High expression of MAPK-14 promoting the death of chondrocytes is an important signal of osteoarthritis process.
Osteoarthritis (OA) is one of the most common degenerative diseases worldwide. Many researchers are studying the pathogenesis of OA, however, it is still unclear. Screening and validation of OA relevant hub genes are an important part of exploring their potential molecular mechanism. Therefore, this study aims to explore and verify the mechanisms of hub genes in the OA by bioinformatics, qPCR, fluorescence and propidium iodide staining. Microarray datasets GSE43923, GSE55457 and GSE12021 were collected in the Gene Expression Omnibus (GEO), including 45 samples, which divided into 23 osteoarthritis knee joint samples and 22 samples of normal knee joint. Thereafter, 265 differentiallyexpressedgenes (DEGs) were identified in all, which divided into 199 upregulated genes and 66 downregulated genes. The hub genes MAPK-14, PTPRC, PTPN12 were upregulated, while B9D1 was downregulated. In order to further confirm the expression of screening differential genes in human chondrocytes, the human chondrocytes were extracted from a joint replacement surgery and stained with toluidine blue for identification. Compared with normal chondrocytes, OA chondrocytes had high expression of COL I protein and low expression of COL II protein. The expression levels of MAPK-14, PTPRC and PTPN12 in OA chondrocytes were significantly higher than the expression levels of B9D1 in normal chondrocytes. Moreover, the inflammatory necrosis of OA chondrocytes was increased compared with the normal chondrocytes by propidium iodide staining. The high expression of MAPK-14 works as a promoter of chondrocytes death and an important signal of the osteoarthritis process.


Chitosan aerogel: a recyclable, heterogeneous organocatalyst for the asymmetric direct aldol reaction in water.
Aerogel microspheres of chitosan, an abundant biopolymer obtained from marine crustaceans, have been successfully applied to catalyze the asymmetric aldol reaction in water, providing the products in high yields and with good stereoselectivity (up to 93% ee) and recyclability (up to 4 runs). Yields were favourably affected by additives such as DNP and stearic acid.


[Comparative study of amantadine and hemantane effects on development of levodopa-induced dyskinesia in rat model of parkinsonian syndrome].
Chronic administration of levodopa and benserazide (10 and 15 mg/kg, respectively) cause the development of dyskinesia in rats with model parkinsonian syndrome induced by injection of 6-hydroxydopamine in left substantia nigra. The chronic administration of these drugs together with amantadine (20 mg/kg) accelerates the onset of latency and increases the magnitude of dyskinesia. Chronic administration of levodopa and benserazide together with hemantane (10 mg/kg) slows down the development and decreases the magnitude of levodopa-induced abnormal involuntary movements as measured for limb, orolingual and rotatory movements.


[Rigid bronchoscope combined with soft electronic bronchoscope for treatment of main airway neoplasma.].
Main airway severe obstruction is a problem facing difficulty flexible bronchoscope because the patient is not able to breath smoothly under prostration, and death from suffocation is a frequent outcome. Managing the airway of patients with critical tracheal stenosis remains a formidable challenge to bronchoscopists. This study is to evaluate the application and efficacy of argon plasma coagulation (APC) and cryoextraction for the treatment of endobronchial neoplasma under rigid bronchoscope combined with flexible bronchoscope. Two groups of airway pathologically proved neoplasma were retrospectively reviewed for the different endobronchial intervation modalities. Group A: Argon plasma coagulation (APC) and cryoextraction were used for the treatment of endobronchial neoplasma under rigid bronchoscope combined with electronic bronchoscope in 19 cases with tracheobronchial carcinoma. Rigid bronchoscope was inserted into trachea with general anesthesia. Then the endobronchial tumor was removed by the combination APC and cryoextraction. Group B: APC and grasp or cryoextraction were used for the debulking of endobronchial tumor under flexible bronchoscope in 20 cases with airway tumor. Both tracheal and bronchial obstruction were more severe in Group A than those in Group B, but the tumor debulking was higher for the first time in Group A than in Group B. There were no difference on debulking volume between trachea and bronchus in the same group. The procedures were less complex in Group A than in Group B. The clinical improvement was better in Group A than in Group B. There were no severe complications directly related to the procedures. The combination of APC and cryoextraction is a rapid and effective method for the treatment of endoluminal airway tumor under rigid bronchoscope combined with electronic bronchoscope. Cryoextraction could rapidly debulk airway tumor and APC could effectively ablate tumor and stop bleeding. Electronic bronchoscope is used for the maintenance after rigid bronchoscope and for the treatment of slightly airway obstruction.


Aging Cell Culture - Genetic and Metabolic Effects of Passage Number on Zebrafish Z3 Cells.
Since cell lines are cultured and extensively used in a variety of different research disciplines, we determined the effects of passage numbers on a commonly used embryonic zebrafish cell line (Z3). Senescence markers, DNA damage, the redox state, gene expression, and metabolic parameters have been investigated in young (passage 5) up to very old (passage 40 and higher) cells. Besides increasing DNA damage, we also found elevated metabolic capacity and a shift to a more reduced cellular redox state in the cells. Interestingly, several parameters showed a non-linear course regarding the passage number or cell age, so that for example young and mid-aged cells appeared to cluster with very old rather than with old cells. This study illustrates the importance of passage number and suggests pre-testing specific parameters to assure the generation of accurate and reproducible data.


Spatial-temporal characteristics of mercury and methylmercury in marine sediment under the combined influences of river input and coastal currents.
Mercury, especially in the form of methylmercury (MeHg), is a global pollutant, and aquatic products are considered the main sources of Hg exposure to humans. The Bohai and Yellow seas are two important epicontinental seas for marine fisheries and aquaculture in China. A decreasing trend of the THg in the Yellow River Estuary toward the outer edge was reported according to 83 surface sediments (27.3 ± 15.0 ng g-1) and 3 sediment cores from the Bohai Sea and Yellow Sea. The relatively higher THg levels in the central Yellow Sea can be primarily attributed to higher organic carbon levels and finer-grained sediment sizes and partly to the particulates from the riverine input of the Yellow River driven by the currents. An increasing trend in THg levels since industrialization in north China around the Bohai and Yellow seas, and a decreasing trend of Yellow River THg input in recent years were recorded by sediment cores. The spatial distribution pattern of surface sediments MeHg (161 ± 130 pg g-1) was different from that of THg. A higher MeHg content and MeHg/THg ratio were found in the Bohai and Yellow seas compared to the East China Sea, and extremely high MeHg levels (714 pg g-1) were found in the Yellow Sea Cold Water Mass (YSCWM) area, which is considered an important region for fishery and marine breeding, suggesting that more attention should be paid to the potential ecological and human health risks in the region due to mercury exposure.


Solubilizing the most easily ionized molecules and generating powerful reducing agents.
Two very soluble compounds having W2(bicyclic guanidinate)4 paddlewheel structures show record low ionization energies (onsets at 3.4 to 3.5 eV) and very negative oxidation potentials in THF (-1.84 to -1.90 V vs Ag/AgCl). DFT computations show the correlation from the gas-phase ionization energies to the solution redox potentials and chemical behavior. These compounds are thermally stable and easy to synthesize in high yields and good purity. They are very reactive and potentially useful stoichiometric reducing agents in nonpolar, nonprotonated solvents.


LncRNA FENDRR sensitizes doxorubicin-resistance of osteosarcoma cells through down-regulating ABCB1 and ABCC1.
Long noncoding RNAs (LncRNAs) act as crucial regulators in various cancers including osteosarcoma (OS), yet their potential roles and molecular mechanisms in OS chemoresistance remain unclear. In the present study, we investigated the role and potential regulatory mechanism of the most down-regulated expressed lncRNA, FENDRR screened by our previous lncRNA microarray analysis between the paired doxorubicin-resistant and sensitive human osteosarcoma cell lines (MG63/DXR vs MG63). FENDRR expression was down-regulated in the doxorubicin-resistant OS cell lines and tissues and negatively correlated to the poor prognosis of OS patients. Overexpression of FENDRR suppressed doxorubicin-resistance, G2/M phase of cell cycle, and promoted cell apoptosis of osteosarcoma cells in vitro and tumor growth in vivo whereas FENDRR knockdown had the opposite effects. In addition, we found that FENDRR was mainly located in the cytoplasm and could regulate the drug resistance of osteosarcoma cells by negatively affecting posttranscriptional expression of ABCB1 and ABCC1. Together, our study demonstrated that lncRNA FENDRR may act as an inhibitory molecule of doxorubicin-resistance through down-regulating the expression of ABCB1 and ABCC1 genes in osteosarcoma cells. These findings may extend the function of FENDRR in tumor progression and provide a novel target for reversing OS chemoresistance.


Neutral zinc, lower-order zincate and higher-order zincate derivatives of pyrrole: synthesis and structural characterisation of zinc complexes with one, two, three or four pyrrolyl ligands.
Towards a systematic development of the zinc chemistry of the important five-membered nitrogen heterocycle pyrrole, this work reports the synthesis and characterisation of five crystalline zinc-pyrrolyl complexes. Pyrrolyl in this context means where conversion of the N-H bond to an N-zinc bond has occurred. Two neutral complexes, [(t)BuZn(NC(4)H(4))(TMEDA)·HNC(4)H(4)] 1 and [Zn(NC(4)H(4))(2)(TMEDA)] 2, containing one and two pyrrolyl ligands, respectively, were synthesised by reacting di-t-butylzinc with different amounts of pyrrole in the presence of TMEDA (TMEDA is N,N,N',N'-tetramethylethylenediamine). X-ray crystallographic studies established that both adopt mononuclear structures with the salient feature of the former the presence of an additional parent protonated pyrrole molecule which engages its anionic counterpart in N-H…πC-C interactions. Employing a similar synthetic approach but adding n-butylsodium to the reaction mixture in attempts to form ate derivatives delivered three distinct sodium zincate (anionic zinc) compounds in [{(THF)(2)·NaZn(THF)(NC(4)H(4))(3)}(∞)] 3, [{(TMEDA)·Na}(2)Zn(NC(4)H(4))(4)] 4, and [{(PMDETA)·Na}(2)Zn(NC(4)H(4))(4)] 5 (PMDETA is N,N,N',N'',N''-pentamethyldiethylenetriamine). From their crystal structures, the 1 : 1, Na:Zn complex 3 can be classified as a lower-order zincate having three pyrrolyl ligands bound to zinc in a polymeric chain arrangement, while the 2 : 1, Na:Zn complexes 4 and 5 are molecular higher-order zincates having Zn centres fully saturated by four pyrrolyl ligands. Discussion of the structures of 1-5 focuses on the interplay of σ-bonding and π-bonding between the pyrrolyl ligands and the metal centres. Revealingly, the zinc-free sodiopyrrole complex [{(PMDETA)·Na(NC(4)H(4))}(2)] 6, made and characterised for comparison, shows that on its own sodium prefers the former type of bonding, but is forced to switch to the latter type when combined with the stronger Lewis acid zinc in the zincate compositions. Complexes 1-6 have also been characterised in solution by NMR spectroscopy.


