Amplification at 11q23 targets protein kinase SIK2 in diffuse large B-cell lymphoma.
In diffuse large B-cell lymphoma (DLBCL), several recurrent chromosomal aberrations have been described where the presumed target genes remain unknown, including gain/amplification at 11q23-24. Here, we characterized amplification at 11q23 in the DLBCL cell line KARPAS-422. Quantitative genomic PCR and FISH analysis were used to define the region altered, thus showing an amplification peak at 111.1 Mb, the region hosting SIK2/SNF1LK2. Expression profiling, quantitative RT-PCR, Western blot, and immunocytology identified overexpression of SIK2, highlighting this gene as a likely key target of 11q23 amplification. SIK2 encodes a protein kinase that has been shown to inhibit transcription factor CREB via phosphorylation of its cofactor TORC2/CRTC2. Accordingly, siRNA-mediated downregulation of SIK2 expression resulted in upregulation of the CREB target gene BIM. Functional analysis by treatments with cAMP, the glucocorticoid dexamethasone, and 2-deoxy-d-glucose revealed a regulatory role for SIK2 in survival and glucose metabolism, respectively. However, overexpression of SIK2 was not detectable in primary DLBCL samples. Nevertheless, identification of SIK2 as an amplification target highlights this kinase along with its regulatory network as potential therapeutic targets in DLBCL.


Development of medicines for rare diseases and inborn errors of metabolism: Toward novel public-private partnerships.
Medicine development for rare diseases, including inborn errors of metabolism (IEMs) is challenging. Many academic innovations fail to reach the patient, either by stranding in the translational stage or due to suboptimal patient access related to pricing or uncertain effectiveness. Expanding and solidifying the role of the academic in public-private partnerships (PPPs) may present an innovative solution to help overcome these complexities. This narrative review explores the literature on traditional and novel collaborative approaches to medicine development for rare diseases and analyzes examples of PPPs, with a specific focus on IEMs. Several academic institutions have introduced guidelines for socially responsible licensing of innovations for private development. The PPP model offers a more integrative approach toward academic involvement of medicine development. By sharing risks and rewards, failures in the translational stage can be mutually absorbed. If socially responsible terms are not included, however, high pricing can impede patient access. Therefore, we propose a framework for socially responsible PPPs aimed at medicine development for metabolic disorders. This socially responsible PPP framework could stimulate successful and accessible medicine development for IEMs as well as other rare diseases if the establishment of such collaborations includes terms securing joint data ownership and evidence generation, fast access, and socially responsible pricing.


[Health and globalization in the San Diego-Tijuana region].
The international process of trading goods and services with significant reduction in barriers known as globalization is clearly observed at the San Diego-Tijuana region. This essay addresses issues arising at this unique geographical area associated with the globalization process and its public health consequences. Social, cultural and political aspects have very important implications on the health status of the U.S-Mexican population and in the health care systems on both sides of the border. One of the most powerful world economies borders a developing country resulting in a dramatic comparison that has negative outcomes such as health disparities, high prevalence of chronic diseases and new epidemiological risks. Poverty and migration are a few of the contributing factors triggering this asymmetrical relationship. Challenges in border health require a comprehensive binational participation and the solutions are yet to be determined.


Post anaesthetic colic in horses: a preventable complication?
There is little information on the prevalence of, and risk factors associated with, post anaesthetic colic (PAC) in horses undergoing nonabdominal operations. To undertake the first prospective study of prevalence of PAC and identify risk factors in its development in nonabdominal procedures. A multicentre prospective case-control study was conducted, on every horse undergoing anaesthesia for a nonabdominal procedure between April 2004 and June 2005. Colic cases were defined as any horse with recognised signs of abdominal pain within 72 h of general anaesthesia that could not be attributed to any concurrent disease. Five control horses per case were selected randomly from the study population at all hospitals. Multivariable logistic regression analysis was used to examine the relationship between predictor variables and the risk of developing PAC. The estimated mean prevalence of PAC in the study population was 5.2% (95% CI, 2.8, 8.0). However, the prevalence of colic varied between each centre. The most commonly diagnosed cause of colic was impaction. Multivariable analyses showed that the centre involved and the type of surgery performed were associated with an increased risk of PAC. Preoperative food deprivation and the use of opioid drugs were confounding factors. Prevalence of PAC varied significantly between the 4 hospitals studied; there may be hospital-related covariates that account for this. The type of surgery performed influenced the risk of PAC. Identifying the risk factors for PAC is a prerequisite for its prevention. This study indicates horses at increased risk of PAC that might benefit from a more critical evaluation of post anaesthetic gastrointestinal function and/or the provision of preventative measures. Further investigation is required to explain the variation in prevalence of PAC between centres.


Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana.
Eukaryotic genomes are regulated by epigenetic marks that act to modulate transcriptional control as well as to regulate DNA replication and repair. In Arabidopsis thaliana, mutation of the ATXR5 and ATXR6 histone methyltransferases causes reduction in histone H3 lysine 27 monomethylation, transcriptional upregulation of transposons, and a genome instability defect in which there is an accumulation of excess DNA corresponding to pericentromeric heterochromatin. We designed a forward genetic screen to identify suppressors of the atxr5/6 phenotype that uncovered loss-of-function mutations in two components of the TREX-2 complex (AtTHP1, AtSAC3B), a SUMO-interacting E3 ubiquitin ligase (AtSTUbL2) and a methyl-binding domain protein (AtMBD9). Additionally, using a reverse genetic approach, we show that a mutation in a plant homolog of the tumor suppressor gene BRCA1 enhances the atxr5/6 phenotype. Through characterization of these mutations, our results suggest models for the production atxr5 atxr6-induced extra DNA involving conflicts between the replicative and transcriptional processes in the cell, and suggest that the atxr5 atxr6 transcriptional defects may be the cause of the genome instability defects in the mutants. These findings highlight the critical intersection of transcriptional silencing and DNA replication in the maintenance of genome stability of heterochromatin.


Time-consciousness in computational phenomenology: a temporal analysis of active inference.
Time plays a significant role in science and everyday life. Despite being experienced as a continuous flow, computational models of consciousness are typically restricted to a sequential temporal structure. This difference poses a serious challenge for computational phenomenology-a novel field combining phenomenology and computational modelling. By analysing the temporal structure of the active inference framework, we show that an integrated continuity of time can be achieved by merging Husserlian temporality with a sequential order of time. We also show that a Markov blanket of the present moment integrates past and future moments of both subjective temporality and objective time in an asynchronous manner. By applying the integrated continuity, it is clear that active inference makes use of both subjective temporality and objective time in an integrated fashion. We conclude that active inference, on a temporal note, qualifies as a computational model for phenomenological investigations.


Intraoperative localization of sensorimotor cortex by cortical somatosensory evoked potentials.
Intraoperative cortical somatosensory potentials were evoked to localize the sensorimotor cortex under general anesthesia by contralateral median nerve stimulation in 12 patients. Eight patients underwent an excision of the epileptogenic focus for intractable complex partial seizures and the other 4 patients underwent tumor surgery following successful localization of the sensorimotor cortex. The relationships between the somatosensory evoked potentials and the anatomy of the sensorimotor cortex allowed rapid and accurate localization of the sensorimotor hand area: (1) the P2 recorded from the postcentral gyrus had a positivity of 49.0 microV on the average with a mean latency of 26.9 msec; (2) the N1 and P2 consistently showed phase-reversal across the Rolandic fissure; and (3) maximum SEP amplitudes were recorded from the hand representation area of the sensorimotor cortex. The neurophysiological and neurosurgical results demonstrate the feasibility of recording cortical SEP's under general anesthesia and the improvement of safety in surgical excisions near the sensorimotor cortex.


Avoidance Distance in Sheltered Cows and Its Association with Other Welfare Parameters.
The human-animal relationship is an important welfare parameter in animal welfare assessment in cows, and the avoidance distance of cows to a stranger at the feed bunk is measured to assess this relationship. The assessment of the human-animal relationship in cow shelters in India, where old, unproductive, and abandoned cows are sheltered, is important to explore the welfare of cows in these shelters. The cows observed were of indigenous Indian breeds and breeds which were crosses between indigenous breeds and pure bred exotic cows. The human-animal contact in this context is of particular interest for welfare assessment as traditional Indian farming and sheltering systems involves regular close human-animal contact. In a cross-sectional study across 6 states, 54 cow shelters were visited and 30 cows in each shelter were randomly selected (1620 in total) for the assessment of avoidance distance and other cow-based (27 parameters) and resource-based (15 parameters) welfare parameters. Avoidance distance was assessed 1 h after morning feeding. Cows standing at the feeding manger were approached from the front at a rate of one step/s, starting 2 m away from the manger. The distance between the assessor's hand and the cow's head was estimated at the moment the cow moved away and turned its head, using a four-point scale (0, touched; 1, 0-50 cm; 2, 51-100 cm; and 3, >100 cm). The majority, 52%, of the cows allowed touch by the assessor and another 32% allowed approach within 50 cm, demonstrating tolerance, or even solicitation of close human-animal relationships by the cows. Avoidance distance increased with the proportion of cows with dirty hind limbs, tarsal joint swellings, and hair loss, and the extent of rumen fill. There was also evidence of reduced avoidance distances in cows with high levels of body condition score (BCS), dirty flanks, tarsal joint ulceration, carpal joint injuries, diarrhoea, hampered respiration, lesions on the body due to traumatic injuries, and body coat condition, probably as a result of moving difficulties. The avoidance distance was thus related to the health and welfare of the cows, providing a vital insight into the factors affecting human-animal contact in the shelters.


