MMPs--role in cardiovascular development and disease.
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes important in the degradation and turnover of extracellular matrix (ECM) components. MMPs and their inhibitors play major roles not only in ECM degradation but also in mediating cell-cell adhesion, cell migration and invasion, cell proliferation and apoptosis, tissue remodeling, and growth factor and cytokine signaling. There is a vast amount of literature regarding changes in MMPs and MMP inhibitor levels during the progression of cardiovascular diseases but a paucity of information regarding their roles in the embryonic cardiovascular development. Yet, by studying cardiovascular development, much can be learned with regard to the pathophysiology and etiology of adult cardiovascular diseases. In fact, the development of many pathological conditions may reflect inappropriate recapitulation of embryonic events. The objective of this review is to provide an overview of what is known regarding the role of MMPs and their inhibitors during embryonic cardiovascular development and to relate these to the pathophysiology of adult cardiovascular diseases whenever possible.


Glycosylphosphatidylinositol-specific phospholipase D influences triglyceride-rich lipoprotein metabolism.
Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is a minor HDL-associated protein. Because many minor HDL-associated proteins exchange between different lipoprotein classes during the postprandial state and are also involved in triglyceride (TG) metabolism, we hypothesized that GPI-PLD may play a role in the metabolism of TG-rich lipoproteins. To test this hypothesis, we examined the distribution of GPI-PLD among lipoprotein classes during a fat tolerance test in C57BL/6 and LDL receptor-deficient (LDLR(-/-)) mice fed either a chow or high-fructose diet. In the fasting state in wild-type mice fed a chow diet, GPI-PLD was only present in HDL, whereas in LDLR(-/-) mice GPI-PLD was present in HDL and intermediate-density lipoproteins (IDL)/LDL. During the fat tolerance test, there was no change in total serum GPI-PLD levels in either model; however, a significant amount of GPI-PLD appeared in both VLDL (0.5-1% of total GPI-PLD) and IDL/LDL (5-10% of total GPI-PLD) in both models. The high-fructose diet increased both fasting and postprandial TG and serum GPI-PLD levels in both strains as well as the amount of GPI-PLD in VLDL. To determine whether GPI-PLD plays a direct role in TG metabolism, we increased liver GPI-PLD expression in C57BL/6 mice by adenovirus-mediated gene transfer, which resulted in a sevenfold increase in serum GPI-PLD levels. This change was associated with an increase in fasting (30%) and postprandial TG (50%) and a twofold reduction in TG-rich lipoprotein catabolism compared with saline or control adenovirus-treated mice. These studies demonstrate that GPI-PLD affects serum TG levels by altering catabolism of TG-rich lipoproteins.


[Direct costs of pharmacotherapy for acute leukemia at a Regional Hospital in Chile].
In Chile, leukemia is one of the diseases whose treatment is guaranteed by a special law called AUGE (universal access and explicit guaranties). Therefore, the knowledge of its treatment costs is of utmost importance. To determine and to characterize the direct costs of pharmacotherapy for leukemia at a regional hospital in Chile. Data were retrospectively obtained from electronic and manual records of the hospital for all patients treated for leukemia between 2003 and 2006. Patients were classified into four groups: pediatric and adult patients treated for acute lymphocytic leukemia (ALL children and ALL adults, respectively), and pediatric and adult patients treated for acute myelogenous leukemia (AML children and AML adults, respectively). Total accumulated costs of pharmacotherapy for acute leukemia between 2003 and 2006 were 304,724,845 Chilean pesos (USD 574,952). The higher total or per patient costs, were generated by drugs for chemotherapy compared to other required medications. The exception were AML children, where support drugs, such as antimicrobials, ant emetic drugs and colony stimulating factors, generated the higher costs per patient. Among ALL adults, AML children and AML adults, the costs were concentrated in the first 6 months of treatment. NO children followed this tendency concentrating the costs between the seventh and twenty-fourth months. Annual costs of pharmacotherapy per patient for acute leukemia in this regional hospital were approximately USD 4,717. Chemotherapy was the item with the greatest impact on cost.


[Ethical dilemmas in caring for patients with SARS].
This paper explored experiences caring for patients with severe acute respiratory syndrome (SARS), with a focus on the suffering between the "private" and "professional" selves, in order to describe the psychological impact and ethical practice of SARS events as related to nursing professionals. Eight small group interviews were conducted with a total of twenty-one nurses with experience caring for SARS patients. Group interviews were audio-taped and transcribed for analysis. Data, analyzed using the constant comparative method, revealed the following three ethical dilemmas: suffering in care giving, response to the calling, and distresses involved in decision making. In this study, the authors further addressed relationships between suffering and ethical practice, the calling and a nurse's professional responsibilities, and transcendence in intersubjectivity. The authors hope that the results of this study will lead to a new understanding of ethical practices nursing and help nurses develop reflected care that promotes personal and professional growth.


Mechanical bioeffects of ultrasound.
Ultrasound is used widely in medicine as both a diagnostic and therapeutic tool. Through both thermal and nonthermal mechanisms, ultrasound can produce a variety of biological effects in tissues in vitro and in vivo. This chapter provides an overview of the fundamentals of key nonthermal mechanisms for the interaction of ultrasound with biological tissues. Several categories of mechanical bioeffects of ultrasound are then reviewed to provide insight on the range of ultrasound bioeffects in vivo, the relevance of these effects to diagnostic imaging, and the potential application of mechanical bioeffects to the design of new therapeutic applications of ultrasound in medicine.


Obstetric and Neonatal Risks Among Obese Women Without Chronic Disease.
To investigate whether prepregnancy obesity is associated with adverse pregnancy outcomes among women without chronic disease. Singleton deliveries (N=112,309) among mothers without chronic diseases in the Consortium on Safe Labor, a retrospective U.S. cohort, were analyzed using Poisson regression with robust variance estimation. Relative risks and 95% confidence intervals (CIs) estimated perinatal risks in relation to prepregnancy obesity status adjusted for age, race-ethnicity, parity, insurance, smoking and alcohol use during pregnancy, and study site. Obstetric risks were variably (and mostly marginally) increased as body mass index (BMI) category and obesity class increased. In particular, the risk of gestational hypertensive disorders, gestational diabetes, cesarean delivery, and induction increased in a dose-response fashion. For example, the percentage of gestational diabetes among obese class III women was 14.6% in contrast to 2.8% among women with normal BMIs (corresponding relative risks [95% CI] 1.99 [1.86-2.13], 2.94 [2.73-3.18], 3.97 [3.61-4.36], and 5.47 [4.96-6.04] for overweight, obese class I, obese class II, and obese class III women, respectively) compared with women with normal BMIs. Similarly, neonatal risks increased in a dose-response fashion with maternal BMI status including preterm birth at less than 32 weeks of gestation, large for gestational age (LGA), transient tachypnea, sepsis, and intensive care unit admission. The percentage of LGA neonates increased from 7.9% among women with normal BMIs to 17.3% among obese class III women and relative risks increased to 1.52 (1.45-1.58), 1.74 (1.65-1.83), 1.93 (1.79-2.07), and 2.32 (2.14-2.52) as BMI category increased. Prepregnancy obesity is associated with increased risks of a wide range of adverse pregnancy and neonatal outcomes among women without chronic diseases.


Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells.
Resistin is a hormone secreted by adipocytes that acts on skeletal muscle myocytes, hepatocytes, and adipocytes themselves, reducing their sensitivity to insulin. In the present study, we investigated how the expression of resistin is affected by glucose and by mediators known to affect insulin sensitivity, including insulin, dexamethasone, tumor necrosis factor-alpha (TNF-alpha), epinephrine, and somatropin. We found that resistin expression in 3T3-L1 adipocytes was significantly upregulated by high glucose concentrations and was suppressed by insulin. Dexamethasone increased expression of both resistin mRNA and protein 2.5- to 3.5-fold in 3T3-L1 adipocytes and by approximately 70% in white adipose tissue from mice. In contrast, treatment with troglitazone, a thiazolidinedione antihyperglycemic agent, or TNF-alpha suppressed resistin expression by approximately 80%. Epinephrine and somatropin were both moderately inhibitory, reducing expression of both the transcript and the protein by 30-50% in 3T3-L1 adipocytes. Taken together, these data make it clear that resistin expression is regulated by a variety of hormones and that cytokines are related to glucose metabolism. Furthermore, they suggest that these factors affect insulin sensitivity and fat tissue mass in part by altering the expression and eventual secretion of resistin from adipose cells.


Dispersionless motion in a periodically rocked periodic potential.
Recently, dispersionless (coherent) motion of (noninteracting) massive Brownian particles, at intermediate time scales, was reported in a sinusoidal potential with a constant tilt. The coherent motion persists for a finite length of time before the motion becomes diffusive. We show that such coherent motion can be obtained repeatedly by applying an external zero-mean square-wave drive of appropriate period and amplitude instead of a constant tilt. Thus, the cumulative duration of coherent motion of particles is prolonged. Moreover, by taking an appropriate combination of periods of the external field, one can postpone the beginning of the coherent motion and can even have coherent motion at a lower value of position dispersion than in the constant tilt case.


Application of ion mobility tandem mass spectrometry to compositional and structural analysis of glycopeptides extracted from the urine of a patient diagnosed with Schindler disease.
Schindler disease is caused by the deficient activity of α-N-acetylgalactosaminidase, which leads to an abnormal accumulation of O-glycopeptides in tissues and body fluids. In this work the Schindler condition is for the first time approached by ion mobility (IMS) tandem mass spectrometry (MS/MS), for determining urine glycopeptide fingerprints and discriminate isomeric structures. IMS-MS experiments were conducted on a Synapt G2s mass spectrometer operating in negative ion mode. A glycopeptide mixture extracted from the urine of a patient suffering from Schindler disease was dissolved in methanol and infused into the mass spectrometer by electrospray ionization using a syringe-pump system. MS/MS was performed by collision-induced dissociation (CID) at low energies, after mobility separation in the transfer cell. Data acquisition and processing were performed using MassLynx and Waters Driftscope software. IMS-MS data indicated that the attachment of one or two amino acids to the carbohydrate backbone has a minimal influence on the molecule conformation, which limits the discrimination of the free oligosaccharides from the glycosylated amino acids and dipeptides. The structural analysis by CID MS/MS in combination with IMS-MS of species exhibiting the same m/z but different configurations demonstrated for the first time the presence of positional isomers for some of the Schindler disease biomarker candidates. The IMS-MS and CID MS/MS platform was for the first time optimized and applied to Schindler disease glycourinome. By this approach the separation and characterization of Neu5Ac positional isomers was possible. IMS CID MS/MS showed the ability to determine the type of the glycopeptide isomers from a series of possible candidates.