Latina mothers' stances on stimulant medication: complexity, conflict, and compromise.
This study was undertaken to understand and describe Latina mothers' cognitions and attitudes toward the use of medication for their young children's behavior problems under the premise that these factors are determinants of noncompliance and inadequate adherence to medication treatments. Quantitative and qualitative data were extracted from a multimethod study of professional help seeking. Participants were 62 mothers from Cuba, Puerto Rico, and the Dominican Republic. Findings indicated that mothers overwhelmingly preferred treatment options other than medication primarily because they understood medication to be addictive, dulling of cognitive processes, and inappropriate for behavior problems. Inadequate adherence was common and logically consistent with maternal cognitions. Maternal choices with respect to the use of medication were transactional and quite complex in nature and changed over time. The strongest agents in this process were schools and the mothers' immediate family. Implications for clinical practice are presented.


[Hybrid repair of the aortic arch. Santa Marta Hospital initial experience].
To retrospectively review the hybrid treatment of the aortic arch with supra-aortic debranching and endo- vascular stent-graft repair in a single institution. From 2007 to 2010, all patients submitted to aortic debranching procedures were entered into a prospective database analysis. For the present study, only patients with sealing zones 0 and 1, according to the Ishimaru classification, were included. Procedure-related morbimortality was analysed for the open and endovascular procedures. During the study period, we electively performed 6 total aortic debranching and 4 partial aortic debranching procedures in 10 patients. According to the etiology the indications were: 6 aortic arch aneurysms, 2 post-dissection aneurysms, 1 false aneurysm and 1 type I endoleak following TEVAR. The proximal sealing zone was Ishimaru zone 0 in six patients and zone 1 in four patients. The TEVAR procedure was delayed in all patients with a completion success of 80% (1 patient died from ruptured aortic aneurysm; 1 patient denied the second procedure and was lost to follow-up). The 30d mortality rate was 10% (patient mentioned above). The main morbidity was: 1 axillar venous thrombosis, 1 case of subclinical myocardial infarction, 1 case of terminal renal insufficiency and 1 case of prolonged ventilation. No permanent cerebral or peripheral neurologic deficit was noted. The hybrid repair of the aortic arch is a feasible and reproducible procedure, and our results are similar to the previously published series. Medium and long-term results are necessary to confirm whether the technique can be regarded as a safe alternative to open surgery in high-risk patients.


Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome.
We examined the incidence, clinical course, and outcome of patients with newly diagnosed acute promyelocytic leukemia (APL) who developed the retinoic acid syndrome (RAS) treated on the Intergroup Protocol 0129, which prospectively evaluated the role of alltrans retinoic acid (ATRA) alone during induction and as maintenance therapy. Forty-four of 167 (26%) patients receiving ATRA for induction developed the syndrome at a median of 11 days of ATRA (range, 2-47). The median white blood cell (WBC) count was 1,450/microL at diagnosis and was 31,000/microL (range, 6,800-72,000/microL) at the time the syndrome developed. ATRA was discontinued in 36 of the 44 patients (82%) and continued in 8 patients (18%), with subsequent resolution of the syndrome in 7 of the 8. ATRA was resumed in 19 of the 36 patients (53%) in whom ATRA was stopped and not in 17 (47%). The syndrome recurred in 3 of those 19 patients, with 1 death attributable to resumption of the drug. Ten of these 36 patients received chemotherapy without further ATRA, and 8 achieved complete remission (CR). Among 7 patients in whom ATRA was not restarted and were not treated with chemotherapy, 5 achieved CR and 2 died. Two deaths were definitely attributable to the syndrome. No patient receiving ATRA as maintenance developed the syndrome. (Blood. 2000;95:90-95)


Natural honey modulates physiological glycemic response compared to simulated honey and D-glucose.
The present study is undertaken to find out the relative glycemic tolerance of natural honey compared with simulated honey and D-glucose using oral glucose tolerance tested up to 180 min. Twenty-six healthy human subjects with mean age of 28.6 +/- 9.3 y were randomly divided into 3 groups, that is, natural honey consumers (NHC; n= 13), simulated honey consumers (AHC; n= 6), and D-glucose consumers (DGC; n= 7). After recording fasting blood glucose, the participants consumed either natural honey or simulated honey or D-glucose (1g/kg body weight). Subsequently, additional plasma glucose levels (PGLs) were recorded at 60, 120, and 180 min. At 60 min, DGC and AHC group members exhibited similar PGL elevation (that is, 52% and 47%, respectively) compared to NHC group with only 20% increment. On the other hand, after 180 min, 20% decrease in PGL was observed in the DGC group compared to 9.75% reduction in the NHC group. These observations are primarily in line with earlier studies. Results analyzed by one-way analysis of variance (ANOVA) showed significant differences between all 3 tested groups with F-statistic (19.96) and P value (< 0.005). Coefficient of variation of the NHC, AHC, and DGC groups were 14.8%, 20.2%, and 27.5%, respectively. Posthoc tests showed that glucose response was significantly lower in the NHC group at all time points (P < 0.005) compared to the AHC and DGC groups. In conclusion, natural honey stabilizes physiological glycemic response with rebound recovery of PGL.


Familial gigantiform cementoma with recurrent ANO5 p.Cys356Tyr mutations: Clinicopathological and genetic study with literature review.
Familial gigantiform cementoma (FGC) is a rare tumor characterized by the early onset of multi-quadrant fibro-osseous lesions in the jaws, causing severe maxillofacial deformities. Its clinicopathological features overlap with those of other benign fibro-osseous lesions. FGC eventually exhibits progressively rapid growth, but no suspected causative gene has been identified. In this study, three patients with FGC were recruited, and genomic DNA from the tumor tissue and peripheral blood was extracted for whole-exome sequencing. Results showed that all three patients harbored the heterozygous mutation c.1067G > A (p.Cys356Tyr) in the ANO5 gene. Furthermore, autosomal dominant mutations in ANO5 at this locus have been identified in patients with gnathodiaphyseal dysplasia (GDD) and are considered a potential causative agent, suggesting a genetic association between FGC and GDD. In addition, multifocal fibrous bone lesions with similar clinical presentations were detected, including five cases of florid cemento-osseous dysplasia, five cases of polyostotic fibrous dysplasia, and eight cases of juvenile ossifying fibromas; however, none of them harbored mutations in the ANO5 gene. Our findings indicate that FGC may be an atypical variant of GDD, providing evidence for the feasibility of ANO5 gene testing as an auxiliary diagnostic method for complex cases with multiple quadrants.


Different approaches to heart valve decellularization: A comprehensive overview of the past 30 years.
Xenogeneic decellularized heart valve scaffolds have the potential to overcome the limitations of existing bioprosthetic heart valves that have limited duration due to calcification and tissue degeneration phenomena. This article presents a review of 30 years of decellularization approaches adopted in cardiovascular tissue engineering, with a focus on the use, either individually or in combination, of different detergents. The safety and efficacy of cell-removal procedures are specifically reported and discussed, as well as the structure and biomechanics of the treated extracellular matrix (ECM). Detergent residues within the ECM, production of hyaluronan fragments, safe removal of cellular debris, and the persistence of the alpha-Gal epitope after the decellularization treatments are of particular interest as parameters for the identification of the best tissue for the manufacture of bioprostheses. Special attention has also been given to key factors that should be considered in the manufacture of the next generation of xenogeneic bioprostheses, where tissues must retain the ability to be remodeled and to grow in weight along with body reshaping.


Enhancing pedicle safety in mastopexy and breast reduction procedures: the posteroinferomedial pedicle, retaining the medial vertical ligament of Würinger.
Nipple necrosis, a potential postoperative complication of breast surgery procedures, should be avoided. Because of the great variation in the blood supply to the nipple, it is advisable to include as many arteries in the pedicle as possible. According to the literature, the perforators of the internal thoracic artery are the most constant and reliable sources of blood to the nipple-areola complex. It is also supplied by the lateral thoracic artery and the anterior intercostal arteries. If two of the above-mentioned main vessel branches are included in the pedicle, the vascular supply to the breast will be more reliable. According to the anatomical studies of Würinger and van Deventer, we can safely include the dual blood supply to the nipple-areola complex. In the authors' technique, a pedicle is raised that includes the horizontal septum and the medial vertical ligament of the breast (i.e., inferior and superomedial pedicles), but with the breast tissue remaining attached to the pectoral fascia. The second, third, and fourth perforators of the internal thoracic artery are found in the medial vertical ligament, and the inferior mammary branches of the anterior intercostal arteries are in the horizontal septum. The authors have performed this technique in 106 consecutive patients (211 breasts) between 2001 and 2009. Good results regarding breast shape, nipple projection, and upper breast fullness were obtained. The posteroinferomedial pedicle technique is safe and versatile and can be used with a periareolar, vertical scar, or inverted-T skin approach. The technique is easy to perform and has a short learning curve.


Activation/dephosphorylation of rabbit muscle glycogen synthase by the catalytic subunits of protein phosphatase-1 and 2A.
Glycogen synthase a was purified from rabbit skeletal muscle by a procedure involving heparin-Sepharose chromatography. Glycogen synthase a was phosphorylated by the catalytic subunit of cAMP-dependent protein kinase to give synthase b1. Dephosphorylation and activation of synthase b1 was investigated using the catalytic subunits of protein phosphatase-1 and 2A. The dephosphorylation and activation of synthase b1 was biphasic with a larger rate constant for the initial phase. Analysis of tryptic phosphopeptides of glycogen synthase during the course of dephosphorylation revealed a faster initial phosphate release from site-2 by both phosphatases comparing to sites-1a and 1b. Ligand effects on synthase phosphatase reactions were also studied. Spermine was found to inhibit protein phosphatase-1 activity and to stimulate type-2A phosphatase using synthase b1 as substrate.


