Evaluation of respiratory function in healthcare workers wearing face masks during the COVID-19 pandemic.
The COVID pandemic, which has caused high mortality rates worldwide, has mainly affected the working environment of healthcare workers. Metabolic and respiratory changes occur in healthcare workers working with surgical masks. Our aim is to identify the metabolic and respiratory problems faced by healthcare personnel working with surgical masks and to produce solutions to minimize them. The study was conducted among emergency service workers who used surgical masks for at least 8 h in the emergency room between June 2020 and July 2020. Venous blood gas samples were taken from the health personnel participating in the study and their vital signs were checked. A total of 60 healthcare professionals with a mean age of 28.20 ± 6.30 years were included in the study. The distribution of men and women in the study was balanced with 30 (50.0%) men and 30 (50.0%) women. When the first and last vital signs (blood pressure, pulse, saturation) of the health workers participating in the study were examined, no statistically significant differences were found (p > 0.05). While there was no statistically significant difference in the Na, Chlorine, Ca values of metabolic indicators (p > 0.05), the first measurements of K (0.017) and Lactate (0.037) values were found to be higher than the last measurements (p > 0.05). The first measurements of the respiratory parameters pH (0.002), pCO2 (0.028), sO2 (0.045) and pO2 (0.048) were lower than the last measurements (p > 0.05). The first measurement value of pCO2 (0.028) was found to be higher than the last (p > 0.05). Regular and long-term use of surgical masks does not harm the body metabolically and respiratorily.


The role of the epitope density and cross-reactivity between two different purine nucleosides coupled to cells.
Cellular immune responses against nucleic acid antigens were analyzed in BALB/C mice. Delayed-type hypersensitivity (DTH) could be elicited by immunizing and challenging with either guanosine-coupled spleen cells (G-SC) or adenosine-coupled spleen cells (A-SC), and measured by footpad swellings. The epitope density was critical for immunization. This cellular reaction was specific to nucleosides, and cross-immunity was observed between A-SC and G-SC. In addition, cross-unresponsiveness was observed between these two nucleosides. In contrast, soluble carrier proteins coupled with either guanosine or adenosine did not induce cross-reactive immunity or unresponsiveness. The significance of the difference between these two forms of antigens in the ability to induce cross-reactivity is discussed in the context of T versus B-cell recognition in the induction or the expression of the immune response.


Beta-thromboglobulin in inflammatory synovial fluid.
Activated platelets release substances which potentially can contribute to joint lesions in inflammatory arthritides. To elucidate a possible participation of platelets in inflammatory joint reactions, the concentrations of the platelet protein beta-thromboglobulin (beta-TG) were measured in 90 inflammatory synovial fluids. Seven percent of the patients with rheumatoid arthritis and none of the patients with other inflammatory joint diseases (e.g., Reiter's disease, reactive or crystal arthritides) had beta-TG concentrations in synovial fluid exceeding the upper normal range of plasma beta-TG. The absent or very modest signs of local platelet activation were contrasted by the pronounced neutrophilic and monocytic activation, as assessed by the measurements of some granule proteins: lactoferrin, myeloperoxidase, lysozyme, and ferritin. No correlation was found between these inflammatory cell markers and beta-TG. A positive correlation (p less than 0.001) was noted between beta-TG and beta 2-microglobulin, which appeared in particularly high amounts in rheumatoid arthritis. This correlation may reflect a disturbed permeability of synovial membrane for LMW proteins or a related activation of platelets and lymphocytes. The present results do not give any evidence of platelet activation playing a major role in proliferative or destructive processes in arthritis.


GENE-IS: Time-Efficient and Accurate Analysis of Viral Integration Events in Large-Scale Gene Therapy Data.
Integration site profiling and clonality analysis of viral vector distribution in gene therapy is a key factor to monitor the fate of gene-corrected cells, assess the risk of malignant transformation, and establish vector biosafety. We developed the Genome Integration Site Analysis Pipeline (GENE-IS) for highly time-efficient and accurate detection of next-generation sequencing (NGS)-based viral vector integration sites (ISs) in gene therapy data. It is the first available tool with dual analysis mode that allows IS analysis both in data generated by PCR-based methods, such as linear amplification method PCR (LAM-PCR), and by rapidly evolving targeted sequencing (e.g., Agilent SureSelect) technologies. GENE-IS makes use of trimming strategies, customized reference genome, and soft-clipped information with sequential filtering steps to provide annotated IS with clonality information. It is a scalable, robust, precise, and reliable tool for large-scale pre-clinical and clinical data analysis that provides users complete flexibility and control over analysis with a broad range of configurable parameters. GENE-IS is available at https://github.com/G100DKFZ/gene-is.


Clarification of apple, grape and pear juices by co-immobilized amylase, pectinase and cellulase.
In this study, the use of co-immobilized amylase, pectinase and cellulase enzymes for clarification of apple, grape and pear juices were investigated. Four different co-immobilization method was applied and the highest activity was observed for co-immobilized enzymes onto silica gel. The effect of the enzyme units used in the co-immobilization, reaction temperature and time on turbidity and reducing sugar concentration were optimized by Response Surface Methodology (RSM) via Design Expert Software 126.96.36.199. applying 3-factor Box-Behnken design. Co-immobilized samples were reacted with the substrate solution in batch type and feedback packed bed column reactors and according to turbidity and reducing sugar concentration values, batch reactor efficiency was found to be higher. Finally, freshly squeezed apple, pear and grape juices were interacted with co-immobilized enzymes in the batch reactor system, and turbidity and reducing sugar concentrations were monitored over time. Changes were also observed in antioxidant activities depending on the enzyme treatment.


Zoonotic transmission of hepatitis E virus from deer to human beings.
Zoonosis has been suggested for hepatitis E virus (HEV) infection, but so far is based only on indirect evidence. We experienced a series of cases of HEV infection among people who had eaten uncooked deer meat 6-7 weeks before. On testing, a left over portion of the deer meat, kept frozen to eat in the future, was positive for HEV RNA, whose nucleotide sequence was identical to those from the patients. Patients' family members who ate none or very little of the deer meat remained uninfected. These findings provide direct evidence for HEV infection to be a zoonosis.


Effects of Long-term Conservation Tillage on Soil Nutrients in Sloping Fields in Regions Characterized by Water and Wind Erosion.
Conservation tillage is commonly used in regions affected by water and wind erosion. To understand the effects of conservation tillage on soil nutrients and yield, a long-term experiment was set up in a region affected by water and wind erosion on the Loess Plateau. The treatments used were traditional tillage (CK), no tillage (NT), straw mulching (SM), plastic-film mulching (PM), ridging and plastic-film mulching (RPM) and intercropping (In). Our results demonstrate that the available nutrients in soils subjected to non-traditional tillage treatments decreased during the first several years and then remained stable over the last several years of the experiment. The soil organic matter and total nitrogen content increased gradually over 6 years in all treatments except CK. The nutrient content of soils subjected to conservative tillage methods, such as NT and SM, were significantly higher than those in soils under the CK treatment. Straw mulching and film mulching effectively reduced an observed decrease in soybean yield. Over the final 6 years of the experiment, soybean yields followed the trend RPM > PM > SM > NT > CK > In. This trend has implications for controlling soil erosion and preventing non-point source pollution in sloping fields by sacrificing some food production.


Horse liver alcohol dehydrogenase: new perspectives for an old enzyme.
The EE subunit of horse liver alcohol dehydrogenase (HLADH-EE) has been subcloned in pRSETb vector to generate a fusion His-tag protein. The migration from a multistep purification protocol for this well-known enzyme to a single-step has been successfully achieved. Several adjustments to the traditional purification procedure for His-tag proteins have been made to retain protein activity. A full characterization of the fusion enzyme has been carried out and compared with the native one. The K (m) for EtOH, NAD and NADH in the His-tag version of HLADH are in line with the ones reported in literature for the native enzyme. A shift in optimal pH activity is also observed. The enzyme retains the same stability and quaternary structure as the wild type and can therefore be easily used instead of the native HLADH for biotechnological applications.


Complications during retrograde approach for chronic coronary total occlusion: Sub-analysis of Japanese multicenter registry.
This study was performed to determine the complications occurring during retrograde percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) based on analysis of the multicenter, prospective, nonrandomized Retrograde Summit registry. Retrograde PCI for CTO has improved treatment success rates, but several complications related to the retrograde approach have been reported, including collateral channel injury and donor artery injury due to their use as retrograde roots. This registry included data from 1,166 patients who underwent retrograde PCI for CTO in 28 Japanese centers between January 2009 and December 2011. Overall procedure success and retrograde procedure success were achieved in 985 (84.5%) and 838 (71.9%) of the 1,166 patients, respectively. In-hospital major adverse cardiac and cerebrovascular events (MACCE) occurred in 18 (1.5%) of the 1,166 patients. With regard to complications related to the retrograde approach, channel injury occurred in 111 (9.5%) of the 1,166 patients, but treatment was required in only 24 (2.1%) patients and subsequent cardiac tamponade occurred in only 4 (0.3%) patients. Donor artery problems occurred in only 10 (0.9%) of the 1,166 patients. In sub-analysis regarding the types of collateral channels, the septal channel was significantly safer than epicardial channel because of the lower frequency of non-Q-wave myocardial infarction (non-QMI) and channel injury requiring treatment. The MACCE rate during retrograde PCI for CTO determined from the Retrograde Summit registry was low and the frequency of complications related to the retrograde approach was acceptable. © 2015 Wiley Periodicals, Inc.


Cyanidin-3-O-glucoside promotes stress tolerance and lifespan extension of Caenorhabditis elegans exposed to polystyrene via DAF-16 pathway.
Microplastic pollution has attracted growing attention due to its prevalent and persistent exposure to general population through the food chain, but few reports have focused on the toxicological prevention of polystyrene (PS). Using the wild-type and mutant strains, this study explored the impacts of PS and cyanidin-3-O-glucoside (C3G) on stress tolerance and lifespan of Caenorhabditis elegans (C. elegans). In N2 nematodes, PS exposure initiated the oxidative stress and subsequent lifespan reduction, while these adverse impacts could be positively improved by C3G treatment. Considering the pivotal role of DAF-16 pathway in stress tolerance and lifespan regulation, the expression of the daf-16 gene and its downstream antioxidant genes (clt-2, hsp-16.1, sod-3, sod-5) were examined, and found to be significantly enhanced by C3G. Since the sod-3 gene was up-regulated the most fold by C3G, the activity of SOD enzyme that encoded by the sod-3 was examined, and could be obviously enhanced upon C3G treatment. This explained the improved oxidative stress and delayed oxidation-associated aging after C3G intervention. Nevertheless, these positive effects of C3G were weakened in daf-16(-) mutant strain (with deleted DAF-16 gene), for which the beneficial effects of C3G in promoting stress resistance and lifespan extension were inhibited. These findings suggested that the DAF-16 gene and its downstream antioxidant genes, have participated in C3G's regulations on redox balance and lifespan that impacted by nano-polystyrene particles. This study highlighted the link between dietary components and environmentally driven disturbance.


