Can we safely monitor posterior fossa intracranial pressure? A cadaveric study.
measuring intracranial pressure (ICP) is considered the gold standard of care for brain injury. While supratentorial ICP monitoring has been adopted everywhere, posterior fossa ICP monitoring is rarely performed. In this study, we aimed to evaluate the feasibility of inserting ICP sensors into the posterior fossa of cadavers, to measure ICP in the posterior fossa. An ICP sensor was transcranially implanted into the posterior fossa of fifteen fresh adult cadavers. An extracranial point was defined in the retroauricular area 2 cm behind the tip of the mastoid process and 2 cm below the transverse sinus, in order to implant an ICP probe. The cranial cavity was opened and measures were taken of the distance that the ICP sensor had penetrated inside the posterior fossa, as well as the distance to nearby venous sinuses (lateral, transverse, sigmoid, inferior petrosal sinus, and jugular bulb). The cerebellar hemisphere was searched for any possible damage. the selected extracranial point (2 cm behind the tip of the mastoid process and 2 cm below the transverse sinus) was a safe location. Intracranial structures such as the brainstem and the cerebellar hemisphere were not damaged. The implanted ICP probe was at least 2 cm away from the venous sinuses, which were not damaged. ICP monitoring is safe and reliable at the described ICP probe placement site of the posterior fossa.


Video and accelerometer-based motion analysis for automated surgical skills assessment.
Basic surgical skills of suturing and knot tying are an essential part of medical training. Having an automated system for surgical skills assessment could help save experts time and improve training efficiency. There have been some recent attempts at automated surgical skills assessment using either video analysis or acceleration data. In this paper, we present a novel approach for automated assessment of OSATS-like surgical skills and provide an analysis of different features on multi-modal data (video and accelerometer data). We conduct a large study for basic surgical skill assessment on a dataset that contained video and accelerometer data for suturing and knot-tying tasks. We introduce "entropy-based" features-approximate entropy and cross-approximate entropy, which quantify the amount of predictability and regularity of fluctuations in time series data. The proposed features are compared to existing methods of Sequential Motion Texture, Discrete Cosine Transform and Discrete Fourier Transform, for surgical skills assessment. We report average performance of different features across all applicable OSATS-like criteria for suturing and knot-tying tasks. Our analysis shows that the proposed entropy-based features outperform previous state-of-the-art methods using video data, achieving average classification accuracies of 95.1 and 92.2% for suturing and knot tying, respectively. For accelerometer data, our method performs better for suturing achieving 86.8% average accuracy. We also show that fusion of video and acceleration features can improve overall performance for skill assessment. Automated surgical skills assessment can be achieved with high accuracy using the proposed entropy features. Such a system can significantly improve the efficiency of surgical training in medical schools and teaching hospitals.


Unusual fast sedimenting mitochondria producing heavy DNA in the cells of aging coleoptiles of wheat seedlings
A fraction of unusual fast sedimenting (10 min at 600-1700g) particles with properties of mitochondria has been detected in wheat seedlings. This fraction conventionally called "heavy" mitochondria amounts (by protein) to about 40% of the total subcellular particle fraction sedimented by 10 min centrifugation at 17,000g. The specific feature of these "heavy" mitochondria in aging tissues is an ability to synthesize and even superproduce heavy (rho = 1.718 g/cm3) mitochondrial DNA (H-mtDNA). The share of "heavy" mitochondria sedimented in the interval between 1000 and 1700g and possessing the maximal H-mtDNA synthesis in aging coleoptiles is about 1.5-fold higher than that in young coleoptiles. Although "heavy" mitochondria are present in young plant organs, they seem to be unable to synthesize H-mtDNA; heavy mtDNA forms only in mitochondria of aging or old cells. Thus, aging in plants is accompanied by a change in population of mitochondria and appearance of the ability for selective H-mtDNA superproduction in a certain mitochondrial fraction. Mitochondria isolated from wheat coleoptiles are practically not stimulated by uncouplers. "Heavy" (600-1700g) and usual (4,300-17,400g) mitochondria are similar in respiration rates, cytochrome compositions, cytochrome c amount (per mg protein) and sensitivities to respiration inhibitors. However, "heavy" mitochondria contain (per mg protein) cytochromes b and aa3 by 10-20% and Ca2+ by 2-3-fold more than normal mitochondria. Ultrastructural analysis showed that the isolated fraction of fast sedimenting mitochondria consists of a suspension of closed membrane vesicles filled with cytoplasm and containing one or a few mitochondria. We observed similar structures in situ in vacuoles of parenchyma cells in the apical part of intact coleoptiles. The process of formation of such structures was detected by serial ultra-thin section analysis. It was shown that tonoplast protrudes into vacuoles, the separate mitochondria translocate into these protrusions, and then these structures separate. As a result, the suspended cytoplasmic bodies containing mitochondria appear in vacuoles. Appearance of these bodies containing mitochondria and, in particular, the superproduction of H-mtDNA in them correlate with processes of aging and cell transition to apoptosis.


Understanding social workers' hidden roles in medication safety for older adults: A qualitative study.
Older adults are vulnerable to risks associated with medications. This study explores the roles of Social Workers in facilitating medication safety for older adults. Eight social workers from federally qualified health centers participated in a case-based and interactive medication safety curriculum. They participated in an in-depth, semi-structured interview to explore their roles and strategies in assisting older adults and caregivers with medication management. Findings were transcribed and analyzed. Six themes characterizing social workers' roles in medication management were identified: a) Referral: matching patients and medication-related resources within the health-care system and community; b) Communication: connecting providers, patients, caregivers, and support system; c) Access to medicine: addressing unique needs of each patient to foster their ability to obtain their medicines; d) Social Determinants of Health: investigating the social challenges of each patient and facilitating specific medication management approaches to meet identified needs; e) Engagement: engaging patients in co-developing a treatment plan; f) Caregiver Support: preparing caregivers to assist in medication management. Social workers are trained and well positioned to provide a multi-faceted approach to improve medication management for older adults. Their unique perspectives and skills are important in addressing the complex challenges of medication management.


Social isolation and domestic violence among female drug users.
The objective of this study was to examine the association between social isolation, domestic violence, and substance dependence among street-recruited female drug users. Hierarchical logistic regression was used to assess the independent contribution of social isolation and substance dependence to the likelihood that women will experience physical abuse. One hundred women (38.2%. N = 262) reported at least one incident of physical violence perpetrated by her most-recent sexual partner. Controlling for substance dependence and relationship status (the only significantly associated demographic variable), women reporting indicators of social isolation were more likely to have been physically abused by their most-recent sexual partners than nonisolated women. Substance dependence was not related significantly to domestic violence. Providers who have contact with female drug users should be aware of the high domestic violence rates and work to counterbalance the isolation these women may experience.


Ab initio study on structural and electronic properties of BanOm clusters.
Density-functional calculation within local density approximation, shows that the electronic property of a barium oxide cluster is strongly correlated with its equilibrium structure. The ground-state structures of BanOm (4 < or = n < or = 9,m < or = n) clusters can be classified into four categories: (a) compact, (b) dangling state, (c) F-center, and (d) stoichiometric. The compact cluster is metallic, almost no energy gap exists between the highest occupied and the lowest unoccupied molecular orbitals. The energy gap for the dangling state cluster is larger than that for the F-center cluster, while the stoichiometric cluster has the largest energy gap.


A computer system for timing and acoustical analysis of crackles: a study in cryptogenic fibrosing alveolitis.
A system for recording and processing lung crackles is described. These are detected by a microphone on the chest wall and recorded simultaneously with flow rate, tidal volume and oesophageal pressure on a four-channel tape recorder. The sound signal is subsequently digitized by an analog-to-digital converter and processed by a minicomputer, using the Time Series Language and the fast Fourier transform algorithm. A preliminary study on seven patients with cryptogenic fibrosing alveolitis (CFA) confirms that crackles typically occur at the end of inspiration; timing seems to be well related to inspired volume and esophageal pressure. Inspiratory crackles of CFA have a well-defined waveform: it consists of a starting component and a damped oscillation, which probably depends on the resonant frequency of the lung. The crackle energy content is mainly concentrated in the frequency range between 100 and 2 000 Hz, the spectrum shape being determined by the energy distribution between the two components of the waveform. This recording and processing system gives more complete information about crackles than auscultation does, allowing their quantification and reproducibility. It may be used to compare crackles in different diseases, and may be simplified and standardized for routine clinical use as an additional noninvasive diagnostic technique.


Periplasm, periplasmic spaces, and their relation to bacterial wall structure: novel secretion of selected periplasmic proteins from Pseudomonas aeruginosa.
A brief overview of thin sections of cryopreserved walls from select eubacteria will be presented to suggest that all bacteria have functional periplasms, but that these are not necessarily confined to a periplasmic space such as found in typical gram-negative bacteria. Pseudomonas aeruginosa contains many components in its periplasmic space, some of which are required for infection. Throughout its growth cycle, P. aeruginosa blebs-off membrane vesicles that can possess DNA, endotoxin, phospholipase, protease, hemolysin, alkaline phosphatase, and autolysin, each of which must have a molecular phase that resides in the periplasm. These membrane packets make good delivery systems to convey these components to other bacteria and, possibly, tissue. Aminoglycoside antibiotics, such as gentamicin, produce a serious perturbation on the bacterium's surface (separate from the ribosomal effect), which contributes to the killing of the microorganism. Antibiotics such as this increase the size and number of the membrane blebs, which could contribute to septic shock of patients under drug therapy.


Influence of excessive exercise on immunity, metabolism, and gut microbial diversity in an overtraining mice model.
The purpose of this study was to evaluate the negative influence of excessive exercise on immunity, substance and energy metabolism as well as gut microbiota in mice. Firstly, an overtraining model of Male Kunming mice was established by high-intensity swimming exercise for 4 weeks. Then, a series of evaluation indicators, including the routine blood analysis, immune organ coefficient, digestive enzymes, and aquaporins expression levels of small intestine and colon tissue, histological examinations of liver, spleen, small intestine, and colon, were determined based on this model. Furthermore, 16S rRNA gene sequencing was also employed to measure the microbial composition in gut. The results found that immune parameters, substance and energy metabolism of all mice was altered and disturbed after high-intensity swimming for 4 weeks, led to an atrophy of thymus and spleen as well as abnormal structural changes in liver when compared to non-swimming mice. Besides, excessive swimming mice had lower microbial diversity compared to non-swimming mice. However, there was no significant difference in gut microbial taxa between the two groups. The data indicated that excessive exercise exhibits negative impacts on immunity, substance and energy metabolism as well as gut microbial diversity.


