalene derivative having two fluorophore moieties, such as fluorescein and rhodamine residues, as the axle ( and , respectively), were prepared. Rotaxane-type receptors and bound histone, a small basic protein component of eukaryotic chromatins, with binding constants of 2.3 x 10(6) and 9.0 x 10(5) M(-1), respectively. The rotaxane-type receptors showed fluorescence sensing ability with remarkable histone selectivity. Moreover, fluorescence resonance energy transfer (FRET) between the fluorescein residues of and the rhodamine residues of took place in the presence of histone, which was a useful method for the detection of histone.


The Role of Radiology in Progressive Fibrosing Interstitial Lung Disease.
In this article, we describe the role of radiology for diagnosis and follow-up of progressive fibrosing interstitial lung disease (PF-ILD). Patients with PF-ILD are at increased risk for early death without treatment. Clinical diagnosis of PF-ILD has been described in the literature. This manuscript reviews the radiographic diagnosis of PF-ILD and the unique CT characteristics associated with specific types of fibrosis. Ultimately, we believe that radiology has the potential to recognize progression early and thus make an important contribution to the multidisciplinary discussion for this important diagnosis.


Intracerebroventricularly administered oxytocin attenuated cortisol secretion, but not behavioral responses, during isolation in Holstein steers.
In rodents, intracerebroventricular oxytocin administration attenuated hypothalamo-pituitary-adrenal (HPA) responses and anxiety behavior during stress. We examined the effects of intracerebroventricular injection of oxytocin on isolation-induced stress responses in cattle. In a methodological test, we determined the dosage of oxytocin applied in a main test which did not induce an increase in plasma cortisol concentration or stereotyped behaviors. In a main test, 5 steers aged from 199 to 250 days were assigned to the following three treatments randomly: T1, no isolation after injection of 200 microl of artificial cerebrospinal fluid (aCSF); T2, isolation after aCSF injection; and T3, isolation after 0.5 microg of oxytocin in 200 microl aCSF injection. The isolation was conducted by leaving the experimental steer alone in its stall for one hour while its peers were taken outside. In T2, the isolation induced a rapid increase in plasma cortisol concentration. The maximum %-changes from the pre-isolation value were significantly attenuated by oxytocin injection (T2 vs. T3, p<0.05). The isolation also induced an increase in the frequency (number of occurrences/1 hr isolation) of vocalizations and body orientation changes, and a decrease in the percentage of time spent lying and ruminating. The effect of oxytocin on these behavioral responses to isolation was not apparent. These results indicate that intracerebroventricularly injected oxytocin at low dose attenuated the cortisol response to isolation in steers while the effect on behavior was very small in this experimental condition.


Adrenomedullin gene delivery is cardio-protective in a model of chronic nitric oxide deficiency combining pressure overload, oxidative stress and cardiomyocyte hypertrophy.
Chronic inhibition of nitric oxide (NO) synthesis is associated with hypertension, myocardial ischemia, oxidative stress and hypertrophy; expression of the vasodilator peptide, adrenomedullin (AM) and its receptors is augmented in cardiomyocytes, indicating that the myocardial AM system may be activated in response to pressure loading and ischemic insult to serve a counter-regulatory, cardio-protective role. The study examined the hypothesis that oxidative stress and hypertrophic remodeling in NO-deficient cardiomyocytes are attenuated by adenoviral vector-mediated delivery of the human adrenomedullin (hAM) gene in vivo. The NO synthesis inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 15mg . kg(-1) . day(-1)) was given to rats for 4 weeks following systemic administration via the tail vein of a single injection of either adenovirus harbouring hAM cDNA under the control of the cytomegalovirus promoter-enhancer (Ad.CMV-hAM-4F2), or for comparison, adenovirus alone (Ad.Null) or saline. Cardiomyocytes were subsequently isolated for assessment of the influence of each intervention on parameters of oxidative stress and hypertrophic remodelling. Cardiomyocyte expression of the transgene persisted for > or =4 weeks following systemic administration of adenoviral vector. In L-NAME treated rats, relative to Ad.Null or saline administration, Ad.CMV-hAM-4F2 (i) reduced augmented cardiomyocyte membrane protein oxidation and mRNA expression of pro-oxidant (p22phox) and anti-oxidant (SOD-3, GPx) genes; (ii) attenuated increased cardiomyocyte width and mRNA expression of hypertrophic (sk-alpha-actin) and cardio-endocrine (ANP) genes; (iii) did not attenuate hypertension. Adenoviral vector mediated delivery of hAM resulted in attenuation of myocardial oxidative stress and hypertrophic remodelling in the absence of blood pressure reduction in this model of chronic NO-deficiency. These findings are consistent with a direct cardio-protective action in the myocardium of locally-derived hAM which is not dependant on NO generation.


The "hot" patella.
Increased patellar uptake on bone scans is seen quite commonly but the possible or probable etiologies of this finding have not been previously well described. A review of 100 consecutive bone scans showed that the incidence of bilateral "hot" patellae is 15%. Identified etiologies include osteoarthritic degenerative disease (35%), fracture, possible metastatic disease, bursitis, Paget's disease, and osteomyelitis. The value of careful history, physical examination, and radiographs is stressed.


Planners, householders and fertility reduction.
Ways to resolve conflicts between individual families and societies as a whole concerning fertility are examined using the example of Singapore. The focus is on how the government developed an effective antinatalist policy during the 1960s and 1970s. The author concludes that the "non-coercive population policies aimed at altering family reproductive life-styles had relatively little to do with fertility reduction", and therefore that measures designed to penalize large families are relatively ineffective.


[Genetics and society].
With the use of mathematical models it was attempted to calculate the probability of eugenic or dysgenic effects as a consequence of medical treatment and of procedures used in human genetics. 1. Modern medicine will cause mainly an increase in multifactorial malformations and diseases. But the resulting burden for the general public most probably will be considerably smaller compared to to-day expenses for the care of those affected with chronic inherited diseases. 2. For many families concerned prenatal diagnosis is the only reasonable approach to obtain healthy children of their own. In order to reduce substantially the number of affected individuals prenatal diagnosis would have to be applied as a prospective mass screening which in many cases would be too demanding.