A new technique for obtaining whole pathogen transcriptomes from infected host tissues.
We propose a novel experimental approach based on coincidence cloning for analyzing sequences of bacterial intracellular pathogens specifically transcribed in affected tissues. Co-denaturation and co-renaturation of excess bacterial genomic DNA with the cDNA prepared on total RNA of the infected tissue allows one to select the bacterial fraction of the cDNA sample. We used this technique for preparing and characterizing the Mycobacterium tuberculosis cDNA pool, representing the transcriptome of infected mouse lungs in the chronic phase of infection. A cDNA pool enriched in fragments of mycobacterial cDNA was analyzed by the high-throughput 454 sequencing procedure. We demonstrated that its composition corresponded to what can be expected in the chronic phase of infection and, after the adaptation of M. tuberculosis to the host immune system, was characterized by an active lipid metabolism and switched from aerobic to anaerobic respiration. The technique is universal and requires no prior knowledge of the pathogen genome sequence. Pools of transcribed sequences obtained by this technique retain the main characteristics of the genome-wide gene transcription pattern within infected tissue, and can be used for in vivo analysis of gene expression of a wide spectrum of infection agents, such as viruses, bacteria, and protista.


Mycobacterium tuberculosis PPE44 (Rv2770c) is involved in response to multiple stresses and promotes the macrophage expression of IL-12 p40 and IL-6 via the p38, ERK, and NF-κB signaling axis.
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a formidable threat to global public health. The successful intracellular persistence of M. tuberculosis significantly contributes to the intractability of tuberculosis. Proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) are mycobacterial exclusive protein families that widely reported to be involved in the bacterial virulence, physiology and interaction with host. Rv2770c (PPE44), a predicted virulence factor, was up-regulated upon the infected guinea pig lungs. To investigate the role of Rv2770c, we heterologously expressed the PPE44 in the nonpathogenic fast-growing M. smegmatis strain. Subcellular location analysis demonstrated that Rv2770c is a cell wall associated protein, suggestive of a potential candidate involved in host-pathogen interaction. The Rv2770c can enhance M. smegmatis survival within macrophages and under stresses such as H2O2, SDS, diamide exposure, and low pH condition. M. smegmatis expressing Rv2770c is more virulent as testified by the increased death of macrophages and the increased expression of interlukin-6 (IL-6) and interlukin-12p40 (IL-12p40). Moreover, Rv2770c altered the secretion of IL-6 and IL-12p40 of macrophages via NF-κB, ERK1/2 and p38 MAPK axis. Taken together, this study implicated that Rv2770c was a virulent factor actively engaged in the interaction with host macrophage.


Label-free profiling of cell dynamics: A sequence of impedance-based assays to estimate tumor cell invasiveness in vitro.
Dynamic properties of cancer cells, most notably their ability to migrate, have been correlated successfully with their invasive nature in vivo. To establish a stronger experimental basis for such a correlation we subjected five different cancer cell lines of well-defined metastatic potential to a sequence of three independent assays reporting on three different aspects of cell dynamics, namely (1) the kinetics of cell spreading, (2) cell shape fluctuations, and (3) cell migration. The sequentially applied assays correspond to different measuring modes of the well-established ECIS technique that is based on non-invasive and label-free impedance readings of planar gold-film electrodes that serve as the growth substrate for the cells under study. Every individual assay returned a characteristic parameter describing the behavior of the cell lines in that particular assay quantitatively. The parameters of all three assays were ranked to establish individual profiles of cell dynamics for every cell line that correlate favorably with the cells' invasive properties. The sequence of impedance-based assays described here requires only small cell populations (< 10.000 cells), it is highly automated and easily adapted to 96-well formats. It provides an in-depth dynamic profile of adherent cells that might be useful in other areas besides cancer research as well.


Early Adverse Events Following Pediatric Mandibular Advancement: Analysis of the ACS NSQIP-Pediatric Database.
This study aims to assess early adverse events and patient factors associated with complications following mandible distraction osteogenesis (MDO). The American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-Pediatric) database, years 2012 to 2019, was queried for patients undergoing mandible advancement via relevant Current Procedural Terminology and postoperative diagnosis codes. Thirty-day adverse events and co-morbidities are assessed. A total of 208 patients were identified with 17.3% (n = 36) experiencing an adverse event, reoperation (n = 14), and readmission (n = 11) being most common. Patients < 365 days old at the time of operation were more likely to experience an adverse event (26.1% vs 10.8%; P = .005). However, among patients less than 1 year of age, differences in the complication rates between patients ≤ 28 days and >28 days (30.2% vs 22.2%; P = .47) and those weighing ≤ 4 kg and >4 kg (31.7% vs 11.5%; P = .063) did not reach statistical significance. Adverse events following mandible advancement are relatively common, though often minor. In our analysis of the NSQIP-Pediatric database, neonatal age ( ≤ 28 days) or weight ≤ 4 kg did not result in a statistically significant increase in complications among patients less than 1 year of age. Providers should consider early intervention in patients who may benefit from MDO.


Taking the Guesswork Out of Stopping TKIs.
More and more patients with chronic myeloid leukemia are discontinuing therapy after their cancer goes into remission, improving their quality of life and remaining disease-free for years. However, this strategy works only in a subset of patients. Researchers are attempting to refine criteria for discontinuing treatment, determine the manner in which therapy should be stopped, and identify prognostic biomarkers.


[Negative serologic and microscopic studies in vivo do not exclude malaria. Autopsy report with positive Plasmodium falciparum culture].
A 31-year old man, who had just flown in from the tropics collapsed certainly. Brain trauma and alcohol withdrawal were excluded. After serological and microscopical malaria tests had been negative, subarachnoidal bleeding or encephalomeningitis were considered as possible. Although repeated malaria tests were negative, antimalarial therapy was begun on the 8th day of illness. The patient died the next day on respiratory difficulties. Cultures from blood and spleen taken three days after death showed malaria rings, and also trophozoites were found in the spleen and the bone marrow etc. The brain contained schizonts. Malaria infection from older corpses is possible. Negative malaria test results should not delay malaria treatment or exclude malaria diagnosis. Plasmodium culture should be taken whenever malaria is suggested. The possibility of malaria should always be considered. To decide in dubio pro reo in doubtful cases, particularly in forensic medicine.


Coenurus infestation of eye and orbit.
Histopathologic examination of an eye with severe anterior uveitis and a whitish retrolental tumor in a 43-year-old woman, and of an orbital cystic tumor in a 2-year-old girl, showed the presence of Coenurus, the bladderworm of Multiceps multiceps. The single bladder of Coenurus may contain hundreds of scoleces. intraocular Coenurus is most often located in the subretinal space.


Lymphocytic Meningitis in Patients with Sympathetic Ophthalmia.
This study aimed at reporting lymphocytic meningitis in patients diagnosed with sympathetic ophthalmia (SO). In this single-center retrospective observational case series, we reviewed cases diagnosed with SO. We analyzed the patients' inciting injuries, the characteristics of uveitis and the cerebrospinal fluid (CSF) analyses. Nine patients were diagnosed with SO and CSF analyses were available in all cases. Four cases had lymphocytic pleocytosis, 3 of which showed marked CSF inflammation with more than 300 lymphocytes/mm3. The inciting event in these 3 patients was a globe perforation injury, whereas 4 patients without meningitis had SO following a surgical intervention. In this case series of patients with SO, lymphocytic meningitis was a common finding. The prevalence of meningitis in patients with SO and its value for the diagnosis of the disease needs to be further studied.


Autoimmune pancreatitis associated with a large pancreatic pseudocyst.
Pancreatic cystic lesions comprise various entities with different histopathological characteristics and their differential diagnosis is often a challenge for clinicians. Autoimmune pancreatitis (AIP) is usually not considered in the differential diagnosis of cystic lesions, but often mimics the morphological aspects of pancreatic neoplasm. We report the case of a 64-year-old male patient with a cystic pancreatic head lesion (diameter 5 cm) and stenosis of the distal bile duct requiring repeated stenting. Because of the clinical presentation together with moderate elevation of serum CA19-9 and massive elevation of cyst fluid CA19-9 (122.695 U/L; normal range: <37.0 U/L), the patient underwent explorative laparotomy and pylorus preserving partial pancreaticoduodenectomy. Histology revealed surprisingly AIP with an inflammatory pseudocyst. In conclusion, cyst fluid analysis of tumor markers and cyst fluid cytology lack high accuracy to clearly differentiate cystic pancreatic lesions. Although AIP is rarely associated with pseudocysts, the disease has to be considered in the differential diagnosis of cystic pancreatic lesions. Early examination of serum IgG, IgG4 and auto-antibodies might save these patients from unnecessary endoscopical and surgical procedures.


Melatonin prevents mitochondrial dysfunctions and death in differentiated skeletal muscle cells.
Oxidative stress increase induces cellular damage and apoptosis activation, a mechanism believed to represent a final common pathway correlated to sarcopenia and many skeletal muscle disorders. The goal of this study is to evaluate if melatonin, a ROS scavenger molecule, is able to counteract or modulate myotube death. Here, differentiated C2C12 skeletal muscle cells have been treated with melatonin before chemicals known to induce apoptotic death and oxidative stress, and its effect has been investigated by means of morpho-functional analyses. Ultrastructural observations show melatonin protection against triggers by the reducing of membrane blebbing, chromatin condensation, myonuclei loss and in situ DNA cleavage. Moreover, melatonin is able to prevent mitochondrial dysfunctions which occur in myotubes exposed to the trigger alone. These findings demonstrate melatonin ability in preventing apoptotic cell death in skeletal muscle fibers in vitro, suggesting for this molecule a potential therapeutic role in the treatment of various muscle disorders.


Atopic dermatitis: a candidate for disease-modifying strategy.
The concept of disease modification has been introduced to define the therapeutic strategies aimed to break, stop, or reverse the natural course of a chronic invalidating disease. This strategy is tightly related to the biomarker-based stratification of affected patients using genetic and other biological markers. With regard to the progress in understanding the genetic background of atopic dermatitis (AD), its natural history and its pivotal role in the emergence of allergic asthma, the time is mature to foster the research field of biomarkers in AD and to consider the elaboration of disease-modifying strategies in the management of AD with the goal to stop or even reverse the atopic march.


