Motor recovery and antidepressant effects of repetitive transcranial magnetic stimulation on Parkinson disease: A PRISMA-compliant meta-analysis.
Clinical symptoms of Parkinson disease (PD) included both motor and nonmotor symptoms. Previous studies indicated inconsistent results for the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on motor and depression in PD. The study aimed to assess the therapeutic effect of rTMS with different mode on motor and depression in PD using a meta-analysis. Articles published before July 2019 were searched based on the following databases (PubMed, Web of Science, Medline, Embase, and Google Scholar). The therapeutic effects were assessed by computing the standard mean difference (SMD) and a 95% confidence interval (CI). The present study indicated that rTMS showed significant therapeutic effects on motor in PD (SMD 2.05, 95% CI 1.57-2.53, I = 93.0%, P < .001). Both high-frequency (HF)-rTMS and low-frequency rTMS showed therapeutic effects on motor; stimulation over primary motor cortex (M1), supplementary motor area, dorsal lateral prefrontal cortex (DLPFC) or M1+DLPFC showed therapeutic effects; stimulation during "on" and "off" states showed therapeutic effects; the study showed long-term effect of rTMS on motor in PD. In addition, the study indicated that rTMS showed significant therapeutic effects on depression in PD (SMD 0.80, 95% CI 0.31-1.29, I = 89.1%, P < .001). Stimulation over left DLPFC showed significant therapeutic effects on depression in PD; only HF-rTMS showed therapeutic effects; ages, disease durations, numbers of pulses, and session durations displayed influence on the therapeutic effects of rTMS on depression in PD; the therapeutic effects on depression was long term. However, no significant difference in therapeutic effects on depression were showed between rTMS and oral Fluoxetine (SMD 0.74, 95% CI -0.83 to 2.31, I = 92.5%, P < .001). The rTMS showed significant therapeutic effects on motor in PD. HF-rTMS showed a significant positive antidepressive effect in PD only over DLPFC.


Vaccine effectiveness of the 7-valent and 13-valent pneumococcal conjugate vaccines in Canada: An IMPACT study.
We used an indirect cohort analysis in children under 5 years-old from 2002 to 2018 to examine vaccine effectiveness (VE) of the 7-valent pneumococcal conjugate vaccine (PCV) (3 + 1 doses in most regions) and the 13-valent PCV (2 + 1 doses in all regions) against invasive pneumococcal disease (IPD) caused by vaccine serotypes in children in Canada. Cases were identified from the Canadian Immunization Monitoring Program ACTive (IMPACT), a national active surveillance network of 12 tertiary care pediatric hospitals that represent about 90% of tertiary care hospital beds in Canada. There were 1477 children evaluated for PCV7 VE and 489 for PCV13 VE. PCV7 VE in children with vaccination up to date for their age was 96% (95% CI: 67-99%) after a single dose and 95% (95% CI: 92-97%) after ≥2 doses. The VE was 91% (95% CI: 85-94%) in children who had received doses but were not up to date for their age. PCV13 VE in children with vaccinations up to date for their age was 55% (95% CI: 28-72%) after ≥2 doses. The PCV13-vaccine serotypes causing breakthrough IPD in children up to date for their age with 2+ doses of PCV13 were 3 (13/27, 48.2%),19A (11/27, 40.7%), and 19F (3/27, 11.1%). When serotype 3 and 19A were excluded, the VE of PCV13 against the remaining vaccine serotypes was 89% (95% CI: 64-97%) in children with ≥2 doses. The lower VE of PCV13 may be due to lower effectiveness against serotypes 3 and 19A, which could be influenced by the change in dosing schedule from 4 to 3 total doses with the introduction of PCV13, combined with vaccine uptake of 80%. However, PCV13 still provides the benefit of protection against more serotypes than PCV7, and good VE against all serotypes except 3 and 19A.


Effects of magnesium, manganese and adenosine triphosphate ions on pyruvate carboxylase from baker's yeast.
1. Pyruvate carboxylase from baker's yeast acts with either MgATP(2-) or MnATP(2-) as substrate. The optimum pH for the enzyme reaction is 8.0 with MgATP(2-) and 7.0 with MnATP(2-). 2. When the reaction velocity is plotted against MgATP(2-) (or MnATP(2-)) concentration slightly sigmoid curves are obtained, either in the presence or in the absence of acetyl-CoA (an allosteric activator). In the presence of excess of free Mg(2+) (or Mn(2+)) the curves turn into hyperbolae, whereas in the presence of excess of free ATP(4-) the apparent sigmoidicity of the curves increases. 3. The sigmoidicity of the plots of v against MgATP(2-) (or MnATP(2-)) concentration can be explained by the inhibitory effect of free ATP(4-), the concentration of which, in the experimental conditions employed, is significant and varies according to the total concentration of the ATP-magnesium chloride (or ATP-manganese chloride) mixture. Free ATP(4-) behaves as a negative modifier of yeast pyruvate carboxylase. 4. The effect of high concentrations of Mg(2+) (or Mn(2+)) on the kinetics of yeast pyruvate carboxylase can be explained as a deinhibition with respect to ATP(4-), instead of a direct enzyme activation. 5. At pH6.5 manganese chloride is more effective than magnesium chloride as enzyme activator even in the presence of a great excess (16-fold) of the latter. This is consistent with a significant contribution of the MnATP(2-) complex to the activity of yeast pyruvate carboxylase, in medium conditions resembling those existing inside the yeast cell (pH6.25-6.75; 12mm-magnesium chloride and 0.75mm-manganese chloride). 6. The physiological significance of the enzyme inhibition by free ATP(4-) is doubtful since the Mg(2+) and Mn(2+) concentrations reported to exist inside the yeast cell are sufficient to decrease ATP(4-) concentrations to ineffective values.


Possible role of acetyl-CoA in the inhibition of CoA biosynthesis by ethanol in rats.
Ethanol, both administered to rats in vivo and added to cultured hepatocyte incubations, inhibits the conversion of [14C]pantothenate to coenzyme A (CoA). Data suggesting that the inhibition by ethanol involves its oxidation to acetate were obtained with rat hepatocytes maintained in primary culture. Ethanol, acetaldehyde and acetate were approximately equally effective inhibitors of [14C]pantothenate conversion to CoA (46-71%) and had no effect on uptake of [14C]pantothenate by hepatocytes. In the presence of saturating levels of acetate, acetaldehyde had no additional inhibitory effect. Cyanamide and diethyldithiocarbamate decreased the inhibition by acetaldehyde at the same concentration (10 microM), which saturated their ability to inhibit acetaldehyde oxidation. Studies with an isolated pantothenate kinase preparation showed that, of the ethanol metabolites, only acetyl-CoA was an effective inhibitor. Acetate and butyrate, which were both inhibitors of [14C]pantothenate conversion to CoA, increased the acetyl-CoA and decreased the free, unacylated CoA (CoASH) content of the cultured hepatocytes. The data were consistent with a mechanism for the inhibitory effect of ethanol that involves inhibition of pantothenate kinase by acetyl-CoA, but did not exclude a possible role of additional regulatory factors.


Intracardiac operations with extracorporeal circulation under acupuncture anaesthesia.
The method and clinical materials of 107 cases of direct vision intracardiac operation with extracorporeal circulation under acupuncture anaesthesia, together with a preliminary consideration of selection of patients, are reported. The most obvious benefit of acupuncture anaesthesia is the marked reduction or the absence of various post-operative respiratory symptoms and complications. Improvements on surgical technique for better result of acupuncture anaesthesia are discussed. It is stressed that further investigations for better analgesic effect are obligatory.


A nuclear factor containing the leucine-rich repeats expressed in murine cerebellar neurons.
A nuclear protein, termed leucine-rich acidic nuclear protein (LANP), has been isolated from among rat cerebellar proteins whose expression was transiently increased during an early stage of postnatal development. The amino acid sequence, deduced from its cDNA, showed that LANP contains 247 amino acids consisting of two distinct structural domains: the N-terminal domain characterized by "leucine-rich repeat," which is found in many eukaryotic proteins and which potentially functions in mediating protein-protein interactions, and the C-terminal domain characterized by a cluster of acidic amino acids with a putative nuclear localization signal. Immunohistochemical study using an antibody against LANP revealed that the protein is localized mainly in nuclei of Purkinje cells. In the rat cerebellum on postnatal day 7, LANP mRNA was expressed moderately in the external granule and Purkinje cells and weakly in the internal granule cells. The expression in these cells, especially in Purkinje cells, increased in the second postnatal week and thereafter decreased to an adult level. The structural characteristics, localization, and the stage- and cell type-specific expression suggest a potential role of LANP in a signal transduction pathway that directs differentiation of cerebellar neurons.


Diagnosis of Pseudoexfoliation Syndrome in Pseudophakic Patients.
The aim of this study was to evaluate the sensitivity and specificity of pseudoexfoliation syndrome diagnosis in pseudophakic patients and potential means of improving it. This prospective, nonrandomized study comprised 41 consecutive patients (41 eyes) scheduled for cataract surgery at a tertiary medical center during 2016 and 2017. Preoperatively, all patients underwent a detailed slit-lamp examination, including gonioscopic assessment of the iridocorneal angle. The examination was performed by a glaucoma specialist who completed an assessment form documenting the presence/absence of clinical signs of pseudoexfoliation syndrome. It was repeated 1-2 weeks postoperatively by a second, masked, glaucoma specialist. Sixteen patients (39.0%) were diagnosed with pseudoex-foliation syndrome preoperatively. The diagnosis was confirmed postoperatively in 11/16 patients (68.8% sensitivity) and in an additional patient not diagnosed preoperatively (96% specificity). The ability to diagnose pseudoexfoliation syndrome postoperatively was significantly worse than preoperatively (Z = 12.161, p < 0.0001). Pupillary border deposits (75% of cases) and the Sampaolesi line (83.3%) were the cornerstones of the postoperative diagnosis; anterior capsular deposits were evident in only 41.6% of cases diagnosed postoperatively (31.3% of the originally diagnosed cases). Underdiagnosis of pseudoexfoliation syndrome is common in pseudophakic patients and may have significant implications for future management. Careful attention to pupillary border anatomy and meticulous gonioscopic assessment of the iridocorneal angle are essential for accurate diagnosis. Preoperative documentation of pseudoexfoliation syndrome could help prevent this diagnostic pitfall.


