Superusers: Drivers of health care resource utilization in the national trauma population.
Health care spending is driven by a very small percentage of Americans, many of whom are patients with prolonged durations of stay. The objective of this study was to characterize superusers in the trauma population. The National Trauma Data Bank for 2008-2012 was queried. Superusers were defined as those with a duration of stay in the top 0.06% of the population and were compared with the remainder of the population to determine differences in demographic characteristics, comorbidities, prehospital factors, and outcomes. Multivariate analysis was used to determine independent predictors of being classified as a superuser. A total of 3,617,261 patients met inclusion criteria, with 34,728 qualifying as superusers. Mean duration of stay for superusers was 58.7 days compared with the average 4.6 days (P < .001). Superusers were more likely to be male, black, Medicaid insured, and have a higher Injury Severity Score and lower Glasgow Coma Scale score. The hospital course of superusers was likely to be complicated by pneumonia, acute respiratory distress syndrome, decubitus ulcer, and acute kidney injury. Age, sex, race, and insurance were associated with prolonged use of inpatient care in the trauma patient population. Specific comorbidities and complications are associated with being a superuser. This subset of the trauma population confers a disproportionate burden on the health care system and can serve as a potential target for intervention.


Evidence of intact histatins in the in vivo acquired enamel pellicle.
Understanding the composition and function of the acquired enamel pellicle (AEP) has been a major goal in oral biology. The aim of this study was to test the hypothesis that intact histatins are part of the in vivo AEP and that histatins after adsorption to HA have effects on in vitro enamel demineralization. This is the first study demonstrating the presence of intact histatins in vivo in the AEP. The in vitro experiments show that all naturally occurring histatins in the AEP have the potential to provide some level of protection against acid injury.


Engineering a 3D in vitro model of human skeletal muscle at the single fiber scale.
The reproduction of reliable in vitro models of human skeletal muscle is made harder by the intrinsic 3D structural complexity of this tissue. Here we coupled engineered hydrogel with 3D structural cues and specific mechanical properties to derive human 3D muscle constructs ("myobundles") at the scale of single fibers, by using primary myoblasts or myoblasts derived from embryonic stem cells. To this aim, cell culture was performed in confined, laminin-coated micrometric channels obtained inside a 3D hydrogel characterized by the optimal stiffness for skeletal muscle myogenesis. Primary myoblasts cultured in our 3D culture system were able to undergo myotube differentiation and maturation, as demonstrated by the proper expression and localization of key components of the sarcomere and sarcolemma. Such approach allowed the generation of human myobundles of ~10 mm in length and ~120 μm in diameter, showing spontaneous contraction 7 days after cell seeding. Transcriptome analyses showed higher similarity between 3D myobundles and skeletal signature, compared to that found between 2D myotubes and skeletal muscle, mainly resulting from expression in 3D myobundles of categories of genes involved in skeletal muscle maturation, including extracellular matrix organization. Moreover, imaging analyses confirmed that structured 3D culture system was conducive to differentiation/maturation also when using myoblasts derived from embryonic stem cells. In conclusion, our structured 3D model is a promising tool for modelling human skeletal muscle in healthy and diseases conditions.


Thermo-Magnetoresponsive Dual Function Nanoparticles: An Approach for Magnetic Entrapable-Releasable Chitosan.
Magnetic polymeric nanoparticles can be used for selective binding in a magnetic field. However, as the magnetic nanoparticles (MAG) are stabilized with polymers, the separation of the MAG from the polymer chains after use is difficult. This work proposes a combination of a thermoresponsive polymer with MAG allows for the as-desired simple removal of MAG from the polymer chains. For this, chitosan (CS) was conjugated with thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) and antibody (Ab) together with the physisorbed MAG as a thermo-magneto dual functional material. The key synthesis steps are (i) radical polymerization of NIPAM in the presence of mercaptoacetic acid so that the PNIPAM obtained contains terminal carboxylic acid groups (PNIPAM-COOH), (ii) the CS-N-hydroxysuccinamide water-based system that allows conjugation of CS with PNIPAM-COOH in water at room temperature, and (iii) the weak interaction between MAG and the CS chain. As a model application, CS is conjugated with the antirecombinant Leptospirosis Ab (rLipL32) to allow the selective binding and collection of the target antigen under the dual functions. This is the first demonstration of a simple but effective solution for MAG exclusion from the target molecules and will be practical for diverse applications, such as diagnosis, sensors, filtration, etc.


Priming of the uterine cervix with oral prostaglandin E2 in the term multigravida.
A double-blind study evaluating two dose schedules of oral prostaglandin E2 (PGE2) was conducted in 56 normal "unripe" multiparas at term. The effect of PGE2 was evaluated by comparing the change in Bishop score of the cervix and patient's response to oxytocin induction of labor after the prostaglandin priming. In the two study groups (one group on a fixed PGE2 dosage and the other on a variable drug regimen) an average change of more than three points in the Bishop score was observed. In control group no significant change in cervical ripeness was observed. Nine of the 32 patients (28%) receiving prostaglandin delivered during the priming phase of the study, whereas only 1 control patient (4.2%) delivered during priming. Six of 24 control patients (25%) failed to deliver, wheras only 3 of 32 study patients (9%) failed. In the successfully induced patients, the response to oxytocin, as expressed by the time to active phase, total time of labor, and mean dose of oxytocin required, did not vary significantly when control and study groups were compared. It is concluded that PGE2 at either dosage schedule is effective in changing the Bishop score of the cervix and that it is not feasible to titrate the PGE2 dose in order to effectively ripen the cervix without a very high incidence of induction of labor. In those cases where priming was completed, without accidental delivery, the induction phase was successful more than 90% of the time. No adverse effect to mother or baby was observed during this study.


Nitrate reductase from winter wheat leaves is activated at low temperature via protein dephosphorylation.
The effect of short-term low temperature treatment on nitrate reductase (NR, EC 184.108.40.206) activity, NR protein and NR transcript levels in excised leaves of winter wheat (Triticum aestivum L. cv. Sadovo-1) was investigated. NR activity, measured in the presence of Mg2+ (NRact), doubled within 2 h at 4 degrees C, whereas NR activity, measured in the presence of EDTA (NRmax), did not respond to the cold treatment. Such an activation of NR occurred only if leaves were exposed to low temperature in the light but not in the dark. It was not affected by feeding cytoplasmic protein synthesis inhibitor, cycloheximide, or protein kinase inhibitor, staurosporin, but was completely prevented by okadaic acid, an inhibitor of protein phosphatases of the type 1 and 2 A. This inhibitory effect decreased gradually when okadaic acid-concentration in the nutrient solution was lowered below 1 &mgr;M and tended to disappear when leaves were fed with 10 nM okadaic acid. It was demonstrated that the cold-induced NR activation was dependent neither on cold-triggered calcium influx nor on high endogenous abscisic acid levels. The increased NRact in cold-exposed leaves was found to correlate with a higher level of NR transcript but not with an increased NR protein level. Feeding okadaic acid to these leaves prevented the cold-induced accumulation of NR mRNA. These data point to protein phosphatases of the type 2 A being involved in NR protein dephosphorylation and NR transcript accumulation as targets of activation by low temperature treatment.


Evaluation of a culturally adapted training course in Indigenous e-mental health.
To report the impact of the Indigenous e-mental health training course 'Yarning about Indigenous Mental Health using the AIMhi Stay Strong App'. Participants were trained in e-mental health and the use of one of the first culturally adapted e-mental health interventions - The AIMhi Stay Strong App. Between October 2013 and December 2014, 138 participants completed the 'Yarning about Indigenous Mental Health using the AIMhi Stay Strong App' training course and 130 completed pre- and post-training questionnaires to explore knowledge and confidence in a number of areas trained. Paired t-tests showed significant improvements across all measures of skill and knowledge except for confidence in using computers. E-mental health is a relatively new development that may contribute to improved access to mental health services for rural and remote Indigenous Australians, particularly where such tools are culturally adapted. Whilst current knowledge and use of e-mental health tools in this group of Northern Territory service providers was limited, perceived knowledge and confidence in use was significantly improved following training.


Mapping of lateral pelvic lymph node recurrences in rectal cancer: a radiation oncologist's perspective.
Patterns of locoregional rectal cancer recurrences following total mesorectal excision (TME) were analyzed to define the irradiation volume, especially the lateral pelvic lymph node (LPLN). Of 1243 patients who underwent TME without pelvic radiotherapy between 2005 and 2012, the data of 826 patients with rectal adenocarcinoma without distant metastases were analyzed for relapse patterns, categorized as distant and locoregional (anastomosis, mesorectum, presacral area, and LPLNs) failure. The median follow-up was 61.8 months. The 5-year local recurrence-free, distant metastasis-free, overall survival rates were 88, 82, and 89%, respectively. Relapse occurred in 108 (13%) patients: 90 (11%) had distant and 28 (3%) had locoregional failure. Eight patients had LPLN recurrence: the 2 recurrences from upper rectal cancers occurred near the bifurcation of the common iliac artery into the external and internal iliac vessels; the 6 mid-lower rectal cancers had 16 recurrences near the internal iliac and obturator arteries-five occurred anterior to the obturator artery and posterior to the external iliac artery, superior to the femoral head. LPLN recurrence was associated with pN2 stage, perinodal extension, and lymphovascular invasion. The LPLN component of pre- or postoperative irradiation volumes could potentially be optimized based on our mapping data. However, since patients in our institution at high risk for relapse received either preoperative or postoperative chemoradiation, further analyses are needed to confirm our findings.


Parent education: an evaluation of STEP on abusive parents' perceptions and abuse potential.
To examine the effects of a structured, time-limited parent training group on abusive or potentially abusive parents. A pretest-posttest control group design was used with consenting parents (N = 18) to examine the effects of Systematic Training for Effective Parenting (STEP) on abusive parents' perceptions of their children's behaviors and on the parents' potential to physically abuse. The Adlerian Parental Assessment of Child Behavior Scale and the Child Abuse Potential Inventory were used to measure treatment effects. After participating in STEP, abusive parents had significantly more positive perceptions of their children and were significantly less potentially abusive. Using volunteers, the project cost an average of $100 for each parent. The research lends empirical support to individual psychology and family systems theory. Future research is indicated using larger samples to examine lay vs. professional leadership of the groups, as well as comparisons of different parenting programs with abusive parents.


