Traces matter: Targeted optimization of monoclonal antibody N-glycosylation based on/by implementing automated high-throughput trace element screening.
The use of high-throughput systems in cell culture process optimization offers various opportunities in biopharmaceutical process development. Here we describe the potential for acceleration and enhancement of product quality optimization and de novo bioprocess design regarding monoclonal antibody N-glycosylation by using an iterative statistical Design of Experiments (DoE) strategy based on our automated microtiter plate-based system for suspension cell culture. In our example, the combination of an initial screening of trace metal building blocks with a comprehensive DoE-based screening of 13 different trace elemental ions at three concentration levels in one run revealed most effective levers for N-glycan processing and biomass formation. Obtained results served to evaluate optimal concentration ranges and the right supplementation timing of relevant trace elements at shake flask and 2 L bioreactor scale. This setup identified manganese, copper, zinc, and iron as major factors. Manganese and copper acted as inverse key players in N-glycosylation, showing a positive effect of manganese and a negative effect of copper on glycan maturation in a zinc-dependent manner. Zinc and iron similarly improved cell growth and biomass formation. These findings allowed determining optimal concentration ranges for all four trace elements to establish control on desired product quality attributes regarding premature afucosylated and mature galactosylated glycan species. Our results demonstrates the power of combining robotics with DoE screening to enhance product quality optimization and to improve process understanding, thus, enabling targeted product quality control.


Effects of Zearalenone Exposure on the TGF-β1/Smad3 Signaling Pathway and the Expression of Proliferation or Apoptosis Related Genes of Post-Weaning Gilts.
Zearalenone (ZEA) is an estrogenic toxin produced by Fusarium species, which is widely distributed and posed a great health risk to both humans and farm animals. Reproductive disorders associated with ZEA such as premature puberty, infertility and abortion have plagued the animal husbandry, but the molecular mechanism is unclear. Because transforming growth factor-β1 (TGF-β1) signaling pathway is involved in the proliferation and apoptosis of cells, proliferating cell nuclear antigen (PCNA), B-cell lymphoma/leukemia-2 (BCL-2) and BCL-2 associated X protein (BAX) that all play indispensable roles in the normal development of the uterus, it is hypothesized that ZEA induces reproductive disorders is closely related to the expression of these genes. The objective of this study was to assess the effects of dietary ZEA at the concentrations of 0.5 to 1.5 mg/kg on the mRNA and protein expression of these genes in the uteri of post-weaning gilts and to explore the possible molecular mechanism. Forty healthy post-weaning female piglets (Duroc × Landrace × Large White) aged 38 d were randomly allocated to basal diet supplemented with 0 (Control), 0.5 (ZEA0.5), 1.0 (ZEA1.0), or 1.5 (ZEA1.5) mg/kg purified ZEA, and fed for 35 d. Piglets were euthanized at the end of the experiment and samples were taken and subjected to immunohistochemistry, qRT-PCR and Western blot analyses. The relative mRNA expressions of PCNA, BCL-2 and Smad3 in the uteri of post-weaning gilts increased linearly (p < 0.05) and quadratically (p < 0.05) as ZEA concentration increased in the diet. The relative protein expressions of PCNA, BAX, BCL-2, TGF-β1, Smad3, and phosphorylated Smad3 (p-Smad3) in the uteri of post-weaning gilts increased linearly (p < 0.05) and quadratically (p < 0.001) with an increasing level of ZEA. The results showed that uterine cells in the ZEA (0.5-1.5 mg/kg) treatments were in a high proliferation state, indicating that ZEA could accelerate the proliferation of uteri and promote the development of the uteri. At the same time, the results suggested that ZEA activates the TGF-β1/Smad3 signaling pathway, suggesting it plays an important role in accelerating the development of the uterus.


Distal Deletion of Chromosome 11q Encompassing Jacobsen Syndrome without Platelet Abnormality.
Terminal 11q deletion, known as Jacobsen syndrome (JBS), is a rare genetic disorder associated with numerous dysmorphic features. We studied two cases with multiple congenital anomalies that were cytogenetically detected with deletions on 11q encompassing JBS region: 46,XX,der(11) del(11)(q24). Array comparative genomic hybridization (aCGH) analysis confirmed partial deletion of 11.8-11.9 Mb at 11q24.1q25 (case 1) and 13.9-14 Mb deletion at 11q23.3q25 together with 7.3-7.6 Mb duplication at 12q24.32q24.33 (case 2). Dysmorphism because of the partial duplication of 12q was not overtly decipherable over the Jacobsen phenotype except for a triangular facial profile. Aberrant chromosome 11 was inherited from phenotypically normal father, carrier of balanced translocation 46,XY,t(11;12)(q23.3; q24.32). In the present study, both cases had phenotypes that were milder than the ones described in literature despite having large deletion size. Most prominent features in classical JBS is thrombocytopenia, which was absent in both these cases. Therefore, detailed functional analysis of terminal 11q region is warranted to elucidate etiology of JBS and their clinical presentation.


Logistics of transfusion support for patients with massive hemorrhage.
Traditionally, trauma resuscitation protocols have advocated sequential administration of therapeutic components, beginning with crystalloid solutions infused to replace lost intravascular volume. However, rapid restoration of the components of blood is essential for ensuring adequate tissue perfusion and for preventing acidosis, coagulopathy, and hypothermia, referred to as the 'lethal triad' in trauma settings. The review summarizes practical approaches for transfusion support of patients with massive hemorrhage. Massive transfusion protocols for blood transfusion support are reviewed, including practical considerations from our own. We maintain an inventory of thawed, previously frozen plasma (four units each of blood group O and A), which can be issued immediately for patients in whom the blood type is known. As frozen plasma requires 45 min to thaw, liquid AB plasma (26 day outdate) functions as an excellent alternative, particularly for patients with unknown or blood group B or AB types. Close monitoring of bleeding and coagulation in trauma patients allows goal-directed transfusions to optimize patients' coagulation, reduce exposure to blood products, and to improve patient outcomes. Future studies are needed to understand and demonstrate improved patient outcomes.


Changes in arterial and transcutaneous oxygen and carbon dioxide tensions during and after voluntary hyperventilation.
The purposes of our study were (1) to investigate whether a 3-min short-term hyperventilation leads to posthyperventilatory hypoxemia and (2) to assess the role of transcutaneous blood gas measurements for monitoring oxygen and carbon dioxide changes during the after the test. In 10 male volunteers arterial and transcutaneous blood gases were measured simultaneously before, during and after a 3-min voluntary hyperventilation maneuver. Baseline arterial PO2 increased from 13.7 +/- 0.4 kPa (103 +/- 3 mm Hg) to 18.6 +/- 0.3 kPa (139 +/- 2.3 mm Hg; p < 0.005 compared to baseline) during hyperventilation. After the provocation test posthyperventilatory hypoxemia occurred with a minimal mean value of 7.8 +/- 1.3 kPa (58.5 +/- 9.8 mm Hg; p < 0.05 compared to baseline). Whereas close agreement between arterial and transcutaneous measurements was obtained for carbon dioxide values before hyperventilation, transcutaneous O2 consistently underestimated arterial O2. A short-term over-breathing of 3 min causes a significant posthyperventilatory hypoxemia. We hypothesize that posthyperventilatory hypoxemia is caused by hypopnea as a result of depleted CO2 body stores. Noninvasive transcutaneous blood gas measurements are not reliable for monitoring blood gas changes during and after hyperventilation, most probably because of the slow response time of the electrodes and the reflex vasoconstriction of the skin vessels.


Stochastic assembly produces heterogeneous communities in the Caenorhabditis elegans intestine.
Host-associated bacterial communities vary extensively between individuals, but it can be very difficult to determine the sources of this heterogeneity. Here, we demonstrate that stochastic bacterial community assembly in the Caenorhabditis elegans intestine is sufficient to produce strong interworm heterogeneity in community composition. When worms are fed with two neutrally competing, fluorescently labeled bacterial strains, we observe stochastically driven bimodality in community composition, in which approximately half of the worms are dominated by each bacterial strain. A simple model incorporating stochastic colonization suggests that heterogeneity between worms is driven by the low rate at which bacteria successfully establish new intestinal colonies. We can increase this rate experimentally by feeding worms at high bacterial density; in these conditions, the bimodality disappears. These results demonstrate that demographic noise is a potentially important driver of diversity in bacterial community formation and suggest a role for C. elegans as a model system for ecology of host-associated communities.


Notes from the field: investigation of leptospirosis underreporting - Puerto Rico, 2010.
Leptospirosis, a zoonosis transmitted through contact with the urine of infected animals, either directly or through exposure to contaminated water or soil, is a frequent cause of acute febrile illness (AFI) and can be difficult to distinguish from dengue in areas where both are endemic. Approximately 5%-10% of patients with leptospirosis are affected severely; the case-fatality rate in those with severe disease is 5%-15%. Early identification of leptospirosis cases and early administration of penicillin G or doxycycline can reduce the duration and severity of illness.


Influence of sampling time on assessment of potential doubling time.
Potential doubling time (Tpot), S-phase transit time (Ts), and labeling index were determined in three experimental rodent tumors by in vivo incorporation of bromodeoxyuridine and flow cytometry. The kinetic parameters were derived from the relative movement method at varying sampling times (time between injection of bromodeoxyuridine and tumor excision). Ts and Tpot were close to the expected (extrapolated) values of the two parameters with sampling time within the range 60-100% of the expected Ts. With short sampling time, Ts and Tpot were considerably over- or underestimated. By use of the original method by (Begg et al., Cytometry 6:620-626, 1985), the Tpot came out with a twofold overestimation with a short sampling time. Generally, modified methods for calculation of Ts did not improve the results. When Tpot is measured in human tumors, there is no a priori knowledge of the kinetic parameters. Consequently, the sampling time must be based on the general experience of tumor cell kinetics in the specific tumor type measured. A relatively long sampling time should be aimed for when measuring Tpot in human tumors. With proper sampling time, Tpot assessed by flow cytometry was found to be a precise and reproducible parameter.