A multi-component model of the developing retinocollicular pathway incorporating axonal and synaptic growth.
During development, neurons extend axons to different brain areas and produce stereotypical patterns of connections. The mechanisms underlying this process have been intensively studied in the visual system, where retinal neurons form retinotopic maps in the thalamus and superior colliculus. The mechanisms active in map formation include molecular guidance cues, trophic factor release, spontaneous neural activity, spike-timing dependent plasticity (STDP), synapse creation and retraction, and axon growth, branching and retraction. To investigate how these mechanisms interact, a multi-component model of the developing retinocollicular pathway was produced based on phenomenological approximations of each of these mechanisms. Core assumptions of the model were that the probabilities of axonal branching and synaptic growth are highest where the combined influences of chemoaffinity and trophic factor cues are highest, and that activity-dependent release of trophic factors acts to stabilize synapses. Based on these behaviors, model axons produced morphologically realistic growth patterns and projected to retinotopically correct locations in the colliculus. Findings of the model include that STDP, gradient detection by axonal growth cones and lateral connectivity among collicular neurons were not necessary for refinement, and that the instructive cues for axonal growth appear to be mediated first by molecular guidance and then by neural activity. Although complex, the model appears to be insensitive to variations in how the component developmental mechanisms are implemented. Activity, molecular guidance and the growth and retraction of axons and synapses are common features of neural development, and the findings of this study may have relevance beyond organization in the retinocollicular pathway.


Transcorporeal tunnel approach for unilateral cervical radiculopathy: a 2-year follow-up review and results.
The long-term complications of traditional discectomy and fusion surgery have led to the need for minimally invasive procedures that do not require a complete discectomy and fusion. Jho developed an anterior unco-foraminotomy that we have modified, with the approach being more medial than that of Jho, into an anterior transcorporeal tunnel approach which we use for cervical spondylotic unilateral radiculopathy. A retrospective analysis was carried out in 30 patients who underwent a transcorporeal "tunnel" anterior micro-foraminotomy for unilateral radicular symptoms with a follow-up more than 2 years. All were operated by a single surgeon using the same technique from the vertebral body proximal to the lesion and proceeding downwards to the herniation. At final follow-up we reviewed the clinical and radiological results. All patients in the immediate post-operative period showed relief of their symptoms, and there were major complications. 3 patients complained about the numbness in the immediate postoperative period which resolved within 3 months. There was a significant improvement in NDI from pre-operative 55.16% to postoperative 5.82% ( P <0.001). Average pre-operative VAS scores for arm and neck were 8.15 and 4.05, respectively; which improved to 1.05 and 1.23 ( P <0.001) postoperatively. There was an average 9% decrease (from 7.8 mm to 7.3 mm) in the post-operative disc height compared to the preoperative disc height; however, it was clinically and radiologically insignificant. The long-term results were favourable and there were no major complications. The transcorporeal tunnel approach can be used as an alternative treatment for cervical spondylotic radiculopathy.


Molecular clones of hepatitis C virus: applications to animal models.
Hepatitis C virus (HCV) is a global public health problem, with approximately 3% of the world population now infected. The clinical course of HCV often involves chronic infection, which can lead to liver dysfunction and hepatocellular carcinoma. Because HCV cannot be efficiently propagated in cell culture, researchers have relied heavily on animal models to study the physical characteristics of HCV and the course of events associated with HCV infection. The chimpanzee is the only nonhuman primate actually proven to be susceptible to HCV infection and has commonly been used to study viral hepatitis induced by HCV. Molecular cloning of the HCV genome has now allowed HCV transmission studies in chimpanzees to progress from the early work of characterizing infectious serum to a current focus of characterizing infectious HCV molecular clones. Moreover, the cloned HCV genome has paved the way for the development of alternative animal models for HCV, most notably transgenic mouse models for the study of HCV pathogenesis. The authors review these animal model applications of the HCV molecular clones, including construction and transmission of mutant viral genomes. The expression of specific viral protein products in these animal models will provide important insight into the structure-function relation that specific HCV genome sequences impart on virus replication and pathogenesis.


Accuracy of rhythm classification using a data log system in implantable cardioverter defibrillators.
Because the presence or absence of symptoms alone may be insufficient to correctly diagnose the rhythm for which implantable cardioverter defibrillator therapy is delivered, we hypothesized that the addition of data log information available in Telectronics ATP 4210 may improve the accuracy of rhythm classification. With this system the recorded ventricular electrogram cycle length is reported on a beat-to-beat basis immediately before, during, and after the tachyarrhythmia is detected. Using this information recorded from the data log in 32 separate tachyarrhythmia episodes in 20 patients, we compared the sensitivity, specificity, and predictive accuracy of rhythm classification on the basis of symptoms alone, data log alone, and data log combined with symptoms. While classification based on symptoms alone is highly specific (10/10 episodes), it is insensitive and has an overall predictive accuracy of 53%. By contrast, data log is sensitive (90%) and specific (91%) with better predictive accuracy (94%) than symptoms alone (P = 0.002). The addition of symptoms to information on beat-to-beat cycle length from data log resulted in a slight increase in predictive accuracy.


Cross-linking methods of type I collagen-based scaffolds for cartilage tissue engineering.
Cartilage defects are one of the hardest injures to cure, given the limited regenerative ability of cartilage tissues. Moreover, cartilage defects affect an increasing number of people worldwide. Therefore, scientists have attempted to develop effective strategies to repair cartilage defects in recent years. Recent advances in tissue engineering have led to the strategies for inducing cartilage regeneration. Among the emerging strategies, scaffolds are commonly used in cartilage tissue engineering (CTE) as they provide favorable environment for the growth and proliferation of chondrocytes. An ideal scaffolding material should be highly biocompatible. Type I collagen is one such material, which is widely used in CTE. However, type I collagen has poor mechanical properties and stability, which limit its use. Cross-linking is a simple method known to improve degradability, biological and mechanical properties of biomaterials by enhancing chemical and physical interactions between polymers. Cross-linking can be induced through chemical, physical or biological processes. In this review, we present cross-linking methods that can enhance the mechanical strength of type I collagen for CTE and highlight future directions in this field.


