Antigen-independent killer cells prepared for adoptive immunotherapy: One source, divergent protocols, diverse nomenclature.
Adoptive cell therapy (ACT) using tumor antigen-independent killer cells has been widely used in clinical trials of cancer treatment. Circumventing the need for identification of a particular tumor-associated antigen on tumor cells, the approach has opened possibilities for the extension of ACT immunotherapy to patients with a wide variety of cancer types. Namely, Natural Killer (NK), Lymphokine-activated Killer (LAK) cells and Cytokine-induced killer (CIK) cells are the most commonly used cell types in antigen-independent adoptive immunotherapy of cancer. They all originate from peripheral blood mononuclear cells and share several common features in their killing mechanisms. However, despite broad application in clinical settings, the boundaries between these cell types are not very clearly defined. The current study aims to review different aspects of these cell populations in terms of phenotypical characteristic and preparation media, to clarify how the boundaries are set.


Safety of prehospital nitroglycerin.
To define changes in vital signs and cardiac rhythm in prehospital patients given sublingual nitroglycerin. A five-month prospective observational study with nitroglycerin administration as the independent variable. Five independent advanced life support services. Three hundred prehospital patients who were given nitroglycerin by advanced life support personnel for presumed myocardial ischemia or congestive heart failure; excluded were those without repeat vital signs or ECG monitoring and those given additional medications. Nitroglycerin was administered by regional emergency medical services protocols or by the order of an on-line medical command physician. Four study patients (1.3%) had adverse effects: One became asystolic and apneic for two minutes, two experienced profound bradycardia with hypotension, and one became hypotensive while tachycardic. All recovered. The 95% confidence interval for adverse effects was 0.5% to 3.4%. Mean fall in systolic blood pressure for the other 296 patients was 14 mm Hg for one dose (confidence interval, 11 to 16 mm Hg) and 8 mm Hg (confidence interval, 2 to 13 mm Hg) for a second dose. Heart rate changed minimally with nitroglycerin administration. The blood pressure drop was linearly correlated with initial systolic pressure (r = -.44; P < .001) but not correlated with number of prior doses of nitroglycerin, initial heart rate, advanced life support time interval, age, or sex. Nitroglycerin seems to be a relatively safe advanced life support drug; however, a few patients experience serious adverse effects. Most of the adverse effects we observed were bradycardic-hypotensive reactions, which appeared to be unpredictable by pretreatment characteristics. Emergency personnel should have an increased awareness of this danger when considering the use of prehospital nitroglycerin.


Optical coherent dot-product chip for sophisticated deep learning regression.
Optical implementations of neural networks (ONNs) herald the next-generation high-speed and energy-efficient deep learning computing by harnessing the technical advantages of large bandwidth and high parallelism of optics. However, due to the problems of the incomplete numerical domain, limited hardware scale, or inadequate numerical accuracy, the majority of existing ONNs were studied for basic classification tasks. Given that regression is a fundamental form of deep learning and accounts for a large part of current artificial intelligence applications, it is necessary to master deep learning regression for further development and deployment of ONNs. Here, we demonstrate a silicon-based optical coherent dot-product chip (OCDC) capable of completing deep learning regression tasks. The OCDC adopts optical fields to carry out operations in the complete real-value domain instead of in only the positive domain. Via reusing, a single chip conducts matrix multiplications and convolutions in neural networks of any complexity. Also, hardware deviations are compensated via in-situ backpropagation control provided the simplicity of chip architecture. Therefore, the OCDC meets the requirements for sophisticated regression tasks and we successfully demonstrate a representative neural network, the AUTOMAP (a cutting-edge neural network model for image reconstruction). The quality of reconstructed images by the OCDC and a 32-bit digital computer is comparable. To the best of our knowledge, there is no precedent of performing such state-of-the-art regression tasks on ONN chips. It is anticipated that the OCDC can promote the novel accomplishment of ONNs in modern AI applications including autonomous driving, natural language processing, and scientific study.


Consideration of Intestinal Failure in Cases of De-Adaptation of Short Bowel Syndrome: A Case Report and Descriptive Review.
Short bowel syndrome (SBS) causes malabsorption due to extensive intestinal resection. While intestinal function declines with age, little is known about the relationship between intestinal failure and ageing. For the first time in Japan, we report a case of de-adaptation of SBS thought to be due to ageing, in a 93-year-old woman who presented with electrolyte imbalance and malnutrition. She had undergone five surgical resections of the small intestine over the past 20 years. She had developed SBS once due to multiple surgeries, but due to compensatory function, the symptoms had abated. However, due to decreased intestinal function caused by ageing, it worsened and symptoms reappeared. A literature search for the period January 1990 to May 2021 in Ichushi a major journal in Japan, found that de-adaptation of SBS occurred in 23 previous cases, of which we were able to confirm the details in 17 cases, with no case reports on "de-adaptation of SBS", demonstrating that the concept of "intestinal failure" has only recently begun to be used in routine practice. Therefore, we stress the importance of re-emphasizing the concept of "intestinal failure" in everyday practice, as well as other organ-related conditions such as cardiac or renal failure, as this may lead to a better understanding of the pathogenesis of malnutrition and diarrhoea in elderly patients.


Long-term zidovudine reduces neurocognitive deficits in HIV-1 infection.
To determine the efficacy of zidovudine (ZDV) in preventing decline of neurocognitive functions in HIV-1 infection. Retrospective evaluation of subjects enrolled in a natural history study. Two analyses were made to evaluate the effect of (1) current ZDV, irrespective of length of treatment and (2) long-term ZDV treatment for at least 1 year. Subjects were recruited from HIV out-patient clinics. HIV-1-seropositive subjects were assigned to one of three groups according to the Centers for Disease Control and Prevention classification: asymptomatic infection (n = 60), symptomatic infection but without AIDS (n = 51), and AIDS (n = 32). Standardized neuropsychological and neurophysiological measures [electroencephalogram (EEG) and long-latency evoked potentials]. Long-term ZDV use was associated with improved cognitive performance in subjects with early symptomatic HIV-1 infection and AIDS, compared to subjects in the same clinical stage but without previous ZDV treatment. This was corroborated by neurophysiological evidence of reduced slow-wave EEG amplitude in the ZDV-treated subjects. The advantage of ZDV treatment was evident despite lower immune status in most treated subjects. The findings in this natural history study indicate that long-term ZDV treatment may be an effective prophylactic to reduce neurocognitive deficits in symptomatic HIV-1 infection, thereby lowering the risk for developing HIV-1-associated dementia.


Blood Pressure Control Following Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers: Insights from a Triple-Blind, Randomized, Clinical Trial.
Data on substituting one antihypertensive medication with the proper dose of another antihypertensive medication, in certain medical conditions, are scarce. Herein, we present the results of replacing angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) with the calcium channel blocker (CCB) amlodipine, with or without the alpha- and beta-blocker carvedilol, to control high blood pressure in patients with coronavirus disease 2019 (COVID-19). Iranian hypertensive patients with COVID-19 and a history of taking ACEI or ARB were randomized to "continue" and "change" groups. The continue group comprised patients who continued using their previous antihypertensive medication regimen as normal, whereas patients in the change group had their antihypertensive drugs changed to the CCB amlodipine, with or without the alpha- and beta-blocker carvedilol, based on their response to amlodipine. Patients' blood pressures were measured for 8 days following their recruitment. A total of 31 and 33 patients were randomly allocated to the ACEI/ARB continue and ACEI/ARB change groups, respectively. No significant deviations were seen in patients' systolic blood pressure by substituting an ACEI/ARB agent with the CCB amlodipine, with or without the alpha- and beta-blocker carvedilol. Moreover, the change group had a more balanced systolic blood pressure (ie, 110-130 mmHg) compared with the continue group (ie, 111.5-140.0 mmHg) throughout their hospitalization period. During their hospitalization, the blood pressure of the change group was well controlled with the proposed equivalent doses. Further investigations of the proposed equivalent doses in larger randomized clinical trials, populations other than Iranian COVID-19 patients, and extended duration are encouraged (clinical trial registration ID: IRCT20151113025025N3).


Surgeon eye lens dose monitoring in interventional neuroradiology, cardiovascular and radiology procedures.
This study investigated the radiation dose to surgeon eye lens for single procedure and normalised to exposure parameters for eight selected neuroradiology, cardiovascular and radiology interventional procedures. The procedures investigated were diagnostic study, Arteriovenous Malformations treatment (AVM) and aneurysm embolization for neuroradiology procedures, Coronary Angiography and Percutaneous Transluminal Coronary Angioplasty (CA-PTCA), Pacemaker and Implantable Cardioverter-Defibrillator implantation (PM-ICD), Endovascular Aortic Repair (EVAR) and Fenestrated Endovascular Aortic Repair (FEVAR) for cardiovascular and electrophysiology procedures. CT-guided lung biopsy was also monitored. All procedures were performed with table-mounted and ceiling-suspended shields (0.5 mm lead equivalent thickness), except for FEVAR and PM-ICD where only a table mounted shield was present, and CT-guided lung biopsy where no shield was used. Dose assessment was performed using a dosemeter positioned close to the most exposed eye of the surgeon, outside the protective eyewear. The surgeon most exposed eye lens median Hp(3) equivalent dose for a single procedure, without protective eyewear contribution, was 18 μSv for neuroradiology diagnostic study, 62 μSv for AVM, 38 μSv for aneurysm embolization, 33 μSv for CA-PTCA, 39 μSv for PM-ICD, 49 μSv for EVAR, 2500 μSv for FEVAR, 153 μSv for CT-guided lung biopsy. In interventional procedures, the 20 mSv/year dose limit for surgeon eye lens exposure might be exceeded if shields or protective eyewear are not used. Surgeon eye lens doses, normalised to single procedures and to exposure parameters, are a valuable tool for determining appropriate radiation protection measures and dedicated eye lens dosemeter assignment.