EGFR assays in lung cancer.
The development of small-molecule inhibitors of the epidermal growth factor receptor (EGFR) resulted in new therapeutic options for patients with advanced lung cancer. It was clear from the experience with targeted therapy for breast cancer that a new standardized assay procedure for assessing and predicting the effects of therapeutic agents must be developed. Three academic groups almost simultaneously reported the discovery of somatic mutations in the exons 18 to 21 of the tyrosine kinase (TK) domain of EGFR that correlated with a high likelihood of response to EGFR TK inhibitors. This observation revolutionized understanding of EGFR in lung carcinogenesis and resulted in numerous retrospective studies that correlated patient's response and molecular profile of the lung adenocarcinoma. The results of these studies indicate that clinical benefits from treatment with EGFR TK inhibitors are variable between the different subsets of patients. Multiple methodologic approaches were used including mutational analysis, fluorescence in situ hybridization, and immunohistochemistry. Conflicting results reflect the lack of standardization of the methodology and interpretation. Sample types, sample processing, and storage should also be taken into consideration as another potentially confounding factor. Therefore, it is important to standardize the approach and decide which assays are best to predict patient response to targeted therapies. It is also essential to determine the most cost-effective way to integrate EGFR molecular assays into clinical practice. This review will address practical aspects of each of the currently proposed assays. Difficulties in standardization of these assays in a clinical practice will be discussed.


Development of polycythemia vera and chronic lymphocytic leukemia during the course of refractory idiopathic thrombocytopenic purpura.
A case in which polycythemia vera and chronic lymphocytic leukemia (CLL) developed during the course of idiopathic thrombocytopenic purpura (ITP) is described. Observations in this case suggest that ITP was a pre-monitor of the clinical development of CLL and preceded the manifestation of polycythemia vera. The polycythemia was mild, requiring infrequent phlebotomies, and, as the CLL progressed, the requirement for phlebotomy diminished. Evidence of both CLL and myeloid proliferation, as well as severe immune thrombocytopenia, persisted throughout her course. Studies on lymphocytes revealed characteristics of those of CLL. Excellent therapeutic response of the CLL was observed with the use of vinblastine and steroids.


[Plastic surgery on the lower eyelid destroyed by a bear's paw].
We present a primary plastic surgery in a rare case of traumatic destruction of an inferior eyelid--it was torn by a bear paw. A 64 years old bear-trainer with almost completely torn inferior eyelid was accepted in the clinic for treatment. The trauma was caused by a circus bear while he was taken out from the cage. During the examination we found the eyelid almost completely torn, extremely deformed, strained, smashed and hanging from the outer eyelid corner area. Under the operational microscope we performed primary plastic operation. The postoperative period was calm, a good adaptation of the wound surfaces, anatomic rehabilitation, fine cosmetic effect and eye ball preservation were reached. The presented case is interesting with the cause of the trauma. Despite the hard eye lid destruction the modern microsurgical techniques allowed us to attain good repositioning and good cosmetic effect. We provided defending holding of the eyeball and especially of the cornea and thus we saved them from serious complications.


Modelling daily yields of milk, fat, protein and lactose of New Zealand dairy goats undergoing standard and extended lactations.
This study aimed to assess the milk production data for New Zealand dairy goats in either a standard lactation (SL; ≤ 305 d in milk) or extended lactation (EL; > 305 and ≤ 670 d in milk) using a random regression (RR) with third and fifth order Legendre polynomials, respectively. Persistency of EL was defined as (B/A) × 100, where A was the accumulated yield from d 1 to 305, and B was the accumulated yield from d 366 to 670. On average, goats in a SL produced 1183 kg milk, 37 kg fat, 37 kg protein and 54 kg lactose. The average production of milk, fat, protein, and lactose in EL were 2,473 kg, 78 kg, 79 kg and 112 kg, respectively. The average persistence's for milk, fat, protein, and lactose yields during EL were 117, 117, 122 and 114%, respectively. The relative prediction errors were close to 10% and the concordance correlation coefficients > 0.92, indicating that the RR model with Legendre polynomials is adequate for modeling lactation curves for both SL and EL. Total yields and persistency were analyzed with a mixed model that included the fixed effects (year, month of kidding, parity, and proportion of Saanen) as covariates and the random effects of animal and residual errors. Effects of year, month-of-kidding, and parity were significant (P < 0.01) on the total yields of milk, fat, protein and lactose for both SL and EL. The total milk yield of first-parity goats with a SL was 946 kg and the total milk yield of second-parity goats with a SL was 1,284 kg, making a total of 2,230 kg over 2 years. The total milk yield of a first-parity goat with an EL was 2,140 kg. Thus, on average, a goat with SL for the first and second parity produced 90 kg more milk than a first-parity goat subjected to extended lactation. However, a second-parity goat subjected to an extended lactation produced 43 kg more milk (2,639 kg) than a goat with SL following the second and third parity (1,284 kg + 1312 kg). These data, along with the various other benefits of EL (e.g., fewer offspring born and reduce risk of mastitis, lameness, metabolic problems in early lactation), indicate that EL as a management strategy holds the potential to improve dairy goat longevity and lifetime efficiency without compromising milk production.


Ubiquitin recognition by FAAP20 expands the complex interface beyond the canonical UBZ domain.
FAAP20 is an integral component of the Fanconi anemia core complex that mediates the repair of DNA interstrand crosslinks. The ubiquitin-binding capacity of the FAAP20 UBZ is required for recruitment of the Fanconi anemia complex to interstrand DNA crosslink sites and for interaction with the translesion synthesis machinery. Although the UBZ-ubiquitin interaction is thought to be exclusively encapsulated within the ββα module of UBZ, we show that the FAAP20-ubiquitin interaction extends beyond such a canonical zinc-finger motif. Instead, ubiquitin binding by FAAP20 is accompanied by transforming a disordered tail C-terminal to the UBZ of FAAP20 into a rigid, extended β-loop that latches onto the complex interface of the FAAP20 UBZ and ubiquitin, with the invariant C-terminal tryptophan emanating toward I44(Ub) for enhanced binding specificity and affinity. Substitution of the C-terminal tryptophan with alanine in FAAP20 not only abolishes FAAP20-ubiquitin binding in vitro, but also causes profound cellular hypersensitivity to DNA interstrand crosslink lesions in vivo, highlighting the indispensable role of the C-terminal tail of FAAP20, beyond the compact zinc finger module, toward ubiquitin recognition and Fanconi anemia complex-mediated DNA interstrand crosslink repair.


Templating in uncemented total hip arthroplasty-on intra- and interobserver reliability and professional experience.
This study examines the intra-, and interobserver reliability of digital templating in uncemented total hip arthroplasty (THA), and assesses whether these values are dependent on professional experience. Three independent observers retrospectively examined digital X-rays of 34 consecutive hips scheduled for uncemented THA. These were templated using templating software. Evaluations were carried out on two occasions at least 6 weeks apart. Findings were compared to each surgeon's own findings, and then to the other surgeons' findings. Data underwent statistical analysis to assess and describe reliability. The intraobserver reliability of the method was found to be good. The intra-class correlation coefficient (ICC) for individual surgeons ranged from 0.81 to 0.87 for acetabular components and 0.74 to 0.91 for femoral components. However, it was somewhat lower for neck length with kappa statistics (κ) from 0.41 to 0.51 with agreement in about 70% of the cases. Interobserver reliability was similar, with an ICC of 0.87 for the acetabular component and 0.79 for the femoral component, but somewhat lower for neck length with κ of 0.27 and agreement in 41% of the cases. We found no association between increasing experience and increasing precision, as the least experienced observer showed the highest intraobserver reliability. The reliability of digital templating of uncemented THA is good for acetabular and femoral components, but inferior for neck length. Precision does not rely on professional experience. Digital templating provides surgeons with a valuable tool for preoperative planning, but cannot supersede the intraoperative assessment and final decision.


Extension block pinning of mallet fractures.
The operative treatment of mallet fractures of more than one third of the articular surface is controversial. The purpose of this study was to evaluate the complications and functional outcome of extension block pinning technique. Thirty-six consecutive patients with mallet fractures that involved more than one third of the joint surface were treated by extension block pinning a median of 3 days after injury (range 0-35, mean 7). Clinical outcome was graded according to Crawford's criteria. At a median follow-up of 16.5 months (range 2.5-52, mean 20) 23 patients had an excellent or good result, 11 patients had a fair, and 2 patients a poor, clinical outcome according to Crawford's criteria. None of the patients complained of pain. The median extension loss was 0 degrees (range 0-20, mean 4) and the median flexion was 70 degrees (range 30-95, mean 68). Eight patients had operative or direct postoperative complications including superficial infection (n = 6), loss of Kirschner wire (K-wire) fixation (n = 1), and K-wire mal position (n = 1). The extension block pinning technique is a minimally invasive method of treating mallet fractures with low morbidity and a good functional outcome.


Does Preoperative Serum Neutrophil to Lymphocyte Ratio (NLR), Platelet to Lymphocyte Ratio (PLR), and Lymphocyte to Monocyte Ratio (LMR) Predict Prognosis Following Radical Surgery for Pancreatic Adenocarcinomas? Results of a Retrospective Study.
Pretherapy serum neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) have been shown to predict prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the published literature is conflicting; hence, we aimed to evaluate their role in predicting survival outcomes in operated patients of PDAC. A retrospective analysis was performed in all operated cases of PDAC who underwent curative resection between 2011 and 2018. The pretherapy NLR, PLR, and LMR were calculated and analyzed with respect to pathological and survival outcomes RESULTS: One hundred thirty-four operated patients were included. The median overall survival for NLR of less than 2, 2.7, and 5 was 30.8, 27.2, and 27.5 months and for NLR of more than 2, 2.7, and 5 was 22.9, 21.6, and 21.5 months, respectively, and was statistically insignificant (p-value-0.32, 0.91, 0.34, respectively). Similarly, the PLR was not significant for a cutoff of 150 (p-value-0.27), and LMR was not significant for a cutoff of 2.8 (p-value-0.13) and 4.8 (p-value-0.11). On univariate analysis age, CA 19-9 levels, perineural invasion, margin positivity, lymph node positivity, and TNM stage were found to have a significant correlation with overall survival. However, on multivariate analysis, only TNM stage was found to be significant. The NLR, PLR, and LMR do not correlate with overall survival in operated patients with PDAC in this study. A combination of inflammatory markers or their dynamic testing might probably achieve prognostic significance.