An fMRI investigation of cerebellar function during verbal working memory in methadone maintenance patients.
Working memory is impaired in opioid-dependent individuals, yet the neural underpinnings of working memory in this population are largely unknown. Previous studies in healthy adults have demonstrated that working memory is supported by a network of brain regions that includes a cerebro-cerebellar circuit. The cerebellum, in particular, may be important for inner speech mechanisms that assist verbal working memory. This study used functional magnetic resonance imaging to examine brain activity associated with working memory in five opioid-dependent, methadone-maintained patients and five matched, healthy controls. An item recognition task was administered in two conditions: (1) a low working memory load "match" condition in which participants determined whether target letters presented at the beginning of the trial matched a probe item, and (2) a high working memory load "manipulation" condition in which participants counted two alphabetical letters forward of each of the targets and determined whether either of these new items matched a probe item. Response times and accuracy scores were not significantly different between the groups. FMRI analyses indicated that, in association with higher working memory load ("manipulation" condition), the patient group exhibited hyperactivity in the superior and inferior cerebellum and amygdala relative to that of controls. At a more liberal statistical threshold, patients exhibited hypoactivity in the left prefrontal and medial frontal/pre-SMA regions. These results indicate that verbal working memory in opioid-dependent individuals involves a disrupted cerebro-cerebellar circuit and shed light on the neuroanatomical basis of working memory impairments in this population.


A patient reflects on chronic illness-and support from family and physicians.
Note: This editorial was a college essay; the assignment was to write an acceptance speech for an award given for something the student had accomplished. Tim Prevou has been treated since age 6 by Dr. Virginia Pascual, a pediatric rheumatologist and researcher at Baylor Research Institute. Dr. Pascual collaborated with Dr. Carol Wise, who found the mutated gene responsible for PAPA syndrome; she and her team later found that IL-1 blockade was an effective therapy. Dr. Pascual commented: "This therapy completely cured Tim's twin brothers and completely resolved Tim's arthritis. Tim's severe pyoderma lesions took more effort, but eventually we also got them under control. ... He is the only patient over 18 years old that I still see in the clinic. ... I am very proud of him."


Flotillin-1 Interacts With and Sustains the Surface Levels of TRPV2 Channel.
Transient receptor potential vanilloid subtype 2 (TRPV2) channel is a polymodal receptor regulating neuronal development, cardiac function, immunity and oncogenesis. The activity of TRPV2 is regulated by the molecular interactions in the subplasmalemmel signaling complex. Here by yeast two-hybrid screening of a cDNA library of mouse dorsal root ganglia (DRG) and patch clamp electrophysiology, we identified that flotillin-1, the lipid raft-associated protein, interacts with TRPV2 channel and regulates its function. The interaction between TRPV2 and flotillin-1 was validated through co-immuoprecipitation in situ using endogenous DRG neurons and the recombinant expression model in HEK 293T cells. Fluorescent imaging and bimolecular fluorescence complementation (BiFC) further revealed that flotillin-1 and TRPV2 formed a functional complex on the cell membrane. The presence of flotillin-1 enhanced the whole-cell current density of TRPV2 via increasing its surface expression levels. Using site-specific mapping, we also uncovered that the SPFH (stomatin, prohibitin, flotillin, and HflK/C) domain of flotillin-1 interacted with TRPV2 N-termini and transmembrane domains 1-4, respectively. Our findings therefore demonstrate that flotillin-1 is a key element in TRPV2 signaling complex and modulates its cellular response.


Fibrous dysplasia.
An atypical presentation of fibrous dysplasia with a very large cystic component is described. The MR pattern was not diagnostic.


Overview of Riociguat and Its Role in the Treatment of Pulmonary Hypertension.
Pulmonary hypertension (PH), which includes pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), is a progressive condition with significant morbidity and mortality due to right heart failure if left untreated. Riociguat is a soluble guanylate cyclase (sGC) stimulator and is the only treatment approved for both PAH and CTEPH. The objectives of this review are to describe the epidemiology and pathophysiology of PAH and CTEPH; synthesize the pharmacology, efficacy, safety, and utilization of riociguat; and discuss the role of the pharmacist in managing patients with these conditions. Data presented in this review is supported by peer reviewed literature, using PubMed and key words including pulmonary hypertension, pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and riociguat. The review draws on key studies and review articles that discuss the pathophysiology of PAH and CTEPH, as well as articles discussing the safety and efficacy of riociguat. The overall goal in the treatment of PAH and CTEPH is to improve long-term survival. Treatment planning depends on the type of PH, treatment goals, comorbidities, and risk profiles. Pharmacists serve a valuable role as part of the multidisciplinary team in the care of patients with PH, many of whom may have comorbidities that contribute to high costs and resource utilization. Riociguat is a first-in-class medication and the only approved treatment for both PAH and CTEPH. In clinical trials, riociguat has demonstrated favorable efficacy and tolerability. Riociguat is a valuable addition to the armamentarium of options for treating patients with PH.


Predictors of mortality for hospitalized young adults aged less than 60 years old with severe COVID-19: a retrospective study.
To analyze the clinical characteristics and predictors for mortality of adult younger than 60 years old with severe coronavirus disease 2019 (COVID-19). We retrospectively retrieved data for 152 severe inpatients with COVID-19 including 60 young patients in the Eastern Campus of Wuhan University affiliated Renmin Hospital in Wuhan, China, from January 31, 2020 to February 20, 2020. We recorded and analyzed patients' demographic, clinical, laboratory, and chest CT findings, treatment and outcomes data. Of those 60 severe young patients, 15 (25%) were died. Male was more predominant in deceased young patients (12, 80%) than that in recovered young patients (22, 49%). Hypertension was more common among deceased young patients (8, 53%) than that in recovered young patients (7, 16%). Compared with the recovered young patients, more deceased young patients presented with sputum (11, 73%), dyspnea (12, 80%) and fatigue (13, 87%). Only sputum, PSI and neutrophil counts were remained as independent predictors of death in a multivariate logistic regression model. Among ARDS patients, the recovered were administrated with corticosteroid earlier and anticoagulation. The addition of neutrophil counts >6.3×109/L to the SMART-COP score resulted in improved area under the curves. Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection in young deceased patients appears to cause exuberant inflammatory responses, leading to compromised oxygen exchange, coagulation and multi-organ dysfunction. In addition, young patients with ARDS could benefit from adjuvant early corticosteroid and anticoagulation therapy. The expanded SMART-COP could predict the fatal outcomes with optimal efficiency.


Association between centralization, depression, somatization, and disability among patients with nonspecific low back pain.
Secondary analysis of a prospective observational cohort study. To evaluate whether depression and somatization subscores of the Symptom Checklist-90-Revised (SCL-90-R), which have been shown to identify chronic disability in individuals with nonspecific low back pain, are applicable to a different population of individuals with low back pain; and to determine if this potential association is confounded by a combination of centralization and subsequent treatment based on centralization. To help direct management of patients with nonspecific low back pain, recommendations include performing tests designed to identify psychosocial risk factors predictive of poor patient outcomes. SCL-90-R depression and somatization subscores have been shown to predict chronic disability among patients with low back pain. SCL-90-R depression and somatization subscores and data on centralization were collected during the initial physical therapy examination of 231 consecutive patients treated for low back pain in 2 clinics. Disability was assessed by the Oswestry Disability Questionnaire at intake and discharge from physical therapy, and work status was determined by patient self-report at 6 and 12 months after discharge. Pain intensity was assessed by the numeric pain rating scale at the initial visit, and at 6- and 12-month follow-ups. Data were analyzed using logistic regression. Odds ratios for the association between depression and somatization subscores and patient outcomes ranged from 0.76 to 2.93. For analyses in which the data suggested a trend toward an association, the association was less evident following adjustment for centralization and centralization-based treatment. In our sample, in which all individuals received physical therapy, and those who centralized received interventions based on the direction of centralization, SCL-90-R depression and somatization subscores were moderately associated with chronic pain and disability. This association was reduced when centralization and centralization-based treatment was considered in multivariable analyses.


In-vivo studies on intraperitoneally administrated poly(vinyl alcohol).
The fate of poly(vinyl alcohol) (PVA, 195,000 g/mol) was studied in rabbits and nude mice after intraperitoneal (i.p.) administration. In-vivo fluorescence imaging using nude mice allowed for studies of tetramethylrhodamine labeled PVA distribution in the body and tracking the urinary excretion. The excreted PVA was studied in detail after collecting the urine of rabbits over a time period of 28 days. The PVA was separated from the urine by dialysis and analyzed by FTIR spectroscopy, (1)H-NMR spectroscopy, and size exclusion chromatography (SEC). Even after extensive dialysis, it was found that the excreted PVA showed a characteristic brownish color. The spectroscopic techniques revealed that this color was caused by the urine pigment (a metabolite of bilirubin) that could not be separated completely from the PVA. SEC showed unambiguously that the PVA with the very high molar mass had a glomerular permeability in the kidneys. Simultaneously, histological studies of the kidneys and the liver demonstrated that the tissues did not show any obvious damage.


Staphylococcus aureus small colony variants are induced by the endothelial cell intracellular milieu.
Recent studies have reported that Staphylococcus aureus small colony variants (SCVs) can cause highly persistent infections in humans and in cultured endothelial cells. To understand the process by which SCVs of S. aureus appear in subjects who have not received antibiotic treatment, bovine endothelial cells were coincubated with a wild S. aureus strain for 72 h in the presence of lysostaphin. Intracellular bacteria were harvested and screened for stable SCVs. Intracellular bacteria developed the SCV phenotype at a greater rate than control bacteria not exposed to endothelial cells: The intracellular induction rate was approximately 10(-3) versus a spontaneous rate of <10(-7). This observation suggest that SCVs are induced by the intracellular milieu and suggest a possible mechanism for the intriguing pathophysiology of tissue persistence of staphylococci.