Long term survival in two children with rhabdomyosarcoma of the biliary tract.
Due to low incidence, rhabdomyosarcoma (RMS) of the biliary tract poses numerous complex management problems especially in diagnosis and local therapy. The two presented patients were diagnosed by biopsy, performed by laparotomy and endoscopic retrograde cholangiopancreatography (ERCP) respectively. Nearly complete tumor regression was achieved by chemotherapy and irradiation according to the CWS-protocol. Subsequent radical resection followed directly in one patient and after local relapse in the other. Both patients are in remission 13 resp. 4 years after diagnosis with a good quality of life. Even in well responding biliary rhabdomyosarcomas, surgery after chemotherapy and radiotherapy seems to be necessary. Adjuvant chemotherapy should be continued after hepatic lobectomy.


Integrated network pharmacology and metabolomics to dissect the combination mechanisms of Bupleurum chinense DC-Paeonia lactiflora Pall herb pair for treating depression.
The compatibility of Bupleurum chinense DC (Chaihu)-Paeonia lactiflora Pall (Baishao) is one of the most accepted herb pairs in traditional Chinese medicine (TCM) prescriptions for treating depression. However, the combination mechanisms of this herb pair for anti-depression remain unclear. In this study, the combined effect of Chaihu-Baishao was evaluated by the chronic unpredictable mild stress (CUMS) rat model. Secondly, network pharmacology was constructed to dissect the united mechanisms. Based on the results of network pharmacology analysis, plasma metabolomics based on ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was performed to discover the collaborative effect on metabolite regulation. Furthermore, the targets from network pharmacology and the metabolites from metabolomics were jointly analyzed to select crucial metabolism pathways by MetaScape. Finally, the key metabolic enzymes and metabolites were experimentally validated by ELISA. The antidepressant effect of Chaihu-Baishao herb pair was significantly better than Chaihu or Baishao in sucrose preference test (SPT), open-field test (OFT), and forced swim test (FST). In network pharmacology, herb pair played synergetic effect through regulating shared pathways, such as MAPK signaling pathway and arachidonic acid metabolism, etc. Besides, by metabolomics, the herb pair improved more metabolites (14) than a single herb (10 & 9) and has a stronger regulation effect on metabolites. Correspondingly, herb pair adjusted more metabolism pathways (5) than individual herb (4 & 4). Furthermore, the arachidonic acid metabolism was selected as crucial metabolism pathways by a joint analysis of 199 targets and 14 metabolites. The results showed that herb pair regulated arachidonic acid metabolism by synergetic reducing the level of arachidonic acid, and inhibiting the enzyme activity of prostaglandin-endoperoxide synthase 1 (PTGS1) and prostaglandin-endoperoxide synthase 2 (PTGS2). This work provided an integrated strategy for revealing the combination mechanisms of Chaihu-Baishao herb pair for treating depression, and also a rational way for clarifying the composition rules of TCM.


Symptoms of anxiety, depression, and aggression in non-clinical children: relationships with self-report and performance-based measures of attention and effortful control.
This study investigated the relation between the regulative trait of effortful control, and in particular attention control, and psychopathological symptoms in a sample of 207 non-clinical children aged 8-12 years. For this purpose, children completed self-report scales for measuring regulative traits and various types of psychopathological symptoms (i.e., anxiety, depression, and aggression) and were tested with a neuropsychological battery for measuring attention/effortful control capacity. Results indicated that self-report and performance-based measures of attention/effortful control were at best moderately correlated. Further, it was found that self-report indexes of attention/effortful control were clearly negatively related to psychopathological symptoms, which provides support for the notion that low regulation is associated with higher levels of psychopathology. Finally, the performance-based measure of attention/effortful control was not convincingly related to psychopathological symptoms.


An analytical solution simulating growth of Lewy bodies.
This paper reports a minimal model simulating the growth of a Lewy body (LB). To the best of our knowledge, this is the first model simulating LB growth. The LB is assumed to consist of a central spherical core, which is composed of membrane fragments and various dysfunctional intracellular organelles, and a halo, which is composed of alpha-synuclein (α-syn) fibrils. Membrane fragments and α-syn monomers are assumed to be produced in the soma at constant rates. The growth of the core and the halo are simulated by the Finke-Watzky model. Analytical (closed-form) solutions describing the growth of the core and the halo are obtained. A sensitivity analysis in terms of model parameters is performed.


The effects of indoor and outdoor dust exposure on the growth, sensitivity to oxidative-stress, and biofilm production of three opportunistic bacterial pathogens.
Within the last decade, many studies have highlighted the radical changes in the components of indoor and outdoor dust. For example, agents like automobile emitted platinum group elements and different kinds of organic phthalates and esters have been reported to be accumulating in the biosphere. Humans consistently face dermal, respiratory, and dietary exposures to these particles while indoors and outdoors. In fact, dust particulate matter has been associated with close to 500,000 deaths per year in Europe and about 200,000 deaths per year in the United States. To date, there has been limited examination of the physiological impact of indoor and outdoor dust exposure on normal flora microbes. In this study, the effect of indoor- and outdoor-dust exposure on three opportunistic bacterial species (Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa) was assessed. Specifically, bacterial growth, oxidative stress resistance, and biofilm production were measured following indoor- and outdoor-dust exposures. Studies were conducted in nutritionally-rich and -poor environments typically encountered by bacteria. Surprisingly, indoor-dust (200μg/mL), enhanced the growth of all three bacterial species in nutrient-poor conditions, but slowed growth in nutrient-rich conditions. In nutrient-rich medium, 100μg/mL exposure of either indoor- or outdoor-dust resulted in significantly reduced oxidative stress resistance in E. coli. Most interestingly, dust (indoor and outdoor), either in nutrient-rich or -poor conditions, significantly increased biofilm production in all three bacterial species. These data suggest that indoor and outdoor dust, can modify opportunistic bacteria through altering growth, sensitivity to oxidative stress, and their virulence potential through enhanced biofilm formation.


Testing alleged mediumistic writing: An experimental controlled study.
Mediumship is understood as a kind of spiritual experience in which a person (i.e., a medium) claims to be in communication with, or under the control of, spiritual beings. In the last decades there has been a resurgence of studies on psychological, psychiatric and neuroscientific aspects of mediumship, as well as studies assessing the claim that mediums can obtain anomalous information from deceased persons. To assess the evidence for anomalous information reception about deceased people in texts produced through alleged mediumistic writing (psychographic letters) under strictly controlled experimental conditions. Eight mediums and ninety-four sitters participated in the study. Eighteen mediumistic writing sessions were carried out using blind proxy sitters. Later, each sitter received the target mediumistic letter and five control letters paired by gender and age. Sitters blindly scored the accuracy of the six letters both with a global score and for each of the objectively verifiable items of information presented on the letters. Scores from target and control letters were compared. There was no difference in global evaluation and specific fit scores between control and target letters. The mediums involved in the research were not able to show evidence for providing anomalous information about deceased people when under our strict controlled conditions. We argue for establishing a reasonable compromise between ecological validity and controlled condition.


AlphaII-spectrin breakdown product increases in principal cells in the gerbil main olfactory bulb following transient ischemia.
In pathological states, calpains in neurons easily degrade spectrin and yield specific fragments called spectrin breakdown products characterized by their high stabilities both in vitro and in vivo. In the present study, we investigated chronological changes in alphaII-spectrin immunoreactivity and protein levels using the antibody to detect both the naïve form and breakdown products of alphaII-spectrin in the gerbil main olfactory bulb (MOB) after 5 min of transient forebrain ischemia. In sham-operated gerbils, weak alphaII-spectrin immunoreactivity was detected in principal (mitral and tufted) cells. Ten days after ischemia/reperfusion, alphaII-spectrin immunoreactivity was increased in principal cells. Fifteen days after ischemia/reperfusion, alphaII-spectrin immunoreactivity in the somata and processes of principal cells was markedly increased. Thereafter, alphaII-spectrin immunoreactivity in the principal cells in the ischemic MOB was decreased with time. In Western blot study, spectrin protein bands were detected in naïve form (230 kDa) and its breakdown product (150 kDa). The breakdown product in MOB homogenates were significantly increased 15 days after ischemia/reperfusion and thereafter decreased with time after ischemia/reperfusion. Our results indicate that alphaII-spectrin breakdown product in the gerbil MOB is changed in principal cells after ischemic insult.


No evidence for an effect of nutritional status at diagnosis on prognosis in children with acute lymphoblastic leukemia.
To test the hypothesis that nutritional status at diagnosis, defined as body mass index standard deviation score (SDS), is related to the prognosis in childhood acute lymphoblastic leukemia (ALL). The sample consisted of 1,025 patients with standard risk ALL who had been randomized to different intensification therapies. Outcome measures were relapse/no relapse and time to first relapse. The influence of body mass index SDS was tested by survival analysis. There was no evidence that body mass index SDS was related to clinical outcome (proportional hazards model, p = 0.72). The study results suggest that nutritional status at diagnosis, defined on the basis of the body mass index, at least in developed countries, has no effect on the prognosis in ALL, and it should not be considered as a prognostic factor.


Education by a dietitian in patients with heart failure results in improved adherence with a sodium-restricted diet: a randomized trial.
Multidisciplinary heart failure (HF) programs reduce hospital readmission and improve clinical outcomes. Although dietitians are often members of such teams, no randomized studies have demonstrated the independent benefit of dietitian-administered dietary counseling for patients with HF. The purpose of this study was to evaluate the effect of dietitian education on adherence to a sodium-restricted diet in ambulatory patients with stable HF. Patients with HF (left ventricular ejection fraction < 35%) were randomized into a dietitian education group (n = 23) or a usual care group (n = 24), then observed for 3 months. Both groups received a 2 g/d dietary sodium prescription. The usual care group received nutrition advice by way of self-help literature, whereas the dietitian education group returned for 2 counseling sessions with a dietitian. Dietitian education resulted in a significant decrease in sodium intake at 3 months (2.80 +/- 0.30 to 2.14 +/- 0.23 g/d, P < .05). In contrast, there was no change in sodium intake in the usual care group (3.00 +/- 0.31 to 2.74 +/- 0.35 g/d, P = ns). Dietitian-administered counseling was more effective than providing literature in reducing dietary sodium intake in patients with stable HF.