Fibrin sealant: scientific rationale, production methods, properties, and current clinical use.
Fibrin sealant is a complex plasma-derived product which is increasingly used as a biodegradable tissue adhesive or sealant to stop or control bleeding or provide air and fluid tightness in many surgical situations. This review describes the historical development of current fibrin sealant preparations and the scientific rationale behind the alleged physiological benefits of its major plasma-derived components. A comparison in the extraction methods and viral reduction treatments applied to current commercial products and autologous preparations, and their respective advantages and limits, are discussed. Application devices used for surgical applications are described. A survey of the major clinical applications in various surgical areas is presented. Current issues in terms of viral safety, definition of optimal fibrin sealant composition, and regulatory concerns, especially to demonstrate clinical efficacy, are also included.


Effect of growth hormone treatment on insulin secretion and glucose metabolism in prepubertal boys with short stature.
The purpose of this study was to evaluate the effect on insulin secretion and glucose metabolism of daily growth hormone (GH) treatment, 0.1 U/kg, for up to 3 years in 42 short prepubertal boys without GH deficiency. Their median height standard deviation (SD) score increased from -2.7 to -1.7, whereas their weight for height SD score was unchanged after 3 years of treatment. Fasting plasma glucose concentrations were unchanged, but median fasting insulin concentrations increased from 6.0 mU/l before treatment to 7.8 mU/l (p < 0.05) after the first year. No further increase was seen during the second or third years. The median insulin area under the curve 10-60 min after an intravenous glucose tolerance test increased from 480 mU.l-1.min-1 before treatment to 799 mU.l-1.min-1 (p < 0.05) after 1 year. The median glucose disposal rate (K value) before GH treatment, 2.2%/min, was unchanged after 1 year of treatment. A significant positive correlation was found between the change in the height SD score and the change in fasting insulin concentration during the first (r = 0.45; p < 0.01) and second (r = 0.56; p < 0.05) years of GH treatment. It was concluded that GH treatment in prepubertal children without GH deficiency caused a moderate increase in fasting and stimulated insulin concentrations during the first year of treatment. There was no further change during the following years of treatment, and there were no negative effects on fasting plasma glucose concentrations or glucose disposal rates. The increase in insulin concentration was related positively to the growth response.


Muscarinic agonists block a late-afterhyperpolarization in medial septum/diagonal band neurons in vitro.
Intracellular recordings were made from neurons located in the medial septum (MS), and nucleus of the diagonal band (nDB) from slices of guinea pig brain. These forebrain nuclei contain both cholinergic and noncholinergic neurons that project to the cortex and hippocampus and are involved in many cortical functions. Muscarinic agonists (bethanechol, 2-30 microM) had the specific action to reduce a long-duration afterhyperpolarization (long-AHP) while leaving other shorter duration AHPs intact. Since the long-AHP was observed in both cholinergic and non-cholinergic neurons, muscarinic agonists were not selective for any one cell type. Block of a long-AHP was not associated with a consistent increase in cell excitability and therefore can not fully explain the excitatory actions of acetylcholine (ACh) observed in vivo within the MS/nDB.


Work environments of different types of nursing subunits.
Based upon organizational theory, the purpose of this research was to identify and describe similarities and differences in the work environments of nine different types of nursing subunits (intensive care, medical, surgical, psychiatric, auxiliary, rehabilitation, rural, paediatric and obstetrical) in hospitals. Six measures of nursing subunit environment were developed: these included measures of nursing subunit autonomy, and the complexity and pervasiveness of other medical and hospital groups interacting with the nursing subunit. Data were collected by questionnaire from headnurses in 157 nursing subunits located in 24 hospitals in Alberta, Canada. The results indicated that the types of nursing subunits were similar in their degree of autonomy from both physicians and administration in the larger context in which they were located but were significantly different in terms of number and heterogeneity of groups outside nurses with which they interacted and the extent to which such groups pervaded the subunits. For example, intensive care units appeared as the type of nursing subunit with the greatest need for interaction with physicians, paramedics, hotel services and so on, whereas, psychiatric subunits appeared to be the least dependent on groups outside nursing in the hospital. These findings have implications for the management practices and educational programme for nursing.


Corneal decompensation following acute angle-closure glaucoma.
Ten eyes of nine patients with endothelial dystrophy requiring iridectomy for acute angle-closure glaucoma developed corneal edema sufficient to require penetrating keratoplasty. Because of the proximity of iris to cornea, simultaneous lens extraction was carried out to prevent malignant glaucoma. Penetrating keratoplasty using techniques presented here provided improved visual acuity and control of glaucoma in all cases.


Nerve agents: pathophysiology and treatment of poisoning.
Nerve agents, the deadliest of the classical chemical warfare agents, primarily function as acetylcholinesterase inhibitors and cause a rapidly progressive cholinergic crisis. Because of the speed of onset of the syndrome, treatment must be rendered emergently and will most likely be performed by first responders. Neurologists should be familiar with the pathophysiology and treatment of syndromes caused by nerve agents, not only to assist with the hospital care of these patients but also to serve as resources to their local medical communities in preparation for chemical terrorism.


Glottic Keratosis: Significance and Identification of Laryngoscopic Findings.
Glottic keratosis poses a challenge because a decision to biopsy must weigh the likelihood of dysplasia and cancer against the voice outcome after biopsy. We determined the significance of laryngoscopic findings and agreement among clinicians to identify those specific findings. Retrospective case-control study. Tertiary care university hospital. Adults with glottic keratosis with preoperative office laryngoscopies were included. Preoperative videostroboscopies were reviewed by a blinded reviewer. Multivariable logistic regression was used to examine the correlation between laryngoscopic appearance of glottic keratosis and presence or absence of high-grade dysplasia or carcinoma on biopsies. Consensus among head and neck cancer surgeons to detect specific laryngoscopic findings was evaluated by presenting representative laryngoscopies to a blinded cohort. Interrater reliability was calculated using Fleiss's κ. Sixty glottic keratotic lesions met inclusion criteria. On logistic regression, both erythroplakia and aberrant microvasculature like vascular speckling were significantly associated with high-grade dysplasia and carcinoma, P = .002 and P = .03, respectively. Interrater reliability among clinicians to identify erythroplakia and aberrant microvasculature was minimal, κ = 0.35 and κ = 0.29, respectively. Interrater reliability was improved with the use of virtual chromoendoscopy. The presence of erythroplakia and aberrant microvasculature in glottic keratosis is associated with the presence of high-grade dysplasia or carcinoma. Virtual chromoendoscopy can be used to improve reliability for detecting erythroplakia and vascular speckling, and this is a potential area for practice-based learning. Clinicians should identify and consider immediate diagnostic biopsy of suspicious glottic keratosis.


Effects of skin mast cells on bleeding time and coagulation activation at the site of platelet plug formation.
We studied the effects of stimulated skin mast cells on bleeding time and thrombin generation which was measured using prothrombin fragment F 1+2 (F 1+2) and thrombin-antithrombin-III-complex (TAT). In 10 patients with urticaria pigmentosa (chronic cutaneous mast cell accumulation) the mean bleeding time was significantly prolonged in wounds made on urticaria pigmentosa lesions vs. normal skin (460 +/- 34 vs. 342 +/- 27 s, p = 0.005). In 10 atopic subjects skin incisions were made on prick-tested sites 30, 60, 120 and 240 min after administration of an allergen (acute mast cell stimulation), histamine or vehicle. The mean bleeding time was significantly prolonged at all time points, being maximal at 120 min (60% prolonged) in wounds made on allergen-stimulated skin areas (p < 0.01) compared with histamine or vehicle sites. Administration of allergen or histamine lowered the TAT concentration in the bleeding-time blood. Furthermore, TAT and F 1+2 levels in the bleeding-time blood were lower at 60, 120 and 240 min after allergen or histamine application in comparison with samples collected at 30 min. We conclude that skin mast cells can regulate primary hemostasis by prolonging bleeding time and by inhibiting thrombin generation.


Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity.
Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP) and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM), insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.


Phosphorylation of the atypical kinesin Costal2 by the kinase Fused induces the partial disassembly of the Smoothened-Fused-Costal2-Cubitus interruptus complex in Hedgehog signalling.
The Hedgehog (Hh) family of secreted proteins is involved both in developmental and tumorigenic processes. Although many members of this important pathway are known, the mechanism of Hh signal transduction is still poorly understood. In this study, we analyse the regulation of the kinesin-like protein Costal2 (Cos2) by Hh. We show that a residue on Cos2, serine 572 (Ser572), is necessary for normal transduction of the Hh signal from the transmembrane protein Smoothened (Smo) to the transcriptional mediator Cubitus interruptus (Ci). This residue is located in the serine/threonine kinase Fused (Fu)-binding domain and is phosphorylated as a consequence of Fu activation. Although Ser572 does not overlap with known Smo- or Ci-binding domains, the expression of a Cos2 variant mimicking constitutive phosphorylation and the use of a specific antibody to phosphorylated Ser572 showed a reduction in the association of phosphorylated Cos2 with Smo and Ci, both in vitro and in vivo. Moreover, Cos2 proteins with an Ala or Asp substitution of Ser572 were impaired in their regulation of Ci activity. We propose that, after activation of Smo, the Fu kinase induces a conformational change in Cos2 that allows the disassembly of the Smo-Fu-Cos2-Ci complex and consequent activation of Hh target genes. This study provides new insight into the mechanistic regulation of the protein complex that mediates Hh signalling and a unique antibody tool for directly monitoring Hh receptor activity in all activated cells.


Blood transfusion: risks and benefits.
This article describes the basic science involved in the provision of a blood transfusion service. Apart from the life-saving properties of blood transfusion following acute blood loss, much modern surgery could not be contemplated without the availability of safe and compatible blood for transfusion. In addition there are many medical conditions whose therapy depends on blood products.


Development and fate of the postovulatory follicle complex, postovulatory follicle, and observations on folliculogenesis and oocyte atresia in ovulated common snook, Centropomus undecimalis (Bloch, 1792).
The common snook, Centropomus undecimalis, was induced to ovulate using a time-release, GnRH analogue. Ovulation occurred the afternoon or evening the day after hormone administration. The time of ovulation was established within half an hour. At ovulation, three fish per time-group were divided into 0, 6, 12, 18 hr and one thru five days post-ovulation to study changes in the postovulatory follicle complex (POC). Histology of the ovaries revealed changes in the POC, postovulatory follicle (POF) and oocyte atresia through five days post-ovulation. Within 24 hr, nuclei of the POF cells lost their initial spherical or oval configuration, and by four days the basement membrane within the POC had fragmented. There was a temporal separation between ovulation and post-ovulation folliculogenesis; that is, in that the formation of new follicles commenced within the germinal epithelium between 12-48 hrs after ovulation. Morphology of the POC was best revealed with the reticulin stain; it is composed of the POF and postovulatory theca (POT). These are separated by a basement membrane, reflecting the origin of a follicle from a germinal epithelium while the theca is derived from stroma. The POF is composed of the former follicle cells that surrounded and contacted the oocyte during its development; the follicle is composed of the oocyte and its surrounding follicle cells. The POC is composed of a prominent basement membrane separating the POT from the POF. The reticulin stain clearly defines compartmentation in the ovary and supports redefinition of the POF as the follicle cells that formerly surrounded the oocyte prior to ovulation. J. Morphol. 278:547-562, 2017. © 2017 Wiley Periodicals, Inc.