Traditional medical records as a source of clinical data in the outpatient setting.
We conducted an observational study at a university hospital clinic to determine the success with which physicians find patient information using traditional hospital records as the source of data. We recorded 168 consecutive patient cases presented to attending physicians by internal medicine residents, and analyzed the transcripts to identify questions indicating that the physicians could not find patient information in the medical record. In 81 percent of the cases, physicians could not find all the patient information that they desired during a patient's visit. We performed thematic analysis to generate a set of 15 prototypical questions asked by physicians regarding patient information. The multiauthored medical record system we studied did not provide effective access to patient information for physicians making clinical decisions in an outpatient setting. Improved methods for addressing prototypical questions arising in routine practice are needed.


[Research on COVID-19 vaccination strategies in Singapore].
As of December 31, 2021, Singapore reported that 4 758 601 had completed at least one dose of COVID-19 vaccination, 4 714 655 had completed two doses of COVID-19 vaccination, and 2 207 341 had received one booster shot of COVID-19 vaccine. This article analyses the current performance of COVID-19 vaccination in Singapore, interprets the content of Singapore's National Vaccination Programme, and systematically introduces specific measures of COVID-19 vaccination in Singapore, such as door-to-door vaccination, vaccination differentiated management, and self-payment of medical expenses for those who refuse to be vaccinated, to provide reference for the COVID-19 vaccination in China.


Calculation algorithms alter the breath-by-breath gas exchange values when abrupt changes in ventilation occur.
The automatic metabolic units calculate breath-by-breath gas exchange from the expiratory data only, applying an algorithm ('expiration-only' algorithm) that neglects the changes in the lung gas stores. These last are theoretically taken into account by a recently proposed algorithm, based on an alternative view of the respiratory cycle ('alternative respiratory cycle' algorithm). The performance of the two algorithms was investigated where changes in the lung gas stores were induced by abrupt increases in ventilation above the physiological demand. Oxygen, carbon dioxide fractions and ventilatory flow were recorded at the mouth in 15 healthy subjects during quiet breathing and during 20-s hyperventilation manoeuvres performed at 5-min intervals in resting conditions. Oxygen uptakes and carbon dioxide exhalations were calculated throughout the acquisition periods by the two algorithms. Average ventilation amounted to 6·1 ± 1·4 l min-1 during quiet breathing and increased to 41·8 ± 27·2 l min-1 during the manoeuvres (P<0·01). During quiet breathing, the two algorithms provided overlapping gas exchange data and noise. Conversely, during hyperventilation, the 'alternative respiratory cycle' algorithm provided significantly lower gas exchange data as compared to the values yielded by the 'expiration-only' algorithm. For the first breath of hyperventilation, the average values provided by the two algorithms amounted to 0·37 ± 0·34 l min-1 versus 0·96 ± 0·73 l min-1 for O2 uptake and 0·45 ± 0·36 l min-1 versus 0·80 ± 0·58 l min-1 for exhaled CO2 (P<0·001 for both). When abrupt increases in ventilation occurred, such as those arising from a deep breath, the 'alternative respiratory cycle' algorithm was able to halve the artefactual gas exchange values as compared to the 'expiration-only' approach.


Dependence of anaphylactic histamine release from rat mast cells on cellular energy metabolism.
The relation between anaphylactic histamine release and the adenosine triphosphate (ATP) content of the mast cells was studied. The cells were incubated with glycolytic (2-deoxyglucose) and respiratory inhibitors (antimycin A and oligomycin) in order to decrease the ATP content of the cells prior to initiation of the release process by the antigen-antibody reaction. The secretory capacity of mast cells was less related to the cellular level of ATP at the time of activation of the release process by the antigen-antibody reaction than to the rate of cellular energy supply. Furthermore, mast cells were pretreated with 2-deoxyglucose. The release of histamine from these cells was reduced when respiratory inhibitors were added to the cell suspension 5 to 20 sec after exposure of the cells to antigen. This may indicate that the secretory process requires energy, and it seems necessary that energy should be produced as the release of histamine takes place.


Longitudinal assessment of the impact of orthodontic treatment on adolescents' quality of life: a comparison between boys and girls using a condition specific questionnaire.
The aim of this study was to compare the impact of the first year of wearing of a fixed orthodontic appliance on the Oral Health-Related Quality of Life (OHRQoL) between boys and girls, by means of a condition-specific instrument. The study included 69 adolescents aged 10 to 18 years, who were undergoing orthodontic treatment with a fixed appliance. Of the 69 adolescents, 38 were girls (55.1%) and 31 were boys (44.9%). They answered the Brazilian version of the Impact of Fixed Appliance Measure (B-IFAM) questionnaire three months (T1) and one year (T2) after the fixed appliance was installed. This questionnaire contains 43 questions, distributed across nine domains. The higher the scores, the more negative the perception of the adolescent concerning the impact of the fixed appliance on his/her OHRQoL. Sociodemographic and clinical variables were also analyzed, and statistical analysis was performed. For the domains, the effect size (the magnitude of the difference between girls and boys) and the minimal clinically important difference were also calculated. The adjusted regression showed that there was a significantly greater increase in the overall B-IFAM score in girls than in boys, indicating a more negative perception of the OHRQoL over the study time [Coefficient=11.77 (3.47- 20.60), p=0.006]. From T1 to T2, there was a significantly greater increase in the scores (more negative perception of OHRQoL over time) in girls than in boys for the domains aesthetics (p=0.034) and physical impact (p=0.011). These differences were clinically significant. The effect size (the magnitude of the difference) was moderate. The impact of wearing a fixed appliance on the OHRQoL was more negative in girls than in boys during the first year of orthodontic treatment.


[Molecular mechanisms of Glanzmann thrombasthenia caused by alphaII b P126H mutation: an in vitro experiment].
To explore the molecular mechanisms of Glanzmann thrombasthenia caused by alpha IIb P126H mutation. Eukaryotic vector of alpha IIb P126H was constructed by PCR site-directed mutagenesis and then co-transfected with eukaryotic vector PCDM8 II a expressing the subunit beta3 into human renal epithelial cells of the line 293& and Chinese hamster ovarian cancer cells of the line CHO after sequencing. The membrane expression of alpha IIb P126H mutant was analyzed by flow cytometry and the whole expression was confirmed by Western blotting. The alpha IIb P126H mutant subcellular localization was determined by laser confocal scanning microscopy. The 293T cells cotransfected with cDNAs of mutated alpha IIb and wild-type beta3 failed to express alpha II bbeta3 on the cell surface as shown by FACS. Western blotting of the cell lysate showed no detectable mature alpha IIb. Immunofluorescence studies demonstrated proa II bbeta3 complex colocalized with an endoplasmic reticulum (ER) marker, but showed minimal colocalization with an Golgi marker. The P126H mutation in alpha IIb prevents transport of the pro-alpha II bbeta3 complex from ER to the Golgi body, thus hindering its maturation and surface expression. The impaired alpha II bp33 transport is responsible for the thrombasthenia.


Assessing the facilitators and barriers of interdisciplinary team working in primary care using normalisation process theory: An integrative review.
Interdisciplinary team working is of paramount importance in the reform of primary care in order to provide cost-effective and comprehensive care. However, international research shows that it is not routine practice in many healthcare jurisdictions. It is imperative to understand levers and barriers to the implementation process. This review examines interdisciplinary team working in practice, in primary care, from the perspective of service providers and analyses 1 barriers and facilitators to implementation of interdisciplinary teams in primary care and 2 the main research gaps. An integrative review following the PRISMA guidelines was conducted. Following a search of 10 international databases, 8,827 titles were screened for relevance and 49 met the criteria. Quality of evidence was appraised using predetermined criteria. Data were analysed following the principles of framework analysis using Normalisation Process Theory (NPT), which has four constructs: sense making, enrolment, enactment, and appraisal. The literature is dominated by a focus on interdisciplinary working between physicians and nurses. There is a dearth of evidence about all NPT constructs apart from enactment. Physicians play a key role in encouraging the enrolment of others in primary care team working and in enabling effective divisions of labour in the team. The experience of interdisciplinary working emerged as a lever for its implementation, particularly where communication and respect were strong between professionals. A key lever for interdisciplinary team working in primary care is to get professionals working together and to learn from each other in practice. However, the evidence base is limited as it does not reflect the experiences of all primary care professionals and it is primarily about the enactment of team working. We need to know much more about the experiences of the full network of primary care professionals regarding all aspects of implementation work. International Prospective Register of Systematic Reviews PROSPERO 2015: CRD42015019362.


Decision support for hemodynamic management: from graphical displays to closed loop systems.
The way hemodynamic therapies are delivered today in anesthesia and critical care is suboptimal. Hemodynamic variables are not always understood correctly and used properly. The adoption of hemodynamic goal-directed strategies, known to be clinically useful, is poor. Ensuring therapies are delivered effectively is the goal of decision support tools and closed loop systems. Graphical displays (metaphor screens) may help clinicians to better capture and integrate the multivariable hemodynamic information. This may result in faster and more accurate diagnosis and therapeutic decisions. Graphical displays (target screens) have the potential to increase adherence to goal-directed strategies and ultimately improve patients' outcomes, but this remains to be confirmed by prospective studies. Closed loop systems are the ultimate solution to ensure therapies are delivered. However, most therapeutic decisions cannot be based on a limited number of output variables. Therefore, one should focus on the development of systems designed to relieve clinicians from very simple and repetitive tasks. Whether intraoperative goal-directed fluid therapy may be one of these tasks remains to be evaluated.


The effects of neural crest deletions on the development of sensory innervation patterns in embryonic chick hind limb.
Selected lumbosacral dorsal root ganglia (d.r.g.s) were eliminated from chick embryos by removing the parent neural crest, and the dermatomes and axonal projection patterns established in the hind limb by the remaining intact d.r.g.s were studied physiologically and/or anatomically. Dermatomes of intact d.r.g.s expanded into denervated skin regions, partially but never completely replacing the lost innervation; some skin regions consistently remained without apparent innervation. Dermatome expansion was detected in young embryos, soon after skin innervation was established, suggesting that skin sensory axons in operated embryos ignored their usual dermatome borders. The axonal pathways (nerve trunks) normally supplied by axons from the deleted d.r.g.s were missing, and axons from intact d.r.g.s were only rarely found in aberrant pathways. In contrast, the relative distribution of axons from intact d.r.g.s within their usual complement of pathways was altered, with axonal projections shifting toward, but not into the deleted pathways. Shifts in axonal projection patterns were observed in embryos prior to the onset of sensory cell death. Thus, d.r.g. deletions appeared to affect the initial growth of axons into the limb. Together these results suggest that during normal development competitive interactions among axons from neighbouring d.r.g.s play an important role in establishing the borders between dermatomes and in determining the distribution of axons within projection pathways in the limb.