Internal Model-Based Robust Tracking Control Design for the MEMS Electromagnetic Micromirror.
The micromirror based on micro-electro-mechanical systems (MEMS) technology is widely employed in different areas, such as scanning, imaging and optical switching. This paper studies the MEMS electromagnetic micromirror for scanning or imaging application. In these application scenarios, the micromirror is required to track the command sinusoidal signal, which can be converted to an output regulation problem theoretically. In this paper, based on the internal model principle, the output regulation problem is solved by designing a robust controller that is able to force the micromirror to track the command signal accurately. The proposed controller relies little on the accuracy of the model. Further, the proposed controller is implemented, and its effectiveness is examined by experiments. The experimental results demonstrate that the performance of the proposed controller is satisfying.


Hidradenitis suppurativa: A folliculotropic disease of innate immune barrier dysfunction?
The innate immune system of human skin consists of a multi-layered barrier consisting of cells and soluble effector molecules charged with maintaining homeostasis and responding to insults and infections. It has become increasingly clear that these barrier layers become compromised in skin diseases, especially in disorders of an (auto)inflammatory nature. In the case of hidradenitis suppurativa, great strides have been made in recent years in characterizing the underlying breakdown in homeostatic innate immunity, including an increasing understanding of the central role of the hair follicle in this process. This breakdown appears to occur at multiple levels: the pilosebaceous unit, associated epithelium, the cutaneous microbiome, alteration of immune cell function and local molecular events such as complement activation. This review seeks to summarize, contextualize and analyse critically our current understanding of how these innate immune barriers become dysregulated in the early stage(s) of hidradenitis suppurativa, and to speculate on where potential hidradenitis suppurativa research could be most fruitful.


Nutrients in vegetarian foods.
Persons who use tables of food composition have often found that foods that vegetarians commonly eat are not included. To help remedy this situation, a table is presented which includes the 49 foods on the vegetarian Exchange Lists and 18 additional nonmeat foods. Nutrient contents of household measures of these foods are given for water, protein, fat, carbohydrate, calcium, phosphorus, iron, potassium, zinc, vitamin A, thiamin, riboflavin, niacin, vitamin C, and folacin. Nutrient amounts were derived from USDA sources and from other published research when available. Nutrient amounts from foods assumed to be identical to those in the table were placed in parentheses. When nutrient amounts were not available, they were estimated from similar foods and placed in brackets. When values found for a single nutrient in a food varied by 20% or more, the total range was shown. When a dash was found in a literature reference and the amount of the nutrient was known to be insignificant, a zero was presented in the table. Thus, there are no gaps in the table. Until accurate laboratory-derived data are available for the nutrients in vegetarian foods, this table, used with appropriate judgment, should be useful for estimating the nutrient intakes of persons who eat vegetarian foods.


Learning disabilities in neuromuscular disorders: a springboard for adult life.
Although the presence of cognitive deficits in Duchenne muscular dystrophy or myotonic dystrophy DM1 is well established in view of brain-specific expression of affected muscle proteins, in other neuromuscular disorders, such as congenital myopathies and limb-girdle muscular dystrophies, cognitive profiles are poorly defined. Also, there are limited characterization of the cognitive profile of children with congenital muscular dystrophies, notwithstanding the presence of cerebral abnormality in some forms, and in spinal muscular atrophies, with the exception of distal spinal muscular atrophy (such as the DYN1CH1- associated form). Starting from the Duchenne muscular dystrophy, which may be considered a kind of paradigm for the co-occurrence of learning disabilities in the contest of a progressive muscular involvement, the findings of neuropsychological (or cognitive) dysfunctions in several forms of neuromuscular diseases will be examined and reviewed.


Periodic hypersomnia, congenital ectodermal disorders and multiple exostosis.
A case of periodic hypersomnia in an 11-year-old female with the unique features of mental deficiency, incontinentia pigmenti, acanthosis nigricans and hereditary multiple exostosis (diaphysial aclasis) is reported. The clinical, polysomnographic and Multiple Sleep Latency test features of this case with a follow up of seven years are consistent with a diagnosis of periodic (intermittent) excessive somnolence. The unique presentation, however, does differ from Kleine-Levin syndrome and suggests a relationship between the predominantly ectodermal, congenital disorders and the sleep-wake pattern dysfunction.


The Hox genes Ultrabithorax and abdominal-A specify three different types of abdominal appendage in the springtail Orchesella cincta (Collembola).
In Drosophila and many other insects, the Hox genes Ultrabithorax (Ubx) and abdominal-A (abd-A) suppress limb formation on most or all segments of the abdomen. However, a number of basal hexapod lineages retain multiple appendages on the abdomen. In the collembolans or springtails, three abdominal segments develop specialized organs that originate from paired appendage primordia which fuse at the midline: the first abdominal segment bears the collophore (ventral tube), involved in osmoregulation; the fourth segment bears the furca, the leaping organ, and the third segment bears the retinaculum, which retains the furca at rest. Ubx and abd-A are known to be expressed in the springtail abdomen, but what role they play in specifying these distinct abdominal appendages is not known. This is largely because no genetic model has been established in collembolans or any other non-insect hexapod. We have developed a convenient method for laboratory culture of the collembolan Orchesella cincta on defined media, a method for in-situ hybridization to embryos and a procedure for gene knockdown by parental injection of double-stranded RNA (RNAi). We show that Orchesella Ubx transcripts are detectable in the first to third abdominal segments, and abd-A transcripts in the second to fourth segments. Knockdown of Oc-Ubx leads to the homeotic transformation of the collophore into a pair of walking legs (a more anterior identity) but the retinaculum into a furca (a more posterior identity). Knockdown of Oc-abd-A leads to the transformation of the retinaculum into a collophore and of the furca into legs (both anterior transformations). Simultaneous silencing of both Oc-Ubx and Oc-abd-A transformed all three of these appendages into paired legs, but did not cause appendages to develop on the second, or on the most posterior abdominal segments. We conclude that, in Orchesella, Oc-Ubx alone specifies the collophore on the first and Oc-abd-A alone specifies the furca on the fourth abdominal segment. Oc-Ubx and Oc-abd-A function together, apparently combinatorially, to specify the retinaculum on the third segment. The efficiency of RNAi in Orchesella makes this an attractive model for further genetic studies of development and physiology in basal hexapods.


Postoperative infection caused by an unusual serotype of Streptococcus pneumoniae associated with multiple drug resistance.
A 15-month-old child developed an infectious pulmonary complication of open heart surgery. Cultures of the respiratory secretions showed growth of a 9L serotype of Streptococcus pneumoniae which was resistant to penicillin, tetracycline, and chloramphenicol. There was no evidence that the organism was spread among the family of the patient or hospital personnel.


Oral appliance therapy versus nasal continuous positive airway pressure in obstructive sleep apnoea syndrome: a randomised, placebo-controlled trial on self-reported symptoms of common sleep disorders and sleep-related problems.
Obstructive sleep apnoea syndrome (OSAS) is associated with several sleep disorders and sleep-related problems. Therefore, the aim of this study was to compare the effects of a mandibular advancement device (MAD) with those of nasal continuous positive airway pressure (nCPAP) on self-reported symptoms of common sleep disorders and sleep-related problems in mild and moderate OSAS patients. In this randomised placebo-controlled trial, sixty-four OSAS patients (52·0 ± 9·6 years) were randomly assigned to an MAD, nCPAP or an intra-oral placebo appliance in a parallel design. All participants filled out the validated Dutch Sleep Disorders Questionnaire (SDQ) twice: one before treatment and one after six months of treatment. With 88 questions, thirteen scales were constructed, representing common sleep disorders and sleep-related problems. Linear mixed model analyses were performed to study differences between the groups for the different SDQ scales over time. The MAD group showed significant improvements over time in symptoms corresponding with 'insomnia', 'excessive daytime sleepiness', 'psychiatric sleep disorder', 'periodic limb movements', 'sleep apnoea', 'sleep paralysis', 'daytime dysfunction', 'hypnagogic hallucinations/dreaming', 'restless sleep', 'negative conditioning' and 'automatic behaviour' (range of P values: 0·000-0·014). These improvements in symptoms were, however, not significantly different from the improvements in symptoms observed in the nCPAP and placebo groups (range of P values: 0·090-0·897). It can be concluded that there is no significant difference between MAD and nCPAP in their positive effects on self-reported symptoms of common sleep disorders and sleep-related problems in mild and moderate OSAS patients. These beneficial effects may be a result of placebo effects.


Quantification of inter-brain coupling: A review of current methods used in haemodynamic and electrophysiological hyperscanning studies.
Hyperscanning is a form of neuroimaging experiment where the brains of two or more participants are imaged simultaneously whilst they interact. Within the domain of social neuroscience, hyperscanning is increasingly used to measure inter-brain coupling (IBC) and explore how brain responses change in tandem during social interaction. In addition to cognitive research, some have suggested that quantification of the interplay between interacting participants can be used as a biomarker for a variety of cognitive mechanisms aswell as to investigate mental health and developmental conditions including schizophrenia, social anxiety and autism. However, many different methods have been used to quantify brain coupling and this can lead to questions about comparability across studies and reduce research reproducibility. Here, we review methods for quantifying IBC, and suggest some ways moving forward. Following the PRISMA guidelines, we reviewed 215 hyperscanning studies, across four different brain imaging modalities: functional near-infrared spectroscopy (fNIRS), functional magnetic resonance (fMRI), electroencephalography (EEG) and magnetoencephalography (MEG). Overall, the review identified a total of 27 different methods used to compute IBC. The most common hyperscanning modality is fNIRS, used by 119 studies, 89 of which adopted wavelet coherence. Based on the results of this literature survey, we first report summary statistics of the hyperscanning field, followed by a brief overview of each signal that is obtained from each neuroimaging modality used in hyperscanning. We then discuss the rationale, assumptions and suitability of each method to different modalities which can be used to investigate IBC. Finally, we discuss issues surrounding the interpretation of each method.