Conducted noise analysis and protection of 45 kJ/s, ±50 kV capacitor charging power supply when interfaced with repetitive Marx based pulse power system.
Pulse power systems with highly dynamic loads like klystron, backward wave oscillator (BWO), and magnetron generate highly dynamic noise. This noise leads to frequent failure of controlled switches in the inverter stage of charging power supply. Designing a reliable and compatible power supply for pulse power applications is always a tricky job when charging rate is in multiples of 10 kJ/s. A ±50 kV and 45 kJ/s capacitor charging power supply based on 4th order LCLC resonant topology has been developed for a 10 Hz repetitive Marx based system. Conditions for load independent constant current and zero current switching (ZCS) are derived mathematically. Noise generated at load end due to dynamic load is tackled effectively and reduction in magnitude noise voltage is achieved by providing shielding between primary and secondary of high voltage high frequency transformer and with LCLC low pass filter. Shielding scales down the ratio between coupling capacitance (Cc) and the collector-emitter capacitance of insulated gate bi-polar transistor switch, which in turn reduces the common mode noise voltage magnitude. The proposed 4th order LCLC resonant network acts as a low pass filter for differential mode noise in the reverse direction (from load to source). Power supply has been tested repeatedly with 5 Hz repetition rate with repetitive Marx based system connected with BWO load working fine without failure of single switch in the inverter stage.


An outbreak of viral hepatitis in Jodhpur city of Rajasthan.
An outbreak of Viral hepatitis occurred in Jodhpur city of Rajasthan during April to June, 1994. The attack rate was 3.04 per cent among 0-14 years age group and 5.49% among the age group above 15 years, the overall attack rate being 4.5 per cent. Males were more affected than females. Epidemiological and serological findings suggest that the outbreak was due to enterically transmitted Non A Non B virus. The source of infection was drinking water contaminated with sewage.


Ancestry and evolution of seasonal migration in the Parulidae.
Seasonal migration in birds is known to be highly labile and subject to rapid change in response to selection, such that researchers have hypothesized that phylogenetic relationships should neither predict nor constrain the migratory behaviour of a species. Many theories on the evolution of bird migration assume a framework that extant migratory species have evolved repeatedly and relatively recently from sedentary tropical or subtropical ancestors. We performed ancestral state reconstructions of migratory behaviour using a comprehensive, well-supported phylogeny of the Parulidae (the 'wood-warblers'), a large family of Neotropical and Nearctic migratory and sedentary songbirds, and examined the rates of gain and loss of migration throughout the Parulidae. Counter to traditional hypotheses, our results suggest that the ancestral wood-warbler was migratory and that losses of migration have been at least as prevalent as gains throughout the history of Parulidae. Therefore, extant sedentary tropical radiations in the Parulidae represent losses of latitudinal migration and colonization of the tropics from temperate regions. We also tested for phylogenetic signal in migratory behaviour, and our results indicate that although migratory behaviour is variable within some wood-warbler species and clades, phylogeny significantly predicts the migratory distance of species in the Parulidae.


KDM3B shows tumor-suppressive activity and transcriptionally regulates HOXA1 through retinoic acid response elements in acute myeloid leukemia.
KDM3B reportedly shows both tumor-suppressive and tumor-promoting activities in leukemia. The function of KDM3B is likely cell-type dependent and its seeming functional discordance may reflect its phenotypic dependence on downstream targets. Here, we first showed the underexpression of KDM3B in acute myeloid leukemia (AML) patients and AML cell lines with MLL-AF6/9 or PML-RARA translocations. Overexpression of KDM3B repressed colony formation of AML cell line with 5q deletion. We then performed global microarray profiling to identify potential downstream targets of KDM3B, notably HOXA1, which was verified by real time PCR and Western blotting. We further showed KDM3B binding at retinoic acid response elements (RARE) but not at the promoter region of HOXA1 gene. KDM3B knockdown resulted in increased mono-methylation but decreased di-methylation of H3K9 at RARE while eschewing the promoter region of HOXA1. Collectively, we found that KDM3B exhibits potential tumor-suppressive activity and transcriptionally modulates HOXA1 expression via RARE in AML.


Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome.
Platelets are essential cellular effectors of hemostasis and contribute to disease as circulating effectors of pathologic thrombosis. These are their most widely known biologic activities. Nevertheless, recent observations demonstrate that platelets have a much more intricate repertoire beyond these traditional functions and that they are specialized for contributions to vascular barrier integrity, organ repair, antimicrobial host defense, inflammation, and activities across the immune continuum. Paradoxically, on the basis of clinical investigations and animal models of disease, some of these newly discovered activities of platelets appear to contribute to tissue injury. Studies in the last decade indicate unique interactions of platelets and their precursor, the megakaryocyte, in the lung and implicate platelets as essential effectors in experimental acute lung injury and clinical acute respiratory distress syndrome. Additional discoveries derived from evolving work will be required to precisely define the contributions of platelets to complex subphenotypes of acute lung injury and to determine if these remarkable and versatile blood cells are therapeutic targets in acute respiratory distress syndrome.


Nanoarchitectonics of biomolecular assemblies for functional applications.
The stringent processes of natural selection and evolution have enabled extraordinary structure-function properties of biomolecules. Specifically, the archetypal designs of biomolecules, such as amino acids, nucleobases, carbohydrates and lipids amongst others, encode unparalleled information, selectivity and specificity. The integration of biomolecules either with functional molecules or with an embodied functionality ensures an eclectic approach for novel and advanced nanotechnological applications ranging from electronics to biomedicine, besides bright prospects in systems chemistry and synthetic biology. Given this intriguing scenario, our feature article intends to shed light on the emerging field of functional biomolecular engineering.


Allergen immunotherapy during the COVID-19 pandemic-A survey of the German Society for Allergy and Clinical Immunology.
When the coronavirus pandemic 2019 (COVID-19) emerged, concerns were also raised regarding the safety of allergen immunotherapy (AIT). The German Society for Allergology and Clinical Immunology (DGAKI) conducted a survey to collect real-world data on the daily routine of administering subcutaneous AIT (SCIT) and sublingual AIT (SLIT) during the COVID-19 pandemic. A web-based retrospective survey using the online platform survio with 26 standardized questions was used to survey physicians treating allergic patients during the pandemic. Three hundred and forty-five physicians who regularly offer and perform AIT in German-speaking countries responded to the questions. 70.4% of the respondents stated that they regularly initiated and dosed up SCIT for inhalant allergies (41.4% venom-SCIT, 73.6% SLIT), and 85.2% of the respondents stated that they continued SCIT for inhalant allergies during the maintenance phase in a regular way (59.1% venom-SCIT, 90.4% SLIT) in healthy patients without current symptoms indicating an infection with COVID-19. With regard to tolerability, there was no evidence for increased occurrence of adverse events in patients without current symptoms of COVID-19 infection during the pandemic. This retrospective study demonstrated adherence to national and international position papers of AIT during the COVID-19 pandemic in German-speaking countries. Besides, the survey has confirmed a good tolerability of AIT for both SCIT and SLIT.


The efficacy and safety of propiverine hydrochloride in patients with overactive bladder symptoms who poorly responded to previous anticholinergic agents.
Objectives. To prospectively examine the efficacy and safety of propiverine hydrochloride in patients with overactive bladder (OAB) symptoms who poorly responded to previous treatment with solifenacin, tolterodine or imidafenacin. Methods. Patients aged ≥20 with persisting OAB symptoms (≥6 in OAB symptom score (OABSS)) even after at least 4-week treatment using solifenacin, tolterodine or imidafenacin were enrolled. Propiverine 20 mg/day was administered for 12 weeks to 70 patients who desired the further improvement of OAB symptoms and 3 who had intolerable adverse events of previous drugs. The OABSS and postvoid residual urine volume (PVR) were determined before and at 4 and 12 weeks of treatment. Results. Of 73 patients enrolled (29 males and 44 females, median age 71 years), 52 completed the protocol treatment. The OABSS was significantly improved by propiverine treatment (9.0 at baseline, 6.2 at 4 weeks, 6.3 at 12 weeks (P < 0.001)). The scores of OAB symptoms (nighttime frequency, urgency and urge incontinence) except daytime frequency also improved significantly. No increase in PVR was observed. The most frequent adverse event was dry mouth (13.7%), followed by constipation (6.8%). Conclusions. Propiverine is useful to improve OAB for patients who poorly respond to solifenacin, tolterodine or imidafenacin.


Age and the human cochlear traveling wave delay.
Cochlear physiologic changes that occur with aging also may affect the mechanics and filtering properties of the cochlea. In studying aging effects, it is also necessary to consider the effects of hearing threshold losses because thresholds generally increase with age, and threshold losses also affect the filtering properties of the cochlea. A distortion product emission (DPE)-based measurement of human cochlear traveling wave delays allows an indirect assessment of the mechanics of the traveling wave and how it might change with age. The cochlear traveling wave delay has been derived from DPE phase measurements using an f1 sweep paradigm (Kimberley, Brown, & Eggermont, 1993). In the present study, traveling wave delay was estimated from DPE phase measurements taken from the left ears of 91 subjects (22 to 78 yr) with auditory thresholds ranging from normal hearing (< or = 25 dB SPL, ANSI 1969) to mild cochlear hearing damage. No one under the age of 65 had hearing losses exceeding 40 dB SPL to 8 kHz. Pure-tone thresholds were determined at eight frequencies through a 4-interval, forced-choice, adaptive-level psychophysical test. DPE phase and amplitude measurements were made at these eight frequencies using CUBeDIS-related software (AT&T Bell Labs). Round-trip traveling wave estimates were calculated from the DPE phase measurements for each of the eight f2 frequencies (places). Traveling wave delays estimated using DPE phase were not significantly affected by mild hearing losses. Traveling wave delay, however, does increase slightly with age. Optimal f2/f1 ratio and associated DPE amplitude also were tested for age or threshold effects. The optimal f2/f1 ratio remained unaffected by age or hearing loss but decreased with increasing frequency. The maximum DPE amplitude decreased with both advancing age and increasing pure-tone threshold, so it was impossible to isolate the contribution of each individual factor. Mild hearing losses do not affect the round-trip traveling wave delay. There is a slight age dependence, however. This may suggest that there are age-related but threshold-independent factors that may alter such properties as basilar membrane stiffness or cochlear fluid composition. The relationship between maximum DPE amplitude and threshold, at the frequencies tested, is a better predictor of hearing thresholds than the DPE amplitude as obtained from a fixed ratio DPE amplitude measurement.