Differential involvement of the Ras and Rap1 small GTPases in vasoactive intestinal and pituitary adenylyl cyclase activating polypeptides control of the prolactin gene.
In pituitary cells, transcriptional regulation of the prolactin (PRL) gene and prolactin secretion are controlled by multiple transduction pathways through the activation of G protein coupled receptors and receptor tyrosine kinases. In the somatolactotrope GH4C1 cell line, we have previously identified crosstalk between the MAPKinase cascade ERK1/2 and the cAMP/protein kinase A pathway after the activation of the VPAC2 receptor by vasoactive intestinal polypeptide (VIP) or pituitary adenylyl cyclase-activating polypeptide (PACAP38). In the present study, we focus on the involvement of the GTPases Ras and Rap1 as downstream components of signal transmission initiated by activation of the VPAC2 receptor. By using pull-down experiments, we show that VIP and PACAP38 preferentially activate Rap1, whereas thyrotropin releasing hormone (TRH) and epidermal growth factor (EGF) mainly activate Ras GTPase. Experiments involving the expression of the dominant-negative mutants of Ras and Rap1 signaling (RasN17 or Rap1N17) indicate that both GTPases Ras and Rap1 are recruited for the ERK activation by VIP and PACAP38, whereas Rap1 is poorly involved in TRH or EGF-induced ERK activation. The use of U0126, a selective inhibitor of MAPKinase kinase, provides evidence that MAPKinase contributes to the regulation of the PRL gene. Moreover, cotransfection of RasN17 or Rap1N17 with the PRL proximal promoter luciferase reporter construct indicates that Rap1 may be responsible for VIP/PACAP-induced activation of the PRL promoter. Interestingly, Ras would be involved as a negative regulator of VIP/PACAP-induced PRL gene activation, in contrast to its stimulatory role in the regulation of the PRL promoter by TRH and EGF.


Immunochemical Characterization of Setaria cervi Microfilarial Antigens Using Novel Antibodies.
Filariasis affects millions of people in tropical and subtropical regions of the world and is caused by nematode roundworm. In order to develop a vaccine and specific diagnostic tests, it is important to characterize different stages of the filarial worms. Microfilariae (Mf) stage of the roundworm is found in host's blood or lymph vessels and can be important not only for developing better immunodiagnostics but also for understanding immune recognition and its relevance to immunepathogenesis and protective immunity. The present study aimed to immunocharacterize Mf and adult worm antigens that could be helpful in future diagnostic tests. Four different immune sera against Setaria cervi intact live, intact live with adjuvant, intact glutaraldehyde fixed with adjuvant and total somatic Mf were prepared and used for the immunocharacterization of Mf antigens. Our study results suggest that compared to fixed intact Mf, live intact Mf are more immunogenic, as the immune sera generated against intact live Mf showed high ELISA reactivity with Setaria cervi Mf and adult worm antigens. All the four immune sera IgG fractions had surface specificity as determined through considerable ELISA reactivity with S. cervi intact Mf. When tested under native conditions (immunoelectrophoresis and crossed immunoelectrophoresis), all the four immune rabbit sera were able to detect antigens of S. cervi Mf and adult stages. These results can be useful in detailed understanding of the complex nature of the Mf and adult antigens, which are prerequisites in the development of vaccine and more specific diagnostic tests.


Synthesis, antitumor activity, and molecular docking of (-)-epigallocatechin-3-gallate-4β-triazolopodophyllotoxin conjugates.
Two new (-)-epigallocatechin-3-gallate-4β-triazolopodophyllotoxin conjugates (7 and 8) were synthesized and evaluated for biological activity. Compound 8 showed highly potent anticancer activity against A-549 cell line with IC50 of 2.16 ± 1.02 μM, which displayed the highest selectivity index value (SI = 14.5) in A-549 cells. Molecular docking indicated that compound 8 could bind with the active site of Top-II. Therefore, compound 8 might be a promising candidate for further development.


Characterization of the Key Odorants in Chinese Zhima Aroma-Type Baijiu by Gas Chromatography-Olfactometry, Quantitative Measurements, Aroma Recombination, and Omission Studies.
Zhima aroma-type Baijiu with typical sesame aroma is particularly popular in northern China. To our knowledge, it is still uncertain which components are important to make contributions to its unique aroma, although a few pieces of research have reported many volatile compounds in this Baijiu. The aroma-active compounds from the Baijiu were researched in this paper. A total of 56 odorants were identified in Chinese Zhima aroma-type Baijiu by aroma extract dilution analysis (AEDA). Their odor activity values (OAVs) were determined by different quantitative measurements, and then 26 aroma compounds were further confirmed as important odorants due to their OAVs ≥ 1, and these had higher values, such as ethyl hexanoate (OAV 2691), 3-methylbutanal (2403), ethyl pentanoate (1019), and so on. The overall aroma of Zhima aroma-type Baijiu could be simulated by mixing of the 26 key odorants in their measured concentrations. The similarity of the overall aroma profiles between the recombination model and the commercial sample was judged to be 2.7 out of 3.0 points. Omission experiments further corroborated the importance of methional and ethyl hexanoate for the overall aroma of Chinese Zhima aroma-type Baijiu.


Transforaminal Endoscopic Excision of Intradural Lumbar Disk Herniation and Dural Repair.
Intradural disk herniation is a rare entity with <0.3%-1% of all disk herniations and at an L2-L3 level even rarer. The dural defects repairs on ventral aspect are technically challenging and may not be possible after durotomy, so many authors have placed fascia, muscle, or plugging by the hemostatic material. The surgical treatment of intradural disk herniation is usually posterior open surgery with formal durotomy to remove the disk fragments with good to fair results. Poorer outcome occurs in late-presenting cases. We report on a 78-year-old man who presented with spontaneous low back pain and bilateral buttock pain aggravated for 1 month with severe walking difficulty without bowel and bladder symptoms. Magnetic resonance imaging revealed disk herniation at the L2-L3 level. He underwent a transforaminal endoscopic removal of intradural disk fragments via the original rent in the anterolateral aspect of the dura, and sealing was performed with dural patch and Gelfoam without any lumbar drain. The patient's symptom significantly improved postoperatively with muscle power improved to grade 5 on day 1 with no cerebrospinal fluid leakage, and he was mobilized with a lumbar orthosis on the first postoperative day. Postoperative and at 6-month follow-up, magnetic resonance imaging revealed adequate decompression and successful sealing of the ventral dural defect. To our knowledge, this is the first case of transforaminal endoscopic treatment of intradural disk herniation at an L2-L3 level in which good clinical outcomes were obtained and maintained until recent follow-up of 8 months.


Evolution of the early Antarctic ice ages.
Understanding the stability of the early Antarctic ice cap in the geological past is of societal interest because present-day atmospheric CO2 concentrations have reached values comparable to those estimated for the Oligocene and the Early Miocene epochs. Here we analyze a new high-resolution deep-sea oxygen isotope (δ18O) record from the South Atlantic Ocean spanning an interval between 30.1 My and 17.1 My ago. The record displays major oscillations in deep-sea temperature and Antarctic ice volume in response to the ∼110-ky eccentricity modulation of precession. Conservative minimum ice volume estimates show that waxing and waning of at least ∼85 to 110% of the volume of the present East Antarctic Ice Sheet is required to explain many of the ∼110-ky cycles. Antarctic ice sheets were typically largest during repeated glacial cycles of the mid-Oligocene (∼28.0 My to ∼26.3 My ago) and across the Oligocene-Miocene Transition (∼23.0 My ago). However, the high-amplitude glacial-interglacial cycles of the mid-Oligocene are highly symmetrical, indicating a more direct response to eccentricity modulation of precession than their Early Miocene counterparts, which are distinctly asymmetrical-indicative of prolonged ice buildup and delayed, but rapid, glacial terminations. We hypothesize that the long-term transition to a warmer climate state with sawtooth-shaped glacial cycles in the Early Miocene was brought about by subsidence and glacial erosion in West Antarctica during the Late Oligocene and/or a change in the variability of atmospheric CO2 levels on astronomical time scales that is not yet captured in existing proxy reconstructions.


Inflammatory acidic pH enhances hydrogen sulfide-induced transient receptor potential ankyrin 1 activation in RIN-14B cells.
Hydrogen sulfide (H2 S), a toxic volcanic gas, functions as a gaseous physiological and pathophysiological molecule. Recently we have shown that H2 S elicits acute pain through the activation of transient receptor potential ankyrin 1 (TRPA1), which is expressed mainly in primary nociceptive neurons. We also demonstrated enhancement of H2 S-induced TRPA1 activation and pain under inflammatory acidic conditions, but the underlying mechanism has not been elucidated. Here, we attempted to clarify this mechanism by using endogenously TRPA1-expressing RIN-14B, a rat pancreatic islet cell line. For this purpose, the intracellular Ca(2+) concentration ([Ca(2+) ]i )], reactive oxygen species (ROS), and intracellular pH (pHi ) were measured with fluorescent imaging techniques. The intracellular H2 S concentration was assayed by the methylene blue method. To clarify the cellular function of H2 S, 5-hydroxytryptamine (5-HT) secretion was analyzed. In RIN-14B, the increase of [Ca(2+) ]i and the release of 5-HT induced by NaHS, an H2 S donor, were enhanced under inflammatory acidic conditions. Transition of H2 S into cells was enhanced at pH 6.8. H2 S failed to increase the intracellular ROS level and only slightly decreased pHi . These results suggest that H2 S directly activates TRPA1 and that its increment of diffusion into cells may be involved in the potentiation of TRPA1 activation under external acidic conditions. Thus, our study supports the pathophysiological functions of H2 S in inflammatory pain.


An inhibitory effect of thymidine on its own conversion to nucleotide in Escherichia coli.
The cellular levels of thymidine nucleotide pool in thymine-requiring mutants of Escherichia coli were followed. The pool levels of dTDP, dTTP and compound-X reached maximal values in much lower concentration of thymidine than those in thymine. In higher concentrations of thymidine, an inhibitory effect on its own conversion to nucleotide was observed. The inhibited step was suggested to be the conversion of dTMP to dTDP.


Acceptability of three convenience chicken products.
Three convenience products--frozen, precooked chicken apple fritters, chicken breast fillets, and chicken patties--provided by one processor were subjectively evaluated by two taste panels of older adults, ranging in age from the sixties to middle eighties. The panelists represented a middle-income group maintaining private homes and a low-income group living in public housing. Both panels rated each product above "good" (score=4) or "fair" (score=3) on four acceptability factors and the overall score. Although mean scores of the low-income taste panel on all factors were generally higher for all products, the only significant difference (P less than .01) pertained to the appearance factor. Both panels indicated willingness to buy all three products.