Comparison of cytotoxic and inflammatory responses of pristine and functionalized multi-walled carbon nanotubes in RAW 264.7 mouse macrophages.
The increased application of carbon nanotubes (CNTs) has raised the level of public concern regarding possible toxicities. Using in vitro cellular assays, we were able to assess the immunotoxicity of pristine multi-wall carbon nanotubes (MWCNTs) and their derivatives, covalently functionalized with carboxyl (COOH) or polyethylene glycol (PEG), in rodent macrophage cells. Moreover, special focus was placed on the role of surface modification and nanotubes aggregation on toxicity. Results showed that pristine MWCNTs reduce cell viability compared with functionalized MWCNTs in RAW 264.7 macrophages when incubated at concentrations of 25, 50, 100, 200, 400, and 800 μg/mL. However, in addition to causing cytotoxicity, functionalized MWCNTs induce serious inflammatory responses, as indicated by the production of inflammatory cytokines including TNF-α, IL-1β and IL-6 at various MWCNTs concentrations (25, 50, 100, and 200 μg/mL). Particle surface modification and dispersion status in biological medium were key factors in determining cytotoxicity. These findings imply that MWCNTs-induced inflammatory responses in macrophages may be associated with surface modification and aggregation of MWCNTs, which is reflected by alteration of inflammatory cytokine expression.


Cyclic-RGDfK peptide conjugated succinoyl-TPGS nanomicelles for targeted delivery of docetaxel to integrin receptor over-expressing angiogenic tumours.
Docetaxel (DTX) is an anticancer drug that is used alone and in combination with other drugs to treat tumours. However, it suffers from the drawback of non-specific cytotoxicity. To improve the therapeutic potential of DTX, we report the synthesis of cRGDfK peptide-conjugated succinoyl-TPGS (tocopheryl polyethylene glycol succinate) nanomicelles for targeted delivery of DTX. Among RGD (Arg-Gly-Asp) peptides, cRGDfK peptide shows specificity towards αvβ3 integrin receptors that are most commonly over-expressed in tumour cells. To cRGDfK peptide, succinoylated TPGS was synthesised and conjugated to cRGDfK peptide using a carbodiimide reaction. Peptide-conjugated DTX loaded nanomicelles (PDNM) displayed small particle size with a narrow distribution, controlled drug release and high physicochemical stability. Cytotoxicity, cellular uptake, apoptosis and anti-angiogenic comparisons of unconjugated nanomicelles to PDNM in DU145 human prostate cancer cells and HUVECs (Human Umblical Vein Endothelial Cells) clearly revealed the importance of the cRGDfK peptide in enhancing the drug delivery performance of nanomicelles. Common to many chemotherapeutic agents for cancer, systemic toxicity remains a big concern. In this article, the authors attempted to address this issue by conjugating RGD based peptides to Docetaxel, which would target integrins expressed on tumor cell surface. The experimental data revealed enhanced drug delivery.


Immobilized lipase for sustainable hydrolysis of acidified oil to produce fatty acid.
Acidified oil is obtained from by-product of crops oil refining industry, which is considered as a low-cost material for fatty acid production. Hydrolysis of acidified oil by lipase catalysis for producing fatty acid is a sustainable and efficient bioprocess that is an alternative of continuous countercurrent hydrolysis. In this study, lipase from Candida rugosa (CRL) was immobilized on magnetic Fe3O4@SiO2 via covalent binding strategy for highly efficient hydrolysis of acidified soybean oil. FTIR, XRD, SEM and VSM were used to characterize the immobilized lipase (Fe3O4@SiO2-CRL). The enzyme properties of the Fe3O4@SiO2-CRL were determined. Fe3O4@SiO2-CRL was used to catalyze the hydrolysis of acidified soybean oil to produce fatty acids. Catalytic reaction conditions were studied, including amount of catalyst, reaction time, and water/oil ratio. The results of optimization indicated that the hydrolysis rate reached 98% under 10 wt.% (oil) of catalyst, 3:1 (v/v) of water/oil ratio, and 313 K after 12 h. After 5 cycles, the hydrolysis activity of Fe3O4@SiO2-CRL remained 55%. Preparation of fatty acids from high-acid-value by-products through biosystem shows great industrial potential.


[Diagnostic limitations of isolated axiography interpretation].
Axiographic images of eccentric condylar paths can be more reliably interpreted by considering the clinical function data, compression test results and the MPI. In the case presented the abnormal position of the right condyle would have gone unnoticed without such a combined approach to the problem.


Does Long-term Soft Contact Lens Wear Affect Corneal and Anterior Chamber Parameters?
To assess the long-term effects of soft contact lenses (SCL) on the cornea and anterior chamber by topography. Thirty-nine eyes of 22 healthy patients were included in this prospective study. Changes in corneal and anterior chamber parameters before and after 12 months of daily SCL use (Air Optix Aqua, Air Optix Aqua for Astigmatism, Acuvue Oasys and Acuvue Oasys for Astigmatism) were evaluated with Pentacam (Oculus, Germany). Best corrected visual acuity with toric SCL was significantly better compared to spectacles in the toric SCL group (0.98±0.34 vs 0.94±0.72, p=0.004). None of the corneal (horizontal and vertical keratometry, corneal volume, anterior and posterior corneal astigmatism, corneal pachymetry of apex and thinnest location) and anterior chamber (anterior chamber depth, volume and angle) parameters showed a statistically significant change after long-term daily wear of SCLs. The results of this study revealed that long-term wear of current high oxygen permeable and relatively low modulus silicone hydrogel SCLs does not impact cornea and anterior chamber morphology or volumetric parameters. Furthermore, toric silicone hydrogel SCLs can provide better visual performance than spectacles.


Successful Applications of NIR Spectroscopy and NIR Imaging in the Food Processing Chain.
Forty years ago, Near InfraRed (NIR) was considered a sleeping technique among the spectroscopic ones [...].


[Is surgical-tocolytic prevention and therapy of cervical insufficiency justified without prenatal diagnostic care?].
We report on our results of the combined operative-tocolytical prophylaxis and therapy of cervical insufficiency from the department for gynecology and obstetrics of our hospital to decrease the mortality of newborn. The possibility of such treatment without optimal antenatal apparatus-control will be discussed.


Low-dose total body irradiation and G-CSF without hematopoietic stem cell support in the treatment of relapsed or refractory acute myelogenous leukemia (AML), or AML in second or subsequent remission.
Patients with relapsed acute myelogenous leukemia (AML), who are not eligible for bone marrow transplantation, have a poor prognosis when treated with chemotherapy alone. Total body irradiation (TBI) is an effective modality against AML when used in doses of 1000-1400 cGy with hematopoietic stem cell support. We undertook a phase I study of TBI with granulocyte-colony-stimulating factor (G-CSF) support, without stem cell support in patients with AML either in relapse or second or subsequent remission. Patients with relapsed AML, or AML in second or subsequent remission were treated in a phase I study of TBI followed by G-CSF. The first dose level was 200 cGy. After the initial cohort of patients it was clear that patients with overt leukemia did not benefit from this treatment, and subsequent patients were required to be in remission at the time of TBI. Eleven patients were treated, 4 in overt relapse, and 7 in remission. 200 cGy was used in all, and dose escalation was not possible due to prolonged thrombocytopenia in all patients but one. Neutrophil recovery was adequate in those patients who remained in remission after TBI. Patients with overt leukemia had transient reduction in blast counts, but rapid recurrence of their leukemia. Patients treated in remission had short remissions, with the exception of one patient who is in remission 32 months after treatment. There is some antileukemic effect of TBI even at 200 cGy, though this dose appears to be too low to help a significant number of patients. If TBI is to be escalated without stem cell support, then a thrombopoietic agent will need to be used.


Molecular characteristics of ofloxacin mono-resistant Mycobacterium tuberculosis isolates from new and previously treated tuberculosis patients.
Ofloxacin (OFX) resistant Mycobacterium tuberculosis (MTB) isolates have been increasingly observed and are a major concern in recent years. This study investigated the genetic mutations associated with OFX resistance among clinical OFX mono-resistant MTB isolates from new and previously treated tuberculosis patients. A total of 50 unrelated OFX mono-resistant MTB isolates were analyzed. For all isolates, the quinolone resistance determining regions of gyrA and gyrB were PCR amplified and sequenced. Single mutations in the quinolone resistance determining regions of gyrA (positions D94A, G, N, and Y; A90V; and S91P) and gyrB (positions T539A and E540D) were observed in 62% (31/50) and 4% (2/50) of all OFX mono-resistant isolates, respectively. No differences were detected between the proportions of isolates with mutations in gyrA/gyrB from new and previously treated tuberculosis patients (P=.820). Although mutations in gyrB were rare, they were as important as mutations in gyrA in predicting OFX resistance in MTB in Tianjin, China.


Occult primary seminoma: eighteen-year delay in presentation.
Primary retroperitoneal seminoma is well documented. A case is reported in which a patient presented with a seminoma of testis eighteen years after removal of a retroperitoneal seminoma. Histologic appearance of the testis was identified to the original pathology, and it is proposed that this represents recurrence of an occult testicular seminoma.