Cortisol levels in the human perilymph after intravenous administration of prednisolone.
Cortisone is used in various inner ear disorders such as sudden hearing loss. However, it is not known if the doses of prednisolone employed in therapy increase the cortisol level in the inner ear. To evaluate the level of cortisol within the perilymph after intravenous administration of 125 and 250 mg of prednisolone, serum and perilymph samples of 29 consecutive patients with clinical otosclerosis subjected to stapedectomy were collected. Cortisol levels were determined by RIA. The perilymphatic cortisol level was significantly increased in the group with 250 mg of prednisolone while the perilymphatic cortisol levels were not significantly different between the control group and the patients treated with 125 mg. Although the therapeutic dose of prednisolone is not known, we conclude that the application of 250 mg has a greater impact on the inner ear than 125 mg.


Double-blind characterization of non-genome-sequenced bacteria by mass spectrometry-based proteomics.
Due to the possibility of a biothreat attack on civilian or military installations, a need exists for technologies that can detect and accurately identify pathogens in a near-real-time approach. One technology potentially capable of meeting these needs is a high-throughput mass spectrometry (MS)-based proteomic approach. This approach utilizes the knowledge of amino acid sequences of peptides derived from the proteolysis of proteins as a basis for reliable bacterial identification. To evaluate this approach, the tryptic digest peptides generated from double-blind biological samples containing either a single bacterium or a mixture of bacteria were analyzed using liquid chromatography-tandem mass spectrometry. Bioinformatic tools that provide bacterial classification were used to evaluate the proteomic approach. Results showed that bacteria in all of the double-blind samples were accurately identified with no false-positive assignment. The MS proteomic approach showed strain-level discrimination for the various bacteria employed. The approach also characterized double-blind bacterial samples to the respective genus, species, and strain levels when the experimental organism was not in the database due to its genome not having been sequenced. One experimental sample did not have its genome sequenced, and the peptide experimental record was added to the virtual bacterial proteome database. A replicate analysis identified the sample to the peptide experimental record stored in the database. The MS proteomic approach proved capable of identifying and classifying organisms within a microbial mixture.


Effects of atorvastatin and insulin in vascular dysfunction associated with type 2 diabetes.
Atorvastatin and insulin have distinct mechanisms of action to improve endothelial function. Therefore, we hypothesized that atorvastatin and insulin therapies alone or in combination could have beneficial effects on endothelium-dependent vascular reactivity, oxidative stress, inflammation and metabolic parameters in Goto-Kakizaki (GK) rats, a model of type 2 diabetes fed with atherogenic diet (GKAD). In parallel with the development of diabetes and lipid profile, the generation of oxidative stress was determined by measurement of lipid peroxides and oxidized proteins and the presence of inflammation was evaluated by assessing C-reactive protein (CRP). Additionally, endothelial dependent and independent vascular sensitivity to acetylcholine and sodium nitroprusside were evaluated. GKAD showed increased carbonyl stress, inflammation, fasting glycemia, dyslipidemia and endothelial dysfunction when compared to control GK rats. Noteworthy, supplementation with insulin deteriorated endothelial dysfunction while atorvastatin induced an improvement. Atorvastatin and insulin therapies in combination improved metabolic parameters, CRP levels and insulin resistance indexes and ameliorated endothelial dysfunction in GKAD rats while they were unable to reduce urinary 8-isoprostranes and plasma carbonyl compounds. The therapeutic association of atorvastatin and insulin provided a better metabolic control with a reduction in endothelial dysfunction in GKAD rats by a mechanism that involves an improvement in systemic inflammation.


IRBIT coordinates epithelial fluid and HCO3- secretion by stimulating the transporters pNBC1 and CFTR in the murine pancreatic duct.
Fluid and HCO3- secretion are vital functions of secretory epithelia. In most epithelia, this entails HCO3- entry at the basolateral membrane, mediated by the Na+-HCO3- cotransporter, pNBC1, and exit at the luminal membrane, mediated by a CFTR-SLC26 transporters complex. Here we report that the protein IRBIT (inositol-1,4,5-trisphosphate [IP3] receptors binding protein released with IP3), a previously identified activator of pNBC1, activates both the basolateral pNBC1 and the luminal CFTR to coordinate fluid and HCO3- secretion by the pancreatic duct. We used video microscopy and ion selective microelectrodes to measure fluid secretion and Cl- and HCO3- concentrations in cultured murine sealed intralobular pancreatic ducts. Short interference RNA-mediated knockdown of IRBIT markedly inhibited ductal pNBC1 and CFTR activities, luminal Cl- absorption and HCO3- secretion, and the associated fluid secretion. Single-channel measurements suggested that IRBIT regulated CFTR by reducing channel mean close time. Furthermore, expression of IRBIT constructs in HEK cells revealed that activation of pNBC1 required only the IRBIT PEST domain, while activation of CFTR required multiple IRBIT domains, suggesting that IRBIT activates these transporters by different mechanisms. These findings define IRBIT as a key coordinator of epithelial fluid and HCO3- secretion and may have implications to all CFTR-expressing epithelia and to cystic fibrosis.


The elderly: the single greatest achievement of mankind.
The single greatest achievement of mankind is very likely the increase in life expectancy which has occurred in the twentieth century. Coupled with a decline in the birth rate worldwide, the mean age of most nations is rapidly increasing and the old (especially the old-old, those 80 years of age and over) represent an increasing percentage of the dependent population of the world. Although the ageing of the population will have ramifications for almost all aspects of society, those concerned with the provision of health care are especially affected. With chronic disease replacing acute illness, and costs of care mounting, health-care providers will require a comprehensive assessment of its older citizens so as to be able to provide cost-effective care across all sites, be that location a hospital or, more frequently, the home. The development of such capabilities is already under way by the InterRA1 group, an international group of investigators.


Paecilomyces lilacinus-induced Scleritis Following Bleb-associated Endophthalmitis after Trabeculectomy.
Paecilomyces lilacinus (P. lilacinus) is a rare cause of fungal scleritis. We herein report a case of P. lilacinus-induced scleritis following bleb-associated endophthalmitis after trabeculectomy that was successfully treated with surgical excision of the affected sclera in combination with antifungal medication. An 85-year-old female underwent trabeculectomy of the left eye. A dellen formed in the corneal periphery due to limbal elevation of the filtering bleb and progressed to an infectious corneal ulcer, leading to blebitis. Eight days after the onset of blebitis, the patient was diagnosed with endophthalmitis, which resolved after vitrectomy. The growth of P. lilacinus was identified on swabs of the conjunctiva and the corneal specimen. Scleritis developed after the resolution of the endophthalmitis, and an early excision of the affected sclera, in addition to antifungal medication, resolved it completely. However, the scleritis recurred in a different region of the left eye. After 7 months of antifungal medication, the left eye showed no residual infection. When treating P. lilacinus-induced scleritis, surgical excision of the affected sclera has been shown to be an effective treatment strategy. Nevertheless, it is possible that the infection may recur in another part of the eyeball after the complete resolution of the primary lesion.


Efficacy of preoperative chemoradiotherapy in patients with cT2N0 distal rectal cancer.
This study was designed to determine the feasibility of preoperative chemoradiotherapy (PCRT) in patients with clinical T2N0 distal rectal cancer. Patients who underwent surgery for clinical T2N0 distal rectal cancer between January 2008 and December 2016 were included. Patients were divided into PCRT and non-PCRT groups. Non-PCRT patients underwent radical resection or local excision (LE) according to the surgeon's decision, and PCRT patients underwent surgery according to the response to PCRT. Patients received 50.0 to 50.4 gray of preoperative radiotherapy with concurrent chemotherapy. Of 127 patients enrolled, 46 underwent PCRT and 81 did not. The mean distance of lesions from the anal verge was lower in the PCRT group (P=0.004). The most frequent operation was transanal excision and ultralow anterior resection in the PCRT and non-PCRT groups, respectively. Of the 46 patients who underwent PCRT, 21 (45.7%) achieved pathologic complete response, including 15 of the 24 (62.5%) who underwent LE. Rectal sparing rate was significantly higher in the PCRT group (11.1% vs. 52.2%, P<0.001). There were no significant differences in 3- and 5-year overall survival and recurrence-free survival regardless of PCRT or surgical procedures. PCRT in clinical T2N0 distal rectal cancer patients increased the rectal sparing rate via LE and showed acceptable oncologic outcomes. PCRT may be a feasible therapeutic option to avoid abdominoperineal resection in clinical T2N0 distal rectal cancer.


[Acute adrenal hemorrhage in newborn infants: the importance of early diagnosis (author's transl)].
Two case reports demonstrate the importance of an early diagnosis for the therapy of adrenal hemorrhage. In the first case with unilateral hemorrhage, the hemorrhage as such was of importance. In the second case with bilateral hemorrhage, the course was dominated by acute adrenal insufficiency with circulatory collapse and major salt loss. The diagnosis was supported by the typical changes in electrolyte levels as well as by radiography, and endocrinological results. With early therapy (in the first instance by surgery, and in the latter by substitution of corticosteroids), both children safely passed the critical period. In the second child ACTH administration did not, in the first phase of the disease, result in a significant rise of plasma cortisol. However, two months later there was a normal rise of the cortisol level following ACTH administration. From this observation we conclude that a favourable regeneration of the adrenal glands has resulted.


Multiple sclerosis-lymphocyte transformation with multiple sclerosis and normal brain myelin basic protein and subcellular fractions.
Possible sensitisation of peripheral blood mononuclear cells from multiple sclerosis (MS) patients was studied in the presence of both normal and MS brain subcellular fractions. Myelin, synaptosomal and microsomal fractions and myelin basic protein were prepared by sucrose density gradient centrifugation from normal and MS brain. These preparations were added to mononuclear cell microcultures from the peripheral blood of nine acute and six chronic MS patients, 10 patients with other neurological diseases and 10 normal subjects. There was no significant increment in the peripheral blood mononuclear cell transformation of any of the acute MS patients with any of the fractions. Therefore there is no evidence that immunity to antigens in any of the fractions of MS or normal brain is of primary pathogenetic importance. A small increment in peripheral blood mononuclear cell transformation in the presence of several fractions was observed in two of six chronic MS patients, which might indicate the development of a secondary immune response after prolonged disease.


