Effects of Chemoradiation Therapy on Hearing in Patients with Malignancy of Head and Neck.
To study effects of chemoradiation therapy on hearing in patients with malignancy of head and neck. Patients receiving drugs other than cisplatin as well as those with any otology-related pathology or abnormalities were excluded from the study. Patients with primary biopsy-proven malignancy of the Nasopharynx, Oropharynx, Paranasal Sinuses, Oral Cavity, and Parotid with chemoradiation by cisplatin and different radiation modalities were all eligible. Areas of interest and OARs are indicated on CT images. All patients' hearing was assessed using pure tone audiometry at the beginning of treatment, at its conclusion, and six months later. Variations in pure tone thresholds from baseline and CTCAE - Common Terminology Criteria for Adverse Events grading are related to cochlear dose. The study involves 75 patients. At cochlear dosage levels of more than 40 Gy, significant SNHL (>10 dB loss) is seen. Absolute PTA threshold values do not statistically differ from baseline to completion at any frequency. For 4000 and 8000 Hz, the absolute PTA threshold values differed from baseline to follow-up, but only for 8000 Hz was the difference statistically significant after six months of follow-up. Following treatment, 64% of patients had grade I CTCAE scoring and 16% and 12%, respectively, had otitis media with effusion and Eustachian tube dysfunction. The inner ear may be harmed in patients receiving radiation to the head and neck. Radiation-induced SNHL typically goes unreported in routine clinical practise because of its long-term nature. In the group of head and neck tumours with high-risk locations, nearly 90% of patients with SNHL were affected. Therefore, it's critical to reduce cochlear dosage in these patient populations. More investigation is needed to distinguish between cochlear and retro-cochlear types of sensorineural hearing loss.


Binocular afferents to the salamander pretectum mediate rotation sensitivity of cells selective for visual background motions.
The majority (85%) of background motion-sensitive pretectal cells in salamanders was found to be binocularly driven. In 70% of the units the binocularity establishes a rotation selectivity with respect to background pattern-movements. This results in a considerable augmentation of the discharge rate when pattern movement is perceived simultaneously in the temporonasal direction by the contralateral eye and nasotemporally by the ipsilateral eye. The response is depressed when the pattern movement is seen in the same direction by both eyes. It is concluded that the rotation-sensitive cells are mainly excited by contralateral retinal afferents selective for temporonasal movements and inhibited by direct or indirect ipsilateral afferents with the same type of direction selectivity.


tmVar 2.0: integrating genomic variant information from literature with dbSNP and ClinVar for precision medicine.
Despite significant efforts in expert curation, clinical relevance about most of the 154 million dbSNP reference variants (RS) remains unknown. However, a wealth of knowledge about the variant biological function/disease impact is buried in unstructured literature data. Previous studies have attempted to harvest and unlock such information with text-mining techniques but are of limited use because their mutation extraction results are not standardized or integrated with curated data. We propose an automatic method to extract and normalize variant mentions to unique identifiers (dbSNP RSIDs). Our method, in benchmarking results, demonstrates a high F-measure of ∼90% and compared favorably to the state of the art. Next, we applied our approach to the entire PubMed and validated the results by verifying that each extracted variant-gene pair matched the dbSNP annotation based on mapped genomic position, and by analyzing variants curated in ClinVar. We then determined which text-mined variants and genes constituted novel discoveries. Our analysis reveals 41 889 RS numbers (associated with 9151 genes) not found in ClinVar. Moreover, we obtained a rich set worth further review: 12 462 rare variants (MAF ≤ 0.01) in 3849 genes which are presumed to be deleterious and not frequently found in the general population. To our knowledge, this is the first large-scale study to analyze and integrate text-mined variant data with curated knowledge in existing databases. Our results suggest that databases can be significantly enriched by text mining and that the combined information can greatly assist human efforts in evaluating/prioritizing variants in genomic research. The tmVar 2.0 source code and corpus are freely available at https://www.ncbi.nlm.nih.gov/research/bionlp/Tools/tmvar/. firstname.lastname@example.com.