Herbal medicine (Danggui Liuhuang decoction) for managing menopausal symptoms: A protocol of systematic review of randomized clinical trials.
Danggui Liuhuang (DLH) decoction is a traditional herbal medicine that is widely used in East Asia to treat menopausal symptoms. Most of the available clinical trials that investigated DLH decoction have been included in this review. The objectives of this protocol are to provide the information of how to evaluate the effectiveness and safety of DLH decoction for the treatment of menopausal symptoms. Fourteen databases will be searched from inception until February 2018. We will include randomized controlled trials (RCTs) testing any type of DLH decoction. All RCTs investigating DLH decoction or modified DLH decoction will be included. The methodological quality of the RCTs will be evaluated using the Cochrane's risk of bias assessment tool. The full systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print. Updates of the review will be conducted to inform and guide healthcare practice and policy. PROSPERO 2017 CRD42017079189.


The effect of compressed air massage on skin blood flow and temperature.
Compressed air massage is a new treatment modality that uses air under pressure to massage skin and muscle. It is claimed to improve skin blood flow but this has not been verified. Several pilot studies were undertaken to determine the effects of compressed air massage on skin blood flow and temperature. Skin blood flow (SBF), measured using laser Doppler fluxmetry and skin temperature was recorded under several different situations: (i) treatment, at 1 Bar pressure using a single-hole (5-mm) applicator head, for 1 min at each of several sites on the right and left lower legs, with SBF measured on the dorsum of the left foot; (ii) at the same treatment pressure, SBF was measured over the left tibialis anterior when treatment was performed at different distances from the probe; (iii) SBF and skin temperature of the lower leg were measured with treatment at 0 or 1 Bar for 45 min, using two different applicator heads; (iv) SBF was measured on the dorsum of the foot of 10 subjects with treatment for 1 min at 0, 0.5, 1, 1.5 and 2 Bar using three different applicator heads. (i) SBF of the left foot was not altered by treatment of the right leg or chest, but was significantly increased during treatment of the left sole and first web, p < 0.0001. (ii) SBF over the tibialis anterior was increased when treatment was 5 cm from the probe, p < 0.0001, but not when 10 cm away. iii) SBF was significantly elevated throughout the 45-min treatments at 1 Bar and returned to normal within 1 min of stopping treatment. Skin temperature fell by 6.8 degrees C and 4.3 degrees C after 45-min treatments at 1 Bar, and slight rewarming occurred within 15 min. At 0 Bar, no change in SBF or temperature was noted. (iv) A near-linear increase in SBF was noted with increasing treatment pressure for two of the three applicator heads. Compressed air massage causes an immediate increase in SBF, and an immediate fall in SBF when treatment is stopped. The effect appears to be locally and not centrally mediated and is related to the pressure used. Treatment cools the skin for at least 15 min after a 45-min treatment.


Effects of Chronic Tobacco Smoking on the Distribution of Tachykinin Receptors in Rat Pial Arteries.
Pial arteries of different diameter were studied in intact rats and after 6-month modeling of chronic tobacco smoking in rats. Expression of tachykinin NK1 receptors in pial arteries was studied by biomicroscopy and immunohistochemical methods. Chronic tobacco smoking induced considerable reorganizations of the arterial bed. The intensity of changes depended on the diameter of vessels. In small pial vessels that directly participate in the blood supply to the brain, pronounced vasodilatation and enhanced expression of NK1 receptors in the endothelium mediating the effects of substance P were observed; the number of these vessels also increased. The intensity of the response to tobacco smoke components decreased with increasing vessel diameter.


Weight-independent cardiovascular fitness and coronary risk factors.
It is unclear whether cardiovascular fitness influences risk factors for coronary artery disease and non-insulin-dependent diabetes mellitus independently of level of body fat because fitness is often measured in tasks that involve moving body weight (eg, running) and because body weight and level of body fat are correlated. To measure fitness during a task in which body weight was controlled experimentally (ie, supine cycling). Cross-sectional. Seventy-four children, 7 to 13 years of age, recruited through school flyers and newspaper advertisements, varying in level of body fat from 7% to 61%. There were 31 boys and 43 girls; 35 were white and 39 were black. Cardiovascular fitness was expressed as submaximal heart rate while cycling at a power output of 49 W, and level of body fat was measured with dual x-ray absorptiometry. Blood pressure and levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, insulin, glucose, and glycohemoglobin. Controlling for age and sex, level of body fat was significantly (P < .01) related to unfavorable levels of systolic blood pressure (r = 0.32), triglycerides (r = 0.42), high-density lipoprotein cholesterol (r = -0.31), insulin (r = 0.50), and total cholesterol to high-density lipoprotein cholesterol ratio (r = 0.37); submaximal heart rate was not significantly correlated with any of the other variables. When cardiovascular fitness was measured in a weight-independent task, it was not significantly related to level of body fat or the major coronary artery disease and non-insulin-dependent diabetes mellitus risk factors. In addition, we confirmed previous findings that higher levels of body fat are associated with a very unfavorable risk profile.


Development of a Control Strategy in an Isokinetic Device for Physical Rehabilitation.
Robotic-assisted rehabilitation is currently being applied to improve the effectiveness of human gait rehabilitation and recover the mobility and strength after a stroke or spinal cord injury; a robotic assistant can allow the active participation of the patient and the supervision of the collected data and decrease the labor required from therapists during the patient's training exercises. The goal of gait rehabilitation with robotic-based assistance is to restore motor function by using diverse control strategies, taking account of the physical interaction with the lower limbs of the patient. Over the last few years, researchers have extracted useful information from the patient's biological signals that can effectively reflect movement intention and muscle activation. One way to evaluate progress in rehabilitation is through isokinetic prototype tests that describe the dynamic characteristics of an isokinetic leg extension device for rehabilitation and control action. These tests use an isokinetic system to assess muscle strength and performance in a patient during isometric or isokinetic contraction. An experimental prototype shown in the following work allows the device's performance to be evaluated in a controlled environment before the patient's use. New features provide a control system that can be teleoperated for distributed structures, enabling the remote operation and management of the device. In order to achieve physical recovery from musculoskeletal injuries in the lower limbs and the reintegration of the affected subject into society as an independent and autonomous individual in their daily activities, a control model that introduces a medical isokinetic rehabilitation protocol is presented, in which the element that carries out such protocol consists of a magnetic particle brake whose control action is strongly influenced by the dynamics of the system when in contact with the end user-specifically, the patient's legs in the stretch from the knee to the ankle. The results of these tests are valuable for health professionals seeking to measure their patient's progress during the rehabilitation process and determine when it is safe and appropriate to advance in their treatment.


External rotation contracture of the extended hip. A common phenomenon of infancy obscuring femoral neck anteversion and the most frequent cause of out-toeing gait in children.
External rotation contracture of the extended hip is common in young infants, decreasing progressively with growth so that it appears to be present in less than 5 per cent of the children over age 18 months. Persistence of the external rotation contracture was the main cause of toeing-out gait in this study. Femoral neck anteversion, as a cause of internal rotation posturing of the limb, does not become clinically recognizable until complete resolution of the external rotation contracture of the hip has occurred, that is, usually after 18 months of age. Femoral neck retroversion was not present clinically in any of the patients examined, and so appears to be quite rare. Approximately 80 per cent of children under 18 months of age who toe-in have internal tibiofibular torsion; most of these also have significant talar neck adductus! Approximately 70 per cent of children over age 2 years who toe-in have excess femoral neck anteversion as the cause. Approximately 75 per cent of the children with metatarsus adductus deformity have coexistent internal tibial torsion and talar neck adductus; only 25 per cent of children with internal tibial torsion have coexistent metatarsus adductus deformity. Physiologic genu varum usually occurs prior to 2 years of age and physiologic genus valgum usually occurs after 2 years of age.


Serum lipoproteinemia in pregnant and lactating rats.
Serum lipoproteins of pregnant and puerperal rats were studied by preparative and analytical ultracentrifugation. The concentration for the fraction with density less than 1.019 was markedly elevated in rats during the 3rd wk of gestation and in lactating rats. This fraction showed similar triglyceride fatty acid composition and immunoelectrophoretic behavior whether it was derived from pregnant or nonpregnant rats, and when partially delipidized, the lipoproteins from both groups showed similar immunoelectrophoretic characteristics and sedimentation rates. When lactation was interrupted during puerperium, serum lipoproteins returned to control levels; but in lactating rats, high levels of serum very low density lipoprotein persisted up to 3 wk post partum.


Quantitative mRNA Expression Assays and Synchronous Breast Cancers: A Case Report.
Quantitative mRNA analysis of breast tumors represents a routinely applied example of precision oncology. Currently the National Comprehensive Cancer Network (NCCN) recommends quantitative mRNA profiling (e.g., 21-gene RT PCR or Oncotype Dx assay) for nearly all surgically resected lymph node (LN) negative hormone receptor (HR) positive, HER2 negative breast cancers in order to predict recurrence risk with endocrine therapy compared to chemotherapy followed by endocrine therapy after surgery. The incidence of synchronous breast cancers is low and evidence concerning distant recurrence risk is limited, but the risk of distant recurrence from one or the other of two primary breast cancers appears to be higher than the recurrence risk of the single largest of the two cancers. In this report, a woman with synchronous primary breast cancers is described. Oncotype Dx testing was done on each of her two cancers. By assuming that the recurrence risk from each with adjuvant endocrine therapy is an independent event, the recurrence likelihood from one or the other or both is calculated. I propose that this calculated value more accurately should predict the recurrence from one or the other or both tumors with endocrine therapy or chemotherapy followed by endocrine therapy compared with using only the higher of the two Oncotype Dx estimated risks.


Is alcoholism learned? Insights from the fruit fly.
Alcohol addiction is a complex, unique human disease. Breaking addiction down into contributing endophenotypes enables its study in a variety of model systems. The Drosophila model system has been most often used to study alcohol sensitivity, tolerance, and physiological dependence. However, none of these endophenotypes can account for the near-permanent quality of the addicted state. It has been recently discussed that addictive drugs may hijack the learning-and-memory machinery to produce persistent behavioral changes. Learning and memory is amenable to experimental study, and provides us with a window into how alcohol affects higher-order mental functions that are likely to contribute compulsive drug use. Here, we review the Drosophila literature that links alcohol-related behaviors to learning and memory.


It's in the mix: psychological distress differs between combinations of alexithymic facets.
Alexithymia is a personality trait characterized by difficulties in identifying, describing, and communicating one's emotions. The aim of the present study is to examine the usefulness of a typological approach considering the interaction between distinct alexithymic features within a population of high-alexithymic German adults (N = 217). Latent profile analysis (LPA) was employed to test for possible underlying profiles. A 3-profile solution showed the best fit: The profiles can be described as (1) "low": lower load on all facets of alexithymia, (2) "mixed": specific problems on identifying emotions, and (3) "high": higher load on all facets of alexithymia. Moreover, this study tested how these profiles differed in psychological distress. "Mixed" profile, with specific problems on identifying emotions showed the highest levels of psychological distress. The present study suggests the importance of a specific combination of alexithymic features, rather than total alexithymia scores, as a risk factor for psychological distress.