The incentive effect of creating a national health city on the ecological welfare performance: based on the evidence of Yangtze River Delta in China.
Under the background of China's high-quality development, improving the ecological environment, enhancing the welfare level of residents and promoting the sustainable development of cities have become a hot issue of widespread concern in society. This paper focuses on the Yangtze River Delta region, aiming to study the direct incentive effect and spatial spillover effect of creating a national health city on the ecological welfare performance. It also further decomposes the spatial spillover effect, to study the path of spatial spillover and the characteristics of heterogeneity in different regions. The results show that (1) the ecological welfare performance in the Yangtze River Delta is increasing year by year, and the average growth rate was 0.23%. There is a spatial effect of "beggar-thy-neighbor." The improvement of local ecological welfare performance will reduce the performance level of the surrounding areas by more than 30%. (2) To create a national health city in local areas, the ecological welfare performance in local areas will be increased by 0.087%, and the ecological welfare performance in the surrounding areas will be increased by 0.031%. Among them, the ecological welfare performance of the surrounding national health cities will be increased by 0.067%, and the ecological welfare performance of the surrounding non-health cities will not be significantly improved. (3) The effect has heterogeneity in coastal and inland areas. In terms of direct incentive effect, coastal areas are more obvious than inland areas. In terms of spatial spillover effect, inland areas show more positive spatial spillover effect than coastal areas, whether in groups or within groups. This paper is the first time to study this issue, enhance the theory, and practice of ecological welfare performance.


Modulation of Escherichia coli UvrD Single-Stranded DNA Translocation by DNA Base Composition.
Escherichia coli UvrD is an SF1A DNA helicase/translocase that functions in chromosomal DNA repair and replication of some plasmids. UvrD can also displace proteins such as RecA from DNA in its capacity as an anti-recombinase. Central to all of these activities is its ATP-driven 3'-5' single-stranded (ss) DNA translocation activity. Previous ensemble transient kinetic studies have estimated the average translocation rate of a UvrD monomer on ssDNA composed solely of deoxythymidylates. Here we show that the rate of UvrD monomer translocation along ssDNA is influenced by DNA base composition, with UvrD having the fastest rate along polypyrimidines although decreasing nearly twofold on ssDNA containing equal amounts of the four bases. Experiments with DNA containing abasic sites and polyethylene glycol spacers show that the ssDNA base also influences translocation processivity. These results indicate that changes in base composition and backbone insertions influence the translocation rates, with increased ssDNA base stacking correlated with decreased translocation rates, supporting the proposal that base-stacking interactions are involved in the translocation mechanism.


Construction and application of a novel electrochemical sensor for trace determination of uranium based on ion-imprinted polymers modified glassy carbon electrode.
In the present work, a novel electrochemical sensor modified glassy carbon electrode with ion-imprinted polymers (IIP-GCE) was applied for uranyl ions (UO22+) determination. Surface modifier was synthesized through precipitation polymerization method, using acrylic acid as a monomer, benzoyl peroxide (BPO) as initiator, and trimethylolpropane triacrylate (TMPTA) as cross-linker. A new uranyl-trans-3-(3-pyridyl) acrylic acid complex was employed, serving as an active and specific site on the synthesized modifier. Next, the synthesized modifier was characterized using X-ray diffraction (XRD), Scanning Electron microscopy (SEM), and Fourier Transform Infrared Spectroscopy (FT-IR) techniques. UO22+ ions were detected using a differential pulse adsorptive anodic stripping voltammetry method. Under the optimized conditions (pH = 8.0, pre-concentration time = 10 min and pre-concentration potential = -0.30 V), the modified electrode exhibited linear behavior in the interval of 1.27-95.49 μg.L-1 with a limit of detection (LOD) of 0.43 μg.L-1. Also, the constructed ion-imprinted sensor showed a successful application for determining UO22+ ions with recovery range of 97.6-101% in real samples.


The impact of physical education on obesity among elementary school children.
In response to the dramatic rise in childhood obesity, the Centers for Disease Control (CDC) and other organizations have advocated increasing the amount of time that elementary school children spend in physical education (PE) classes. However, little is known about the effect of PE on child weight. This paper measures that effect by instrumenting for child PE time with the state's mandated minimum number of minutes of PE, using data from the Early Childhood Longitudinal Study, Kindergarten Cohort (ECLS-K) for 1998-2004. Results from IV models indicate that PE lowers BMI z-score and reduces the probability of obesity among 5th graders. This effect is concentrated among boys; we find evidence that this gender difference is partly attributable to PE being a complement with other physical activity for boys, whereas they are substitutes for girls. This represents some of the first evidence of a causal effect of PE on youth obesity, and thus offers at least some support for the assumptions behind the CDC recommendations. We find no evidence that increased PE time crowds out time in academic courses or has spillovers to achievement test scores.


Assertive outreach teams in London: staff experiences and perceptions. Pan-London Assertive Outreach Study, part 2.
The job satisfaction, burn-out and work experiences of assertive outreach team staff are likely to be important to the model's sustainability. To describe self-reported views and work experiences of staff in London's 24 assertive outreach teams and to compare these with staff in community mental health teams (CMHTs) and between different types of assertive outreach team. Confidential staff questionnaires in London's assertive outreach teams (n=187, response rate=89%) and nine randomly selected CMHTs (n=114, response rate=75%). Staff in assertive outreach teams and CMHTs were moderately satisfied with their jobs, with similar sources of satisfaction and stress. Mean scores were low or average for all sub-scales of the Maslach Burnout Inventory for the assertive outreach team and the CMHT staff, with some differences suggesting less burn-out in the assertive outreach teams. Nine of the 24 assertive outreach teams had team means in the high range for emotional exhaustion and there were significant differences between types of assertive outreach team in some components of burn-out and satisfaction. These findings are encouraging, but repeated investigation is needed when assertive outreach teams have been established for longer.


Trypanosoma cruzi strain-specific monoclonal antibodies: identification of Colombian strain flagellates in the insect vector.
Spleen cells from mice immunized with insect-derived Trypanosoma cruzi metacyclic trypomastigotes were used to obtain Colombian strain-specific monoclonal antibodies. At least 4 different strain-specific antigens were recognized by the monoclonal antibodies on epimastigotes or metacyclic trypomastigotes. There was no reactivity with other stages of Colombian strain T. cruzi, nor with any stage of 15 other T. cruzi strains or isolates, nor with 22 other Trypanosomatidae. One of the monoclonal antibodies was used to identify, by indirect immunofluorescence, Colombian strain flagellates in cryostat sections or glass-slide smears of the insect vector's intestine.


Pharmacologic management of systemic hypertension in blacks.
This article contrasts the characteristics of essential hypertension found in the black population with that seen in the nonblack population. Socioeconomic and pathophysiologic factors are discussed. Different pharmacologic classes of drugs are compared for their effectiveness in treating the black hypertensive patient. Because black hypertensives tend to have salt-sensitive, low-renin hypertension coupled with decreased cardiac output and high peripheral vascular resistance, an ideal antihypertensive should have natriuretic effects but also the physiologic capability of reducing vascular resistance. Such an ideal hypertensive drug would be able to lower systemic blood pressure while improving organ perfusion and function.


Effect of clinic-based single-lead electrocardiogram rhythm assessment on oral anticoagulation prescriptions in patients with previously diagnosed atrial fibrillation.
Despite benefits of oral anticoagulation (OAC), many individuals with diagnosed atrial fibrillation (AF) do not receive OAC. The purpose of this study was to assess whether cardiac rhythm assessment for AF impacted use of OAC in patients with previously diagnosed AF. VITAL-AF was a cluster randomized controlled trial conducted in 16 primary care practices assessing the efficacy of AF rhythm assessment with single-lead electrocardiogram in routine care. Patients 65 years and older were offered rhythm assessment at visits. In this secondary analysis, we evaluated rhythm assessment uptake and compared initiation and discontinuation of OAC in patients with previously diagnosed AF from intervention and control arms over 1 year. The study included 4593 patients with previously diagnosed AF (2250 intervention; 2343 control). In the intervention arm, 2022 (89.9%) completed rhythm assessment (median 2 visits with rhythm assessment) and 40.1% had ≥1 "Possible AF" result. Initiation of OAC was similar in the intervention (17.7%) and control (19.1%) arms but was influenced by the rhythm assessment result: higher with a "Possible AF" (26.1%; adjusted odds ratio [aOR] 1.62; 95% confidence interval [CI] 1.04-2.51), and lower with a "Normal" result (9.9%; aOR 0.45; 95% CI 0.29-0.71) compared to control. OAC discontinuation was similar in the intervention (6.3%) and control (7.2%) arms, with lower discontinuation with a "Possible AF" result (3.8%; aOR 0.51; 95% CI 0.32-0.81). Including patients with previously diagnosed AF in a point-of-care rhythm assessment strategy did not increase overall OAC use compared to the control arm. However, the rhythm assessment result influenced both initiation and discontinuation of OAC.


Determining the PASS cut-off points for the FIQR, FASmod and PSD in patients with fibromyalgia: a registry-based study.
To determine the cut-off values of Patient Acceptable Symptom State (PASS) for the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Scale (FASmod), and the Polysymptomatic Distress scale (PSD) and to determine the predictors of PASS in patients with fibromyalgia (FM). FM patients belonging to the Italian Fibromyalgia Registry (IFR) completed the FIQR, the FASmod and the PSD. The PASS was assessed using a dichotomous answer. The cut-off values were obtained through the receiver operating characteristic curve (ROC) analyses. A multivariate logistic regression analysis was performed to determine predictors of achieving the PASS. 5545 women (93.7%) and 369 males (6.3%) were included in the study. The 27.8% of patients reported an acceptable symptom state. Patients in PASS differed in all patient-reported outcome measures (p <0.001). The FIQR PASS threshold was ≤58 (area under the ROC curve [AUC] = 0.819). The FASmod PASS threshold was ≤23 (AUC = 0.805) and the PSD PASS threshold was ≤16 (AUC = 0.773). In the pairwise AUC comparison, the discriminatory power of the FIQR PASS outperforms both FASmod PASS (p = 0.0124) and PSD PASS (p <0.0001). Multivariate logistic analysis showed that FIQR items related to memory and pain were the only predictors of PASS. The FIQR, FASmod, and PSD PASS cut-off points for FM patients have never been determined before. This study provides additional information to facilitate interpretation of the severity assessment scales in daily practice and clinical research related to FM patients.