Evaluation of Asymptomatic Contralateral Foot Deformities Using the Tripod Index.
The primary aim of this study was to determine the prevalence of asymptomatic pes planus and cavovarus foot deformities using the tripod index (TI). A retrospective study was conducted on 122 adult subjects over the age of 18 from January 2010 to December 2016 with symptomatic pes planus (n=78) or cavovarus (n=44) foot deformities. We subdivided both groups into subjects who presented with unilateral symptomatic deformities (pes planus unilateral symptomatic; cavovarus unilateral symptomatic) and bilateral symptomatic foot deformities (pes planus bilateral symptomatic feet and cavovarus bilateral symptomatic feet). The severity of TI was compared between sides. The prevalence of asymptomatic pes planus and cavovarus foot deformities was 52% and 67.6%, respectively. Subjects with unilateral symptomatic foot deformities had significantly more severe TI values for the symptomatic cavovarus foot -98.96% (-288.89 to 0%) compared to asymptomatic cavovarus -67.41% (-270.59 to 14.71%) (p=0.015). Subjects with unilateral symptomatic pes planus deformity also had more severe TI on the symptomatic foot 57.49 (-9.38 to 141.67%) compared to the asymptomatic foot 30.43 (-51.52 to 119.23%) (p<0.01). Subjects with bilateral symptomatic foot deformities had no significant difference in severity of Tripod Index between feet. Although half of subjects with unilateral symptomatic deformities had a foot deformity on the contralateral side, the severity of deformity between symptomatic and asymptomatic feet was significantly different for both pes planus and cavovarus feet. Further studies should prospectively follow postoperative radiographs to determine whether a correction in foot alignment directly improves symptoms.Level of evidence: III.


Risk factors for SARS-CoV-2 infection among health workers in India: a case control study.
COVID-19 was declared as a Public Health Emergency of International Concern on 30th January 2020. Compared to the general population, healthcare workers and their families have been identified to be at a higher risk of getting infected with COVID-19. Therefore, it is crucial to understand the risk factors responsible for the transmission of SARS-CoV-2 infection among health workers in different hospital settings and to describe the range of clinical presentations of SARS-CoV-2 infection among them. A nested case-control study was conducted among healthcare workers who were involved in the care of COVID-19 cases for assessing the risk factors associated with it. To get a holistic perspective, the study was conducted in 19 different hospitals from across 7 states (Kerala, Tamil Nadu, Andhra Pradesh, Karnataka, Maharashtra, Gujarat, and Rajasthan) of India covering the major government and private hospitals that were actively involved in COVID-19 patient care. The study participants who were not vaccinated were enrolled using the incidence density sampling technique from December 2020 to December 2021. A total of 973 health workers consisting of 345 cases and 628 controls were recruited for the study. The mean age of the participants was observed to be 31.17 ± 8.5 years, with 56.3% of them being females. On multivariate analysis, the factors that were found to be significantly associated with SARS-CoV-2 were age of more than 31 years (adjusted odds ratio [aOR] 1.407 [95% CI 1.53-1.880]; p = 0.021), male gender (aOR 1.342 [95% CI 1.019-1.768]; p = 0.036), practical mode of IPC training on personal protective equipment (aOR 1. 1.935 [95% CI 1.148-3.260]; p = 0.013), direct exposure to COVID-19 patient (aOR 1.413 [95% CI 1.006-1.985]; p = 0.046), presence of diabetes mellitus (aOR 2.895 [95% CI 1.079-7.770]; p = 0.035) and those received prophylactic treatment for COVID-19 in the last 14 days (aOR 1.866 [95% CI 0.201-2.901]; p = 0.006). The study was able to highlight the need for having a separate hospital infection control department that implements IPC programs regularly. The study also emphasizes the need for developing policies that address the occupational hazards faced by health workers.


[Difficult diagnosis of cholelithiasis: advantages and disadvantages of laparoscopic cholangiography and ERCP. Our own experience].
On the basis of personal experience (104 LTC and 88 ERCP), the value of direct cholangiography in the diagnosis of biliary lithiasis especially in the event of failure of traditional radiology and in the presence of icterus is confirmed. LTC in 37 patients and ERCP in 18 revealed calculosis of the bile ways, thus correcting a falsely negative echography and i.v. cholangiography to the extent of 70% and 25% respectively. Stress is laid on the importance of direct cholangiography because it is able to establish the site of the stones and, above all, the pathology associated with calculosis, involving not only the bile ways, but the papilla, pancreas and liver too.


IDH-1 polymorphisms in pilocytic astrocytomas.
As of 2016, isocitrate dehydrogenase (IDH)-1 and IDH-2 mutations are part of the definition of an oligodendroglioma and may be seen in a significant subset of grade II-IV fibrillary astrocytomas. Reports of IDH-1 and IDH-2 alterations in pilocytic astrocytomas have been rare. This study reports two cases of pilocytic astrocytomas which harbored IDH-1 polymorphisms (G105G) (c.315C > T) discovered on polymerase chain reaction (PCR) testing and sequencing. The first was encountered in a 21-year-old male with a right orbital frontal pole mass. The second occurred in a 19-year-old female with a right frontal tumor. Neither tumor stained with antibody to IDH-1 (R132H). No BRAF V600E immunostaining, minimal p53 staining (<5%) and no loss of ATRX staining was noted in both cases. The significance of the IDH-1 findings at this juncture is uncertain. Misdiagnosis of the tumor as a fibrillary astrocytoma or oligodendroglioma due to the presence of an IDH alteration should be avoided.


Characteristics of harringtonine-resistant human leukemia HL60 cell.
To study the mechanisms of the resistance to harringtonine (Har) in the HL60 cells. Growth inhibition, karyotype analysis, flow cytometry, Western blotting and polymerase chain reaction. The Har-resistant HL60 cell line, named HR20, showed cross resistance to homoharringtonine, doxorubicin, daunorubicin, vincristine, and colchicine. The growth doubling time and the cell numbers in G1 phase were increased. The accumulation of cellular daunorubicin in the resistant cells was obviously reduced, but distinctly increased by tetrandrine and verapamil. The numbers of telocentromeric chromosome increased and the chromosomal aberration more occured in the resistant cells. The resistant cells overexpressed multidrug resistant mdr-1 gene and P-glycoprotein 150 kDa. The Har-resistant HL60 cell strain belonged to a multidrug resistance strain, overexpressing mdr-1 gene and P-glycoprotein.


Plant tissue-based chemiluminescence biosensor for ethanol.
A plant tissue-based chemiluminescence biosensor for ethanol based on using mushroom (Agaricus bisporus) tissue as the recognition element is proposed in this paper. The principle for ethanol sensing relies on the luminol-potassium hexacyanoferrate(III)-hydrogen peroxide transducer reaction, in which hydrogen peroxide is produced from the ethanol enzymatic catalytic oxidation by oxygen under the catalysis of alcohol oxidase in the tissue column. Under optimum conditions, the method allowed the measurement of ethanol in the range of 0.001 - 2 mmol/l with a detection limit (3 sigma) of 0.2 micromol/l. The relative standard deviation (RSD) was 4.14% (n = 11) for 0.05 mmol/l ethanol. The proposed method has been applied to the determination of ethanol in biological fluids and beverages with satisfactory results.


Enantioseparation of binaphthol and its mono derivatives by cyclodextrin-modified capillary zone electrophoresis.
Chiral binaphthols belong to the group of most effective ligands for asymmetrical catalysis. In this context, various binaphthols presenting original substituents have been synthesized. Their study through capillary electrophoresis is the object of this work. The literature dedicated to the separation of atropisomers by capillary electrophoresis, corresponding only to binaphthol, reveals that its enantioseparation is always delicate because of the influence of many factors and the resolutions obtained are weak. Therefore, for a structured optimization, we first successfully evaluated the acidity constants of different binaphthols by means of capillary electrophoresis. With these known physicochemical characteristics, we could successfully carry out enantiomeric separations of the different binaphthols at pH 11.5, practically in completely ionized form, in phosphate medium, and in the presence of cyclodextrin (CD), with analysis times lower than 8min. The nature of CDs (alpha-CD, beta-CD, gamma-CD, hydroxypropyl-alpha-cyclodextrin (HP-alpha-CD), HP-beta-CD, HP-gamma-CD and trimethyl-beta-CD (TM-beta-CD)) and other factors in relation to enantiomeric resolution (applied voltage, nature and concentration of the electrolyte, and concentration of cyclodextrin) were optimized. These studies allowed us to determine the optimal conditions of separation (concentration and nature of CD) for each of the studied binaphthols. It is necessary to mention that, for the 1,1'-binaphthyl-2,2'-diol (Binol) at pH 11.5, the S atropisomer always migrated first, regardless of the nature and concentration of the cyclodextrin used. Moreover, an inversion in elution order of the two atropisomers as a function of pH was observed with gamma-CD (pH range: 10-11.5). The R atropisomer migrated first at pH 10. At pH 10.8 the migration order of the two atropisomers of Binol was reversed as a function of gamma-CD concentration. Finally, the addition of chiral ionic liquids (R(-)-1-hydroxy-N,N,N-trimethylbutan-2-aminium bis(trifluoromethylsulfonyl)imide and S(+)-tetrabutylammonium camphorsulfonate) was conducted. In the case of S(+)-tetrabutylammonium camphorsulfonate, a weak antagonistic effect was observed with modeling the evolution of enantiomeric resolution by means of the experimental design, while in the case of R(-)-1-hydroxy-N,N,N-trimethylbutan-2-aminium bis(trifluoromethylsulfonyl)imide the effect was neutral.


Antibody-cytokine fusion proteins: Biopharmaceuticals with immunomodulatory properties for cancer therapy.
Cytokines have long been used for therapeutic applications in cancer patients. Substantial side effects and unfavorable pharmacokinetics limit their application and may prevent dose escalation to therapeutically active regimens. Antibody-cytokine fusion proteins (often referred to as immunocytokines) may help localize immunomodulatory cytokine payloads to the tumor, thereby activating anticancer immune responses. A variety of formats (e.g., intact IgGs or antibody fragments), molecular targets (e.g., extracellular matrix components and cell membrane antigens) and cytokine payloads have been considered for the development of this novel class of biopharmaceuticals. This review presents the basic concepts on the design and engineering of immunocytokines, reviews their potential limitations, points out emerging opportunities and summarizes key features of preclinical and clinical-stage products.


Regulation of copper transporters in human cells.
Copper is essential for normal growth and development of human organisms. The role of copper as a cofactor of important metabolic enzymes, such as cytochrome c oxidase, superoxide dismutase, lysyl oxidase, dopamine-β-hydroxylase, and many others, has been well established. In recent years, new regulatory roles of copper have emerged. Accumulating evidence points to the involvement of copper in lipid metabolism, antimicrobial defense, neuronal activity, resistance of tumor cells to platinum-based chemotherapeutic drugs, kinase-mediated signal transduction, and other essential cellular processes. For many of these processes, the precise mechanism of copper action remains to be established. Nevertheless, it is increasingly clear that many regulatory and signaling events are associated with changes in the intracellular localization and abundance of copper transporters, as well as distinct compartmentalization of copper itself. In this review, we discuss current data on regulation of the localization and abundance of copper transporters in response to metabolic and signaling events in human cells. Regulation by kinase-mediated phosphorylation will be addressed along with the emerging area of the redox-driven control of copper transport. We highlight mechanistic questions that await further testing.