Effect of wear of bearing surfaces on elastohydrodynamic lubrication of metal-on-metal hip implants.
The effect of geometry change of the bearing surfaces owing to wear on the elastohydrodynamic lubrication (EHL) of metal-on-metal (MOM) hip bearings has been investigated theoretically in the present study. A particular MOM Metasul bearing (Zimmer GmbH) was considered, and was tested in a hip simulator using diluted bovine serum. The geometry of the worn bearing surface was measured using a coordinate measuring machine (CMM) and was modelled theoretically on the assumption of spherical geometries determined from the maximum linear wear depth and the angle of the worn region. Both the CMM measurement and the theoretical calculation were directly incorporated into the elastohydrodynamic lubrication analysis. It was found that the geometry of the original machined bearing surfaces, particularly of the femoral head with its out-of-roundness, could lead to a large reduction in the predicted lubricant film thickness and an increase in pressure. However, these non-spherical deviations can be expected to be smoothed out quickly during the initial running-in period. For a given worn bearing surface, the predicted lubricant film thickness and pressure distribution, based on CMM measurement, were found to be in good overall agreement with those obtained with the theoretical model based on the maximum linear wear depth and the angle of the worn region. The gradual increase in linear wear during the running-in period resulted in an improvement in the conformity and consequently an increase in the predicted lubricant film thickness and a decrease in the pressure. For the Metasul bearing tested in an AMTI hip simulator, a maximum total linear wear depth of approximately 13 microm was measured after 1 million cycles and remained unchanged up to 5 million cycles. This resulted in a threefold increase in the predicted average lubricant film thickness. Consequently, it was possible for the Metasul bearing to achieve a fluid film lubrication regime during this period, and this was consistent with the minimal wear observed between 1 and 5 million cycles. However, under adverse in vivo conditions associated with start-up and stopping and depleted lubrication, wear of the bearing surfaces can still occur. An increase in the wear depth beyond a certain limit was shown to lead to the constriction of the lubricant film around the edge of the contact conjunction and consequently to a decrease in the lubricant film thickness. Continuous cycles of a running-in wear period followed by a steady state wear period may be inevitable in MOM hip implants. This highlights the importance of minimizing the wear in these devices during the initial running-in period, particularly from design and manufacturing points of view.


Neural ECM proteases in learning and synaptic plasticity.
Recent studies implicate extracellular proteases in synaptic plasticity, learning, and memory. The data are especially strong for such serine proteases as thrombin, tissue plasminogen activator, neurotrypsin, and neuropsin as well as matrix metalloproteinases, MMP-9 in particular. The role of those enzymes in the aforementioned phenomena is supported by the experimental results on the expression patterns (at the gene expression and protein and enzymatic activity levels) and functional studies, including knockout mice, specific inhibitors, etc. Counterintuitively, the studies have shown that the extracellular proteolysis is not responsible mainly for an overall degradation of the extracellular matrix (ECM) and loosening perisynaptic structures, but rather allows for releasing signaling molecules from the ECM, transsynaptic proteins, and latent form of growth factors. Notably, there are also indications implying those enzymes in the major neuropsychiatric disorders, probably by contributing to synaptic aberrations underlying such diseases as schizophrenia, bipolar, autism spectrum disorders, and drug addiction.


The spectrum of calvarial bone grafting: introduction of the vascularized calvarial bone flap.
Two techniques of calvarial bone grafting (split-thickness and single-table) are reviewed. A new vascularized bone flap based on the temporal vasculature is presented. The indications and relative advantages of each are discussed. The calvarial bone flap is emphasized and strongly recommended. Since the flap is vascularized and contains membranous bone, it is particularly suited for bone grafting in clinically unfavorable recipient sites, such as scarred or irradiated beds or the hypoplastic zygomatic-maxillary complex in the Treacher Collins syndrome.


The effects of zilpaterol hydrochloride and shade on blood metabolites of finishing beef steers.
The effects of feeding zilpaterol hydrochloride (ZH) and shade were evaluated on blood metabolites in finishing beef steers ( = 480). Cattle were fed 0 or 8.33 mg/kg of diet DM ZH for 21 d with a 3- or 4-d withdrawal before harvest and were housed in open or shaded pens. Blood samples were collected the day before ZH was fed and on the day the cattle were shipped to the commercial abattoir. Lactate concentration was not different between cattle fed ZH in open or shaded pens ( = 0.12). Nonetheless, a tendency for a diet × time interaction was detected for lactate concentration ( = 0.09), in which it was greater in cattle fed the control diet in open pens before being fed ZH. Cortisol concentration was less before and after ZH was fed ( = 0.01). Glucose was greater for cattle fed the control diet than cattle fed ZH for 21 d ( = 0.03). Cattle fed in open vs. shaded pens did not differ in glucose concentration ( = 0.12), whereas glucose concentrations were greater before ZH was fed than after ( = 0.02). In contrast, plasma urea nitrogen (PUN) concentration was not different in response to diet ( = 0.24), housing type ( = 0.65), or before vs. after being fed ZH ( = 0.60). Lactate concentrations were not different across diet or shade treatments before ZH was fed, whereas after ZH, lactate concentrations were greater in control cattle than cattle fed ZH. Additionally, cortisol was less after feeding ZH. Glucose was greater before than after feeding ZH.


Absorption of diazepam and its transfer through the blood-brain barrier after intraperitoneal administration in the rat.
Unlabeled diazepam of 0.9 mg/kg was administered i.p. to the rat of 21 days of age with a trace amount of [N-methyl-3H] diazepam and the drug concentrations in the blood and the brain tissues were determined at various time intervals. A two-compartment open model was applied and the absorption and distribution rate constants were distinctly determined on the theoretical basis established in the present study with the aid of a computer. The specific rate constants for absorption, distribution (k12 and k21) and elimination were 0.158, 0.015 and 0.136 and 0.013/min, respectively. A full description of the drug concentration in the central compartment as a function of time enabled us to calculate directly the transfer rate constants between the blood and the brain (k'12 and k'21), resulting in 4.49 and 2.66/min on the average of the five regions in the brain. A time-dependent change of the rate constants through the blood-brain barrier was suggested from a computer simulation.


Effect of decentration of wavefront-corrected intraocular lenses on the higher-order aberrations of the eye.
To evaluate the theoretical effect of decentration of aspherical intraocular lenses (IOLs) and wavefront-corrected IOLs up to the sixth order on higher-order aberrations (HOAs) (third through sixth order) of the eye. An aspherical IOL with HOAs of fourth-order spherical aberrations only (-0.287 microm with a 6-mm pupil) and a wavefront-corrected IOL with HOAs of equal magnitude and opposite from the corneal HOAs were created and laterally shifted up to 1 mm to simulate decentered IOLs. The residual HOAs for pupils of 3 to 6 mm were calculated by combining the HOAs from the cornea and the decentered IOL. Based on the residual HOAs, optical quality was rated by 3 criteria: the Marechal criterion, a diffraction-limited optical system with an aberration less than lambda/14; P(10), the lower 10th percentile of the corneal HOAs in this study group; and decreased HOA, residual ocular HOAs less than the corresponding corneal HOAs. Simulated implantation of the aspherical IOLs and wavefront-corrected IOLs was performed in 154 eyes of 94 patients aged 40 to 80 years. For a centered aspherical IOL and a 6-mm pupil, no eyes met the Marechal criterion, and the P(10) and decreased-HOA criteria were met by 46% and 93% of eyes, respectively. For a 6-mm pupil, the required centration was 0.47 mm to meet the decreased-HOA criterion in 50% of eyes. With a wavefront-corrected IOL and a 6-mm pupil, the centrations required to meet the criteria for 90% of eyes were 0.04 mm for the Marechal criterion, 0.36 mm for P(10), and 0.48 mm for the decreased-HOA criterion. Excellent centration is required to maximize the visual outcome of wavefront-corrected IOLs. With current surgical techniques, implantation of aspherical IOLs and wavefront-corrected IOLs will reduce total ocular HOAs below corneal HOAs in approximately 45% and 86% of eyes (6-mm pupil), respectively.


The Gender Lens: Development of a learning aid to introduce gender medicine.
Background and aim: Gender medicine takes into account biological and social differences between men and women in terms of prevalence and course of disease, diagnosis and therapy. Medical students should be made aware of this in the early stages of medical education. However, there is hardly any teaching material currently available. This article presents the adaption and first use of the German "Gender Lens," a tool to introduce gender medicine to medical students. Method: The original Canadian "Gender Lens Tool" was translated into German, tested by (n=5) teachers and adapted based on current scientific concepts. The instrument was applied and evaluated using qualitative methods in a student focus group (n=4). It was then piloted in a cohort of fourth-semester students (n=247) in a seminar addressing gender medicine. These experiences were evaluated using quantitative methods. Results: The German translation of the Gender Lens offers students a framework with which to analyze sex and gender differences in terms of the "prevalence, diagnosis, course, therapy and prevention" of a specific disease. Furthermore, it enables a refined search for causes such as "biological disposition, attitudes and behaviors, family and social networks, occupational and material circumstances and experiences with the health care system." Recommendations were received from the student groups regarding teaching methods. Male and female fourth-semester students agreed that the Gender Lens is useful as an introduction to gender medicine. Discussion: Initial experiences with the Gender Lens adapted for the German curriculum suggest that such a learning aid can contribute to raising awareness of gender medicine in medical students.


[Evaluation and incorporation of health technologies: process and methodology adopted by a high-complexity care university].
The demographic and epidemiological transitions tend to increase the role of hospitals in medical care. Within such organizations, effective, safe, and cost-effective health technologies ensure better quality of care and increase users' survival, thus emphasizing the importance of evaluation of such hospital-based technologies. This article aims to present a model for the evaluation and incorporation of technology in a teaching hospital that provides high-complexity care. The article describes an approach to methods/processes assessment that can be used easily by any hospital. The model allowed proper health technology assessment (HTA), thereby legitimizing decisions on technology incorporation by the hospital administration with high levels of acceptance and adoption by the clinical staff, suggesting that hospital-based HTA (provided that it is well-structured, with the support of institutional administration) can be a powerful tool for dissemination and valorization of HTA culture in an environment with the widest use and the greatest impact on the health system's budget.