In vivo retinal imaging is associated with cognitive decline, blood-brain barrier disruption and neuroinflammation in type 2 diabetic mice.
Type 2 diabetes (T2D) is associated with chronic inflammation and neurovascular changes that lead to functional impairment and atrophy in neural-derived tissue. A reduction in retinal thickness is an early indicator of diabetic retinopathy (DR), with progressive loss of neuroglia corresponding to DR severity. The brain undergoes similar pathophysiological events as the retina, which contribute to T2D-related cognitive decline. This study explored the relationship between retinal thinning and cognitive decline in the LepR db/db model of T2D. Diabetic db/db and non-diabetic db/+ mice aged 14 and 28 weeks underwent cognitive testing in short and long-term memory domains and in vivo retinal imaging using optical coherence tomography (OCT), followed by plasma metabolic measures and ex vivo quantification of neuroinflammation, oxidative stress and microvascular leakage. At 28 weeks, mice exhibited retinal thinning in the ganglion cell complex and inner nuclear layer, concomitant with diabetic insulin resistance, memory deficits, increased expression of inflammation markers and cerebrovascular leakage. Interestingly, alterations in retinal thickness at both experimental timepoints were correlated with cognitive decline and elevated immune response in the brain and retina. These results suggest that changes in retinal thickness quantified with in vivo OCT imaging may be an indicator of diabetic cognitive dysfunction and neuroinflammation.


[Synthesis and maturation of RNA after proliferative stimulation: comparison between fibroblasts and lymphocytes].
Comparison of the regulation of RNA metabolism following stimulation of mammalian fibroblasts in culture and of lymphocytes reveals that in both systems it is the processing and transport of gene transcripts which are the initial targets of the activation process rather than the gene transcription itself. In the case of the human lymphocyte, the time required for appearance of labeled RNA in cytoplasm after addition of labeled uridine diminishes progressively with duration of incubation with mitogen. Using adenine as a marker diminishes the latent period between addition of label and its appearance in cytoplasmic RNA. This may be due to polyadenylation of preexisting transcripts which are turned over at a high rate in the nucleus of resting cells but stabilized, processed and exported to the cytoplasm after stimulation.


The Inhibitory Effect of Mesenchymal Stem Cells with rAd-NK4 on Liver Cancer.
Mesenchymal stem cells (MSCs) can migrate to the tumor site and integrate into the tumor tissue. As a delivery vehicle of antitumor factors, MSCs have been tried in various tumor therapies. NK4 can both inhibit the growth, metastasis, and invasion of tumor cells induced by hepatocyte growth factor (HGF) and suppress tumor angiogenesis that is independent on HGF/cellular-mesenchymal-to-transition factor pathway. Adenovirus can directly deliver NK4 for tumor treatment but may induce immunological rejection. We combined MSCs with an adenovirus vector to deliver NK4 for liver tumor treatment. This study detected the migration of MSCs to high metastasis liver carcinoma cells MHCC-97H in vitro, investigated the inhibitory effect of rAd-NK4-MSCs on the growth and metastasis of MHCC-97H cells, further explored the inhibitory mechanism of rAd-NK4-MSCs to MHCC-97H cell metastasis, and examined the inhibitory effect of rAd-NK4-MSCs on the migration of human umbilical vein endothelial cells (HUVECs) in vitro. In this study, migration experiment was used for the potential capacity of MSCs and inhibition on migration of rAd-NK4-MSCs. Western blot was used for detecting the inhibition mechanism of rAd-NK4-MSCs to MHCC-97H cells. And, animal transplantation experiment was used for the inhibition of rAd-NK4-MSCs in vivo. MSC migration assay showed MSCs can significantly migrate to MHCC-97H cells. Co-culture results indicated that rAd-NK4-MSCs significantly inhibited the proliferation and migration of MHCC-97H cells in vitro. Western blot results proved that rAd-NK4-MSCs inhibited MHCC-97H cell migration correlating with suppressing Erk1/2 phosphorylation. HUVEC migration experiment suggested that rAd-NK4-MSCs had a potential of inhibiting tumor angiogenesis. Animal transplantation experiment showed that the tumor growth was significantly inhibited in the rAd-NK4-MSC group. Taken together, this study proved that NK4-modified MSCs had an inhibitory effect on the growth and migration of MHCC-97H cells and tumor angiogenesis, which provided a new strategy for liver tumor target therapy.


A review of cost-effectiveness analysis: From theory to clinical practice.
Cost-effectiveness analysis has long been practiced; registries date back to the United States of America War Department in 1886. In addition, everyone does intuitive cost-effectiveness analyses in their daily lives. In routine medical care, health economic assessment becomes increasingly important due to progressively limited resources, rising demands, population increases, and continuous therapeutic innovations. The health economic assessment must analyze the outcomes and costs of actions and technologies as objectively as possible to guarantee efficient assessment of novel interventions for Public Health Policy. In other words, it is necessary to determine how much society or patients are willing to or able to pay for novel interventions compared with existing alternatives, given the available resources. In addition, increased cost may displace other health care services already provided in case of fixed budget health care systems. To conduct such analyses, researchers must use standard methodologies and interpretations in light of regional characteristics according to social and economic determinants as well as clinical practice. Such an approach may be essential for transforming the current healthcare system to a value-based model. In this narrative review, concepts of the importance of and some approaches to health economic evaluation in clinical practice will be discussed.


Repair of Large Abdominal Wall Defects Using Total Anterior Aponeurotic Flap: Anatomical Feasibility Study and Comparison with Ramirez's Technique.
In this cadaveric study, we explored the feasibility of a maximal mobilization of the superficial abdominal fascia, in a continuous flap, to achieve a tension-free covering of midline defects. The aponeurosis of the external oblique muscle was incised along the anterior axillary line and then detached up to the anterior rectus sheath. The latter was opened between the external and the internal oblique aponeurosis while keeping the continuity with the external oblique fascia. The obtained flap was solid and uninterrupted. The width gain reached 15 ± 3 cm on each sides, providing tissue advancement 60% longer than Ramirez's technique (n = 8). The described technique allows large covering with respect to the anatomical planes. Further clinical tests should evaluate the validity of such concept in the repair of giant and asymmetrical hernias.


Mycophenolate mofetil substitution for cyclosporine-dependent myasthenia gravis and nephrotoxicity.
Severe autoimmune myasthenia gravis is difficult to manage and may require immunosuppression with cyclosporine. However, cyclosporine dependency is associated with the risk of nephrotoxicity. Mycophenolate mofetil is a non-nephrotoxic alternative which should be considered to rescue cyclosporine-dependent, severe myasthenia gravis sufferers with renal impairment from progression to end-stage renal failure. However, the evidence is limited and studies have not assessed the outcome of a direct substitution in these cyclosporine-dependent patients. We study three such patients who successfully converted to mycophenolate mofetil, and briefly examine the evidence behind this option. We believe that total cyclosporine withdrawal is feasible, but strongly recommend overlapping mycophenolate mofetil treatment with cyclosporine.


Fertilization in Arabidopsis thaliana wild type: developmental stages and time course.
We describe some previously uncharacterised stages of fertilization in Arabidopsis thaliana and provide for the first time a precise time course of the fertilization process. We hand-pollinated wild type pistils with wild type pollen (Columbia ecotype), fixed them at various times after pollination, and analysed 600 embryo sacs using Confocal Laser Scanning Microscopy. Degeneration of one of the synergid cells starts at 5 Hours After Pollination (HAP). Polarity of the egg changes rapidly after this synergid degeneration. Karyogamy is then detected by the presence of two nucleoli of different diameters in both the egg and central cell nuclei, 7-8 HAP. Within the next hour, first nuclear division takes place in the fertilized central cell and two nucleoli can then be seen transiently in each nucleus produced. In a second set of experiments, we hand-pollinated wild type pistils with pollen from a transgenic promLAT52::EGFP line that expresses EGFP in its pollen vegetative cell. Release of the pollen tube contents into the synergid cell could be detected in living material. We show that the timing of synergid degeneration and pollen tube release correlate well, suggesting that either the synergid cell degenerates at the time of pollen tube discharge or very shortly before it. These observations and protocols constitute an important basis for the further phenotypic analysis of mutants affected in fertilization.


A computational study of microsolvation effect on ethylene glycol by density functional method.
This study focuses on the conformational analysis of ethylene glycol-(water)n (n=1-3) complex by using density functional theory method and the basis set 6-311++G*. Different conformers are reported and the basis set superposition error corrected total energy is -306.767 5171, -383.221 3135, and -459.694 1528 for lowest energy conformer with 1, 2, and 3 water molecules, respectively, with corresponding binding energy -7.75, -15.43, and -36.28 kcal/mol. On applying many-body analysis it has been found that relaxation energy, two-body, three-body energy have significant contribution to the binding energy for ethylene glycol-(water)3 complex whereas four-body energies are negligible. The most stable conformers of ethylene glycol-(water)n complex are the cyclic structures in which water molecules bridge between the two hydroxyl group of ethylene glycol.


Patterns of consumption of alcohol in Seville, Spain. Results of a general population survey.
The results of a general population survey of the patterns of consumption of alcohol in a representative sample of the province of Seville, Spain, are analysed in this article. The proportions of drinkers and abstainers and distribution by age, by sex and by urban-rural residency are discussed. Frequency of consumption declines as age increases in both sexes but the negative slope is more marked in females. Analysis of the results on quantity of alcohol consumed during the week prior to the interview shows that men drink more heavily than women in all age-groups and young people drink more heavily than other age-groups. The combination of data on frequency of consumption and maximum quantity of alcohol reportedly consumed on the highest drinking occasion shows that the majority of men belong to the High Frequency-Low Quantity typology, followed by High Frequency-Medium Quantity, but in women nearly 60% belong to the Low Frequency-Low Quantity typology, followed by High Frequency-Low Quantity. The highest proportions of both abstainers and heavy drinkers are found in the group of people with the lowest income.