Application of KU812 cells for assessing complement activation related effects by nano(bio)materials.
Immunocompatibility issues related to nano(bio)materials, particularly liposomal formulations, involving activation of the complement system have been relatively well described however, they highlight the importance of preclinical evaluation of such interactions. These complement-mediated hypersensitivity reactions, in which basophils are implicated, are associated with complement activation-related pseudoallergy (CARPA). Ex vivo investigation of such events using primary basophils is technically challenging due to the relatively limited number of circulating basophils in peripheral blood. In the current work, the KU812 cell line has been applied as an in vitro model for basophil activation to investigate CARPA-related responses following exposure to test materials obtained from the REFINE consortium. To that end, we developed a standard operating procedure measuring a panel of cell-surface markers indicative of basophilic activation. Two laboratories performed the assays, demonstrating a clear difference in responses between liposomal and polymeric nano(bio)materials, while interlaboratory comparison of the standard operating procedure demonstrated reproducibility in results, between the two facilities. These results suggest the potential to use this protocol as a screening method for such responses however, validation using primary basophils is now warranted.


In silico identification of natural fungicide from Melia azedarach against isocitrate lyase of Fusarium graminearum.
Isocitrate Lyase (ICL) is a crucial enzyme involved in the Glyoxylate pathway, essential for the virulence of several fungal pathogens including Fusarium graminearum. ICL is a novel target for the discovery of antifungal compounds and F. graminearum ICL inhibitors can be used to control the growth of this fungus. Although, several inhibitors of ICL have been identified, however, most of these inhibitors are not environment-friendly. Hence there is still a need to discover natural inhibitors of ICL that can be more effective. To identify a potential antifungal compound, we performed a structure-based screening of phytochemicals of Melia azedarach against the FgICL structure by molecular docking and 104 ligands were found to have a better docking score as compared to the reference molecule. These compounds were assessed for drug-likeness and ADMET prediction. After molecular docking, drug-likeness and toxicity analysis, six potential compounds (Melianoninol (-6.6 kcal/mol), Nimbinene (-7.7 kcal/mol), Vilasinin (-8.1 kcal/mol), Fraxinellone (-6.7 kcal/mol), Gedunin (-7.8 kcal/mol), and Meldenin (-7.8 kcal/mol)) were subjected for rescoring by X-Score. The structural stability and dynamics of screened compounds at the active site of FgICL were examined using MD simulation and MM-PBSA analysis. The result of MM-PBSA revealed that four phytochemicals viz. Melianoninol, Nimbinene, Vilasinin, and Fraxinellone had binding free energy of -17.25 kcal/mol, -59.35 kcal/mol, -64.79 kcal/mol, and -29.86 kcal/mol, respectively. Molecular dynamics simulation and MM-PBSA demonstrated that these four phytochemicals displayed considerable significant structural and pharmacological properties and could be probable antifungal drug candidates against F. graminearum. These phyotchemicals of M. azedarach may be suitable candidates for further experimental analysis. [Formula: see text]Communicated by Ramaswamy H. Sarma.


Influence of the hydric environment on sexual differentiation of turtles.
Phenotypic sex of hatching painted turtles (Chrysemys picta), a species known to exhibit temperature-dependent sex determination, is influenced by the hydric environment to which developing embryos are subjected. Hatching sex ratios vary significantly over the range of 26.5 to 28.5 degrees C due to effects of the hydric environment.


Evaluating the relationship between working memory and information processing speed in multiple sclerosis.
The aim of the present study was to evaluate the effect of information processing speed on the functioning of specific working memory components, i.e. phonological loop, visuospatial sketchpad, central executive and episodic buffer. Cognitive tasks that assess working memory ("word lists recall" for the phonological loop, "block recall" for the spatial component of visuospatial sketchpad, "listening recall" for the central executive and "immediate story recall" for the episodic buffer) and information processing speed (symbol digit modalities test- oral form) were administered to 38 patients with multiple sclerosis. Results showed that the central executive and episodic buffer components were significantly related to information processing speed. However, when age was included in the regression model, information processing speed significantly predicted only the episodic buffer scores. Further research on the relationship between the episodic buffer and information processing speed is recommended.


How Recent Advances in Biology of Waldenström's Macroglobulinemia May Affect Therapy Strategy.
Waldenström macroglobulinemia (WM) is a rare lymphoproliferative disorder. Up to now, therapeutic choice was not influenced by the biological characteristics of the disease. Here, we will review how recent advances in biology in WM may affect therapy strategy. Recently, WM has been described as a new oncogenic model. MyD88 mutation has been described as a key driver mutation and has functional consequences which could be targeted. Other mutations, such as CXCR4 or TP53, have been reported. These mutations are associated with different clinical presentation, prognosis, and treatment response. Mutational status may influence therapeutic choice in some patients but additional data are required. New targeted therapies are on development.


Purification and characterization of wheat germ 2',3'-cyclic nucleotide 3'-phosphodiesterase.
The 2',3'-cyclic nucleotide 3'-phosphodiesterase which hydrolyzes nucleoside 2',3'-cyclic phosphates (N greater than p) to nucleoside 2'-phosphates has been purified 16,000-fold to near homogeneity from wheat germ. The purified enzyme is a single polypeptide with a molecular weight of 23,000-24,000. It has a pH optimum of 7.0. The apparent Km values for A greater than p, G greater than p, C greater than p, and U greater than p are 13.1, 9.2, 25.2, and 25.3 mM, respectively. Vmax values for A greater than p, G greater than p, C greater than p, and U greater than p are 2090, 280, 2140, and 600 mumol/min/mg of purified protein, respectively. Wheat germ 2',3'-cyclic nucleotide 3'-phosphodiesterase does not hydrolyze 2',3'-cyclic esters in cyclic phosphate-terminated oligoribonucleotides or in nucleoside 5'-phosphate, 2',3'-cyclic phosphate (pN greater than p). This is in contrast to the 3'-phosphodiesterase activity associated with a wheat germ RNA ligase which hydrolyzes cyclic phosphate-terminated oligonucleotides and pN greater than p substrates much more efficiently than nucleoside 2',3'-cyclic phosphates. The enzyme characterized in this work appears to be the only known 2',3'-cyclic nucleotide 3'-phosphodiesterase specific for 2',3'-cyclic mononucleotides.


6-Formylindolo[3,2-b]carbazole reduces apoptosis induced by benzo[a]pyrene in a mitochondrial-dependent manner.
Benzo[a]pyrene (B[a]P), a potent carcinogen, has been proved that it can induce apoptosis via activation of the aryl hydrocarbon receptor (AhR) pathway. The metabolite of tryptophan 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous activator of AhR, plays bifunctional roles in cell growth and apoptosis. However, whether and how FICZ can reduce the toxicity of B[a]P and the mechanism underlying this remain unclear. In this study, FICZ interfered with the toxicity of B[a]P in mouse hepatocarcinoma cell line Hepa1-6. The results of the MTT assay indicated that FICZ and B[a]P made opposite effects on cell proliferation. The scratch-wound healing assay showed that B[a]P (1 µM for 24 hr) exposure triggered cell migration and that was inhibited by FICZ (10 nM). In addition, FICZ ameliorated B[a]P-induced apoptosis by inhibiting reactive oxygen species generation and caspase-3 activation, as well as increasing reduced glutathione level in mitochondria. Furthermore, gene expression analyses indicated that FICZ competed with B[a]P, which reduced the transcriptional activation of the cyp1a1 and cyp1b1 genes, as well as Bcl2 and P53. Accordingly, the interaction between FICZ and B[a]P in the AhR pathway inhibited apoptosis in a mitochondrial-dependent manner, suggesting that endogenous compound may reduce the toxicity of exogenous pollutant in vivo and providing an available way to improve health condition related to the hepatic metabolic disorder.


Parental knowledge of pre-school child oral health.
The dental health of preschool children has extensive implications on the oral heath of the individual as he grows into an adult. Parents/guardians of preschool children play a central role in enforcing proper oral hygiene and preventive regime in these children. This study was conducted with the aim of describing the views of parents/guardians about the dental health of pre-school children. Response was obtained on a 21 point questionnaire from randomly visiting parents of the outpatient section of Rajah Muthiah dental college and Hospital, Annamalainagar, India. The findings of the present study point towards poor awareness among the parents/guardians of preschool children, pertaining to their childs' oral health and this could directly translate to poor oral health among the children in this area.


Antenatal hormone therapy for fetal lung maturation.
In summary, several agents have been studied, but only CS and thyroid hormones have been found to accelerate fetal lung maturation in animal studies. Thirty years of research has documented the beneficial effect of antenatal CS on fetal lung maturation, and antenatal steroid in combination with postnatal surfactant remains the mainstay of prevention and therapy for RDS in preterm infants. The efficacy and safety of postnatal steroids have yet to be demonstrated. Unfortunately, the addition of antenatal TRH to this regimen has not provided further benefit to the neonatal outcome of preterm infants as evidenced by the recently completed multicenter trials. In addition, the optimal number of courses of antenatal CS for lung maturation remains unclear.


Functional roles in S-adenosyl-L-methionine binding and catalysis for active site residues of the thiostrepton resistance methyltransferase.
Resistance to the antibiotic thiostrepton, in producing Streptomycetes, is conferred by the S-adenosyl-L-methionine (SAM)-dependent SPOUT methyltransferase Tsr. For this and related enzymes, the roles of active site amino acids have been inadequately described. Herein, we have probed SAM interactions in the Tsr active site by investigating the catalytic activity and the thermodynamics of SAM binding by site-directed Tsr mutants. Two arginine residues were demonstrated to be critical for binding, one of which appears to participate in the catalytic reaction. Additionally, evidence consistent with the involvement of an asparagine in the structural organization of the SAM binding site is presented.