Acute phase proteins as promising biomarkers: Perspectives and limitations for human and veterinary medicine.
Acute phase proteins (APPs) are highly conserved plasma proteins that are increasingly secreted by the liver in response to a variety of injuries, independently of their location and cause. APPs favor the systemic regulation of defense, coagulation, proteolysis, and tissue repair. Various APPs have been applied as general diagnostic parameters for a long time. Through proteomic techniques, more and more APPs have been discovered to be differentially altered. Since they are not consistently explainable by a stereotypic hepatic expression of sets of APPs, most of these results have unfortunately been neglected or attributed to the nonspecificity of the acute phase reaction. Moreover, it appears that various extrahepatic tissues are also able to express APPs. These extrahepatic APPs show focally specific roles in tissue homeostasis and repair and are released primarily into interstitial and distal fluids. Since these focal proteins might leak into the circulatory system, mixtures of hepatic and extrahepatic APP species can be expected in blood. Hence, a selective alteration of parts of APPs might be expected. There are several hints on multiple molecular forms and fragments of tissue-derived APPs. These differences offer the chance for multiple selective determinations. Thus, specific proteoforms might indeed serve as tissue-specific disease indicators.


Cost-Effectiveness of Using Standardized Patients to Assess Student-Pharmacist Communication Skills.
Objective. To explore the cost-effectiveness of including standardized patients (SP) in the didactic curriculum for application and assessment of students' pharmacist-patient communication skills. Methods. Five role play/case study (RP/CS) activities from a communication skills curriculum were replaced with five SP encounters. Communication was assessed using a rubric. This study developed an economic model to examine the costs and effectiveness of replacing RP/CS events with SP events in knowledge-application and communication assessment. Costs consisted of SP hourly wages for training and delivery of SP events. Outcomes examined were the incremental cost-effectiveness ratio (ICER) per student. Results. The ICER comparing SP to RP/CS was $100.93 higher per student on first-attempt pass rates and $9.04 per one-point increase in the mean score. Conclusion. SP was more effective and more costly than RP/CS. Further research into students' willingness to pay needs to occur before determining if using SPs is cost-effective in teaching communication skills.


Progress in understanding and managing natural killer-cell malignancies.
The World Health Organization classification of haematolymphoid tumours recognizes three categories of natural killer (NK)-cell neoplasms: blastic NK-cell lymphoma, aggressive NK-cell leukaemia, and extranodal NK/T-cell lymphoma, nasal-type. Recent studies indicate that CD4+CD56+ blastic NK-cell lymphoma is of plasmacytoid dendritic cell origin, and true tumours of precursor NK-cell origin may be present mainly in the CD4-CD56+ subset. Myeloid/NK-cell precursor acute leukaemia may also develop from precursor NK cells. However, because the developmental pathway of normal NK cells is not well understood, tumours of precursor NK-cell origin are not clearly identified. Among mature NK-cell tumours, extranodal NK/T-cell lymphoma is relatively common in Asia and Latin America. In localized disease, chemoradiotherapy seems to be promising, and in advanced disease, new combination chemotherapies are under active investigation. Aggressive NK-cell leukaemia is rare and has a poor prognosis. Because NK-cell neoplasms are rare and difficult to manage, rigorous studies are required for their understanding and management.


Neurogenic constrictor response of isolated small renal arteries in rats after 2-week simulated microgravity.
The study was aimed at investigation of the effects of 2-week tail suspension upon the constrictor responses of isolated small renal arteries in rats. 1st-2nd-order branches of renal artery were perfused with saline under the constant flow conditions. Constrictor responses to electrical stimulation of periarterial nerves, noradrenaline and serotonin were investigated. In post-suspension rats as compared to controls the response to nerve stimulation was slightly reduced during 15-Hz stimulation, but similar at smaller frequencies. Thus, simulated microgravity has no prominent effect of neurogenic responses of renal vessels, in agreement with non-changed density of periarterial adrenergic nerve plexus. Along with that, in post-suspension rats impairment of prejunctional sympathetic mechanisms might be compensated by augmented sensitivity of vascular smooth muscle to vasoconstrictors.


[Influence of inflammation on prostaglandin metabolism in rat skin (author's transl)].
Influence of inflammation on prostaglandin metabolism in rat abdominal skin was studied. Prostaglandin F2alpha content was determined by the radioisotope dilution method. Prostaglandin F2alpha content in rat abdominal skin was increased by thermal burn and application of 2, 4-dinitrochlorobenzene. The incorporation of 3H-arachidonic acid into prostaglandin F2alpha in rat abdominal skin was not increased by inflammation. Indomethacin caused a significant reduction of prostaglandin F2alpha content. These results suggest that the prostaglandin may play an important role in the inflammatory process of rat skin.


Comparative Profiling and Discovery of Novel Glycosylated Mycosporine-Like Amino Acids in Two Strains of the Cyanobacterium Scytonema cf. crispum.
The mycosporine-like amino acids (MAAs) are a group of small molecules with a diverse ecological distribution among microorganisms. MAAs have a range of physiological functions, including protection against UV radiation, making them important from a biotechnological perspective. In the present study, we identified a putative MAA (mys) gene cluster in two New Zealand isolates of Scytonema cf. crispum (UCFS10 and UCFS15). Homology to "Anabaena-type" mys clusters suggested that this cluster was likely to be involved in shinorine biosynthesis. Surprisingly, high-performance liquid chromatography analysis of S cf. crispum cell extracts revealed a complex MAA profile, including shinorine, palythine-serine, and their hexose-bound variants. It was hypothesized that a short-chain dehydrogenase (UCFS15_00405) encoded by a gene adjacent to the S cf. crispum mys cluster was responsible for the conversion of shinorine to palythine-serine. Heterologous expression of MysABCE and UCFS15_00405 in Escherichia coli resulted in the exclusive production of the parent compound shinorine. Taken together, these results suggest that shinorine biosynthesis in S cf. crispum proceeds via an Anabaena-type mechanism and that the genes responsible for the production of other MAA analogues, including palythine-serine and glycosylated analogues, may be located elsewhere in the genome. Recently, New Zealand isolates of S cf. crispum were linked to the production of paralytic shellfish toxins for the first time, but no other natural products from this species have been reported. Thus, the species was screened for important natural product biosynthesis. The mycosporine-like amino acids (MAAs) are among the strongest absorbers of UV radiation produced in nature. The identification of novel MAAs is important from a biotechnology perspective, as these molecules are able to be utilized as sunscreens. This study has identified two novel MAAs that have provided several new avenues of future research related to MAA genetics and biosynthesis. Further, we have revealed that the genetic basis of MAA biosynthesis may not be clustered on the genome. The identification of the genes responsible for MAA biosynthesis is vital for future genetic engineering.


Searching for new strategies against biofilm infections: Colistin-AMP combinations against Pseudomonas aeruginosa and Staphylococcus aureus single- and double-species biofilms.
Antimicrobial research is being pressured to look for more effective therapeutics for the ever-growing antibiotic-resistant infections, and antimicrobial peptides (AMP) and antimicrobial combinations are promising solutions. This work evaluates colistin-AMP combinations against two major pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, encompassing non- and resistant strains. Colistin (CST) combined with the AMP temporin A (TEMP-A), citropin 1.1 (CIT-1.1) and tachyplesin I linear analogue (TP-I-L) was tested against planktonic, single- and double-species biofilm cultures. Overall synergy for planktonic P. aeruginosa and synergy/additiveness for planktonic S. aureus were observed. Biofilm growth prevention was achieved with synergy and additiveness. Pre-established 24 h-old biofilms were harder to eradicate, especially for S. aureus and double-species biofilms; still, some synergy and addictiveness was observed for higher concentrations, including for the biofilms of resistant strains. Different treatment times and growth media did not greatly influence AMP activity. CST revealed low toxicity compared with the other AMP but its combinations were toxic for high concentrations. Overall, combinations reduced effective AMP concentrations, mainly in prevention scenarios. Improvement of effectiveness and toxicity of therapeutic strategies will be further investigated.


Constitutive expression of the adenovirus E3-14.7K protein does not prolong adenovirus vector DNA persistence but protects mice against lipopolysaccharide-induced acute hepatitis.
First-generation adenovirus vectors, deleted in the E1 and E3 regions of the genome, induce a strong inflammatory response that affects persistence of vector DNA in transduced organs and causes toxicity in the host. Wild-type adenovirus encodes a number of proteins that are nonessential for viral propagation in vitro but that dampen the inflammatory and immune responses mounted by the host during infection. The adenovirus E3 region-encoded 14.7K protein inhibits tumor necrosis factor alpha (TNF-alpha)-induced apoptosis and arachidonic acid synthesis. To evaluate the impact of constitutive expression of the 14.7K protein on vector-induced pathology, toxicity, and DNA persistence, we constructed vectors that contain a cytomegalovirus promoter-driven 14.7K expression cassette. Although these vectors inhibit TNF-alpha-induced apoptosis in vitro, they do not show better vector DNA persistence, or lower inflammation or pathology than E3-deleted first-generation vector in mouse models. However, the 14.7K protein is functional in mice because animals injected intravenously with a 14.7K-constitutive vector were fully protected against a lethal dose of lipopolysaccharide 5 days after vector administration. These results open new applications for the E3-encoded 14.7K protein, which can be used to protect organs against inflammatory reactions and TNF-alpha-mediated apoptosis.


Mucinous carcinoma in Crohn's disease originating in a fistulous tract.
Malignant disease, including mucinous carcinomas of the colorectum, may complicate long-standing Crohn's disease. An 18-year-old male with extensive small and large bowel involvement with Crohn's disease developed recurrent peri-rectal fistulous disease that persisted for more than a decade despite pharmacological and surgical therapy as well as later therapy with biological agents. Eventually, an extensive and difficult-to-detect mucinous carcinoma developed in the fistulous tract. Although fistula cancer is rarely described in Crohn's disease, use of immunosuppressant and biological agents may play an initiating or exacerbating role in its development or progression. As potent biological agents are frequently used, often to avoid surgical treatment, clinicians should have an increasingly high index of suspicion for this potential complication, especially if fistulous drainage persists and remains refractory to medical therapy.