[A cross-sectional study on dyslipidemia in migrants in Inner Mongolia Autonomous Region].
Objective: To investigate the prevalence of dyslipidemia in migrants in Inner Mongolia Autonomous Region. Methods: A stratified multi-stage cluster equal size sampling was performed among the migrants aged ≥18 years who were engaged in manufacturing, wholesale retail, accommodation and catering service, social service, construction and other and 1 501 migrants from five area in Inner Mongolia Autonomous Region was investigated by means of questionnaires survey, physical measurements and laboratory detection. Results: Complete data was obtained in 1 496 study subjects. The prevalence of dyslipidemia was 42.65% (638/1 496), the age-standardized prevalence was 42.05%; the prevalence of hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia and low high-density lipoprotein hyperlipidemia were 4.90% (73/1 491), 14.76% (220/1 491), 4.83% (72/1 496), 25.27% (378/1 496), respectively. Dyslipidemia characterized by high triglyceride (HTG) and low high-density lipoprotein cholesterol (LHDL-C) accounted for 81.97% (523/638). The prevalence of dyslipidemia and HTG/LHDL-C dyslipidemia were similar, which increased significantly with age in both females and males, but was significantly higher in males. The prevalence among migrants with other occupations was highest. The prevalence of HTG/LHDL-C dyslipidemia didn't significantly increase with the duration of migration. However, the prevalence of high TG and dyslipidemia increased significantly with the duration of migration, the prevalence of high TG in age group <45 years showed the same characteristics. Conclusions: The prevalence of dyslipidemia in migrants in Inner Mongolia was high, and the main form was HTG/LHDL-C dyslipidemia. The prevalence in males, the middle aged and aged as well as those with other occupations were high. Migrants with longer duration of migration had higher prevalence of dyslipidemia.


Inhibition of soluble tumor necrosis factor ameliorates synaptic alterations and Ca2+ dysregulation in aged rats.
The role of tumor necrosis factor α (TNF) in neural function has been investigated extensively in several neurodegenerative conditions, but rarely in brain aging, where cognitive and physiologic changes are milder and more variable. Here, we show that protein levels for TNF receptor 1 (TNFR1) are significantly elevated in the hippocampus relative to TNF receptor 2 (TNFR2) in aged (22 months) but not young adult (6 months) Fischer 344 rats. To determine if altered TNF/TNFR1 interactions contribute to key brain aging biomarkers, aged rats received chronic (4-6 week) intracranial infusions of XPro1595: a soluble dominant negative TNF that preferentially inhibits TNFR1 signaling. Aged rats treated with XPro1595 showed improved Morris Water Maze performance, reduced microglial activation, reduced susceptibility to hippocampal long-term depression, increased protein levels for the GluR1 type glutamate receptor, and lower L-type voltage sensitive Ca(2+) channel (VSCC) activity in hippocampal CA1 neurons. The results suggest that diverse functional changes associated with brain aging may arise, in part, from selective alterations in TNF signaling.


A Novel and Innovative Way of Nasogastric Tube Insertion in Anesthetized Intubated Patient.
Nasogastric tube (NGT) placement in anesthetized and intubated is sometimes very challenging with more than 50% failure rate in the first attempt. We describe a newer innovative Sahu's three in one, technique with use of GlideScope and forward placement of intubated trachea by external laryngeal maneuver, these both techniques lead to separation of trachea from esophagus so that endoscopic jejunal feeding tube guide wire strengthen NGT can be guided and manipulated to esophagus under direct vision. After informed consent, we used Sahu's three in one combo technique to insert NGT in adult anesthetized and intubated patients of both the sexes with high success in the first attempt. We found this technique easy, helpful, less time consuming with high success rate.


Smart Farming Revolution: Portable and Real-Time Soil Nitrogen and Phosphorus Monitoring for Sustainable Agriculture.
Precision agriculture is crucial for ensuring food security in a growing global population. Nutrients, their presence, concentration, and effectiveness, are key components in data-driven agriculture. Assessing macro and micro-nutrients, as well as factors such as water and pH, helps determine soil fertility, which is vital for supporting healthy plant growth and high crop yields. Insufficient soil nutrient assessment during continuous cropping can threaten long-term agricultural viability. Soil nutrients need to be measured and replenished after each harvest for optimal yield. However, existing soil testing procedures are expensive and time-consuming. The proposed research aims to assess soil nutrient levels, specifically nitrogen and phosphorus concentrations, to provide critical information and guidance on restoring optimal soil fertility. In this research, a novel chip-level colorimeter is fabricated to detect the N and P elements of soil onto a handheld colorimeter or spectrophotometer. Chemical reaction with soil solution generates color in the presence of nutrients, which are then quantitatively measured using sensors. The test samples are collected from various farmlands, and the results are validated with laboratory analysis of samples using spectrophotometers used in laboratories. ANOVA test has been performed in which F value > 1 in our study indicates statistically significant differences between the group means. The alternate hypothesis, which proposes the presence of significant differences between the groups, is supported by the data. The device created in this paper has crucial potential in terms of environmental and biological applications.


DEHP-plasticised PVC: relevance to blood services.
Phthalates are the most widely used plasticisers in the world and have been in medical use since 1955. Di(2-ethylhexyl)phthalate (DEHP) is present in many industrial and domestic products, and is a common plasticiser used in blood bags and tubing sets. Concerns have been raised by environmental groups that DEHP exposure may result in gender birth defects and the feminisation of boys although there were no studies performed of intravenous exposure to DEHP on higher mammals or humans which report similar effects. This article reports on the toxicology of DEHP and considers concerns regarding its use in the context of transfusion medicine. The benefits of using DEHP are evaluated and the use of alternative plasticisers to DEHP is explored. The article reports on international and European regulatory recommendations for DEHP use in transfusion medicine and examines the impact of legislation on the medical devices and blood industries. The article also reviews labelling considerations for blood components and offers some guidance for blood establishments in respect of DEHP use.


Morphopathological particularities of cerebrovascular diseases for patients in the northeastern area of Romania.
Cerebrovascular diseases (CVD) are pathologies caused by the primary or secondary damage of one or more arteries supplying the brain. Our study aims to create a link between the modifiable risk factors, the affected vascular territory and the clinical manifestation of CVD in patients from our geographical area. Our study proposes the retrospective analysis of a group of 70 patients diagnosed with ischemic stroke with spontaneous hemorrhagic transformation over a period of five years, between April 1, 2015 and April 1, 2018, admitted in the 1st Neurology Clinic, "Prof. Dr. Nicolae Oblu" Clinical Emergency Hospital, Iaşi, Romania. The pathology of strokes is determined by risk factors and comorbidities, which have a clear demographic pattern. The existence of a correlation between demographic risk factors of CVD and the clinical manifestation allows for the individualization of a clinical examination protocol leading to a rapid diagnosis.


Induction of apoptosis and modulation of activation and effector function in T cells by immunosuppressive drugs.
Immunosuppressive drugs (ISD) are used for the prevention and treatment of graft rejection, graft-versus-host-disease (GVHD) and autoimmune disorders. The precise mechanisms by which ISD interfere with T cell activation and effector function or delete antigen-specific T cells are defined only partially. We analysed commonly used ISD such as dexamethasone (DEX), mycophenolic acid (MPA), FK506, cyclosporin A (CsA), rapamycin (RAP), methotrexate (MTX) and cyclophosphamide (CP) for apoptosis-induction and modulation of activation and effector function in human peripheral T cells, cytotoxic T cell lines (CTL) and Jurkat T cells. Of all drugs tested only CP and MTX prevented antigen-specific proliferation of T cells and decreased cytotoxicity of alloantigen specific CTL lines by direct induction of apoptosis. MTX and CP also slightly increased activation-induced cell death (AICD) and CD95-sensitivity. In contrast, all other drugs tested did not induce T cell apoptosis, increase CD95-sensitivity or AICD. CsA and FK506 even prevented AICD by down-modulation of CD95L. DEX, MPA, CsA, FK506 and RAP inhibited activation of naive T cells, but were not able to block proliferation of activated T cells nor decrease cytotoxic capacity of CTL lines. These results show that ISD can be classified according to their action on apoptosis-induction and inhibition of proliferation and would favour a rational combination therapy to delete existing reactive T cells and prevent further T cell activation.


Antifibrotic Effects of the Thiazolidinediones in Eosinophilic Esophagitis Pathologic Remodeling: A Preclinical Evaluation.
Eosinophilic esophagitis (EoE) is a T-helper 2 (Th2), eosinophilic disease associated with pathologic tissue remodeling that leads to end-organ dysfunction. During early-stage disease, inflammation and subepithelial fibrosis are coupled and reversible, but in late-stage or therapy-resistant disease, there can be uncoupling of these features with progressive esophageal rigidity and strictures contributing to clinical dysphagia and food impactions. No current pharmacotherapeutic interventions directly target esophageal fibrosis. Based on the ability of the thiazolidinediones (TZD) to regulate intestinal and hepatic fibrosis, we tested the antifibrotic effects of the TZDs, rosiglitazone and pioglitazone, in preclinical studies using primary human esophageal fibroblasts. Primary fibroblasts isolated from normal or EoE esophagi were treated with transforming growth factor (TGF)-β1 in the absence or presence of TZDs and, in some experiments, without or with budesonide and analyzed by quantitative real-time PCR and immunoblotting. Immunohistochemical analysis of human esophageal biopsies was performed. EoE esophageal biopsies and esophageal fibroblasts expressed higher levels of the TZD receptor, peroxisome proliferator-activated receptor-γ (PPAR-γ), than normal controls. PPAR-γ was inducible by the Th2 cytokine, interleukin 4 (IL-4). TZD significantly reduced TGF-β1-induced myofibroblast and fibrotic gene and protein expression preferentially in EoE, but not normal esophageal fibroblasts. In esophageal fibroblasts, TGF-β1 increased phosphorylated Smad2/3 and p38, but TZDs preferentially inhibited p38 phosphorylation, suggesting signaling pathway-specific effects. The TZDs were more potent than budesonide at decreasing collagen-1α1 expression. The TZDs preferentially exert antifibrotic effects in TGF-β1-activated EoE fibroblasts and provide a preclinical foundation for further investigation of the potential of the TZDs in EoE pathologic remodeling.