A multi-institutional study of 1,111 men with 4K score, multiparametric magnetic resonance imaging, and prostate biopsy.
Prostate magnetic resonance imaging (MRI) and biomarkers are often used in conjunction to enhance the selection process for prostate biopsy. However, the optimal sequence of ordering these tests has not been established. A comprehensive evaluation was conducted on a large multi-institutional cohort of patients who underwent MRI, 4K score, and biopsy of the prostate to examine the impact of utilizing both tests vs. either test alone and to determine if the order in which these tests are administered affects the ability to detect clinically significant prostate cancer (csCaP). We evaluated men from 8 different institutions who were referred for prostate cancer evaluation and underwent MRI, 4K score test, and prostate biopsy. The primary outcome was the presence of csCaP, defined as grade group 2 or higher cancer on a biopsy of the prostate. We used logistic regression, calibration plots, and decision curve analysis to evaluate using a 4K score or MRI alone vs. both tests together for detecting csCaP. In addition, we evaluated several strategies using one or both tests for selecting men for biopsy and compared them based on the proportion of biopsies avoided and the csCaP's missed. Among the 1,111 men who formed the final cohort, 553 (49.8%) had prostate cancer, and 353 (31.8%) had csCaP. We found that using MRI and 4K score together had better discrimination, calibration, and a higher clinical utility on decision curve analysis compared to using either test individually. Using both tests together resulted in fewer biopsies avoided and missed cancers compared to using either test alone. Strategies that sequence MRI and 4K score tests resulted in the largest biopsy reduction, with no appreciable difference between starting with an MRI vs. a biomarker. We found that using both an MRI and 4K score together was superior to using either test alone but found no appreciable difference between starting with an MRI vs. starting with a 4K score. Prospective studies are needed to identify the best strategy to sequence MRI and biomarkers in the evaluation of csCaP.


Individual risk profiles for postoperative delirium after joint replacement surgery.
Delirium occurs in nearly half of older patients after joint replacement surgery. However, risk profiles for developing delirium have not been established. We sought to identify risk profiles for delirium in patients following joint replacement surgery. Based on data from a randomized, double-blind, placebo-controlled trial of olanzapine (10 mg) as delirium prophylaxis in 400 patients (67-81 years old) undergoing hip or knee replacement surgery, we performed a signal detection analysis to develop risk profiles for postsurgical delirium (using baseline patient characteristics, iatrogenic factors, and physiologic response parameters). Olanzapine reduced the incidence of delirium by 63% relative to placebo. Among patients receiving placebo, those with an ASA class = 3 and age ≥ 74 years had a 64% risk of delirium. Those with ASA class < 3 still had a 67% risk of delirium if postoperative oxygen saturation was < 95%. Patients who received olanzapine had an 83% risk of developing delirium if they received ≥ 42.5 mg equivalents of intra-operative morphine, were ≥ 74 years old, and had a mean arterial pressure (MAP) < 90 mm Hg at the presurgical screening visit. Patients with the lowest risk (6%) of developing delirium received olanzapine had a hematocrit ≥ 28%, and a presurgical MAP ≥ 90. Although use of prophylactic olanzapine reduced the incidence of delirium, subsets of patients remained likely to develop delirium. The risk of developing delirium may be reduced through prophylactic dispensation of olanzapine, maintaining optimal perfusion and oxygenation, and limiting intra-operative opioids.


Successful resolution of a preputial prolapse in an alpaca using medical therapy.
A 2-year-old intact male alpaca was presented for a post-breeding preputial prolapse of 5 days duration. The internal lamina of the prepuce was prolapsed approximately 6 cm and the exposed preputial epithelium was edematous and necrotic. Following 7 days of medical treatment, resolution of the preputial prolapse was achieved.


Study of breast cancer incidence in patients of lymphangioleiomyomatosis.
Molecular evidence has linked the pathophysiology of lymphangioleiomyomatosis (LAM) to that of metastatic breast cancer. Following on this observation, we assessed the association between LAM and subsequent breast cancer. An epidemiological study was carried out using three LAM country cohorts, from Japan, Spain, and the United Kingdom. The number of incident breast cancer cases observed in these cohorts was compared with the number expected on the basis of the country-specific incidence rates for the period 2000-2014. Immunohistochemical studies and exome sequence analysis were performed in two and one tumors, respectively. All cohorts revealed breast cancer standardized incidence ratios (SIRs) ≥ 2.25. The combined analysis of all cases or restricted to pre-menopausal age groups revealed significantly higher incidence of breast cancer: SIR = 2.81, 95 % confidence interval (CI) = 1.32-5.57, P = 0.009; and SIR = 4.88, 95 % CI = 2.29-9.99, P = 0.0007, respectively. Immunohistochemical analyses showed positivity for known markers of lung metastatic potential. This study suggests the existence of increased breast cancer risk among LAM patients. Prospective studies may be warranted to corroborate this result, which may be particularly relevant for pre-menopausal women with LAM.


Comparative analysis of glutaredoxin domains from bacterial opportunistic pathogens.
Glutaredoxin proteins (GLXRs) are essential components of the glutathione system that reductively detoxify substances such as arsenic and peroxides and are important in the synthesis of DNA via ribonucleotide reductases. NMR solution structures of glutaredoxin domains from two Gram-negative opportunistic pathogens, Brucella melitensis and Bartonella henselae, are presented. These domains lack the N-terminal helix that is frequently present in eukaryotic GLXRs. The conserved active-site cysteines adopt canonical proline/tyrosine-stabilized geometries. A difference in the angle of α-helix 2 relative to the β-sheet surface and the presence of an extended loop in the human sequence suggests potential regulatory regions and/or protein-protein interaction motifs. This observation is consistent with mutations in this region that suppress defects in GLXR-ribonucleotide reductase interactions. These differences between the human and bacterial forms are adjacent to the dithiol active site and may permit species-selective drug design.


Acute Mesenteric Ischemia in Patients with COVID-19: Review of the literature.
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global health emergency. In addition to common respiratory symptoms, some patients with COVID-19 infections may experience a range of extra-pulmonary manifestations, such as digestive system involvement. Patients with COVID-19 have been reported to suffer from acute mesenteric ischemia (AMI) that is associated with disease-related severity and mortality. However, in the context of COVID-19, the exact cause of AMI has yet to be clearly defined. This review provides a comprehensive overview of the available data and elucidates the possible underlying mechanisms linking COVID-19 to AMI, in addition to highlighting therapeutic approaches for clinicians. Finally, given the severe global impact of COVID-19, we emphasize the importance of coordinated vaccination programs.


Size-specific sensitivity of cladocerans to freshwater salinization: Evidences from the changes in life history and population dynamics.
The salinization of the global freshwater system caused by various human activities and climate change has become a common problem threatening freshwater biodiversity and resources, which may affect a variety of species of cladocerans at individual and population levels. In order to comprehensively evaluate the impact of salinization on different-sized cladocerans at individual and population levels, we exposed two species of cladocerans with obvious body size difference, Daphnia magna and Moina macrocopa, to seven salinities (0, 0.02, 0.04, 0.06, 0.08, 0.10, 0.12 M), recorded individual life history traits and population growth dynamics, and used multiple mechanistic models to fit the data. At the individual level, the median effect concentration of survival time, total offspring per female, and number of broods of D. magna were significantly higher than those of M. macrocopa. At the population level, the decrease in carrying capacity of D. magna with increasing salinity was significantly less than that of M. macrocopa. At the same salinity treatment, the integrated biomarker response indexes value of M. macrocopa is higher than that of D. magna. Therefore, it was further inferred that the sensitivity of small-sized species M. macrocopa to salinity stress is significantly higher than that of big-sized species D. magna. Thus, freshwater salinization may result in the replacement of smaller salt-intolerant cladocerans with larger salt-tolerant cladocerans, which may have dramatic effects on freshwater communities and ecosystems. Additionally, the increase of salinity had a greater impact on the population level of D. magna and M. macrocopa than on the individual level, indicating that population level of cladocerans was more susceptible to salinity stress. Experiments only based on individuals may underestimate the ecologically related changes in populations and communities, thus understanding the impact of salinization on freshwater systems needs to consider multiple ecological levels.


Hair Cell Loss, Spiral Ganglion Degeneration, and Progressive Sensorineural Hearing Loss in Mice with Targeted Deletion of Slc44a2/Ctl2.
SLC44A2 (solute carrier 44a2), also known as CTL2 (choline transporter-like protein 2), is expressed in many supporting cell types in the cochlea and is implicated in hair cell survival and antibody-induced hearing loss. In mice with the mixed C57BL/6-129 background, homozygous deletion of Slc44a2 exons 3–10 (Slc44a2(Δ/Δ)resulted in high-frequency hearing loss and hair cell death. To reduce effects associated with age-related hearing loss (ARHL) in these strains, mice carrying the Slc44a2Δ allele were backcrossed to the ARHL-resistant FVB/NJ strain and evaluated after backcross seven(N7) (99 % FVB). Slc44a2(Δ/Δ) mice produced abnormally spliced Slc44a2 transcripts that contain a frame shift and premature stop codons. Neither full-length SLC44A2 nor a putative truncated protein could be detected in Slc44a2(Δ/Δ) mice, suggesting a likely null allele. Auditory brain stem responses (ABRs) of mice carrying the Slc44a2Δ allele on an FVB/NJ genetic background were tested longitudinally between the ages of 2 and 10 months. By 6 months of age,Slc44a2(Δ/Δ) mice exhibited hearing loss at 32 kHz,but at 12 and 24 kHz had sound thresholds similar to those of wild-type Slc44a2(+/+) and heterozygous +/Slc44a2Δ mice. After 6 months of age, Slc44a2(Δ/Δ) mutants exhibited progressive hearing loss at all frequencies and +/Slc44a2(Δ) mice exhibited moderate threshold elevations at high frequency. Histologic evaluation of Slc44a2(Δ/Δ) mice revealed extensive hair cell and spiral ganglion cell loss, especially in the basal turn of the cochlea. We conclude that Slc44a2 function is required for long-term hair cell survival and maintenance of hearing.


[Application of computer systems in perinatology. II. Organization of computer systems in intensive care of the fetus and newborn].
The main computer systems used in perinatal medicine are described, with particular reference to the systems of analysis of perinatal data, analysis of cardiotocogram, obstetric ultrasonogram, assessment of the heart function of the newborn, records of respiratory activity in newborns, and use of computers in parenteral alimentation of newborns.


Economical, green and dual-function pyridyl iodides as electrolyte components for high efficiency dye-sensitized solar cells.
Pyridyl iodides were synthesized to serve as effective, economical, green and dual function additives for high efficiency and stable DSCs. Using commercial P25 as the photoanode, a high PCE of 7.81% was achieved with a pyridyl iodide-containing electrolyte. Meanwhile, DSCs based on our novel electrolytes demonstrated better stability.