Effect of Local Laser Treatment on the Strengthening of Thin-Walled Structures Fabricated from Non-Alloy Steel.
This paper describes the development of new metal-processing technologies that enable the control and improvement of the microstructure and properties of metals. This study investigates the impact of one such technology, laser treatment, on the surface of a thin sheet of non-alloy structural steel. This research aims to address a crucial challenge in expanding the industrial applications of thin-sheet steel products by developing a laser processing technology to create structural strengthening ribs, which can significantly influence the overall strength and stiffness of metal components.


Predicting response to vascular endothelial growth factor inhibitor and chemotherapy in metastatic colorectal cancer.
Bevacizumab improves progression free survival (PFS) and overall survival (OS) in metastatic colorectal cancer patients however currently there are no biomarkers that predict response to this treatment. The aim of this study was to assess if differential protein expression can differentiate patients who respond to chemotherapy and bevacizumab, and to assess if select proteins correlate with patient survival. Pre-treatment serum from patients with metastatic colorectal cancer (mCRC) treated with chemotherapy and bevacizumab were divided into responders and nonresponders based on their progression free survival (PFS). Serum samples underwent immunoaffinity depletion and protein expression was analysed using two-dimensional difference gel electrophoresis (2D-DIGE), followed by LC-MS/MS for protein identification. Validation on selected proteins was performed on serum and tissue samples from a larger cohort of patients using ELISA and immunohistochemistry, respectively (n = 68 and n = 95, respectively). 68 proteins were identified following LC-MS/MS analysis to be differentially expressed between the groups. Three proteins (apolipoprotein E (APOE), angiotensinogen (AGT) and vitamin D binding protein (DBP)) were selected for validation studies. Increasing APOE expression in the stroma was associated with shorter progression free survival (PFS) (p = 0.0001) and overall survival (OS) (p = 0.01), DBP expression (stroma) was associated with shorter OS (p = 0.037). Increasing APOE expression in the epithelium was associated with a longer PFS and OS, and AGT epithelial expression was associated with a longer PFS (all p < .05). Increasing serum AGT concentration was associated with shorter OS (p = 0.009). APOE, DBP and AGT identified were associated with survival outcomes in mCRC patients treated with chemotherapy and bevacizumab.


Design of peptides with high affinity binding to a monoclonal antibody as a basis for immunotherapy.
About half of the US population is sensitized to one or more allergens, as found by a National Health and Nutrition Examination Survey (NHANES). The most common treatment for seasonal allergic responses is the daily use of oral antihistamines, which can control some of the symptoms, but are not effective for nasal congestion, and can be debilitating in many patients. Peptide immunotherapy is a promising new approach to treat allergic airway diseases. The small size of the immunogens cannot lead to an unwanted allergic reaction in sensitized patients, and the production of peptides with sufficient amounts for immunotherapy is time- and cost-effective. However, it is not known what peptides are the most effective for an immunotherapy of allergens. We previously produced a unique monoclonal antibody (mAb) E58, which can inhibit the binding of multiple groups of mAbs and human IgEs from patients affected by the major group 1 allergens of ragweed (Amb a 1) and conifer pollens (Jun a 1, Cup s 1, and Cry j 1). Here, we demonstrated that a combined approach, starting from two linear E58 epitopes of the tree pollen allergen Jun a 1 and the ragweed pollen allergen Amb a 1, and residue modifications suggested by molecular docking calculations and peptide design could identify a large number of high affinity binding peptides. We propose that this combined experimental and computational approach by structural analysis of linear IgE epitopes and peptide design, can lead to potential new candidates for peptide immunotherapy.


Paracetamol Versus Ondansetron for Prevention of Postoperative Shivering in Liposuction Surgeries Under Combined General Epidural Anaesthesia: A Randomized Controlled Trial.
Postoperative shivering (POS) is considered one of the most common complications that is encountered by the anaesthetists worldwide. Despite using several treatment options, there has not been a clear consensus regarding this issue. This trial was conducted to investigate the efficacy and safety of paracetamol and ondansetron in preventing POS in patients undergoing liposuction procedures under combined general epidural anaesthesia. One hundred twenty patients scheduled for liposuction were randomly allocated to one of three groups: group P (paracetamol group) which received 1 g paracetamol intravenously, group O (ondansetron group) which received 8 mg of ondansetron intravenously, and group S (saline group), which received 100 mL normal saline intravenously; all medications were given postoperatively. The primary outcome was the incidence of POS, and the secondary outcomes included shivering score, tympanic temperature, and the occurrence of side effects. The incidence of occurrence of POS was found to be lower in groups P and O compared to group S with values of 25% and 37.50% vs. 77.50%, respectively, with a P value <0.001. Additionally, the severity of POS was found to be lower in groups P and O compared to group S (P <0.001). Tympanic temperature and complications were comparable between the groups with no significant differences. Prophylactic use of paracetamol or ondansetron at the end of the procedure was shown to be of great value in reducing the incidence and severity of POS, with no statistically significant difference between the paracetamol and ondansetron groups. Moreover, no significant drawbacks were reported as a result of using these medications.


Managing diabetes in patients with diabetes of long duration.
The purpose of this article is to review clinical issues related to the management of hyperglycemia in older patients with diabetes of long duration. Older adults represent an extensive proportion of patients with type 2 diabetes. Treatment goals need to be individualized to take into account comorbid conditions, life expectancy, diabetes complications, and the benefits of glycemic control. For both older patients and especially those with chronic renal insufficiency, the most important drug-related adverse effect to avoid is hypoglycemia, and avoidance of any severe hypoglycemia should be paramount. Patients with long duration of diabetes are often treated with insulin. Recent data show that glucagon-like peptide-1 receptor agonists may be used in combination with insulin for patients not achieving glycemic goals, with reductions in the doses of insulin used and with a low risk of hypoglycemia and possible weight loss.


PROTEOFORMER: deep proteome coverage through ribosome profiling and MS integration.
An increasing amount of studies integrate mRNA sequencing data into MS-based proteomics to complement the translation product search space. However, several factors, including extensive regulation of mRNA translation and the need for three- or six-frame-translation, impede the use of mRNA-seq data for the construction of a protein sequence search database. With that in mind, we developed the PROTEOFORMER tool that automatically processes data of the recently developed ribosome profiling method (sequencing of ribosome-protected mRNA fragments), resulting in genome-wide visualization of ribosome occupancy. Our tool also includes a translation initiation site calling algorithm allowing the delineation of the open reading frames (ORFs) of all translation products. A complete protein synthesis-based sequence database can thus be compiled for mass spectrometry-based identification. This approach increases the overall protein identification rates with 3% and 11% (improved and new identifications) for human and mouse, respectively, and enables proteome-wide detection of 5'-extended proteoforms, upstream ORF translation and near-cognate translation start sites. The PROTEOFORMER tool is available as a stand-alone pipeline and has been implemented in the galaxy framework for ease of use.


Identification of apoB-100 Peptide-Specific CD8+ T Cells in Atherosclerosis.
T cells are found in atherosclerotic plaques, with evidence supporting a potential role for CD8+ T cells in atherogenesis. Prior studies provide evidence of low-density lipoprotein and apoB-100 reactive T cells, yet specific epitopes relevant to the disease remain to be defined. The current study was undertaken to identify and characterize endogenous, antigen-specific CD8+ T cells in atherosclerosis. A peptide fragment of apoB-100 that tested positive for binding to the mouse MHC-I allele H2Kb was used to generate a fluorescent-labeled H2Kb pentamer and tested in apoE-/- mice. H2Kb pentamer(+)CD8+ T cells were higher in apoE-/- mice fed an atherogenic diet compared with those fed a normal chow. H2Kb pentamer (+)CD8+ T cells in atherogenic diet-fed mice had significantly increased effector memory phenotype with a shift in Vβ profile. H2Kb pentamer blocked lytic activity of CD8+ T cells from atherogenic diet-fed mice. Immunization of age-matched apoE-/- mice with the apoB-100 peptide altered the immune-dominant epitope of CD8+ T cells and reduced atherosclerosis. Our study provides evidence of a self-reactive, antigen-specific CD8+ T-cell population in apoE-/- mice. Immune modulation using the peptide antigen reduced atherosclerosis in apoE-/- mice.


The suprachiasmatic nucleus: a 25-year retrospective.
The suprachiasmatic nuclei (SCN) of the anterior hypothalamus contain the master circadian pacemaker in mammals. On the occasion of the 25th anniversary of the discovery of the SCN as the circadian clock, Charles A. Czeisler and Steven M. Reppert organized a meeting to review milestones and recent developments in the study of the SCN. The discovery that the SCN contain tissue necessary for generation of circadian rhythmicity was established by lesion studies published in 1972. The second phase of study demonstrated unequivocally that the SCN contain an autonomous circadian pacemaker. The principal studies in this period showed the presence of metabolic and electrical activity rhythms in the SCN in vivo and progressed to studies showing that the SCN maintain rhythmicity in vitro, demonstrating that the transplanted SCN can restore circadian function following destruction of the host SCN and ultimately showing that single SCN "clock cells" exhibit independent rhythms in firing rate. The third phase of study, aimed at identifying the biochemical and molecular mechanisms responsible for rhythmicity within the SCN, has begun with the identification of circadian mutants (tau mutant hamsters and Clock mutant mice) and the isolation of the Clock gene. This report traces the important steps forward in our understanding of the suprachiasmatic circadian clock by recounting the information presented at the SCN Silver Anniversary Celebration.


An osmium-ferricyanide staining method for the intercellular space in the small intestinal epithelium.
The post-fixation with osmium tetroxide and potassium ferricyanide (OsFeCN) produced dense deposits on the outer surface of the lateral plasma membrane in the mouse small intestinal epithelium. The deposits also filled up the intercellular space. No deposits were found on the surface of apical and basal plasma membranes. This staining pattern was highly reproducible when pH of the OsFeCN solution was adjusted to 7.0 by cacodylate buffer without calcium ion. Thus, our modified OsFeCN method is useful to selectively stain the intercellular space in epithelial tissues.