Experimentally induced rhythmic jaw muscle activities during non-rapid eye movement sleep in freely moving guinea pigs.
Rhythmic jaw muscle activities frequently occur during non-rapid eye movement sleep in patients with sleep bruxism. The present study aimed to investigate the response characteristics of the masticatory rhythm generation during non-rapid eye movement sleep in animals. Eleven guinea pigs were surgically prepared for polygraphic recordings by electromyography, electrooculography, electroencephalography and electrocardiography with the implantation of a stimulating electrode. Repetitive electrical microstimulations at three intensities were applied to the corticobulbar tract under freely moving conditions. The rhythmic electro-myographic responses of the digastric and masseter muscles were scored and analysed. Changes in cortical electro-encephalographic power and heart rate in association with these stimulations were quantified. Microstimulations to the corticobulbar tract induced rhythmic jaw muscle activities in digastric muscles, occasionally with masseter activities during wakefulness and non-rapid eye movement sleep. The response rate of rhythmic jaw muscle activities was significantly lower (p < 0.01) and the response latency was significantly longer (p < 0.01) during non-rapid eye movement sleep than during wakefulness. At higher stimulus intensities, the response rate increased and response latency decreased. The mean burst intervals of the digastric and masseter muscles were similar regardless of vigilance states and stimulus intensities. Induced rhythmic jaw muscle activities during non-rapid eye movement sleep were followed by a transient decrease in delta power and increases in beta power and heart rate. During non-rapid eye movement sleep, the masticatory motor system is able to generate rhythmic outputs to the jaw muscles in response to facilitatory inputs although the responsiveness was decreased from wakefulness.


Deep Venous Thrombosis and Bilateral Pulmonary Embolism Revealing Silent Celiac Disease: Case Report and Review of the Literature.
Celiac disease (CD) is a systemic, chronic autoimmune disease that occurs in genetically predisposed individuals following dietary gluten exposure. CD can present with a wide range of gastrointestinal and extraintestinal manifestations and requires lifelong adherence to a gluten-free diet [GFD]. Venous thromboembolism (VTE) as a presentation of celiac disease is unusual and rarely reported. We present a case of a 46-year-old man who was admitted for shortness of breath and pleuritic chest pain and was found to have iron deficiency anemia, deep venous thrombosis, and bilateral pulmonary emboli (PE). After work-up for his anemia, the patient was diagnosed with CD. Comprehensive investigation for inherited or acquired prothrombotic disorders was negative. It is becoming increasingly recognized that CD is associated with an increased risk for VTE. PE, however, as a presentation of CD is exceedingly rare and to the best of our knowledge this is the third case report of such an occurrence and the only case report of a patient from North America. It is important to recognize that the first symptoms or signs of celiac disease might be extraintestinal. Furthermore, VTE as a presentation of CD is rare but life-threatening.


Description of Neoxantholinus koghianus sp. n. and its larva from New Caledonia (Coleoptera, Staphylinidae, Xantholinini).
Neoxantholinus koghianus sp. n. (Coleoptera, Staphylinidae, Xantholinini) and the detailed external structure of its late (L2-3) and early (L1) larval instars from New Caledonia are described and illustrated. The morphological differences between L1 and L2-3 of N. koghianus sp. n. involve four characters. Diagnostic larval characters for the genus Neoxantholinus are given for the first time.


Phosphines as Efficient Dioxygen Scavengers in Nitrous Oxide Sensors.
A current challenge for development of amperometric sensors for the greenhouse gas nitrous oxide (N2O) is their sensitivity toward dioxygen and trace water. The need for aqueous dioxygen scavengers in front of the sensor implies a background signal from penetrating water vapor. In this paper, we introduce substituted phosphines as dioxygen scavengers and demonstrate the application in a dioxygen-insensitive N2O sensor. Suitably substituted phosphines have been synthesized to achieve good solubility properties in the electrochemically inert solvent propylene carbonate. Several sensors with and without physical separation of the sensing and dioxygen scavenging compartments were made and compared to current commercial sensors. The use of phosphines soluble in organic solvents as dioxygen scavengers yielded a higher sensitivity, albeit with longer response time. Proof-of-concept N2O sensors without the physically separated dioxygen scavenger chamber showed a greatly enhanced sensitivity with a comparable response time, thus demonstrating the possibility for greatly simplified sensor construction.


No Relationship Between Binocular Rivalry Rate and Eye-Movement Profiles in Healthy Individuals: A Bayes Factor Analysis.
Binocular rivalry (BR) is an intriguing phenomenon in which conflicting images are presented, one to each eye, resulting in perceptual alternations between each image. The rate of BR has been proposed as a potential endophenotype for bipolar disorder because (a) it is well established that this highly heritable psychiatric condition is associated with slower BR rate than in controls, and (b) an individual's BR rate is approximately 50% genetically determined. However, eye movements (EMs) could potentially account for the slow BR trait given EM anomalies are observed in psychiatric populations, and there has been report of an association between saccadic rate and BR rate in healthy individuals. Here, we sought to assess the relationship between BR rate and EMs in healthy individuals (N = 40, mean age = 34.4) using separate BR and EM tasks, with the latter measuring saccades during anticipatory, antisaccade, prosaccade, self-paced, free-viewing, and smooth-pursuit tasks. No correlation was found between BR rate and any EM measure for any BR task (p > .01) with substantial evidence favoring this lack of association (BF(01) > 3). This finding is in contrast to previous data and has important implications for using BR rate as an endophenotype. If replicated in clinical psychiatric populations, EM interpretations of the slow BR trait can be excluded.


Coulomb Explosion of Multi-charged Atomic Alkaline Metal Clusters.
In the present work, a computational study of the Coulomb explosions of atomic metal clusters of the type X82+ was carried out, X = (Li-Cs). The work was done within the Kohn-Sham methodology using the Born-Oppenheimer molecular dynamics approximation. The dominant fission channels were established and the electron bonding patterns were analyzed with the help of the Electron Localization Function (ELF). A simple theoretical model was developed to understand and describe, in a qualitatively way, the main physical mechanism involved in the fission of these multicharged clusters. It has been found that the most possible fragments after explosion are the same considering the dynamics or the thermodynamics results. The bonds breaking and formation are well depicted by the ELF, and the main physical effects are well described by the developed model.


Myricetin against myocardial injury in rat heat stroke model.
Heat stroke-induced mortality is rising across the globe. So, the design of prophylactic and/or therapeutic modalities for heat stroke is pressing need. The common plant derived flavonoid exhibits strong anti-oxidant and anti-inflammatory activities; however, its effects in heat stroke remain unknown. The study aimed to investigate the cardioprotective effects of myricetin on heat stroke induced acute myocardial injury as well as lethality in rats and to explore the underlying mechanisms. Myocardial injury was induced by subjecting the anesthetized rats to a high ambient temperature of 43 °C for 70 min. An intragastrical dose of myricetin (5-25 mg/kg body weight) was given to rats once per day for one week prior to the start of heat stress. Heat shock protein 72 antibodies was given intraperitoneally to rats 24 h before the start of heat stress. Myocardial injury severity was estimated by determing myocardial damage scores, myocardial injury indicators, myocardial oxidative and inflammatory factors. Western blot analysis was used for cardiac expression of heat shock protein (HSP)72. Significant (P < 0.05) up-regulation of HSP-72 after chronic administration of myricetin coincided with significant (P < 0.05) reduction in hyperthermia, hypotension, cardiac inflammatory and oxidative damage and lethality. Inhibition of HSP-72 showed a significant (P < 0.05) reversal in the cardiaprotection as well as survival. Our results indicate that myricetin diminishes myocardial injury as well as lethality in heat stroke by up-regulating HSP-72 and show promise as a novel prevention therapeutic for heat stroke.


Multiple splicing signals control alternative intron retention of bovine growth hormone pre-mRNA.
A fraction of bovine growth hormone (bGH) pre-mRNA undergoes alternative splicing in which the last intron is retained and transported to the cytoplasm. Our goal was to characterize the cis-acting signals in bGH pre-mRNA that collectively determine the distribution between intron splicing and intron retention. We now demonstrate that the balance between splicing and intron retention in cytoplasmic mRNA is primarily determined by the interaction of three splicing signals and the degree to which these signals deviate from consensus splicing signals. Intron retention requires the presence of both suboptimal 5'- and 3'-splice sites. Mutation of either splice site toward consensus leads to complete splicing of the intron. In the presence of both wild-type, suboptimal splice sites, efficient splicing of this intron is ensured by the presence of a third splicing element, a purine-rich exonic splicing enhancer (ESE). Although strong ESEs can be contained within very small sequences, the bGH ESE activity appears to be composed of multiple sequences spread throughout a 115-nucleotide region of exon 5. Consequently, the final ratio of splicing to intron retention depends on the balance between the relative strengths of each of these three splicing signals, which still allow intron-containing coding sequences to be transported to the cytoplasm.


Prevalence of Plasmodium falciparum and Non-falciparum Infections by Photo-Induced Electron Transfer-PCR in a Longitudinal Cohort of Individuals Enrolled in a Mass Drug Administration Trial in Southern Province, Zambia.
Malaria burden in Zambia has significantly declined over the last decade because of improved coverage of several key malaria interventions (e.g., vector control, case management, bed net distributions, and enhanced surveillance/responses). Campaign-based mass drug administration (MDA) and focal MDA (fMDA) were assessed in a trial in Southern Province, Zambia, to identify its utility in elimination efforts. As part of the study, a longitudinal cohort was visited and tested (by PCR targeting the 18s rRNA and a Plasmodium falciparum-specific rapid diagnostic test [RDT] from SD Bioline) every month for the trial duration (18 months). Overall, there was high concordance (> 97%) between the PCR and RDT results, using the PCR as the gold standard. The RDTs had high specificity and negative predictive values (98.5% and 98.6%, respectively) but low sensitivity (53.0%) and a low positive predictive value (53.8%). There was evidence for persistent antigenemia affecting the low specificity of the RDT, while false-negative RDTs were associated with a lower parasite density than true positive RDTs. Plasmodium falciparum was the dominant species identified, with 98.3% of all positive samples containing P. falciparum. Of these, 97.5% were mono-infections and 0.8% coinfections with one other species. Plasmodium malariae was found in 1.4% of all positive samples (50% mono-infections and 50% coinfections with P. falciparum), whereas Plasmodium ovale was found in 1.1% of all positive samples (90% mono-infections and 10% coinfections with P. falciparum). Although MDA/fMDA appeared to reduce P. malariae prevalence, P. ovale prevalence appeared unchanged.