Location of interneurones in the recurrent inhibitory circuit of the rabbit lateral geniculate nucleus.
Injection of horseradish peroxidase (HRP) into the dorsal lateral geniculate nucleus (LGN) of the rabbit gave rise to retrograde labeling of neurones in the caudal part of the thalamic reticular nucleus. Electrophysiological observations demonstrated that these neurones met all criteria for interneurones in the recurrent inhibitory circuit of the geniculo-cortical pathway. They responded to stimulation of the visual cortex (Cx) or the optic chiasm (OX) with a burst of repetitive discharges, in agreement with the long-lasting IPSP from Cx or OX in relay cells of LGN. Results of collision test showed that the reticular neurones received excitatory input via axonal collaterals of relay cells. The latency of their response to stimulation of Cx or OX is about 1.8 ms shorter than that of the corresponding IPSP in the relay cells. Stimulation of LGN evoked an antidromic spike in reticular neurones with a latency of about 1.1 ms, indicating a monosynaptic projection from the latter to the relay cells. All evidence indicates that interneurones in the recurrent inhibitory circuit are most likely located in the caudal part of the thalamic reticular nucleus of the rabbit.


Myeloid differentiation of HL-60 cells induced by anti-tumor drug 3-nitrobenzothiazolo[3,2-a]quinolinium.
Drugs which elicit cell differentiation might have an important role in the treatment of leukemias and other neoplasias. Various chemotherapeutic agents promote leukemic cell differentiation. The HL-60 cell line is a useful model to study in vitro myeloid differentiation. Sublethal concentrations of 3-nitrobenzothiazolo[3,2-a]quinolinium (NBQ), an antitopoisomerase II drug, were given to HL-60 cells from one to five days to evaluate its capacity to induce differentiation. NBQ-induced HL-60 cells reduced nitroblue tetrazolium (NBT), increased MY-4 receptors, increased phagocytic activity and displayed the granulocytic morphology. Flow cytometric DNA analysis of NBQ-induced cells revealed an arrest in the G1 phase a reduction in the relative percentage of cells in S and G2+M phases. Our results suggest that NBQ induces an S-phase specific differentiation of HL-60 cells comparable to that previously described with dimethyl sulfoxide and retinoic acid. NBQ and its analogs, as differentiation inducers, may have potential utility as a novel therapeutic modality for leukemias.


National comparison of oncologic quality indicators between open and robotic-assisted radical cystectomy.
Despite increased adoption of robotic-assisted radical cystectomy (RARC), no national data have validated its oncologic efficacy compared to the "standard" open radical cystectomy (ORC). Positive surgical margins (PSM) and lymph node (LN) yield during radical cystectomy (RC) have an established relationship with bladder cancer outcomes. Here, we propose these 2 as quality indicators for RC and assess their differences to compare the oncologic efficacy between RARC and ORC. Using the National Cancer Data Base for the years 2010 to 2012, all patients who underwent ORC or RARC were analyzed. Baseline demographic and cancer stage information were compared as well as unadjusted rates of PSM and LN yield. Survival effect of each indicator was assessed. Using propensity score adjustment, rates of PSM and LN yield were compared between RARC and ORC. A total of 12,036 patients are included who underwent RC, 20% (2,397) of which were performed robotically. Percentage RARC of total RC increased from 16.2% to 23.3% over the 3 study years. Compared to ORC, patients who underwent RARC were no different in age but were more often men (78.4% vs. 73.6%, P<0.001), had less-advanced cancer stage, and were more likely to have received neoadjuvant chemotherapy (20.9% vs. 14.5%, P<0.001). Most RARC procedures were performed at academic medical centers (66.1%). Unadjusted rates of PSM were lower in the RARC group (10.8% vs. 13.2%, P = 0.002) whereas median LN yield was higher in RARC patients (16 [interquartile range 9, 25] vs. 11 [interquartile range 5, 19], P<0.001). After propensity score covariate adjustment, there was no significant difference in PSM rate between RARC and ORC (-1.12% difference, [95% CI:-2.8, 0.32%]. However, RARC was associated with a higher node yield (+3.32 LN, [95% CI: 2.61, 4.03]) than ORC (P<0.001). The RARC is becoming more prevalent. In a national cohort, RARC was performed more often on men, with lower stage cancer, who were more likely to receive neoadjuvant chemotherapy. Controlling for these factors, RARC had comparable PSM rates but slightly higher LN yield than ORC.