[Erosion and abrasion of the dental enamel. Experimental study].
The clinical aspects, epidemiology, etiology and pathogenesis of dental erosions in man and experimental animals are reviewed. Abrasion of enamel, softened in orange juice for 3 minutes and brushed with various dentifrices, was studied with Knoop hardness measurements and scanning electron microscopy. Knoop indentations made on softened enamel surfaces were almost totally removed by 2-minute brushings with highly abrasive tooth pastes. Brushing without dentifrices only slightly changed the distinctness of the indentation outlines. Recommendations for primary and secondary prevention of erosions are given.


[A nursing experience of applying Watson's caring theory to a primary caregiver in an ICU].
The authors present a case study of a nursing experience applying Watson's caring theory to a critical patient's primary caregiver in the intensive care unit. Data were collected by observation, discussion, and telephone interviews between 20th April and 10th May 2004. Major nursing problems were: (1) anxiety, (2) anticipatory grieving, and (3) poor social support system. The authors describe the details of the primary intervention effort, using Watson's caring theory in accordance with the spirit of nursing as conducted by the Mutual Confidence Foundation, providing individual protective nursing, reducing the caregiver's anxiety, facilitating constructive anticipatory grieving, and providing appropriate social resources. This relieved the caregiver's stress caused by physical, mental, emotional and social factors.


[Role of exhaled nitric oxide in predicting steroid response in chronic obstructive pulmonary disease].
Exhaled nitric oxide is the most extensively studied exhaled biomarker. In patients with stable chronic obstructive pulmonary disease exhaled nitric oxide level appears to be normal or only slightly elevated. As exhaled nitric oxide is a good surrogate marker for eosinophilic airway inflammation and eosinophilic inflammation is steroid responsive, patients with elevated exhaled nitric oxide levels may benefit more from a short course of inhaled or systemic corticosteroid treatment. In acute exacerbation most studies report elevated exhaled nitric oxide levels that decrease along with treatment. More importantly, exhaled nitric oxide levels at exacerbation correlate with functional improvements after treatment suggesting the possibility of a role for exhaled nitric oxide in predicting the response to treatment. In conclusion, assessment of airway inflammation using exhaled nitric oxide may identify a subgroup of patients with chronic obstructive pulmonary disease that is likely to benefit from corticosteroid treatment.


Studies on Dibenzylamines as Inhibitors of Venezuelan Equine Encephalitis Virus.
Alphaviruses are arthropod-transmitted members of the Togaviridae family that can cause severe disease in humans, including debilitating arthralgia and severe neurological complications. Currently, there are no approved vaccines or antiviral therapies directed against the alphaviruses, and care is limited to treating disease symptoms. A phenotypic cell-based high-throughput screen was performed to identify small molecules that inhibit the replication of Venezuelan Equine Encephalitis Virus (VEEV). The compound, 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-(3-fluoro-4-methoxybenzyl)ethan-1-amine (1), was identified as a highly active, potent inhibitor of VEEV with an effective concentration for 90% inhibition of virus (EC90) of 0.89 μM and 7.49 log reduction in virus titers at 10 μM concentration. These data suggest that further investigation of compound 1 as an antiviral therapeutic against VEEV, and perhaps other alphaviruses, is warranted. Experiments suggested that the antiviral activity of compound 1 is directed at an early step in the VEEV replication cycle by blocking viral RNA and protein synthesis.


Psychometric properties of the Neuropsychiatric Inventory for adults with intellectual disability.
Problem behaviours are common among people with intellectual disabilities (ID), but psychometrically evaluated instruments for assessing such behaviours are scarce. The present study evaluated the psychometric properties of the Neuropsychiatric Inventory-Intellectual Disability (NPI-ID). We assessed 108 residents with intellectual disabilities living in group-homes using the NPI-ID, which included the 12 symptoms of the original NPI-Nursing Home and two supplementary symptoms: self-injurious behaviour and impulsive risk-taking behaviour. The NPI-ID showed adequate internal consistency (α = 0.76) and test-retest reliability (intraclass correlation coefficient = 0.88). Exploratory factor analysis revealed five factors accounting for 64.1% of the variance. Cluster analysis revealed that residents were clustered in three groups with distinctly different symptom profiles. The psychometric properties were satisfactory, supporting the use of the NPI-ID as a screening tool for people with intellectual disabilities. Additional research is needed to further evaluate the utility of the NPI-ID among people with intellectual disabilities.


'Fruit-flavoured' mask for isoflurane induction in children.
The effect of disguising the odour of isoflurane with fruit flavouring, upon the quality of inhalational induction, was studied in 41 children aged 3-10 years in a double-blind, randomised trial. Facemasks were either lightly coated with fruit extract or moistened with water so that their appearance was identical to children, anaesthetist and observer. Children allocated to receive fruit flavouring were significantly quieter than the placebo group, but their degree of movement during induction was unchanged. The incidence of respiratory complications including breath-holding, laryngospasm and coughing was similar in both groups. Overall impression of the quality of induction as assessed by the anaesthetist showed no difference between the groups. This simple, cheap modification of inhalational induction warrants further appraisal while the case for disguising the odour of isoflurane remains unproven.


[The imaging study of internal mammary artery and its branches ].
To investigate the distribution of the internal mammary artery and its branches by the multi-slice spiral CT angiography, and to explore the feasibility of transferring pedicled transverse rectus abdomials myocataneous (TRAM) flap for breast reconstruction through resection of inferior costicartilages. 30 female patients received abdominal CT angiography. (1) The distance between internal mammary artery and the sternum midline were recorded; (2) The position and the numbers of branches from bilateral internal mammary arteries at the level of 5th, 6th, 7th rib was observed; (3) The points where the superior epigastric artery gets through the rectus abdominis muscle were located. ( The average distance between left internal mammary artery to the sternum midline is from 1. 66 cm (0. 62-2. 39 cm ) to 2.34 cm (0.69-3.36 cm) at the level from 4th to 6th intercostal space. The average distance between right internal mammary artery to the sternum midline is from 1.55 cm(0. 66-2. 29 cm) to 2.29 cm(0. 73-3. 67 cm) at the level from 4th to 6th intercostal space; ) The number of branches is the most at the level of 6th intercostal space; (3) There are 235 branches in the superior epigastric artery. This imaging study of internal mammary artery explores the feasibility of transferring pedicled transverse rectus abdominals myocataneous flap for breast reconstruction. It has important significance in the breast reconstruction using TRAM flap with lengthened pedicle.


Intradendritic release of calcium induced by glutamate in cerebellar Purkinje cells.
The ability of excitatory amino acids to induce increases in the intracellular Ca2+ concentration ([Ca2+]i) of cerebellar Purkinje cells was examined by digital fluorescence ratio imaging of voltage-clamped Purkinje cells dialyzed with the Ca2+ indicator fura-2. Purkinje cells responded with large inward currents accompanied by increases in dendritic [Ca2+]i when challenged with the excitatory amino acid agonists glutamate and quisqualate. The rise in [Ca2+]i was transient and reached peak values of several hundred nanomolar. The response subsisted in the absence of extracellular Ca2+, a condition that eliminates Ca2+ entry through voltage-gated Ca2+ channels, indicating that Ca2+ arose in large part from an intracellular compartment. In support of this hypothesis, only the first agonist application elicited a [Ca2+]i increase in slices maintained in Ca(2+)-free medium, as expected if the intracellular stores become depleted. These results indicate that metabotropic glutamate receptors are functional in Purkinje cells and point to glutamate as a possible modulator of [Ca2+]i in these neurons.


2-LP mode few-mode fiber amplifier employing ring-core erbium-doped fiber.
A fiber amplifier supporting 2 LP modes that employs a ring-core erbium-doped fiber (RC-EDF) is investigated to reduce differential modal gain (DMG). The inner and outer radii of the ring-core of the RC-EDF are clarified for 2-LP mode operation of the amplifier, and are optimized to reduce the DMG. It is shown that using the overlap integral between the erbium-doped core area and the signal power mode distribution is a good way to optimize the inner and outer radii of the ring-core of the RC-EDF and thus minimize the DMG. A fabricated RC-EDF and a constructed 2-LP mode EDFA are described and a small DMG of around 1 dB is realized for LP01, LP11 and LP21 pumping.


A multinational report to characterise SARS-CoV-2 infection in people with cystic fibrosis.
Information is lacking on the clinical impact of the novel coronavirus, SARS-CoV-2, on people with cystic fibrosis (CF). Our aim was to characterise SARS-CoV-2 infection in people with cystic fibrosis. Anonymised data submitted by each participating country to their National CF Registry was reported using a standardised template, then collated and summarised. 40 cases have been reported across 8 countries. Of the 40 cases, 31 (78%) were symptomatic for SARS-CoV-2 at presentation, with 24 (60%) having a fever. 70% have recovered, 30% remain unresolved at time of reporting, and no deaths have been submitted. This early report shows good recovery from SARS-CoV-2 in this heterogeneous CF cohort. The disease course does not seem to differ from the general population, but the current numbers are too small to draw firm conclusions and people with CF should continue to strictly follow public health advice to protect themselves from infection.


MYC Deregulation in Primary Human Cancers.
MYC regulates a complex biological program by transcriptionally activating and repressing its numerous target genes. As such, MYC is a master regulator of many processes, including cell cycle entry, ribosome biogenesis, and metabolism. In cancer, the activity of the MYC transcriptional network is frequently deregulated, contributing to the initiation and maintenance of disease. Deregulation often leads to constitutive overexpression of MYC, which can be achieved through gross genetic abnormalities, including copy number alterations, chromosomal translocations, increased enhancer activity, or through aberrant signal transduction leading to increased MYC transcription or increased MYC mRNA and protein stability. Herein, we summarize the frequency and modes of MYC deregulation and describe both well-established and more recent findings in a variety of cancer types. Notably, these studies have highlighted that with an increased appreciation for the basic mechanisms deregulating MYC in cancer, new therapeutic vulnerabilities can be discovered and potentially exploited for the inhibition of this potent oncogene in cancer.


Medical services provided at the 1982 Southern Open Golf Tournament.
This study describes the medical services provided the players, players' families, caddies, Professional Golf Association (PGA) officials, tournament workers, and spectators during the 1982 Southern Open Golf Tournament. One first aid center, staffed by one physician and one nurse, was available to approximately 12,000 people during the 7 day event. The facility was stocked with routine diagnostic and therapeutic supplies, as well as routine and emergency drugs. Of the 92 patients seen, only one, who presented with a seizure, required hospital management. Spectators accounted for 20% of the visits. The remaining visits were by the tournament population for acute care. It was concluded that additional orthopaedic supplies needed to be readily available. Additional emergency equipment and drugs are recommended. The available and needed supplies should provide a reference for stocking first aid stations at future similar outdoor events that attract large crowds with varied medical needs.