Efficient expression of a Toxoplasma gondii dense granule Gra4 antigen in tobacco leaves.
A His-tagged truncated version of Toxoplasma gondii dense granule 4 protein (Gra4(163-345)) was transiently expressed in tobacco leaves. Two genetic constructions were used to accomplish this goal. In one of them, based in a Potato virus X (PVX) amplicon, the sequence encoding His-Gra4(163-345) was placed under control of an additional PVX coat protein subgenomic promoter. In the other, the same sequence was fused to an apoplastic transport signal and placed under the direction of the cauliflower mosaic virus 35S promoter. His-Gra4(163-345) accumulation in agroinfiltrated tobacco leaves was estimated by Western blot analysis using mouse anti-Gra4 antibody and a seropositive human serum. Here, we demonstrated the feasibility of producing a Gra4 antigen using transient expression methods in plants.


Immunoparalysis in critically ill children.
Immunoparalysis is associated with poorer outcomes in the paediatric intensive care unit (PICU) setting. We aimed to determine the group of patients with higher chances of immunoparalysis and correlate this status with increased risks of nosocomial infection and adverse clinical parameters. We conducted an exploratory study with prospective data collection in a university-affiliated tertiary medical, surgical, and cardiac PICU. Fifteen patients with multiple organ dysfunction syndrome were included over a period of 6 months. Monocyte's human leucocyte antigen (HLA)-DR expression and tumour necrosis factor (TNF)-α and interleukin (IL)-6 production were measured by flow-cytometry at three time points (T1 = 1-2 days; T2 = 3-5 days; T3 = 6-8 days). Using the paediatric logistic organ dysfunction-2 score to assess initial disease severity, we established the optimal cut-off values of the evaluated parameters to identify the subset of patients with a higher probability of immunoparalysis. A comparative analysis was performed between them. Sixty per cent were males; the median age was 4.1 years. Considering the presence of two criteria in T1 (classical monocytes mean fluorescence intensity [MFI] for HLA-DR ≤ 1758.5, area under the curve (AUC) = 0.775; and frequency of monocytes producing IL-6 ≤ 68.5%, AUC = 0.905) or in T3 (classical monocytes MFI of HLA-DR ≤ 2587.5, AUC = 0.675; and frequency of monocytes producing TNF-α ≤ 93.5%, AUC = 0.833), a variable to define immunoparalysis was obtained (100% sensitivity, 81.5% specificity). Forty per cent of patients were assigned to the immunoparalysis group. In this: a higher frequency of nosocomial infection (p = 0.011), vasoactive inotropic score (p = 0.014) and length of hospital stay (p = 0.036) was observed. In the subgroup with the diagnosis of sepsis/septic shock (n = 5), patients showed higher percentages of non-classical monocytes (p = 0.004). No mortality was recorded. A reduction in classical monocytes HLA-DR expression with lower frequencies of monocytes producing TNF-α and IL-6 during the first week of critical illness, appears to be a good marker of immunoparalysis; these findings relate to an increased risk of nosocomial infection and deleterious outcomes. The increased frequency of non-classical monocytes in patients with sepsis/septic shock is suggestive of a better prognosis.


Investigating the impact of adapted physical education service-learning projects on preservice teachers' attitudes toward individuals with disabilities.
Service-learning (SL) has been implemented widely in teacher education to connect knowledge and practical experiences. In the field of Physical Education Teacher Education, Adapted Physical Education (APE) Courses have been implemented SL to provide hands-on experiences to promote preservice teachers' attitudes toward individuals with disabilities. The purpose of this study is to investigate the effectiveness of two SL projects, the volunteer project, and the parasports project, in the Intro APE course on preservice teachers' attitudes toward individuals with disabilities. A total of 130 preservice teachers participated in this study taking the Multidimensional Attitude Scale Toward Persons with Disabilities (MAS) before and after completing two SL projects. The result of the t-test indicated that there is no difference in overall MAS scores between pre- and posttest (Meanpre=2.954, SDpre=0.689, Meanpost=3.01, SDpost=0.679; t(129)=0.390, P=0.784). However, the significant increase observed in affects subscale of MAS (Meanpre=3.47, SDpre=0.374, Meanpost=3.52, SDpost=0.188; t(129)= 0.347, P=0.327). Our finding indicated cognition and behavior of preservice teachers toward individuals with disabilities were positively increased, but not significantly improved yet. Evidence suggested that two SL projects in this study did not significantly improve the overall positive attitudes of preservice teachers toward individuals with disabilities, but it was meaningful to observe that preservice teachers increased their affects toward individuals with disabilities.


Modern microelectronics and microfluidics on microneedles.
Possessing the attractive advantages of moderate invasiveness and high compliance, there is no doubt that microneedles (MNs) have been a gradually rising star in the field of medicine. Recent evidence implies that microelectronics technology based on microcircuits, microelectrodes and other microelectronic elements combined with MNs can realize mild electrical stimulation, drug release and various types of electrical sensing detection. In addition, the combination of microfluidics technology and MNs makes it possible to transport fluid drugs and access a small quantity of body fluids which have shown significant untapped potential for a wide range of diagnostics. Of particular note is that combining both technologies and MNs is more difficult, but is promising to build a modern healthcare platform with more comprehensive functions. This review introduces the properties of MNs that can form integrated systems with microelectronics and microfluidics, and summarizes these systems and their applications. Furthermore, the future challenges and perspectives of the integrated systems are conclusively proposed.


Distinct RB1 gene mutations with low penetrance in hereditary retinoblastoma.
The interfamilial diversity in penetrance and expressivity of hereditary retinoblastoma was investigated in 29 families. By using a simple parameter for estimating the severity of the disease (diseased-eye-ratio), we were able to identify four families with a discrete low-penetrance phenotype. The underlying genetic defect was identified in three families. One family has a 3-bp deletion in exon 16 that results in the deletion of Asn480. In two further unrelated families, the identical missense mutation at codon 661 in exon 20 (CGG to TGG, Arg to Trp) was identified. These mutations are distinct from the majority of retinoblastoma gene alterations, as they do not result in the disruption of the gene product. We propose that reduced penetrance of retinoblastoma is the result of a residual function of these alleles in retinoblastoma precursor cells.


Cardiovascular effects of ginger aqueous extract and its phenolic constituents are mediated through multiple pathways.
Ginger is a world known food plant which is equally reputed for its medicinal properties. We report here the hypotensive, endothelium-dependent and independent vasodilator and cardio-suppressant and stimulant effects of its aqueous extract (Zo.Cr). Zo.Cr, which tested positive for saponins, flavonoids, amines, alkaloids and terpenoids, induced a dose-dependent (3.0-10.0 mg/kg) fall in the arterial blood pressure (BP) of anaesthetized rats which was partially blocked by atropine (1 mg/kg). In isolated endothelium-intact rat aorta, Zo.Cr (0.01-5.0 mg/ml) relaxed the phenylephrine (1 microM)-induced contractions, effect partially blocked by atropine (1 microM). Zo.Cr inhibited the K+ (80 mM)-induced contractions and also shifted the Ca++ dose-response curves to the right, similar to verapamil, indicating Ca++ antagonist activity. An atropine-resistant and l-NAME-sensitive vasodilator activity was also noted from ginger phenolic constituents 6-, 8- and 10-gingerol, while 6-shogaol showed a mild vasodilator effect. In guinea-pig atria, Zo.Cr (0.1-5.0 mg/ml) inhibited the force and rate of atrial contractions. Pretreatment with atropine blocked the inhibitory effect and a stimulatory effect was unmasked which was resistant to propranolol and verapamil but sensitive to ryanodine, blocker of Ca++ release from intracellular stores. Later at doses >or=1.0 mg/ml, the extract completely suppressed the atrial tissue, effect resistant to glibenclamide, pyrilamine, aminophylline and L-NAME. These data indicate that the aqueous ginger extract lowers BP through a dual inhibitory effect mediated via stimulation of muscarinic receptors and blockade of Ca++ channels and this study provides sound mechanistic basis for the use of ginger in hypertension and palpitations.


[Bilateral persistent pupillary membrane and high myopia].
After birth, remnants of pupillary membrane which constitute the vascular supply to the crystalline lens can persist. These are contiguous to the iris collarette causing possible deprivation amblyopia by obstructing the pupillary area. We here report the case of a 4-year-old child, born to consanguineous parents, presenting with bilateral persistent pupillary membrane associated with high myopia. Clinical examination showed bilateral remnants of pupillary membrane, intact iris sphincter and diffuse chorioretinal atrophy in the fundus of eye . Visual acuity was difficult to assess. On the other hand, refraction test showed high myopia RE -10.75 (-3.25, 29°) LE -10 (-0.75, 180°). Treatment of bilateral persistent pupillary membrane is based on mydriatic agents, surgical excision or laser destruction. We opted for the use of mydriatic agents with total optical correction and amblyopia treatment.


Ludwik Bierkowski and the early days of general anaesthesia in the Polish soil in February 1847.
Ludwik Bierkowski belonged to the elite of surgeons of the first half of the 19th century. Educated in an excellent German university, Bierkowski had in-depth and comprehensive knowledge, a wide range of practical skills and was continuously eager to search for new solutions. He introduced cotton wool for wound dressings, experimentally determined the conditions of blood transfusions and published two outstanding anatomo-surgical atlases, which ranks him among the leading physicians of those days. Moreover, he was the first to use ether for effective general anaesthesia in the Polish lands, the procedure that changed the course of the history of medicine. Bierkowski performed ether anaesthesia in less than four months after the first world and in less than two months after the first European demonstration, which rates him among the most modern surgeons of those times. This year we celebrate the 170th anniversary of this event.