Polyp on ultrasound: now what? The association between gallbladder polyps and cancer.
The association between gallbladder polyps (GBP) and gallbladder cancer (GBC) is unclear. We sought to determine the association between preoperative diagnosis of GBP on imaging and GBC. A retrospective review of patients over 9 years was conducted using International Classification of Diseases, 9th Revision codes for GBP and GBC who underwent cholecystectomy at our institution. Demographics, imaging findings, and pathology results were recorded. A total of 2416 patients underwent cholecystectomy during the study period. Twenty-seven had an operation for GBP either as a result of concern for size or symptoms. Polyp sizes were categorized as less than 1 cm, 1 to 2 cm, or 2 cm or greater. Twenty-four patients in this group (88.9%) had no evidence of high-grade dysplasia or cancer and all of these benign polyps were 2 cm or less on imaging. One patient with a 2.4-cm polyp had high-grade dysplasia, and two patients with polyps over 3 cm had adenocarcinoma. During the same period, 20 patients had an operation for GBC with two patients common to the polyp group. The group of patients with noncancerous polyps was significantly younger than the cancer group (polyps and no polyps). The cancer group was more likely to be symptomatic. Therefore, polyps over 2 cm should be removed given the risk of high-grade dysplasia and cancer above this size. Polyps less than 2 cm were not associated with high-grade dysplasia or cancer and thus surgery may not be required. Intermediate- and small-sized polyps can be monitored with serial ultrasound, especially in younger, asymptomatic patients in whom the risk of malignancy is low.


Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation.
An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.


EEG Contribution to the Diagnosis of Antibody-Negative Autoimmune Encephalitis: A Case Report.
Autoimmune encephalitis (AE) is a group of inflammatory brain diseases that are characterized by prominent neuropsychiatric symptoms. Early therapeutic intervention is important for AE. Therefore, without waiting for autoantibody test results, clinicians must consider the possibility of AE based solely on clinical symptoms and conventional test results. The case described herein is of antibody-negative encephalitis with abnormalities shown only by EEG, which contributed to the diagnosis and treatment. The patient, a 20-year-old woman, showed autonomic seizures in addition to movement disorders, psychiatric symptoms, and cognitive dysfunction, which worsened subacutely. Her seizures and movement disorders were not responsive to antiepileptic medications. Results obtained from MRI and cerebrospinal fluid (CSF) were normal; EEG findings showed repeated spikes in the right temporal area, with changes over time. Based on the clinical course and EEG, along with administered immunotherapy, which resolved seizures, movement disorders, and psychiatric symptoms, we suspected AE. For diagnosis of AE and for evaluating treatment responsiveness, EEG was useful. Results indicate that EEG can assist clinicians even with AE cases for which MRI and CSF findings are normal.


Using freelisting to understand shared decision making in ADHD: parents' and pediatricians' perspectives.
To compare and contrast notions of ADHD among pediatricians and parents of affected children to understand the perspectives they bring to shared decision making (SDM). In this freelisting study, 60 parents of children with ADHD and 30 primary care pediatricians listed words reflecting their understanding of (1) Attention Deficit Hyperactivity Disorder (ADHD), (2) getting/offering help for ADHD, (3) talking to doctors/families about ADHD, and (4) "mental health." Smith's salience score established terms that were salient and cultural consensus analysis identified variation within subgroups of participants. Parents' terms reflected ADHD's effects on the child and family, while clinicians often mentioned school. Lists suggested differing needs and goals for clinicians and subgroups of parents in SDM: "time" for clinicians, "learning" and "understanding" for non-college educated parents, and "comfort" and "relief" for college educated parents. Neither parents nor clinicians framed ADHD in the same way as "mental health." Parents and clinicians, who conceptualize ADHD differently, should negotiate a shared understanding of ADHD as a basis for SDM. Treatment discussions should be tailored to encompass families' varied emotional and educational needs. Fostering SDM in primary care is consonant with notions of ADHD as distinct from mental health.


Treatment of facial rhytides with a high-energy pulsed carbon dioxide laser.
Facial rhytides are a common problem that often presents for treatment. Because of the tendency for rhytides to involve delicate tissue areas, traditional treatment modalities have been limited by complications of scarring or pigmentary alterations. With the advent of the new-generation high-energy pulsed carbon dioxide lasers, skin requiring resurfacing can now be treated successfully with minimal risk and side effects. This study included 259 patients with facial rhytides (104 perioral, 83 periorbital, 53 glabellar, and 17 forehead). Each patient received treatment with a high-energy pulsed CO2 laser system, and individual responses were evaluated independently by two blinded assessors at 1, 4, 8, 12, and 24 weeks postoperatively. While clinical response rates were uniformly excellent, they varied in different locations. On average, there was a 90 percent improvement in all areas under study. The periorbital regions responded best, an average 93 percent improvement being seen. The facial rhytides with the lowest response rates (86.8 percent) were those which were most severe and those caused by excessive muscle movement (i.e., frown lines at the glabella). No incidences of scarring were noted, but erythema persisting 1 to 3 months (mean 2.2 months) following laser irradiation was typical. Transient postinflammatory hyperpigmentation of 3 months' average duration was seen in 30 percent of patients and was not limited to those individuals with darker skin tones. The high-energy pulsed carbon dioxide laser is a safe and effective treatment for facial rhytides. Treatment can be delivered in an outpatient setting without the need for general anesthesia, and preliminary evidence suggests long-lasting results.


Muscle hypertrophy driven by myostatin blockade does not require stem/precursor-cell activity.
Myostatin, a member of the TGF-beta family, has been identified as a powerful inhibitor of muscle growth. Absence or blockade of myostatin induces massive skeletal muscle hypertrophy that is widely attributed to proliferation of the population of muscle fiber-associated satellite cells that have been identified as the principle source of new muscle tissue during growth and regeneration. Postnatal blockade of myostatin has been proposed as a basis for therapeutic strategies to combat muscle loss in genetic and acquired myopathies. But this approach, according to the accepted mechanism, would raise the threat of premature exhaustion of the pool of satellite cells and eventual failure of muscle regeneration. Here, we show that hypertrophy in the absence of myostatin involves little or no input from satellite cells. Hypertrophic fibers contain no more myonuclei or satellite cells and myostatin had no significant effect on satellite cell proliferation in vitro, while expression of myostatin receptors dropped to the limits of detectability in postnatal satellite cells. Moreover, hypertrophy of dystrophic muscle arising from myostatin blockade was achieved without any apparent enhancement of contribution of myonuclei from satellite cells. These findings contradict the accepted model of myostatin-based control of size of postnatal muscle and reorient fundamental investigations away from the mechanisms that control satellite cell proliferation and toward those that increase myonuclear domain, by modulating synthesis and turnover of structural muscle fiber proteins. It predicts too that any benefits of myostatin blockade in chronic myopathies are unlikely to impose any extra stress on the satellite cells.