Endogenous hippocampal, not peripheral, estradiol is the key factor affecting the novel object recognition abilities of female rats.
Estradiol (E2) is involved in the regulation of emotional behavior, cognitive function, and neuroplasticity. However, peripheral E2 and central E2 levels do not always fluctuate together. The relationships of peripheral and central E2 with cognitive function are not clear. The aim of this study was to investigate whether peripheral E2, hippocampal E2, or both play a critical role in novel object recognition (NOR), and whether Kalirin-7, an important regulator of spine plasticity, is involved in the modulation of E2 on cognitive behavior. Our results showed that ovariectomy (OVX) significantly reduced serum E2 levels in the 14 weeks following the procedure. However, hippocampal E2 levels did not decrease in the OVX group compared to the sham group until after 14 weeks. Consistent with the changes in hippocampal E2 levels, the investigation ratio in the NOR test and hippocampal Kalirin-7 expression was also not lower in the OVX group than in the sham group until 14 weeks after the procedure. To confirm the relationship between hippocampal E2 levels and NOR ability, we inhibited the production of hippocampal E2 via microinjection of letrozole (LTZ; an aromatase inhibitor) into the hippocampi of rats in the control group and 8-week OVX group. The data indicated that a reduction in E2 levels in the hippocampus significantly impaired NOR ability and simultaneously decreased Kalirin-7 levels in the hippocampus. In conclusion, our study strongly demonstrates that hippocampal E2, but not peripheral E2, plays a critical role in NOR ability and that Kalirin-7 may be involved in this mechanism. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Sodium transport across erythrocyte membranes in diabetes mellitus.
The activity of the erythrocyte ouabain sensitive Na/K ATPase pump was studied in 20 Type 1 diabetics, 15 Type 2 diabetics and 20 healthy controls. All diabetics were normotensive, caucasian and non-obese diabetics. The diabetics were assessed for retinopathy and had HbA1 estimated. The erythrocyte sodium concentration, membrane permeability to sodium and ouabain-sensitive sodium efflux rate constant (ERCos) were determined. The Type 1 diabetics had a significantly reduced ERC, mean +/- SD 0.198 +/- 0.028 hr-1 vs control 0.264 +/- 0.054 hr-1 (p less than 0.001). A similar reduction in ERCos was seen in the Type 2 diabetics when compared to controls (0.229 +/- 0.059 hr-1 p less than 0.005). There was also a significant difference between the 2 groups of diabetics (p less than 0.05). There was no significant difference in intracellular sodium concentrations. Membrane permeability was reduced in the Type 1 diabetics (3.69 +/- 0.79 mmol/kg dry wt/hr) compared to the control group (4.56 +/- 0.79 mmol/kg dry wt/hr, p less than 0.01). Diabetic control (HbA1) was positively correlated with ERCos, but no significant differences were seen in the ERCos between complicated and uncomplicated Type 1 diabetics. In vitro studies of normal erythrocytes did not show an effect on pump activity of increasing glucose or insulin concentration during a preincubation study. These results demonstrate that there is a reduction in activity of the ouabain-sensitive Na/K ATPase pump and a reduction in membrane permeability on the diabetic erythrocyte which is most marked in Type 1 diabetics.


Safety of repeated cell-free and concentrated ascites reinfusion therapy for malignant ascites from gastrointestinal cancer.
Malignant ascites due to peritoneal metastasis is one of the major problems caused by advanced gastrointestinal cancer. Although drainage of a large amount of ascitic fluid improves symptoms such as abdominal fullness, it may lead to protein loss and renal dysfunction. Cell-free and concentrated ascites reinfusion therapy (CART) may help avoid such complications due to paracentesis. The purpose of this study was to evaluate the safety of CART. We performed a total of 51 sessions of CART in 5 patients, 4 of whom had gastric cancer and 1 appendiceal cancer. We retrospectively evaluated laboratory data immediately prior to CART, on the following day, 1 week later and 2 weeks later. We also measured the amount of total protein and albumin in collected and concentrated ascites. The mean amount of collected ascites was 4,007 ml. All the patients exhibited improvement of symptoms such as abdominal fullness. Four patients developed fever (>38°C) immediately after reinfusion of the concentrated ascites and 3 of these patients required corticosteroid administration. The mean total protein and albumin in the collected ascites were 122 and 64 g, respectively, and those in the concentrated ascites 75 and 39 g, respectively. The serum levels of total protein, albumin and creatinine after CART were almost identical to those prior to CART. Blood hemoglobin concentration was significantly decreased 1 day after CART and returned to baseline levels in 1-2 weeks. CART does not cause renal dysfunction and does not decrease serum albumin; therefore, repeated CART is safe and may be used to improve the symptoms of malignant ascites from gastrointestinal cancer.


Recent advances in developing vaccines against Toxoplasma gondii: an update.
Toxoplasma gondii, a significant public health risk, is able to infect almost all warm-blooded animals including humans, and it results in economic losses in production animals. In the last three years, a large number of vaccination experiments have been performed to control T. gondii infection, with the target of limiting the acute infection and reducing or eliminating tissue cysts in the intermediate hosts. In this paper, we summarize the latest results of the veterinary vaccines against T. gondii infection since 2013. Immunization with live-attenuated whole organisms of non-reverting mutants has been shown to induce remarkably potent immune responses associated with control of acute and chronic toxoplasmosis. The non-cyst-forming mutants are promising new tools for the development of veterinary vaccines against T. gondii infection.


Disruption of TCF/β-Catenin Binding Impairs Wnt Signaling and Induces Apoptosis in Soft Tissue Sarcoma Cells.
Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin and represent around 1% of adult cancers, being a very heterogeneous group of tumors with more than 50 different subtypes. The Wnt signaling pathway is involved in the development and in the regulation, self-renewal, and differentiation of mesenchymal stem cells, and plays a role in sarcomagenesis. In this study, we have tested pharmacologic inhibition of Wnt signaling mediated by disruption of TCF/β-catenin binding and AXIN stabilization, being the first strategy more efficient in reducing cell viability and downstream effects. We have shown that disruption of TCF/β-catenin binding with PKF118-310 produces in vitro antitumor activity in a panel of prevalent representative STS cell lines and primary cultures. At the molecular level, PKF118-310 treatment reduced β-catenin nuclear localization, reporter activity, and target genes, resulting in an increase in apoptosis. Importantly, combination of PKF118-310 with doxorubicin resulted in enhanced reduction of cell viability, suggesting that Wnt inhibition could be a new combination regime in these patients. Our findings support the usefulness of Wnt inhibitors as new therapeutic strategies for the prevalent STS. Mol Cancer Ther; 16(6); 1166-76. ©2017 AACR.


Multitaper estimates of phase-amplitude coupling.
Phase-amplitude coupling (PAC) is the association of the amplitude of a high-frequency oscillation with the phase of a low-frequency oscillation. In neuroscience, this relationship provides a mechanism by which neural activity might be coordinated between distant regions. The dangers and pitfalls of assessing PAC with commonly used statistical measures have been well-documented. The limitations of these measures include: (1) response to non-oscillatory, high-frequency, broad-band activity, (2) response to high-frequency components of the low-frequency oscillation, (3) adhoc selection of analysis frequency-intervals, and (4) reliance upon data shuffling to assess statistical significance.Objective.To address issues (1)-(4) by introducing a nonparametric multitaper estimator of PAC.Approach.In this work, a multitaper PAC estimator is proposed that addresses these issues. Specifically, issue (1) is addressed by replacing the analytic signal envelope estimator computed using the Hilbert transform with a multitaper estimator that down-weights non-sinusoidal activity using a classical, multitaper super-resolution technique. Issue (2) is addressed by replacing coherence between the low-frequency and high-frequency components in a standard PAC estimator with multitaper partial coherence, while issue (3) is addressed with a physical argument regarding meaningful neural oscillation. Finally, asymptotic statistical assessment of the multitaper estimator is introduced to address issue (4).Main results.Multitaper estimates of PAC are introduced. Their efficacy is demonstrated in simulation and on human intracranial recordings obtained from epileptic patients.Significance.This work facilitates a more informative statistical assessment of PAC, a phenomena exhibited by many neural systems, and provides a basis upon which further nonparametric multitaper-related methods can be developed.


The dis-ease of nursing academia: putting the vulnerability 'out there' (Part 2).
In this article, the second in a two-part series on research investigating the lived experiences of women nurse academics in australia, the results of the study are revealed. The major findings indicated that the Australian university system remains competitive and non-supportive of women nurse academics. The women who participated in this study had a strong desire to share their stories and reveal their vulnerability associated with their everyday life experiences in universities. Cultural descriptions revealed the complexity of women nurse academics' vulnerability as well as the dimensions of emotional resilience and optimism for their associated emotional healing.


[Textual research on circulation of the Ming edition of Li Heng's Xiu zhen fang (Pocket Formulary)].
Xiu zhen fang (Pocket Formulary) is a recipe book of the Ming Dynasty, inspired and managed by Zhu Su, compiled by Li Heng of liangyisuo (good physician house) in Zhou wangfu (Zhou's royal palace). The book was compiled and published twice during the reigns of the Hongwu and Yongle Emperors of the Ming Dynasty. Because of its high practicability, there were some editions in circulation, and the book was published several times only in the Ming Dynasty. At present, the earliest extanteditionwas the little character version of Yongle, and the version in the 4(th) year of Zhengde Emperor of the Ming Dynasty was a reprinting edition based on the Yongle edition, sharingthe same edition system. Most of the editions appeared after the reign of Zhengtong Emperor of the Ming Dynasty, titled by "kui ben (head version)" and "da quan (complete edition)" were the editionspublished in the local bookshops, which had rather distinct differences from the Yongle edition system not only in the its format but also in its contents.