[First Danish case of Mycobacteriumchimaerainfection from cardiac surgery with contaminated heater-cooler unit].
Infection with Mycobacterium chimaera has globally been linked to cardiac surgery using cardiopulmonary bypass devices with contaminated heater-cooler units (HCU). This is a case report of M. chimaera infection linked to HCU in Denmark in which we show, how difficult the diagnosis can be. A 67-year-old man had an aortic graft and valvular replacement using HCU. Post-operatively he developed progressing symptoms of intermittent fever, malaise and endocarditis with septic embolic events, and despite extensive diagnostic work-up, he remained undiagnosed for 16 months following surgery.


The finger of an angel: memory return with epigenetic manipulation.
Scientists have been trying to crack the memory code for hundreds of years; however, centuries later, even the simplest elements of memory formation are still not fully understood. Recent studies in epigenetics indicate neuronal activity can induce transient reprogramming of epigenetic codes required for long-term memory consolidation. This suggests epigenetics as a basic mechanism in the regulation of long-term memory; and highlights the possibility that epigenetic modifications, as well as environmental factors, can change certain gene expression of brain neurons to restore the ability to remember, even with an aging brain or innate mental deficits. This article is an overview of basic knowledge and current research on epigenetic regulation of long-term memory, and prospects for future research.


CYP2D6 polymorphisms may predict occurrence of adverse effects to tamoxifen: a preliminary retrospective study.
Tamoxifen is an adjuvant drug effective in treating hormone receptor - positive breast cancer. However, 30%-50% of patients relapse and many develop adverse effects, such as hot flashes and fatty liver. Allelic variations altering the activity of cytochrome P450-2D6 enzyme affect response to tamoxifen by modulating metabolism of tamoxifen into its pharmacologically active metabolite endoxifen. Although association between CYP2D6 polymorphisms and recurrence of breast cancer in patients on tamoxifen had been reported, little evidence exists on association between these polymorphisms and adverse effects to tamoxifen. This study explored the association between CYP2D6 polymorphisms and tamoxifen effects, hitherto not studied in Sri Lanka. A retrospective preliminary study was carried out on 24 breast cancer patients on tamoxifen for minimally 3 months attending National Cancer Institute, Maharagama, Sri Lanka. They were not on CYP2D6-inhibiting drugs, chemotherapy or other endocrine therapy, and had no conditions that could occur as adverse effects to tamoxifen before starting the therapy. Their blood samples were collected, DNA was extracted and genotyped using SNaPshot Multiplex sequencing based single-nucleotide polymorphism (SNP) assay. SNP/allele frequencies detected: 1846G>A (confirmatory of *4 null allele)=8.3%; 2549delA (confirmatory of *3 null allele)=50%; 100C>T (suggestive of *10 reduced functional allele, in addition to other alleles)=0%; combination of 2988G>A, -1584C and 2850C>T (strongly suggestive of *41 or other reduced functional allele)=4.8%. Occurrence of heterozygous 2988G>A SNP with -1584C and 2850C>T was significantly higher among those with ultrasound-diagnosed fatty liver following the commencement of tamoxifen therapy (P=0.029). Adverse effects occurred at a significantly higher frequency among postmenopausal women (P=0.041). Three patients who developed recurrence of breast cancer had no association with SNPs tested. CYP2D6 SNP combination 2988G>A, -1584C and 2850C>T, strongly suggestive of *41 reduced functional allele, is likely to be useful in predicting occurrence of adverse effect fatty liver in breast cancer patients on tamoxifen, thereby alternative treatment can be considered and lifestyle modifications implemented. Larger sample studies are recommended with the measurement of tamoxifen and metabolite levels. Alternative therapy should be considered for postmenopausal patients.


PHYLOGENETIC POSITION OF THE OOCYSTACEAE (CHLOROPHYTA).
The complete 18S rRNA gene sequences of three Oocystis A. Braun species (Oocystaceae) and three other chlorococcal algae, Tetrachlorella alternans (G. M. Smith) Korš. (Scenedesmaceae), Makinoella tosaensis Okada (Scenedesmaceae), and Amphikrikos cf. nanus (Fott & Heynig) Hind. (Chlorellaceae) were determined and subjected to four different phylogenetic analysis algorithms. Independent of the reconstruction method, these taxa clustered together as a monophyletic group (Oocystaceae) within the Trebouxiophyceae. This result was supported by high bootstrap values. A comparison of morphological data with the phylogenetic reconstructions indicated that the evolution of Oocystaceae was accompanied by a reduction in the number of plastids. This study fully supports the taxonomic assignment of the Oocystaceae as a distinct family. The diacritic criterion that the cell walls are composed of several cellulose layers with perpendicular fibril orientations is in accordance with the molecular data.


Assessing Relevance of External Cognitive Measures.
The arrival of modern brain imaging technologies has provided new opportunities for examining the biological essence of human intelligence as well as the relationship between brain size and cognition. Thanks to these advances, we can now state that the relationship between brain size and intelligence has never been well understood. This view is supported by findings showing that cognition is correlated more with brain tissues than sheer brain size. The complexity of cellular and molecular organization of neural connections actually determines the computational capacity of the brain. In this review article, we determine that while genotypes are responsible for defining the theoretical limits of intelligence, what is primarily responsible for determining whether those limits are reached or exceeded is experience (environmental influence). Therefore, we contend that the gene-environment interplay defines the intelligent quotient of an individual.


A patient-centered methodology that improves the accuracy of prognostic predictions in cancer.
Individualized approaches to prognosis are crucial to effective management of cancer patients. We developed a methodology to assign individualized 5-year disease-specific death probabilities to 1,222 patients with melanoma and to 1,225 patients with breast cancer. For each cancer, three risk subgroups were identified by stratifying patients according to initial stage, and prediction probabilities were generated based on the factors most closely related to 5-year disease-specific death. Separate subgroup probabilities were merged to form a single composite index, and its predictive efficacy was assessed by several measures, including the area (AUC) under its receiver operating characteristic (ROC) curve. The patient-centered methodology achieved an AUC of 0.867 in the prediction of 5-year disease-specific death, compared with 0.787 using the AJCC staging classification alone. When applied to breast cancer patients, it achieved an AUC of 0.907, compared with 0.802 using the AJCC staging classification alone. A prognostic algorithm produced from a randomly selected training subsample of 800 melanoma patients preserved 92.5% of its prognostic efficacy (as measured by AUC) when the same algorithm was applied to a validation subsample containing the remaining patients. Finally, the tailored prognostic approach enhanced the identification of high-risk candidates for adjuvant therapy in melanoma. These results describe a novel patient-centered prognostic methodology with improved predictive efficacy when compared with AJCC stage alone in two distinct malignancies drawn from two separate populations.


Different profiles of onion bulb in CIDP and CMT1A in relation to extracellular matrix.
Hypertrophic neuropathy is usually intractable, and chronic inflammatory demyelinating polyneuropathy (CIDP) and Charcot-Marie-Tooth disease Type 1A (CMT1A) are the representative disorders. The two disorders are sometimes confused both clinically and pathologically. The aim of this study was to clarify the differences in the pathology of large onion bulbs, focusing on the extracellular matrix (ECM) proteins. Nine patients with CIDP and 14 with CMT1A were included. The opened interspaces in OB were frequently shown in CMT1A patients. In CIDP, interspaces of OB packed with collagen fibers were prominent. The mean ratio of opened OB was significantly increased in CMT1A (37.9%) compared to CIDP patients (10.6%) (p = 0.003). Among the ECM examined, tenascin-C (TNC) showed a distinct difference in the pattern of immunoreactivity of OB. The mean ratio of OB showing TNC immunoreactivity was significantly larger in CIDP (29.7%, p = 0.005) than in CMT1A (5.0%). TNC immunoreactivity was confined to the area around myelin sheaths in CMT1A. The increased deposition of collagen fibers in CIDP suggests the activity of nerve regeneration. TNC expression in Schwann cell lamellae comprising OB may also suggest the activity of regeneration. Schwann cell phenotypes in CIDP may be different from CMT1A regarding the production of ECM proteins.


The peroxide complex of yeast cytochrome c peroxidase contains two distinct radical species, neither of which resides at methionine 172 or tryptophan 51.
The nature of the free radical species observed in the peroxide complex of yeast cytochrome c peroxidase is described for protein variants containing amino acid substitutions at Met-172 and Trp-51. As was the case with Met-172 mutations (Goodin, D.B., Mauk, A.G., and Smith, M. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 1295-1299), Trp-51 can be substituted to give active enzyme. Phe-51-containing enzyme has a higher turnover rate than the original enzyme and exhibits an altered pH dependence. The properties of the isotropic and axial components (Hoffman, B.M., Roberts, J.E., Kang, C.H., and Margoliash, E. (1981) J. Biol. Chem. 256, 6556-6564; Hori, H., and Yonetani, T. (1985) J. Biol. Chem. 260, 349-355) of the EPR signal of the wild-type enzyme-peroxide complex, studied as a function of H2O2 stoichiometry, support proposals (Goodin et al. (1985) and Hori and Yonetani (1985), see above) that two distinct radical species are formed, and spin quantification shows that the isotropic radical is always formed in substoichiometric amounts. The peroxide complexes for proteins containing amino acid substitutions at either Met-172 or Trp-51 exhibit somewhat larger than normal levels of the isotropic radical signal. In addition, these mutants are unlike wild-type enzyme in that the axial EPR signal associated with the peroxide complex is seen only at 10 K and not at 90 K. Thus, neither amino acid can be considered to be the molecular species responsible for either radical signal, but both mutations appear to affect the physical properties of the axial signal representing the major radical species.


Endoscopic survey of post-extubation stridor in children.
Endotracheal intubation is an important airway procedure in the management of neonates and infants. Prolonged intubation may result in severe laryngeal injury which may lead to chronic laryngeal disability. The nature and causes of post-extubation airway obstruction were evaluated with videoendoscopy. From June 1998 to September 2000, detailed videoendoscopic examination of pediatric airway was performed in 30 children who had persistent stridor after endotracheal extubation or failure of elective extubation. Common locations of post-extubation lesion are the posterior glottis and subglottis. Retrospective analysis of the causes of stridor included: (1) isolated intubation laryngotracheitis (n = 19); (2) intubation laryngotracheitis with neuromuscular dysfunction which resulted in tongue drop, laryngotracheal incoordination, saliva pooling over the larynx or poor cough reflex(n = 5); and (3) specific airway problems such as laryngomalacia, subglottic stenosis or vocal paralysis(n = 6). We favored the term of "intubation laryngotracheitis" instead of "intubation injury" or 'intubation trauma". Although most cases of intubation laryngotracheitis heal, leaving a normal or near-normal larynx, some of them still suffer from airway obstruction after endotracheal extubation. Specific airway problems such as severe laryngomalacia or vocal cords paralysis and neurogenic defects should also be taken into consideration.