Nuclear genome-wide associations with mitochondrial heteroplasmy.
The role of the nuclear genome in maintaining the stability of the mitochondrial genome (mtDNA) is incompletely known. mtDNA sequence variants can exist in a state of heteroplasmy, which denotes the coexistence of organellar genomes with different sequences. Heteroplasmic variants that impair mitochondrial capacity cause disease, and the state of heteroplasmy itself is deleterious. However, mitochondrial heteroplasmy may provide an intermediate state in the emergence of novel mitochondrial haplogroups. We used genome-wide genotyping data from 982,072 European ancestry individuals to evaluate variation in mitochondrial heteroplasmy and to identify the regions of the nuclear genome that affect it. Age, sex, and mitochondrial haplogroup were associated with the extent of heteroplasmy. GWAS identified 20 loci for heteroplasmy that exceeded genome-wide significance. This included a region overlapping mitochondrial transcription factor A (TFAM), which has multiple roles in mtDNA packaging, replication, and transcription. These results show that mitochondrial heteroplasmy has a heritable nuclear component.


Clinical outcomes of patients with unresectable primary liver cancer treated with MR-guided stereotactic body radiation Therapy: A Six-Year experience.
Magnetic resonance-guided stereotactic body radiation therapy (MRgSBRT) with optional online adaptation has shown promise in delivering ablative doses to unresectable primary liver cancer. However, there remain limited data on the indications for online adaptation as well as dosimetric and longer-term clinical outcomes following MRgSBRT. Patients with unresectable hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and combined biphenotypic hepatocellular-cholangiocarcinoma (cHCC-CCA) who completed MRgSBRT to 50 Gy in 5 fractions between June of 2015 and December of 2021 were analyzed. The necessity of adaptive techniques was evaluated. The cumulative incidence of local progression was evaluated and survival and competing risk analyses were performed. Ninety-nine analyzable patients completed MRgSBRT during the study period and 54 % had planning target volumes (PTVs) within 1 cm of the duodenum, small bowel, or stomach at the time of simulation. Online adaptive RT was used in 53 % of patients to correct organ-at-risk constraint violation and/or to improve target coverage. In patients who underwent adaptive RT planning, online replanning resulted in superior target coverage when compared to projected, non-adaptive plans (median coverage ≥ 95 % at 47.5 Gy: 91 % [IQR: 82-96] before adaptation vs 95 % [IQR: 87-99] after adaptation, p < 0.01). The median follow-up for surviving patients was 34.2 months for patients with HCC and 10.1 months for patients with CCA/cHCC-CCA. For all patients, the 2-year cumulative incidence of local progression was 9.8 % (95 % CI: 1.5-18 %) for patients with HCC and 9.0 % (95 % CI: 0.1-18) for patients with CCA/cHCC-CCA. Grade 3 through 5 acute and late clinical gastrointestinal toxicities were observed in < 10 % of the patients. MRgSBRT, with the option for online adaptive planning when merited, allows delivery of ablative doses to primary liver tumors with excellent local control with acceptable toxicities. Additional studies evaluating the efficacy and safety of MRgSBRT in the treatment of primary liver cancer are warranted.


Functionalization of Single-walled Carbon Nanotubes with Thermo-reversible Block Copolymers and Characterization by Small-angle Neutron Scattering.
We demonstrate a protocol for single-walled carbon nanotube functionalization using thermo-sensitive PEO-PPO-PEO triblock copolymers in an aqueous solution. In a carbon nanotube/PEO105-PPO70-PEO105 (poloxamer 407) aqueous solution, the amphiphilic poloxamer 407 adsorbs onto the carbon nanotube surfaces and self-assembles into continuous layers, driven by intermolecular interactions between constituent molecules. The addition of 5-methylsalicylic acid changes the self-assembled structure from spherical-micellar to a cylindrical morphology. The fabricated poloxamer 407/carbon nanotube hybrid particles exhibit thermo-responsive structural features so that the density and thickness of poloxamer 407 layers are also reversibly controllable by varying temperature. The detailed structural properties of the poloxamer 407/carbon nanotube particles in suspension can be characterized by small-angle neutron scattering experiments and model fit analyses. The distinct curve shapes of the scattering intensities depending on temperature control or addition of aromatic additives are well described by a modified core-shell cylinder model consisting of a carbon nanotube core cylinder, a hydrophobic shell, and a hydrated polymer layer. This method can provide a simple but efficient way for the fabrication and in-situ characterization of carbon nanotube-based nano particles with a structure-tunable encapsulation.


Temporal and spatial evolution and obstacle diagnosis of resource and environment carrying capacity in the Loess Plateau.
Natural resources are scarce in the Loess Plateau, and the ecological environment is fragile. Sustainable development requires special attention to resource and environmental carrying capacity (RECC). This study selected 24 representative cities in five natural areas of the Loess Plateau; used the entropy-weight-based TOPSIS method to evaluate and analyze the RECC of each city and region from 2013 to 2018; established a diagnosis model to identify the obstacle factors restricting the improvement of RECC; and constructed the theoretical framework of the RECC system mechanism. The results show that the RECC of the Loess Plateau is increasing in general but is relatively small. The environmental and social subsystems have the highest and lowest carrying capacities, respectively. There is an evident contradiction between economic development and the environment. Population density, investment in technological innovation, per capita sown area, and per capita water resources are the main obstacles affecting the improvement of RECC in the Loess Plateau. Such evaluations and diagnoses can support ecological civilization and sustainable development.


Inversion of silica-stabilized emulsions induced by particle concentration.
Emulsions of equal volumes of a cyclic silicone oil and water stabilized by fumed silica nanoparticles alone can be inverted from oil-in-water (o/w) to water-in-oil (w/o) by simply increasing the concentration of particles. The phenomenon is found to be crucially dependent both on the inherent hydrophobicity of the particles and on their initial location. Inversion only occurs in systems with particles of intermediate hydrophobicity when dispersed in oil; emulsions prepared from the same particles but initially dispersed in water remain o/w at all particle concentrations. The stability and drop size distributions in the different emulsions are compared. Various hypotheses are put forward and argued to explain this novel inversion route including adsorption of oil onto particle surfaces, hysteresis of contact angle affecting particle wettability in situ, and the structure of particle dispersions in oil or water prior to emulsification inferred from rheology and light scattering measurements. We propose that the tendency for particles to behave more hydrophobically at higher concentrations in oil is due to the reduction in the effective silanol content at their surfaces as a result of gel formation via silanol-silanol hydrogen bonds. In water, solvation of particle surfaces prevents this from occurring and particles behave as hydrophilic ones at all concentrations. A concentration-induced change in particle wettability is thus advanced.


Epidermal Growth Factor Receptor Expression in Triple Negative and Nontriple Negative Breast Carcinomas.
The panel of markers used for molecular classification include estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor (HER)-2/neu, p53, Bcl-2 and basal markers like cytokeratin 5/6 or epidermal growth factor receptor (EGFR). Among these, EGFR plays an important role and is associated with bad prognosis. To study EGFR expression in triple negative breast carcinoma (TNBC) and non-TNBCs (NTNBCs). Fifty cases of breast carcinomas were classified and graded according to World Health Organization and Nottingham modification of Scarff-Bloom-Richardson (SBR) system, respectively. The age of the patients ranged from 28 to 69 years. Histological features such as necrosis, pushing borders, lymphocytic infiltrate and periductal elastosis were noted. The panel of markers used in our study included ER, PR, HER-2/neu and EGFR. EGFR expression was assessed based on membrane staining. Chi-square test was applied for statistical analysis to compare EGFR expression with hormonal status and prognostic factors. P < 0.05 was considered significant. The mean age was 49.8 ± 7.2 years. There were 44 (88%) infiltrating ductal carcinoma, 3 (6%) medullary carcinoma and 3 (6%) mucinous carcinoma. EGFR expression was common in young patients and was predominant in TNBC (89.47%), was also expressed in few cases of NTNBC. There was a positive correlation of EGFR expression (P = 0.03491) with a high grade. Medullary carcinomas were triple negative and strongly expressed EGFR. EGFR expression was inversely associated with ER status and showed strong association with necrosis and lymphocytic infiltrate, but not with pushing border and periductal elastosis. EGFR is an important marker to stratify patients with breast cancer according to molecular classification. Its expression correlated positively with young age, higher SBR grade, necrosis, lymphocytic infiltrate and inversely with hormonal receptor expression.


Simultaneous treatment of multiple basal cell carcinoma lesions.
We present a rare case of advanced basal cell carcinoma where multiple large lesions, located on the anterior chest wall and back, were treated simultaneously using tomotherapy (TomoTherapy HiArt; TomoTherapy Inc, Madison, WI). A 74-year-old man presented with seven to eight separate extensive lesions on his body, some with a duration of 7 years or more. The image-guidance component of tomotherapy allowed daily verification of the position of the target and critical structures, enabling accurate targeting in the vicinity of sensitive critical structures. Intensity-modulated radiotherapy on a conventional linear accelerator would have required junctioning of multiple complex plans, owing to the large treatment area, and most likely sequential treatment strategies to target anterior and posterior lesions. Helical tomotherapy allowed the three largest lesions to be treated simultaneously and thus eliminated the need for multiple courses of treatment.


[Clinicopathological study of 145 childhood rhabdomyosarcoma cases].
To study the clinicopathological, immunohistochemical and electron microscopic characteristics of pediatric rhabdomyosarcomas (RMS). One hundred and forty-five cases of pediatric rhabdomyosarcomas were studied by routine histological, immunohistochemical and electron microscopic studies. There were 97 male and 48 female patients with ages ranging from 4 months to 13 years and a mean of 4.2 years. The follow-up period of 100 patients was from 1 year to 20 years with a mean of 5 years after diagnosis. All cases were subtyped into the following histological categories: embryonal RMS, botryoid RMS, spindle cell RMS, alveolar RMS and solid RMS. Histopathological subtypes, tumor site and tumor stage correlated significantly with the patients' 5 years survival. The best prognosis was observed in spindle cell and botryoid RMS. Embryonal RMS carried an intermediate prognosis. Patients with alveolar RMS and solid RMS had the worst prognosis. Tumors involving bladder, head and neck carried a favorable clinical outcome. Patients with tumors involving trunk extremities retroperitoneum and pelvis did poorly. Immunohistochemically, all cases were positive for Vimentin. The positive staining rates for desmin, SMA and myoglobin were 78%, 75% and 37%, respectively. All tumors were negative for NSE, CD99 and LCA. Electron microscopy study showed features of myofilament and sarcomere in 10 of 15 cases. RMS is the most common soft tissue sarcoma of childhood. Immunohistochemistry and electron microscopy are helpful in diagnosis and classification of RMS.