Posterior rhythmic slow activity in EEG after eye closure.
During a 20 month period, EEGs in 7 patients, ages 6-16 years, showed a distinctive posterior rhythmic slow (PRS) activity brought on by eye closure. Following eye opening for 5-10 sec, eye closure on command was followed by a rhythmic high amplitude (100-250 microV) slow wave discharge of 3-4 c/sec lasting for 1.5-3 sec after a latency of 300-500 msec. Its distribution was limited to the occipital, posterior temporal and parietal regions. It was always bilaterally synchronous, occurred symmetrically or asymmetrically and fatigued easily. Of the 7 initial EEGs, only 2 had other EEG abnormalities. One patient, in a subsequent EEG, developed spontaneous PRS unrelated to eye closure. Clinical histories on the 7 patients showed 5 with various types of seizure disorders, 1 with attention deficit disorder, and 1 with Tourette syndrome. Neurological examination was normal in all patients, while computerized tomography or radioisotope brain scan was normal in 4. We suggest that PRS after eye closure represents a variant of the non-specific spontaneously occurring PRS described by Aird and Gastaut and others. It was found only in children and was not found to be helpful in diagnosing a seizure disorder or structural abnormality. Furthermore, such a discharge should not be interpreted as epileptiform activity.


Wet laboratory training using porcine eyes with eyelids.
This study aimed to evaluate the usefulness of a new wet laboratory (wet lab) system using porcine eyes with eyelids. Teaching device trial. Porcine eyes with orbital tissues and eyelids. Twenty porcine eyes with orbital tissues and eyelids were enucleated from pigs butchered at age 6 months. These eyes were positioned in the eye sockets of a model head and stabilized with a pin. Eye draping, dressing with tape, and speculum placement were conducted. The vertical and horizontal widths of the palpebra under the speculum setting were compared with those of 55 patients who underwent cataract surgery. The rotation and torsion of the porcine eye in the new wet lab system were also compared with those of a conventional wet lab system. For comparison with actual cataract surgery, 5 ophthalmologists, including residents, were asked to respond to a questionnaire survey. The horizontal widths of the palpebra under the speculum setting were 27.5 ± 3.1 mm in porcine eyes and 28.6 ± 5.1 mm in human eyes, and the vertical widths were 16.9 ± 1.3 mm and 16.1 ± 1.5 mm (p = 0.53, 0.05). The amounts of rotation and torsion were significantly greater with the new wet lab system. Ophthalmologists evaluated the new wet lab system as being more realistic than the conventional system, in terms of both natural eye movement and restriction of the surgical field by the eyelid and the speculum. Wet lab training using porcine eyes with eyelids is more practical than older systems as it reproduces an ocular surgical field very similar to that of humans.


Combining the new biologic agents with our current psoriasis armamentarium.
Combination therapy, rotational therapy, and sequential therapy have been used for psoriasis in attempts to achieve greater efficacy and greater safety. The purpose of this manuscript is to review potential advantages and disadvantages of new biologic agents as we look forward to their use in combination regimens with other systemic, topical, and light therapies. Data on the efficacy and toxicity of existing systemic therapies and new biologic agents is reviewed with an emphasis on potential additive or synergistic benefits or toxicities. The mechanism of action of biologic agents differs from systemic agents currently in use, suggesting that there may be additive effects in treating psoriasis. The absence of hepatotoxicity and nephrotoxicity are important advantages when considering combination therapy with biologic agents. The advantages of the use of biologic therapies in combination or rotation with other systemic agents will have to be demonstrated in clinical trials. Mechanisms of action of the biologic therapies suggest that there is potential for additive benefit when used in combination regimens.