Effect of desloratadine versus placebo on nasal airflow and subjective measures of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in an allergen-exposure unit.
Unlike many antihistamines, desloratadine can reduce nasal congestion in patients with seasonal allergic rhinitis (SAR). We compared the effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms, including nasal congestion, in response to grass pollen in an allergen-exposure unit. In a randomized, double-blind, placebo-controlled, crossover trial, 47 subjects with histories of SAR received desloratadine or placebo every morning for 7 days and, after a 10-day washout period, were crossed over to the other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on day 7 of each treatment period. Nasal airflow and nasal secretion weights were measured before and every 30 minutes during allergen exposure; SAR symptoms (including nasal congestion) were scored before exposure and every 15 minutes thereafter. Nasal obstruction, as measured by nasal airflow, was less severe with desloratadine than with placebo (P <.02). Individual and combined SAR symptom severity scores, including nasal congestion and sneezing, were significantly lower with desloratadine than with placebo (all P < or =.003). Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P <.02), less nasal secretions (P <.001), and less severe symptoms, including nasal congestion (P <.002), rhinorrhea, and sneezing, occurred with desloratadine compared with placebo, and this continued throughout (0-6 hours) allergen exposure. Desloratadine was well tolerated, with an adverse event profile similar to that of placebo. In subjects with allergen-induced SAR symptoms, desloratadine significantly reduced the severity of nasal obstruction and accompanying complaints of nasal congestion and other SAR symptoms compared with the effects of placebo.


Essential role of the transcription factor Ets-2 in Xenopus early development.
The fibroblast growth factor (FGF)/MAPK pathway plays an important role in early Xenopus developmental processes, including mesoderm patterning. The activation of the MAPK pathway leads to induction of Xenopus Brachyury (Xbra), which regulates the transcription of downstream mesoderm-specific genes in mesoderm patterning. However, the link between the FGF/MAPK pathway and the induction of Xbra has not been fully understood. Here we present evidence suggesting that Ets-2 is involved in the induction of Xbra and thus in the development of posterior mesoderm during early embryonic development. Overexpression of Ets-2 caused posteriorized embryos and led to the induction of mesoderm in ectodermal explants. Expression of a dominant-negative form of Ets-2 or injection of antisense morpholino oligonucleotides against Ets-2 inhibited the formation of the trunk and tail structures. Overexpression of Ets-2 resulted in the induction of Xbra, and expression of the dominant-negative Ets-2 inhibited FGF- or constitutively active MEK-induced Xbra expression. Moreover, overexpression of Ets-2 up-regulated the transcription from Xbra promoter reporter gene constructs. Ets-2 bound to the Xbra promoter region in vitro. These results taken together indicate that Xenopus Ets-2 plays an essential role in mesoderm patterning, lying between the FGF/MAPK pathway and the Xbra transcription.


Aortic dissection in a cardiac allograft recipient: a case report.
Ascending aortic dissection is rare in cardiac allograft recipients. Only two patients with dissection arising from the native aorta have been reported previously and, unfortunately, the diagnosis was made postmortem in each instance. We report the first case of successful surgical treatment of aortic dissection confined to the donor aorta in a recipient of an orthotopic cardiac allograft.


Effect of protein kinase C activators on the phosphorylation and the surface expression of the CDw50 leukocyte antigen.
The CDw50 antigen is a constitutively non-phosphorylated leukocyte surface molecule which becomes highly phosphorylated in all the normal and lymphoblastoid cells analyzed (peripheral blood mononuclear cells, Molt 4, CEM, 8402, Namalwa), after stimulation with tumor promoter agents (phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate, mezerein). This phosphorylation is rapid (within 1-5 min), dose-dependent and results in the incorporation of PO(3-)4 groups on serine residues. Furthermore, the level of CDw50 phosphorylation induced by tumor promoter agents is decreased by the protein kinase C inhibitors staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine. Activation of peripheral lymphocytes with concanavalin A, phytohemagglutinin and cross-linking of CD3 molecules also induces CDw50 phosphorylation, but the response is delayed and less intense than when tumor promoting agents are used. Treatment with any of the aforementioned agents is not accompanied by quantitative changes in the CDw50 surface expression. We therefore conclude that protein-kinase-C-mediated mechanisms are involved in phosphorylation, but not in regulation of the surface expression of the CDw50 leukocyte antigen.


[Hainan population growth].
According to statistics, the birth rate in 1980 in Hainan was reduced by 1.77/1000 over 1979, while the natural population growth rate was reduced by 1.75/1000. The number of couples having only 1 child also increased. With the exception of Wanning, Chengmai, and Lingshui Counties, the natural population growth rate in the remaining 15 counties and municipalities declined. In accordance with the 30 regulations of the Guangdong Provincial CCP Committee, the Hainan Regional CCP Committee has formulated 10 supplementary regulations. At the end of 1979, the region and autonomous prefecture again held a massive inspection of planned parenthood work. The leading cadres at all levels have also taken the lead in educating their sons and daughters to have only 1 child/couple.


Renal biopsy in a child with nephrotic syndrome.
A 6-year-old girl with nephrotic syndrome was treated with prednisone, without response. A renal biopsy was obtained. Following the format used at the Tulane Renal Biopsy Conferences, the clinical presentation, differential diagnosis and clinical discussion in this young patient will be presented first. The second part will include the renal biopsy findings, the final diagnosis and the pathology discussion.


Tooth cementum annulation for age estimation: results from a large known-age validation study.
Recent research indicates that tooth-cementum annulations (TCA) may be used more reliably than other morphological or histological traits of the adult skeleton to estimate age. Until now, however, confidence intervals for age estimated by this method have not been available for paleodemographic and forensic applications. The present study addresses this problem. Based on a large known-age sample, age estimates by TCA were conducted in a blind study involving 363 teeth. Tooth-root cross sections were made using a refined preparation technique. Improved digital graphic procedures and enhancement strategies were used to produce digital images with a specially adapted software package. This resulted in high concordance between the TCA age estimates and chronological age. Assessment of the method's accuracy, as expressed by 95% confidence intervals, showed that error bounds for age estimates do not exceed 2.5 years. Sex differences, intraindividual correlations, and the effects of periodontal disease were studied. None of these indicators had a quantitative effect on the number of TCA bands when the proposed methodological standard was followed. We conclude that the TCA technique is a reliable method for estimating a subject's age from cementum annulations.


Early diagnosis and surgical management of heterotopic pregnancy allows us to save the intrauterine pregnancy.
Heterotopic pregnancy is a rare but intriguing disease, which poses a high risk for pregnant women and for intrauterine pregnancy. Clinically, it is mainly characterized by pain and vaginal bleeding. b-hCG serum dosage is used to detect the pregnancy, but transvaginal ultrasound is needed to diagnose heterotopic pregnancy. From all the risk factors, the assisted reproductive treatments represent the most important, especially when multiple embryos are transferred. Patients with a heterotopic pregnancy are at risk of having a spontaneous or medically induced abortion, and for this reason appropriate and tailored treatment should be considered, pursuing the optimal risk/benefit ratio. Although conservative treatments are available in the case of only extrauterine pregnancy, such as methotrexate, often the laparoscopic approach seems unavoidable in heterotopic pregnancy. To preserve the intrauterine pregnancy, a conservative treatment is remarkable, both salpingotomy or salpingostomy. In this case report, we present a successful laparoscopic treatment of an extrauterine pregnancy with the prosecution of the intrauterine pregnancy up to the third trimester. In particular, a 25-year-old girl referred to the Villa Sofia Cervello Hospital complaining of abdominopelvic pain and vaginal bleeding for 2 days. The salpingectomy approach was performed, and every anatomical piece was sent for histopathology.


Twist1 promotes heart valve cell proliferation and extracellular matrix gene expression during development in vivo and is expressed in human diseased aortic valves.
During embryogenesis the heart valves develop from undifferentiated mesenchymal endocardial cushions (EC), and activated interstitial cells of adult diseased valves share characteristics of embryonic valve progenitors. Twist1, a class II basic-helix-loop-helix (bHLH) transcription factor, is expressed during early EC development and is down-regulated later during valve remodeling. The requirements for Twist1 down-regulation in the remodeling valves and the consequences of prolonged Twist1 activity were examined in transgenic mice with persistent expression of Twist1 in developing and mature valves. Persistent Twist1 expression in the remodeling valves leads to increased valve cell proliferation, increased expression of Tbx20, and increased extracellular matrix (ECM) gene expression, characteristic of early valve progenitors. Among the ECM genes predominant in the EC, Col2a1 was identified as a direct transcriptional target of Twist1. Increased Twist1 expression also leads to dysregulation of fibrillar collagen and periostin expression, as well as enlarged hypercellular valve leaflets prior to birth. In human diseased aortic valves, increased Twist1 expression and cell proliferation are observed adjacent to nodules of calcification. Overall, these data implicate Twist1 as a critical regulator of valve development and suggest that Twist1 influences ECM production and cell proliferation during disease.


Specificity and cross-reactivity of monoclonal antibodies against bovine insulin.
The positions of antigenic determinants were determined for six monoclonal antibodies against bovine insulin. Three antibodies bound to a determinant around amino acid residue A-10 and the other three to a determinant near the carboxy-terminal of the B-chain. The monoclonal antibodies discriminated between insulin of various species better than did a guinea pig anti-bovine insulin antiserum. One monoclonal antibody discriminated between porcine and human insulin and was used to show that, in principle, it is possible to determine the amount of porcine insulin contained in a mixture of porcine and human insulin.


Reversibility of structural rearrangements in lipid membranes induced by adsorption-desorption of a polycation.
Interaction of poly(N-ethyl-4-vinylpyridinium bromide) with mixed cardiolipin/phosphatidyl-choline (1/9) liposomes was studied by differential scanning calorimetry and photon correlation spectroscopy. It was found that the adsorption of polycation on the surface of liquid liposomes was accompanied by transmembrane migration of negatively charged cardiolipin molecules from the inner to outer membrane leaflet and lateral lipid segregation. At the same time, the liposome integrity was retained, and the adsorbed polycation can be displaced from the membrane by recomplexation with polyanions. As a result, the initial transmembrane and lateral lipid distribution in the membrane was restored.


Valproate-Induced Hyperammonemic Encephalopathy.
Valproate is the best choice drug for a variety of medical conditions. As with any other drug, it has adverse effects, and it is important to emphasize the possibility of those adverse effects to prevent complications. We present the case history of a 44-year-old male with valproate-induced hyperammonemic encephalopathy, despite having normal liver function tests. This case includes a detailed literature review of this rare adverse event. In the light of this case report, we illustrate the importance of checking ammonia levels in all psychiatric patients receiving valproate as a treatment who present with new onset neurological symptoms or altered mental status.