Vagal mechanisms controlling serotonin release from the gastrointestinal tract and pyloric motor function.
This chapter focuses on investigations of two mechanisms controlled by the vagal nerve; serotonin (5-HT) release from the small intestine and pyloric motor function. Morphological, physiological, pharmacological and biochemical methods were combined in these studies. 5-HT is mainly stored in enterochromaffin cells (EC), but is present also in mast cells and nerve terminals of the gut, as observed by immunocytochemistry. Vagal nerve stimulation causes a release of 5-HT from EC to the portal circulation and to the gut lumen. Morphological evidence for the endoluminal release of 5-HT was obtained by autoradiography and immunofluorescence. The 5-HT release from EC is mediated by a beta-adrenoceptor mechanism via sympathetic adrenergic fibers in the vagal nerve, originating from sympathetic ganglia, e.g. the superior cervical ganglion. This vagal adrenergic pathway was studied by fluorescence microscopy and retrograde tracing of horseradish peroxidase. The vagal peptidergic (nonadrenergic, noncholinergic) control of pyloric motor function was studied in chloralosed cats by means of an in vivo model, where changes of an applied flow of body-warm saline through the pylorus were recorded. Also, gastric volume changes were monitored. By means of immunofluorescence the presence of VIP-, enkephalin (ENK)- and substance P (SP)-like immunoreactivity was demonstrated in pyloric neurons and in the vagal nerve. Physiological evidence for a vagal VIPergic relaxatory mechanism was obtained, while ENK-neurons seem to mediate the vagally induced pyloric contraction, prevented by naloxone pretreatment. SP may mediate part of the vagally induced pyloric and gastric contraction, the latter probably via axon collaterals on final cholinergic neurons. ENKergic and SPergic vagal contractile mechanisms seem to be additive for the pylorus.


Nonparallel secretion of enzymes in human duodenal juice and pure pancreatic juice collected by endoscopic retrograde catheterization of the papilla.
Duodenal juice was collected from 50 healthy patients in the basal state, and after intravenous injection of 1 clinical unit of secretin kg-1 + 3 Crick-Harper-Raper units of cholecystokinin-pancreozymin (CCK-PZ) kg-1. Amylase to chymotrypsin and amylase to lipase ratios were significantly decreased by stimulation. Pure pancreatic juice was collected from 7 healthy subjects by endoscopic retrograde catheterization of the papilla. Secretin (1 clinical unit kg-1 hr-1) was infused intravenously during 30 min, and a single intravenous injection of CCK-PZ (3 Crick-Harper-Raper units kg-1) was done at the 15th min of the secretin infusion. Chymotrypsinogen and lipase secretions did not parallel that of amylase during CCK-PZ stimulation. As in the first set of experiments, amylase secretion was proportionally less stimulated by CCK-PZ injection than were chymotrypsinogen and lipase secretions. However, in approximately 20% of subjects the secretion of the enzymes was parallel in both duodenal and pancreatic juice.


[Secular trend of physical development and its significance for pediatric practice].
A review is given on the secular trend of the somatic development, on its part-phenomena and on the mutual interest of the human biology as well as the pediatric practice. The author presents two example of a positive secular trend in Hungary concerning the growth of height and the maturation in girls, respectively. This last one, however, shows also a negative tendency in the last decades.


Development and validation of the interview version of the Hong Kong Chinese WHOQOL-BREF.
The Hong Kong Chinese version of the WHOQOL-BREF was designed as a self-administered questionnaire and has limitations in clinical application on subjects who have limitations in reading or writing. An interview version is therefore needed to avoid sampling biases in clinical studies. Since there are significant differences in the written Chinese and spoken Cantonese, which is a dialect commonly spoken among people in Hong Kong, and adaptation process for converting the written Chinese into spoken Cantonese was necessary. The interview version was designed to allow administration in both face-to-face interview and telephone interview mode. Three members of the research team translated the formal written Chinese in the self-administered version of the WHOQOL-BREF(HK) into colloquial Cantonese separately. Brief notes extracted from the facet definitions of the WHOQOL-100 were added in brackets after some questions to further explain the intention of the questions. Two series of focus groups were conducted and subsequently the field test version was produced. 329 subjects were recruited by convenient sampling method for the field test. The interview version and the self-administered version was found equivalent. The ICC values of the domain scores ranged from 0.73 in the environment domain to 0.83 in the psychological domain. The face-to-face interview and telephone interview mode of administration were also found equivalent. The ICC for the domain scores ranged from 0.76 in the social interaction domain to 0.84 in the psychological domain. The other psychometric properties of the interview version were found comparable to the self-administered version. The self-administered and the interview version of the WHOQOL-BREF are regarded as identical in group comparison. The authors advise that it is acceptable to use different versions on different subjects in the same study, provided that the same version is applied on the same subject throughout the study.


An expert curated global legume checklist improves the accuracy of occurrence, biodiversity and taxonomic data.
The Legume Phylogeny Working Group's Taxonomy Working Group was tasked to create a community endorsed global legume checklist that will serve as a primary source of taxa for biodiversity data platforms and legume-related research. The checklist was published in June 2021, recognising 772 genera and 22,360 species. It is disseminated through the new Legume Data Portal as part of the Global Biodiversity Information Facility (GBIF) hosted portal initiative. The process that was followed to publish and disseminate the checklist and its content is described here. The impact of the work by the Taxonomy Working Group are quantified by comparing the published checklist with the GBIF taxonomic backbone. A total of 44,157 names overlapped with the GBIF taxonomic backbone while 30,456 names were added, which enabled more accurate name matching of 61,235 legume occurrences. Continuous improvement to the World Checklist of Vascular Plants (WCVP): Fabaceae checklist will allow the GBIF taxonomic backbone and other checklist managers to converge to a consistent and comprehensive list of legume taxa globally over time.


Expression and localization of relaxin family peptide receptor 4 in human spermatozoa and impact of insulin-like peptide 5 on sperm functions.
Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily peptide that interacts with the relaxin family peptide receptor 4 (RXFP4). Numerous recent studies have focused on the functional effects of INSL5 on fat and glucose metabolism. Although there is no evidence that the human sperm may be a candidate target of INSL5, it has been detected in mice testis and sperm. Therefore, the present study sought to analyze the localization and expression of RXFP4 on human sperm and determine the efficiency of INSL5 in human sperm. Normal semen samples were incubated in different doses and exposure time periods of INSL5. We analyzed sperm motility by computer-assisted sperm analysis (CASA) and ROS levels by flow cytometry using the MitoSOX™ Red probe. Localization and expression of RXFP4 were assayed by immunofluorescence and RT-PCR, respectively. The results confirmed the presence of RXFP4 in human spermatozoa, which localized in the neck and midpiece of sperm. Nested PCR showed the expression of RXFP4 in human sperm. INSL5 could attenuate generation of mitochondrial ROS at the 1, 10, 30, and 100nmol/L doses. This result was particularly noted in the 30nmol/L treated samples after 4h incubation. Total motility of sperm was significantly preserved in the 100nmol/L after 2h and in 30nmol/L after 4h incubation period. This study, for the first time, clarified the expression and localization of RXFP4 on human sperm and revealed the role of INSL5 in sperm motility and mitochondrial ROS generation in a dose-dependent manner.


[Progression of Myopia - which Preventive Measures Can be Recommended?]
The prevalence of myopia shows a worldwide increase with large regional differences. Especially high myopia enhances the risk of irreversible vision loss due to myopic maculopathy or other secondary effects. Reducing the prevalence and progression of myopia in schoolchildren is therefore a main goal in ophthalmology. Spending at least two hours a day outdoors is the easiest way to reduce myopia progression. Another modifiable factor is to reduce continuous near work with distances of less than 30 cm. Low-dose atropine eye drops administered once daily over two or more years have been shown to reduce myopia progression. Optical interventions which have been effective are multifocal contact lenses or orthokeratology contact lenses, but these have the risk of microbial keratitis. Whereas neither under- nor overcorrection of myopia have been proven effective, new so-called multisegment glasses have reduced myopia progression. Most of the studies concerning atropine and optic interventions have been performed in groups of Asian children, which are known to have more severe myopia progression, although actually there are many studies being conducted on Caucasian children. Still, there is also a lack of studies contrasting pharmacologic against optic interventions and comparing these with a combination of methods. The decision to start optic or pharmacologic measures can therefore only be an individual decision and is mainly based on age, refraction and progression in the past, while environmental factors should be assessed first.


Comparable seropositivity for ascariasis and toxocariasis in tropical slum children.
The seropositivities for infection by Ascaris lumbricoides and Toxocara canis were determined in children (1-15 years old) of a slum area of Caracas, Venezuela, and the levels that indicate the presence of active infection were defined. In children aged from 1 to 3 years, approximately 10% were positive for either parasite, and this figure increased to about 30% in 4- to 6-year-olds. For toxocariasis, the percentage of positivity remained at this level up to the age of 15 years. Whilst the positivity in children 10-15 years of age was comparable for Ascaris and Toxocara, a peak of positivity (50%) was found for Ascaris at 7-9 years of age. These results indicate that for these urban slum children, infection by Toxocara is essentially as common as that by Ascaris and, thus, that toxocariasis represents a potential public health problem in the tropical environment that is largely overlooked.


Tracheostomy and infection prolong length of stay in hospital after surgery for head and neck cancer: a population based study.
To determine the factors that predict length of stay (LOS) in hospital after head and neck cancer (HNC) surgery for patients treated in public hospitals in Ireland between 2002 and 2010. Cancer registry data on patients with carcinoma of the oropharynx/larynx were identified and linked with hospital in-patient discharge records. Associations between clinical (e.g., surgery type, neoadjuvant chemoradiation), health service factors, and LOS were investigated by using negative binomial regression. Of the patients diagnosed with HNC, 50% (n = 1651) underwent HNC surgery. Median LOS was 10 days (range: 1-289). Variables associated with prolonged LOS included tracheostomy (neck dissection + tracheostomy versus neck dissection only: incident rate ratio [IRR] 2.66; 95% confidence interval [CI] 2.01-3.50); postoperative infection (IRR 2.26; 95% CI 1.94-2.62); and neoadjuvant radiotherapy (IRR 2.15; 95% CI 1.64-2.82). Advanced stage, gastrostomy, and reconstruction were also associated with prolonged LOS. Tracheostomy and postoperative infection were associated with prolonged LOS. Further investigation of these modifiable risk factors is warranted.