Neuronal ceroid lipofuscinoses: a review.
Neuronal ceroid lipofuscinoses (NCLs) are among the most common neurodegenerative diseases in childhood but rarely present in adulthood. The main symptoms are psychomotor deterioration, visual failure, epilepsy and motor disturbances. The NCLs are morphologically characterized by the accumulation of lipopigments within numerous cell types and loss of neurons. Pathogenesis is unknown. The current clinical classification recognizes six classic types of NCL and several atypical forms. Electrophysiological and neuroradiological findings may be of diagnostic significance, but disease recognition rests on the demonstration of a typical ultrastructural pattern. Genetic studies have demonstrated that several different genetic loci are involved in the pathogenesis of NCL, but the molecular mechanisms underlying neuronal death and lipopigment accumulation are not understood.


Iminated aminoglycosides in self-emulsifying drug delivery systems: Dual approach to break down the microbial defense.
Aminoglycosides are well known, cationic antimicrobial drugs. However, biofilm-based antibiotic resistance significantly limits their efficacy. Masking the polycationic character of these drugs, followed by incorporation into self-emulsifying drug delivery systems (SEDDS) can improve biofilm eradication. Imine derivatives were synthesized via coupling with trans-cinnamaldehyde and characterized regarding degree of substitution, logP, cytotoxicity and antimicrobial efficacy on the opportunistic human pathogens Escherichia coli, Staphylococcus aureus and Candida albicans. Imines were loaded into newly developed SEDDS formulations and the antimicrobial efficacy was assessed on these pathogens in planktonic state and after biofilm formation. Successful synthesis of imine derivatives with almost entirely masked amine groups was confirmed by NMR, FT-IR, TLC and MS. Imines exhibited a marked elevation in logP value of 8 units for kanamycin and 7.7 units for tobramycin. They showed low toxicity profiles while fully preserving antimicrobial efficacy on all tested pathogens. Incorporation into SEDDS resulted in nanoemulsions, which exhibited equal antimicrobial efficacy on the model germs compared to the corresponding aminoglycosides. Moreover, the biofilm eradication assay revealed superior anti-biofilm properties of the nanoemulsions. Native aminoglycosides were largely prone to reduced microbial susceptibility due to biofilm formation, while the combination of SEDDS with iminated aminoglycosides provided overall enhanced biofilm eradication.


Ryanodine-sensitive, thapsigargin-insensitive calcium uptake in rat ventricle homogenates.
Thapsigargin is a natural product that specifically inhibits all known SERCA calcium pumps with high affinity. We investigated the effects of thapsigargin on cardiac sarcoplasmic reticulum (SR) by measuring the oxalate-supported calcium uptake rate in the unfractionated homogenate and in the isolated SR fraction. The uptake rate in both the isolated SR and unfractionated homogenate are stimulated about two-fold by preincubation with high concentrations of ryanodine, which closes the SR efflux channel. Thapsigargin stoichiometrically and completely inhibited the calcium uptake rate in the isolated SR, both in the presence and absence of SR channel blockade. In contrast, thapsigargin nearly completely inhibited the homogenate calcium uptake only in the absence of SR channel blockade; in the presence of blockade, about 20% of the uptake activity was insensitive to thapsigargin. This result unmasks a thapsigargin-insensitive, ryanodine-sensitive component of calcium uptake in the heart. This activity is in an oxalate-permeable pool and is inhibited by cyclopiazonic acid, another inhibitor of the SERCA calcium pumps. There was no TG-insensitive activity in the rat EDL muscle homogenate. The absence of thapsigargin-insensitive uptake activity in the isolated SR can be attributed to its inactivation during the isolation of the SR. The oxalate permeability and ryanodine sensitivity suggest that the TG-insensitive calcium uptake activity is closely related to the classical SR. The different thapsigargin sensitivities suggests the existence of two kinds of intracellular calcium pumps in the heart.


Protein identification by MALDI-TOF mass spectrometry.
MALDI-TOF mass spectrometers are now commonplace and their relative ease of use means that most non-specialist labs can readily access the technology for the rapid and sensitive analysis of biomolecules. One of the main uses of MALDI-TOF-MS is in the identification of proteins, by peptide mass fingerprinting (PMF). Here we describe a simple protocol that can be performed in a standard biochemistry laboratory, whereby proteins separated by 1D or 2D gel electrophoresis can be identified at femtomole levels. The procedure involves excision of the spot or band from the gel, washing and destaining, reduction and alkylation, in-gel trypsin digestion, MALDI-TOF-MS of the tryptic peptides and database searching of the PMF data. Up to 96 protein samples can easily be manually processed at one time by this method.


Etiology of unilateral hearing loss in a national hereditary deafness repository.
The aim of this study was to characterize the genetic, audiologic, and epidemiologic characteristics of unilateral hearing loss (HL) in a national hereditary deafness repository. This is a prospective clinical study involving 34 subjects identified in a national hereditary deafness repository. Clinical data and family history of HL were obtained on enrollment. Candidate deafness genes were screened by single-stranded conformation polymorphism, and mutations were confirmed with sequencing. Thirty-four subjects (19 males, 15 females) with unilateral HL were identified, ranging in age from 2 months to 36 years. The mean age at diagnosis was 7 years, and the left ear was affected in 62% of the cases. The racial distribution of our sample was 62% white, 23% African American, and 15% Hispanic. Imaging results were available in 47%, and most (69%) were considered normal. Nineteen percent had enlarged vestibular aqueducts, 2 had ipsilateral Mondini dysplasia, and 1 had a common cavity deformity. Twenty subjects (59%) had a family history of HL, with 26% specifically reporting familial unilateral HL. Mutational screening revealed sequence variants in the GJB2 (connexin 26), GJB3 (connexin 31), TECTA, and COCH genes. Two novel mutations were detected in COCH and TECTA. Sequence variants in known deafness genes were detected in more than one-third of our study population, suggesting that gene/gene or gene/environmental interactions may indeed play a role in the etiology of some cases of unilateral deafness. Further prospective studies including congenital cytomegalovirus screening at birth and molecular screening of deafness genes in children with congenital unilateral HL will be required to establish the etiology of unilateral deafness with certainty.


Isolation of xanthomegnin from Penicillium viridicatum by preparative high-pressure liquid chromatography.
A method was developed for the production and purification of xanthomegnin from Penicillium viridicatum (NRRL 6430) cultured on rice at 15 degrees C for 29 days. Liquid-liquid extraction followed by high-pressure liquid chromatography afforded 440 mg of crystalline xanthomegnin per kg of rice.


N-Terminal domain of Bombyx mori fibroin mediates the assembly of silk in response to pH decrease.
Fibroins serve as the major building blocks of silk fiber. As the major component of fibroin, the fibroin heavy chain is a considerably large protein comprising N-terminal and C-terminal hydrophilic domains and 12 highly repetitive Gly-Ala-rich regions flanked by internal hydrophilic blocks. Here, we show the crystal structure of the fibroin N-terminal domain (FibNT) at pH 4.7, revealing a remarkable double-layered anti-parallel β-sheet with each layer comprising two FibNT molecules entangled together. We also show that FibNT undergoes a pH-responsive conformational transition from random coil to β-sheets at around pH 6.0. Dynamic light scattering demonstrates that FibNT tends to oligomerize as pH decreases to 6.0, and electron microscopy reveals micelle-like oligomers. Our results are consistent with the micelle assembly model of silk fibroin and, more importantly, show that the N-terminal domain in itself has the capacity to form micelle-like structures in response to pH decrease. Structural and mutagenesis analyses further reveal the important role of conserved acidic residues clustered in FibNT, such as Glu56 and Asp100, in preventing premature β-sheet formation at neutral pH. Collectively, we suggest that FibNT functions as a pH-responsive self-assembly module that could prevent premature β-sheet formation at neutral pH yet could initiate fibroin assembly as pH decreases along the lumen of the posterior silk gland to the anterior silk gland.


The shortest way to reach nutritional goals is to adopt Mediterranean food choices: evidence from computer-generated personalized diets.
Dietary guidelines can be derived from dietary patterns known to be healthy such as the traditional Mediterranean diet. They can also be deduced by translating a set of nutrient recommendations into food combinations. However, the latter may vary depending on the decisions made by different expert committees. The objective was to compare the effect of removing or adding selected nutrient recommendations on the dietary changes needed to fulfill a whole set of nutrient recommendations. For each adult participating in the French INCA dietary survey (Enquête Individuelle et Nationale sur les Consommations Alimentaires) (n = 1171), a nutritionally adequate diet was modeled that simultaneously met a whole set of nutrient goals (proteins, fiber, essential fatty acids, 10 vitamins, 9 minerals, sodium, saturated fatty acids, free sugars) while deviating the least from the observed diet in terms of food content. Eight sets of models were developed according to the inclusion or not of constraints on total fats, total carbohydrates, total MUFAs, and cholesterol. Compared with the observed intakes, fulfilling the whole set of nutrient constraints systematically decreased total fats and increased total carbohydrates, even in the absence of specific constraints on those macronutrients. For whichever model used, a strong consistency was observed in the dietary changes needed to fulfill the constraints, and the greatest increases were seen for unsalted nuts, unrefined grains, legumes, fruit, fish and shellfish, and vegetables. Whether recommendations on total fats, MUFAs, or total carbohydrates are included or not in the definition of overall nutrient adequacy, foods typical of the Mediterranean diet are needed to reach overall nutrient adequacy.