Nicotinic acetylcholine receptors in the nematode Caenorhabditis elegans.
Two cDNAs (Ce21 and Ce13) were isolated from a Caenorhabditis elegans library screened with a probe encoding conserved domains of the avian alpha5 neuronal nicotinic acetylcholine receptor (nAChR). Alignments to all nAChR subunits in the EMBL/Swissprot data base demonstrate that the Ce21 protein most resembles the vertebrate alpha7 subunit, whereas Ce13 is closest to the ARD subunit of Drosophila. The corresponding genes were isolated and hybridized to YAC grids: Ce21 maps on chromosome V near the his-23 gene, and Ce13 on chromosome I very near or at unc-29. The structure of the Ce21 gene was compared with that of other vertebrate and invertebrate nAChR genes and found to share by far the largest number of conserved splice sites with the vertebrate alpha7 gene. Upon expression in the Xenopus oocyte system, the Ce21 subunit assembled into a functional homomeric nAChR, whose properties were compared with those of the chicken alpha7 receptor. The anthelmintic nicotinic agonist levamisole is unable to activate the Ce21 and alpha7 receptors, but efficiently antagonises their responses to ACh. Both receptors desensitise quickly upon agonist application, are more sensitive to nicotine than to acetylcholine, and are efficiently blocked by dihydro-beta-erythroidine. Unlike the alpha7 receptor, however, the Ce21 receptor is relatively insensitive to methyllycaconitine and to alpha-bungarotoxin. The similarities in protein sequence, gene structure and physiological properties between alpha7 and Ce21 suggest a very ancient lineage for the alpha7 class of nAChR subunits.


Role of epithelial chemokines in the pathogenesis of airway inflammation in asthma (Review).
As the first barrier to the outside environment, airway epithelial cells serve a central role in the initiation and development of airway inflammation. Chemokines are the most direct and immediate cell factors for the recruitment and migration of inflammatory cells. The present review focused on the role of epithelial chemokines in the pathogenesis of airway inflammation in asthma. In addition to traditional CC family chemokines and CXC family chemokines, airway epithelial cells also express other chemokines, including thymic stromal lymphopoietin and interleukin‑33. By expressing and secreting chemokines, airway epithelial cells serve a key role in orchestrating airway inflammation in asthma.


Feeding disorders in infancy: classification and treatment considerations.
This paper critically discusses conceptualizations of failure to thrive as an organic and nonorganic dichotomy. Research findings are used to refute this type of categorization. Instead, an approach which recognizes both organic and nonorganic influences and consequences of the syndrome are suggested. Physical, psychological and interpersonal systems and their interactions are explored. Potential contributions of the psychiatrist in the context of a multidisciplinary team approach to treatment are described.


Selecting an appropriate alcohol pharmacotherapy: review of recent findings.
Only a few pharmacological treatments are available for treating alcohol use disorders (AUDs). Disulfiram, naltrexone and acamprosate are Food and Drug Administration (FDA)-approved and nalmefene is EMA-approved in European Union. Off-label medications, such as baclofen, gabapentin, ondansetron and topiramate are medications commonly prescribed for the treatment of AUD. The aim of this review is to give an update on recent randomized controlled trials (RCTs) and reviews evaluating pharmacological treatment for AUD. A literature search was conducted for pharmacological treatment for alcohol use disorder, published from January 2017 to January 2019. An additional search from two ongoing-study databases was performed. A total of 13 studies, 11 reviews and 7 on-going clinical trials were identified. Interest in studying baclofen as a treatment for AUD was greater compared with other medications, yet with inconclusive results. Three new RCTs of first-line medication naltrexone showed reduction in drinking. Three new published RCTs focus on baclofen and naltrexone. These results are consistent with old findings demonstrating that naltrexone reduces heavy drinking. Several RCT on baclofen do not support the use of baclofen for treatment of AUD. Encouraging results have been reported for topiramate, gabapentin and also varenicline, which might be useful in patients with comorbid nicotine dependence.


Administrators' perspectives of the challenges in recruiting and retaining psychiatrists for New Zealand: a national study.
Administrators' perceptions of significant factors that might affect the recruitment and retention of psychiatrists for New Zealand's public mental health Services have not been previously investigated. A postal questionnaire was sent to managers of all 21 of New Zealand's mental health Services. The questionnaire requesting information about any difficulties managers experienced in recruiting and retaining psychiatrists, factors they thought attract psychiatrists to join and stay, reasons why psychiatrists left, strategies they had tried to alleviate any psychiatrist shortages, and their relative success. Responses were received from 3 of 8 metropolitan Services and 8 of 13 non-metropolitan Services. Every service had experienced problems in recruiting and retaining psychiatrists over the past 5 years. New Zealand's general shortage of psychiatrists and limitations on recreational activities available in their area were reasons unanimously held to account for this. Factors unanimously identified as significant in influencing psychiatrists to join a mental health service were lifestyle, professional opportunities, functional multidisciplinary teams, and adequate staffing and training activities. Factors unanimously identified in retaining psychiatrists were levels of professional satisfaction, a reasonable on-call roster, functional multidisciplinary teams, adequate resources, and the ability to practise safely and within their area of expertise. There was no unanimity as to why psychiatrists would leave a service. Every service which attempted to assist psychiatrists with their relocation, and which found locums to cover so that they could take leave when they wanted, reported that these strategies had been wholly or partially successful in alleviating their psychiatrist shortage. Administrators' perspectives (which are often different to those of psychiatrists) about factors affecting recruitment and retention are worth investigating.


Histopathology of neurosensory deafness in sarcoidosis.
Sarcoidosis is an idiopathic systemic granulomatous disease which occasionally causes fluctuating auditory and vestibular dysfunction. The temporal bones from a 32-year-old man deaf for 5 years from CNS sarcoidosis were examined histologically and compared with other nervous system tissues. It was found that the acoustic, vestibular, and facial nerves were involved in a striking perivascular lymphocytic infiltration resulting in myelin and axonal degeneration. The cochlear and labyrinthine neuroepithelium and stria vascularis had degenerated. It is hypothesized that neurosensory deafness and vestibular dysfunction in sarcoidosis starts as a reversible neuropathy. In some patients, an ischemia secondary to the vasculitis results in irreversible damage to the inner ear neuroepithelium.