Discovery of Biased Mu-Opioid Receptor Agonists for the Treatment of Pain.
G protein-biased mu-opioid receptor (MOR) agonists have been developed as promising new potent analgesic drugs with fewer adverse side effects than standard MOR agonists. PZM21 represents a unique chemotype unrelated to known opioids, which makes it a desirable lead for modification to find analgesics with new chemical entities. In the present study, we synthesized and tested novel PZM21 derivatives as potent biased MOR agonists by introducing a benzodioxolane group to replace the hydroxybenzene of PZM21. The new compounds displayed more potent analgesic activities in vivo and greater bias toward G protein signaling in vitro than did PZM21. These results suggest that the benzodioxolane group is essential for the maintenance of bias. Compounds 7 i ((S)-1-(3-(benzo[d][1,3]dioxol-4-yl)-2-(dimethylamino)propyl)-3-phenethylurea) and 7 j ((S)-1-(3-(benzo[d][1,3]dioxol-4-yl)-2-(dimethylamino)propyl)-3-benzylurea) could serve as new leads for further modifications to find novel biased MOR agonists with greater G protein signaling potency and less β-arrestin-2 recruitment.


Effect of reperfusion on vascular smooth muscle reactivity in three contraction models.
Ischemia and reperfusion remain inseparable elements of numerous medical procedures such as by-pass surgery, organ transplantation or other cardiology and intervention radiology. The contraction of the smooth muscle of the vessel is considered to be one of the basic components leading to impaired perfusion, an increase in the oxygen deficit of the endothelium of the vessel, and subsequently also to tissues vascularized by the vessel. Main aim of this study was to evaluate the effect of ischemia and reperfusion on vascular smooth muscle cells stimulated pharmacologically with mastoparan-7 (direct G-protein activator) in comparison to stimulation of G-protein coupled receptor agonist - phenylephrine, and direct calcium channel activator - Bay K8644. Experiments were performed on isolated and perfused tail artery of Wistar rats. Contraction force in our model was measured by increased level of perfusion pressure with a constant flow. Concentration-response curves obtained for phenylephrine, mastoparan-7 and Bay K8644 presented a sigmoidal relation. Ischemia induced hyporreactivity of vessels, whereas during reperfusion the significant time related hyperreactivity for phenylephrine and mastoparan-7 only but not for Bay K8644. These reactions were secondary to the modulation of calcium influx from intra- and extracellular calcium stores. Results of our experiments suggest that mastoparan-7 significantly induces contraction of vascular smooth muscle cells not only for controls but in the presence of ischemia and reperfusion too. Potential therapeutic applications of the observed reactions are important. They may include regenerative processes within the nervous system, studies on the improvement of blood flow within the microcirculation, or antimicrobial activity. Modulation of the G protein-phospholipase C response may also be an interesting point of action of future drugs modifying the response to stimulation during ischemia in particular, such activities could take place during the transport of organs for transplantation.


Complication Risk Factors in Anterior Choroidal Artery Aneurysm Treatment.
The anterior choroidal artery (AChoA) is a rare location for intracranial aneurysms. The treatment of these aneurysms may be challenging due to the risk of occlusion of such a small and eloquent artery as the AChoA. We aimed to evaluate the risk factors for complications in AChoA aneurysm treatment. We retrospectively analyzed 47 consecutive AChoA aneurysms in 40 patients treated in our institution from 1999 and 2014 by endovascular means (87%) or surgical clipping (13%). Minor (transient or minor neurological deficits) and major complications (severe permanent neurological deficits or death) were systematically recorded. The influence of patient age, sex, aneurysm size, neck size, shape, dome-to-neck ratio and treatment technique on the occurrence of procedure-related complications was evaluated. Of the patients 11 experienced procedure-related complications (5 major, 6 minor). Aneurysms with multilobed shape were significantly associated with a higher procedure-related complication rate. There was a tendency for higher major procedure-related complication rate in small volume aneurysms. We did not find any association between the other factors analyzed and occurrence of procedure-related complications. Treatment of AChoA aneurysms has an acceptable complication risk. We did not find any significant differences between surgical and endovascular treatment in terms of procedure-related complication rates. Multilobed aneurysms were significantly associated with a higher procedure-related complication rate.


Interleukin-10 promoter polymorphisms in Chinese patients with Parkinson's disease.
Interleukin-10 (IL-10), an important anti-inflammatory cytokine, may influence the risk for the development of onset of sparadic Parkinson's disease (PD) in the inflammatory process. In this study, two DNA polymorphisms at IL-10 gene promoter (-819 T/C and -592 A/C) were examined in 355 sporadic PD patients and 200 healthy controls in Han Chinese Population. For both polymorphisms, no significant difference in genotype or allele distribution was found between PD patients and the controls. For -819 T/C polymorphisms, there was significant difference in genotype distribution between EOPD (EOPD, <50 years of age) patients and each healthy-matched control subgroup (P=0.011), as well as between female PD patients and each healthy-matched control subgroup (P=0.024), For -592 A/C polymorphisms, there were no significant gender- and age-related differences in genotype distribution between PD patients and the controls subgroup. Results from our study revealed that the IL-10 promoter (-819 and -592) polymorphism is not a risk factor of sporadic Parkinson's disease, but the IL-10 promoter -819 polymorphism is a risk factor of EOPD and female PD patients in Han Chinese population.


Superhydrophilic molecularly imprinted polymers based on a water-soluble functional monomer for the recognition of gastrodin in water media.
In this study, the first successfully developed superhydrophilic molecularly imprinted polymers (MIPs) for gastrodin recognition have been described. MIPs were prepared via the bulk polymerization process in an aqueous solution using alkenyl glycosides glucose (AGG) as the water-soluble functional monomer. The non-imprinted polymers (NIPs) were also synthesized using the same method without the use of the template. The dynamic water contact angles and photographs of the dispersion properties confirmed that the molecularly imprinted polymers displayed excellent superhydrophilicity. The results demonstrated that the MIPs exhibited high selectivity and an excellent imprinting effect. A molecularly imprinted solid phase extraction (MISPE) method was established. Optimization of various parameters affecting MISPE was investigated. Under the optimized conditions, a wide linear range (0.001-100.0μgmL(-1)) and low limits of detection (LOD) and quantification (LOQ) (0.03 and 0.09ngmL(-1), respectively) were achieved. When compared with the NIPs, higher recoveries (90.5% to 97.6%) of gastrodin with lower relative standard deviations values (below 6.4%) using high performance liquid chromatography were obtained at three spiked levels in three blank samples. These results demonstrated one efficient, highly selective and environmentally-friendly MISPE technique with excellent reproducibility for the purification and pre-concentration of gastrodin from an aqueous extract of Gastrodia elata roots.


Inhibition of equine neutrophil chemotaxis and chemokinesis by a Taenia taeniaeformis proteinase inhibitor, taeniaestatin.
Taeniaestatin, a recently isolated Taenia taeniaeformis proteinase inhibitor, was used to inhibit equine neutrophil migration. Taeniaestatin itself was not chemotactic when used as a chemotactic factor but taeniaestatin did inhibit neutrophil chemokinesis when tested in a Zigmond-Hirsch checkerboard assay. A dose-dependent inhibition of both chemokinesis and chemotaxis was observed when zymosan activated bovine sera (ZABS) was used as the chemotactic factor. This inhibition was greater than 95% when 5 mu of taeniaestatin was present on both the cell and chemotactic factor side of the chambers. Equine neutrophils gave dose- and time-dependent migration responses to purified bovine C5a with an ED50 of 1.04 X 10(-7)M. Taeniaestatin inhibited the C5a-mediated chemotactic and chemokinetic neutrophil responses (51% using 1 mu and greater than 95% with 5 mu of taeniaestatin). The inhibition of leucocyte motility by taeniaestatin was reversible and without cytotoxicity at the highest doses of taeniaestatin tested.


Defining, classifying, and placing incipient caries lesions in perspective.
A caries lesion begins with the introduction of a disease state, likely due to bacterial strains, in the oral cavity. If accompanied or followed by alterations to salivary flow, frequent periods of reduced salivary pH, or frequent intake of refined carbohydrates, the demineralization of tooth structure is likely to begin. The subsequent lesions first will be visible as white spot lesions, which if ignored, eventually will cavitate. Modern dentistry is capable of testing for the presence of caries lesions before cavitation, and it is suggested that routine testing should be mandatory for all patients who are at risk. If the disease is to be identified and treated before cavitation, it is desirable to adopt a new classification for the recognition and recording of caries lesions.


Design of space-multiplexed three-dimensional Omega networks and their optical implementation.
A method is described for arrangement of channels from different stages of a three-dimensional shuffle/exchange network so that only a single set of optics is needed to perform the two-dimensional shuffles. This arrangement is based on our earlier one-copy algorithm. It requires a feedback system and is an example of a space-multiplexed optical multistage network. We discuss the design issues and experimental results.


Enumerating tree-like chemical graphs with given upper and lower bounds on path frequencies.
Enumeration of chemical graphs satisfying given constraints is one of the fundamental problems in chemoinformatics and bioinformatics since it leads to a variety of useful applications including structure determination of novel chemical compounds and drug design. In this paper, we consider the problem of enumerating all tree-like chemical graphs from a given set of feature vectors, which is specified by a pair of upper and lower feature vectors, where a feature vector represents the frequency of prescribed paths in a chemical compound to be constructed. This problem can be solved by applying the algorithm proposed by Ishida et al. to each single feature vector in the given set, but this method may take much computation time because in general there are many feature vectors in a given set. We propose a new exact branch-and-bound algorithm for the problem so that all the feature vectors in a given set are handled directly. Since we cannot use the bounding operation proposed by Ishida et al. due to upper and lower constraints, we introduce new bounding operations based on upper and lower feature vectors, a bond constraint, and a detachment condition. Our proposed algorithm is useful for enumerating tree-like chemical graphs with given upper and lower bounds on path frequencies.


Natural Clearance of Chlamydia trachomatis Infection Is Associated With Distinct Differences in Cervicovaginal Metabolites.
Natural clearance of Chlamydia trachomatis in women occurs in the interval between screening and treatment. In vitro, interferon-γ (IFN-γ)-mediated tryptophan depletion results in C. trachomatis clearance, but whether this mechanism occurs in vivo remains unclear. We previously found that women who naturally cleared C. trachomatis had lower cervicovaginal levels of tryptophan and IFN-γ compared to women with persisting infection, suggesting IFN-γ-independent pathways may promote C. trachomatis clearance. Cervicovaginal lavages from 34 women who did (n = 17) or did not (n = 17) naturally clear C. trachomatis were subjected to untargeted high-performance liquid chromatography mass-spectrometry to identify metabolites and metabolic pathways associated with natural clearance. In total, 375 positively charged metabolites and 149 negatively charged metabolites were annotated. Compared to women with persisting infection, C. trachomatis natural clearance was associated with increased levels of oligosaccharides trehalose, sucrose, melezitose, and maltotriose, and lower levels of indoline and various amino acids. Metabolites were associated with valine, leucine, and isoleucine biosynthesis pathways. The cervicovaginal metabolome in women who did or did not naturally clear C. trachomatis is distinct. In women who cleared C. trachomatis, depletion of various amino acids, especially valine, leucine, and isoleucine, suggests that amino acids other than tryptophan impact C. trachomatis survival in vivo.