Population pharmacokinetics and pharmacogenetics analyses of imatinib in Chinese patients with chronic myeloid leukemia in a real-world situation.
Imatinib is presently the first-line choice for the treatment of chronic myeloid leukemia. However, there are limited real-world data on Chinese patients to support individualized medicine. This work aims to characterize population pharmacokinetics in Chinese patients with chronic myeloid leukemia, investigate the effects of several covariates on imatinib exposure, and provide support for personalized medicine and dose reduction. A total of 230 patients with chronic myeloid leukemia were enrolled, and 424 steady-state concentration measurements were taken to perform the population pharmacokinetic analysis and Monte Carlo simulations with Phoenix NLME software. The effects of the demographic, biological, and pharmacogenetic (ten SNP corresponding to CYP3A4, CYP3A5, ABCB1, ABCG2, SCL22A1 and POR) covariates on clearance were evaluated. A one-compartmental model best-described imatinib pharmacokinetics. The hemoglobin and the estimated glomerular filtration rate (< 85 mL⋅min-1⋅1.73 m2) were associated with imatinib clearance. The genetic polymorphisms related to pharmacokinetics were not found to have a significant effect on the clearance of imatinib. The final model estimates of parameters are: ka (h-1) = 0.329; Vd/F (L) = 270; CL/F (L⋅h-1) = 7.60. Key covariates in the study population accounting for variability in imatinib exposure are hemoglobin and the estimated glomerular filtration rate. There is some need for caution when treating patients with moderate-to-severe renal impairment and significant hemoglobin changes.


Cerebral evoked potentials. A method of quantification of central nervous system response to esophageal pain.
Cerebral evoked potentials (EPs) represent a new technique for the evaluation of afferent outflow from the gastrointestinal tract. We compared EPs obtained with distension of the distal and proximal esophagus. Responses were recorded with the balloon 5 cm proximal to the lower esophageal sphincter and 3 cm distal to the upper esophageal sphincter. Balloon stimulation resulted in cortical responses recorded by midline scalp electrodes (CZ', PZ, and OZ by the International 10-20 system) in normal volunteers. EP responses consisted of two negative (N1, N2) and one positive (P1) deflections. The proximal esophageal latency of N1 was shorter in all three leads. The latency to P1 was shorter with proximal stimulation in lead CZ' only, and N2 latencies were not different. Amplitudes expressed as the difference between N1 and P1, and P1 and N2 were not different. When two sets of potentials several minutes apart from the proximal position were compared, a decrease in amplitude with the second set of stimulations was noted. Esophageal EP recording is a new technique that may provide information about the integrity and function of the sensory innervation of the esophagus.


Development of fatal bilateral xanthogranulomatous pyelonephritis in a paraplegic patient: case report.
The first case of a bilateral xanthogranulomatous pyelonephritis (XGPN) is reported in a paraplegic patient who did not practise intermittent catheterisation after discharge from the hospital but resorted to the Crede manoeuvre which predisposed to a fatal urinary tract infection and development of XGPN over a period of 5 weeks. The advantages of clean, unsterile, intermittent self catheterisation over the Crede manoeuvre in patients with a neuropathic bladder are discussed especially in preventing infective complications of the upper urinary tract which may prove life threatening as occurred in this patient.


Limited Wegener's granulomatosis. Unusual cutaneous, radiographic, and pathologic manifestations.
A case of limited Wegener's granulomatosis is presented with unusual black linear and circular digital infarcts, unilateral bursitis and subcutaneous nodules, interstitial pneumonitis, and unusual pulmonary pathology. Response to cyclophosphamide was curative.


Patient-Reported Quality Measures for Palliative Care: The Time is now.
While progress has been made in the ability to measure the quality of hospice and specialty palliative care, there are notable gaps. A recent analysis conducted by Center for Medicare and Medicaid Services (CMS) revealed a paucity of patient-reported measures, particularly in palliative care domains such as symptom management and communication. The research team, consisting of quality measure and survey developers, psychometricians, and palliative care clinicians, used established state-of-the art methods for developing and testing patient-reported measures. We applied a patient-centered, patient-engaged approach throughout the development and testing process. This sequential process included 1) an information gathering phase; 2) a pre-testing phase; 3) a testing phase; and 4) an endorsement phase. To fill quality measure gaps identified during the information gathering phase, we selected two draft measures ("Feeling Heard and Understood" and "Receiving Desired Help for Pain") for testing with patients receiving palliative care in clinic-based settings. In the pre-testing phase, we used an iterative process of cognitive interviews to refine draft items and corresponding response options for the proposed measures. The alpha pilot test supported establishment of protocols for the national beta field test. Measures met conventional criteria for reliability, had strong face and construct validity, and there was diversity in program level scores. The measures received National Quality Forum (NQF) endorsement. These measures highlight the key role of patient voices in palliative care and fill a much-needed gap for patient-reported experience measures in our field.


Predictive Ability of an Emergency Medical Dispatch Stroke Diagnostic Tool in Identifying Hospital-Confirmed Strokes.
Early hospital notification of a possible stroke arriving via emergency medical services (EMS) can prepare stroke center personnel for timely treatment, especially timely administration of tissue plasminogen activator. Stroke center notification from the emergency dispatch center-before responders reach the scene-may promote even earlier and faster system activation, meaning that stroke center teams may be ready to receive patients as soon as the ambulance arrives. This study evaluates the use of a Medical Priority Dispatch System (MPDS; Priority Dispatch Corp., Salt Lake City, UT) Stroke Diagnostic Tool (SDxT) to identify possible strokes early by comparing the tools' results to on-scene and hospital findings. The retrospective descriptive study utilized stroke data from 3 sources: emergency medical dispatch, EMS, and emergency department/hospital. A total of 830 cases were collected between June 2012 and December 2013, of which 603 (72.7%) had matching dispatch records. Of the 603 cases, 304 (50.4%) were handled using MPDS Stroke Protocol 28. The SDxT had an 86.4% ability (OR [95% CI]: 2.3 [1.5, 3.5]) to effectively identify strokes among all the hospital-confirmed stroke cases (sensitivity), and a 26.6% ability to effectively identify nonstrokes among all the hospital-confirmed nonstroke cases (specificity). The SDxT demonstrated a very high sensitivity, compared to similar tools used in the field and at dispatch. The specificity was somewhat low, but this was expected-and is intended in the creation of protocols to be used over the phone in emergency situations. The tool is a valuable method for identifying strokes early and may allow early hospital notification.


Pregnancy in sickle cell disease: maternal and fetal outcomes in a population receiving prophylactic partial exchange transfusions.
To describe pregnancy outcomes for pregnant women with sickle cell disease (SCD) receiving prophylactic transfusions. This retrospective case-control study compared pregnancy outcomes among women with SCD receiving prophylactic transfusions and women without any hemoglobinopathy, matched for ethnicity, parity, age and hospital. The study included two groups of pregnancies: 128 in women with SCD (95 with SS phenotype and 33 with SC) and 128 in women with AA phenotype. No woman died. Two perinatal deaths (2.1%) and five alloimmunizations (5.3%) occurred, all in the SS group. Compared with the control group, HbSS disease was more often associated with pre-eclampsia (9.4% versus 2.3%, p=.03), preterm delivery (15.8% versus 6.2%, p=.01), birth weight <10th percentile (13.7% versus 3.9%, p=.008) and caesarean delivery (73.6% versus 26.4%, p<.01). Despite prophylactic blood transfusions, SCD remains a severe complicating factor in pregnancy. The policy of systematic transfusions should be analyzed in a sufficiently large randomized trial.


3D Bioprinting a human iPSC-derived MSC-loaded scaffold for repair of the uterine endometrium.
Common events in the clinic, such as uterine curettage or inflammation, may lead to irreversible endometrial damage, often resulting in infertility in women of childbearing age. Currently, tissue engineering has the potential to achieve tissue manipulation, regeneration, and growth, but personalization and precision remain challenges. The application of "3D cell printing" is more in line with the clinical requirements of tissue repair. In this study, a porous grid-type human induced pluripotent stem cell-derived mesenchymal stem cell (hiMSC)-loaded hydrogel scaffold was constructed using a 3D bioprinting device. The 3D-printed hydrogel scaffold provided a permissive in vitro living environment for hiMSCs and significantly increased the survival duration of transplanted hiMSCs when compared with hiMSCs administered locally in vivo. Using an endometrial injury model, we found that hiMSC transplantation can cause early host immune responses (the serological immune response continued for more than 1 month, and the local immune response continued for approximately 1 week). Compared with the sham group, although the regenerative endometrium failed to show full restoration of the normal structure and function of the lining, implantation of the 3D-printed hiMSC-loaded scaffold not only promoted the recovery of the endometrial histomorphology (endometrial tissue and gland regeneration) and the regeneration of endometrial cells (stromal cells and epithelial cells) and endothelial cells but also improved endometrial receptivity functional indicators, namely, pinopode formation and leukemia inhibitory factor and αvβ3 expression, which partly restored the embryo implantation and pregnancy maintenance functions of the injured endometrium. These indicators were significantly better in the 3D-printed hiMSC-loaded scaffold group than in the unrepaired (empty) group, the hiMSCs alone group and the 3D scaffold group, and the empty group showed the worst repair results. Our study confirm that the 3D-printed hiMSC-loaded hydrogel scaffold may be a promising material for endometrial repair.


Inflammatory infiltrates and natural killer cell presence in human brain tumors.
Immunohistochemical analysis of subpopulations of inflammatory cells in 81 primary and secondary human brain tumors was done. Natural killer (NK) cells, representing non-major histocompatibility complex-restricted, spontaneous cytotoxicity and monocytic cells are virtually absent in infiltrates of gliomas and account only for a minor percentage of inflammatory cells in brain metastases of carcinoma and in craniopharyngeomas. Infiltrates in gliomas consist almost exclusively of T-cells of the suppressor/cytotoxic type whereas infiltrates in carcinoma metastases and craniopharyngeomas contain considerable numbers of T-helper/inducer cells and B-cells. From this the authors conclude (1) that NK cells do not play a major role in tumor rejection, and (2) that the kind of inflammatory reaction does not depend upon the tumor site but more likely on the tumor type. No correlation between tumor differentiation and infiltrate composition is evident.