A conservative approach for restoring anterior guidance: a case report.
One of the most common dental problems in today's clinics is tooth wear, specifically when related to bruxism. In such cases, the esthetics of anterior teeth may be compromised when excessive wear to the incisal surfaces occurs. Anterior tooth wear resulting from parafunctional bruxism can be conservatively treated with the use of direct resin composite restorations. This restorative approach has the advantages of presenting good predictability, load resistance, acceptable longevity, preservation of healthy dental tissues, and lower cost when compared with indirect restorations. The use of resin composites to solve esthetic problems, however, requires skill and practice. Thus, the present article demonstrates a conservative approach for restoring the esthetics and function of worn anterior teeth with the aid of direct resin composite restorations and selective occlusal adjustment. A conservative approach to restore anterior teeth with excessive wear is possible with direct resin composites.


Facile synthesis of gold nanoparticle (AuNP)-carbon nanotube (CNT) hybrids through an interfacial Michael addition reaction.
A CNT-AuNP hybrid has been synthesized through the Michael addition reaction between thiol-functionalized single-wall CNT and small water-soluble Maleimide-AuNP. The resilience and stability of this hybrid nanosystem is ensured by a covalent bond linking the nanoparticle to the CNT and by the fact that the functionalization reaction involves the organic shell of the AuNP and not its metallic core.


Identification of marker proteins for Bacillus anthracis using MALDI-TOF MS and ion trap MS/MS after direct extraction or electrophoretic separation.
Direct extraction of bacterial vegetative cells or spores followed by matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI TOF MS) has become popular for bacterial identification, since it is simple to perform and mass spectra are readily interpreted. However, only high-abundance proteins that are of low mass and ionize readily are observed. In the case of B. anthracis spores, small acid-soluble spore proteins (SASPs) have been the most widely studied. Additional information can be obtained using tandem mass spectrometry (MS-MS) to confirm the identity of proteins by sequencing. This is most readily accomplished using ion trap (IT) MS-MS. However, enzymatic digestion of these proteins is needed to generate peptides that are within the mass range of the ion trap. The use of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), or other forms of electrophoresis, allows one to focus on specific proteins of interest (e.g. the high mass exosporium glycoproteins BcIA and BcIB) that provide additional species- and strain-specific discrimination.


Frequency of Trypanosoma cruzi parasitemia among infected blood donors with a potential association between parasite lineage and transfusion transmission.
Trypanosoma cruzi is endemic to the Americas where it demonstrates multiple lineages over a vast geographic range (i.e., United States to Argentina). These lineages possess divergent geographic and biologic characteristics, including variations in disease manifestations. Herein, we report the frequency of parasitemia among seropositive US blood donors and the potential association between parasite lineage and transfusion transmission. Blood donors identified as T. cruzi seropositive during screening were enrolled in follow-up studies, including hemoculture testing and a risk factor questionnaire. Positive hemocultures were expanded to obtain sufficient parasites for molecular lineage determination and analysis. Country of birth, obtained from the questionnaire, was used to predict parasite lineage in the absence of demonstrable parasitemia for infected donors. Eighteen (6.8%) of 263 seropositive donors were hemoculture positive. Among the 17 hemocultures expanded for lineage determination, TcV was identified more frequently (n = 12), compared to TcI (n = 2), TcII (n = 1), and TcVI (n = 2). When presumptive parasite lineages were compared to hemoculture results, only two of 157 (1.3%) TcI versus 13 of 38 (34.2%) TcII/TcV/TcVI non-US donors were parasitemic; three of 44 (6.8%) US donors were TcV or TcVI. Based on lineage determination for donors with parasitemia; hemoculture positivity associated with presumptive parasite lineage; and implicated donors from US, Canadian, and Spanish transfusion cases, donors from Southern South America are significantly more likely to have parasitemia and transmit infection to blood recipients (TcII, TcV, or TcVI vs. TcI). Thus, parasite lineage may be associated with risk of transfusion-transmitted T. cruzi.


Overlooked role of African-American males' hypermasculinity in the epidemic of unintended pregnancies and HIV/AIDS cases with young African-American women.
This article looks at multiple lines of converging evidence relevant to the 72% unintended pregnancy rate, and recently emerged heterosexually-based HIV/AIDS epidemic with young African-American women. Evidence recently reveals a convergence of these epidemics, in a vulnerable subpopulation segment of African-American women. Overlooked, as a unique contributing factor in these epidemics is the hypermasculine behaviors of African-American males. Among the risky behaviors linked with this hypermasculinity are a greater tendency with African-American males to have more multiple sexual partners, and a stronger aversion to condom use than other male ethnic groups. As a contributing factor in these epidemics, African-American males' hypermasculinity has several implications for intervention strategies to reduce the epidemics, which are discussed.


Bronchial and intercostal angiography with ioxaglate and diatrizoate in man. A comparative investigation.
A low osmolality contrast medium, ioxaglate, was compared with diatrizoate of high osmolality in selective bronchial and intercostal angiography. The frequency and degree of pain, heat sensation, cough and involuntary movement were significantly lower with ioxaglate. In addition haemodynamics recorded in 17 cases of bronchial angiography revealed that ioxaglate induced significantly less effect on systemic blood pressure and heart rate.


Progress in measles control--Kenya 2002-2007.
In 2000, countries represented by the World Health Organization (WHO) Regional Office for Africa established a goal to reduce, by the end of 2005, measles mortality to 50% of the 506,000 deaths from measles estimated in 1999. Strategies adopted included strengthening routine vaccination, providing a second opportunity for measles vaccination through supplemental immunization activities (SIAs), monitoring disease trends, and improving measles case management. In Kenya, an east African country with a population estimated at 33.4 million in 2005, the Kenya Expanded Programme on Immunization (KEPI) in the Ministry of Health began implementing these strategies in 2002 with a wide age range catch-up SIA and reduced the number of reported measles cases by >99%, from 11,304 in 2001 to 20 in 2004. A follow-up SIA, initially scheduled for July 2005, was postponed to 2006 to include concurrent distribution of long-lasting insecticide-treated bednets (LLINs). This report documents progress made in reducing measles morbidity and mortality in Kenya and describes the consequences of a large measles outbreak, beginning in September 2005, on the integrated measles follow-up SIA.


A distributed pharmacokinetic model of two-step imaging and treatment protocols: application to streptavidin-conjugated monoclonal antibodies and radiolabeled biotin.
Two-step imaging and treatment protocols involve injecting a suitably prepared monoclonal antibody that can bind both to a specific tumor antigen and to a second reagent which carries a drug or radionuclide. The second component is injected later, after the antibody has distributed throughout the target tumors and been largely cleared from the plasma and normal tissues. We introduce a mathematical model for the analysis of such protocols and apply it to the case of a streptavidinylated monoclonal antibody and radiolabeled biotin diffusing into small, prevascular, densely cellular nodules that represent either primary or metastatic tumors. We examine the distribution of streptavidinylated antibody and radiolabeled biotin within a tumor nodule and compare the two-step protocol to a one-step protocol using radiolabeled antibody. Our analysis predicts that (1) streptavidinylation reduces both the amount of antibody that distributes into the tumor nodule and the homogeneity of that distribution; (2) streptavidinylated antibody in the nodule can be saturated by initial plasma concentrations of free radiolabeled biotin substantially lower than the initial plasma concentration of free streptavidinylated antibody; (3) radiolabeled biotin diffuses rapidly, but binds so quickly that it will not penetrate deeply into the nodule if too low a dose is given. Hence, nonuniform localization of radiolabel may result from a "binding site barrier" to diffusion of either or both components; and (4) the two-step protocol permits imaging sooner after injection of radiolabeled material than the one-step protocol and produces a higher exposure in tumor relative to plasma, even in the presence of antigen turnover.


Enhanced thermoelectric performance of Bi2Te3 through uniform dispersion of single wall carbon nanotubes.
The advancement in nanostructured powder processing has attracted great interest as a cost effective and scalable strategy for high performance thermoelectric bulk materials. However, the level of technical breakthrough realized in quantum dot supperlattices/wires has not yet been demonstrated in these materials. Here, we report the first ever study on the uniform dispersion of single wall carbon nanotubes (SWCNTs) in nanostructured Bi2Te3 bulk, and their effect on thermoelectric parameters above room temperature. The Bi2Te3 based SWCNT composites were prepared through controlled powder processing, and their thermoelectric properties were finely tuned at the nanoscale by regulating various (0.5, 0.75, 1.0 and 1.5) vol% of SWCNTs in the matrix. The flexible ropes of SWCNT, making an interconnected network through the inter/trans granular positions of Bi2Te3, thus substantially change the transport properties of the composites. The perfect one-dimensional (1D) conducting structure of SWCNTs acts as a source of electrical transport through a percolating network, with significantly suppressed lattice thermal conductivity, via intensified boundary scattering. The remarkable increase in power factor is ascribed to energy filtering effects and excellent electrical transport of 1D SWCNTs in the composites. Consequently, with a considerable reduction in thermal conductivity, the figure of merit culminates in a several-fold improvement, at 0.5 vol% of SWCNTs, over pristine bulk Bi2Te3.