High-resolution vessel wall magnetic resonance imaging for depicting imaging features of unruptured intracranial vertebrobasilar dissecting aneurysms.
To demonstrate the application value of high-resolution vessel wall magnetic resonance imaging (HR-VW-MRI) for depicting the imaging features of unruptured intracranial vertebrobasilar dissecting aneurysms (VBDAs). HR-VW-MRI data of 49 patients with suspected unruptured VBDAs were retrospectively analyzed. The presence of intramural hematomas (IMH), double lumens, intimal flaps, and outer diameter enlargements were recorded. Specificity and sensitivity were calculated for both two-dimensional (2D) and three-dimensional (3D) sequences. Additionally, IMH volumes were measured and posterior inferior cerebellar artery (PICA) involvement was analyzed. Thirty-five VBDAs were confirmed in 34 patients. The overall sensitivity and specificity were 0.889 (95% confidence interval [CI]: 0.730-0.964) and 0.769 (95% CI: 0.460-0.938) for 2D sequences, and 0.917 (95% CI: 0.764-0.978) and 0.846 (95% CI: 0.537-0.973) for 3D sequences, respectively. Intimal flaps were detected in 57.1%, 87.5%, and 71.4% of all cases on 2D pre-contrast T1-weighted, contrast-enhanced T1-weighted, and 3D T1-weighted black-blood (BB) images, respectively. There was no significant difference in IMH volume between 3D T1-weighted BB and magnetization-prepared rapid gradient-echo sequences. PICA involvement was best visualized using 3D T1 sequences. 3D T1-weighted BB MRI provided good visualization of VBDA features, with large coverage, and was useful for detecting dissection flaps.


Thermodynamic properties of triangle-well fluids in two dimensions: MC and MD simulations.
With the aim of providing complementary data of the thermodynamics properties of the triangular well potential, the vapor/liquid phase diagrams for such potential with different interaction ranges were calculated in two dimensions by Monte Carlo and molecular dynamics simulations; also, the vapor/liquid interfacial tension was calculated. As reported for other interaction potentials, it was observed that the reduction of the dimensionality makes the phase diagram to shrink. Finally, with the aid of reported data for the same potential in three dimensions, it was observed that this potential does not follow the principle of corresponding states.


Upregulation of casein kinase 1epsilon in dorsal root ganglia and spinal cord after mouse spinal nerve injury contributes to neuropathic pain.
Neuropathic pain is a complex chronic pain generated by damage to, or pathological changes in the somatosensory nervous system. Characteristic features of neuropathic pain are allodynia, hyperalgesia and spontaneous pain. Such abnormalities associated with neuropathic pain state remain to be a significant clinical problem. However, the neuronal mechanisms underlying the pathogenesis of neuropathic pain are complex and still poorly understood. Casein kinase 1 is a serine/threonine protein kinase and has been implicated in a wide range of signaling activities such as cell differentiation, proliferation, apoptosis, circadian rhythms and membrane transport. In mammals, the CK1 family consists of seven members (alpha, beta, gamma1, gamma2, gamma3, delta, and epsilon) with a highly conserved kinase domain and divergent amino- and carboxy-termini. Preliminary cDNA microarray analysis revealed that the expression of the casein kinase 1 epsilon (CK1epsilon) mRNA in the spinal cord of the neuropathic pain-resistant N- type Ca2+ channel deficient (Cav2.2-/-) mice was decreased by the spinal nerve injury. The same injury exerted no effects on the expression of CK1epsilon mRNA in the wild-type mice. Western blot analysis of the spinal cord identified the downregulation of CK1epsilon protein in the injured Cav2.2-/- mice, which is consistent with the data of microarray analysis. However, the expression of CK1epsilon protein was found to be up-regulated in the spinal cord of injured wild-type mice. Immunocytochemical analysis revealed that the spinal nerve injury changed the expression profiles of CK1epsilon protein in the dorsal root ganglion (DRG) and the spinal cord neurons. Both the percentage of CK1epsilon-positive neurons and the expression level of CK1epsilon protein were increased in DRG and the spinal cord of the neuropathic mice. These changes were reversed in the spinal cord of the injured Cav2.2-/- mice. Furthermore, intrathecal administration of a CK1 inhibitor IC261 produced marked anti-allodynic and anti-hyperalgesic effects on the neuropathic mice. In addition, primary afferent fiber-evoked spinal excitatory responses in the neuropathic mice were reduced by IC261. These results suggest that CK1epsilon plays important physiological roles in neuropathic pain signaling. Therefore CK1epsilon is a useful target for analgesic drug development.


Development and developmental potential of cortical thymic epithelial cells.
The thymic cortex provides a microenvironment for the development and positive selection of immature T cells. Cortical thymic epithelial cells (cTECs), which structurally and functionally support the thymic cortical microenvironment, originate from endodermal epithelial progenitors that arise in the third pharyngeal pouch. Recent studies have revealed that thymic epithelial progenitors pass through a stage where the cells express cTEC-associated molecules prior to lineage separation into cTECs and medullary TECs (mTECs). Here, we review the molecular signatures of cTECs and highlight the development and developmental potential of cTECs.


Text Analysis of Suicide Risk in Adolescents and Young Adults.
Suicide is of primary public concern for adolescents and young adults (AYAs) who commonly use social media platforms to express their suicidal thoughts and behaviors. Understanding how AYAs communicate their suicide-related thoughts and behaviors in texts can support early detection of suicide risk from their social media posts. Therefore, this study sought to identify themes relevant to suicide risk in AYAs and explore words or terms used by AYAs when they described suicidal thoughts and behaviors. This secondary data analysis utilized an existing data set collected from 255 AYAs between 12 and 25 years of age, who provided brief descriptions of how they and their peers expressed their experiences of self-harm, suicidal thinking, and attempts. Text analysis was conducted using KH Coder software. Three-step theory of suicide was used to guide a content analysis to explore the key themes from the narratives. A word co-occurrence network with 24 clusters of words was generated from the text analysis. These word clusters were further grouped into pain or hopelessness, connectedness, and capacity to attempt suicide in the content analysis. Six subthemes corresponding to these three themes were identified to provide detailed information: psychological or physical pain, hopelessness, relationship, help seeking, methods, and outcomes. Moreover, several slang terms and acronyms (e.g., Kermit Sewage Slide, KMS) were also identified. The findings of this study, including themes and slang terms and acronyms, are valuable to facilitate the use of terms or phrases within social media texts to identify suicide risk in AYAs.