Solexa sequencing of microRNAs on chromium metabolism in broiler chicks.
The aim of this study was to determine the effect of chromium picolinate (CrPic) on the differential expression of the known microRNAs (miRNAs) in broiler skeletal muscle. A total of 288 1-day-old male Arbor Acres broilers were randomly assigned to one of four dietary treatments supplemented with 0, 0.4, 2.0, or 10.0 mg·kg(-1) CrPic, respectively. Dietary CrPic supplementation at 10.0 mg·kg(-1) increased the average daily feed intake in broilers (p < 0.05). On day 42, the serum total protein level was highest in animals treated with 2.0 mg·kg(-1) (p < 0.05) and 10.0 mg·kg(-1) CrPic (p < 0.05). Dietary supplementation with 10.0 mg·kg(-1) CrPic decreased the levels of serum glucose (p < 0.05) on day 42 and of serum triglyceride (p < 0.05) on days 21 and 42. To further identify miRNAs from broiler skeletal muscles, we sequenced two small RNA libraries using the Solexa sequencing approach, and 57 miRNAs were found to be significantly differentially expressed (p < 0.05). Among them, 6 upregulated and 2 downregulated miRNAs were validated by real-time qPCR (p < 0.05). The results of the present study provide a valuable clue regarding the role of miRNA target genes in the mechanism of the dietary CrPic effect on protein synthesis in skeletal muscles of broilers.


Effects of the therapist's philosophical premises on psychotherapeutic process.
This article focuses on differences in assumptions forming the philosophical foundations of psychotherapy leading to profound differences in the interpretation of the clinical data of psychotherapy and corresponding variations of basic technique. These differences are not reconcilable because they are directly opposed; only the principle of complementarity, as described in the paper, permits a constructive approach to the antinomies.


Assignment of the human progesterone receptor to the q22 band of chromosome 11.
The human progesterone receptor gene was localized by in situ hybridization to the q22 band of chromosome 11.


Mosaic loss of the Y chromosome and men's health.
Although Y chromosomal genes are involved in male sex development, spermatogenesis, and height growth, these genes play no role in the survival or mitosis of somatic cells. Therefore, somatic cells lacking the Y chromosome can stay and proliferate in the body. Several molecular technologies, including next-generation sequencing and multiplex PCR-based assays, are used to detect mosaic loss of the Y chromosome (mLOY) in the blood of men. Accumulating evidence suggests that mLOY represents the most common acquired chromosomal alteration in humans, affecting >40% of men over 70 years of age. Advanced age, tobacco smoking, and some SNPs in cell cycle genes are known to increase the frequency of mLOY. The developmental process of mLOY in elderly men remains to be clarified, but it possibly reflects recurrent mitotic elimination of Y chromosomes or clonal expansion of 45,X cell lineages. In rare cases, mLOY also occurs in young men and fetuses. MLOY has been associated with early death, cancers, and other disorders in elderly men, infertility in reproductive-aged men, and developmental defects in children. Y chromosomes in men can be lost at every life stage and Y chromosomal loss is associated with various health problems.


Thyroxine replacement therapy reverses sleep-disordered breathing in patients with primary hypothyroidism.
Anecdotal reports suggest that sleep-disordered breathing (SDB) is common among patients with primary hypothyroidism. This study was undertaken to determine the prevalence of SDB and to evaluate the effect of thyroxine replacement therapy on SDB in patients with primary hypothyroidism. Fifty consecutive newly diagnosed, untreated symptomatic patients with primary hypothyroidism (age: 34+/-11 years; males: 21 [42%]) were prospectively studied. Physical examination, anthropometry, fasting blood glucose and serum lipids were performed in all patients at baseline. Polysomnography was done at baseline in all patients and was repeated after adequate thyroxine replacement in those who had SDB. SDB defined as apnea-hypopnea index (AHI) > or =5 was present in 15 patients (30%) at baseline and was reversible in 10 of the 12 patients evaluated following thyroxine replacement therapy (P=0.006). Thyroxine replacement therapy was associated with improvement in findings that reflect a compromised upper airway, such as macroglossia (4 [33%] vs. 1 [8%]; P=0.083), myoedema (5 [42%] vs. 1 [8%]; P=0.046) and facial puffiness (10 [83%] vs. 1 [8%]; P=0.003). Reversible SDB is common among patients with primary hypothyroidism. Changes in upper airway anatomy resulting from hypothyroidism probably contribute to the development of SDB in these patients.


Inhibition of melanin production and promotion of collagen production by the extract of Kuji amber.
Kuji amber is fossilized tree resin of the Late Cretaceous in Japan. In this study, new biological activities of ethanol extract of Kuji amber (EtOH ext.) and supercritical carbon dioxide fluid extract of Kuji amber (scCO2 ext.) were examined. Both EtOH ext. and scCO2 ext. inhibited melanin production in B16 mouse melanoma cells and promoted collagen production in human skin fibroblast SF-TY cells. The scCO2 ext. had more potent activity than that of EtOH ext. and may depend on the efficiency of the extraction. The main new biologically active compound in Kuji amber, kujigamberol had no activities against melanin production, however, it promoted collagen production at low concentrations. A biologically active compound having a different structure, spirolactone norditerpenoid, showed both the inhibition activity against melanin production and the promotion activity of collagen production in a dose dependent manner. EtOH ext. and scCO2 ext., which include both kujigamberol and spirolactone norditerpenoid, have not only anti-allergy activity, but also inhibit melanin production and promote collagen production.


ICU Care Before and After Lung Transplantation.
Lung transplantation (LTx) has become an accepted treatment for carefully selected patients with end-stage lung disease. Critical care issues have gained importance concerning bridging of candidates by mechanical respiratory support and are involved in the care after transplantation. The nature of respiratory support varies from oxygen supply and noninvasive ventilation, to mechanical respiratory support either by mechanical ventilation and/or extracorporeal life support. Recent innovations in extracorporeal life support technology have resulted in its more widespread use. Retrospective studies have demonstrated promising outcomes in candidates on mechanical respiratory support as a bridge to lung transplantation. The role of mechanical respiratory support has influenced the selection criteria for LTx, although bridging remains technically and ethically challenging. Critical care is integral to manage and prevent postoperative complications of LTx. Primary graft dysfunction and prolonged mechanical ventilation are major obstacles to hospital survival after LTx. Clear evidence is lacking on how to ventilate and optimally manage patients after LTx. Prolonged extracorporeal life support after LTx may improve outcome in selected patients with a primary graft dysfunction.


Posttraumatic stress symptoms in children diagnosed with type 1 diabetes.
Studies consistently found remarkable rates of posttraumatic stress symptoms (PTSS) in children with chronic diseases. But, only one study had searched PTSS in children with diabetes, until now. So, the present study aimed to examine incidence rate and predictors of PTSS in children with type 1 diabetes. PTSS were evaluated by Child Posttraumatic Stress Reaction Index in fifty four children with diabetes (aged between 8-18 years). This assessment was based on hypoglycaemia as the potential traumatic event. Children were also introduced a brief questionnaire about demographic and disease related information. Some other information was obtained from families, medical stuff and records. Among 54 children, forty two had complete information. Hence, to evaluate possible predictive factors related with PTSS, multiple regression analysis was conducted for 42 children. 18.5% of children were reported PTSS at severe or very severe level, and 51.9% were reported PTSS at moderate level or above. Multiple regression analyses were shown that child PTSS were not significantly related with possible predictive factors other than number of hypoglycaemic attacks for the last month. The study results support that posttraumatic stress symptoms are not rarely seen in paediatric patients with diabetes, and even if not severe, hypoglycaemic attacks may be perceived as traumatic by the children with diabetes. But, because of some limitations, the results should be carefully interpreted.


Proteomic and bioinformatic analysis of a nuclear intrinsically disordered proteome.
Intrinsically disordered proteins (IDPs) are biologically active and crucial for cell function although they do not possess defined three-dimensional architecture. IDPs are especially prevalent in eukaryotic proteomes, and large-scale experiments have shown that many IDPs are nuclear proteins. Bioinformatic analyses have also demonstrated that the vast majority of transcription factors contain extended regions of intrinsic disorder. In the current study, we isolated and functionally analyzed IDPs expressed in the nuclei of HEK293 human cells. According to the results of MS analysis followed by subsequent analysis with the bioinformatic tools IUPred and RAPID (regression-based accurate predictor of intrinsic disorder), a heat-treatment method was able to enrich the nuclear lysate in IDPs. For approximately 85% of the proteins obtained, IUPred predicted a sequence of 30 or more consecutive disordered residues (DRs), and for approximately 83% of the proteins RAPID reported a content of at least 25% DRs (compared to ~66% and 49%, respectively, for the nuclear lysate). Gene Ontology analysis in terms of molecular function revealed that the obtained fraction was generally enriched in proteins involved in the process of transcription and especially in transcription factors. We also showed experimentally that IDPs are overrepresented in the cell nucleus. Intrinsically disordered proteins (IDPs) are crucial cellular molecules and are especially numerous in eukaryotes. In particular, IDPs act as signaling and regulatory proteins, and impairment in their functioning may lead to serious diseases. Large-scale bioinformatic studies of IDPs have provided essential knowledge about this group of proteins. However, experimental data reflect the actual situation in living cells. Our study is the first large-scale proteomic analysis of nuclear IDPs. We showed experimentally that IDPs are overrepresented in the nucleus in comparison to the whole cell. Analysis of molecular function indicated that the nuclear intrinsically disordered proteome (IDP-ome) is enriched in proteins involved in transcription regulation and especially in transcription factors. The IDP isolation method from human cell nuclei presented in this article could be further applied in differential proteomic studies.


Atrial septal defect of secundum type in patients under 40 years of age. A review of 481 operated cases. Symptoms, signs, treatment and early results.
In the period 1957--1976 481 patients under 40 years of age were operated on. Dyspnoea and increased fatigue were dominating symptoms in more than half of the series. In 202 cases the anomaly was discovered at routine examination in the absence of relevant symptoms. Almost half of the patients were operated under hypothermia, in the others extracorporeal perfusion was used. Four hospital deaths occurred, two of which were related to cardiopulmonary bypass.