Wire Strikes and In-Air Obstacle Collisions During Agricultural Aviation Operations.
INTRODUCTION: Wire strikes and in-air collisions with obstacles are a leading cause of accidents in the aerial application industry. While some of these collisions occur due to unseen obstacles, some pilots report being previously aware of the obstacles that they collide with. Whether or not pilots are aware of obstacles pre-collision is an important factor to inform methods of accident prevention.METHODS: Final reports from the National Transportation Safety Board were analyzed for Part 137 Agricultural Operation accidents that took place between January 2020 and December 2022. A deeper analysis of cases that involved an in-air collision with an obstacle was performed, excluding cases that were attributable to an external cause (e.g., aerodynamic stall). The pilot's awareness of the obstacle pre-accident was inferred from accident narratives if available.RESULTS: Nearly half of all accidents (N = 45 of 107) involved an in-air collision with an obstacle (e.g., wire, tree, pole) as the defining event. In cases where pilot awareness of the obstacle was determinable through the accident report, over half of pilots (N = 21 of 39) had previously seen this obstacle yet still made contact with it.DISCUSSION: In-air obstacle collisions make up a substantial portion of accidents within Part 137 Agricultural Operations. Nearly half of pilots were already aware of the obstacle before collision, indicating that inadequate preparation in scoping the field is not a predominant driver of these events. Instead, these findings suggest that other factors including distractions, high task difficulty, and errors in decision-making may contribute.Baumgartner HM. Wire strikes and in-air obstacle collisions during agricultural aviation operations. Aerosp Med Hum Perform. 2023; 94(11):852-856.


RNAProt: an efficient and feature-rich RNA binding protein binding site predictor.
Cross-linking and immunoprecipitation followed by next-generation sequencing (CLIP-seq) is the state-of-the-art technique used to experimentally determine transcriptome-wide binding sites of RNA-binding proteins (RBPs). However, it relies on gene expression, which can be highly variable between conditions and thus cannot provide a complete picture of the RBP binding landscape. This creates a demand for computational methods to predict missing binding sites. Although there exist various methods using traditional machine learning and lately also deep learning, we encountered several problems: many of these are not well documented or maintained, making them difficult to install and use, or are not even available. In addition, there can be efficiency issues, as well as little flexibility regarding options or supported features. Here, we present RNAProt, an efficient and feature-rich computational RBP binding site prediction framework based on recurrent neural networks. We compare RNAProt with 1 traditional machine learning approach and 2 deep-learning methods, demonstrating its state-of-the-art predictive performance and better run time efficiency. We further show that its implemented visualizations capture known binding preferences and thus can help to understand what is learned. Since RNAProt supports various additional features (including user-defined features, which no other tool offers), we also present their influence on benchmark set performance. Finally, we show the benefits of incorporating additional features, specifically structure information, when learning the binding sites of an hairpin loop binding RBP. RNAProt provides a complete framework for RBP binding site predictions, from data set generation over model training to the evaluation of binding preferences and prediction. It offers state-of-the-art predictive performance, as well as superior run time efficiency, while at the same time supporting more features and input types than any other tool available so far. RNAProt is easy to install and use, comes with comprehensive documentation, and is accompanied by informative statistics and visualizations. All this makes RNAProt a valuable tool to apply in future RBP binding site research.


[DNA degradation in the leaves of the sugar beet (Beta vulgaris L.) in the process of senescence].
Programmed cell death (PCD) is a characteristic of all living beings in process of their development and in response to biotic and abiotic factors effects. On the pattern of the growing old 7-8th leaves of the sugar-beet (Beta vulgaris L.) of the first year vegetation of Belocerkovskaya singl-seed-45 sort character of the degradation and state of the methylation GTCGAC- and CTGCAG-sequences of the DNA were investigated. It was established by a method of electrophoresis that in the growing old leaves which didn't have any external indications of the senescence yet the DNA fragmentation didn't have place. The degradation of the total and nuclear DNA became intensive as far as senescence was gradually increasing with the age. The DNA degradation is accompanied by high level of its methylation in recognition sites of Pst I and Sal I which doesn't change during senscence of the leaves.


Divergent differentiation in malignant melanomas: a review.
The aim of this review was to document and discuss diagnostic problems associated with divergent differentiation ('metaplastic change') in malignant melanomas, defined as the development in these tumours of morphologically, immunohistochemically and/or ultrastructurally recognizable non-melanocytic cell or tissue components. Types of divergent differentiation reported in malignant melanoma include: fibroblastic/myofibroblastic, Schwannian and perineurial, smooth muscle, rhabdomyosarcomatous, osteocartilaginous, ganglionic and ganglioneuroblastic, neuroendocrine and probable epithelial. Divergent differentiation is certainly a rare phenomenon and, when it occurs, can be missed by unwary pathologists and lead to diagnostic uncertainty. A carefully chosen immunohistochemical panel and the input of electron microscopy can help to clarify the nature of the cellular differentiation of these tumours and lead to a correct final diagnosis. The clinical significance of such aberrations is uncertain, nor are the underlying mechanisms as yet well defined.


Surgical versus medical treatment of spontaneous posterior fossa haematomas: a cooperative study on 205 cases.
22 Italian centres have joined together in a cooperative study aiming to define the ideal management of spontaneous posterior fossa haematomas. 205 cases have been evaluated: 155 cerebellar haematomas and 50 brainstem haematomas. Out of these, 190 cases, all studied by CT scan, are the subject of the present study. Cerebellar haematomas have been divided, according to a tomographic classification, into 3 groups: group 1 (4th ventricle not shifted), group 2 (4th ventricle shifted or obliterated) and group 3 (intraventricular blood). Each group has been subdivided into: A (no hydrocephalus), and B (hydrocephalus). Regardless of therapeutical modalities, mortality rate was 38% for cerebellar haematomas; level of consciousness a few hours after haemorrhage and size of the lesion appeared to be significant prognostic factors. As a whole, medical treatment gave better results than surgical treatment. Considering each tomographical group in detail, surgery should be limited to patients in group 2B and 3B, especially when exhibiting neurological deterioration. For brainstem haematomas, overall mortality was 57%. The possibility of survival was linked to the presence or absence of initial loss of consciousness and to the size of the lesion; while hydrocephalus did not influence the final outcome, ventricular blood was a risk factor. Surgical evacuation showed some value in chronic cases. However, medical treatment appears to be the best policy for brainstem haematomas of limited size; for larger lesions, the outcome appears to be uniformly fatal, regardless of the treatment employed.


Fabry disease: a review of ophthalmic and systemic manifestations.
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by accumulation of Gb-3 (globotriaosylceramide) in cellular lysosomes of tissues throughout the body. With advancing age, lysosomal Gb-3 accumulates in blood vessel walls, nerve cells, smooth muscle, and vital organs. Premature death commonly results from renal failure, heart attack, and stroke when the diagnosis is delayed or overlooked. One of the earliest and most distinctive physical features of FD is a whorl-like keratopathy. This finding is easily identifiable during a routine eye examination with a slit lamp, making eye care practitioners uniquely postured to identify patients and families with this incurable genetic disorder. Much of the pain, suffering, and adverse impact of FD can be avoided if an alert eye care expert sees the patient at an early age, identifies the condition, and makes the appropriate referral. The importance of obtaining a thorough medical history, ancestral health history, and review of systems to correlate ocular and systemic manifestations is emphasized. This report reviews the multisystem involvement of FD and describes the clinical characteristics and expected chronological appearance of ophthalmic and systemic manifestations. The discoveries of late-onset variants, increased prevalence, and modified inheritance pattern of FD are discussed. The profound therapeutic effects of recombinant enzyme replacement therapy (ERT) on multiple organ systems are detailed and demonstrated in a Fabry proband. Improved quality and quantity of life after initiation of ERT underscore the importance of early recognition and correlation of FD symptoms and clinical signs. Treatment strategies and the effectiveness of new adjunctive chaperone therapy are addressed.


[Design and validation of the telework perception scale (Tele-Cov-19) in Peruvian primary schoolteachers].
To design and validate a scale of perception of teleworking in Peruvian primary schoolteachers. This was a cross-sectional study of 400 primary schoolteachers (61.5% women) between 21 and 61 years of age, from six cities in Peru. Eight items were proposed, corresponding to indicators of training, safety, and flexibility of schedules, derived from the scientific literature. The scale was validated by seven experts who evaluated the relevance, representativeness and clarity of the items. Subsequently, we applied exploratory f (EFA) and confirmatory factor analysis (CFA), using the FACTOR Analysis program and SPSS AMOS version 21. The Aiken V indicators were statistically significant for the eight items. Before running the AFE, we calculated the KMO coefficient (0.93) and Bartlett's test (1832.9; gl = 28; p = 0.00). A single factor explained 62.27% of the total variance of the scale and its factor loadings ranged from 0.65 to 0.84. The CFA corroborated the internal structure of the scale (?2 = 58.24, df = 20, p < 0.01; RMR = 0.03; TLI = 0.97; CFI = 0.97; and RMSEA = 0.06) and the reliability was acceptable (? = 0.93; 95% CI = 0.89 - 0.92). The scale demonstrates evidence of content-based validity, internal structure and reliability.


Polyaniline hollow fibres for organic solvent nanofiltration.
Intrinsically-skinned asymmetric PANi hollow fibres, fabricated using a process of directly adding large organic acids to highly concentrated PANi solutions, show stability in a wide variety of organic solvents and have shown promising nanofiltration properties, giving high rejections of nanosolutes in acetone.


Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model.
Immunotherapy in the form of anticancer vaccination relies on the mobilization of the patient's immune system against specific cancer antigens. Instead of focusing on an autologous cell lysate, which is not always available in clinical practice, the present study investigates vaccines utilizing xenogeneic foetal tissue that are rich in oncofoetal antigens. Lewis lung carcinoma (LLC)-challenged C57BL/6 mice were treated with either a xenogeneic vaccine made from chicken whole embryo, or a xenogeneic vaccine made from rat embryonic brain tissue, supplemented with a Bacillus subtilis protein fraction as an adjuvant. Median and overall survival, size of metastatic foci in lung tissue and levels of circulating CD8a+ T cells were evaluated and compared with untreated control mice. Following primary tumour removal, a course of three subcutaneous vaccinations with xenogeneic chicken embryo vaccine led to significant increase in overall survival rate (100% after 70 days of follow-up vs. 40% in untreated control mice), significant increase in circulating CD8a+ T cells (18.18 vs. 12.6% in untreated control mice), and a significant decrease in the area and incidence of metastasis foci. The xenogeneic rat brain tissue-based vaccine did not improve any of the investigated parameters, despite promising reports in other models. We hypothesize that the proper selection of antigen source (tissue) can constitute an effective immunotherapeutic product.