Hyperthermic Intraperitoneal Chemotherapy - Fading Perspective in the Light of Modern Systemic Chemotherapy?
Peritoneal metastasis (PM) in a gastrointestinal cancer is associated with a poor prognosis. Various guidelines recommend palliative chemotherapy in these patients as cure is not achievable. However, hyperthermic intraperitoneal chemotherapy (HIPEC) in combination with cytoreductive surgery (CRS) can achieve long-term survival with low morbidity in selected patients. During the last decades, CRS and HIPEC have been performed in a number of indications, aiming for long-term survival. What is more, new drugs and treatment regimens demonstrate favorable results. The recently published important literature on PM in gastrointestinal cancer was analyzed. Resection of isolated PM in a gastrointestinal cancer should be considered, and HIPEC is feasible. However, there is a lack of well-designed randomized controlled trials (RCTs) in gastrointestinal cancer-related PM. Many RCTs are being conducted across the world whose results will be available in 1-2 years. Systemic chemotherapy alone as an adequate management plan for isolated PM in a gastrointestinal cancer is not compatible with a high standard of care. Formulating an optimal plan combining the benefits of CRS and HIPEC coupled with systemic chemotherapy is a necessary task of the multidisciplinary team. Proper selection of the patients for CRS and HIPEC is necessary to achieve maximal oncological benefit and minimal perioperative morbidity and mortality. A multidisciplinary approach combining the benefits of both CRS and HIPEC, and systemic chemotherapy is the way forward to manage those patients with gastrointestinal cancer and PM. Further studies are warranted to identify the selection variables for CRS and HIPEC.


Technology of water-jet dissection.
For about 20 years, water-jet dissection has been used as a surgical technique. Due to the development of suitable instruments, devices, and operation strategies, water-jet dissection is becoming increasingly interesting for applications, especially for dissections where the atraumatical and/or tissueselective preparation or separation of tissue structures is mandatory. Prerequisites for the effective and safe application of the water-jet dissection are, on the one side, the knowledge of the relevant physical characteristics of the tissues in question, as well as their mechanical connections, and, on the other side, the knowledge of the relevant physical effects of a water-jet. The present paper will deal with these aspects.


Improvement of Luminescence Properties of Eulytite Single-Phase White Emitting Ca3Bi (PO4)3: Ce3+/Dy3+ Phosphor.
To reduce the issue of tri-primary color reabsorption, a new approach for single-phase phosphors as light-emitting diodes (LEDs) has been recommended. The structures, morphology, photoluminescence, thermal stability, and luminescence mechanism of a variety of Ca3Bi (PO4)3 (CBPO): Ce3+/Dy3+ phosphors were investigated. XRD characterization showed that all CBPO samples were eulytite structures. Furthermore, the energy transfer process from Ce3+ to Dy3+ in CBPO is systematically investigated in this work, and the color of light can be adjusted by changing the ratio of doped ions. Under UV light, energy is transferred from Ce3+-Dy3+ mainly through quadrupole-quadrupole interactions in the CBPO host, and doping with different Dy3+ concentrations tunes the emission color from blue to white. The thermal stability of the CBPO: 0.04Ce3+, 0.08Dy3+ samples is outstanding, and the CIE coordinates of the samples after emission have little effect with temperature, while their emission intensity at 423 K is as strong as that at room temperature, reaching 90%. The above results indicate that this CBPO material has great potential as a white light phosphor under near-UV excitation at the optimized concentration of Ce3+ and Dy3+.


THE EVOLUTIONARY ECOLOGY OF AN ANTIPREDATOR REACTION NORM: DAPHNIA PULEX AND CHAOBORUS AMERICANUS.
Ponds containing the parthenogenetic zooplankter Daphnia pulex with and without chaoborid predators were sampled over the course of a season. A significant (P < 0.05) Spearman rank correlation was found between predator density and the expression of an antipredator defense (neckteeth) by the Daphnia. The reaction norms (percent induction of a single genotype versus predator density) of clones isolated from predator-free and predator-rich habitats were determined in a laboratory setting. There was a statistically significant different response among the six clones tested (P < 0.05). Clones isolated from chaoborid ponds showed significantly greater sensitivity to the presence of predator than clones from predator-free ponds (P < 0.05). In the laboratory, food levels under which prey were cultured affected induction of the antipredator response. Highest induction was found at the lowest food level used.


Dietary fat consumption and non- communicable chronic diseases in China.
Fat consumption at a national level is largely determined by the economic development of a country. Based on the data of nationwide nutrition surveys undertaken in China in 1982 and 1992, the average intake per capita per day of meat increased from 62.6 to 100.5 g in urban areas and from 22.9 to 37.6 g in rural areas. The consumption per capita per day of eggs increased from 15.5 to 29.4 g in urban areas and from 3.8 to 8.8 g in rural areas. The daily consumption of cooking oil was 12 g in 1982 and reached 22.4 g in 1992, while the consumption of animal fat remained stable. The average fat intake accounted for 18.1% of total energy intake in 1982 and 22.0% in 1992. The daily fat intake of Beijing urban residents was 92.9 g per capita per day in 1992, accounting for 32.7% of total energy intake, which was beyond the top limit suggested by the World Health Organisation. The change of disease patterns in Chinese people has been great during the past two decades. The mortality rate due to cerebro-cardiovascular disease accounted for 12.07% of deaths in 1957, and increased to 40.72% in 1994. The non-communicable chronic diseases (NCCD) accounted for approximately 70% of total deaths. Twenty-five percent of the total population and 60% of day care patients suffered from chronic diseases. The risk factors of NCCD are increasing in China and more attention should be given to the prevention and intervention of NCCD in the future.


Photo-induced events in the human melanocytic system: photoaggression and photoprotection.
The human skin is submitted to solar, essentially ultraviolet radiation (UVR), aggressions, and develops, for sufficient doses, erythema and pigmentation. The individual sun-sensitivity depends on the nature and the quantity of melanins present in the epidermis. These parameters are inherited as genetic traits which account for the large variations of the constitutive and adaptive pigmentation encountered in the caucasian populations. From red-haired skin-sensitive individuals, to dark-haired sun-resistant individuals, phaeomelanins (red) and eumelanins (black) are mixed in variable proportions. Pure melanins extracted from red hairs and black hairs behave differently when submitted to ultraviolet radiations: phaeomelanins develop aggressive species of molecules responsible for DNA damages, mutations, and cell death. On the contrary, eumelanins are less toxic for the major cellular metabolisms. The sun-sensitive populations suffer from more skin cancer of all types than the dark ones. In particular, they are exposed significantly to higher risk of melanoma and to the risk of bearing more nevi following large solar exposures early in the life.


Adding the "in" to justice: a qualitative and quantitative investigation of the differential effects of justice rule adherence and violation.
Although justice scholars often assume that individuals react to injustice in a manner that is distinct from their reactions to justice, few studies have examined this assumption. Indeed, the most widely utilized measures in the literature assess only the adherence to rules of justice--not their violation. We conducted 2 studies to build and test theory about differential reactions to justice and injustice. An inductive study revealed that reactions to the adherence to justice rules reflected different constructs than reactions to the violations of justice rules. In a follow-up field study, we derived hypotheses for those patterns by drawing on the negativity bias and regulatory focus literatures. Specifically, justice rule violation was predicted to be more relevant to prevention-laden outcomes that represent a high level of vigilance and concerns about safety. Justice rule adherence was predicted to be more relevant to promotion-laden outcomes that represent concerns about becoming the ideal self. The field study supported many of those predictions while showing that a full-range justice measure (i.e., one that sampled both justice rule adherence and justice rule violation) explained more variance in outcomes than existing "truncated" justice measures.


The Synergistic Priming Effect of Exogenous Salicylic Acid and H2O2 on Chilling Tolerance Enhancement during Maize (Zea mays L.) Seed Germination.
Chilling stress is an important constraint for maize seedling establishment in the field. To examine the role of salicylic acid (SA) and hydrogen peroxide (H2O2) in response to chilling stress, we investigated the effects of seed priming with SA, H2O2, and SA+H2O2 combination on maize resistance under chilling stress (13°C). Priming with SA, H2O2, and especially SA+H2O2 shortened seed germination time and enhanced seed vigor and seedling growth as compared with hydropriming and non-priming treatments under low temperature. Meanwhile, SA+H2O2 priming notably increased the endogenous H2O2 and SA content, antioxidant enzymes activities and their corresponding genes ZmPAL, ZmSOD4, ZmAPX2, ZmCAT2, and ZmGR expression levels. The α-amylase activity was enhanced to mobilize starch to supply metabolites such as soluble sugar and energy for seed germination under chilling stress. In addition, the SA+H2O2 combination positively up-regulated expressions of gibberellic acid (GA) biosynthesis genes ZmGA20ox1 and ZmGA3ox2, and down-regulated GA catabolism gene ZmGA2ox1 expression; while it promoted GA signaling transduction genes expressions of ZmGID1 and ZmGID2 and decreased the level of seed germination inhibitor gene ZmRGL2. The abscisic acid (ABA) catabolism gene ZmCYP707A2 and the expressions of ZmCPK11 and ZmSnRK2.1 encoding response receptors in ABA signaling pathway were all up-regulated. These results strongly suggested that priming with SA and H2O2 synergistically promoted hormones metabolism and signal transduction, and enhanced energy supply and antioxidant enzymes activities under chilling stress, which were closely relevant with chilling injury alleviation and chilling-tolerance improvement in maize seed. Highlights:Seed germination and seedling growth were significantly improved under chilling stress by priming with SA+H2O2 combination, which was closely relevant with the change of reactive oxygen species, metabolites and energy supply, hormones metabolism and regulation.


The "Pooh Corner" vision study.
Two groups of children were screened by selected optometrical tests. Infants between the ages of 3 and 24 months and kindergarten children aged from 2 to 5 years were tested. The results indicated that meaningful data can be obtained from both groups and that the tests revealed visuosensory and visuomotor defects, correction of which at an early stage is not only desirable but, in most cases, essential.


Nationwide survey of cancer center programs in Korea.
This study was conducted to investigate cancer centers established for the purpose of satisfying various needs about cancer, improving the cancer treatment environment, and subdividing services ranging from diagnosis, treatment, and rehabilitation to palliative care. To this end, the authors have surveyed programs in 17 cancer centers representing Korea, including 12 national cancer centers and five major hospitals. As a result, it was found that the most common type of lecture program was disease management, followed by health care and hospitalization, while the most common type of participation program was psychological relief, followed by physical activity. The most frequently operated type of program was found to be psychological relief, followed by physical activity and health care in the regional cancer centers, while the most frequently operated type was disease management, followed by psychological relief and health care in the five major hospitals. The proportion of physical activity was very high in two regional cancer centers, whereas five regional cancer centers did not offer physical activity programs at all. In the five major hospitals, physical activity programs were conducted regularly at least once a month or at least once a week. In addition, further studies are required to provide professional and detailed medical services for the establishment and operation of programs for cancer patient management and the environmental aspects of the hospital.