Narrowing resection margins for patients with low-risk melanoma.
Surgeons hesitate to accept lesser cancer operations for several reasons. Paramount, however, is the fear that they might jeopardize cure rates by inadvertently leaving residual tumor behind. In cutaneous melanoma, for example, wide excision of the primary tumor site, usually in combination with skin grafting, has been the standard for years. Recently, as the biologic characteristics of this neoplastic system have become better understood, a subset of patients has been identified who can be cured readily by surgical excision alone. It is in this low-risk group of patients that lesser margins of excisions have been advocated. To date, a majority of surgeons have not accepted this thesis. In an effort to study this further, one of us prospectively treated 45 patients with thin, low-risk melanomas by conservative excision of their primary tumor sites. The margins invariably were 2 cm or less, and two thirds of the patients were operated on as out-patients utilizing local anesthesia. After a mean follow-up period of 36 months, no recurrences of melanoma developed. Acceptance of this treatment appears appropriate in this subset of patients.


Purified human early pregnancy factor from preimplantation embryo possesses immunosuppresive properties.
This study was undertaken to determine whether early pregnancy factor secreted by preimplantation embryos has immunosuppressive properties. Human early pregnancy factor was purified from embryo growth media of in vitro fertilized ova with ion-exchange and gel filtration chromatography. During each step of purification the fractions were tested for (1) early pregnancy factor activity with the rosette inhibition assay, (2) immunosuppressive properties with a concanavalin A-stimulated lymphocyte proliferation assay, and (3) purity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Results indicate that (1) human early pregnancy factor has a basic molecular weight of 14 kd, (2) early pregnancy factor has immunosuppressive activity, (3) polymers of early pregnancy factor also appear to be present in the embryo growth media, and (4) immunosuppressive factors other than early pregnancy factor are also secreted by preimplantation human embryos. Early pregnancy factor and other factor(s) produced by the preimplantation embryo may play a role in suppressing maternal cellular immune responses, thereby preventing maternal rejection of the embryo.


Trends in treatment and long-term survival of thyroid cancer in southeastern Netherlands, 1960-1992.
Thyroid cancer (TC), comprising less than 1% of all cancers in the Netherlands, has a good prognosis in general. Controversy still remains on the extent of surgical treatment and the indication for additional Iodine-131 (131I) therapy in the management of differentiated TC. The aim of this study was to describe (changes in) the treatment of TC and to determine independent prognostic factors for crude and relative survival of differentiated TC diagnosed in general hospitals. This population-based, retrospective study was based on data from the Eindhoven Cancer Registry, Comprehensive Cancer Centre South (I.K.Z.), Eindhoven, the Netherlands. Data were collected on all 343 TC patients diagnosed from 1 January 1960 to 31 December 1992. All available information on treatment (initial and additional) and survival (on 1 April 1994) were recorded. Initial surgical treatment was defined as limited or extended. Multivariate analysis of crude and relative survival to determine prognostic factors for differentiated TC was performed. Mean follow-up was 7.6 years. The proportion of patients with differentiated TC increased from 60% in 1960-1972 to 84% in 1985-1992. TC patients were treated in all hospitals in the region, approximately 2-4/year. Ninety per cent of all TC patients initially underwent surgical treatment; the extended procedures increasing from 27% in 1960-1974 to 61% in 1985-1992. 131I was also administered increasingly (from 18-44%) to patients with differentiated TC. The relative 5, 10 and 20 year survival rates for all TC were 80, 75 and 75%, respectively. In the first 5 years after diagnosis the crude death ratio was higher with the rise of age and for the follicular type and after 5 years for males and advanced disease. After inclusion of surgical treatment into the model, the estimates of the other death ratios did not change. Patients treated with 131I did better only during the first 5 years. Although the prognosis for TC patients treated in general hospitals in Southeastern Netherlands was similar to that found for patients treated in referral centres, concentration of treatment should be considered.


Mobile endoscopy: a treatment and training model for childhood hydrocephalus.
Hydrocephalus, largely a disease of poverty in many developing regions such as Sub-Saharan Africa, becomes even more challenging to treat because of lack of trained neurosurgical personnel, inadequately equipped public health care facilities, meager resource allocation, high rates of neonatal infection, difficulty of access to tertiary care hospitals able to treat hydrocephalus, and high complication rates in patients who are able to access and receive shunting procedures. Furthermore, conventional methods of training of neurosurgeons and nursing staff to become proficient in neuroendoscopic procedures involve a lengthy period of training, often at specialized centers in Western or local Western-style institutions. The novel approach promoted by volunteer neurosurgical teams from Neurosurgery Education Development Foundation is described, and its potential role in successfully providing neuroendoscopic ventriculostomy at hospitals in regional sites away from main referral tertiary hospitals is outlined. The impact on the training of local neurosurgical specialists and residents in training as well as nursing staff is highlighted. With the use of a single portable neuroendoscopy system and a versatile free-hand, single-operator neuroendoscope, this outreach, mobile, and readily portable model has been successfully used to perform more than 250 procedures in 21 different hospital sites around seven different countries in two continents. The local courses have imparted hands-on training to 62 neurosurgeons and trainee residents and a further 110 operating room nurses at these 21 institutions. Neuroendoscopy is not only a priority surgical tool for East Africa. It offers a medical philosophy as an application that serves as an art and a science dedicated to the development of a complex surgical specialty: neurosurgery.


C2-symmetrical hexaazatriphenylene derivatives as colorimetric and ratiometric fluorescence chemsensors for Zn2+.
Two C2-symmetrical hexaazatriphenylene (HAT) derivatives, 2,3-diphenyl-6,7,10,11-tetra(pyridin-2-yl)dipyrazino[2,3-f:2',3'-h]quinoxaline (1) and 2,3,6,7-tetraphenyl-10,11-di(pyridin-2-yl)dipyrazino[2,3-f:2',3'-h]quinoxaline (2), were designed and synthesized by the condensation reaction of 1,2-diamines and 1,2-diketones. Both compounds 1 and 2 exhibit sensitive, ratiometric and colorimetric fluorescence selectivity for Zn(2+) ion over alkali ions, alkaline earth ions and a wide range of transition metal ions upon excitation at 350 nm in acetonitrile/water. The interactions between 1 or 2 and Zn(2+) can be observed by naked eyes with an obvious color change of the solution from colorless to yellow. For fluorescence intensity of 2 toward Zn(2+), a good linearity (correlation coefficient R(2)=0.993) was established with a detection limit of 0.095 μM, which is more sensitive than that of 1 (0.2 μM). The binding modes of the free ligands 1 and 2 with Zn(2+) are discussed in context to their photophysical and electrochemical properties as well as single X-ray crystallographic structures of 1, 2 and 1-Zn.


Monitoring of SARS-CoV-2 antibodies using dried blood spot for at-home collection.
The utilization of vaccines to fight the spread of SARS-CoV-2 has led to a growing need for expansive serological testing. To address this, an EUA approved immunoassay for detection of antibodies to SARS-CoV-2 in venous serum samples was investigated for use with dried blood spot (DBS) samples. Results from self-collected DBS samples demonstrated a 98.1% categorical agreement to venous serum with a correlation (R) of 0.9600 while professionally collected DBS samples demonstrated a categorical agreement of 100.0% with a correlation of 0.9888 to venous serum. Additional studies were performed to stress different aspects of at-home DBS collection, including shipping stability, effects of interferences, and other sample-specific robustness studies. These studies demonstrated a categorical agreement of at least 95.0% and a mean bias less than ± 20.0%. Furthermore, the ability to track antibody levels following vaccination with the BioNTech/Pfizer vaccine was demonstrated with serial self-collected DBS samples from pre-dose (Day 0) out to 19 weeks.


Characterisation of Dichelobacter nodosus isolates from Norway.
An outbreak of ovine footrot in Norway in 2008, the first reported since 1948, prompted action to investigate Norwegian isolates of Dichelobacter nodosus. A total of 579 isolates from 124 different farms were characterised. These included 519 isolates from sheep, 52 isolates from cattle and 8 isolates from goats. The potential virulence of the isolates was assessed by the gelatin gel test (GG-test) and the elastin agar test, that test the heat stability and elastase activity of bacterial proteases, respectively. The isolates were also tested for the presence of intA by PCR, and allocated to serogroups by differentiation of fimA variants using multiplex PCR or sequencing. Thirty of the isolates were also serogrouped by slide agglutination. Three hundred and five isolates were defined as virulent by the GG-test. All these were from sheep from 52 farms located in the county of Rogaland in the south west of Norway. All isolates from cattle and goats were defined as benign by the GG-test. IntA was only detected in 6 (2.0%) of the virulent isolates. All serogroups except D and F were detected. Three hundred and seventy-two (64.3%) of the isolates belonged to serogroup A, and 96% of the virulent isolates belonged to this serogroup. On the grounds that virulent isolates were only found in one county, and that the majority belonged to the same serogroup (A), it is believed that a virulent D. nodosus strain was introduced to Norway relatively recently and that so far it has only spread locally.


Family cooperation and effectiveness in a cholesterol-lowering diet.
An average reduction in serum cholesterol approximating 10 per cent was achieved in a short-term, family-centered study in which intakes of cholesterol and saturated fats were decreased and sunflower oil and margarine were added as the major sources of polyunsaturated fats. Dietary Achievement Scores demonstrated shifts in food consumption between baseline and diet periods. Changes were evident in all fat-containing food groups; meat was the least altered. A high degree of cooperation was evident in participating families, implying the possibilities for complete family cooperation in preventive or therapeutic dietary programs. Approximately three months after the end of the test period, cholesterol levels had returned to pre-diet levels, indicating the need for continuation of the changed regimen if cholesterol-lowering is to be maintained.