Does surgical debulking for advanced stages of thymoma improve survival?
A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was 'Does surgical debulking for advanced stages of thymoma improve survival?' Altogether, only 17 papers were found using the reported search, of which only 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated; these studies have mainly reported the survival and recurrence rates after total vs subtotal resection of thymic tumours in patients receiving or not receiving adjuvant chemoradiotherapy. These studies confirmed that complete resection is the best prognostic factor in thymomas. With regard to subtotal tumour resection/debulking, we did not find any randomized controlled trials. The evidence on this topic is scarce and these 10 reported were retrospective reviews of the operative, histology and survival data of patients with thymoma who had subtotal vs partial resection for advanced stages of thymoma. Although debulking surgery for thymoma had positively affected survival, in six studies, the difference failed to reach statistical significance. Three of the studies, on the other hand, showed a higher survival rate in thymomas in which maximum debulking was performed and the treatment was followed by high-dose irradiation. None of these studies showed any benefit in debulking surgery for thymic carcinoma. Besides histology and tumour cell-type, other factors influencing survival included the tumour stage and the presence of symptoms such as myasthenia gravis as a warning sign at an early stage. Current evidence in the literature on the survival after debulking surgery for thymoma is contradictory, and most of the studies do not show any survival benefit after debulking for thymoma. However, debulking surgery minimizes the tumour size and area for irradiation postoperatively, hence it can result in less damage to the adjacent tissue during radiotherapy and may be considered for patients in advanced stages of thymoma in whom extensive radiotherapy will be required. In these cases, however, the risks of surgery followed by radiotherapy or radiotherapy alone should carefully be assessed prior to the initiation of treatment.


MORPHOMETRICS AND CLADISTICS: MEASURING PHYLOGENY IN THE SEA URCHIN ECHINOCARDIUM.
A phylogenetic approach to the study of evolutionary patterns is based on taxic homologies (synapomorphies). In contrast, the recognition of evolutionary processes (namely heterochronies) involves analysis of the entire morphology. Recent developments in geometric morphometry permit analysis of morphological similarities grounded in operational homologies. Such morphometric techniques are explored (1) at the level of evolutionary processes, and (2) as a complement in exploration of phylogenetic relationships. To examplify this, we perform a two-part study of the ontogeny and phylogeny of the spatangoid sea urchin Echinocardium. First, a phylogenetic analysis of ten Recent species in the genus is performed on 18 informative characters of the test. Second, morphological divergences among the species are analyzed using procrustean (superimposition) methods based on 49 homologous points. An additive distance tree is built from a matrix of morphometric distances among adult specimens. This tree is fully congruent with the phyletic results. Ontogenetic processes are explored by inserting ontogenetic series into the analysis. A distance tree including the juvenile stages shows that the general evolutionary trend of the genus is peramorphic, but species-to-species comparisons attest that no general clinal trend exists. Our analysis emphasizes the importance of morphometric approaches in evolutionary studies (1) for the understanding of heterochronies; (2) to trace the morphological implications of phylogenetic patterns; and (3) to estimate the impact of homoplasies.


Expression-Invariant Age Estimation Using Structured Learning.
In this paper, we investigate and exploit the influence of facial expressions on automatic age estimation. Different from existing approaches, our method jointly learns the age and expression by introducing a new graphical model with a latent layer between the age/expression labels and the features. This layer aims to learn the relationship between the age and expression and captures the face changes which induce the aging and expression appearance, and thus obtaining expression-invariant age estimation. Conducted on three age-expression datasets (FACES , Lifespan and NEMO ), our experiments illustrate the improvement in performance when the age is jointly learnt with expression in comparison to expression-independent age estimation. The age estimation error is reduced by 14.43, 37.75 and 9.30 percent for the FACES, Lifespan and NEMO datasets respectively. The results obtained by our graphical model, without prior-knowledge of the expressions of the tested faces, are better than the best reported ones for all datasets. The flexibility of the proposed model to include more cues is explored by incorporating gender together with age and expression. The results show performance improvements for all cues.


High seroprevalence of Helicobacter pylori infection in patients with systemic sclerosis: association with esophageal involvement.
To determine the prevalence and clinical relevance of Helicobacter pylori infection in patients with systemic sclerosis (SSc). Serum samples were obtained from 124 patients with SSc (67 with limited cutaneous SSc, 57 with diffuse cutaneous SSc). Fifty samples from age and sex matched individuals were used as controls. IgG antibodies to H. pylori infection were measured by ELISA. IgG antibodies to H. pylori were found in 55.6% (69 of 124) of the patients with SSc, significantly more than in the controls. There was a significant correlation of the presence of antibodies to H. pylori with the prevalence of esophageal hypomotility in the patients with SSc (p < 0.02). Patients with SSc have H. pylori infection at a higher prevalence than the general population. H. pylori might play a role in the development of esophageal dysfunction in SSc.


The etiology and pathogenesis of ovine pulmonary carcinoma (sheep pulmonary adenomatosis).
Ovine pulmonary carcinoma (OPC, sheep pulmonary adenomatosis, jaagsiekte) occurs naturally as a contagious bronchioloalveolar carcinoma of sheep in the Americas, Europe, Africa and Asia. The disease is endemic and economically important in Peru and apparently more common than previously suspected in the U.S.A. The tumor is a result of transformation of type II alveolar epithelial cells or non-ciliated bronchiolar cells of the lung. Clinically affected sheep develop dyspnea, tachypnea and often a watery nasal discharge that originates from tumor secretions. The course is progressive and death usually occurs within a few weeks. To study the viral etiology and pathogenesis of OPC in the U.S.A., the disease was experimentally transmitted to neonatal or young lambs with a success rate of 69%. Ovine lentivirus (OvLV), present in the inocula, was concurrently transmitted and induced lymphoid interstitial pneumonia in most animals. While morphological, immunological and other studies implicate a type D or type B retrovirus as the etiologic agent of OPC, this virus has not yet been cultured and the role of ovine lentivirus in the disease remains unknown.


Residential alcohol detoxification: new role for mental health nurses.
This article discusses the philosophy and practice of a community-based residential detoxification service for people with alcohol problems. The service is provided on a direct-access basis and has a team of 19 nurses who are supported by a GP practice. The article highlights issues relevant to nursing in this community facility by referring to three case studies. The case studies demonstrate that this client group finds it difficult to access other forms of health and social care. The case examples emphasize both the qualitative aspects of nursing care and the decision-making involved in this type of service. The authors suggest that large populations with complex needs can be served by nursing-led services adopting a 'direct access' approach.


[Multi-slice computed tomography of myocardial bridge and mural coronary artery and clinical significance thereof].
To investigate the diagnosis of myocardial bridge and mural coronary artery (MB-MCA) with multi-slice computed tomography (MSCT) and clinical significance thereof. 900 patients suspected as with coronary artery disease (CHD) underwent 64-slice computed tomography performed by 3 radiologists independently. When consistency was obtained among the independent interpretations of the tomogram among them the diagnosis of MB-MCA could be confirmed. The length of MCA and thickness of MB were measured, and the situation of the nearby arteries were observed and recorded. Based on the above mentioned 3 items the reference scoring criteria were established. 180 sites of MB-NCA were found in 167 (18.56%) of the 900 patients, 112 males and 55 females, aged 54.46 (33 - 84). 167 of the 180 sites of MB-MCA were located on the LAD (92.7%). MCA could be covered by MB in a form of semi-circularity (63.89%, 115/180) or circularity (36.11%, 65/180) The length of MCA was 18.7 mm +/- 10.2 mm, and the thickness of MB was 1.7 mm +/- 1.2 mm. 70% of the arteries proximal and/or distal to the MB-MCA were tortuous. Length of MCA < 10 mm, half-surrounding of MB, and smoothness of the proximal and distant vessels were scored as 1; length of MCA of 10 approximately 20 mm, thickness of MB < 1 mm, and tortuousness of the unilateral proximal or distant vessel were scored as 2; and length of MCA > 20 mm, thickness of MB > 1 mm, and tortuousness of the bilateral proximal and distant vessels were scored as 3. Coronary atherosclerosis was found in 88 of the 167 patients (52.69%). No significant correlation was found between coronary atherosclerosis and MB-MCA grade (u = 1.234, P > 0.05). Sixty-four-slice CT can be used to confirm the presence of MB = MCA and the morphology of coronary artery with MB-MCA. Coronary atherosclerosis is not significantly correlated with MB-MCA grade.


GISH analysis of meiotic chromosome pairing in Solanum lycopersicoides introgression lines of cultivated tomato.
Meiotic chromosome pairing was studied in introgression lines of cultivated tomato, Lycopersicon esculentum (= Solanum lycopersicum), containing 1 or 2 chromosome segments from the wild species Solanum lycopersicoides. Genomic in situ hybridization (GISH) was used to compare the relative lengths at diakinesis of the different introgressed segments and to measure the chiasmate arm frequency for the chromosome pair involved in the introgression(s). Longer segments generally produced stronger GISH signals than shorter segments. GISH signal intensity also depended on whether or not an introgressed segment encompassed the centromeric region. For example, a 29 cM segment that included the centromeric region produced a stronger GISH signal than a 42 cM segment that did not. In each line the chromosome arm containing the homeologous segment showed a reduction in chiasmate arm frequency that was most pronounced in lines with long segments. This reduction was accompanied by an increased chiasmate arm frequency on the other arm. Double introgression lines, heterozygous in repulsion phase for 2 introgressions on opposite chromosome arms, showed a lower frequency of chiasmata than single introgression lines. Pairing failure, indicated by the presence of univalents, was highest in the double introgression and whole chromosome substitution lines. These results are discussed with respect to observations of suppressed recombination in these stocks and potential practical implications for reducing linkage drag in breeding programs.