Effectiveness of Radial Extracorporeal Shock Wave Therapy (rESWT) When Combined With Supervised Exercises in Patients With Subacromial Shoulder Pain: A Double-Masked, Randomized, Sham-Controlled Trial.
Subacromial shoulder pain is a common complaint, and radial extracorporeal shock wave therapy (rESWT) is increasingly used to treat this condition. Although many therapists use rESWT in combination with supervised exercises, no studies have evaluated the additional effect of rESWT with supervised exercises for subacromial shoulder pain. To assess whether rESWT is more effective than sham rESWT when combined with supervised exercises for improving pain and function in patients with subacromial shoulder pain. Randomized controlled trial; Level of evidence, 1. Patients between 25 and 70 years of age with subacromial shoulder pain with and without calcification in the rotator cuff lasting at least 3 months were assessed for eligibility; 143 patients were recruited. Participants were allocated (1:1) by computer-generated randomization in blocks of 20 to receive either rESWT or sham rESWT in addition to supervised exercises. The rESWT and sham rESWT were performed once a week with additional supervised exercises once a week for the first 4 weeks. The following 8 weeks, the patients received supervised exercises twice a week. The primary outcome was change in the Shoulder Pain and Disability Index (SPADI) after 24 weeks. Patients and outcome assessors were masked to group assignment. At 24 weeks, participants in both the sham group and the rESWT group had improved ( P < .001) in SPADI score compared with baseline (-23.9 points [SD, 23.8 points] and -23.3 points [SD, 25.0 points], respectively), but there were no differences between the groups (mean difference 0.7; 95% CI, -6.9 to 8.3; P = .76). Prespecified subgroup analysis of patients with calcification in rotator cuff showed that the rESWT group had a greater improvement in SPADI score after 24 weeks (mean difference -12.8; 95% CI, -24.8 to -0.8; P = .018). Radial ESWT offered no additional benefit to supervised exercises in the treatment of subacromial shoulder pain after 24 weeks, except in the subgroup of patients with calcification in the rotator cuff. Registration: NCT01441830 ( ClinicalTrials.gov identifier).


Randomized, placebo controlled, double blinded pilot superiority phase 2 trial to evaluate the effect of curcumin in moderate to severe asthmatics.
Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment. This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500 mg or matching placebo by mouth twice daily for the study period of 12 weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time. The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin's role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19. This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://clinicaltrials.gov/ct2/show/NCT04353310 .


Effect of acute hypertension on sodium reabsorption by the proximal tubule.
The effect of acute hypertension on sodium reabsorption by the proximal tubule was studied in rats by means of micropuncture methods. Hypertension was induced by bilateral carotid artery ligation and cervical vagotomy. Within a few minutes after blood pressure rose (30-60 mm Hg above control levels), a moderate natriuresis and diuresis began. Proximal sodium reabsorption, measured by two independent methods, was found to be markedly suppressed, both in absolute amount per unit length and per unit of tubular volume (C/pir(2)). The ratio between tubular volume and glomerular filtration rate (GFR) (pir(2)d/V(0)) was found to be increased. These observations indicate that the inhibition of proximal sodium reabsorption induced by hypertension cannot be explained by the tubular geometry hypothesis of sodium regulation. Several possible hormonal mechanisms were investigated. Intravenous d-aldosterone did not prevent the suppression of sodium transport due to acute hypertension, nor did chronic oral saline loading to reduce the renal content of renin. Constriction of the suprarenal aorta, with maintenance of a normal renal perfusion pressure, did prevent the inhibition of proximal transport during carotid artery occlusion, thus excluding an extrarenally produced natriuretic hormone as the mechanism. The observations are compatible with the view that sodium transport was inhibited either by an intrarenal natriuretic hormone or by an increase in the interstitial volume of the kidney produced by a transient hydrostatic pressure gradient across the peritubular capillaries. The latter seems more likely to us because of the rapidity of onset of the natriuresis, and because removing the renal capsule and releasing the surface interstitial fluid prevented the effect of hypertension on proximal sodium transport.


Nicorandil elevates tissue cGMP levels in a nitric-oxide-independent manner.
The K(+) channel opener nicorandil is a hybrid compound that contains nitrate in its structure. It has been reported that nicorandil can relax vascular tissue in vitro via a mechanism that involves activation of K(ATP) channels and stimulation of soluble guanylyl cyclase. However, it is not known whether the increase of cGMP levels occurs through an elevation of nitric oxide (NO). The aim of the present study was to determine whether NO release was a direct effect of nicorandil. We reported here that nicorandil did not generate NO using ozone chemiluminescence detection methods in human or rat liver microsomes (P450-rich fractions) with addition of NADPH. However, nicorandil elevated cGMP levels in rat liver, aorta, and human coronary smooth muscle cells in vitro. The elevation was not inhibited by the NO trapping agent carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (carboxy-PTIO). These results suggest that nicorandil elevates cGMP without NO generation.


Dental occlusion and body balance: A question of environmental constraints?
In the past few years, growing interest was given to the relationship between the dental occlusion and the body balance. While most research focused on this relationship at static conditions, it is evident that the contribution of the sensory information for balance control is different depending on the environmental constraints. The aim of the present paper was to elucidate whether the stomatognathic system (SS) contributes differently on body balance regulation according to the presence of external disturbances. Literature regarding the different sources involved in the proprioceptive information to the SS was reviewed. The influence of dental occlusion on balance control at different external environments was then explored. The main findings are: (a) a plausible evidence between the masticatory and cervical muscles can be described; (b) a reciprocal connection between the trigeminal and vestibular nuclei supports the influence of the SS on body balance; (c) traditionally, research involving the relationship between the SS and balance control has focused on strictly controlled situations, thus, ignoring the sensory reweighting which occurs depending on the external disturbances; and (d) the afferences of dental occlusion for balance control seem strengthened when more difficult conditions are present. Results of the present review suggest that afferent signals from dental occlusion effectively contribute to balance control when more external perturbations are present, that is unstable support surface, fatigue and tasks being performed. However, more studies are needed to elucidate the mechanisms by which dental occlusion may influence balance control focusing on different external environments.


Effectiveness and Safety of Long-Term Dupilumab Treatment in Elderly Patients with Atopic Dermatitis: A Multicenter Real-Life Observational Study.
The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks. A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures included the mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52. One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent. In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.


Magnetic ordering in solid oxygen up to room temperature.
Oxygen is the only elemental molecule which carries an electronic magnetic moment. As a consequence, the different solid phases encountered on cooling show various degrees of magnetic order, and similar behavior is expected under compression. Here we present neutron diffraction data which reveal the magnetic ordering under high pressure in the delta ("orange") phase, i.e., in the range 6-8 GPa and 20-240 K. We show that delta-O2 contains in total three different magnetic structures, all of them being antiferromagnetic and differing in the stacking sequence of O2 sheets along the c axis. This structural diversity can be explained by the quasi-two-dimensional nature of delta-O2 and the strong orientation dependence of the magnetic exchange interaction between O2 molecules. The results show that delta-O2 is a room temperature antiferromagnet.


Biocompatible nanogel derived from functionalized dextrin for targeted delivery of doxorubicin hydrochloride to MG 63 cancer cells.
The present article demonstrates the targeted delivery of doxorubicin hydrochloride to human osteosarcoma cancer cell lines (MG 63) using functionalized dextrin based crosslinked, pH responsive and biocompatible nanogel. The nanogel has been prepared through Michael-type addition reaction using dextrin (Dxt), N, N'-methylene bisacrylamide (MBA, as crosslinker), acrylic acid (AA, as monomer) and potassium persulfate (KPS, as initiator). The structure, composition, morphology of the nanogel have been explored using FTIR and 1H NMR spectroscopy, XRD, TGA, DSC, CHN and AFM analyses. The TEM analysis confirmed that the size of nanogel appeared within 100nm, while DLS study indicates that the diameter of the nanogel remained between 113 and 126nm. The AFM study implied the porous morphology of the synthesized nanogel. The rheological study suggests the gel behaviour of the synthesized nanogel at 37±0.1°C. Difference in% swelling at pH 5.5 and 7.4 indicates pH-responsiveness of the nanogel. The in vitro cytocompatibility results ascertained that the nanogel is non-toxic to human mesenchymal stem cells (hMSCs). In vitro cellular uptake study confirmed that FITC-loaded nanogel can cross the cellular membrane and be well uptake by the cell cytoplasm. The nanogel could efficiently encapsulate doxorubicin hydrochloride (Dox) with the loading efficiency of 27±0.2% after 72h. The Dox-loaded nanogel demonstrates anti-cancer activity towards MG 63 cancer cells and release the encapsulated drug in a controlled way.


The human LT serum. X. The initial form released by T-enriched lymphocytes is 150,000 m.w., associated with small nonlytic components, and can dissociate into the smaller alpha, beta, and gamma m.w. classes.
The present studies examine the various lymphotoxin (LT) forms released in vitro by phytohemagglutinin- (PHA) activated T-enriched (Te) human peripheral blood lymphocytes. It is clear that Te cells rapidly released (24 to 48 hr) these molecules in vitro. The 1st cell-lytic form detected in these supernatants is a 140-160,000 m.w. molecule(s) termed precursor alpha heavy (P alpha H). This form does not express alpha-LT antigenic determinants but is neutralized by antisera from animals injected with serum-free PHA-activated unseparated lymphocyte supernatants (anti-WS). The P alpha H is converted into alpha H, which expresses alpha determinants, by passage through molecular sieving columns or by treatment with low levels of Nonidet P-40 or urea. These treatments dissociate a small nontoxic 10-20,000 m.w. molecule(s), termed precursor factor (Pf), which masks the alpha-LT determinant on the P alpha H molecule. The dissociation of Pf is reversible, since alpha H from the molecular sieving columns will reassociate with the Pf. The alpha H LT class can further dissociate into the smaller alpha, beta, and gamma LT forms upon chromatography on a molecular sieving column, and a certain small percentage of the alpha H forms appear capable of associating to form the high m.w. complex (Cx) LT class. These findings suggest P alpha H may represent an intermediate that requires additional processing in order to proceed down 1 of 2 pathways: a) formation of complexes that are highly cell-lytic, or b) degradation by dissociation into the smaller weakly cell-lytic molecules identified as LT forms.