The south-east Scotland dermatology workload study: 30 years' analysis.
Dermatological activity data have been collected for the same region of south-east Scotland (population 1·24 million), approximately every 5 years, since 1981. This has allowed assessment of trends in demand from primary and secondary care, and activity within secondary care dermatology services, assisting planning of dermatological services. To quantify dermatology outpatient workload across the same population to allow comparison with previous studies for trends in practice. During November 2010, a standardized proforma was completed for all National Health Service and private practice dermatology outpatient consultations. Demographic data, source and reason for referral, diagnoses, investigations, treatments and disposal were recorded, and comparisons made with five previous studies. A total of 5470 consultations were recorded: 2882 new and 2588 review patients (new to review ratio 1 : 0·9, male to female 1 : 1·3, mean age 49 years, range 1 month to 101 years). Ninety-one per cent of referrals came from primary care and 9% from secondary care. Fifty-eight per cent of referrals were for diagnosis and 32% for hospital management. Diagnostic concordance between referrer and dermatologist ranged from 94% for acne to 14% for melanoma. Benign tumours accounted for 30% of referrals, malignant tumours 13%, dermatitis 13·3%, psoriasis 6·2% and acne/rosacea 5%. The referral rate rose to 23·2/1000 population per annum, with the increase coming mainly from primary care. Demand for dermatology continues to increase: new referrals have risen by 134% in 30 years, with a 36% increase in the last 5 years, despite corresponding population increases of 5·3% and 3%, respectively.


A priming dose of protons alters the early cardiac cellular and molecular response to (56)Fe irradiation.
Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a "priming" dose of protons on the cardiac cellular and molecular response to a "challenge" dose of (56)Fe in a mouse model. Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of (56)Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of (56)Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. Exposure to (56)Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before (56)Fe prevented all of the responses to (56)Fe. This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions.


Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice.
In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC). All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan-Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates. A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01). In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.


On early and mid-adolescent schizophrenia.--Part II: prognosis, course and defect.
Twenty-three adolescent schizophrenics were studied in regard to the problems of the course of illness, prognosis and defect. Illustrations of cases (follow-up for three to 15 years) were presented. 1) The course was considered chiefly from the viewpoint of positive symptoms, namely paranoid-hallucinatory experiences. It was divided into the following four categories; remittent, persistent, scanty and fading types. At the same time, general characteristics of each type were discussed. 2) As to the changes in clinical forms, hebephrenia was gradually manifested in more than half of the cases. There were some cases in which the expansion of paranoid activities were observed. These two prominent tendencies might be explained in terms of personality disintegration and maturation. We were impressed, in this regard, that autistic tendencies and behavior disturbances were more manifest in the initial stages in patients who later turned more hebephrenic. 3) A mild defect was observed in fourteen cases, while a medium or severe defect was recognized in eight cases. Generally, the degree of defect seemed to be more manifest in female patients than in males. Moreover, the defect was generally more severe in early adolescent cases and in patients with insidious onsets as well as in those with a longer duration of illness than in mid-adolescent patients and those with acute onsets and a shorter duration of illness. 4) As the result of this investigation, it was substantiated that the prognosis in adolescent schizophrenia, especially in early adolescence, was unfavorable. 5) Finally, we were impressed by the fact that there were many patients who were treated mainly in ambulatory clinics or who stayed at home in spite of the above-mentioned unfavorable prognosis.


Measurement of the capillary interaction force between Janus colloidal particles trapped at a flat air/water interface.
The capillary interaction force between spherical Janus particles trapped at the air-water interface is measured using a time-sharing optical tweezer (bond number ≪ 1). One face of the particles is hydrophilic, and the other one, hydrophobic. Measured force goes from almost pure quadrupolar to almost pure hexapolar interaction due to the three-phase contact line corrugation. Measured force curves are modeled as a sum of power laws, Ar-α + Br-β + Cr-γ, obtained from an expansion in capillary multipoles. The mean values for the exponents of particle pairs of 3 μm are 〈α〉 = 5.05 ± 0.12, 〈β〉 = 7.02 ± 0.03, and 〈γ〉 = 5.96 ± 0.03. For particles pairs of 5 μm, we find 〈α〉 = 5.02 ± 0.04, 〈β〉 = 6.94 ± 0.06, and 〈γ〉 = 5.80 ± 0.05. In both cases, A < 0, B < 0, and C > 0.


Simulation-based education to improve emergency management skills in caregivers of tracheostomy patients.
Children with tracheostomies are medically complex and may be discharged with limited and variably trained home nursing support. When faced with emergencies at home, caregivers must often take the lead role in management, and many lack experience with troubleshooting these emergencies prior to initial discharge. A high-fidelity simulation-based tracheostomy education program was designed using a programmable mannequin (Gaumard HAL S3004 one-year-old pediatric simulator). At the conclusion of our standard education program, caregivers completed three simulation scenarios: desaturation, mucus plugging, and dislodgement. A trained simulation facilitator graded performance. A self-assessment tool was used to analyze comfort with emergency management at the beginning of training, before and after simulation. Caregivers rated confidence using a 10 cm visual analog scale. All participants completed a post-simulation debriefing session. 39 caregivers completed all three scenarios and returned pre- and post-simulation self-assessments. Mean scores from the caregiver self-assessments increased for all three scenarios, with mean increases of 9 mm for desaturation, 16 mm for mucus plugging, and 10 mm for decannulation. Two patterns of responses emerged: caregivers with progressive increase in confidence through training, and caregivers who initially rated confidence highly, and had confidence decrease as the complexity of true emergency management became apparent. All participants found the simulations to be realistic and helpful. High-fidelity simulation training allows for realistic exposure to trach-related emergencies. Many caregivers overestimate their ability to handle emergencies and gain important insight through simulation. Identification of skills and knowledge gaps prior to discharge allows for targeted re-education in emergency management.


Specific transcription and RNA splicing defects in five cloned beta-thalassaemia genes.
Transcriptional analysis of five different cloned beta-thalassaemia genes introduced into cultured mammalian cells revealed specific defects in transcription and RNA splicing. A single base change 87 base pairs to the 5' side of the mRNA cap site significantly lowers the level of transcription and therefore appears to represent a promoter mutation. Three genes contain different single base changes in the first intervening sequence (IVS) 5' splice site. One mutation, at IVS1 position 1, inactivates the splice site completely; the other two, at IVS1 positions 5 and 6, reduce its activity. Each mutation activates the same three cryptic splice sites. The fifth gene contains a single base change within IVS2 at position 745, which results in the formation of abnormal beta-globin RNA that contains an extra exon.


Occlusion of the left common femoral artery after total hip replacement. Report of a case and review of the literature.
Total occlusion of the left common femoral artery occurred after total hip replacement. Presumably the occlusion was caused by polymerization heat produced by the methyl-methacrylate. Only two similar cases have been reported previously. The vascular complications after hip surgery are discussed.


Monokine depression of bile flow in the isolated perfused rat liver.
Multiple system organ failure (MSOF) is a progressive dysfunction of vital organs that may develop in clinical settings such as sepsis or multiple trauma. One component of this syndrome is cholestasis and impaired liver function. The mechanism(s) for this liver failure (and the failure of other organs) remains obscure. Macrophages and Kupffer cells have been shown to secrete cytokines such as interleukin-1 and tumor necrosis factor. These cytokines mediate many aspects of the acute phase response, and they also can produce cellular injury. The purpose of this study was to evaluate the effects of a semipurified murine monokine preparation having interleukin-1 activity on bile flow in the rat isolated perfused liver (IPL). The monokine preparation produced a significant reduction of bile flow in the IPL system. The effect could not be explained by a venoocclusive phenomenon or residual endotoxin in the monokine preparation. We conclude that a semipurified monokine preparation having interleukin-1 but not tumor necrosis activity produced a significant depression of bile flow in the IPL, and we suggest that macrophage secretory product(s) may be responsible for the cholestasis in MSOF.


Where are the Sunday babies? Observations on a marked decline in weekend births in Germany.
In 5-year intervals, data from 722,306 individuals born between 1988 and 2003 in North Rhine Westphalia, Germany's largest state, were analyzed for the weekday of birth. In contrast to data from 1900 to 1950 (n=149,267), serving as historical controls, a very marked nonrandom distribution was discovered, with decreasing numbers of births on weekends, especially on Sundays, reaching deviations from the expected distribution of -17.8% in 2003, while births on weekdays are more frequent than expected (Fridays: +8.1% in 2003). The increasing avoidance of births during weekends by elective labor induction on weekdays is discussed as a consequence of practical and increasing financial constraints of hospitals.


Synthetic studies on Et-743. Asymmetric, stereocontrolled construction of the tetrahydroisoquinoline core via radical cyclization on a glyoxalimine.
[Structure: see text] The asymmetric synthesis of a highly functionalized tetrahydroisoquinoline relevant to the total synthesis of Et-743 is described. The key step involves a highly diastereoselective radical cyclization on a glyoxalimine derivative.


MiR-181c-5p Regulates Lung Adenocarcinoma Progression via Targeting PRKN.
Accumulating evidence indicates that microRNAs (miRNAs) have a vital effect on lung adenocarcinoma. However, the contributions and possible mechanisms of miR-181c-5p to lung adenocarcinoma remain largely unclear. Our objective is to clarify the potential mechanism by which miR-181c-5p regulates lung adenocarcinoma progression. RT-qPCR was performed to determine the levels of miR-181c-5p in lung adenocarcinoma tissues and cells. CCK-8 and Transwell assays were conducted to evaluate the viability, migration, and invasion of H460 cells, respectively. The putative target association between miR-181c-5p and the Parkin gene (PRKN) was predicted using miRDB and confirmed by dual-luciferase reporter assay. MiR-181c-5p expression was found to be up-regulated in both lung adenocarcinoma tissues and cells. Suppression of miR-181c-5p resulted in the inhibition of viability, migration, and invasion in lung adenocarcinoma cells. PRKN level was negatively related to miR-181c-5p expression and mediated with the miR-181c-5p's functions on lung adenocarcinoma progression. MiR-181c-5p regulates lung adenocarcinoma progression via targeting PRKN, indicating miR-181c-5p is expected to be a diagnostic and predictive marker for lung adenocarcinoma, providing new insights into the development of treatment strategies for lung adenocarcinoma.