Shifting Paradigms for Suppressing Fibrosis in Kidney Transplants: Supplementing Perfusion Solutions With Anti-fibrotic Drugs.
Great efforts have been made toward addressing the demand for donor kidneys. One of the most promising approaches is to use kidneys from donation after circulatory death donors. These kidneys, however, suffer from more severe ischemia and reperfusion injury than those obtained via donation after brain death and are thus more prone to develop interstitial fibrosis and tubular atrophy. Even though machine perfusion is increasingly used to reduce ischemia and reperfusion injury, there are no effective treatments available to ameliorate interstitial fibrosis and tubular atrophy, forcing patients to resume dialysis, undergo re-transplantation, or suffer from premature death. Safe and effective anti-fibrotic therapies are therefore greatly desired. We propose a new therapeutic approach in which machine perfusion solutions are supplemented with anti-fibrotic compounds. This allows the use of higher concentrations than those used in humans whilst eliminating side effects in other organs. To the authors' knowledge, no one has reviewed whether such an approach could reduce interstitial fibrosis and tubular atrophy; we therefore set out to explore its merit. In this review, we first provide background information on ischemia and reperfusion injury as well as interstitial fibrosis and tubular atrophy, after which we describe currently available approaches for preserving donor kidneys. We then present an evaluation of selected compounds. To identify promising compounds, we analyzed publications describing the effects of anti-fibrotic molecules in precision-cut kidneys slices, which are viable explants that can be cultured ex vivo for up to a few days whilst retaining functional and structural features. LY2109761, galunisertib, imatinib, nintedanib, and butaprost were shown to exert anti-fibrotic effects in slices within a relatively short timeframe (<48 h) and are therefore considered to be excellent candidates for follow-up ex vivo machine perfusion studies.


The Indirect Costs of the SARS-CoV-2 Pandemic: A Case of Severe Malaria in Brooklyn.
Severe malaria due to the infection of Plasmodium falciparum is a critical infection that may lead to multisystem abnormalities if not promptly and adequately treated. We present a case of severe malaria in a patient recently repatriated from Conakry, Guinea, West Africa, marooned during the recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the direct costs of the SARS-CoV-2 pandemic and its indirect effect on neighboring industries have been analyzed, the indirect costs of other ailments in medicine have yet to be fully established. This case explores the ramifications of the SARS-CoV-2 pandemic on what would otherwise have been routine prophylaxis of malaria in a traveler. Given the pandemic, the healthcare industry has had fundamental changes that have impacted access to healthcare, particularly in the outpatient setting.


United airway disease.
Nose and lungs are considered as anatomic and functional unit, as they share morphological, pathophysiological and immunological basis. Allergic rhinitis and asthma often coexist in the same individual, and the treatment of one also improves the symptoms of the other (one airway, one disease). The aim of this review is to discuss the interaction between upper and lower airways, based on recent scientific evidence and, critically, analyze the important implications the new findings have for the future therapy and prevention of these common diseases.


Congenital malignant melanoma: a case report with cytogenetic studies.
Although rare, congenital malignant melanoma (CMM) should be considered in the differential diagnosis of congenital skin lesions. We report a case of CMM in a 4-month-old infant presenting with an enlarging scalp mass, initially thought to be a hemangioma. Incisional biopsy of the lesion showed a compound congenital nevus with atypical cells suggestive of a proliferative nodule versus malignancy on histopathology. Subsequent excisional biopsy revealed malignant melanoma, and further workup confirmed extensive disease with distant metastases. Cytogenetic analysis of both the tumor sites showed highly abnormal karyotypes including pseudotetraploidy, telomere associations, and evidence of gene amplification, all consistent with malignancy. Fluorescence in situ hybridization demonstrated amplification of the MYC gene, with no copy number changes in CDKN2A (INK4/ARF), PTEN, or Cyclin D1. Our report details the cytogenetic and molecular studies of CMM, which provide insight into the biologic behavior of the lesions and may confirm diagnosis when histopathology is not determinant.


Worth Remembering: Cardiac Memory Presenting as Deep Anterior T-Wave Inversions Explained by Intermittent Left Bundle Branch Block.
Cardiac memory is a common cause of deep T-wave inversions (TWI) in the anterior precordial leads and can be difficult to distinguish from alternative causes of TWI such as myocardial ischemia. Cardiac memory is generally a benign condition except in the setting of prolonged QT when it can contribute to the precipitation of torsades de pointes. Herein, we describe the presentation and clinical course of a case of cardiac memory due to intermittent left bundle branch block (LBBB) that presented asymptomatically to our outpatient cardiology clinic with deep anterior TWI. We discuss common causes of and mechanisms underlying cardiac memory and how to distinguish it from alternative causes of TWI based on 12-lead electrocardiogram. In conclusion, intermittent LBBB is an under-recognized cause of cardiac memory that can present as deep anterior TWI mimicking cardiac ischemia, and awareness of this clinical entity may help prevent unnecessary invasive and expensive testing on otherwise healthy patients.


The Non-pregnant and Pregnant Human Cervix: a Systematic Proteomic Analysis.
Appropriate timing of cervical remodeling (CR) is key to normal term parturition. To date, mechanisms behind normal and abnormal (premature or delayed) CR remain unclear. Recent studies show regional differences exist in human cervical tissue structure. While the entire cervix contains extracellular matrix (ECM), the internal os is highly cellular containing 50-60% cervical smooth muscle (CSM). The external os contains 10-20% CSM. Previously, we reported ECM rigidity and different ECM proteins influence CSM cell function, highlighting the importance of understanding not only how cervical cells orchestrate cervical ECM remodeling in pregnancy, but also how changes in specific ECM proteins can influence resident cellular function. To understand this dynamic process, we utilized a systematic proteomic approach to understand which soluble ECM and cellular proteins exist in the different regions of the human cervix and how the proteomic profiles change from the non-pregnant (NP) to the pregnant (PG) state. We found the human cervix proteome contains at least 4548 proteins and establish the types and relative abundance of cellular and soluble matrisome proteins found in the NP and PG human cervix. Further, we report the relative abundance of proteins involved with elastic fiber formation and ECM organization/degradation were significantly increased while proteins involved in RNA polymerase I/promoter opening, DNA methylation, senescence, immune system, and compliment activation were decreased in the PG compared to NP cervix. These findings establish an initial platform from which we can further comprehend how changes in the human cervix proteome results in normal and abnormal CR.


Quantification of (15)N-nitrate in urine with gas chromatography combustion isotope ratio mass spectrometry to estimate endogenous NO production.
The use of stable isotope labeled substrates and subsequent analysis of urinary nitrate, forms a noninvasive test for evaluation of the in vivo NO metabolism. The present paper describes a new method for simultaneous quantification of (15)N-nitrate and total nitrate with gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS). Nitrate, isolated from urine with a nitrate selective resin, was reduced to nitrite using copperized cadmium. Subsequently, Sudan I was formed by diazotation. Sudan II was added as internal standard, and both molecules were analyzed with GC-C-IRMS as tert-butyldimethylsilyl derivatives. The accuracy was determined during a recovery study of two different known nitrate concentrations and two (15)N-enrichments. A recovery of 101.6% and 103.9% for total nitrate and 107.6% and 91.2% for (15)N-nitrate was obtained, respectively. The validated method was applied on complete 72 h urine collections after intravenous administration of (15)N-nitrate and (15)N-arginine in humans. On average, 51.8% (47.0-71.0%) of administered (15)N-nitrate was excreted, while 0.68% (0.44-1.17%) of (15)N-arginine was metabolized to nitrate. In conclusion, this method can be used for accurate simultaneous determination of (15)N-nitrate and total nitrate concentrations in urine and can be applied in clinical studies for noninvasive evaluation of NO metabolism in vivo.


Congenital myasthenic syndromes and transient myasthenia gravis.
Hypotonia in the neonatal period and early infancy is a common clinical finding. It can be caused by various heterogeneous disorders of different origin which might lead to diagnostic difficulties. Disorders of the neuromuscular junction, such as congenital myasthenic syndromes and neonatal transient myasthenia gravis are among the aetiologies. We report on a case of congenital myasthenia caused by mutation in the long cytoplasmic loop of the epsilon subunit of the acetylcholine receptor and a neonate of a myasthenic mother diagnosed with transient myasthenia gravis.


Aqueous shunts: single-plate Molteno vs ACTSEB.
A retrospective study was done to compare the results of the single-plate Molteno implant surgery with those of the anterior chamber tube shunt to an encircling band procedure in eyes with refractory glaucoma. Both Molteno implant and anterior chamber tube shunt to an encircling band are made of silicone. There were 19 eyes in the Molteno group, 17 eyes in the anterior chamber tube shunt to an encircling band group, with at least 6 months of follow-up. Preoperative intraocular pressure in the Molteno group and anterior chamber tube shunt to an encircling band group was 47.5 +/- 11.4 and 46.5 +/- 10.3 mmHg, respectively. Intraocular pressure at 6 months postoperatively was 20.4 +/- 15.1 and 15.5 +/- 10.4 mmHg, respectively. The difference in pressure reduction between the two groups was not significant statistically. Serious complication rate for 6 months was 11% and 47%, respectively.


Effect of miR-129-3p on autophagy of interstitial cells of Cajal in slow transit constipation through SCF C-kit signaling pathway.
To explore the mechanism by which miR-129-3p affected the autophagy of interstitial cells of Cajal (ICCs) in slow transit constipation tissues through the SCF C-kit signaling pathway. Colon samples from 20 Slow transit constipation (STC) patients who underwent total colectomy plus ileorectal anastomosis or subtotal colon resection plus anti-peristaltic rectal anastomosis were collected in our hospital. The colon of 20 non-STC patients was used as control. The control of this study was 20 patients undergoing radical surgery for colon cancer (left colon cancer) in our hospital. Fifty healthy SPF Kunming mice were purchased from Liaoning Changsheng Biotechnology Co., Ltd. The mRNA expression of miR-129-3p in the STC group was lower than that in the control group (CTLR) group (P<0.05). The mRNA expression of miR-129-3p in STC group was lower than that in the NC group (P<0.05), and mRNA expression in STC+miR-129-3p group was higher than that in STC+miR-NC group (P<0.05). In the first week, the weight of dry and wet feces of the STC group was lower than that of the NC mice (P<0.05), and the weight of dry feces and wet feces of the STC group was lower than that of the NC group at the 2, 3, and 4 weeks, STC+miR-129 -3p was higher than that in the STC group (P<0.05). The increased expression of C-kit and SCF regulated by miR-129-3p contributed to the protection of interstitial cells. Knockdown of miR-129-3p expression could inhibit the activation of AKT/mTOR signaling pathway, reduce cell proliferation activity.