Schwann-like cells from human melanocytes and their fate in sciatic nerve injury.
We induced human melanocyte dedifferentiation to Schwann cell-like cells in vitro by a combination of forskolin, neuregulin-β1, neurotrophin-3, platelet-derived growth factor-aa, basic fibroblast growth factor, laminin, and heparin. Cultured human melanocytes constitutively expressed neural cell and melanocyte markers but melanocyte-specific marker, including microphthalmia-associated transcription factor and tyrosinase, expression was selectively lost after induction. In the sciatic nerve injury site, the induced cells were engrafted and closely aligned to axons and P0-expressing myelin sheaths, whereas uninduced cells were not colocalized with axons and myelin sheaths and reexpressed melanocyte-specific tyrosinase activity in vivo. Human melanocytes lose their melanocyte phenotype and transdifferentiate into Schwann cells under specific induction conditions and display their Schwann cell phenotype after transplantation to injured sciatic nerve tissue.


Media devices, family relationships and sleep patterns among adolescents in an urban area.
This study aimed to describe sleep patterns and to examine the association between short sleep time and family relationships and the availability of media devices among adolescents. A cross-sectional study based on a self-reported questionnaire was performed among a representative sample of adolescents (13-19 years old) enrolled during the 2011-2012 academic year in high schools in Barcelona, Spain. Adolescents reported sleep patterns and family-related variables such as family relationships, the availability of media devices in the bedroom, and watching television at dinner. Sleep time was then calculated from sleep patterns. Multivariate Poisson regression analyses with robust variance were conducted to determine the association between short sleep time (<8 h/day) and family characteristics. A total of 51.3% of the 3492 students were girls (mean age: 15.9 years). Sleep time was shorter than recommended on school days in almost half of the compulsory schooling students and in around 75% of post-compulsory schooling students. More than 80% of adolescents had at least one media device (television, console, or computer) in their bedroom. Adolescents with a computer in their bedroom and with poorer family relationships were more likely to be short sleepers. In boys, frequently watching TV at dinner and living in a disorganized family were also associated with short sleep time. There is a high prevalence of short sleepers. Media availability, media use and family relationships should be considered in multi-component educational interventions addressed to both adolescents and parents to reduce short sleep time.


Mitochondrial dehydrogenases in different taxa of tetrahymena: effect of insulin.
Mitochondrial dehydrogenase activity was measured in seven taxa of Tetrahymena (T. pyriformis G1. T. hegewishi, T. malaccensis, T. pigmentosa, T. shapiro, T. thermophila CU-399, T. thermophila MS-1). Enzyme activity was different in the taxa investigated. Insulin reduced enzyme activity in six of the seven taxa studied. The duration of activity reduction was relatively long (5-10 min.) in most of the cases, and in T. hegewishi this lasted up to the end of the measurements (30 min.). There was no interrelation between the basic dehydrogenase activity of the taxon and the effect of insulin. There was also no correlation between the degree of relationship (of the taxa) and the dehydrogenase profile after insulin treatment.


D-2-hydroxyglutaric aciduria and glutaric aciduria type 1 in siblings: coincidence, or linked disorders?
Glutaric aciduria type 1 (GA1) and D-2-hydroxyglutaric aciduria ( D-2-HGA) are cerebral organic acidurias characterized by the excretion of 3-hydroxyglutaric and D-2-hydroxyglutaric acids, respectively. GA1 is caused by a deficiency of glutaryl-CoA dehydrogenase encoded by the GCDH gene; the biochemical and genetic basis of D-2-HGA is unknown. We diagnosed GA1 in the son of consanguineous Palestinian parents, and D-2-HGA in his sister and brother. All three siblings were neurologically and developmentally normal. A small but abnormal increase in excretion of D-2-hydroxyglutaric acid was also found in the sibling with GA1. These observations suggested a possible pathophysiological link between these two disorders. The sibling with GA1 was homozygous whilst his siblings with D-2-HGA were heterozygous for a 1283 C>T missense mutation (T416I) in exon 11 of the GCDH gene. However, sequence analysis of the GCDH gene in 8 additional unrelated patients with D-2-HGA and 3 with combined D/ L-2-HGA did not reveal any pathogenic mutations. The biochemical and genetic basis of D-2-HGA remains to be determined.


Precision measurements of deuterium isotope effects on the chemical shifts of backbone nuclei in proteins: correlations with secondary structure.
Precision NMR measurements of deuterium isotope effects on the chemical shifts of backbone nuclei in proteins ((15)N, (13)CO, (13)C(α), and (1)HN) arising from (1)H-to-(2)H substitutions at aliphatic carbon sites. Isolation of molecular species with a defined protonation/deuteration pattern at carbon-α/β positions allows distinguishing and accurately quantifying different isotope effects within the protein backbone. The isotope shifts measured in the partially deuterated protein ubiquitin are interpreted in terms of backbone geometry via empirical relationships describing the dependence of isotope shifts on (φ; ψ) backbone dihedral angles. Because of their relatively large magnitude and clear dependence on the protein secondary structure, the two- and three-bond backbone amide (15)N isotope shifts, (2)ΔN(C(α,i)D) and (3)ΔN(C(α,i-1)D), can find utility for NMR structural refinement of small-to-medium size proteins.


Computerized training in breast self-examination: a test in a community health center.
Fifty-eight women recruited from a community health center completed either a brief interactive multimedia training program on breast self-examination using a breast model and computer guided feedback on accuracy of lump detection or read a National Cancer Institute pamphlet on breast self-examination and breast lumps. Women using the computer program as compared to the pamphlet group reported a higher sense of self-efficacy for being able to perform a breast self-examination immediately after their educational session and 1 month later. However, the increase in self-efficacy for the computer group diminished over 4 weeks, underscoring the importance of an environment that reminds and reinforces learning for women about the performance of regular breast self-examination. The increase in sense of self-efficacy to perform breast self-examination with roughly 20 minutes of computer-based training and the partial maintenance of that self-efficacy 30 days later suggests the utility of incorporating short, focused interventions in busy primary healthcare settings.


Coadministration of Compound Danshen dripping pills and bezafibrate has a protective effect against diabetic retinopathy.
Diabetic retinopathy (DR) is increasingly becoming a main complication of diabetes, and is difficult to cure. In our research, network pharmacology analysis suggested that both compound Danshen dripping pills (CDDP) and bezafibrate (BZF) have potential protective effects against DR and the two drugs may act synergistically. The pharmacological effects of the coadministration of CDDP and BZF were elucidated in db/db mice, which simulate DR. Fluorescein fundus angiography showed that coadministration attenuated vascular leakage. Optical coherence tomography and hematoxylin and eosin staining showed that coadministration improved retinal thickness better than CDDP monotherapy. In addition, cell fluorescence images of reactive oxygen species revealed that coadministration of CDDP and BZF had more potent effects against oxidative stress than CDDP monotherapy. Metabolomics analysis showed that coadministration reduced the ratio of oxidized glutathione to reduced glutathione further than CDDP monotherapy. Coadministration of CDDP and BZF may provide additional protective effects by resisting vascular leakage, increasing retinal thickness, and inhibiting inflammation and oxidative stress in DR.


The evolving impact of aging America on dental practice.
American dentistry has recognized for a quarter century that the growth in the proportion of elderly in the population is impacting on the profession. Multiple articles in the professional literature have speculated on the ways in which this change will be manifested. Data and projections from earlier articles are revisited and five trends are offered to guide professionals as they position their practices for the coming years. The increase in number and proportion of elderly in dental practices stems from successes in preventing and controlling infectious diseases during the last century. The trend has not peaked but will continue for at least two more decades. Retention of teeth into advanced age has resulted from emerging and improved preventive and restorative dental advances directed at children and adults beginning mid-century, and dental utilization studies confirm the elderly are seeking dental care at an unprecedented and growing rate. Chronic disease and infirmity that accompany advanced age make dental care more challenging for this group. Dentists and their staff will need to continuously undertake educational opportunities that will foster and maintain their facility in providing care to the elderly. They will need to do this because Americans of advanced age are becoming the dominant age group seeking, and able to pay for, sophisticated dental services. The blend of those services is shifting away from removable prostheses to a rising demand for restorative, periodontic, and endodontic care. Root caries, in particular, will be a growing challenge to both providers and patients. There is mounting evidence oral disease impacts endocrine, cardiovascular, and pulmonary health, particularly in frail elders, and will likely provide many elderly additional stimuli to seek dental care. Providers who seek an alternative approach for delivering their services will find growing demand for and satisfaction with traveling to patients, rather than the other way around.


Sleep pattern in Charcot-Marie-Tooth disease type 2: report of family case series.
Charcot-Marie-Tooth (CMT) disease is the most prevalent hereditary motor and sensory polyneuropathy, and a condition in which sleep has rarely been studied, particularly in relation to the type 2 (CMT2). Thus, we aimed to characterize the sleep patterns of a family affected by CMT2 disease. Sixteen volunteers with CMT2 from the same multigenerational family agreed to participate in the study (refusal rate = 31%). All participants answered sleep questionnaires and came to the sleep laboratory to perform a diagnostic polysomnography (PSG). Clinical manifestation and severity of the disease were also evaluated. 56% of the sample were male and 44% female, with a mean age of 32 ± 17 years, of normal weight (body mass index 21 ± 3 kg/m(2)); 64% presented moderate to severe CMT2. Regarding subjective sleep, 31% had excessive daytime sleepiness and 75% reported poor sleep quality. The PSG results revealed that CMT2 patients had an increase in stage N3 and a reduction in REM sleep, in addition to a high arousal index. Although 81% of the sample were snorers, only 13% had an apnea-hypopnea index (AHI) > 5. However, a positive correlation was found between the severity of disease and the AHI. Taken together, these data show that CMT2 disease is characterized by important changes in sleep architecture, probably due to sleep fragmentation. Although these alterations may worsen with disease severity, it seems that they are not related to sleep breathing or movement disorders.