Improving the quality of nursing care in Austria: 10 years of success.
We provide more updated and comprehensive insights, including descriptions of changes that have taken place in the quality of pressure injury care provided in hospitals over a 10-year period. Various nursing quality measurements do not present a comprehensive view on nursing-sensitive quality indicators or place a focus on one specific care problem. It is a repeated cross-sectional multicentre study conducted annually on 1 day including comprehensive data regarding nursing-sensitive care problems and quality indicators on the structure, process and outcome levels. The prevalence of pressure injuries decreased over the years from 4.4% to 2.9%, and the frequency of interventions increased. The Nursing Quality Measurement 2.0 initiative shows considerable improvements over a 10-year period. Therefore, the maintenance of such nursing databases should be treated as a prerequisite to providing high-quality nursing care and safe nursing practice. One main benefit of creating and maintaining such databases is that allow users to screen for improvements, for example in pressure injury care. These observations can be used to develop marketing strategies and/or to empower and engage nursing staff. Participation in such quality measurements allows the comparison of data collected in wards and institutions in many different countries, enabling them to set appropriate benchmarks. Furthermore, the results can be compared over a period of time, highlighting systematic changes, trends or improvements (e.g., due to implemented innovations).


[High dose intravenous immunoglobulins in treating systemic lupus erythematosus-associated thrombocytopenia].
To study the effect of high dose intravenous immunoglobulins(IvIg) in systemic lupus erythematosus (SLE)-associated thrombocytopenia. A case-control study was undertaken to assess the effectiveness of different therapeutic regimens (oral prednisone, IvIg, bolus methylprednisolone(MP), and IvIg plus bolus MP) in improving SLE-associated thrombocytopenia. For SLE-associated thrombocytopenia, IvIg, bolus MP, and IvIg plus bolus IvIg significantly shorten the time to reach a peak platelet count, which was (6.2 +/- 4.4) days, (7.3 +/- 4.9) days, and (3.8 +/- 2.4) days respectively in comparison with oral prednisone, which was (31.0 +/- 17.8) days (P< 0.01); if high dose IvIg and MP in combination, the time was also shorter than bolus MP alone (P < 0.05). The elevation of platelet count in groups receiving IvIg, bolus MP, and IvIg plus bolus MP were significantly higher than as in group receiving oral prednisone therapy(P < 0.05). High dose IvIg is a useful therapy in improving SLE-associated thrombocytopenia.


Multifocal aggressive lymphoma of the gastrointestinal tract in a renal transplant patient treated with cyclosporin A and prednisone.
This is a case report of an aggressive multifocal non-Hodgkin's lymphoma in a cadaver kidney recipient arising in the early phase of her immunosuppressive maintenance therapy program with cyclosporin A and prednisone.


Potassium-wasting nephropathy secondary to chemotherapy simulating Bartter's syndrome.
A patient with a potassium wasting nephropathy secondary to chemotherapy simulating Bartter's syndrome is described. A 64-year-old woman with diffuse histiocytic lymphoma developed persistent hypokalemia following a course of Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), vincristine, and prednisone (CHOP)-Bleo. The diagnosis of a functional Bartter's syndrome was concluded following evaluation of serial plasma renins, aldosterone levels, and urinary electrolytes. Evidence is suggestive that a subpopulation of patients receiving chemotherapy may develop a functional Bartter's syndrome, and it is important to consider this diagnosis in patients who develop hypokalemia subsequent to chemotherapy introduction.


Risk factors for and circumstances of needlestick and sharps injuries of doctors in operating rooms: A study focusing on surgeries using general anesthesia at Kurume University Hospital, Japan.
Healthcare workers are exposed to serious infectious diseases via needlestick and sharps injuries. The operating room is a particularly important environment in which the risk for needlestick injuries is increased for surgical doctors. According to national surveillance studies, the proportion of needlestick and sharps injuries in operating rooms has been increasing for unknown reasons. In this study, we examined risk factors for and circumstances of injuries in operating rooms by combining and analyzing incidence reports and electronic records of every surgery in Kurume University Hospital (Kurume, Japan). The annual injury rate (reflecting the reporting rate) rose continuously from fiscal years 2007-2012. We conducted analyses focusing on surgeries that used general anesthesia, which accounted for 88.1% of the injuries. An analysis of the time of injury found that the number of injuries increased toward the end of the surgical procedure. A comparative analysis of surgeries by doctors who had experienced injury revealed risk for the injury increased when a procedure ended after 20:00. In addition, a comparative analysis of doctors with and without injury experience who had similar level of operating time per year revealed that the number of working years was not lower in the injured doctors. Although the data analyzed in this study were confined to one university hospital, our approach and these results will form a basis on which to consider more effective measures to prevent injury in operating rooms.


Dual metal and Lewis base catalysis approach for asymmetric synthesis of dihydroquinolines and the α-arylation of aldehydes via N-acyliminium ions.
A dual catalytic system consisting of indium triflate and a chiral imidazolidinone catalyzes the asymmetric addition of aldehydes to N-acyl quinoliniums furnishing optically active dihydroquinolines in good yields and excellent selectivities. The products were further functionalized into optically active tetrahydroquinolines, quinolines and 6-oxa-2-aza-bicyclo[3.3.1]nonanes.


Transient responses to tone bursts.
Investigating theoretical conditions under which linearly-operating tuned structures produce click-like transient responses to onsets and offsets of trapezoidal tone bursts, we come to the following conclusions: (1) each of the four corners of the trapezoidal tone burst is capable of eliciting such a response; (2) the amplitude of the response and its dependence on the frequency of the modulated tone both depend on the phase of the modulated sinusoid at the time a corner occurs; (3) such responses will arise in structures having sufficiently steep band edges, provided that the frequency of the modulated tone is well outside the pass band of the structure--for a corner in cosine phase, the sustained slope of the low-frequency band edge must be greater than zero and that of the high-frequency band edge must be greater than 12 dB/Oct, for a corner in sine phase the sustained slope of the low-frequency band edge must be greater than 6 dB/Oct and that of the high-frequency band edge must be greater than 18 dB/Oct; (4) they will not arise in response to tone bursts whose frequencies fall within the pass band of the structure; (5) nor will they arise in response to a trapezoidal tone burst of any frequency applied to structures (such as simple microphones or drivers) following second-order dynamics and having both spectral zeros at infinity. We present theoretically derived relationships between the amplitude of transient responses and the tone-burst frequency, not only for the corners of trapezoidal tone bursts, but also for tone bursts of more general shapes. We conclude that, owing to its extraordinarily steep high-frequency rolloff, the filter associated with each cochlear axon is well suited to extracting temporal information from onset or offset singularities in modulated tones whose frequencies are above the characteristic frequency of the filter. Applying the theory to observed onset and offset responses to high-intensity tone bursts in auditory afferents of the Mongolian gerbil, we conclude that some of the responses we observed must have been sculpted in part by cochlear nonlinearities.


Effectiveness of suction valve button removal in retrieving resected colon polyps for better histological assessment: Propensity score matching analysis.
Fragmentation of endoscopically resected colorectal polyps during retrieval is one of the limitations for appropriate pathological diagnosis; however, little is known about steps to reduce it. We aimed to evaluate the effect of removing the suction valve button, which is one of the intricate parts of the endoscope, during polyp suction retrieval for fragmentation and pathological diagnosis. We retrospectively reviewed the polyps retrieved by suctioning. We used the propensity score matching method to adjust for difference between the button-attached and button-removed groups. Outcomes of fragmentation, pathological diagnosis of non-neoplastic polypectomy (NNP), and pathological cut-end among neoplastic lesions were evaluated. On the basis of propensity score matching, 322 pairs of cases were selected for analysis. After matching, the difference in the variables between the two groups was closely balanced. The fragmentation rate was significantly different between the groups (button-attached 36.6% vs. button-removed 22.4%, P < 0.001). No significant difference in the NNP rate was observed between the two groups (button-attached 8.4% vs. button-removed 9.9%). The rate of unclear cut-end was lower in the button-removed group than in the button-attached group (16.2% vs. 9.1%, P = 0.010). In the multivariate analysis, button removal was independently associated with reductions of fragmentation (odds ratio [OR] 0.508, P < 0.001) and unclear cut-end (OR 0.503, P = 0.009). Also, NNP was associated with smaller lesion size (OR 0.364, P < 0.001), but not with button removal. Suction valve button removal during polyp suction retrieval was an effective method to decrease the rates of fragmentation and histological unclear margins.


3D-4K exoscope-assisted temporal bone dissection: a new frontier in surgical training.
To assess if 3D-4K exoscope is a valuable tool for temporal bone dissection and to evaluate its teaching potential. Six consecutive 3D-4K-exoscope-assisted cortical mastoidectomies were performed by a novice, an intermediate and an expert surgeon (two dissections each). All dissections were entirely recorded and later evaluated independently by three other experienced surgeons. The dissection end-product was evaluated according to the Melbourne Mastoidectomy Scale (MMS). Paired t test was used to assess whether novice and intermediate surgeons have a score improvement in the second dissection compared to the first one. Surgeons' interactions, depth effect, and 3D impression were also assessed to perform a subjective analysis. Mean MMS scores for the novice, intermediate and expert surgeon were 11.3 ± 2.8, 13.8 ± 3.9 and 19 ± 1.3, respectively. Paired t test demonstrated a statically significant improvement between the first and the second dissection both for the novice and the intermediate surgeon (+ 4.7 and + 7 points; p = 0.0002). A high-quality magnification of the temporal bone was obtained, allowing the expert surgeon to identify all the anatomical structures without injuring them. The exoscope was capable of providing a high involvement in the dissections with very effective interactions between the expert surgeon and the trainees, that had access to the same surgical field view. 3D-4K-exoscope resulted adequate for a safe and effective mastoidectomy and showed a high potential for training and educational purposes. It can represent a valid option for surgical training of temporal bone dissection and a new interactive tool to understand the complex temporal bone anatomy.