Design and rationale of a prospective, multi-institutional registry for patients with sinonasal malignancy.
Assessment of patients with sinonasal malignancy is challenging due to the low disease incidence and diverse histopathology. The current literature is composed mainly of retrospective studies with heterogeneous cohorts, and the rarity of cases limits our understanding of disease characteristics and treatment outcomes. We describe the development of a prospective, multi-institutional registry that utilizes cloud-based computing to evaluate treatment outcomes in patients with sinonasal cancer. A web-based, secure database was built to prospectively capture longitudinal outcomes and quality-of-life (QoL) data in patients diagnosed with sinonasal malignancy. Demographics, tumor staging, and treatment outcomes data are being collected. The Sinonasal Outcome Test-22 and University of Washington Quality of Life Questionnaire are administered at presentation and at recurring intervals. To date, seven institutions are participating nationally. This prospective, multi-institutional registry will provide novel oncological and QoL outcomes on patients with sinonasal malignancy to inform management decisions and disease prognostication. The application of cloud-based computing facilitates secure multi-institutional collaboration and may serve as a model for future registry development for the study of rare diseases in otolaryngology. 2C Laryngoscope, 126:1977-1980, 2016.


Giant Right Coronary Artery Aneurysm Resembling Cardiac Tumor: A Case Report.
Coronary artery aneurysms are not uncommon vascular anomalies, but giant coronary artery aneurysms mimicking cardiac tumors are extremely rare and easily misdiagnosed as tumors. The management and prognosis are not well defined. We describe a case of a 50-year-old woman, who had a transthoracic echocardiogram that suggested a cardiac tumor in the right ventricle adjacent to the tricuspid valve and without ventricular wall akinesia. Her medical history was unremarkable, and she had no obvious symptoms. A transesophageal echocardiogram and computed tomography angiogram examination suggested the tumor-like structure was a giant coronary aneurysm, originating from the distal portion of right coronary artery. The patient underwent surgical intervention and recovered uneventfully. Histopathology of the excised aneurysm showed fibrous tissue hyperplasia with collagenization and calcification in the wall of the artery. Giant coronary artery aneurysms resembling heart tumors are extremely rare. Differentiating them from cardiac tumors can sometimes be difficult. This rare case emphasizes the importance of combining multiple imaging methods, which helps make accurate diagnosis. For treatment, surgical intervention may be the appropriate therapeutic strategy for the rare lesion.


Developing guided self-help for depression using the Medical Research Council complex interventions framework: a description of the modelling phase and results of an exploratory randomised controlled trial.
Current guidelines for the management of depression suggest the use of guided self-help for patients with mild to moderate disorders. However, there is little consensus concerning the optimal form and delivery of this intervention. To develop acceptable and effective interventions, a phased process has been proposed, using a modelling phase to examine and develop an intervention prior to preliminary testing in an exploratory trial. This paper (a) describes the modelling phase used to develop a guided self-help intervention for depression in primary care and (b) reports data from an exploratory randomised trial of the intervention. A guided self-help intervention was developed following a modelling phase which involved a systematic review, meta synthesis and a consensus process. The intervention was then tested in an exploratory randomised controlled trial by examining (a) fidelity using analysis of taped guided self-help sessions (b) acceptability to patients and professionals through qualitative interviews (c) effectiveness through estimation of the intervention effect size. Fifty eight patients were recruited to the exploratory trial. Seven professionals and nine patients were interviewed, and 22 tapes of sessions analysed for fidelity. Generally, fidelity to the intervention protocol was high, and the professionals delivered the majority of the specific components (with the exception of the use of feedback). Acceptability to both professionals and patients was also high. The effect size of the intervention on outcomes was small, and in line with previous analyses showing the modest effect of guided self-help in primary care. However, the sample size was small and confidence intervals around the effectiveness estimate were wide. The general principles of the modelling phase adopted in this study are designed to draw on a range of evidence, potentially providing an intervention that is evidence-based, patient-centred and acceptable to professionals. However, the pilot outcome data did not suggest that the intervention developed was particularly effective. The advantages and disadvantages of the general methods used in the modelling phase are discussed, and possible reasons for the failure to demonstrate a larger effect in this particular case are outlined.


Protective Effects of Human Chorionic Gonadotropin Against Breast Cancer: How Can We Use This Information to Prevent/Treat the Disease?
Breast cancers (BCs) are the most common malignancies among women worldwide. Giving birth to a first child before 24 years of age decreases the BC risk by about half, when women reach menopausal years. The scientific evidence suggests that the actions of human chorionic gonadotropin (hCG) are responsible for this decrease. Human BC cells and tissues contain hCG/luteinizing hormone receptors. The activation of the receptors results in an increase in cell differentiation and apoptosis. Conversely, it decreases the cell proliferation, invasion, and survival. The hCG actions are primarily cyclic adenosine monophosphate/protein kinase A mediated, require the presence of receptors, and involve blocking the activation and nuclear translocation of the transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The women with a higher hCG levels during pregnancy tend to have a lower BC incidence and those with the receptor-positive tumors have a longer metastasis-free survival. The long-term benefits of pregnancy/hCG seem to come from permanent signature genomic imprinting and expression changes, which are characterized by low cell proliferation, increased efficiency of DNA repair mechanisms, cell differentiation, and cells resistance to carcinogenesis. These findings could provide clinical opportunities to use hCG for the prevention of BC in this modern era of increasing number of young women in our societies waiting longer than ever to have their first child. In addition, hCG may be useful to reduce and/or eliminate cellular targets of carcinogenic changes during an active ongoing disease.


The effect of Pro NanoLipospheres (PNL) formulation containing natural absorption enhancers on the oral bioavailability of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a rat model.
The lipophilic phytocannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) show therapeutic efficacy in various medical conditions. Both molecules are poorly water soluble and subjected to extensive first pass metabolism in the gastrointestinal tract, leading to a limited oral bioavailability of approximately 9%. We have developed an advanced lipid based Self-Emulsifying Drug Delivery System termed Advanced Pro-NanoLiposphere (PNL) pre-concentrate. The PNL is composed of lipid and emulsifying excipients of GRAS status and are known to increase solubility and reduce Phase I metabolism of lipophilic active compounds. Advanced PNLs are PNLs with an incorporated natural absorption enhancers. These molecules are natural alkaloids and phenolic compounds which were reported to inhibit certain phase I and phase II metabolism processes. Here we use piperine, curcumin and resveratrol to formulate the Advanced-PNL formulations. Consequently, we have explored the utility of these Advanced-PNLs on CBD and THC oral bioavailability. Oral administration of CBD-piperine-PNL resulted in 6-fold increase in AUC compared to CBD solution, proving to be the most effective of the screened formulations. The same trend was found in pharmacokinetic experiments of THC-piperine-PNL which resulted in a 9.3-fold increase in AUC as compared to THC solution. Our Piperine-PNL can be used as a platform for synchronized delivery of piperine and CBD or THC to the enterocyte site. This co-localization provides an increase in CBD and THC bioavailability by its effect at the pre-enterocyte and the enterocyte levels of the absorption process. The extra augmentation in the absorption of CBD and THC by incorporating piperine into PNL is attributed to the inhibition of Phase I and phase II metabolism by piperine in addition to the Phase I metabolism and P-gp inhibition by PNL. These novel results pave the way to utilize piperine-PNL delivery system for other poorly soluble, highly metabolized compounds that currently cannot be administered orally.


Prenatal diagnosis of fetal hepatoblastoma: case report and review of the literature.
Hepatoblastoma is the most common liver malignancy in childhood. The reported incidence is 11.2 cases per 1 million during the first year of life. Genetic predispositions include Beckwith-Wiedemann syndrome and familial polyposis. The prognosis depends on the extent of tumor spreading at the time of initial treatment, which typically includes chemotherapy and surgery. Imaging of hepatoblastoma has only rarely been reported prenatally. Here we report a recent case with a successful outcome and discuss issues of differential diagnosis and treatment.


Computation of local directivity, speed of sound and attenuation from ultrasonic reflection tomography data.
Ultrasound reflection tomography based on the compound scan principle, allows one to produce reflectivity images with high quality and reproducibility. In this paper, methods are discussed on how to extract additional physical parameters from the same set of reflection data for medical applications. Experimental results from a phantom object and in-vivo measurements illustrate the capabilities of such tomographic reflection systems.


Acupuncture as adjunctive therapy for patients with AECOPD: study protocol for a multicenter, randomized controlled trial.
The acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common respiratory disease among older adults, which imposes a significant burden on individuals and society and poses a major challenge to the global public health system due to its high morbidity and mortality. Acupuncture is effective for AECOPD, but its efficacy has been questioned due to the limited methodological quality. Thus, we aim to investigate the efficacy of acupuncture as adjunctive therapy for AECOPD and determine whether the efficacy of acupuncture differs with the type of acupoint combinations. This study proposes a prospective, multicenter randomized controlled trial that will comprise four groups, including two acupuncture treatment groups, one sham acupuncture group, and one basic treatment group. The acupuncture treatment groups will be distinguished by their focus on different patterns of acupoint combination, namely the Xi-cleft and He-sea acupoint combination and the Eight Confluence points acupoint combination, which may vary in clinical efficacy based on traditional acupuncture theories. The study aims to randomize 556 patients in a 1:1:1:1 ratio across the four groups. Each patient in acupuncture group or sham acupuncture group will receive routine drug therapy and 7 sessions of acupuncture treatment over 1 week. Participants in the basic treatment group will only receive routine drug therapy. The trial will be conducted in seven hospitals located in China. The primary outcomes in this trial will include differences in the Breathlessness, Cough, and Sputum Scale (BCSS) before randomization, 7 days after randomization, 5 and 9 weeks after randomization. Ethical approval was obtained from the Sichuan Regional Ethics Review of Committee on Traditional Chinese Medicine (Approval ID: 2022KL-068). The results of this study will be distributed through peer-reviewed journals.Clinical Trial Registration: ClinicalTrials.gov, identifier ChiCTR2200064484.


Immature Stages of Six Species of Adelpha Hübner (Lepidoptera: Nymphalidae: Limenitidinae) from Southern Brazil Coastal Forests.
Six species of Adelpha Hübner from Balneário Barra do Sul (Santa Catarina) and Morretes (Paraná) were collected as eggs or larvae and reared in captivity, aiming to provide descriptions and photography of the immature stages and imagoes. The species studied were Adelpha radiata radiata Fruhstorfer; Adelpha serpa serpa (Boisduval); Adelpha plesaure plesaure Hübner; Adelpha thesprotia (C. Felder & R. Felder); Adelpha lycorias lycorias (Godart); and Adelpha capucinus velia (C. Felder & R. Felder). Two new records of host plants were provided, Tapirira guianensis Aubl. for A. radiata radiata and Heteropterys for A. capucinus velia. This study provides a summary of host plants and the seasonality of occurrence of immature stages of these species. Data were organized in photographic plates that could be useful for the identification process.