Is there a difference between simultaneous or staged decompressions for combined cervical and lumbar stenosis?
We evaluated 43 patients diagnosed with tandem spinal stenosis (TSS) from 1999 to 2005 in an academic hospital. The purpose of this study is to compare outcomes after simultaneous decompression of the cervical and lumbar spine versus staged operations. TSS is a rare degenerative disease affecting multiple spinal levels with limited research describing operative management. Of our patients, 21 underwent simultaneous decompression of both the cervical and lumbar spine and 22 underwent staged decompression of the cervical spine followed by the lumbar spine at a later date. Medical records were reviewed for patient demographics, type and duration of symptoms, operative time, combined blood loss, cervical myelopathy modified Japan Orthopaedic Association Score, Oswestry Disability Index (ODI), major and minor complications, and average length of follow up. Each category was evaluated by Pearson correlations and unpaired Student t tests. With a mean follow-up of 7 years, both groups improved in JOA and ODI without a significant difference between the 2 operative groups in terms of major or minor complications, JOA, or ODI. Independent of the surgical algorithm, age above 68 years, estimated blood loss ≥400 mL, and operative time ≥150 minutes significantly increased the number of complications. These results indicate that TSS can be effectively managed by either surgical intervention, simultaneous, or staged decompressions. However, patient age, blood loss, and operative time do significantly impact outcomes. Therefore, operative management should be tailored to the patient's age and the option which will limit blood loss and operative time, whether that is by simultaneous or staged procedures.


A highly sensitive affinity-column-mediated immunometric assay, as exemplified by digoxin.
We describe a highly sensitive heterogeneous enzyme-linked immunoassay in which digoxin is used as the model analyte. An excess of enzyme-labeled monovalent antibody is incubated with sample containing the analyte such that all analyte is rapidly and quantitatively bound. Excess antibody that does not acquire a antigen in its binding site is rapidly removed from the mixture by passage through a porous affinity column containing immobilized analyte (or analog), present in vast excess. Only the labeled monovalent antibody that possesses an antigen in its binding site elutes from the column in the unbound fraction. The label present in this fraction is then quantified. Such an assay is extremely sensitive and obviates the limitations imposed by antibody affinity constants on homogeneous and competitive heterogeneous immunoassays. This assay can be performed rapidly and is readily amenable to automation.


Maternity nurses' knowledge of factors promoting successful breastfeeding. A survey at two hospitals.
An investigator-designed questionnaire was used to survey 53 RNs and LPNs at two urban hospitals concerning knowledge for support of breastfeeding mothers. Maternity nurses demonstrated limited knowledge, especially in drugs, maternal emotions, and neonatal physiology as related to breastfeeding. Level of education affected test scores positively; length of experience affected test scores negatively.


Neural stem cells in the subventricular zone are resilient to hypoxia/ischemia whereas progenitors are vulnerable.
Perinatal hypoxic-ischemic (H/I) brain injury remains a major cause of neurologic disability. Because we have previously demonstrated that this insult depletes cells from the subventricular zone (SVZ), the goal of the present investigation was to compare the relative vulnerability to H/I of neural stem cells versus progenitors. The dorsolateral SVZs of P6 rats were examined at 2 to 48 hours of recovery from H/I using hematoxylin and eosin, in situ end labeling (ISEL), terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL), electron microscopy, and immunofluorescence. Pyknotic nuclei and ISEL cells were observed by 4 hours of recovery, peaked at 12 hours, and persisted for at least 48 hours. Many active-caspase-3 cells were observed at 12 hours and they comprised one third of the total TUNEL population. Electron microscopy revealed that hybrid cell deaths predominated at 12 hours of recovery. Importantly, few dying cells were observed in the medial SVZ, where putative stem cells reside, and no nestin medial SVZ cells showed caspase-3 activation. By contrast, active-caspase-3/PSA-NCAM progenitors were prominent in the lateral SVZ. These data demonstrate that early progenitors are vulnerable to H/I, whereas neural stem cells are resilient. The demise of these early progenitors may lead to the depletion of neuronal and late oligodendrocyte progenitors, contributing to cerebral dysgenesis after perinatal insults.


[Uro-gynecologic protocol for studying urinary stress incontinence].
Regarding the difficulty in using a common and standardised language in the diagnosis of Stress Urinary Incontinence (SUI) the authors developed a research protocol based on anamnestic, clinical, urodynamic and imaging forms, in order to have a numerous elements for the evaluation of this pathology. The preliminary study had to identify the most meaningful and common parameters, encoded according to broadly approved literature or the classification proposed by International Continence Society (ICS). One of the fundamental purposes was to clarify the role of ultrasonography technique applied to the field of Stress Incontinence. In this article the authors explain the choices they make, the technique employed for such a study and the ultrasonic images that are pathognomonic of the specific anatomo-functional disorders.


Laparoscopic Liver Resection: A South American Experience with 2887 Cases.
Laparoscopic liver resections (LLR) have been increasingly performed in recent years. Most of the available evidence, however, comes from specialized centers in Asia, Europe and USA. Data from South America are limited and based on single-center experiences. To date, no multicenter studies evaluated the results of LLR in South America. The aim of this study was to evaluate the experience and results with LLR in South American centers. From February to November 2019, a survey about LLR was conducted in 61 hepatobiliary centers in South America, composed by 20 questions concerning demographic characteristics, surgical data, and perioperative results. Fifty-one (83.6%) centers from seven different countries answered the survey. A total of 2887 LLR were performed, as follows: Argentina (928), Brazil (1326), Chile (322), Colombia (210), Paraguay (9), Peru (75), and Uruguay (8). The first program began in 1997; however, the majority (60.7%) started after 2010. The percentage of LLR over open resections was 28.4% (4.4-84%). Of the total, 76.5% were minor hepatectomies and 23.5% major, including 266 right hepatectomies and 343 left hepatectomies. The conversion rate was 9.7%, overall morbidity 13%, and mortality 0.7%. This is the largest study assessing the dissemination and results of LLR in South America. It showed an increasing number of centers performing LLR with the promising perioperative results, aligned with other worldwide excellence centers.


Gender-biased evaluation or actual differences? Fairness in the evaluation of faculty teaching.
How do we know if a faculty teaching evaluation is biased? Biasing factors studies are an influential source of evidence for arguing about biased teaching evaluations. These studies examine existing evaluation data and compare the results by gender, race, or ethnicity, interpreting a significant difference between subgroups as evidence of bias. However, only a difference explained by irrelevant aspects embedded in the evaluation would compromise its fairness. The study aims to amend how practitioners and researchers address gender bias concerns in faculty teaching evaluations by defining fairness, disparate impact, and statistical bias from an educational measurement standpoint. The study illustrates the use of differential item functioning (DIF) analysis, a strategy to examine whether the meaning of an item changes depending on the gender of the instructor. The study examines instructor's gender bias using responses to a course evaluation questionnaire from education graduate students from two academic departments within the same institution. In one of the departments, the analysis suggested a fair evaluation and no gender gap. In the other department, four of the eight items in the rating scale were easier for women than men with similar teaching ability, and women achieved better evaluations than men. The discussion addresses the conceptual and methodological advantages of adopting an educational measurement perspective on fairness in faculty teaching evaluation. Findings encourage practitioners and administrators to use the best available tools to strengthen the credibility of faculty teaching evaluations and prevent unfair personnel decisions affecting underrepresented subgroups in academia by gender, race, or ethnicity.


Hydrogen peroxide-induced growth of hierarchical Ni3S2 nanorod/sheet arrays for high performance supercapacitors.
The rational design and simple synthesis of high performance electrodes are important aspects of energy storage fields. However, it is difficult to determine a facile preparation method to obtain hierarchical Ni3S2 nanorod/sheet arrays. Herein, hydrogen peroxide-induced growth by the hydrothermal method is used to fabricate the hierarchical Ni3S2 nanorod/sheet arrays on nickel foam substrates. Hydrogen peroxide can accelerate the hydrolysis of Na2S2O3 to release sulfur ions and then induce formation of the hierarchical nanorod/sheet. The one-dimensional nanorod skeleton acting as high-speed electron transfer channels can support the nanosheets. The two-dimensional nanosheets can provide abundant active edge sites and protect the backbone from electrochemical corrosion. The hierarchical structure integrates the advantages of sufficient active sites, effective protection and high-speed electron transfer. The electrode based on the Ni3S2 nanorod/sheet delivers a high specific capacitance of 6.87 F cm-2 at 2 mV s-1 (6.24 F cm-2 at 5 mA cm-2) and long cycling stability (85.7% capacitance retention at 15 mA cm-2 after 3000 cycles). The asymmetric supercapacitor gains a high energy density of 1.16 mWh cm-3 at 15.00 W cm-3. The hierarchical Ni3S2 nanorod/sheet arrays are expected to be candidates for the electrodes of practical supercapacitors.


Ophthalmic manifestations of perinatally acquired HIV in a US cohort of long-term survivors.
To determine the ophthalmic manifestations of HIV in a cohort of long-term survivors of perinatally acquired HIV. Twenty-two patients with perinatally acquired HIV who were aged ≥12 years were prospectively studied at a university clinic. They underwent complete ophthalmic examinations and fundus photography. Their medical histories, medications and CD4 counts were abstracted from the medical records. To evaluate for keratoconjunctivitis sicca, both HIV patients and 44 healthy controls (matched by age, gender and contact lens wear) underwent Schirmer testing and ocular surface staining. Nine male and 13 female HIV patients with mean age of 16.6 years (SD, 3.4) were examined. Of the 22 HIV patients, 21 had been treated with highly active antiretroviral therapy (HAART). Only one patient had a CD4 count nadir of <200 cells/µL. The mean visual acuity of the eyes of the HIV subjects was 20/22 (SD, 1.6 lines). No patient had cytomegalovirus retinitis. Four of the 22 (18%) HIV patients had strabismus. HIV subjects and controls had similar rates of abnormal Schirmer (9% and 14%, p=0.62) and ocular staining scores (p=0.29). In the post-HAART era, long-term survivors of perinatally acquired HIV exhibited little vision-threatening disease, but had a high prevalence of strabismus.