Purification and kinetic analysis of the two recombinant arogenate dehydrogenase isoforms of Arabidopsis thaliana.
The present study reports the first purification and kinetic characterization of two plant arogenate dehydrogenases (EC 126.96.36.199), an enzyme that catalyses the oxidative decarboxylation of arogenate into tyrosine in presence of NADP. The two Arabidopsis thaliana arogenate dehydrogenases TyrAAT1 and TyrAAT2 were overproduced in Escherichia coli and purified to homogeneity. Biochemical comparison of the two forms revealed that at low substrate concentration TyrAAT1 is four times more efficient in catalyzing the arogenate dehydrogenase reaction than TyrAAT2. Moreover, TyrAAT2 presents a weak prephenate dehydrogenase activity whereas TyrAAT1 does not. The mechanism of the dehydrogenase reaction catalyzed by these two forms has been investigated using steady-state kinetics. For both enzymes, steady-state velocity patterns are consistent with a rapid equilibrium, random mechanism in which two dead-end complexes, E-NADPH-arogenate and E-NADP-tyrosine, are formed.


Attitudes of medical practitioners towards "Do Not Resuscitate" orders.
When the desires of a patient are unknown or cannot be ascertained, cardio-pulmonary resuscitation (CPR) is the default procedure. Explicit, Do Not Resuscitate (DNR), orders are required to prevent implementation of CPR. We studied the response of general medical internists in specific clinical situations demanding consideration of DNR orders and respect for patient preferences; their current practice regarding slow codes and participation in CPR attempts considered futile provide information as to how often they discuss DNR issues with patients or families. Eighty-five internists attending the monthly meeting of the Internal Medicine Forum participated in the study. The physicians demonstrated their consent to participate by accepting a remote transmitter that elicited a response 2-3 minutes following the presentation of case vignettes or practice-related questions. The survey showed that 73% of the physicians agreed to assign a DNR order for a terminally ill patient unable to express her preferences. Only 55% agreed to do the same for a competent patient who specifically requested that CPR be withheld in the event of a cardiopulmonary arrest (p<0.05). 77% reported to have performed CPR, at least three times, in situations where they expected no benefit. 59% affirmed that their team had performed a partial CPR (slow code) at least once. Only 28% discussed the subject of DNR with patients or family more than 5 times a year. Paternalism, disregard for patients' preferences and poor communication skills influence normative behaviour in end-of-life decision-making.


Multi-cusp ion source for doping process of flat panel display manufacturing.
We developed a multi-cusp ion source for Nissin ion doping system iG5 which is used in low temperature poly-crystalline silicon processes for flat panel display (FPD) manufacturing. In this ion source, BF3 or PH3 diluted H2 plasmas are produced and large area ribbon ion beams are extracted. In general, ion ratio of B(+) in BF3 plasma is much smaller than BF2 (+) in multi-cusp ion sources. We developed a new method to increase B(+) ratio and obtained mass analyzed B(+) target current of 130 mA. We employed newly improved multi-slot type electrodes for the beam extraction system and obtained stable beams with the uniformity of below 3%. In BF3 plasmas, several undesirable metal fluorides are produced in the plasma chamber and deposited on the electrode system, which cause glitches and poor beam uniformity. We introduce several cleaning methods.


Plant sterol 14 alpha-demethylase affinity for azole fungicides.
Azole fungicides were thought to have much greater affinity for the fungal cytochrome P450 enzyme, sterol 14 alpha-demthylase (CYP51) than the plant orthologue. Using purified CYP51 from the plant Sorghum bicolor L Moenech, a direct comparison of the sensitivity to the fungicides triadimenol and tebuconazole has been carried out. S. bicolor CYP51 was purified to homogenity as determined by SDS--PAGE and specific heme content. Addition of the azole fungicides triadimenol and tebuconazole induced type II spectral changes, with saturation occurring at equimolar azole/P450 concentrations. Inhibition of reconstituted activities revealed only a threefold insensitivity of the plant CYP51 compared to a fungal CYP51, from the phytopathogen Ustilago maydis, as judged by IC(50) values. The implications for fungicide mode of action and application are discussed.


Obesity among adults in the United States--no statistically significant change since 2003-2004.
Over 34% of adults aged 20 years and older are obese, but there has been no significant change in the prevalence since 2003-2004. The increasing trend in obesity over the last 25 years is a result of a shift in the entire BMI distribution and an increase in the prevalence of those who are extremely obese. In addition, disparities continue to exist. Non-Hispanic black and Mexican-American women continue to experience a higher prevalence of obesity than their non-Hispanic white counterparts. Although approximately two-thirds of obese individuals have been told by a health care provider that they are "overweight," obesity is extremely difficult to treat and the prevalence of obesity is not declining. Nonetheless, even without reaching ideal weight, research has shown that a moderate amount of weight loss can be beneficial in terms of reducing risk factors, such as high blood pressure. Maintenance of weight loss, however, remains difficult.


Hydroxytyrosol 4-beta-D-glucoside, an important phenolic compound in olive fruits and derived products.
There is increasing interest in olive polyphenols because of their biological properties as well as their contribution to the color, taste, and shelf life of olive products. However, some of these compounds remain unidentified. It has been shown that hydroxytyrosol 4-beta-D-glucoside (4-beta-D-glucosyl-3-hydroxyphenylethanol) coeluted with hydroxytyrosol [(3,4-dihydroxyphenyl)ethanol] under reversed phase conditions in the phenolic chromatograms of olive pulp, vegetation water, and pomace of olive oil processing. A method to separate this compound from hydroxytyrosol by HPLC has been developed. The concentration of this glucoside increased in olive pulp with maturation and could be the main phenolic compound in mature olives. In contrast, the presence of this compound was not detected in olive oil by using HPLC-MS. The compound must be considered both in table olives and olive oil processing because of its glucose and hydroxytyrosol contribution to these products.


Inhibition of serine beta-lactamases by vanadate-catechol complexes.
All three classes of serine beta-lactamases are inhibited at micromolar levels by 1:1 complexes of catechols with vanadate. Vanadate reacts with catechols at submillimolar concentrations in aqueous buffer at neutral pH in several steps, initially forming 1:1, 1:2, and, possibly, 1:3 complexes. Formation of these complexes is followed by the slower reduction of vanadate (V (V)) to vanadyl (V (IV)) and oxidation of the catechol. Vanadyl-catechol complexes, however, do not inhibit the beta-lactamases. Rate and equilibrium constants of formation of the 1:1 and 1:2 complexes of vanadate with catechol itself and with 2,3-dihydroxynaphthalene were measured by stopped-flow spectrophotometry. Typical examples of all three classes of serine beta-lactamases (the class A TEM-2, class C P99, and class D OXA-1 enzymes) were competitively inhibited by the 1:1 vanadate-catechol complexes. The inhibition was modestly enhanced by hydrophobic substituents on the catechol. The 1:1 vanadate complexes are considerably better inhibitors of the P99 beta-lactamase than 1:1 complexes of catechol with boric acid and are likely to contain penta- or hexacoordinated vanadium rather than tetracooordinated. Molecular modeling showed that a pentacoordinated 1:1 vanadate-catechol complex readily fits into the class C beta-lactamase active site with coordination to the nucleophilic serine hydroxyl oxygen. Such complexes may resemble the pentacoordinated transition states of phosphyl transfer, a reaction also catalyzed by beta-lactamases.


Resolving high-speed colloidal dynamics beyond detector response time via two pulse speckle contrast correlation.
We report an alternate light scattering approach to measure intermediate scattering function and structures of colloidal suspension by using two-pulse speckle contrast correlation analysis. By systematically controlling time-delays between two laser pulses incident on the sample, we are able to monitor transient evolution of coherent diffraction pattern, from which particle dynamics at different length and time scales are obtained simultaneously. Our result demonstrates the feasibility of utilizing a megapixel detector to achieve sufficient data statistics in a short amount of time while enabling microsecond time-resolution. Ultimately, this method provides means to measure high-speed dynamics well beyond the time response limit of a large area two-dimensional (2D) detector.


Treatment of thrombus formation associated with the MicroMed DeBakey VAD using recombinant tissue plasminogen activator.
The latest generation of left ventricular assist devices consists of nonpulsatile impeller pumps. In these small pumps, thrombus formation inside the device does not lead to thromboembolic end-organ dysfunction but may dramatically impair pump flow. We report on our experience with thrombus-related pump dysfunctions of the MicroMed DeBakey left ventricular assist device and its treatment. Eight of 22 patients with a MicroMed DeBakey VAD presented with a critically reduced pump flow. In 7 cases, an increased power demand indicative of progressive thrombus formation associated with the device was evident, whereas 1 case presented with thrombus formation within the inflow conduit associated with a very low power demand. Brief spontaneously resolving pump stops had been noted in 6 patients. All 8 patients were treated with 100 mg of recombinant tissue plasminogen activator (rt-PA), administered via an IV line. Rt-PA lysis led to an increase of pump flow along with a reduction of power demand within a short time in all patients. No severe bleeding complications occurred. However, 4 patients experienced transient epistaxis. All patients could be discharged from intensive care immediately after discontinuation of thrombolytic therapy. Rt-PA lysis is a very effective tool for thrombus-related pump dysfunction in patients with impeller pumps, which renders emergency surgical exchange unnecessary in most cases.


Immunolocalization of tenascin in the chinchilla inner ear.
Tenascin was immunolocalized in the chinchilla cochlea and vestibular system to better understand the functional morphology of the inner ear. Inner ear tissues were fixed with acetone, decalcified and cryosectioned. Indirect immunofluorescence, using antibodies directed against human tenascin epitopes, were used to detect tenascin. As a positive control, tenascin immunoreactivity was found in kidney, cortical mesangial cells and the extracellular matrix of glomeruli and medullary tubule interstitial spaces, concurring with previously reported results. In the cochlea, tenascin immunoreactivity was present in osteocytes, the mesothelial cells underlying the basilar membrane (BM) and within the fibrous matrix of the BM. Greater reactivity was observed in the mesothelial cells than in the fibrous matrix of the BM. In the vestibular system, tenascin immunoreactivity formed a diffuse band directly beneath the basal lamina of the ampullary and otoconial organs. Tenascin immunoreactivity was also observed in cup-shaped regions between the type I vestibular hair cells and their surrounding VIII nerve calyces in the ampullary and otoconial organs. This is the first report of the anatomical distribution of tenascin in the adult, mammalian inner ear, other than our previously published abstract P.A. Santi and D. Swartz, Soc. Neurosci. Abstr. 23 (1997) 731.