Intralesional steroid injections in addition to endoscopic dilation in benign refractory esophageal strictures : a systematic review.
Benign esophageal strictures are primarily treated with dilation therapy, but strictures can recur or can be unresponsive, requiring additional or repeated treatment. This study investigates the efficacy and safety of intralesional steroid injections in addition to dilation in comparison to dilation alone in patients with benign refractory or recurrent esophageal strictures. A systematic search was carried out in PubMed, using the search terms "Esophageal Stenosis"[Mesh] AND "Injections, Intralesional"[Mesh]. In addition, the reference list of all selected articles was searched manually for other relevant articles. All clinical trials and case series were considered. This systematic review included four randomized controlled trials, six case series and two cohort studies, comprising 341 patients with benign esophageal strictures of different etiologies. A benefit of adding intralesional steroid injections to dilation in reducing the need for repeat dilation was seen in the subgroups of peptic, radiation-induced and corrosive strictures. Results were inconsistent for anastomotic strictures and too limited for strictures due to eosinophilic esophagitis, sclerotherapy or pill esophagitis. Complications were rare and of limited severity. Endoscopic dilation remains the first-line treatment, since its efficacy and safety are mostly satisfactory. In recurrent or refractory strictures, intralesional steroid injections are advised in peptic strictures and can be considered in radiation- induced, corrosive strictures and anastomotic strictures. It is recommended to restrict the steroid use to a maximum of three sessions and to consider alternative treatment if treatment effects remain insufficient.


When the physician-researcher gets cancer: understanding cancer, its treatment, and quality of life from the patient's perspective.
The authors, both medical researchers, describe their personal experiences with cancer, its treatment, and its effects on their lives. They discuss the "eight Ds" that represent their concerns as they navigated this permanent disruption in their lives: diagnosis, dying, discomfort, disability, drug and other treatment effects, dependency, doubt, and death. They also discuss the beneficial effects that cancer has had on their lives and end with suggestions for clinicians and outcomes researchers who seek to assess and improve quality of life among persons with cancer.


[Visualising lymph nodes by aclarubicin bound to activated carbon particles in breast cancer surgery].
A new dosage formulation (ACR-CH), composed of aclarubicin (ACR) bound to fine activated carbon particles, has been developed for the treatment of lymph node metastases in breast cancer. ACR-CH is designed to (a) adsorb a great amount of aclarubicin and desorb in a free state; (b) distribute a greater amount of ACR for a longer period of time selectively to the regional lymph nodes; (c) be decreased in the systemic toxicity; and (d) enhance its therapeutic effect on lymph node metastases. In this clinical trial in 20 patients with breast cancer, ACR-CH was injected intra- and peritumorally just before operation for breast cancer, and we examined the extent of blackened nodes produced by ACR-CH. ACR-CH blackened about 70% of the axillary lymph nodes with cancer metastasis as well as the nodes without metastasis. In conclusion, ACR-CH will be useful for dissection of lymph nodes by visualizing the nodes during operation for breast cancer.


Long-term cardiac effects of treatment for childhood leukemia.
Late cardiac complications in cancer survivors may develop from subclinical myocardial damage. Biochemical correlates of minimal myocardial changes can be analyzed using a commercially available rapid assay. Biomarkers are considered more sensitive markers of subclinical cardiotoxicity than conventional electrocardiographic and echocardiographic methods. The aim of this study was to determine the values of plasma N-terminal pro brain natriuretic peptide (NT-pro-BNP) and cardiac troponin T (cTnT) in asymptomatic childhood leukemia survivors after anthracycline therapy in comparison with healthy volunteers. The survivors also underwent a detailed echocardiography. Twenty six survivors of leukemia previously treated with anthracyclines with total cumulative dose 95-600 (median 221) mg/m(2) were evaluated. Analyses of cTnT and NT-proBNP from blood samples and echocardiography were performed 5-25 years after completion of therapy for childhood leukemia. Control group for biochemical analyses consisted of 22 age- and gender- matched apparently healthy volunteers. Values of NT-proBNP were significantly elevated in ANT group compared to controls (35.1 +/- 37.8 vs. 9.6 +/- 6.7 pg/ml, P<0.010). CTnT remained below the diagnostic cut-off values in both groups. All echocardiographic parameters of patients remained normal. In conclusion, differences in NT-proBNP values between patients treated with anthracyclines and healthy volunteers might signal an initial stage of anthracycline-induced myocardial damage. The potential of this biomarker to detect subclinical anthracycline-induced myocardial alterations before development of echocardiographic and clinical changes is promising.


Metabolic modulation and cellular therapy of cardiac dysfunction and failure.
At present the prevalence of heart failure rises along with aging of the population. Current heart failure therapeutic options are directed towards disease prevention via neurohormonal antagonism (beta-blockers, angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers and aldosterone antagonists), symptomatic treatment with diuretics and digitalis and use of biventricular pacing and defibrillators in a special subset of patients. Despite these therapies and device interventions heart failure remains a progressive disease with high mortality and morbidity rates. The number of patients who survive to develop advanced heart failure is increasing. These patients require new therapeutic strategies. In this review two of emerging therapies in the treatment of heart failure are discussed: metabolic modulation and cellular therapy. Metabolic modulation aims to optimize the myocardial energy utilization via shifting the substrate utilization from free fatty acids to glucose. Cellular therapy on the other hand has the goal to achieve true cardiac regeneration. We review the experimental data that support these strategies as well as the available pharmacological agents for metabolic modulation and clinical application of cellular therapy.