Evaluation of canine adverse food reactions by patch testing with single proteins, single carbohydrates and commercial foods.
Adverse food reaction (AFR) is an important differential diagnosis for the pruritic dog. It is usually diagnosed by feeding an elimination diet with a novel protein and carbohydrate source for eight weeks followed by subsequent food provocation. A previous study demonstrated that patch testing dogs with foods had a high sensitivity and negative predictability for selection of elimination diet ingredients. The aim of this study was to investigate patch testing with proteins, carbohydrates and dry commercial dog food in dogs to determine whether there was value in patch testing to aid the diagnosis of canine adverse food reaction. Twenty five privately owned dogs, with confirmed AFR, underwent provocation trials with selected food antigens and patch testing. For proteins, carbohydrates and dry dog food the sensitivity of patch testing was 100%, 70% and 22.2%, respectively; the negative predictive values of patch testing were 100%, 79% and 72%. The positive predictive values of patch testing for proteins and carbohydrates were 75% and 74%, respectively. This study confirmed that patch testing may be useful for the selection of a suitable protein source for an elimination diet in dogs with suspected AFR, but not as a diagnostic tool for canine AFR. Results for proteins are more reliable than for carbohydrates and the majority of positive patch test reactions were observed with raw protein. Patch testing with commercial dog food does not seem to be useful.


Recovery of Cryptococcus neoformans from sputum using new technics for the isolation of fungi from sputum.
Three sputum-digesting agents, N-acetyl-l-cytseine, dithiothreitol, and pancreatin-trypsin, were shown to be equally effective in allowing for the isolation of Cryptococcus neoformans from sputum samples in quantitative comparisons. By quantitative plating on bird-seed medium it was also shown the centrifugation after digestion concentrated C. neoformans into a platable sediment and, further, that the organisms, when present in concentrations as low as 10 yeasts per ml. of sputum, could be isolated with much higher frequencies than when no digestion-centrifugation procedure was used.


Challenging the coherence of social justice as a shared nursing value.
Normative and prescriptive claims regarding social justice are often inadequately developed in the nursing literature and, in consequence, they must be rejected in their current form. Thus, claims regarding social justice are frequently presented as mere assertion (without clarification or supporting argument) or, alternatively, when assertions are supported that support may be weak (e.g. social justice is repeated juxtaposed against contentious assumptions regarding market disutility). This paper challenges the coherence of social justice as a shared nursing value and it is suggested that claims regarding the concept should be tempered.


Interleukin-10 overexpression improves the function of endothelial progenitor cells stimulated with TNF-α through the activation of the STAT3 signaling pathway.
Lentivirus vector-interleukin-10 green fluorescent protein (LV-IL-10-GFP) was transfected into endothelial progenitor cells (EPCs) in the present study. The aim was to detect the function of IL‑10‑modified EPCs and analyze the molecular mechanism. EPCs were cultured and identified by fluorescent labeling with the von Willebrand factor antibody, vascular endothelial growth factor (VEGF) receptor, Ulex europaeus agglutinin-1 and acetylated low‑density lipoprotein. Subsequently, EPCs were transfected with LV-IL-10-GFP and lentivirus vector‑noncontain‑GFP as the control group. Enzyme‑linked immunosorbent assay (ELISA) was used to detect the concentrations of cytokines in the supernatant with or without tumor necrosis factor‑α (TNF‑α). All types of cells were assessed by a tube formation assay, adhesion assay and migration assay induced with or without TNF‑α. Cell cycle was assessed by flow cytometry. Western blot analysis was applied to detect the expression of proteins in the cells. ELISA analysis showed that the levels of TNF‑α and IL‑8 in the supernatant without TNF‑α significantly decreased in EPC‑LV‑IL‑10‑GFP (P<0.05 for all). By contrast, the levels of IL‑10 and VEGF were contrasting in association with these. The concentrations of cytokines in the supernatant with TNF‑α were consistent to the supernatant without TNF‑α. There was no statistically significant difference in the average number of EPCs undergoing migration, adhesion, total length and cell growth among the EPC, EPC‑LV‑IL‑10‑GFP and EPC‑LV‑NC‑GFP groups without TNF‑α. Further study showed that EPC‑LV‑IL‑10‑GFP with TNF‑α significantly enhanced EPC migration, adhesion and promoted tube formation (P<0.05 for all). Western blot analysis revealed that the expression of VEGF, matrix metallopeptidase‑9 and phosphorylated‑signal transducer and activator of transcription 3 (p‑STAT3) significantly increased in the EPC‑LV‑IL‑10‑GFP group. Conversely, STAT‑3 expression decreased in the EPC‑LV‑IL‑10‑GFP group. The present study suggested that overexpression of IL‑10 had no effect on migration, adhesion, tubule formation and cell growth of EPCs without TNF‑α. Furthermore, in EPCs stimulated with TNF‑α, the overexpression of IL‑10 improved EPC function, including migration, adhesion and tubule formation by activating the STAT3 signal pathway.


Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives.
The antioxidant activities of curcumin, its natural demethoxy derivatives (demethoxycurcumin, Dmc and bisdemethoxycurcumin, Bdmc) and metabolite hydrogenated derivatives (tetrahydrocurcumin, THC; hexahydrocurcumin, HHC; octahydrocurcumin; OHC) were comparatively studied using 2,2-diphenyl-1-picrylhydrazyl (DDPH) radical, 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) induced linoleic oxidation and AAPH induced red blood cell hemolysis assays. Hydrogenated derivatives of curcumin exhibited stronger DPPH scavenging activity compared to curcumin and a reference antioxidant, trolox. The scavenging activity significantly decreased in the order THC>HHC=OHC>trolox>curcumin>Dmc>>>Bdmc. Stronger antioxidant activities toward lipid peroxidation and red blood cell hemolysis were also demonstrated in the hydrogenated derivatives. By the model of AAPH induced linoleic oxidation, the stoichiometric number of peroxyl radical that can be trapped per molecule (n) of hydrogenated derivatives were 3.4, 3.8 and 3.1 for THC, HHC and OHC, respectively. The number (n) of curcumin and Dmc were 2.7 and 2.0, respectively, which are comparable to trolox, while it was 1.4 for Bdmc. The inhibition of AAPH induced red blood cell hemolysis significantly decreased in the order OHC>THC=HHC>trolox>curcumin=Dmc. Results in all models demonstrated the lower antioxidant activity of the demethoxy derivatives, suggesting the ortho-methoxyphenolic groups of curcumin are involved in antioxidant activities. On the other hand, hydrogenation at conjugated double bonds of the central seven carbon chain and beta diketone of curcumin to THC, HHC and OHC remarkably enhance antioxidant activity.


Mycoplasma-dependent activation of normal lymphocytes: mitogenic potential of mycoplasmas for mouse lymphocytes.
Nonviable preparations of a wide variety of glucose-utilizing mycoplasma species, including Acholeplasma laidlawii and Spiroplasma citri, were found to be mitogenic for mouse lymphocytes. Particularly strong reactions were obtained with Mycoplasma synoviae, M. gallisepticum, M. pneumoniae, S. citri, and a strain of M. fermentans that was previously isolated from a leukemic patient. Nonviable preparations of arginine-utilizing mycoplasmas inhibited the uptake of [3H]thymidine by lymphocytes, but this effect could be reversed by heat treatment or arginine supplementation, and a stimulatory effect was then observed. Viable M. arthritidis was also found to have a mitogenic effect, as detected by an increased uptake of [3H]thymidine by normal lymphocytes and by autoradiographic techniques in which an increase in the numbers of transformed cells was seen. These observations provide the potential for enhanced immunological responsiveness or lymphokine-mediated inflammation in mycoplasma-infected hosts.


[Stimulation of endogenous TSH secretion and endocrine orbitopathy].
In 81 patients the thyrotoxicosis was controlled with antithyroid drugs only. Ophthalmopathy was seen in 53 patients when therapy was started. Patients with ophthalmopathy stage V or VI were excluded from this study. Maximal pathological eye signs were seen in 24 patients before starting therapy. Worsening occurred during treatment in 16 patients and some months after therapy was stopped in 13 patients. In summary, 40 patients passed a phase of subnormal thyroid hormone levels. Although stimulated, thyrotrophin secretion during this phase of antithyroid drug treatment took place in 19 patients a time related, reversible progression of endocrine ophthalmopathy was seen only in one subject. During medical treatment of a relapse in this patient worsening of eye signs had been seen once more despite thyrotrophin secretion was suppressed. The results are discussed in view of an immunologic concept of the pathogenesis of Graves' disease.


Malodorous consequences: what comprises negligence in anosmia litigation?
Our objectives were to evaluate factors raised in malpractice litigation in which plaintiffs alleged that physician negligence led to olfactory dysfunction. We analyzed publically available federal and court records using Westlaw, a widely used computerized legal database. Pertinent jury verdicts and settlements were comprehensively examined for alleged causes of malpractice (including procedures for iatrogenic causes), defendant specialty, patient demographics, and other factors raised in legal proceedings. Of 25 malpractice proceedings meeting inclusion criteria, 60.0% were resolved for the defendant, 12.0% were settled, and 28.0% had jury-awarded damages. Median payments were significant ($300,000 and $412,500 for settlements and awards, respectively). Otolaryngologists were the most frequently named defendants (68.0%), with the majority of iatrogenic cases (55.0%) related to rhinologic procedures. Associated medical events accompanying anosmia included dysgeusia, cerebrospinal fluid leaks, and meningitis. Other alleged factors included requiring additional surgery (80.0%), unnecessary procedures (47.4% of iatrogenic procedural cases), untimely diagnosis leading to anosmia (44.0%), inadequate informed consent (35.0%), dysgeusia (56.0%), and psychological sequelae (24.0%). Olfactory dysfunction can adversely affect quality of life and thus is a potential area for malpractice litigation. This is particularly true for iatrogenic causes of anosmia, especially following rhinologic procedures. Settlements and damages awarded were considerable, making an understanding of factors detailed in this analysis of paramount importance for the practicing otolaryngologist. This analysis reinforces the importance of explicitly including anosmia in a comprehensive informed consent process for any rhinologic procedure.