The effects of alginate encapsulation on NIT-1 insulinoma cells: viability, growth and insulin secretion.
Transplantation of microencapsulated insulin-secreting cells is proposed as a promising therapy for the treatment of type I diabetes mellitus. In recent years, important advances have been made in the field of immunoisolation and many studies have shown that alginate provides some major advantages for encapsulation over other systems. Since it is known that the extracellular matrix influences the behaviour of encapsulated cells, the aim of the present work has been to study the consequences of encapsulation on some cell functions. For this purpose, cell growth and dynamics of insulin release of NIT-1 cells entrapped in alginate capsules compared with those exhibited by free NIT-1 cells were investigated by means of growth curves, assays, Trypan blue staining and ELISA test. All investigations performed allowed us to conclude that alginate-entrapped NIT-1 cells maintain their growth features and secretory functions although with some important differences. In particular, alginate encapsulation affects the cellular growth profile and causes the lost of time dependence of insulin secretion profile.


Optimal Product Placement.
We model a market, such as an online software market, in which an intermediary connects sellers and buyers by displaying sellers' products. With two vertically-differentiated products, an intermediary can place either: (1) one product, not necessarily the better one, on the first page, and the other hidden on the second page; or (2) both products on the first page. We show that it can be optimal for the intermediary to obfuscate a product-possibly the better one-since this weakens price competition and allows the sellers to extract a greater surplus from buyers; however, it is not socially optimal. The choice of which one to obfuscate depends on the distribution of search costs.


Inverse-scattering-theory approach to the exact n→∞ solutions of O(n) ϕ⁴ models on films and semi-infinite systems bounded by free surfaces.
The O(n) ϕ(4) model on a strip bounded by a pair of planar free surfaces at separation L can be solved exactly in the large-n limit in terms of the eigenvalues and eigenfunctions of a self-consistent one-dimensional Schrödinger equation. The scaling limit of a continuum version of this model is considered. It is shown that the self-consistent potential can be eliminated in favor of scattering data by means of appropriately extended methods of inverse scattering theory. The scattering data (Jost function) associated with the self-consistent potential are determined for the L=∞ semi-infinite case in the scaling regime for all values of the temperature scaling field t=(T-T(c))/T(c) above and below the bulk critical temperature T(c). These results are used in conjunction with semiclassical and boundary-operator expansions and a trace formula to derive exact analytical results for a number of quantities such as two-point functions, universal amplitudes of two excess surface quantities, the universal amplitude difference associated with the thermal singularity of the surface free energy, and potential coefficients. The asymptotic behaviors of the scaled eigenenergies and eigenfunctions of the self-consistent Schrödinger equation as function of x=t(L/ξ(+))(1/ν) are determined for x→-∞. In addition, the asymptotic x→-∞ forms of the universal finite-size scaling functions Θ(x) and ϑ(x) of the residual free energy and the Casimir force are computed exactly to order 1/x, including their x(-1)ln|x| anomalies.


Treatment settings and metabolic monitoring for people experiencing first-episode psychosis.
Monitoring for metabolic sequelae of antipsychotic medications is inconsistent in clinical settings. In this study, frequency of such monitoring in 40 individuals experiencing a first episode of psychosis was analyzed according to the setting in which they received treatment (i.e., inpatient unit, outpatient clinic, or metabolic screening clinic). The traditional outpatient clinic was the least likely of the three settings to monitor blood glucose, blood pressure, weight, and waist circumference. In any setting, blood lipids were measured in only 2 of the 40 patients. Reasons for these findings and recommendations for reducing barriers to screening are presented.


Surveying the damage: the challenges of developing nucleic acid biomarkers of inflammation.
Epidemiological evidence points to a cause and effect relationship between chronic inflammation and human maladies such as cancer, atherosclerosis and autoimmune disease. A critical link between inflammation and disease may lie in the secretion of highly reactive oxygen and nitrogen species by macrophages and neutrophils, including hypohalous acids, nitrous anhydride, and nitrosoperoxycarbonate. Exposure of host epithelial cells to the resulting oxidation, nitration, nitrosation and halogenation chemistries leads to damage of all types of cellular molecules. Since nucleic acids sustain damage representative of the full spectrum of different chemistries and the damage likely plays a causative role in disease etiology, DNA and RNA damage products can serve as surrogates for the short-lived chemical mediators of inflammation, and as markers that provide both mechanistic understanding of the disease process and a means to quantify risk of disease. However, the very small quantities of the damaged molecules pose a challenge to the simultaneous quantification of the spectrum of lesions in the manner of proteomics or metabolomics. The goal of this Highlight is to provide an update on the chemistry of inflammation and the development of biomarkers of inflammation in the age of -omics technologies.


[Acute orthogeriatric care (I). Healthcare issues].
The present article reviews the historical development of several collaborative care models between orthopaedic and geriatrics departments for the care of patients with hip fracture. Subacute orthogeriatric units are described and special emphasis is placed on geriatric consulting teams and acute orthogeriatric units, as well as on their benefits for the patient and the healthcare service. We also review evidence-based studies that support this type of care for patients with acute hip fracture and guidelines from scientific associations involved in the care of these patients. The cost of care is also analyzed. Lastly, the term "orthogeriatrics" is proposed as a common term for this activity and the need for improved future care is discussed.


Cloning and expression of a human CDC42 GTPase-activating protein reveals a functional SH3-binding domain.
CDC42, a member of the Rho family of small GTP-binding proteins, regulates cytoskeletal rearrangements required for cell division. Activating mutations in CDC42 that are refractory to GTPase activation confer a phenotype of large, multinucleated cells. Like other small GTP-binding proteins, CDC42 is activated by a guanosine exchange factor and inactivated by a GTPase-activating protein (GAP). An unidentified 25-kDa platelet protein has been shown to function as a specific CDC42GAP. Here we report the cloning of a cDNA encoding this GAP from a human platelet-precursor cell line. Sequence analysis reveals the presence of three consensus box regions characteristic of rhoGAPs. A glutathione S-transferase fusion protein containing the three boxes derived from the new clone strongly stimulated the GTPase activity of CDC42 but was much less effective on other Rho proteins. This indicates that the cDNA clone encodes a specific GAP for CDC42. Sequence analysis also reveals a potential proline-rich Src homology 3 (SH3)-binding domain preceding the first consensus box. Binding experiments show that this motif can interact with the SH3 domains of p85 alpha and of c-Src. Thus, CDC42GAP may function as a link between CDC42 and other signaling pathways.


Technical challenges of total knee arthroplasty in skeletal dysplasia.
Total knee arthroplasty (TKA) in patients with skeletal dysplasias is particularly challenging as a result of the anatomic variances and substantial bony deformities. Little has been written regarding technical considerations that should be made when performing TKA in skeletal dysplasia. We describe special operative considerations that must be made when performing TKA on patients with skeletal dysplasia, including implant selection and ligamentous balancing. We retrospectively reviewed 12 TKAs in eight patients with varying degrees of deformity (ranging from 30° of varus to 45° of valgus) secondary to three types of skeletal dysplasias: multiple hereditary exostosis, achondroplasia, and osteogenesis imperfecta. Clinical notes, operative records, and radiographic data were reviewed. Minimum followup was 1 year (average, 4 years; range, 1-10 years). We used customized implants in three of the 12 knees. Constrained tibial inserts were used in five knees. All 12 knees underwent releases (soft tissue or epicondylar osteotomy) to address gap balancing or patellar tracking. Average Knee Society scores improved from 35.9 preoperatively to 82.9 postoperatively and average function scores improved from 47.9 preoperatively to 96.7 postoperatively. Complications included two transient peroneal nerve palsies. Special considerations must be made with regard to implant selection and ligamentous balancing as a result of the unusual anatomy and deformities that accompany skeletal dysplasia, but the short-term clinical results reveal consistent improvements in pain and function. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Distinct signals control the hematopoiesis of lymphoid-related dendritic cells.
The molecular and cellular requirements for the development of different populations of human dendritic cells (DC) were studied. Conditions were defined that support DC production from lymphoid progenitors but that fail to induce DC formation from peripheral monocytes. The production of these lymphoid-related DC was severely blocked when hematopoietic progenitors overexpressed Ik7, a mutant dominant-negative Ikaros protein. In contrast, Ik7 did not block the formation of DC in conditions supporting the development of monocyte-derived DC. Furthermore, Ik7 did not block the formation of monocyte/macrophages and enhanced granulopoiesis. One of the molecular mechanisms mediated by Ik7 appears to be down-regulation of the flt3-receptor mRNA. Thus, distinct signals control the formation of DC demonstrating that some aspects of DC diversity are determined in part by distinct molecular cues at the hematopoietic level. (Blood. 2000;95:128-137)


Real-Time Photographic- and Fluorescein Angiographic-Guided Management of Diabetic Retinopathy: Randomized PRIME Trial Outcomes.
To assess the safety and efficacy of as-needed (PRN) intravitreal aflibercept injections (IAI) in managing diabetic retinopathy (DR) guided by the real-time DR severity scale (DRSS) level or panretinal leakage index (PLI) assessment among eyes without diabetic macular edema (DME). Prospective, randomized phase 2 trial (PRIME). A total of 40 eyes with nonproliferative (NPDR) or proliferative DR (PDR) received monthly IAIs until a DRSS improvement of ≥2 steps was achieved and eyes were randomized (1:1) to DRSS-guided or PLI-guided management strategies graded by a central reading center. Main outcome measurements included safety and changes in DRSS and PLI. Through week 52, 95% of eyes achieved a DRSS improvement of ≥2 steps. Following DRSS improvement, 97% of eyes required at least 1 PRN IAI. In eyes requiring PRN IAI and completing week 52, 100% and 59% experienced DRSS worsening (P = .01) in the DRSS- and PLI-guided arms, respectively. Through week 52, mean PLI decreased 18.2% (P = .49) and 54.6% (P <.0001), respectively, in the DRSS- and PLI-guided arms. NPDR versus PDR eyes at baseline achieved a DRSS improvement of ≥2 steps after a mean 4.9 and 3.6 IAIs (P = .03). Two eyes developed a PDR event at week 52 following 5 months of quiescence. The randomized PRIME study analyzed 2 imaging-based biomarkers to guide PRN management with IAI of DR without DME: DRSS level and PLI. Within the context of this study with limitations, most patients required IAI re-treatment every 3-4 months, and deterioration of PLI appeared to precede DRSS level worsening. Finally, these findings reaffirm the fact that close clinical follow-up is important even among eyes that achieve substantial DRSS improvements with apparently quiescent disease.