Biochemical and molecular analysis of carotenoid biosynthesis in flavedo of orange (Citrus sinensis L.) during fruit development and maturation.
Changes in carotenoid content and composition and expression of carotenoid biosynthetic genes were analyzed in the flavedo of sweet orange (Citrus sinensis L. Osbeck, cv. Navelate) fruit during development and maturation. Lutein and all-E-violaxanthin were the major carotenoids in chloroplast-containing tissues. During fruit coloration, phytoene, beta-cryptoxanthin, zeaxanthin, and mainly (9Z)-violaxanthin progressively accumulated, and a large proportion of apocarotenoids was also found in the flavedo of full-colored fruits. We have cloned partial and full-length cDNAs corresponding to genes involved in early condensation and desaturase reactions [phytoene synthase (PSY), phytoene desaturase (PDS), and zeta-carotene desaturase (ZDS)], coupled redox reaction (plastid terminal oxidase), cyclizations [beta-lycopene cyclase (beta-LCY) and epsilon-lycopene cyclase (epsilon-LCY)], hydroxylation [beta-carotene hydroxylase (beta-CHX)], and epoxidation [zeaxanthin epoxidase (ZEP)] and analyzed their mRNA accumulation in the flavedo of fruits during development and ripening as compared with those of leaves. Collectively, the results indicated that PDS gene expression correlated with carotenoid content in developing fruit and that up-regulation of PSY and ZDS genes at the onset of fruit coloration would enhance the production of linear carotenes and the flux into the pathway. The shift from the beta,epsilon-branch to the beta,beta-branch of the pathway that originates the changes in carotenoid composition during fruit coloration may be explained by a down-regulation of epsilon-LCY and by the increase of the beta-CHX transcript.


Refinement in reanimation of the lower face.
Both the temporalis muscle transfer and the static sling procedure are techniques that improve deglutition, speech, and aesthetics in patients who are afflicted with paralysis of the lower part of the face. A refinement that is applicable to either of these procedures is described. By bringing the perioral attachment of either the muscle or the static sling exactly to the midline of the upper and lower lips, the surgeon can make the patient's mouth more symmetrical. This simple refinement will improve the results obtained with either procedure and has not been associated with any increased perioperative risks or complications.


T Cell Subsets and Natural Killer Cells in the Pathogenesis of Nonalcoholic Fatty Liver Disease.
Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by hepatic accumulation of excess lipids. T cells are commonly classified into various subsets based on their surface markers including T cell receptors, type of antigen presentation and pathophysiological functions. Several studies have implicated various T cell subsets and natural killer (NK) cells in the progression of NAFLD. While NK cells are mainly components of the innate hepatic immune system, the majority of T cell subsets can be part of both the adaptive and innate systems. Several studies have reported that various stages of NAFLD are accompanied by the accumulation of distinct T cell subsets and NK cells with different functions and phenotypes observed usually resulting in proinflammatory effects. More importantly, the overall stimulation of the intrahepatic T cell subsets is directly influenced by the homeostasis of the gut microbiota. Similarly, NK cells have been found to accumulate in the liver in response to pathogens and tumors. In this review, we discussed the nature and pathophysiological roles of T cell subsets including γδ T cells, NKT cells, Mucosal-associated invariant T (MAIT) cells as well as NK cells in NAFLD.


Tuning the auxin transcriptional response.
How does auxin provoke such a diverse array of responses? This long-standing question is further complicated by a remarkably short nuclear auxin signalling pathway. To crack the auxin code, several potential sources of specificity need to be evaluated. These include: specificity of interactions among the core auxin response components, specificity resulting from higher order complex dynamics, and specificity in interactions with global factors controlling protein turnover and transcriptional repression. Here, we review recent progress towards characterizing and quantifying these interactions and highlight key gaps that remain.


Using Technology to Facilitate Collaboration in Community-Based Participatory Research (CBPR).
This study explores the use of Computer-Supported Collaborative Work (CSCW) technologies, by way of a computer-based system called iCohere. This system was used to facilitate collaboration conducting Community-Based Participatory Research (CBPR). Data was gathered from 13 members of a Community Collaborative Board (CCB). Analysis revealed that iCohere served the following functions: facilitating communication, providing a depository for information and resource sharing, and allowing for remote meeting attendance. Results indicated that while iCohere was useful in performing these functions, less expensive technologies had the potential to achieve similar goals if properly implemented. Implications for future research on CSCW systems and CBPR are discussed.


Renal medullary carcinoma. Case report and review of the literature.
Young patients with sickle cell trait or disease present a higher risk for renal medullary carcinoma, an aggressive renal tumor, with dismal prognosis, with a median survival of 4 months from the time of diagnosis. We report a 26-year-old patient with a 2-month history of bone pain at the right iliac crest, loss of weight, recurrent macroscopic hematuria and abdominal mass. Imaging studies demonstrated a 10-cm mass in the right kidney. Pathological evaluation revealed a medullary carcinoma and the patient died after 4 months, despite adjuvant treatment. Whenever a patient with sickle cell trait or disease presents with hematuria and/or flank pain, the possibility of a renal medullary carcinoma should always be kept in mind, with thorough investigation and expeditious treatment.


Elevated Cystatin-C Levels Are Associated with Increased Mortality in Acute Coronary Syndrome Patients: An HIJ-PROPER Sub-Analysis.
We investigated the association between serum cystatin-C (Cys-C) levels and cardiovascular events in patients with acute coronary syndrome (ACS). Data of 1,100 patients from the prospective parent study were included. Patients hospitalized for ACS were divided into 4 groups based on quartiles (Q) of Cys-C levels (mg/L) within 24 h of admission: Q1, ≤0.82; Q2, 0.82 < estimated level ≤0.95; Q3, 0.95< estimated level ≤1.12; and Q4, >1.12. The primary endpoint of this study was all-cause mortality, and the secondary endpoint was composite of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina pectoris, or ischemia-driven revascularization. During a median observation period of 4.0 years, the primary endpoint was noted in 5, 12, 18, and 36 patients in Q1-Q4, respectively, with corresponding incidence rates of 1.8%, 4.4%, 6.5%, and 13.5%, respectively (p < 0.0001 for difference among 4 groups). This association persisted even after adjusting for patient characteristics and other laboratory results at baseline (p = 0.04). A stepwise increase in the incidence rate of the secondary endpoint with an incline in Cys-C levels was observed in the nonadjusted model (26.6%, 33.3%, 32.3%, and 39.1% in Q1-Q4, respectively; p = 0.01) but not in the adjusted model (p = 0.3). No difference was observed in the incidence rate of nonfatal myocardial infarction (p = 0.89), nonfatal stroke (p = 0.3), unstable angina pectoris (p = 0.49), and ischemia-driven revascularization (p = 0.47) with an incline in Cys-C levels. Elevated Cys-C levels were associated with increased all-cause mortality but not cardiovascular events other than mortality in ACS patients.