Neonatal risk factors associated with attention-deficit/hyperactivity disorder: an umbrella review.
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is being encountered more frequently. In this study, by compiling the evidence from available meta-analyses, an umbrella systematic review was performed of the neonatal risk factors associated with ADHD. The PubMed, Scopus, and Web of Science databases were searched for eligible studies. Only systematic reviews were included. Using a random-effects model, 95% prediction intervals were reported for each risk factor. Three studies were ultimately included in the review. Congenital heart disease, short-duration or incomplete breastfeeding, low birth weight, and 5-minute Apgar scores <7 were significant risk factors for ADHD. However, the quality of the included systematic reviews was low to moderate and the evidence credibility level was suggestive to weak. The results of this umbrella review proposed that congenital anomalies, short-duration or incomplete breastfeeding, low birth weight, and low Apgar scores were important factors for the manifestation of ADHD symptoms. However, the inclusion of more high-quality studies is needed to validate our results.


The complete chloroplast genome sequence of Rhaponticum uniflorum, the first of the genus Rhaponticum.
Rhaponticum uniflorum is commonly used as a source for traditional medicines with the main effect of clearing heat. Here, we sequenced the complete chloroplast (cp) genome of R. uniflorum to develop molecular markers for taxonomic classification and species determination of R. uniflorum. It was 152,760 bp in size and has a typical circular structure, including a pair of inverted repeats with 25,205 bp, a large single-copy region with 83,687 bp, and a small single copy region with 18,663 bp. The genome encodes 110 unique genes, including 80 protein-coding, four rRNA and 26 tRNA genes. Phylogenomic analysis shows that R. uniflorum is closely related to the Saussurea. The study is useful for phylogenetic and population genetic studies of Rhaponticum plants.


Hyperventilation syndrome: measurement of objective symptoms and subjective complaints.
In 303 subjects, amongst whom 250 patients suspected of suffering from the hyperventilation syndrome, lung functions were measured, a hyperventilation provocation test was performed and a questionnaire was taken. The subjects were subdivided into categories of nonhyperventilators, and 3 categories of hyperventilators, on the basis of objective measurable lung function parameters and the result of the provocation test. The outcome of the questionnaire in the various categories was evaluated. Some subjective complaints were related to age, sex, PaCO2 and lung function of the subjects. There was no clear correlation between PaCO2 and neurological signs. Hypoventilation after the provocation test occurred in only 5 subjects. No indications were found that hyperventilation might be an early sign of chronic obstructive lung disease.


β2 integrins rather than β1 integrins mediate Alternaria-induced group 2 innate lymphoid cell trafficking to the lung.
Group 2 innate lymphoid cells (ILC2s) expand in the lungs of mice during type 2 inflammation induced by the fungal allergen Alternaria alternata. The increase in ILC2 numbers in the lung has been largely attributed to local proliferation and whether ILC2s migrate from the circulation to the lung after Alternaria exposure is unknown. We examined whether human (lung, lymph node, and blood) and mouse lung ILC2s express β1 and β2 integrin adhesion molecules and whether these integrins are required for trafficking of ILC2s into the lungs of mice. Human and mouse ILC2s were assessed for surface expression of β1 and β2 integrin adhesion molecules by using flow cytometry. The role of β1 and β2 integrins in ILC2 trafficking to the lungs was assessed by in vivo blocking of these integrins before airway exposure to Alternaria in mice. Both human and mouse lung ILC2s express high levels of β1 and β2 integrin adhesion receptors. Intranasal administration of Alternaria challenge reduced ILC2 numbers in the bone marrow and concurrently increased blood and lung ILC2 numbers. In vivo blocking of β2 integrins (CD18) significantly reduced ILC2 numbers in the lungs but did not alter ILC2 proliferation, apoptosis, and function. In contrast, in vivo blocking of β1 integrins or α4 integrins did not affect lung ILC2 numbers. ILC2 numbers increase in the mouse lung not only through local proliferation but also through trafficking from the circulation into the lung using β2 rather than β1 or α4 integrins.


Gastric parietal cell acid secretion in mice can be regulated independently of H/K ATPase endocytosis.
Gastric parietal cells secrete acid into the lumen of the stomach. They express a proton pump, the gastric H(+)/K(+) ATPase, the activity of which is tightly regulated. The H(+)/K(+) ATPase traffics between an intracytoplasmic compartment (tubulovesicles) in quiescent parietal cells and the apical plasma membrane in activated cells. These trafficking events are considered to contribute to the control of acid secretion by modulating access to apical K(+) and Cl(-) conductances that are required for transmembrane H(+) ion transport by the H(+)/K(+) ATPase. Here, we have determined whether the control of acid secretion in vivo requires membrane trafficking of the H(+)/K(+) ATPase. We developed mice that only express an H(+)/K(+) ATPase beta subunit in which a putative tyrosine-based endocytosis motif in the cytoplasmic tail is mutated. Location of the H(+)/K(+) ATPase and parietal cell ultrastructure and gastric acid secretion were then examined. Parietal cells of these mice lacked a tubulovesicular compartment, and the H(+)/K(+) ATPase was resident exclusively on the apical plasma membrane. Despite the inability of the H(+)/K(+) ATPase to be endocytosed, the gastric acid secretory response to histamine or an antagonist was very similar to that of wild-type mice, indicating that control of H(+)/K(+) ATPase activity can occur independently of intracellular trafficking. We were able to dissociate the regulation of H(+)/K(+) ATPase activity from intracellular trafficking of the protein. Thus, it is likely that direct regulation of apical K(+) and Cl(-) conductances are sufficient to control gastric acid secretion.


5-Hydroxytryptamine: a potential therapeutic target in amyotrophic lateral sclerosis.
Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis (ALS) is closely linked to 5-hydroxytryptamine (5-HT). To investigate this further, we administered 5-HT receptor antagonists to SOD1*G93A transgenic (ALS mouse model) and wide-type mice. This involved intraperitoneal injections of either granisetron, piboserod, or ritanserin, which inhibit the 5-HT3, 5-HT4, and 5-HT2 receptors, respectively. The transgenic mice were found to have fewer 5-HT-positive cells in the spinal cord compared with wide-type mice. We found that the administration of granisetron reduced the body weight of the transgenic mice, while piboserod and ritanserin worsened the motor functioning, as assessed using a hanging wire test. However, none of the 5-HT receptor antagonists affected the disease progression. We analyzed the distribution and/or expression of TAR DNA binding protein 43 (TDP-43) and superoxide dismutase 1 G93A (SOD1-G93A), which form abnormal aggregates in ALS. We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists. In addition, the disease-related mislocalization of TDP-43 to the cytoplasm increased markedly for all three drugs. In certain anatomical regions, the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons. These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells. 5-HT could therefore be a potential therapeutic target for amyotrophic lateral sclerosis.


[Primary intraosseous hemangioma of the orbit: report of two cases].
Primary intraosseous hemangioma, though rarely affect the bones of the orbit, should be considered in the differential diagnosis when a patient presents an enlarging mass fixed to the bone in the orbit or signs of progressive painless proptosis. Assessing the exact site and extent of the hemangioma by means of a CT scan and MRI and establishing the vascular origin of the lesion, is critical in the therapeutical planning, since an inadequate management may result in a severe hemorrhage. Progressive proptosis and contour deformity require surgical treatment. Two cases of patients with primary intraosseus hemangioma of the supra-lateral orbital rim are reported. A bony healthy margin excision was performed, followed by immediate reconstruction of the orbit with calvarial bone grafts fixed with resorbable plates. After three-year follow-up there have not been evidence of local recurrence, and the functional and aesthetic results obtained have been very satisfactory.


Screening for developmental and behavioral problems.
Early detection of developmental and behavioral/mental health problems is greatly facilitated when quality instruments are deployed. This article describes how to identify accurate measures and presents standards for screening tests. Included is a table delineating accurate tools for primary care: typically those relying on information from parents (e.g., PEDS, ASQ, PSC, etc.) as well as measures useful in settings where providers have more time and skill at eliciting behaviors from children (e.g., Brigance screens). Screening measures should be used in the context of developmental surveillance; the longitudinal process of incorporating professional observations into decision-making about children's developmental needs.


Food intake, diet quality and behavioral problems in children: results from the GINI-plus/LISA-plus studies.
To assess the association between food intake and diet quality and behavioral problems at the 10-year follow-up of the two population-based birth cohorts of the studies German Infant Nutritional Intervention and 'Influences of lifestyle-related factors on the immune system and the development of allergies in childhood'. Cross-sectional data on food intake over the past year were collected by a parent-reported food frequency questionnaire. Diet quality was based on reference values of food amounts of the optimized mixed diet. Behavioral problems were assessed by a parent-reported Strengths and Difficulties Questionnaire. Relationships between food category intake, diet quality and behavior problems were examined using multivariable regression modeling adjusted for gender, sociodemographic characteristics, body mass index, physical exercise, television viewing/PC use and total energy intake. A total of 3,361 children with complete data were analyzed. Children with increased intake of confectionery had increased odds of having emotional symptoms [adjusted odds ratio (OR(adj)) 1.19, 95% confidence interval (CI) 1.08-1.32] compared to children with low intake. A higher diet quality score was associated with lower likelihood of emotional symptoms (OR(adj) 0.89, 95% CI 0.80-0.98). The unadjusted significant relationship between diet quality and hyperactivity/inattention was attenuated by adjusting for several confounders to an OR(adj) of 0.92 (95% CI 0.82-1.03). Increased consumption of high-sugar products and lower diet quality are associated with a higher likelihood of emotional symptoms in children.


Rights Disappear When US Policy Engages Children as Weapons of Deterrence.
In 1989, the United Nations adopted the Convention on the Rights of the Child (CRC), which the United States provided significant guidance in drafting. The CRC focused on those under 18 years of age, recognizing the rights most other international conventions and declarations accorded to adults. This article explores the ethical and health implications of the United States' failure to ratify the CRC with an emphasis on refugees. Federal policies have led to separation of families, mass detention of children and families, and accelerated removal, revealing the United States' disregard for global concern about children and families. By failing to ratify the CRC, the United States not only abdicates moral leadership, but also invites other nations to emulate its lack of care for children.