Variants of papillary carcinoma of the thyroid: experience at Asir Central Hospital.
Papillary carcinoma of the thyroid is now further subclassifiable into its different variants. We report incidence, clinical behaviour and outcome of rare variants of papillary thyroid cancers at Asir Central Hospital, Saudi Arabia. These variants differ from each other not only on a morphometric basis, but also in clinical behaviour. Accordingly, we report our experience of different variants in a series of 35 papillary carcinomas. These cases were received in the surgical pathology laboratory of Asir Central Hospital from January 1987 to December 1994. We have reviewed clinical charts, microscopic slides and pathological reports of these carcinomas. The following results have been obtained: 20 cases were classical (usual) papillary thyroid carcinomas: seven were follicular variants; three were tall cell/ columnar variants; two were oxyphilic variants; and one was a diffuse sclerosing variant. There were two de-differentiated papillary carcinomas (anaplastic carcinomas with foci of well-differentiated papillary carcinomas). These variants were also correlated with clinical parameters such as age, sex and nationality of the patients, aggressiveness of the tumours, types of surgery required, and follow-up when available.


Age-related differences in phosphodiesterase activity and effects of chronic phosphodiesterase inhibition in idiopathic dilated cardiomyopathy.
Despite the application of proven adult heart failure therapies to children with idiopathic dilated cardiomyopathy (IDC), prognosis remains poor. Clinical experience with phosphodiesterase 3 inhibitors (PDE3i) in pediatric patients with IDC, however, demonstrates improved heart failure symptoms without the increased incidence of sudden death seen in adults treated with PDE3i. We sought to determine age-related differences in PDE activity and associated intracellular signaling responsible for the efficacy and relative safety of chronic PDE3i in pediatric heart failure. cAMP levels, PDE activity, and phospholamban phosphorylation (pPLB) were determined in explanted human left ventricular myocardium (pediatric n=41; adult n=88). Adults and children with IDC (not treated with PDE3i) had lower cAMP and pPLB compared with nonfailing controls. In contrast to their adult counterparts, pediatric IDC patients chronically treated with PDE3i had elevated cAMP (P=0.0403) and pPLB (P=0.0119). In addition, total PDE- and PDE3-specific activities were not altered in pediatric IDC patients on PDE3i, whereas adult IDC patients on PDE3i demonstrated higher total PDE-specific (74.6±13.8 pmol/mg per minute) and PDE3-specific (48.2±15.9 pmol/mg per minute) activities in comparison with those of nonfailing controls (59.5±14.4 and 35.5±12.8 pmol/mg per minute, respectively). Elevated cAMP and higher pPLB may contribute to sustained hemodynamic benefits in pediatric IDC patients treated with PDE3i. In contrast, higher total PDE and PDE3 activities in adult IDC patients treated with PDE3i may perpetuate lower myocardial cAMP and pPLB levels, limiting the potential benefits of PDE3i therapy.


Cytokinin-Mediated Regulation of Reactive Oxygen Species Homeostasis Modulates Stomatal Immunity in Arabidopsis.
Stomata play an important role in preinvasive defense responses by limiting pathogen entry into leaves. Although the stress hormones salicylic acid (SA) and abscisic acid (ABA) are known to regulate stomatal immunity, the role of growth promoting hormones is far from understood. Here, we show that in Arabidopsis thaliana, cytokinins (CKs) function in stomatal defense responses. The cytokinin receptor HISTIDINE KINASE3 (AHK3) and RESPONSE REGULATOR2 (ARR2) promote stomatal closure triggered by pathogen-associated molecular pattern (PAMP) and resistance to Pseudomonas syringae pv tomato bacteria. Importantly, the cytokinin trans-zeatin induces stomatal closure and accumulation of reactive oxygen species (ROS) in guard cells through AHK3 and ARR2 in an SA-dependent and ABA-independent manner. Using pharmacological and reverse genetics approaches, we found that CK-mediated stomatal responses involve the apoplastic peroxidases PRX4, PRX33, PRX34, and PRX71, but not the NADPH oxidases RBOHD and RBOHF. Moreover, ARR2 directly activates the expression of PRX33 and PRX34, which are required for SA- and PAMP-triggered ROS production. Thus, the CK signaling pathway regulates ROS homeostasis in guard cells, which leads to enhanced stomatal immunity and plant resistance to bacteria.


[Lithium intoxication mimics Alzheimer's disease in PET and clinical findings].
To improve specificity and sensitivity in the diagnosis of Alzheimer's disease, neuropsychological tests and fluorine-18-FDG-PET are increasingly used. Here we present a patient whose lithium intoxication mimicked Alzheimer's disease both clinically and in 18-FDG-PET. This case serves as a reminder of the importance of the differential diagnosis of dementias and is intended to highlight one potential pitfall.


The mitophagosome, a novel ultrastructure of mitophagy in the alcoholic steatohepatitis mouse model: a transmission electron microscope study.
Acute alcohol feeding can activate autophagy and promotes the selection of autophagic vacuoles in the mitochondria, which is a key process regulating the occurrence and progression of alcohol steatohepatitis (ASH). In this study, ASH mice expressed more autophagy-associated proteins than healthy controls, as revealed by immunohistochemistry. In addition, transmission electron microscopy (TEM) detected a unique autophagy ultrastructure in ASH mouse liver cells, consisting of a large vesicle fused directly with mitochondria, which differed from the classical pattern. This novel type of mitophagy may provide a new avenue for a protective mechanism targeting mitophagy, which would benefit patients with ASH.Abbreviations: ASH: alcoholic steatohepatitis; ALD: Alcoholic liver disease; ALT: alanine aminotransferase; AST: aspartate aminotransferase; HE: hematoxylin and eosin; TEM: transmission electron microscope; LC3: microtubule-associated protein 1 light chain 3; SQSTM1/p62: sequestosome 1; UQCRC2: ubiquinol-cytochrome c reductase core protein 2; PINK1: PTEN induced kinase 1; AMPK: AMP-activated protein kinase.


Effect of an active metabolite of the antiallergic agent tazanolast on histamine release from rat mast cells.
WP-871 (3'-(1H-tetrazol-5-yl)oxanilic acid monohydrate, CAS 114607-46-4) is a monohydrate of a main active metabolite of tazanolast (butyl 3'-(1H-tetrazol-5-yl) oxanilate, CAS 82989-25-1), an orally active antiallergic drug. WP-871 inhibited dose-dependently compound 48/80-induced histamine release from rat peritoneal mast cells. In a similar dose range, WP-871 was effective in inhibiting compound 48/80-induced 45Ca uptake into mast cells from extracellular medium and compound 48/80-induced translocation of protein kinase C from the cytosol to the membrane fraction of mast cells. WP-871 also inhibited inositol trisphosphate production but did not exhibit a direct inhibitory effect on phospholipase C in mast cells. WP-871 caused no increase in cAMP content in mast cells. These results suggest that WP-871 may inhibit histamine release mainly by preventing the increase in intracellular Ca2+ concentration, which is a critical event in signal transduction leading to histamine release in mast cells.


The permanent electric dipole moments of calcium monohydride, CaH.
Numerous branch features in the (0,0) A 2Pi-X 2Sigma+ band system of calcium monohydride CaH have been studied by optical Stark spectroscopy. The Stark shifts, Stark splittings, and appearance of electric-field-induced transitions in the high resolution laser-induced fluorescence spectra are analyzed to produce values for the magnitude of the permanent electric dipole moments mid R:micromid R: of 2.94(16) D and 2.372(12) D for the X 2Sigma+(v=0) and A 2Pi(v=0) states, respectively. A comparison with values predicted from a semiempirical electrostatic model and previous ab initio calculations for mid R:micromid R: (X 2Sigma+) is presented. The change in mid R:micromid R: upon excitation from the X 2Sigma+ state to the A 2Pi state is rationalized using a simple molecular orbital description.


Role of dipeptidyl peptidase-4 inhibitors in patients with diabetes infected with coronavirus-19.
The pandemic infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is widely increasing the patients affiliated with coronavirus disease 2019 (COVID-19) from last December of 2019. It is reported that the entry receptor of SARS-CoV-2 has been confirmed to be angiotensin-converting enzyme 2 (ACE2). Notably, whether the ACE-related inhibitors or drugs modulated ACE2 activity in affecting the viral activity and disease severity of SARS-CoV-2 is still an open question. Dipeptidyl peptidase-4 (DDP-4), a well-known anti-diabetic drug, has been widely used to control the glycemic condition in patients with diabetes. In this article, we are focusing on the impact of ACE inhibitors (ACEI) and DPP4 inhibitors used on SARS-CoV-2 activity and discussions about those drugs that may be related to infectious condition of COVID-19 diseases.


RGD peptides protects against acute lung injury in septic mice through Wisp1-integrin β6 pathway inhibition.
Acute lung injury is a common consequence of sepsis, a life-threatening inflammatory response caused by severe infection. In this study, we elucidate the attenuating effects of synthetic Arg-Gly-Asp-Ser peptides (RGDs) on acute lung injury in a sepsis mouse model. We further reveal that the beneficial effects of RGDs stem from their negative regulation of the Wisp1 (WNT1-inducible signaling pathway)-integrin β6 pathway. After inducing sepsis using cecal ligation and puncture (CLP), mice were randomized into experimental and control groups, and survival rates were recorded over 7 days, whereas only 20% of mice subjected to CLP survived when compared with untreated controls; the addition of RGDs to this treatment regimen dramatically increased the survival rate to 80%. Histological analysis revealed acute lung injury in CLP-treated mice, whereas those subjected to the combined treatment of CLP and RGDs showed a considerable decrease in lung injury severity. The addition of RGDs also dramatically attenuated other common sepsis-associated effects, such as increased white blood cell number in bronchoalveolar lavage fluid and decreased pulmonary capillary barrier function. Furthermore, treatment with RGDs decreased the serum and bronchoalveolar lavage fluid levels of inflammatory cytokines such as tumor necrosis factor α and interleukin 6, contrary to the CLP treatment alone that increased the levels of these proteins. Interestingly, however, RGDs had no detectable effect on bacterial invasion following sepsis induction. In addition, mice treated with RGDs showed decreased levels of wisp1 and integrin β6 when compared with CLP-treated mice. In the present study, a linkage between Wisp1 and integrin β6 was evaluated in vivo. Most strikingly, RGDs resulted in a decreased association of Wisp1 with integrin β6 based on coimmunoprecipitation analyses. These data suggest that RGDs ameliorate acute lung injury in a sepsis mouse model by inhibiting the Wisp1-integrin β6 pathway.