Subcutaneous administration of recombinant human thyrotropin as an alternative to thyroid hormone withdrawal in patients with anticoagulated thyroid cancer: preliminary results.
For patients with thyroid cancer taking anticoagulants, because of hematoma risk at the injection site, intramuscular injections (IM) of recombinant human thyrotropin (rhTSH) are usually avoided and patients remain hypothyroid. The aim of the present study was to evaluate if subcutaneous injections (SC) of rhTSH are an alternative to IM. Five consecutive patients receiving anticoagulants were evaluated. The dose regimen was similar to the traditional follow-up protocol (2 x 0.9 mg, SC route). rhTSH administration elicited a sharp and prompt increase in serum TSH that peaked at day 3 (24 hours after the second rhTSH injection), with mean values of 246 +/- 68 mU/L. In one patient with a large thyroid remnant, thyroglobulin (Tg) rose from 18 ng/mL to 450 ng/mL. No adverse effects were observed. We conclude that SC injection of rhTSH represents a safe and efficient procedure in the monitoring of patients with thyroid cancer taking anticoagulants.


Antitumor effect of folate-targeted liposomal doxorubicin in KB tumor-bearing mice after intravenous administration.
The effect of folate-targeted liposomal doxorubicin (FTL-Dox) has been well characterized in folate receptor (FR) overexpressing tumors in vitro, particularly in KB human carcinoma cells. However, there are few studies evaluating the in vivo efficacy of FTL-Dox in KB murine xenograft models. In this study, we investigated the antitumor activity of FTL-Dox injected intravenously in mice bearing KB tumors. Folate ligands comprising of folate-polyethyleneglycol-distearoylphosphatidylethanolamine (FA-PEG-DSPE) were synthesized with different MW PEG. To design an optimum FTL-Dox formulation for therapeutic studies, we prepared various FTLs and characterized their in vitro targeting and in vivo tissue biodistribution. Mice were administered a single intravenous injection of free Dox, nontargeted PEGylated liposomal Dox (PL-Dox), or FTL-Dox. FTLs and PLs accumulated similarly in tumor tissue, despite FTLs' faster clearance from circulation. Mice treated with FTL-Dox 20 mg/kg had a slightly greater tumor growth inhibition and almost a 50% increase in life span than mice receiving PL-Dox 20 mg/kg (P = 0.0121; log-rank test). We conclude that FTLs administered systemically have the potential to enhance the delivery of anticancer drugs in vivo; however, their removal by FR expressing normal tissues may have to be blocked if the benefits of tumor targeting are to be realized.


Exposure to oxides of nitrogen: respiratory symptoms and lung function in British coalminers.
Five hundred and sixty British coalminers with relatively high or relatively low exposures to oxides of nitrogen, based on measurements of concentrations of these gases at nine collieries over four years, and records of the men's places of work and colliery mining conditions over a total of eight years have been studied. Data on these men's respiratory symptoms and ventilatory capacity (FEV1), obtained as part of an epidemiological study of British coalminers, have been used to investigate possible adverse effects of exposure to oxides of nitrogen. Exposures to oxides of nitrogen were generally well below threshold limit values, though occasional peaks after shotfiring and during diesel locomotive use did exceed short term limits. No relationship was found between exposure and respiratory symptoms or decline in FEV1 nor was there any evidence of differences in symptoms of FEV1 between 44 pairs of men matched for age, dust exposure, smoking habit, coal rank, and type of work, but differing in respect of exposure to oxides of nitrogen. It has not been possible to detect any adverse effects on the health of this working population of the levels of nitrogen oxides that have occurred in British mines over the past decade. With the current levels of these gases, any long term effects on respiratory health are so small as to be undetectable in the presence of smoking and dust exposure.


Immunohistochemical expression of D2-40 in benign and malignant sebaceous tumors and comparison to basal and squamous cell carcinomas.
The diagnosis of sebaceous carcinoma presents an important challenge to both clinicians and pathologists, as many cases are initially misdiagnosed both clinically and histopathologically, potentially leading to adverse medical and legal outcomes. The distinction of sebaceous carcinoma from benign sebaceous proliferations and other tumors is therefore of utmost importance, and immunohistochemistry may be useful in this differential. We studied the expression of D2-40 (podoplanin) by immunohistochemistry to determine if it can aid in this differential diagnosis and to evaluate the possibility of lymphangiogenesis in sebaceous carcinoma. A total of 36 cases of sebaceous lesions, including 16 sebaceous carcinomas, 7 sebaceous adenomas, 6 sebaceomas, and 7 cases of normal glands and sebaceous hyperplasia, and 17 cases of basal cell carcinoma and 10 cases of squamous cell carcinoma, were also examined. We found no significant increase in tumor lymphangiogenesis by semiquantitative scoring of lymphovascular density per square millimeter of tumoral/peritumoral stroma in sebaceous carcinoma versus benign sebaceous proliferations. However, D2-40 staining showed a different pattern in the benign tumors, which were positive only in the basaloid cells (most pronounced in sebaceoma), versus sebaceous carcinoma, which was either negative or focally positive in a haphazard pattern in most cases, although some cases of basaloid sebaceous carcinomas showed strong positivity. We also found D2-40 to be only weakly and focally positive in basal cell carcinoma and weakly to moderately positive in squamous cell carcinoma, which showed increased staining with decreased differentiation. Therefore, overall, D2-40 is, of limited diagnostic utility in sebaceous lesions but may be useful in distinguishing sebaceoma and basaloid sebaceous carcinoma from basal cell carcinoma.


Expression and characterization of a pleckstrin homology domain in phospholipase C, PLC-eta1.
Phospholipase C (PLC) plays an important role in intracellular signal transduction by hydrolyzing phosphatidylinositol 4,5-bis-phosphate, a membrane phospholipid. Currently, thirteen mammalian PLC isozymes have been identified, which are divided into six classes on the basis of structure and mechanisms. All the PLC isozymes share common domains including catalytic X and Y domains, protein kinase C conserved region 2 (C2) domain, EF-hand motif and pleckstrin homology (PH) domain. In this study, the PLC-eta1 PH domain has been over-expressed and purified. The most undesirable feature of the protein was instability, resulting in precipitation during the purification process. With the aim of structural characterization, a solution condition was optimized using SDS-PAGE and NMR spectroscopy. A circular dichroism spectrum indicated that the PLC-eta1 PH domain mainly comprised beta-strands, which was also suggested by the 2D 1H-15N HSQC spectrum.


Incidence, presentation and outcome of toxoplasmosis in HIV infected in the combination antiretroviral therapy era.
HIV-associated incidence and prognosis of cerebral toxoplasmosis (CTX) is not well established during later years. From the Danish HIV Cohort Study, we identified 6325 HIV-infected individuals. We assessed incidence, mortality, predictive and prognostic factors of CTX during the pre-combination antiretroviral therapy (pre-cART; 1995-1996) and cART-era (1997-2014). Adjusted incidence rate ratios (aIRR), mortality rate ratios (aMRR) and 95% confidence intervals (CI) were assessed using Poisson regression analysis. CTX IR was 1.17/1000 PYR (95% CI 0.93-1.47). We observed no change in CTX-risk in the first year after HIV-diagnosis, but a substantial reduction in mortality in the first 3 months after CTX diagnosis when comparing the cART-era to the pre-cART-era; {(aIRR: 0.79; 95% CI: 0.37-1.72) (aMRR: 0.15; 95% CI: 0.06-0.38)}. For individuals surviving the first year after HIV-diagnosis or the first 3 months after CTX-diagnosis, IRR and MRR had declined to minimal levels {(aIRR: 0.06; 95% CI: 0.03-0.10); (aMRR: 0.02; 95% CI: 0.01-0.05)}. Three years after CTX-diagnosis 30% of the patients still had neurological deficits. Although, CTX remains an important cause of morbidity and mortality in the cART-era, with high prevalence of neurological sequelae, incidence and mortality has largely declined, especially among those surviving the first year after diagnosis.


Variations in perinatal mortality in Gloucestershire: preliminary communication.
The perinatal mortality rate (PNMR) was calculated for each rural parish in Gloucestershire for the years 1968-79. The characteristics of high- and low-rate parishes (each set comprising about 10% of all births) were contrasted according to routinely recorded fetal, maternal and environmental variables. The overall PNMR in the high-rate set was six times higher than in the low-rate set; congenital malformations and low birth weight distribution could explain about one-third of this difference but the residue was not attributable to fetal gestation, maternal age or parity or social class as may have been expected. However, there was a strong association with population and housing density. It is suggested that comparisons within districts may provide more sensitive associations with PNMR than comparisons between districts, regions and countries.


A review of evidence linking disrupted neural plasticity to schizophrenia.
The adaptations resulting from neural plasticity lead to changes in cognition and behaviour, which are strengthened through repeated exposure to the novel environment or stimulus. Learning and memory have been hypothesized to occur through modifications of the strength of neural circuits, particularly in the hippocampus and cortex. Cognitive deficits, specifically in executive functioning and negative symptoms, may be a corollary to deficits in neural plasticity. Moreover, the main excitatory and inhibitory neurotransmitters associated with neural plasticity have also been extensively investigated for their role in the cognitive deficits associated with schizophrenia. Transcranial magnetic stimulation (TMS) represents some of the most promising approaches to directly explore the physiological manifestations of neural plasticity in the human brain. Three TMS paradigms (use-dependent plasticity, paired associative stimulation, and repetitive TMS) have been used to evaluate neurophysiological measures of neural plasticity in the healthy brain and in patients with schizophrenia, and to examine the brain's responses to such stimulation. In schizophrenia, deficits in neural plasticity have been consistently shown which parallel the molecular evidence appearing to be entwined with this debilitating disorder. Such pathophysiology may underlie the learning and memory deficits that are key symptoms of this disorder and may even be a key mechanism involved in treatment with antipsychotics.