Nephrolithiasis is associated with an increased prevalence of cardiovascular disease.
Nephrolithiasis has been associated with hypertension, obesity and diabetes mellitus. The prevalence of adverse cardiovascular outcomes among kidney stone formers (KSF) is unknown. We examined the IV Portuguese National Health Survey for documenting possible associations between nephrolithiasis, cardiovascular diseases, diabetes and obesity in the Portuguese adult population. We obtained 23 349 questionnaires from individuals ≥ 15 years old. The prevalence of kidney stone disease (KSD) was 7.3%. The prevalence of hypertension was higher among KSF when compared with the general population (50.4 vs 30.2%; P < 0.001). Age and obesity significantly increase the risk for nephrolithiasis. After adjusting for age and body mass index, KSF have higher prevalence of hypertension [odds ratio (OR), 1.841; 95% CI, 1.651-2.053], diabetes mellitus (OR, 1.475; 95% CI, 1.283-1.696; P < 0.001), myocardial infarction (OR, 1.338; 95% CI, 1.003-1.786; P < 0.05) and stroke (OR, 1.330; 95% CI, 1.015-1.743; P < 0.05) compared with non-stone formers. KSD is associated with a higher prevalence of chronic diseases and adverse cardiovascular outcomes when compared with the general population.


[The organo-clinical hiatus today. Some thoughts about Neurosciences, Psychopathology and Clinical Psychiatry in the early twenty-first century].
The concept of "organo clinical-hiatus" prepared by Henri Ey the mid-twentieth century has transcended the boundaries of time and has an amazing utility if it is considered from the point of view of both epistemological and clinical. Current developments in the field of neuroscience on the one hand and effective in clinical practice of psychopathological concepts born in the nineteenth century on the other, pose a challenge for psychiatrists today. It is important not to take a naive position on the new neuroscientific knowledge adopting a dogmatic stance that keeps us patient and while maintaining a clear position that avoids specialty contempt by those who argue that mental illness is a mere construct sustained by the medical hegemonic power. We believe the best way to protect our psychiatric practice of involuntary biases and attacks blinded by reductionist ideas is having a historical knowledge of our discipline and a solid epistemological basis. That way we will have the largest options to help our patients.


Risk of suicide ideation associated with problem-solving ability and attitudes toward suicidal behavior in university students.
The present paper investigates the risk of lifetime suicide ideation associated with problem-solving ability and attitudes toward suicidal behavior in a sample of 328 university students (41% male, 59% female). The response rate was 77% based on the total number of students registered for the relevant courses. A series of questions assessed lifetime suicide ideation, while problem solving and attitudes toward suicide were measured using the Self-Rating Problem Solving scale and four subscales of the Suicide Opinion Questionnaire, respectively (McLeavey, 1986; Domino et al., 1989). Almost one-third of the students surveyed had lifetime suicide ideation. Both genders were similar in terms of their suicide ideation history, problem solving, and attitudes toward suicidal behavior with the exception that male students were more in agreement with the attitude that suicidal behavior lacks real intent. Compared with 2% of nonideators and ideators, one in four planners reported that they would more than likely attempt suicide at some point in their life. Greater agreement with the attitude that suicidal behavior is normal was associated with significantly increased risk of being an ideator, as was poor problem solving and less agreement with the attitude that suicidal behavior is associated with mental illness.


Sequential catecholamine and serotonin depletion in mirtazapine-treated depressed patients.
This study was aimed at determining whether patient- or antidepressant-related variables are most important to the mood response to serotonin (5-HT) or catecholamine depletion. Depressed patients treated with open-label mirtazapine (>or=6 wk) received two depletion tests (5-HT and catecholamine depletion) 1 wk apart. Both 5-HT and catecholamine depletion led to a partial return of depression in most patients. Antidepressant response to mirtazapine is dependent on its dual actions on norepinephrine and 5-HT neurotransmission. Mood response to tryptophan or catecholamine depletion is dependent on the pharmacological properties of the antidepressant being taken during depletion.


The close relationships of Lesbians and gay men.
This article reviews empirical studies of same-sex couples in the United States, highlighting consistent findings, drawing comparisons to heterosexual couples, and noting gaps in available research. U.S. Census data indicate that there were more than 600,000 same-sex couples living together in 2000. Research about relationship formation, the division of household labor, power, satisfaction, sexuality, conflict, commitment, and relationship stability is presented. Next, we highlight three recent research topics: the legalization of same-sex relationships through civil unions and same-sex marriage, the experiences of same-sex couples raising children, and the impact of societal prejudice and discrimination on same-sex partners. We conclude with comments about the contributions of empirical research to debunking negative stereotypes of same-sex couples, testing the generalizability of theories about close relationships, informing our understanding of gender and close relationships, and providing a scientific basis for public policy.


Dissociation between the effect of nitrous oxide on spontaneous and reflexly evoked sympathetic activity in dogs.
We have examined the effect of nitrous oxide on spontaneous sympathetic activity and A delta- and C-fibre mediated somatosympathetic reflexes in renal nerves, evoked by supramaximal electrical stimulation of radial nerves in anaesthetized, paralysed dogs undergoing mechanical ventilation. In six preparations, nitrous oxide was administered at end-tidal concentrations of 10%, 30%, 50% and 70%, each for 20 min. Spontaneous renal sympathetic activity increased significantly to 147.8% and 151.2% of control values with 50% and 70% nitrous oxide, respectively (P < 0.05), but there were no significant changes in A delta and C reflexes. We conclude that the large increase in spontaneous sympathetic activity was dissociated from somatosympathetic reflexes which remained unchanged at these concentrations of nitrous oxide.


Biological standards in haemostasis and thrombosis.
International standards are used to assess the potency of a variety of biological drugs employed in the field of haemostasis and thrombosis. These include therapeutic concentrates for the treatment of inherited coagulation defects, such as haemophilia, thrombolytic drugs such as streptokinase for the treatment of heart attacks, and anticoagulant drugs such as heparin. Some of these standards have existed for over 25 years, and they continue to play a vital role in ensuring consistent potency, and hence safety, of manufactured drugs. The growing complexity of new products, particularly in the area of recombinant technology, represents a continuing challenge for the field of biological standardization.