Clinical management of severely hypoxemic patients.
To describe a physiopathological-based approach to clinical management of severely hypoxemic patients that integrates the most recent findings on the use of rescue therapies. Several techniques are available to improve oxygenation in severely hypoxemic patients. Survival benefits have not been proved for most of these techniques. In a recent randomized trial, centralization of acute respiratory distress syndrome patients to a specialized center able to provide extracorporeal membrane oxygenation showed better survival as compared to conventional treatment. Randomized trials failed to prove survival benefits with the use of high levels of positive end-expiratory pressure (PEEP) or prone positioning. However, pooled data from two meta-analyses showed significant higher survival in the most severe patients both with the use of higher PEEP and prone positioning. Treatment of severely hypoxemic patients should aim to improve oxygenation while limiting ventilator-induced lung injury. A physiopathological approach that accounts for the underlying mechanisms of hypoxemia, and physiological and clinical effects of different treatments is likely the best guide we have to treat severely hypoxemic patients.


Beamline 14: a new multipole wiggler beamline for protein crystallography on the SRS.
A new multipole wiggler device has been designed for the 2.0 GeV Synchrotron Radiation Source at Daresbury Laboratory in the UK. The nine-pole 2.0 T device will provide radiation for two beamlines dedicated to protein crystallography, one of which will be of high intensity. This article provides details of the design of the two stations and outlines methods being developed to combine dealing with the high heat load from the radiation while allowing both stations to be built as close to the centre of the fan as possible.


Efficacy and Mechanism of Electroacupuncture Treatment of Rabbits With Different Degrees of Knee Osteoarthritis: A Study Based on Synovial Innate Immune Response.
Knee osteoarthritis (KOA) is a chronic degenerative bone and joint disease, which is often clinically manifested as pain, joint swelling, and deformity. Its pathological manifestations are mainly synovial inflammation and cartilage degeneration. This study aims to investigate the efficacy of electro-acupuncture (EA) on model rabbits with varying degrees of KOA and to study the mechanism of EA on KOA based on the innate immune response. Mild and moderate rabbit KOA models were established using a modified Hluth method, and EA was given to both the mild and moderate model groups. The Lequesne-MG index was used to evaluate the behavioral changes in the rabbits before and after EA treatment. Morphological changes in the synovial membrane and cartilage of each group were observed by H&E staining. The Mankin scoring standard and the Krenn scoring standard were used to score the pathology of the cartilage tissue and synovial tissue, respectively. The inflammatory factors and metalloproteinases were detected in the serum of each group by ELISA. The protein and messenger RNA (mRNA) expressions of important elements related to Toll-like receptors (TLRs)-mediated innate immune response in the synovial tissue were detected by Western blot and quantitative PCR (qPCR). The Lequesne-MG index score of the rabbits gradually increased with the modeling prolonged but decreased significantly after EA treatment, indicating that EA has a better effect on alleviating the pain and improving the dysfunction. The morphological analysis showed that the inflammation of and the damage to the synovial membrane and the cartilage tissue gradually deteriorated with the modeling prolonged. However, the synovial membrane inflammation was significantly relieved after EA treatment, and the cartilage injury showed signs of repair. The ELISA analysis showed that, with the modeling prolonged, the serum-related inflammatory factors and mechanism of metalloproteinases gradually increased but decreased after EA treatment. The tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and matrix metalloproteinase3 (MMP3) of EA1 group were significantly lower than those of EA2 group. Both Western blot and qPCR results showed that the protein and mRNA expressions of the elements related to the innate immune response in the synovial membrane increased gradually with the modeling prolonged, but decreased significantly after EA treatment. Additionally, the expression of some components in EA1 group was significantly lower than that in EA2 group. These results confirm that synovial inflammation gradually aggravated with time from the early to mid-stage of KOA. EA alleviated the inflammation and histological changes in KOA rabbits by inhibiting the TLRs-mediated innate synovial immune response. This suggests that using EA in the early stage of KOA may achieve a desirable efficacy.


MicroRNA-499a-5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling.
A number of studies have attempted to elucidate the association between mircoRNAs (miRNAs/miRs) and cancer-associated processes. The aim of the present study was to determine how miR-499a-5p intervenes in human osteosarcoma cell proliferation and differentiation. The cancerous tissues and adjacent non-cancerous tissues of 62 patients with osteosarcoma (OS) were collected. miRNA microarray analysis revealed that 29 miRNAs were upregulated while 26 were downregulated, among which miR-499a-5p expression was the most decreased. Western blot analysis and reverse transcription-quantitative polymerase chain reaction demonstrated that the mRNA and protein expression of miR-499a-5p was lower, while that of protein phosphatase 1D (PPM1D) was higher in OS tissues compared with expression levels in normal tissues. Furthermore, miR-499a-5p expression was markedly decreased in the metastatic tumors and in those at stage III+IV compared with the non-metastatic tumors and those at stage I, respectively. In addition, following transfection of the human OS MG-63 cell line with an miR-499a-5p mimic, the expression of miR-499a-5p was elevated while the protein and mRNA expression of PPM1D was decreased. When combining these findings with the information obtained from the Targetscan predictive software, it was confirmed that PPM1D was targeted by miR-499a-5p. In MG-63 cells transfected with an miR-499a-5p mimic, PPM1D-associated downstream proteins phosphorylated protein kinase B (p-Akt) and phosphorylated glycogen synthase kinase 3β (p-GSK-3β) were significantly downregulated compared with the negative control (NC) group, while the expression of p-Akt and p-GSK-3β were significantly elevated in the tumor tissues compared with the adjacent non-tumor tissues. Simultaneously, the growth and proliferation activity of MG-63 cells were notably reduced when transfected with the miR-499a-5p mimic, compared with the NC group. Therefore, it may be concluded that miR-499a-5p suppresses OS cell proliferation and differentiation by targeting PPM1D through modulation of Akt/GSK-3β signaling.


Vaporization of Kitaev spin liquids.
The quantum spin liquid is an exotic quantum state of matter in magnets. This state is a spin analog of liquid helium that does not solidify down to the lowest temperature due to strong quantum fluctuations. In conventional fluids, the liquid and gas possess the same symmetry and adiabatically connect to each other by bypassing the critical end point. We find that the situation is qualitatively different in quantum spin liquids realized in a three-dimensional Kitaev model; both gapless and gapped quantum spin liquid phases at low temperatures are always distinguished from the high-temperature paramagnet (spin gas) by a phase transition. The results challenge the common belief that the absence of thermodynamic singularity down to the lowest temperature is a symptom of a quantum spin liquid.


Anticoagulant Therapy for Cancer-Associated Venous Thromboembolism after Cancer Remission.
Objectives: To examine the outcomes of anticoagulant therapy for patients with venous thromboembolism (VTE) with active cancer and the outcomes after cancer remission with and without anticoagulant therapy. Materials and Methods: Of the 338 patients with cancer-associated VTE who received anticoagulant therapy, we evaluated therapeutic outcomes over 1 year for 112 patients whose cancers were in remission (cancer remission group) and 226 patients who continued cancer treatment (continued cancer treatment group). Further, the cancer remission group was divided into 89 and 23 patients who completed (completion of anticoagulation group) and continued (continued anticoagulation group) anticoagulant therapy, respectively. Treatment outcomes after completing anticoagulant therapy were compared between these two groups. The follow-up period was 1 year, and the endpoints were all-cause death, VTE recurrence, and bleeding events. Results: The event-free survival rates were 99.1% and 42.9% in the cancer remission and continued cancer treatment groups, respectively. For treatment outcomes after the completion of anticoagulant therapy, the event-free survival rates were 98.9% and 87% in the completion of anticoagulation and continued anticoagulation groups, respectively (log rank, P=0.005). Conclusion: When cancer is in remission, recurrence is low even if anticoagulant therapy is terminated after a certain period.


Simulation study on light color conversion enhancement through surface plasmon coupling.
A theoretical model together with a numerical algorithm of surface plasmon (SP) coupling are built for simulating SP-enhanced light color conversion from a shorter-wavelength radiating dipole (representing a quantum well - QW) into a longer-wavelength one (representing a quantum dot - QD) through QD absorption at the shorter wavelength. An Ag nanoparticle (NP) located between the two dipoles is designed for producing strong SP couplings simultaneously at the two wavelengths. At the QW emission wavelength, SP couplings with the QW and QD dipoles lead to the energy transfer from the QW into the QD and hence the absorption enhancement of the QD. At the QD emission wavelength, SP coupling with the excited QD dipole results in the enhancement of QD emission efficiency. The combination of the SP-induced effects at the two wavelengths leads to the increase of overall color conversion efficiency. The color conversion efficiencies in using Ag NPs of different geometries or SP resonance behaviors for producing different QD absorption and emission enhancement levels are compared.


Effect of nutrition on the GH responsiveness of liver and adipose tissue in dairy cows.
Dairy cows enter a period of energy insufficiency after parturition. In liver, this energy deficit leads to reduced expression of the liver-specific GH receptor transcript (GHR1A) and decreased GHR abundance. As a consequence, hepatic processes stimulated by GH, such as IGF-I production, are reduced. In contrast, adipose tissue has been assumed to remain fully GH responsive in early lactation. To determine whether energy insufficiency causes contrasting changes in the GH responsiveness of liver and adipose tissue, six lactating dairy cows were treated for 4 days with saline or bovine GH when adequately fed (AF, 120% of total energy requirement) or underfed (UF, 30% of maintenance energy requirement). AF cows mounted robust GH responses in liver (plasma IGF-I and IGF-I mRNA) and adipose tissue (epinephrine-stimulated release of non-esterified fatty acids in plasma, IGF-I mRNA, and p85 regulatory subunit of phosphatidylinositol 3-kinase mRNA). Reductions of these responses were seen in the liver and adipose tissue of UF cows and were associated with decreased GHR abundance. Reduced GHR abundance occurred without corresponding reductions of GHR1A transcripts in liver or total GHR transcripts in adipose tissue. In contrast, undernutrition did not alter the abundance of proteins involved in the early post-receptor signaling steps. Thus, a feed restriction reproducing the energy deficit of early lactation depresses GH actions not only in liver but also in adipose tissue. It remains unknown whether a similar reduction of GH action occurs in the adipose tissue of early lactating dairy cows.