Comparison of automated quantification of amyloid deposition between PMOD and Heuron.
Several programs are widely used for clinical and research purposes to automatically quantify the degree of amyloid deposition in the brain using positron emission tomography (PET) images. Given that very few studies have investigated the use of Heuron, a PET image quantification software approved for clinical use, this study aimed to compare amyloid deposition values quantified from 18F-flutemetamol PET images using PMOD and Heuron. Amyloid PET data obtained from 408 patients were analysed using each quantitative program; moreover, the standardized uptake value ratios (SUVRs) of target areas were obtained by dividing the standardized uptake value (SUV) of the target region by the SUV of cerebellar grey matter as a reference. Compared with PMOD, Heuron yielded significantly higher SUVRs for all target areas (paired sample t-test, p < 0.001), except for the PC/PCC (p = 0.986). However, the Bland-Altman plot analysis indicated that the two quantitative methods may be used interchangeably. Moreover, receiver operating characteristic curve analysis revealed no significant between-method difference in the performance of the SUVRs in evaluating the visual positivity of amyloid deposits (p = 0.948). In conclusion, Heuron and PMOD have comparable performance in quantifying the degree of amyloid deposits in PET images.


Recent advancements in role of TAM receptors on efferocytosis, viral infection, autoimmunity, and tissue repair.
Evolutionarily conserved highly regulated process of apoptosis has been a major physiological process throughout the entire evolutionary history of living beings that has impacted the process of evolution itself. One of the key features of this highly researched field of science is the process of phosphatidylserine (PS) externalization by the different membrane bound enzymes. The process is a result of series of biological events and is associated with various biological outcomes depending on the proper recognition of this ligand. In this review, we will briefly summarize the recent advancement in the field pertaining to the set of receptors, known as TAM (Tyro3, Axl and Mertk) receptors, for their influence in the recognition of various PS externalization events and mediation of pathological outcomes such as autoimmunity, cancer, and tissue repair.


Effects of microbial floras on the distributions of five domestic Drosophila species across fruit resources.
The distributions of five Drosophila species and four components of the microflora have been compared across a total of 48 traps baited with four different fruit and vegetable substrates in two domestic compost heaps in Canberra (Australia). Large and consistent differences are found, both among the Drosophila and among the microbial classes, in their distributions across traps baited with different substrates. Moreover the distribution of each Drosophila species shows a unique set of strong associations with the microbial distributions. Thus the distributions of both D. simulans and D. melanogaster are found to be strongly negatively correlated with the abundance of bacteria while D. simulans is also strongly positively correlated with the titre of fermenter yeasts. D. immigrans is strongly positively correlated both with bacteria and with non-fermenter yeasts. D. hydei is positively correlated with nonfermentery yeasts and D. busckii is negatively correlated with fermenter yeasts. Moulds are the only microbial class not consistently associated with the distribution of any of the Drosophila species. The correlations with the other microbial classes are sufficient to explain the majority of the abundance differences of the Drosophila species among the trap types. It is therefore proposed that the clear partitioning of the fruit resources by the Drosophila is due to their differing primary interactions with the microflora.