Association of Reversal of Renin Suppression With Long-Term Renal Outcome in Medically Treated Primary Aldosteronism.
Renin suppression in primary aldosteronism indicates mineralocorticoid receptor activation via excessive aldosterone secretion, inducing renal damage. We investigated whether the reversal of renin suppression after the initiation of mineralocorticoid receptor antagonist therapy was associated with long-term renal outcomes in medically treated patients with primary aldosteronism. This retrospective cohort study included 318 patients with primary aldosteronism treated with mineralocorticoid receptor antagonist between 2008 and 2020 at the Yokohama Rosai Hospital in Japan. The posttreatment renin status was defined as unsuppressed (ie, reversal of renin suppression) when individual plasma renin activity after the initiation of mineralocorticoid receptor antagonist (post-plasma renin activity) was ≥1.0 ng/mL per hour; otherwise, it was defined as suppressed. We analyzed the association of posttreatment renin status with subsequent longitudinal estimated glomerular filtration rate changes using linear mixed-effects models for repeated measurements, adjusting for potential confounders. The posttreatment renin status of 119 patients was unsuppressed (median post-plasma renin activity, 1.7 ng/mL per hour) and that of 199 patients was suppressed (median post-PRA, 0.5 ng/mL per hour). Through the median follow-up period of 3.1 years, the decline in estimated glomerular filtration rate was milder among patients with the unsuppressed posttreatment renin (-0.46 [95% CI, -0.63 to -0.28] mL/min per 1.73 m2 per year) than those with suppressed posttreatment renin (-1.41 [95% CI, -1.56 to -1.27] mL/min per 1.73 m2 per year; difference, 0.96 [95% CI, 0.72-1.20] mL/min per 1.73 m2 per year). Our findings may highlight the importance of reversing renin suppression with optimal mineralocorticoid receptor antagonist titration in medically treated primary aldosteronism, which could mitigate adverse renal outcomes.


Patient survival with pacemaker therapy at regional hospital, Orebro, Sweden, 1964-1974.
The results of pacemaker therapy in the Regional Hospital, Orebro, during its first 10 years are presented. In general, patients with a history of temporary heart failure either before or at the time of implantation, had a better prognosis than those with such a history. Myocardial infarction had a detrimental effect on the prognosis in the first year of the patients pacing, but not thereafter.


Differential expression of connective tissue growth factor gene in cutaneous fibrohistiocytic and vascular tumors.
Connective tissue growth factor (CTGF) is a member of a family of immediate early gene products that may play an important role during tissue regeneration, wound repair and skin fibrosis. In this study, CTGF gene expression in mesenchymal tumors was investigated by in situ hybridization and CD34 antigen expression was studied by means of immunohistochemical staining. CTGF mRNA was expressed in fibroblasts of all nine dermatofibromas examined, but five of seven dermatofibrosarcoma protuberans (DFSP) or two cases of malignant fibrous histiocytoma were negative for its expression. In contrast, CD34 antigen was expressed only in DFSP. In vascular tumors, CTGF mRNA was expressed in pyogenic granuloma but not in angiosarcoma. In addition, the endothelial cells in angiolipoma and angioleiomyoma, but not in venous lake, expressed CTGF mRNA. These vascular lesions were all positive for CD34 expression. Tumors of other origins were negative for CTGF mRNA. Our findings indicated that benign fibroblasts and/or vascular endothelial cells have the capability to express CTGF mRNA when activated, but these cells lose this ability when they achieve malignant potency. Thus, examination of CTGF gene expression may be useful for differentiating between benign and malignant mesenchymal tumors, or to determine the origin of the tumors in connective tissue.


Robotic lobectomy: tips, pitfalls and troubleshooting.
The robotic approach in thoracic surgery has rapidly gained popularity in recent years. As with the introduction of any new technology, this warrants not only adaptation of the operative technique itself, but also the evolution of appropriate troubleshooting strategies. A selected number of helpful tips and technical procedural manoeuvres have been compiled to prevent intraoperative problems, as well as to overcome challenging situations that can arise during robotic lobectomies. In robotic surgery, as opposed to open surgery or video-assisted thoracic surgery, these tips serve an important purpose for the operating surgeon, as well as the entire surgical team involved in the procedure. All the assembled recommendations have proved their effectiveness and have been successfully used by the authors in many procedures. Furthermore, these manoeuvres have been found to be of great importance in the training and proctoring of thoracic surgeons, fellows and residents (bed-side assistants). This guide of clearly arranged tips and troubleshooting strategies offers surgeons a useful tool to overcome difficult situations in robotic lobectomy and preferably improve the reproducibility and safety of their procedures.


Hydrogen-Bonded Polymer-Porphyrin Assemblies in Water: Supramolecular Structures for Light Energy Conversion.
In this study, a new type of functional, self-assembled nanostructure formed from porphyrins and polyamidoamine dendrimers based on hydrogen bonding in an aqueous solution is presented. As the aggregates formed are promising candidates for solar-energy conversion, their photocatalytic activity is tested using the model reaction of methyl viologen reduction. The self-assembled structures show significantly increased activity as compared to unassociated porphyrins. Details of interaction forces driving the supramolecular structure formation and regulating catalytic efficiency are fundamentally discussed.


Maternal comprehension of two growth monitoring charts in Sri Lanka.
To investigate the maternal comprehension of two different growth charts and to identify the group of mothers with poor comprehension. An experimental prospective study. A child welfare clinic at the De Soysa Hospital for Women, Colombo, Sri Lanka. 932 mothers were studied regarding their interpretation of the type of growth chart their infants had been allocated. A total of 413 mothers interpreted the 'road-to-health' chart and 519 mothers interpreted the revised chart. A validated scoring system was used to assess comprehension. The two groups of mothers were comparable. 62.4% (324) mothers who interpreted the revised chart had good comprehension. Only 20.6% (85) mothers had similar comprehension with the road-to-health chart. Education up to or beyond grade 8 in school significantly improved comprehension. The design of the growth chart has a powerful effect on maternal comprehension of growth patterns. Length of schooling rather than literacy alone is a marker of a comprehending mother. The policy implications of these findings are that governments and agencies may need to redesign parent held growth charts to achieve better comprehension by mothers.


[Clinical outcomes of treatment of glenohumeral osteoarthritis with new generation shoulder prosthesis].
To investigate the clinical effects of arthroplasty with UNIVERS 3-D prosthesis, the representative of fourth generation of shoulder joint prosthesis proved to be more suitable to shoulder anatomy, in treatment of glenohumeral osteoarthritis. Seventy-four patients with glenohumeral osteoarthritis, aged 67.07 (47 - 84), received shoulder arthroplasty with UNIVERS 3-D prosthesis and were followed up for 31.9 months (12 - 74 months). Roentgenography was conducted to observe the acromion, and acromion-humeral distance (AHD), glenohumeral distance (GHD), humerus height (HH), and humerus width (HW). Constant scoring and normalized Constant scoring were used to evaluate the function of the shoulder joint. The Constant score at the last follow-up was 68.40 +/- 16.91 points, significantly higher than that at beginning (34.094 +/- 15.00, P < 0.05), The normalized Constant score at the last follow-up was 92.27 +/- 22.53%, significantly higher than that at the beginning (45.29 +/- 19.87%, P < 0.05). The post-operative pain, daily life, activity score, and myodynamia scores were all significantly higher than those evaluated pre-operatively (all P < 0.05). Pre-operative roentgenography showed 93.47% of the cases with humeral head periarticular osteophytes located at the inferior side; 36.96% with humeral head necrosis; 8.69% with humeral head cyst; and 39.13% with periarticular osteophytes of glenoid, and showed that AHD was shortened (1.83 +/- 1.64 mm), and GHD, HH, and HW were all narrowed (10.91 +/- 3.03 mm; 5.71 +/- 4.32 mm, and 3.34 +/- 4.82 mm respectively). After the operation, the AHD, GHD, and HH were all significantly increased, and HW did not significantly changed. The humeral inclination angle was changed postoperatively from 126 degrees to 142 degrees. The incidence of radiolucent lines around the prosthesis of humeral shaft was 5.41%, most in the zones d, c, and e, all with the radiolucent index of less than 1. The overall complication rate was 12.2%. Treatment of glenohumeral osteoarthritis with UNIVERS 3-D prosthesis effectively reconstructs the anatomy of glenohumeral joint, and shows excellent clinical results with low incidence of radiolucency and postoperative complications.


Role of ErbB2 in Corneal Epithelial Wound Healing.
Human corneal epithelial cells (HCECs) were functionally depleted of erbB2 to elucidate its role in epidermal growth factor (EGF) receptor (EGFR) activation-dependent cell migration. The retrovirus pBabe-5R, which encodes an erbB2 single-chain antibody with an endoplasmic reticulum (ER)-targeting sequence, and control pBabe-puro were used to infect THCE cells (an SV40-immortalized HCEC line). Several cell lines expressing 5R were selected along with a pBabe-puro control line. The depletion of erbB2 was verified by cell surface biotinylation of proteins, followed by streptavidin precipitation and subsequent detection of erbB2 by immunoblot analysis. Activation of erbBs was analyzed by immunoprecipitation using the phosphotyrosine antibody pY20, followed by Western blot analysis with erbB1 or erbB2 antibodies. Phosphorylation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3'-kinase (PI3K) was analyzed by Western blot with antibodies specific to phosphorylated proteins. Effects of erbB2 depletion on heparin-binding EGF-like growth factor (HB-EGF)-induced cell migration were determined by Boyden chamber migration assay and by scratch wound assay. Wounding induced erbB2 tyrosine phosphorylation. Expression of 5R encoding an erbB2 single-chain antibody with an endoplasmic reticulum-targeting sequence depleted the cell surface expression of erbB2 in HCECs. Wounding resulted in a rapid increase in the phosphorylation of erbB1 in both 5R-expressing and control cells, whereas wound-induced erbB2 phosphorylation in 5R-expressing cells was not detectable. Depletion of functional erbB2 attenuated the healing of scratch wounds in the presence of HB-EGF and impaired both chemotactic migration stimulated by HB-EGF and haptotactic migration toward a fibronectin-collagen I (3:1; FNC) coating mix. Expression of 5R affected both the intensity and the duration of wound-induced, EGFR-elicited ERK and PI3K activation. Inhibition of ERK and PI3K pathways in cultured porcine corneas impaired ex vivo epithelial wound healing. ErbB2 serves as a critical component that couples erbB receptor tyrosine kinase to the migration machinery of corneal epithelial cells.