Pharmacokinetics, drug interactions, and tolerability of paroxetine and paroxetine CR.
The development of paroxetine hydrochloride began in the late 1970s. An abundance of data have been accumulated from clinical investigations demonstrating the efficacy of paroxetine in the treatment of major depression and anxiety disorders. The published literature contains a substantial amount of supportive data documenting the safety, tolerability, and pharmacokinetic and pharmacodynamic properties of paroxetine. The role of paroxetine in clinically significant drug-drug interactions, especially involving metabolic inhibitory effects on the substrates of cytochrome p450 2D6, has long been suspected, but only isolated cases provide any evidence. Published data for widespread patient morbidity from drug interactions with paroxetine are almost nonexistent. Considerations of the pharmacokinetic properties of paroxetine support a rationale for the development of new dosage forms that maintain the efficacy yet improve the tolerability profile of the selective serotonin reuptake inhibitors. Paroxetine controlled-release is an enteric-coated formulation with release features that may enhance clinical outcome by modifying absorption-related pharmacokinetics, improving tolerability, and maintaining therapeutic benefits


The crystal structure of the bacterial chaperonin GroEL at 2.8 A.
The crystal structure of Escherichia coli GroEL shows a porous cylinder of 14 subunits made of two nearly 7-fold rotationally symmetrical rings stacked back-to-back with dyad symmetry. The subunits consist of three domains: a large equatorial domain that forms the foundation of the assembly at its waist and holds the rings together; a large loosely structured apical domain that forms the ends of the cylinder; and a small slender intermediate domain that connects the two, creating side windows. The three-dimensional structure places most of the mutationally defined functional sites on the channel walls and its outward invaginations, and at the ends of the cylinder.


Disseminated encephalomyelitis and multiple sclerosis: two different diseases - a critical review.
The practice of initiating immunomodulatory treatment immediately after a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) emphasizes the need to distinguish between disseminated encephalomyelitis (DEM) and MS. Their clinical, genetic, imaging, and histopathological characteristics establish that they are distinct disease entities. Acute and recurrent DEM are more common in children, but also occur in adults. DEM is polysymptomatic and includes signs and symptoms rarely encountered in MS, such as fever, alterations of the state of consciousness, cognitive and aphasic symptoms, and meningism. Cerebrospinal oligoclonal bands are rare. Magnetic resonance imaging (MRI) is the best means of distinguishing between DEM and MS. In the former, the lesion load is heavy, thalamus or basal ganglia are often affected, and early in the disease most of the lesions are usually larger than those of MS and enhance with gadolinium. The MRI spinal cord lesions are longer than three vertebral segments, and define neuromyelitis optica (NMO). Antibodies against aquaporin-4 are present in some NMO, but are also found in cases of MS and DEM. Most NMO are forms of DEM, not MS, and are identical with the 'Oriental' or 'optico-spinal' form of MS.


Impersonal medical care. Role of the pathologist in its evolution.
An evaluation of the change in the former close relationship between the patient and his physician, and the contribution of the pathologist to its development, is presented. The effect of these changes on the interest in and care of the patient by all in the hospital in this changing medical scene is decried; the patient loses much. The problem of impersonal care now involves all hospital care and all fields of medicine. The decline of interest in the autopsy and the formalization of this denigration of the autopsy by the Accreditation Commission has done harm to pathology and the care of the patient; the autopsy is still an important quality control of such care. Further, this change in the medical scene has promoted the development of the employee status of the doctor, with its further loss of independence, individual interest, and personalized care by all in the hospital, even the physician, and inevitably has led to his loss of the protection of due process. Seven recommendations are offered to recapture the old one-to-one doctor-patient arrangement, to yield a combination of tender loving and scientific care for the patient. An active effort must be made to reverse the influence of some of the forces working to the disadvantage of doctor and patient in the changing medical scene.


The biological sense of cancer: a hypothesis.
Most theories about cancer proposed during the last century share a common denominator: cancer is believed to be a biological nonsense for the organism in which it originates, since cancer cells are believed to be ones evading the rules that control normal cell proliferation and differentiation. In this essay, we have challenged this interpretation on the basis that, throughout the animal kingdom, cancer seems to arise only in injured organs and tissues that display lost or diminished regenerative ability. According to our hypothesis, a tumor cell would be the only one able to respond to the demand to proliferate in the organ of origin. It would be surrounded by "normal" aged cells that cannot respond to that signal. According to this interpretation, cancer would have a profound biological sense: it would be the ultimate way to attempt to restore organ functions and structures that have been lost or altered by aging or noxious environmental agents. In this way, the features commonly associated with tumor cells could be reinterpreted as progressively acquired adaptations for responding to a permanent regenerative signal in the context of tissue injury. Analogously, several embryo developmental stages could be dependent on cellular damage and death, which together disrupt the field topography. However, unlike normal structures, cancer would have no physiological value, because the usually poor or non-functional nature of its cells would make their reparative task unattainable. The hypothesis advanced in this essay might have significant practical implications. All conventional therapies against cancer attempt to kill all cancer cells. However, according to our hypothesis, the problem might not be solved even if all the tumor cells were eradicated. In effect, if the organ failure remained, new tumor cells would emerge and the tumor would reinitiate its progressive growth in response to the permanent regenerative signal of the non-restored organ. Therefore, efficient anti-cancer therapy should combine an attack against the tumor cells themselves with the correction of the organ failure, which, according to this hypothesis, is fundamental to the origin of the cancer.


Sudden infant death syndrome/unexplained infant deaths in Sri Lanka.
Sudden Infant Death Syndrome (SIDS), also known as 'unexplained deaths under one year', is rarely reported in Sri Lanka as a cause of post-neonatal mortality. The aim of this study was to assess the opinion of paediatricians and pathologists regarding the reasons for this rarity. Members of the Colleges of Paediatricians, Pathologists and Forensic Pathologists who met the inclusion criteria were selected as the study population. A brief self-administered questionnaire was used for data collection. Results were analysed using standard statistical methods. The sample consisted of 50 paediatricians, 15 histopathologists and seven forensic pathologists with a mean career span of 26.3 years. SIDS was reportedly diagnosed by only nine (12.5%) of the respondents while the other 63 (87.5%) have never encountered SIDS during their careers. Of the nine doctors, three (33.3%) based their diagnosis on autopsy findings but histological and toxicological studies had not been performed. The other six doctors (66.6%) relied on clinical history alone. Twenty-five doctors (34.7%) believed that keeping babies under close adult supervision was the reason SIDS is so rare in Sri Lanka. Twenty paediatricians (40%) and four histopathologists (26.7%) agreed with this view while five forensic pathologists (71.4%), believed the reason was under-diagnosis. In conclusion, the majority of doctors believe the most likely reason for the rarity of SIDS in Sri Lanka is that babies are kept under close adult supervision, in comparison with developed countries. By contrast, most forensic pathologists are of the opinion that SIDS is under-diagnosed.


Thickness constraints on the icy shells of the galilean satellites from a comparison of crater shapes.
A thin outer ice shell on Jupiter's large moon Europa would imply easy exchange between the surface and any organic or biotic material in its putative subsurface ocean. The thickness of the outer ice shell is poorly constrained, however, with model-dependent estimates ranging from a few kilometres to ten or more kilometres. Here I present measurements of depths of impact craters on Europa, Ganymede and Callisto that reveal two anomalous transitions in crater shape with diameter. The first transition is probably related to temperature-dependent ductility of the crust at shallow depths (7 8 km on Europa). The second transition is attributed to the influence of subsurface oceans on all three satellites, which constrains Europa's icy shell to be at least 19 km thick. The icy lithospheres of Ganymede and Callisto are equally ice-rich, but Europa's icy shell has a thermal structure about 0.25 0.5 times the thicknesses of Ganymede's or Callisto's shells, depending on epoch. The appearances of the craters on Europa are inconsistent with thin-ice-shell models and indicate that exchange of oceanic and surface material could be difficult.


Evidence and mechanisms of fat depletion in cancer.
The majority of cancer patients experience wasting characterized by muscle loss with or without fat loss. In human and animal models of cancer, body composition assessment and morphological analysis reveals adipose atrophy and presence of smaller adipocytes. Fat loss is associated with reduced quality of life in cancer patients and shorter survival independent of body mass index. Fat loss occurs in both visceral and subcutaneous depots; however, the pattern of loss has been incompletely characterized. Increased lipolysis and fat oxidation, decreased lipogenesis, impaired lipid depositionand adipogenesis, as well as browning of white adipose tissue may underlie adipose atrophy in cancer. Inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β) produced by the tumor or adipose tissue may also contribute to adipose depletion. Identifying the mechanisms and time course of fat mass changes in cancer may help identify individuals at risk of adipose depletion and define interventions to circumvent wasting. This review outlines current knowledge of fat mass in cancer and illustrates the need for further studies to assess alterations in visceral and subcutaneous adipose depots and possible mechanisms for loss of fat during cancer progression.


Use of inorganic salts to minimize serum interference in a sandwich enzyme immunoassay for human growth hormone using Fab'-horseradish peroxidase conjugate.
In a sandwich enzyme immunoassay (EIA) for human growth hormone (hGH) with anti-hGH Fab'-peroxidase conjugate, the effects of inorganic salts on serum interference were examined, and serum interference was eliminated by incubation of serum samples with anti-hGH IgG-coated polystyrene balls in the presence of 0.4 mol/l NaCl, avoiding the need for hGH-free serum. The sensitivity for hGH was 60 fg/tube or 3 ng/l of serum. No cross-reaction was observed with prolactin, chorionic gonadotropin or luteinizing, thyroid-stimulating and follicle-stimulating hormones. The coefficients of within-assay and between-assay variations were 2.8-6.5% and 4.8-8.7%, respectively. The regression equation and correlation coefficient to radioimmunoassay (RIA) were y(EIA) = 0.89x(RIA) + 0.11 and 0.98 (n = 100), respectively. hGH levels in normal male and female adult serum taken between 9:00 and 10:00 a.m. after overnight fasting and 1 h rest were 312 ng/l (range 53-940 ng/l; n = 10) and 662 ng/l (112-2195 ng/l; n = 13), respectively.