Clinical and biochemical aspects of depressive disorders: II. Transmitter/receptor theories.
The present document is the second of three parts in a review that focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. Various receptor/transmitter theories of depressive disorders are discussed in this section. Specifically, data supporting noradrenergic, serotonergic, cholinergic, dopaminergic, GABAergic, and peptidergic theories, as well as interactions between noradrenergic and serotonergic, or cholinergic and catecholaminergic systems are presented. Problems with the data and future directions for research are also discussed. A previous publication, Part I of this review, dealt with the classification of depressive disorders and research techniques for studying the biochemical mechanisms of these disorders. A future publication, Part III of this review, discusses treatments for depression and some of the controversies in this field.


Ethnic variation in sinonasal anatomy on CT-scanning.
Computed tomography (CT) scanning of the paranasal sinuses provides valuable information in assessing extent of disease and fine detailed anatomy prior to endoscopic sinus surgery. Awareness of the different anatomic variants of the bony sinonasal anatomy will help the rhinologic surgeon's orientation during the procedure. We conducted a study to look at the incidence of the anatomic variation within the lateral wall of the nose and sinuses and to determine if there is any ethnic difference in these variants between a cohort of 100 Caucasian patients undergoing endoscopic sinus surgery in London and 100 Chinese patients treated in Hong Kong. We compared the two groups with chi-square test and the significant areas are those with p value of less than 0.05. The results show a higher incidence of pneumatisation of the middle turbinate (concha bullosa) and paradoxical bending of the middle turbinate in the Caucasian population. The infraorbital and suprabullar cell development was greater in the Caucasian population though the incidence of sphenoethmoidal cells was much greater in the Chinese population. When asymmetry of the anterior ethmoidal roof was considered, the left was consistently the highest in both groups, though there was no difference in the depth of the cribiform niche between right and left or between Caucasian and Chinese. The incidence of bent uncinate process and of complete absence of a sinus was higher in the Chinese population. There was no difference in the presence of pneumatisation of the agger nasi, of the uncinate process, or of the anterior clinoid process. There was no difference in the presence of septation adjoining the carotid in the lateral wall of sphenoid or in the exposure of the optic nerve within sphenoid or posterior ethmoid sinuses. Although there is no evidence that variants of the sinonasal anatomy seen on CT Scan have a causative effect in the disease process; a knowledge of their presence is paramount in minimising the potential for surgical complications.


DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview.
In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.


Full-genome sequence analysis of a variant strain of porcine epidemic diarrhea virus in South Korea.
In March of 2014, a variant of novel porcine epidemic diarrhea virus (PEDV) was first identified in South Korea and found to be most closely related to the U.S. variant strain OH851. The complete genome of the KOR/KNU-1406/2014 strain was sequenced and analyzed to investigate the U.S.-strain-like variant circulating in South Korea.


FTNIR Spectrometry of Micafungin Sodium Quality.
Intra-lot and inter-lot variability in the spectra of micafungin was detected in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). Two vials of 6 vials sampled from Fresenius Kabi lot ACP106 appeared 7.9 and 14.0 standard deviations (SDs) from the center of the rest of the vials on the DQS FTNIR screening assay. Spectra of 48 vials from 7 lots in the library showed 2 outliers at 8.3 and 9.8 SDs from the center of the rest of the library, suggesting they represent different material.


Metagenomic-based impact study of transgenic grapevine rootstock on its associated virome and soil bacteriome.
For some crops, the only possible approach to gain a specific trait requires genome modification. The development of virus-resistant transgenic plants based on the pathogen-derived resistance strategy has been a success story for over three decades. However, potential risks associated with the technology, such as horizontal gene transfer (HGT) of any part of the transgene to an existing gene pool, have been raised. Here, we report no evidence of any undesirable impacts of genetically modified (GM) grapevine rootstock on its biotic environment. Using state of the art metagenomics, we analysed two compartments in depth, the targeted Grapevine fanleaf virus (GFLV) populations and nontargeted root-associated microbiota. Our results reveal no statistically significant differences in the genetic diversity of bacteria that can be linked to the GM trait. In addition, no novel virus or bacteria recombinants of biosafety concern can be associated with transgenic grapevine rootstocks cultivated in commercial vineyard soil under greenhouse conditions for over 6 years.


Drosophila DBT lacking protein kinase activity produces long-period and arrhythmic circadian behavioral and molecular rhythms.
A mutation (K38R) which specifically eliminates kinase activity was created in the Drosophila melanogaster ckI gene (doubletime [dbt]). In vitro, DBT protein carrying the K38R mutation (DBT(K/R)) interacted with Period protein (PER) but lacked kinase activity. In cell culture and in flies, DBT(K/R) antagonized the phosphorylation and degradation of PER, and it damped the oscillation of PER in vivo. Overexpression of short-period, long-period, or wild-type DBT in flies produced the same circadian periods produced by the corresponding alleles of the endogenous gene. These mutations therefore dictate an altered "set point" for period length that is not altered by overexpression. Overexpression of the DBT(K/R) produced effects proportional to the titration of endogenous DBT, with long circadian periods at lower expression levels and arrhythmicity at higher levels. This first analysis of adult flies with a virtual lack of DBT activity demonstrates that DBT's kinase activity is necessary for normal circadian rhythms and that a general reduction of DBT kinase activity does not produce short periods.


Dry eye in the beaver dam offspring study: prevalence, risk factors, and health-related quality of life.
To estimate dry eye prevalence in the Beaver Dam Offspring Study (BOSS), including a young adult population, and investigate associated risk factors and impact on health-related quality of life. Cohort study. The BOSS (2005-2008) is a study of aging in the adult offspring of the population-based Epidemiology of Hearing Loss Study cohort. Questionnaire data on health history, medication use, risk factors, and quality of life were available for 3275 participants. Dry eye was determined by self-report of frequency of symptoms and the intensity of those symptoms. Associations between dry eye and risk factors were analyzed using logistic regression. The prevalence of dry eye in the BOSS was 14.5%: 17.9% of women and 10.5% of men. In a multivariate model, statistically significant associations were found with female sex (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.33-2.11), current contact lens use (OR, 2.01; 95% CI, 1.53-2.64), allergies (OR, 1.59; 95% CI, 1.22-2.08), arthritis (OR, 1.44; 95% CI, 1.12-1.85), thyroid disease (OR, 1.43; 95% CI, 1.02-1.99), antihistamine use (OR, 1.54; 95% CI, 1.18-2.02), and steroid use (OR, 1.54; 95% CI, 1.16-2.06). Dry eye was also associated with lower scores on the Medical Outcomes Study Short Form 36 (β = -3.9, P < .0001) as well as on the National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) (β = -3.4, P < .0001) when controlling for age, sex, and comorbid conditions. The prevalence of dry eye and its associated risk factors in the BOSS were similar to previous studies. In this study, dry eye was associated with lower quality of life on a health-related quality-of-life instrument and the vision-specific NEI VFQ-25.


A Fluorescence Resonance Energy Transfer Probe Based on DNA-Modified Upconversion and Gold Nanoparticles for Detection of Lead Ions.
We report a new sensor for the specific detection of lead ions (Pb2+) in contaminated water based on fluorescence resonance energy transfer (FRET) between upconversion nanoparticles (UCNPs) as donors and gold nanoparticles (Au NPs) as receptors. The UCNPs modified with Pb2+ aptamers could bind to Au NPs, which were functionalized with complementary DNA through hybridization. The green fluorescence of UCNPs was quenched to a maximum rate of 80% due to the close proximity between the energy donor and the acceptor. In the presence of Pb2+, the FRET process was broken because Pb2+ induced the formation of G-quadruplexes from aptamers, resulting in unwound DNA duplexes and separated acceptors from donors. The fluorescence of UCNPs was restored, and the relative intensity had a significant linear correlation with Pb2+ concentration from 0 to 50 nM. The sensor had a detection limit as low as 4.1 nM in a buffer solution. More importantly, the sensor exhibited specific detection of Pb2+ in complex metal ions, demonstrating high selectivity in practical application. The developed FRET prober may open up a new insight into the specific detection of environmental pollution.


Clinical Experience with Telavancin for the Treatment of Patients with Bacteremia and Endocarditis: Real-World Results from the Telavancin Observational Use Registry (TOUR™).
Bacteremia and endocarditis caused by Staphylococcus aureus (S. aureus), particularly methicillin-resistant S. aureus (MRSA), are challenging to treat and are associated with high morbidity and mortality. Telavancin is a lipoglycopeptide antibacterial active against susceptible Gram-positive pathogens, including MRSA. This registry study assessed the real-world use and clinical outcomes of telavancin in patients with bacteremia or endocarditis enrolled in the Telavancin Observation Use Registry (TOUR™). The subset of patients enrolled in TOUR who were diagnosed with endocarditis and/or bacteremia with a known or unknown primary source (N = 151) were analyzed. Data including demographics, infection type, baseline pathogens, prior or concomitant antimicrobial therapy, dosing regimen, clinical response, treatment-emergent adverse events (TEAEs) of interest, and mortality were collected by retrospective medical chart review. Telavancin was primarily used as a second-line or greater therapy (n = 132, 87.4%). MRSA was present in 87 (57.6%) patients. Median telavancin dose was 740.6 mg (interquartile range (IQR) 206.0 mg) and median duration of therapy was 9.0 days (IQR 24.0 days). Of the 132/151 (87.4%) patients with an available assessment at the end of telavancin therapy, a positive clinical response was achieved in 98/132 (74.2%), while 14/132 (10.6%) failed therapy and 20/132 (15.2%) had an indeterminant outcome. TEAEs occurred in 24 (15.9%) patients. The most frequent TEAE was renal failure (n = 12, 7.9%); seven of these patients were receiving concomitant nephrotoxic medications. There was no change in creatinine clearance for 67/89 (75.3%) patients with values recorded at the beginning and the end of telavancin therapy. In real-world clinical practice, overall positive clinical outcomes are observed in patients with bacteremia or endocarditis treated with telavancin, including in those patients infected with MRSA or another S. aureus pathogen. Telavancin may be an alternative treatment option for these patients. This trial was registered with clinicaltrials.gov (NCT02288234) on 11 November 2014.