Age-related changes in hypothalamic androgen receptor and estrogen receptor alpha in male rats.
The control of reproductive function involves actions of sex steroids upon their nuclear receptors in the hypothalamus and preoptic area (POA). Whether hypothalamic hormone receptors change their expression in aging male mammals has not been extensively pursued, although such changes may underlie functional losses in reproductive physiology occurring with aging. We performed a stereologic analysis of immunoreactive androgen receptor (AR) and estrogen receptor alpha (ERalpha) cells in three POA nuclei of male Sprague-Dawley rats (anteroventral periventricular nucleus [AVPV], median preoptic area [MePO], and medial preoptic nucleus [MPN]), at young (3 months), middle-aged (12 months), and old (20 months) ages. Serum testosterone and estradiol levels were assayed. Testosterone concentrations decreased significantly and progressively with aging. Estradiol concentrations were significantly higher in middle-aged than either young or old rats. Stereologic analyses of the POA demonstrated that AR-immunoreactive cell numbers and density in the AVPV, MePO, and MPN were significantly higher in old compared with young or middle-aged rats. No change in the total number or density of ERalpha-immunoreactive cells was detected with age, although when cells were subdivided by intensity of immunolabeling, the most heavily labeled ERalpha cells increased in number with aging in the AVPV and MePO, and in density in the AVPV. There are several interpretations to our finding of substantially increased AR cell numbers during aging, including a potential compensatory upregulation of the AR under diminished testosterone concentrations. These results provide further information about how the neural targets of steroid hormones change with advancing age.


Perception of Workforce Skills Needed Among Public Health Professionals in Local Health Departments: Staff Versus Top Executives.
To examine how top executives and staff from local health departments (LHDs) perceive the importance of various types of workforce skills, and to assess the differences in the perception of the importance of these workforce skills between these 2 groups and among LHDs serving different-sized jurisdictions. Data for this study were drawn from the 2014 Public Health Workforce Interests and Needs Survey (PH WINS) and the 2015 Forces of Change survey. While PH WINS collected data from LHD staff, the Forces of Change survey was administered to LHD top executives. Ratings of perceived importance of workforce skills from LHD staff and top executives were compared. Overall, LHD workers at all levels believe that core competencies are important for their jobs. The perceived importance of these skills differed somewhat across supervisory level (nonsupervisory staff vs supervisory staff vs top executives). Communication was rated as one of the most important skills by all groups. For top executives, ensuring that programs are managed within budget constraints was the most important skill for their employees. However, this skill was rated much lower among staff. Policy development skills were rated to be of lowest importance by LHD leaders and staff. LHD leaders and staff agree on the relative importance of some competencies, although they also show some clear differences in the relative importance that they place on other competencies. It is essential to strengthen the communication between public health leaders and staff regarding the importance of workforce skills. More investigation is needed to assess whether and how gaps in staff competencies are addressed in the workforce development strategies.


The homing cursor: a tool for three-dimensional chromosome analysis.
When studying the three-dimensional shape of prophase chromosomes (or any other tubular structure), it is useful to represent these structures as a string of three-dimensional Cartesian coordinates along the medial axis. This procedure was automated in order to limit the number of human interactions and to improve reproducibility. In this paper the design, implementation, and validation of the automated method is presented. From the data presented it can be concluded that the cursor algorithm provides an objective and therefore reproducible method to trace the medial axes of prophase chromosomes automatically. This method could allow a more extensive understanding of the (changes in) chromosome organisation throughout the cell cycle, its relation to cell function, and the complex process of chromosome condensation.


Regional cerebral blood flow and language dominance: SPECT during intracarotid amobarbital testing.
We examined the relation between language dominance and regional cerebral blood flow (rCBF) during the intracarotid amobarbital procedure (IAP). A previous report limited to three patients suggested that dominant rather than nondominant hemisphere IAP may have a differential effect on rCBF. Behavioral assessment during the IAP also suggests that dominant hemisphere injection results in a differential effect on memory and affective symptoms rather than nondominant injection. Thirteen patients were assessed using single-photon emission CT (SPECT) brain imaging during both left and right IAP. The SPECTs were coregistered with the individual's MRI. Changes in rCBF during each IAP were compared with the patient's baseline SPECT. Nine patients had left hemisphere dominance, two were right dominant, and two had bilateral speech representation. In the left dominant subjects, left-hemisphere injection had a consistently greater effect on rCBF than right-hemisphere injection in the anterior (p < 0.005) and posterior (p < 0.01) temporal neocortex. There was also a trend for greater hypoperfusion in the frontal lobe of the left hemisphere. rCBF in the ipsilateral hippocampus was not significantly different after each injection (p > 0.05). In the two patients with right hemisphere speech, the reverse pattern was seen, with greater hypoperfusion after right (dominant) hemisphere injection. There was no consistent asymmetry in the two patients with bilateral speech. Dominant hemisphere IAP results in significantly greater hypoperfusion than does nondominant injection. These data provide a physiologic basis for behavioral differences noted after dominant versus nondominant IAP.


A retrospective study of optimal surgical management for occult breast carcinoma: Mastectomy or quadrantectomy?
The diagnosis and treatment for occult breast carcinoma (OBC) remain controversial because of no detectable primary lesions. We aimed to analyze optimal surgical management for OBC.A total of 26 female patients diagnosed with OBC, which were based on available criteria, were collected at a single clinic center from January 2005 to May 2016. We classified all patients into 4 groups: group A1, mastectomy with axillary lymph node dissection (ALND) + radiotherapy (RT); group A2, mastectomy with ALND; group B1, quadrantectomy with ALND + RT; group B2, quadrantectomy with ALND. Patient characteristics, disease-free survival, and overall survival were compared between groups.There were 14 cases in group A1, 5 cases in group A2, 4 cases in group B1, and 3 cases in group B2. Baseline characteristics were similar among groups. Compared with OBC patients treated with quadrantectomy, the disease-free survival (DFS) and overall survival (OS) rate of those treated with mastectomy had significantly improved (A1 vs. B1, DFS: hazard ratio [HR] 0.018, 95% confidence interval [CI] 0.001-0.241, P = .002; OS: HR 0.002, 95% CI 0.000-0.102, P = .002). Patients treated with radiotherapy had higher local recurrence and OS rate compared with patients treated with no radiotherapy on univariate survival analysis (A1 vs. A2, DFS: HR 0.018, 95% CI 0.001-0.240, P = .002; OS: HR 0.005, 95% CI 0.000-0.170, P = .003).The diagnosis of OBC will need continuous improvement with advances of diagnostic breast imaging. Modified radical mastectomy + RT is still a safe and effective choice.


Combined treatment of ulinastatin and tranexamic acid provides beneficial effects by inhibiting inflammatory and fibrinolytic response in patients undergoing heart valve replacement surgery.
To investigate the effect of ulinastatin and tranexamic acid administered alone or in combination on inflammatory cytokines and fibrinolytic system in patients undergoing heart valve replacement surgery during cardiopulmonary bypass (CPB). CPB-induced fibrinolytic hyperfunction and systemic inflammatory response syndrome (SIRS) are the leading causes responsible for the occurrence of postsurgical complications such as postsurgical cardiac insufficiency and lung injury, which may lead to an increase in postsurgical bleeding, prolongation of hospital stay, and increased costs. One hundred twenty patients undergoing heart valve replacement surgery during CPB were randomly assigned into 4 groups of 30 patients each: blank control group (Group C), tranexamic acid group (Group T), ulinastatin group (Group U), and tranexamic acid-ulinastatin combination group (Group D). Physiological saline, tranexamic acid, ulinastatin, and a combination of tranexamic acid and ulinastatin were given to each group, respectively. Arterial blood was collected from the radial artery at 4 time points: after induction of anesthesia (T1), unclamping the ascending aorta (T2), and at 1 hour (T3) and 24 hours (T4) after CPB. The levels of plasma tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), neutrophil elastase (NE), and the concentrations of tissue plasminogen activator (t-PA) and α2-antiplasmin (α2-AP) were detected. The changes in the volume of pericardial mediastinal drainage after surgery were observed and recorded. The plasma TNF-α, IL-6, and NE levels significantly increased in patients from all 4 groups at time points of T2, T3, and T4 in comparison to those before CPB (P < .05), and the plasma TNF-α and IL-6 levels in groups U and D were significantly lower than those in the other 2 groups (P < .05). The plasma t-PA, α2-AP, and D-dimer concentrations significantly increased in patients from all 4 groups at T2 and T3 compared with those before CPB (P < .05), and the plasma t-PA and D-dimer concentrations were significantly lower in groups T and D than those in groups U and C (P < .05) at T2 and T3. The plasma α2-AP concentrations in groups T and D were significantly higher than those in Group C at T3 (P < .05). The volumes of pericardial mediastinal drainage per body surface area were significantly lower in groups T and D than those in Group C 6 hours after the surgery (P < .05). Ulinastatin inhibits the release of inflammatory medium and reduces the inflammatory response during CPB. Tranexamic acid can effectively inhibit the fibrinolytic hyperfunction caused by CPB and thus decreases postsurgical bleeding. In addition, it exhibits a minor anti-inflammatory response. As a consequence, a combined treatment of ulinastatin and tranexamic acid reduces postsurgical bleeding and shortens postoperative hospital stay in patients undergoing heart valve replacement surgery.


[Sleep in neurodegenerative disorders].
Neurodegenerative disorders are a group of heterogeneous, progressive disorders of varying etiology that affect one or more systems. They occur predominantly at older age, during which the structure and amount of sleep undergo changes. Neurodegenerative processes cause structural changes of the sleep/wake generators in the brainstem which result in disorders such as daytime sleepiness, insomnia, sleep-related movement and breathing disturbances, and disorders of the circadian rhythms. Some sleep disorders manifest years before the onset of neurodegenerative disorders and may serve as predictors. Polysomnography shows sleep fragmentation, tonic or phasic movements of the extremities, alteration of respiratory muscles, reduced slow wave sleep, REM sleep absence or without muscle atonia, increased arousal or wake activity, epileptiform EEG activity, and changes in sleep-related breathing. Very frequently, REM sleep behaviour disorder is associated with neurodegenerative disorders. In this overview we present symptoms, pathophysiology, and polysomnographic findings of sleep disorders in prevalent neurodegenerative disorders.