Six practical recommendations for improved implementation outcomes reporting.
Implementation outcomes research spans an exciting mix of fields, disciplines, and geographical space. Although the number of studies that cite the 2011 taxonomy has expanded considerably, the problem of harmony in describing outcomes persists. This paper revisits that problem by focusing on the clarity of reporting outcomes in studies that examine them. Published recommendations for improved reporting and specification have proven to be an important step in enhancing the rigor of implementation research. We articulate reporting problems in the current implementation outcomes literature and describe six practical recommendations that address them. Our first recommendation is to clearly state each implementation outcome and provide a definition that the study will consistently use. This includes providing an explanation if using the taxonomy in a new way or merging terms. Our second recommendation is to specify how each implementation outcome will be analyzed relative to other constructs. Our third recommendation is to specify "the thing" that each implementation outcome will be measured in relation to. This is especially important if you are concurrently studying interventions and strategies, or if you are studying interventions and strategies that have multiple components. Our fourth recommendation is to report who will provide data and the level at which data will be collected for each implementation outcome, and to report what kind of data will be collected and used to assess each implementation outcome. Our fifth recommendation is to state the number of time points and frequency at which each outcome will be measured. Our sixth recommendation is to state the unit of observation and the level of analysis for each implementation outcome. This paper advances implementation outcomes research in two ways. First, we illustrate elements of the 2011 research agenda with concrete examples drawn from a wide swath of current literature. Second, we provide six pragmatic recommendations for improved reporting. These recommendations are accompanied by an audit worksheet and a list of exemplar articles that researchers can use when designing, conducting, and assessing implementation outcomes studies.


[Intentional limited resection for small adenocarcinoma with ground-glass opacity component more than 50% on computed tomography].
Fifty-eight patients who had small lung tumors 2 cm or less with ground-glass opacity (GGO) component more than 50% on high resolution computed tomography (HRCT) underwent intentional limited resection. After bronchioloalveolar carcinoma without both active fibroblastic proliferation and invasive sign to the stroma was confirmed, limited resection was completed in 50 patients. In 8 patients, procedure was converted lobectomy because of microscopic invasive sign in 4, active fibroblastic proliferation in 2, and other reasons in 2. Unexpected invasive sign was found by detailed post-operative examination in 2 cases. Five-year survival rate was 98% with a mean follow-up period of 48.8 months. A limitation of intra-operative diagnosis was revealed and the accuracy of diagnosis should be improved by not only intra-operative pathological diagnosis but also HRCT images.


Coexisting Prolactin-Secreting Macroadenoma, Hypopituitarism and Type 1 Diabetes Mellitus in a Young Adult Male Patient.
The association between type 1 diabetes mellitus (DM) and pituitary prolactinoma is rarely reported in the literature. Herein we present a 23-year-old male patient with co-existing type 1 DM, pituitary macro-prolactinoma and panhypopituitarism secondary to mass effect. The patient presented with generalised symptoms including fatigability, cold hands, decreased insulin requirement secondary to frequent hypoglycaemic episodes two weeks following the diagnosis of type 1 DM. Initial blood workup showed evidence of possible secondary hypothyroidism. The full pituitary profile screen showed profound anterior hypopituitarism with a prolactin level of 67,168 miu/L (normal range 86-324 miu/L). Pituitary MRI showed macroadenoma, 37mm in size, with a suprasellar cystic extension but no chiasmal compression. It was treated medically with cabergoline and a repeat pituitary MRI after eight weeks of initiating treatment showed a 4-mm reduction in the size of the adenoma, and prolactin level decreased to 6,794 miu/L. The case was discussed at the Neurosurgical MDT and the outcome was to continue to monitor while on cabergoline. This case report is the second in the literature, which documented the association between type 1 DM and pituitary prolactinoma in adolescents. These patients might not present with the classical clinical features of hyperprolactinemia, and instead, they present with frequent hypoglycaemia and decreased insulin requirement due to secondary adrenal insufficiency as a consequence of the mass effect of the prolactinoma. Furthermore, non-specific symptoms, such as generalised tiredness and fatiguability, despite reasonable blood sugar control, in young patients with type 1 DM should trigger screening for all anterior pituitary hormones to exclude hypopituitarism.


Clinical usefulness of Somatostatin Receptor Scintigraphy in the Diagnosis of Neuroendocrine Neoplasms.
We investigated the detectability of somatostatin receptor scintigraphy (SRS) for neuroendocrine neoplasms (NEN). From January 2016 to October 2020, 125 SRS examinations using indium-111 pentetreotide performed for patients with NEN lesions were retrospectively evaluated. The detection rate of NEN lesions was determined according to histopathological classification by primary site and by organ. At least one NEN lesion was detected in 73% (91/125) with a positive Krenning score of ≥2 in SRS. The detection of abdominal NENs (gastrointestinal tract, 38; pancreas, 62; and others, 14) was 89% (49/55) for neuroendocrine tumor (NET)-grade (G) 1, 78% (32/41) for NET-G2, 66% (2/3) for NET-G3, 31% (4/13) for neuroendocrine carcinoma (NEC), 100% (1/1) for mixed neuroendocrine-non-neuroendocrine neoplasm, and 0% (0/1) for non-classified NEN. That of thoracic NENs was 33% (2/6) for typical carcinoid tumor and 40% (2/5) for atypical carcinoid tumor. For a total of 226 organ lesions, hepatic lesions were 76% (58/76); pancreatic lesions, 61% (31/51); lymph node lesions, 77% (27/35); bone lesions, 83% (20/24); duodenal lesions, 82% (9/11); and other lesions, 41% (11/27). The detectability of SRS for NEN in Japan was verified at a center, and its usefulness was confirmed.


The Long Noncoding RNA LINC00963 Inhibits Corneal Fibrosis Scar Formation by Targeting miR-143-3p.
Corneal fibrosis is a complication of severe corneal injury, one of the major causes of vision loss. The formation of myofibroblasts has emerged as a key stimulative factor of corneal fibrosis. In the current study, we focused on the role of LINC00963 in regulating corneal fibrosis. Transforming growth factor β1 (TGF-β1) was used to induce human corneal stromal cells differentiating into corneal myofibroblasts, and the significant increase of α-smooth muscle actin (α-SMA) was verified by quantitative real-time PCR (qRT-PCR), western blot, and immunofluorescence, respectively. LINC00963 was identified to be one-half decreased compared with nonstimulated human corneal stromal cells, indicating that it might play a role in corneal fibrosis. Interestingly, overexpression of LINC00963 resulted in decreased formation of myofibroblasts indicating that it might exhibit an inhibiting effect. Moreover, bioinformatics tool was applied to predict the downstream target of LINC00963. We investigated that LINC00963 suppressed α-SMA induced by TGF-β1 in corneal fibroblasts, at least in part, by downregulating the expression of miR-143-3p. In addition, either LINC00963 promotion or miR-143-3p inhibition could significantly decrease myofibroblast contractility and collagen I and III secretion, which are the key to contribute to corneal fibrosis. Taken together, our study identified LINC00963 as a promising therapeutic target.


Chemical and structural characterization of Pholiota nameko extracts with biological properties.
Edible mushrooms including Pholiota nameko are excellent sources of extractable bioactive compounds with much to explore. Enzymatic extractions with Cellulase and Viscozyme were responsible for highest extraction yields (67-77%). No strong antioxidant activity was observed although extracts were able to scavenge ABTS(+) and OH(+). Potential prebiotic activity was observed in all extracts, some increasing 1.4-2 Log cycles of Lactobacillus acidophilus La-5 and Bifidobacterium animalis BB12. 30-50% α-glucosidase inhibition was observed in ultrasound, Flavourzyme and Cellulase extracts. Flavourzyme and Cellulase extracts are richer in macro (Mg, K and P) and micro elements (Zn, Mn and Fe) in comparison to mushroom. Monosaccharides content and profile varied slightly among both extracts with predominance of glucose, galactose and mannose with no uronic acids detection; Flavourzyme extract reported higher free amino acids content. Presence of α and β-glycosidic structures such as glucans and glucan-protein complexes are among the polysaccharides found in both extracts.


'Side effects' of health promotion: an example from Austrian schools.
While the existence of side effects of medical interventions is common knowledge and widely investigated, possible unintended effects of health promotion (HP) interventions are only sparsely discussed in the HP literature. Drawing on qualitative evaluation data generated within an on-going process evaluation of a regional health-promoting schools network in Austria, we demonstrate which desirable and undesirable effects HP practice can have for teachers. Thirteen group discussions with teachers (n = 63) and headteachers (n = 9) acting as health coordinators in the network schools were conducted between 2010 and 2013. These data were analysed using systems and thematic analyses. In our example, desirable side effects included health coordinators gaining new relationships, new skills and benefiting from improved infrastructure. The undesirable side effects centred on stress, work overload and frustration, due to the additional work brought about by HP practice, negative reactions by colleagues as well as by technicalities of the network. The undesirable side effects of HP predominated in our study, pointing to several implications like the need to accommodate the concept of HP in the teachers' core responsibilities; the participation of all staff members and students in a whole-school approach toward SHP, and the need for changes on an organizational level. Based on this study, we come to the conclusion that a systematic approach to investigating and analysing side effects of HP is currently lacking in HP research and suggest that theoretical examination and more empirical research is needed.


[Effects of laryngeal mask airway on circulation and on incidence of postoperative sore throat and hoarseness].
We studied the effects of laryngeal mask airway (LM) insertion on circulation and on the incidence of postoperative sore throat or hoarseness as compared with tracheal intubation in 50 pediatric patients. LM insertion caused less change of heart rate and systolic blood pressure than tracheal intubation. The incidence of postoperative sore throat and hoarseness was less in the patient of LM group. We conclude that LM is useful in pediatric anesthesia when less circulatory changes are desirable or when the postoperative sore throat or hoarseness is to be avoided.