Thermal unfolding of three acclimation temperature-associated isoforms of carp light meromyosin expressed by recombinant DNAs.
Differential scanning calorimetry (DSC) was performed to investigate thermodynamic properties of three carp fast skeletal light meromyosin (LMM) isoforms expressed in Escherichia coli by recombinant DNAs. Three isoforms were the 10 degreesC-, intermediate-, and 30 degreesC-type LMM predominantly expressed in carp acclimated to 10, 20, and 30 degreesC. The isoforms expressed in E. coli by recombinant DNAs exhibited a typical pattern of alpha-helix in CD spectroscopy with two minima at 222 and 208 nm. Moreover, the three isoforms formed paracrystals typical of LMM, suggesting that expressed proteins retained intact structural properties. When the LMM isoforms were subjected to DSC analysis, the 10 degreesC and 30 degreesC types showed endotherms having transition temperatures (Tm) at 35.1 and 39.5 degreesC, respectively, which are responsible for thermal unfolding of alpha-helix. The intermediate type exhibited two comparable endotherms with Tm values at 34.9 and 40.6 degreesC, implying that it has intermediate thermodynamic properties between those of 10 degreesC and 30 degreesC types. However, a chimeric LMM having the 10 degreesC and 30 degreesC type as N- and C-terminal halves, respectively, showed the DSC pattern typical of the whole 30 degreesC-type molecule. On the other hand, another chimeric LMM composed of the N-terminal 30 degreesC type and C-terminal 10 degreesC type gave the pattern of the full 10 degreesC type. These results suggest that thermodynamic properties of the C-terminal half largely account for thermal unfolding of the whole molecule.


The preoperative platelet to neutrophil ratio and lymphocyte to monocyte ratio are superior prognostic indicators compared with other inflammatory biomarkers in ovarian cancer.
Previous studies have suggested that the ratios of immune-inflammatory cells could serve as prognostic indicators in ovarian cancer. However, which of these is the superior prognostic indicator in ovarian cancer remains unknown. In addition, studies on the prognostic value of the platelet to neutrophil ratio (PNR) in ovarian cancer are still limited. A cohort of 991 ovarian cancer patients was analyzed in the present study. Receiver operator characteristic (ROC) curves were utilized to choose the optimal cut-off values of inflammatory biomarkers such as neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and PNR. The correlation of inflammatory biomarkers with overall survival (OS) and relapse-free survival (RFS) was investigated by Kaplan-Meier methods and log-rank test, followed by Cox regression analyses. Kaplan-Meier curves suggested that LMR<3.39, PLR≥181.46, and PNR≥49.20 had obvious associations with worse RFS (P<0.001, P=0.018, P<0.001). Multivariate analysis suggested that LMR (≥3.39 vs. <3.39) (P=0.042, HR=0.810, 95% CI=0.661-0.992) and PNR (≥49.20 vs. <49.20) (P=0.004, HR=1.351, 95% CI=1.103-1.656) were independent prognostic indicators of poor RFS. In addition, Kaplan-Meier curves indicated that PLR≥182.23 was significantly correlated with worse OS (P=0.039). Taken together, PNR and LMR are superior prognostic indicators compared with NLR, PLR, and SII in patients with ovarian cancer.


[Photodynamic therapy in classic chorioidal neovascularisation in patients with angioid streaks].
The development of subfoveal or juxtafoveal choroidal neovascularisation (CNV) secondary to angioid streaks poses a great therapeutic challenge. The relevance of the photodynamic therapy (PDT) with verteporfin is still unclear. We present the functional and anatomic outcome of 5 patients with CNV due to angioid streaks treated by PDT. We reviewed 4 eyes with subfoveal and 1 eye with juxtafoveal CNV in angioid streaks of 5 patients (4 male, 1 female) treated by PDT between 2000 and 2005. The age ranged from 20 to 74 years (median 63 years). PDT was performed according to the TAP criteria. Best corrected visual acuity was measured using ETDRS charts. Visual acuity (VA) ranged between 20/63 and 20/32 (median 20/32) at first presentation and between 20/2000 (counting fingers) and 20/20 (median 20/400) at last presentation. Median follow-up time was 13 months with a range of 5 to 45 months. The visual acuity in one patient decreased by 1 line, in 3 patients by more than 6 lines whereas VA of one patient (juxtafoveal CNV) increased by 2 lines. PDT was repeated in 4 patients once because of persistent leakage and in one patient twice. At the end of the follow-up period a fibrous disciform lesion was seen in 4 patients, in one patient subfoveal membranectomy was performed due to a recurrence. In general, PDT of CNV is less favourable in angioid streaks than in AMD. However, in the natural course final VA is counting fingers. Therefore the good results of individual cases justify the PDT under a critical indication.


Carbapenem-Resistant Klebsiella pneumoniae in Southwest China: Molecular Characteristics and Risk Factors Caused by KPC and NDM Producers.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has attracted worldwide concern and became a serious challenge for clinical treatment. The aims of this study were to evaluate the molecular characteristics and risk factors for CRKP infection. All the CRKP strains were screened for antimicrobial resistance genes, virulence genes, and integron by polymerase chain reaction (PCR). Plasmid typing was performed by plasmid conjugation assay and PCR-based replicon typing (PBRT). The genetic environments of bla KPC-2 and bla NDM-1 were analyzed by using overlapping PCR and molecular typing was performed by multi-locus sequence typing (MLST). Risk factors for CRKP infection were analyzed by logistic regression model. All the 66 CRKP isolates were multidrug-resistant, but all of them were susceptible to tigecycline and polymyxin B. Among the CRKP isolates, 42 bla KPC-2-positive strains were identified carrying IncFII plasmids. Meanwhile, 24 bla NDM-positive strains were found on lncX3 plasmids, including 20 bla NDM-1 isolates and 4 bla NDM-5 isolates. Most of CRKP isolates contained several virulence genes and the class I integron (intl1). The genetic environments of bla KPC-2 and bla NDM-1 revealed that the conserved regions (tnpA-tnpR-ISkpn8-bla KPC-2) and (bla NDM-1-ble MBL -trpF-tat) were associated with the dissemination of KPC-2 and NDM-1. ST11 was the most common type in this work. Hematological disease, tracheal cannula, and use of β-lactams and β-lactamase inhibitor combination were identified as independent risk factors for CRKP infection. This study established the resistance pattern, molecular characteristics, clonal relatedness, and risk factors of CRKP infection. The findings of the novel strain that co-harboring bla NDM-5 and bla IMP-4, and the novel ST4495 indicated that the brand-new types have spread in Southwest China, emphasizing the prevent and control the further dissemination of CRKP isolates are highly needed.


Catalytic, asymmetric alpha-fluorination of acid chlorides: dual metal-ketene enolate activation.
In this Communication, we disclose a catalytic, highly enantioselective (up to >99% ee) alpha-fluorination of acid chlorides to produce a variety of optically active carboxylic acid derivatives from readily accessible and commercially available starting materials. The reaction depends on dually activated ketene enolates generated from two discrete catalysts--a chiral nucleophile and an achiral transition metal complex working in tandem. The active, putative alpha-fluorobis(sulfonimide) intermediates readily transacylate in situ under mild conditions upon addition of a wide variety of nucleophiles, including complex natural products. As a consequence, the power of this method is witnessed by the broad range of alpha-fluorinated products that can be accessed efficiently depending on the work up conditions.


Acute pancreatitis in children: 10-year experience in a medical center.
Acute pancreatitis is uncommon in children compared with adults. The purpose of this study was to evaluate the etiologies, clinical presentations, image findings and outcome of children's acute pancreatitis. The medical records of children and adolescent patients admitted due to pancreatitis from July 1992 to July 2002 were reviewed. The diagnosis of pancreatitis was based on clinical symptoms, at least threefold elevation of serum pancreatic enzymes, and image findings. This study comprised 75 patients with 96 episodes of pancreatitis. There were 36 males and 39 females, with a mean age of 10 years. The leading etiologies were idiopathic (26.7%), systemic diseases (22.7%), biliary tract disease (21.3%), and trauma (16%). Common initial manifestations included abdominal pain (93.8%), vomiting (64.2%), and fever (33.3%). The sensitivities of ultrasonography (US) and computed tomography (CT) in detecting pancreatitis were 57.3% and 74.4%, respectively. The morbidity included 6 pseudocysts and 16 repeated pancreatitis. Four pseudocysts were resulted from traumatic pancreatitis. Patients with hyperlipidemia and biliary tract disorder were more likely to have repeated attacks. Fifty-five (73.3%) patients recovered after conservative management, the remaining 20 (26.7%) patients needed surgical or other interventional treatment. The mortality rate was 5.3%. Three fatal cases (75%) had underlying medical diseases. The etiologies of acute pancreatitis are diverse. Abdominal CT is more sensitive than US in the diagnosis of pancreatitis. Pseudocysts are more likely to occur in patients with traumatic pancreatitis. Patients with hyperlipidemia are prone to recurrent pancreatitis. The prognosis of children's pancreatitis is good. Most patients with fatal outcome had coexistent medical diseases.


[Child-friendly restorations of primary molars using the Hall technique].
Minimally invasive dentistry is being used increasingly often, especially in paediatric dentistry. It involves replacing traditional 'drilling and filling' with treatment modalities that are tissue-saving and minimally burdensome to the patient. One of these techniques for treating carious dentine lesions is the Hall technique. A stainless-steel crown is cemented onto the primary molar without the use of anaesthesia or any form of preparation. The molar is 'sealed' under the crown and this stops the carious process in the cavity. Usually, the procedure requires 2 sessions. The Hall technique is well tolerated by children and provides the primary molar with a durable restoration. Together with this technique, the patient is also guided in an individual prevention process. The survival rates of Hall crowns are very high.


Clinical examination and classification systems of congenital clubfoot: a narrative review.
Clinical examination of the newborn's foot is a complex exercise that requires a lot of sensitivity, practice and deep understanding of normal and pathological anatomy, and the clinical assessment of a child with congenital talipes equinovarus, or congenital clubfoot, must be complete and it should not be limited to a simple orthopedic evaluation of the foot; the search for a cause is a pressing concern. This narrative review article aims to provide the key information about clinical examination of children with congenital clubfoot; classification systems are also described. Clinical examination of children with congenital clubfoot is essential. In particular, it is important to evaluate the mental age of the child (developmental milestones), to rule out the presence of a spinal dysraphism, to eliminate a mild form of neurological disease (congenital myopathy or arthrogryposis), as well as to carefully examine the face and hands of the patient. The examination of the foot and the classification of the clubfoot deformity complete the clinical evaluation. In the end, the pediatric orthopedic surgeon must not underestimate any clinical signs, and must act as a pediatrician. This narrative review summarizes the key points in taking a history and performing a comprehensive clinical examination for patients with congenital clubfoot; the review also briefly describes the normal foot anatomy and growth as to give the reader the opportunity to better understand the morphological and functional modifications secondary to congenital clubfoot.