New insights on laser-induced graphene electrodes for flexible supercapacitors: tunable morphology and physical properties.
In certain polymers the graphenization of carbon atoms can be obtained by laser writing owing to the easy absorption of long-wavelength radiation, which generates photo-thermal effects. On a polyimide surface this process allows the formation of a nanostructured and porous carbon network known as laser-induced graphene (LIG). Herein we report on the effect of the process parameters on the morphology and physical properties of LIG nanostructures. We show that the scan speed and the frequency of the incident radiation affect the gas evolution, inducing different structure rearrangements, an interesting nitrogen self-doping phenomenon and consequently different conduction properties. The materials were characterized by infrared and Raman spectroscopy, XPS elemental analysis, electron microscopy and electrical/electrochemical measurements. In particular the samples were tested as interdigitated electrodes into electrochemical supercapacitors and the optimized LIG arrangement was tested in parallel and series supercapacitor configurations to allow power exploitation.


NOD-scid mouse as an experimental animal model for cysticercosis.
The major three species of human taeniid cestodes, Taenia solium, T. saginata and T. saginata asiatica (= T. asiatica) which require humans as the definitive host are still not rare in developing countries. Among these, T. solium is the most serious with medical and economic importance. Neurocysticercosis (NCC) in humans is now recognized as the major cause of neurologic disease in the world. As these human taeniid cestodes obligatory require domestic animals such as swine, cattle and swine as the major intermediate host animals respectively, it is not easy to analyze the basic research in these domestic animals. In this brief review, we introduce experimental animal model for these three species in order to obtain fully developed metacestode stage in severe combined immunodeficiency (scid) mice. Non-obese diabetic scid (NOD-scid) mice are expected to be a satisfactory animal model and to have advantages for analysis by several view points of developmental biology with gene expression throughout development, antigenic homology of cyst fluid of these three species, evaluation of drug efficacy or metacestocidal drug designs, confirmation of unknown taeniid gravid segments for identification based on the morphology and DNA analysis of metacestodes. The animal model is not only available for human Taenia spp but can also be applied to other taeniid cestodes of economic importance or in veterinary parasitology.


Sulfur-Doped Porphyrinic Carbon Nanostructures Synthesized with Amorphous MoS2 for the Oxygen Reduction Reaction in an Acidic Medium.
To develop doped carbon nanostructures as non-precious metal cathode catalysts, nanocomposites were synthesized by using SBA-15 and 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin-iron(III) chloride with different ratios of amorphous MoS2 precursor. From various analyses, it was found that, during pyrolysis at 900 °C under an N2 atmosphere, the amorphous MoS2 precursor decomposed into Mo and S, facilitating the formation of graphene sheet-like carbon with MoC and doping of sulfur in the carbon. In the nanocomposite formed from 10 wt % MoS2 precursor (denoted as Mo/S/PC-10), most of the MoS2 was decomposed, thus forming S-doped carbon, which was grown on the MoC phase without crystalline MoS2 . Furthermore, Mo/S/PC-10 exhibited better performance in the oxygen reduction reaction (specific activity of 1.23 mA cm-2 at 0.9 V and half-wave potential of 0.864 V) than a commercial Pt catalyst, owing to a heteroatom-doped carbon nanostructure with a fairly high specific surface area. In the polarization curve of the unit-cell performance measured at 80 °C under ambient pressure, Mo/S/PC-10 as a cathode catalyst exhibited an optimal power density of 314 mW cm-2 and a current density of 280 mA cm-2 at 0.6 V.


Comparison of clinical and radiographic outcomes of arthroscopic-assisted percutaneous fixation versus open reduction internal fixation of lateral tibial plateau fractures.
Treatment for tibial plateau fractures continues to evolve but maintains primary objectives of anatomic reduction of the joint line and a rapid recovery course. Arthroscopic-assisted percutaneous fixation (AAPF) has been introduced as an alternative to traditional open reduction internal fixation (ORIF). The purpose of the study is to compare clinical and radiographic outcomes in patients with low-energy Schatzker type I-III tibial plateau fractures treated with AAPF versus ORIF. A retrospective chart review was performed at a level 1 trauma centre to compare outcomes of 120 patients (57 AAPF, 63 ORIF) with low-energy lateral Schatzker type I-III tibial plateau fractures who underwent tibial plateau fixation between 2009 and 2018. Demographic information, injury characteristics, and surgical treatment were recorded. The main outcome measurements included reduction step-off, joint space narrowing, time to weight bearing, and implant removal. There was no difference in age, gender distribution, BMI, ASA, Schatzker classification distribution, initial displacement, blood loss, and reduction step-off between the two groups (p > 0.05). Shorter tourniquet time (74.1 ± 21.7 vs 100.0 ± 21.0 min; p < 0.001), shorter time to full weight bearing (47.8 ± 15.2 vs. 69.1 ± 17.2 days; p < 0.001), and lower rate of joint space narrowing (3.5% vs. 28.6% with more than 1 mm, p < 0.001) were associated with the AAPF cohort, with no difference in pain, knee range of motion, or implant removal rate between the two cohorts. AAPF may be a viable alternative to ORIF for the management of low-energy tibial plateau fractures with outcomes not inferior compared to the traditional ORIF method.


N-heterocyclic carbene catalyzed highly chemoselective intermolecular crossed acyloin condensation of aromatic aldehydes with trifluoroacetaldehyde ethyl hemiacetal.
A highly chemoselective intermolecular crossed acyloin condensation between aromatic aldehydes and trifluoroacetaldehyde ethyl hemiacetal has been developed under mild reaction conditions using N-heterocyclic carbene as a catalyst. A wide range of aromatic aldehydes bearing electron-withdrawing and -donating substituents underwent a smooth transformation to their corresponding trifluoromethyl containing acyloin derivatives in moderate to good yields.


[Transvenous xerotom-angiography of the pulmonary hilus (author's transl)].
Normal-size lymph-nodes and air-filled bronchi do not contribute significantly to the shadow of the normal hilus. This consists mainly in pulmonary arteries and veins of the upper lobes. Any enlargement beyond the vascular shadow has to be considered as pathologic. Xerotom-angiography following injection of contrast medium into the cubital vein shows the pulmonary vessels near the hilus more clearly. Pulmonary arteries towards the truncus are better shown. This improves the clarity of the hilus. Coincident demonstration of the superior vena cava may show pathologic processes in the upper mediastinum.


A review of the psychoneuroimmunologic concepts on the etiology of depressive disorders.
The brain is no longer considered an immunoprivileged organ which is completely separated from the circulating immune cells by the blood-brain barrier and which shows a lowered or changed immunoreactivity. It has become clear that there are numerous interactions between the neurological, immune and neuroendocrinologic systems. The psychiatric disorder which is supposed to be connected to changes in the functioning of the immune system is depression. One of the hypotheses suggesting the pathophysiology of depression is the cytokine hypothesis of depression. According to it, the behavior changes in depressed patients are a consequence of changes in cytokines. Physiological and psychological effects of the immune activation during an infection, primarily mediated by central activity of peripherally excreted proinflammatory cytokines, are called "sickness behavior". Depression is connected with the activation of the inflammatory response system. When it comes to the immune characteristics of depressive disorders, it should be stressed that depression is a heterogeneous disorder, so different types of depression can differ not only psychopathologically but also at the immune level. Depression is characterized by disorders in noradrenergic and serotonergic neurotransmission. Proinflammatory cytokines are included in the noradrenergic and serotonergic neurotransmission in the brain areas that are thought to be involved in the pathogenesis of depression. According to this model, depression can be considered a psychoneuroimmune disease in which the peripheral immune activation is responsible (by excreting the inflammatory mediator) for various behavioral, neuroendocrinologic and neurochemical changes connected to the psychiatric condition.


Flexor aponeurotic release for resistant adaptive shortening of long flexors in claw hands in leprosy.
Adaptive shortening of long flexors (ASLF) is a consequence of long-standing neglected claw finger deformity. While adaptive shortening of muscle fibres is correctable by physiotherapy, concurrent shortening of fascia/aponeurosis/intermuscular septum, composed of inelastic collagen fibres is not. Surgical excision of these structures has been advised in ASLF in cerebral palsy. This procedure in which a 3-4 cm wide band of deep fascia of the forearm, about 6 cm distal to the medial epicondyle, along with the intermuscular septum is excised was tried in seven patients having severe or moderately severe ASLF with good results. This procedure is worth a more extensive trial.


Generation of functional organs from stem cells.
We are now well entering the exciting era of stem cells. Potential stem cell therapy holds great promise for the treatment of many diseases such as stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral-sclerosis, myocardial infarction, muscular dystrophy, diabetes, and etc. It is generally believed that transplantation of specific stem cells into the injured tissue to replace the lost cells is an effective way to repair the tissue. In fact, organ transplantation has been successfully practiced in clinics for liver or kidney failure. However, the severe shortage of donor organs has been a major obstacle for the expansion of organ transplantation programs. Toward that direction, generation of transplantable organs using stem cells is a desirable approach for organ replacement and would be of great interest for both basic and clinical scientists. Here we review recent progress in the field of organ generation using various methods including single adult tissue stem cells, a blastocyst complementation system, tissue decellularization/recellularization and a combination of stem cells and tissue engineering.


In vitrodifferentiation of human cardiac fibroblasts into myofibroblasts: characterization using electrical impedance.
Cardiac arrhythmias represent about 50% of the cardiovascular diseases which are the first cause of mortality in the world. Implantable medical devices play a major role for treating these arrhythmias. Nevertheless the leads induce an unwanted biological phenomenon called fibrosis. This phenomenon begins at a cellular level and is effective at a macroscopic scale causing tissue remodelling with a local modification of the active cardiac tissue. Fibrosis mechanism is complex but at the cellular level, it mainly consists in cardiac fibroblasts activation and differentiation into myofibroblasts. We developed a simplifiedin vitromodel of cardiac fibrosis, with human cardiac fibroblasts whom differentiation into myofibroblasts was promoted with TGF-β1. Our study addresses an unreported impedance-based method for real-time monitoring ofin vitrocardiac fibrosis. The objective was to study whether the differentiation of cardiac fibroblasts in myofibroblasts had a specific signature on the cell index, an impedance-based feature measured by the xCELLigence system. Primary human cardiac fibroblasts were cultured along 6 days, with or without laminin coating, to study the role of this adhesion protein in cultures long-term maintenance. The cultures were characterized in the presence or absence of TGF-β1 and we obtained a significant cell index signature specific to the human cardiac fibroblasts differentiation.