Association of calpain-10 rs2975760 polymorphism with type 2 diabetes mellitus: a meta-analysis.
Type 2 diabetes mellitus (T2DM) accounts for the majority of diabetes cases and affects a significant proportion of the adult population worldwide. Calpain-10 has been implicated in the development of type 2 diabetes, and some polymorphisms in the CAPN10 gene have been associated with an increased risk of developing this disease. Several molecular epidemiological studies were conducted in recent years to evaluate the association between the CAPN10 rs2975760 polymorphism and T2DM risk in diverse populations. However, the results remain conflicting rather than conclusive. We performed a meta-analysis of 8 case-control studies that included 2758 T2DM cases and 2762 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confi dence intervals (CIs). Overall, this meta-analysis showed that the CAPN10 rs2975760 polymorphism was not associated with a significantly type 2 diabetes risk in three genetic models. However, after excluding two study for its heterogeneity, a significantly increased risk was found in all comparisons (for C vs T: OR=1.14, 95% CI=1.03-1.27, I (2)=0, P heterpgeneity=0.420, P b=0.012; for TC vs TT: OR=1.15, 95% CI=1.01-1.30, I (2)=3.8%, P heterpgeneity=0.392, P b=0.030; for CC+TC vs TT: OR=1.16, 95% CI=1.03-1.31, I (2)=3.7%, P heterpgeneity=0.393, P b=0.015). No publication bias was found in the present study. This meta-analysis suggests that the C allele of the CAPN10 rs2975760 polymorphism is associated with an increased T2DM risk. Further large and well-designed studies are needed to confi rm this association.


High-dynamic-range fluorescence laminar optical tomography (HDR-FLOT).
Three-dimensional fluorescence laminar optical tomography (FLOT) can achieve resolutions of 100-200 µm and penetration depths of 2-3 mm. FLOT has been used in tissue engineering, neuroscience, as well as oncology. The limited dynamic range of the charge-coupled device-based system makes it difficult to image fluorescent samples with a large concentration difference, limits its penetration depth, and diminishes the quantitative accuracy of 3D reconstruction data. Here, incorporating the high-dynamic-range (HDR) method widely used in digital cameras, we present HDR-FLOT, increasing penetration depth and improving the ability to image fluorescent samples with a large concentration difference. The method was tested using an agar phantom and a B6 mouse for brain imaging in vivo.


Analyzability of Photoplethysmographic Smartwatch Data by the Preventicus Heartbeats Algorithm During Everyday Life: Feasibility Study.
Continuous heart rate monitoring via mobile health technologies based on photoplethysmography (PPG) has great potential for the early detection of sustained cardiac arrhythmias such as atrial fibrillation. However, PPG measurements are impaired by motion artifacts. The aim of this investigation was to evaluate the analyzability of smartwatch-derived PPG data during everyday life and to determine the relationship between the analyzability of the data and the activity level of the participant. A total of 41 (19 female and 22 male) adults in good cardiovascular health (aged 19-79 years) continuously wore a smartwatch equipped with a PPG sensor and a 3D accelerometer (Cardio Watch 287, Corsano Health BV) for a period of 24 hours that represented their individual daily routine. For each participant, smartwatch data were analyzed on a 1-minute basis by an algorithm designed for heart rhythm analysis (Preventicus Heartbeats, Preventicus GmbH). As outcomes, the percentage of analyzable data (PAD) and the mean acceleration (ACC) were calculated. To map changes of the ACC and PAD over the course of one day, the 24-hour period was divided into 8 subintervals comprising 3 hours each. Univariate analysis of variance showed a large effect (ηp2> 0.6; P<.001) of time interval (phase) on the ACC and PAD. The PAD ranged between 34% and 100%, with an average of 71.5% for the whole day, which is equivalent to a period of 17.2 hours. Between midnight and 6 AM, the mean values were the highest for the PAD (>94%) and the lowest for the ACC (<6×10-3 m/s2). Regardless of the time of the day, the correlation between the PAD and ACC was strong (r=-0.64). A linear regression analysis for the averaged data resulted in an almost perfect coefficient of determination (r2=0.99). This study showed a large relationship between the activity level and the analyzability of smartwatch-derived PPG data. Given the high yield of analyzable data during the nighttime, continuous arrhythmia screening seems particularly effective during sleep phases.


Expression of SPRR3 is associated with tumor cell proliferation and invasion in glioblastoma multiforme.
Esophagin, also known as small proline-rich protein 3 (SPRR3), has been demonstrated to be important in the initiation and progression of numerous types of tumor, including colorectal and breast cancer. However, studies concerning the biological functions of SPRR3 in glioblastoma multiforme (GBM) are limited. Therefore, we aimed to identify the functions and molecular mechanisms underlying the role of SPRR3 in GBM. Hypomethylation of SPRR3 was observed and associated with a poor clinical outcome in GBM patients compared with healthy individuals by using gene methylation profiling. The present study was performed to investigate the expression status and effects of SPRR3 in GBM. The U251 cell line was used in the functional analyses. Cell growth was examined by MTT and colony formation assay. Cell invasion was measured using the Transwell invasion assay. The expression of SPRR3 in tissue samples was examined by immunohistochemistry. The results revealed that the overexpression of SPRR3 accelerates U251 cell proliferation and invasion. It was also observed that SPRR3 was markedly upregulated in 72.7% of GBM samples (24/33) compared with the normal tissue. These results suggest that an increased expression of SPRR3 is involved in tumorigenesis.


Absent effect of zinc deficiency on the oxidative stress of erythrocytes in chronic uremic rats.
Both anemia and zinc deficiency are commonly observed in patients with chronic uremia. Oxidative stress of red blood cells (RBC) has been suggested to participate in the development of anemia in these patients with chronic uremia due to reduced life span of RBC. Whether zinc deficiency aggravates the effect of oxidative stress on RBC of chronic uremia is still not understood. We thus performed the study to determine the influence of zinc deficiency on the oxidative stress of RBC in uremic rats. Zinc deficiency was induced by long-term dietary zinc deficiency. Five-sixth nephrectomy (5/6 Nx) was used to produce chronic uremia. Experiment was carried out in the following five groups: normal control (NL), chronic uremia (Nx), chronic uremia + dietary zinc deficiency (Nx-D), Nx-D + zinc supplement (Nx-DZ) and Chronic uremia + pair-fed (Nx-PF). Osmotic fragility and lipid peroxidation of RBC were used to evaluate the oxidative stress of RBC. Five weeks after 5/6 nephrectomy (Nx), 5/6 Nx rats present a syndrome of uremia to elevate the levels of plasma creatinine and urea, and reduce the level of plasma zinc (1.12 +/- 0.08 vs 1.35 +/- 0.05 ug/ml). But they does not find to produce anemia and to increase osmotic fragility and lipid peroxidation in RBC. Dietary zinc deficiency in Nx-D group produced severe anorexia and reduced plasma zinc and selenium levels and the activity of RBC-GPX. Yet in Nx-D rats, osmotic fragility and susceptibility of lipid peroxidation in red cells did not increase, because of the increase of plasma copper level (1.85 +/- 0.3 vs 1.41 +/- 0.05 microg/ml) and RBC-SOD activity (1.95 +/- 0.27 vs 0.78 +/- 0.05 unit/g Hb). Zinc supplement in Nx-D rats (Nx-DZ group) recovered the appetite and normalized the levels of plasma zinc, copper and selenium. Food restriction in 5/6 Nx rats (Nx-PF group) decreased plasma copper level and increased osmotic fragility of RBC and elevated the susceptibility of lipid peroxidation after stressing RBC with H2O2 Because Nx-PF rats presented a lower RBC-SOD activity (0.44 +/- 0.11 vs 0.78 +/- 0.05 unit/g Hb) and a lower plasma copper level. We further found a positive relationship (r=0. 802,p<0.01) between plasma copper level and RBC-SOD activity in normal and uremic rats. This study suggests that RBC-SOD activity may play an important role in preventing RBC oxidative stress. Plasma copper level may be a marker of RBC-SOD activity. We conclude, in chronic uremia, zinc deficiency doses not result in RBC oxidative stress as plasma copper level is normal, but may affect the absorption of intestinal nutrition.


Lest we forget Hansen's disease (leprosy): an unusual presentation with an acute onset of inflammatory polyarthritis and the rheumatology experience.
Several forms of arthritis and rheumatism can sometimes complicate leprosy. However, its presentation as an acute onset arthritis is unusual. We report two adult male naïve patients who presented to our rheumatology outpatient clinic with acute onset inflammatory polyarthritis, skin rash and mild sensory neurodeficit. Borderline lepromatous leprosy (in type I lepra reaction) was diagnosed. We also refer to 19 case records of Hansen arthritis in the clinic database (1998-2007) from approximately 35,000 patients and a community study to highlight the missed diagnosis of Hansen's disease and its unusual association with rheumatoid arthritis. In countries like India where leprosy is endemic, this disease also merits attention in rheumatology clinics.


Theophylline clearance. Lack of effect of influenza vaccination and ascorbic acid.
Warnings have been issued regarding safety in the use of theophylline preparations in patients receiving influenza vaccination. These were prompted by reports that influenza vaccination caused inhibition of metabolism of theophylline and aminopyrine. Previous work has indicated a role for ascorbic acid in mixed function oxidase activity, and ascorbic acid is commonly used by the public. We studied the effect of influenza vaccination and ascorbic acid supplementation on the rate of elimination of theophylline. In 11 patients and 12 normal subjects no significant effects of influenza vaccination or ascorbic acid supplementation on theophylline clearance, serum half-life, or apparent volume of distribution were detected (p greater than 0.3). We conclude that neither influenza vaccination nor ascorbic acid supplementation induce a predictable effect on theophylline disposition.


Synaptophysin. A new marker for pancreatic neuroendocrine tumors.
Synaptophysin (SYP) is a glycoprotein recently isolated from presynaptic vesicles of bovine neurons. Initial studies have demonstrated its presence in neurons in the brain, spinal cord and retina, and in adrenal medullary cells. A subsequent study demonstrated it in pancreatic islet cells and certain neuroendocrine (NE) neoplasms, including several pancreatic islet cell tumors. Based on these preliminary observations, we examined, by immunohistochemistry, conventionally fixed, paraffin sections of 57 pancreatic endocrine tumors with a monoclonal antibody to SYP. Furthermore, we compared the SYP immunoreactivity of 30 of these same tumors with that of neuron-specific enolase (NSE) and of chromogranin (CG). SYP was demonstrated in all but one of the 57 tumors. In the comparative study, for which material was available in only 30 cases, SYP and NSE were present in 29 of the tumors, whereas CG was seen in only 15 cases. We conclude that SYP is a highly sensitive and useful marker for pancreatic NE neoplasms. Moreover, in view of the increasingly evident limited specificity of NSE, SYP should be considered the marker of choice for pancreatic NE neoplasms.