Hydrophobins: the protein-amphiphiles of filamentous fungi.
Hydrophobins are surface active proteins produced by filamentous fungi. They have a role in fungal growth as structural components and in the interaction of fungi with their environment. They have, for example, been found to be important for aerial growth, and for the attachment of fungi to solid supports. Hydrophobins also render fungal structures, such as spores, hydrophobic. The biophysical properties of the isolated proteins are remarkable, such as strong adhesion, high surface activity and the formation of various self-assembled structures. The first high resolution three dimensional structure of a hydrophobin, HFBII from Trichoderma reesei, was recently solved. In this review, the properties of hydrophobins are analyzed in light of these new data. Various application possibilities are also discussed.


LDL = 5: Virtues and dangers of multidrug therapy of low-density lipoprotein cholesterol.
Multiple-drug therapy of dyslipidemia is frequently used to achieve treatment goals in high-risk patients with coronary artery disease. The authors report a case of a patient treated with a statin, fibrate, ezetimibe, and niacin in whom a calculated low-density lipoprotein cholesterol level of 5 mg/dL was achieved.


The clinical use of macrolides.
Macrolides are active against Streptococcus pneumoniae, Legionella spp. and Mycoplasma pneumoniae, the main causes of community-acquired pneumonia They may therefore be used for the empirical treatment of community-acquired pneumonia, although emergent resistance in Str. pneumoniae limits their use in some parts of the world. In patients with bronchitis the use of macrolides reduces the severity and duration of symptoms. Macrolides have also been used successfully in the treatment of otitis media and sinusitis; combination with sulphonamides may be desirable. They may be effective in eradicating the carrier state of Str. pyogenes, Bordetella pertussis, Corynebacterium diptheriae, and Neisseria meningitidis. Macrolides provide alternative therapy for the prophylaxis of recurrent acute rheumatic fever and of infective endocarditis after dental treatment. The cure rate with macrolides of streptococcal skin infections and of minor staphylococcal infections is equal to that achieved with penicillins. In diarrhoea due to Campylobacter jejuni, the administration of macrolides shortens the duration of the faecal excretion of organisms and may give clinical improvement in severe disease. Macrolides are the drugs of choice for infections due to Chlamydia trachomatis in pregnancy and for Haemophilus ducreyi infections. They are effective alternative therapy to benzylpenicillin for the treatment of N. gonorrhoeae and Treponema pallidum infections.


Systolic hypertension.
Approximately one-third of the adult population has hypertension. Large-scale clinical trials have convincingly demonstrated that the treatment of isolated systolic and systolic/diastolic hypertension reduces rates of total mortality, cardiovascular mortality, and stroke in older adults, yet control of systolic hypertension remains poor. This article reviews systolic blood pressure as a cardiovascular risk factor and discusses effective management of elevated systolic blood pressure. The role of combination therapy is emphasized, focusing on the combination of a calcium-channel blocker and an angiotensin-converting enzyme inhibitor. In addition to blood pressure-lowering efficacy, the combination of these two classes of metabolically neutral agents may offer benefit in terms of tolerability and cognitive function.


[Type 2 diabetes mellitus could predict a sub-optimal weight loss after bariatric surgery].
bariatric surgery does not benefit all patients. Identifying severely obese patients who will succeed after bariatric surgery remains a challenge for the transdiciplinary team. The objective of this retrospective study was to analyze preoperative dietary factors that could predict a successful weight loss after bariatric surgery. the retrospective study included patients undergoing laparoscopic Roux-en-Y gastric bypass surgery as a procedure for severe obesity (n = 84). Patient demographics, comorbidities, dietary factors, and weight loss results were extracted from the electronic medical record. type 2 diabetes mellitus (DM2) was associated with suboptimal weight loss after laparoscopic Roux-en-Y gastric bypass surgery. although bariatric surgery continues being the most effective treatment for patients with severe obesity, developing strategies to improve and maintain weight loss, especially in patients with DM2, is fundamental. Assessing the dietary characteristics of candidates for bariatric surgery is crucial.


Silver nano - a trove for retinal therapies.
Pathological retinal angiogenesis (neovascularization) is one of the most feared complications among retinal diseases, leading to visual impairment and irreversible blindness. Recent findings made by us on therapeutic applications of biologically synthesized silver nanoparticles (AgNPs) against VEGF induced retinal endothelial cells, elucidates the effectual inhibitory activities of AgNPs over the downstream signaling pathways (Src and AKT/PI3K) leading to retinal angiogenesis. The current review focuses on the imperative role of VEGF induced angiogenesis in the development of retinal neovascularization and despite the fact that several VEGF targeting ocular drugs are available; the review examines the need for a cost economic alternative, thereby suggesting the role of AgNPs as an emerging economic ocular drug for retinal therapies. The current technologies available for the development of targeted and controlled release of drugs is being discussed and a model has been proposed for the amenable targeting mechanism, by which Poly gamma glutamic acid (PGA) capsulated AgNPs conjugated to cyclic RGD peptides carry out a sustained controlled release specifically targeting the neovascularization cells and induce apoptosis unaffecting the normal retinal cells. These constructs consequently affirm the futuristic application of silver nanoparticles as a boon to ocular therapies.


Trichophyton erinacei in pet hedgehogs in Spain: Occurrence and revision of its taxonomic status.
Hedgehogs have increased in popularity as pets in Spain but there are no data of infection rates of this exotic animal with dermatophytes in our country. During the period of 2008-2011 a total of 20 pet hedgehogs (19 African pygmy hedgehogs and 1 Egyptian long-eared hedgehog) suspected of having dermatophytoses were studied. This is the first survey of the occurrence of T. erinacei in household hedgehogs in Spain. The T. erinacei infection rate was 50% (9 out of 19 African pygmy hedgehogs, and the one Egyptian long-eared hedgehog surveyed). Morphological identification of the isolates was confirmed by molecular analysis. All the strains had the same ITS sequence and showed 100% sequence similarity to T. erinacei type strain CBS 511.73 (AB 105793). The Spanish isolates were confirmed as T. erinacei urease positive. On the basis of ITS sequences, T. erinacei is a species close to but separate from the taxa included in the A. benhamiae complex. Review of the current literature on DNA-based methods for identification of species included in this complex has highlighted the urgent need to reach a consensus in species circumscription and classification system accepted by all mycologists.


An Unusual Presentation of Pyloric Stenosis: A Case Report.
A full-term newborn female presented with non-bilious emesis immediately after feeding and abdominal distension on day one of life with neither palpable abdominal mass nor electrolyte derangements. The baby was initially admitted to rule out gastrointestinal obstruction versus sepsis as a cause of vomiting and abdominal distension. Initial imaging studies involving an upper gastrointestinal (GI) series showed obstruction at the level of the duodenum, but it was only during surgical exploration that the diagnosis of infantile hypertrophic pyloric stenosis was made. This case report highlights the atypical presentation of pyloric stenosis and the need to investigate cases of vomiting immediately after feeding in a newborn with ultrasonography at the least to minimize complications.


Random Forest Refinement of Pairwise Potentials for Protein-Ligand Decoy Detection.
An accurate scoring function is expected to correctly select the most stable structure from a set of pose candidates. One can hypothesize that a scoring function's ability to identify the most stable structure might be improved by emphasizing the most relevant atom pairwise interactions. However, it is hard to evaluate the relevant importance for each atom pair using traditional means. With the introduction of machine learning (ML) methods, it has become possible to determine the relative importance for each atom pair present in a scoring function. In this work, we use the Random Forest (RF) method to refine a pair potential developed by our laboratory (GARF; Zhang , Z. J. Chem. Theory Comput. 2018 , 14 , 5045 ) by identifying relevant atom pairs that optimize the performance of the potential on our given task. Our goal is to construct a ML model that can accurately differentiate the native ligand binding pose from candidate poses using a potential refined by RF optimization. We successfully constructed RF models on an unbalanced data set with the "comparison" concept, and the resultant RF models were tested on CASF-2013 ( Li , Y. J. Chem. Inf.Model. 2014 , 54 , 1700 ). In a comparison of the performance of our RF models against 29 scoring functions, we found that our models outperformed the other scoring functions in predicting the native pose. In addition, we created two artificially designed potential function sets to address the importance of the GARF potential in the RF models: (1) a scrambled probability function set, which was obtained by mixing up atom pairs and probability functions in GARF, and (2) a uniform probability function set, which shares the same peak positions with GARF but has fixed peak heights. The results of accuracy comparison from RF models based on the scrambled, uniform, and original GARF potential clearly showed that the peak positions in the GARF potential are important while the well depths are not. All code and data used in this work are available at https://github.com/JunPei000/random_forest_protein_ligand_decoy_detection .


[The concept of cancer, especially during the nineteenth century].
The role of the black bile in the genesis of cancer was 200 years ago replaced by the lymph. The terminology was, however, confusing. The antique concept of humoral pathology then still existed. When the cellular pathology was introduced in the middle of the 19th century the interest in the genesis of cancer was focused on connective tissue. There were also some attempts linking the lymph to connective tissue in understanding cancer development.


[Recent advances and problems in peripheral arterial reconstruction].
Recent advances in the field of peripheral arterial reconstruction have been remarkable. These advances are mainly derived from the development of diagnostic technology such as Doppler ultrasound analysis, further refinement of surgical technique including surgical instruments and materials, and naturally improvement of patient care in the pre-, peri- and postoperative period. During the past 14 years we have performed peripheral arterial reconstruction in 1,200 cases (1,660 limbs) mainly with occlusive lesion due to arteriosclerosis obliterans. In our hand, aorto-iliac occlusive lesion has been routinely bypassed with Dacron prostheses and the secondary patency rate at eleven years reached 96.5%. The main problems encountered in this region were anastomotic aneurysm in the femoral artery (3.9%) and graft infection (1.2%). In the infrainguinal region there are still problems to be solved, although the primary (secondary) 5 year patency rates of reversed vein graft as well as in situ vein graft including femoro-popliteal below knee and femoro-crural bypasses have exceeded 70% (85%). First, there is no graft material comparable to the autogenous vein (AVG). Secondly, many of the AVG should suffer occlusive pathological changes from the environment in the long term following surgery. At the present time, we have no effective method to solve these problems, therefore we should follow up the patients heedfully to maintain the graft patency as well as to improve their quality of life and prognosis.