[C-reactive protein and neonatal infections. Diagnostic importance].
Serum C Reactive Protein (CRP) levels were measured in 36 neonates with a suspicion of sepsis. In the 11 children in whom septicemia was proven, CRP levels were abnormal in all cases, while hematologic data were significantly changed in 3 cases only (27%). In the 16 neonates who were not infected, CRP was abnormal in only one case, and hematologic data significantly changed in 2 (12%). In 9 neonates with at least 2 peripheral samples positive for the same organism, CRP and hematologic data were respectively abnormal in 6 (66%) and one (11%) cases.


Foreign body in the vallecula presenting as acute epiglottitis with unilateral supraglottitis.
Life threatening inflammatory swelling of the epiglottic and supraglottic regions secondary to a foreign body in the vallecula is an unusual occurrence. Upper airway obstruction is potentially a life threatening sequela. We present a unique case of acute epiglottitis with unilateral supraglottitis secondary to foreign body in the vallecula, which gradually improved after emergency endotracheal intubation for respiratory arrest, followed by intensive conservative management with intravenous antibiotics, cortisone and intravenous fluids. This case emphasizes that a foreign body in the vallecula presenting with severe dysphagia should be taken seriously as it may lead to life threatening complications.


A phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer.
Cabozantinib is a multi-kinase inhibitor that targets MET, AXL, and VEGFR2, and may synergize with EGFR inhibition in NSCLC. Cabozantinib was assessed alone or in combination with erlotinib in patients with progressive NSCLC and EGFR mutations who had previously received erlotinib. This was a phase Ib/II study (NCT00596648). The primary objectives of phase I were to assess the safety, pharmacokinetics, and pharmacodynamics and to determine maximum tolerated dose (MTD) of cabozantinib plus erlotinib in patients who failed prior erlotinib treatment. In phase II, patients with prior response or stable disease with erlotinib who progressed were randomized to single-agent cabozantinib 100 mg qd vs cabozantinib 100 mg qd and erlotinib 50 mg qd (phase I MTD), with a primary objective of estimating objective response rate (ORR). Sixty-four patients were treated in phase I. Doses of 100 mg cabozantinib plus 50 mg erlotinib, or 40 mg cabozantinib plus 150 mg erlotinib were determined to be MTDs. Diarrhea was the most frequent dose-limiting toxicity and the most frequent AE (87.5% of patients). The ORR for phase I was 8.2% (90% CI 3.3-16.5). In phase II, one patient in the cabozantinib arm (N = 15) experienced a partial response, for an ORR of 6.7% (90% CI 0.3-27.9), with no responses for cabozantinib plus erlotinib (N = 13). There was no evidence that co-administration of cabozantinib markedly altered erlotinib pharmacokinetics or vice versa. Despite responses with cabozantinib/erlotinib in phase I, there were no responses in the combination arm of phase II in patients with acquired resistance to erlotinib. Cabozantinib did not appear to re-sensitize these patients to erlotinib.


Arthroscopically Assisted Anterior Treatment of Symptomatic Large Talar Bone Cyst.
Symptomatic cystic lesions of the talus are rare. The traditional operations usually do not provide visualization to reveal the deep structure of the lesion and could cause cartilage damage or other severe traumatic injury. We report an operative technique to reach the cystic lesion without talar cartilage damage, remove the lesion, and fill defect with a bone graft assisted by anterior arthroscopy and evaluate its safety and reliability for future study. Seven cases of talar bone cyst were included. The patients were placed in the supine position after anesthesia induction and noninvasive ankle traction was applied. Standard anteromedial and anterolateral portals were established to observe the ankle; the distal end of the medial approach was moderately enlarged to 2 to 3 cm. The biopsy specimen of the cyst was obtained under arthroscopic guidance; the cyst wall was abraded and the sclerotic rim drilled. Arthrocare radiofrequency ablation was performed to prevent recurrence. The defect was tightly impacted with autologous or allograft cancellous bone. All cysts in these cases were located in the medial talus; anteroposterior radiographs and computed tomographic coronary scan showed a cyst diameter of >1 cm. Intraoperative inspection showed a tiny chondral gap on the talar dome in 1 case and on the medial wall of talus in 1 case; no cartilage injury was found in the remainder. Two cases were impacted with grafted autogenous iliac bone into the talar defect and 5 cases with allograft cancellous bone. Computed tomography confirmed that the cysts had healed, with no signs of recurrence found in any patient at 1 year postoperatively. The mean American Orthopaedic Foot and Ankle Society ankle-hindfoot scale score increased from 65 preoperatively to 91 points postoperatively, a statistically significant difference (p < .01). No complications developed and no reoperations were required postoperatively. Arthroscopically assisted anterior treatment with autologous or allograft bone graft is an effective method for symptomatic large talar bone cysts.


Genotypic and phenotypic characteristics of Yersinia enterocolitica isolated from the surface of chicken eggshells obtained in Argentina.
The prevalence of Yersinia enterocolitica on chicken eggshell surfaces in San Luis, Argentina, was investigated. The pathogenic potential of recovered isolates was assessed by means of phenotypic virulence tests and the presence of the 72-kb pYV plasmid. Antimicrobial susceptibility was determined by the agar diffusion method. DNA digested with XbaI was analyzed by pulsed-field gel electrophoresis (PFGE), and relationships between genomic DNA profiles were established. Eight Y. enterocolitica B2 O:9 strains were recovered after enrichment, for a prevalence of 2.27%. All strains harbored the virulence pYV plasmid, bound Congo red, grew in a low-calcium medium, and autoagglutinated at 37 degrees C. They lacked pyrazinamidase activity and did not hydrolyze esculin. These Y. enterocolitica strains were susceptible to amikacin, ciprofloxacin, chloramphenicol, and trimethoprim-sulfamethoxazole and were resistant to rifampin. According to the genomic DNA patterns obtained by PFGE, the isolates clustered into two groups, I and II. The highest similarity coefficient observed between Y. enterocolitica strains was 0.947. Microbiological controls on production stages of eggs and good culinary practices are necessary to reduce the risk of Y. enterocolitica infection for consumers.


Exposure-effect and exposure-response relationships between occupational exposure to styrene and neuropsychological functions.
A neuropsychological test battery was administered to 50 workers exposed to styrene and to 50 sex-, intelligence-, and age-matched controls. The main styrene metabolites, ie, mandelic acid (MA) and phenylglyoxylic acid (PGA), were measured as exposure indices in the urine collected on Saturday mornings, just before neuropsychological testing. Exposure-response and exposure-effect relationships were found between the intensity of the exposure (as reflected by the sum of MA and PGA) and the scores of the neuropsychological tests. Verbal learning skills were significantly impaired in workers with a sum of MA and PGA higher than 150 mmole/mole creatinine, corresponding to styrene airborne concentrations higher than 25 ppm (mean daily exposure). Logical memory and visuo-constructive abilities were shown to be significantly affected in workers with MA and PGA higher than 300 mmole/mole creatinine, corresponding to exposure levels of more than 50 ppm of styrene in air.


In vitro bioactivity of akermanite ceramics.
In this study, the bone-like apatite-formation ability of akermanite ceramics (Ca2MgSi2O7) in simulated body fluid (SBF) and the effects of ionic products from akermanite dissolution on osteoblasts and mouse fibroblasts (cell line L929) were investigated. In addition, osteoblast morphology and proliferation on the ceramics were evaluated. The results showed that akermanite ceramics possessed bone-like apatite-formation ability comparable with bioactive wollastonite ceramics (CaSiO3) after 20 days of soaking in SBF and the mechanism of bone-like apatite formation on akermanite ceramics is similar to that of wollastonite ceramics. The Ca, Si, and Mg ions from akermanite dissolution at certain ranges of concentration significantly stimulated osteoblast and L929 cell proliferation. Furthermore, osteoblasts spread well on the surface of akermanite ceramics, and proliferated with increasing the culture time. The results showed that akermanite ceramics possess bone-like apatite-formation ability and can release soluble ionic products to stimulate cell proliferation, which indicated good bioactivity.


The influence of platelet membranes on tumour cell behaviour.
The significant role of platelets in the protection of tumour cells from immune attack and shear forces and the promotion of tumour cell extravasation from the bloodstream in the process of haematogenous metastasis have been extensively studied. The role of platelets, and in particular platelet membranes, in the promotion of a more metastatic phenotype in tumour cells is a more recent and, therefore, less well-recognised area of research. This review article summarises studies that have focused on the impact of tumour cell interactions with platelets and platelet membranes on tumour cell behaviour in vitro and in vivo. Furthermore, the gene expression changes that occur within tumour cells following contact with platelet membranes are also extensively reviewed. Overall, the interaction of platelet membranes with tumour cells results in a more invasive phenotype and the promotion of epithelial to mesenchymal transition with our own genetic studies revealing that matrix metalloproteinase-1, plasminogen activator inhibitor-1 and interleukin-8 are globally upregulated in a range of tumour cell lines.


Unusual case of pyogranulomatous hepatitis of suspected infectious etiology in a 3-year-old Labrador retriever dog.
A 3-year-old spayed female Labrador retriever dog was presented with clinical signs of lethargy, vomiting, hyporexia, and increased respiratory effort. An exploratory laparotomy was conducted and a liver biopsy submitted for histopathologic evaluation revealed moderate multifocal coalescing pyogranulomatous hepatitis. Clinical signs, hematological parameters, and liver histopathology suggested an infectious etiology, such as leptospirosis, mycobacteriosis, or fungal infection. Polymerase chain reaction (PCR) and immunohistochemistry (IHC) for leptospirosis were negative. The infectious etiology was not identified, but leptospirosis may have played a role in the disease.