Data-based modeling of breast cancer and optimal therapy.
Excessive accumulation of β-catenin proteins is a vital driver in the development of breast cancer. Many clinical assessments incorporating immunotherapy with targeted mRNA of β-catenin are costly endeavor. This paper develops novel mathematical models for different treatments by invoking available clinical data to calibrate models, along with the selection and evaluation of therapy strategies in a faster manner with lower cost. Firstly, in order to explore the interactions between cancer cells and the immune system within the tumor microenvironment, we construct different types of breast cancer treatment models based on RNA interference technique and immune checkpoint inhibitors, which have been proved to be an effective combined therapy in pre-clinical trials associated with the inhibition of β-catenin proteins to enhance intrinsic anti-tumor immune response. Secondly, various techniques including MCMC are adopted to estimate multiple parameters and thus simulations in agreement with experimental results sustain the validity of our models. Furthermore, the gradient descent method and particle swarm algorithm are designed to optimize therapy schemes to inhibit the growth of tumor and lower the treatment cost. Considering the mechanisms of drug resistance in vivo, simulations exhibit that therapies are ineffective resulting in cancer relapse in the prolonged time. For this reason, parametric sensitivity analysis sheds light on the choice of new treatments which indicate that, in addition to inhibiting β-catenin proteins and improving self-immunity, the injection of dendritic cells promoting immunity may provide a novel vision for the future of cancer treatment. Overall, our study provides witness of principle from a mathematical perspective to guide clinical trials and the selection of treatment regimens.


A distant upstream locus control region is critical for expression of the Kit receptor gene in mast cells.
The Kit receptor tyrosine kinase functions in hematopoiesis, melanogenesis, and gametogenesis and in interstitial cells of Cajal. We previously identified two upstream hypersensitive site (HS) clusters in mast cells and melanocytes. Here we investigated the roles of these 5' HS sequences in Kit expression using transgenic mice carrying Kit-GFP reporter constructs. In these mice there is close correspondence between Kit-GFP reporter and endogenous Kit gene expression in most tissues analyzed. Deletion analysis defined the 5' upstream HS cluster region as critical for Kit expression in mast cells. Furthermore, chromatin immunoprecipitation analysis in mast cells showed that H3 and H4 histone hyperacetylation and RNA polymerase II recruitment within the Kit promoter and in the 5' HS region were associated with Kit expression. Therefore, the 5' upstream hypersensitivity sites appear to be critical components of locus control region-mediated Kit gene activation in mast cells.


Significance of Doppler-detected mitral regurgitation in acute myocardial infarction.
To define the incidence of mitral regurgitation (MR) and elucidate its potential contribution to the development of severe congestive heart failure after acute myocardial infarction (AMI), Doppler echocardiograms were obtained within 48 hours of onset of AMI in 59 patients. The presence of MR was determined from the apical 4-chamber and parasternal long-axis views with pulsed Doppler. MR was detected in 23 of the 59 patients (39%) and was similarly frequent in patients with anterior (11 of 24 or 46%) and inferior AMI (12 of 34 or 35%). Patients with MR were older (71 +/- 3 vs 62 +/- 2 years, p less than 0.005), had a higher incidence of prior AMI (8 of 23 vs 4 of 36, p less than 0.05) and larger end-diastolic volume indexes by radionuclide ventriculography (112 +/- 9 vs 72 +/- 4, p less than 0.005). A systolic murmur was heard in only 10 of 23 patients with MR detected by Doppler. Mortality determined 8 to 14 months after the index AMI was 48% (11 of 23) in patients with MR but only 11% (4 of 30) in those without it (p less than 0.01). Thus, this study determined that clinically silent MR frequently complicates AMI and its presence is associated with and is a potential determinant of severe congestive heart failure and mortality.


Evolution of lung adenocarcinoma from preneoplasia to invasive adenocarcinoma.
Mutations in driver genes contribute to the development and progression of lung adenocarcinoma (LUAD). However, in the dynamic evolutionary process from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and eventually to invasive adenocarcinoma (IAC), the role of driver genes is currently unclear. This study aimed to analyse the role of driver gene status in the progression of LUAD from preneoplasia to IAC. Patients with LUAD who underwent surgery in our centre from March 2015 to December 2019 were retrospectively analysed, and LUAD patients with tumour sizes ≤3.0 cm and pN0 were included in the final analysis. The mutation status of common driver genes, including EGFR, ALK and ROS1, was detected. According to the pathological characteristics, the patients were divided into three stages: AIS, MIA and IAC. We analysed the distribution of driver gene mutation frequencies across three stages of LUAD. In addition, we performed univariate and multivariate analyses of IAC patients to screen for relevant variables (driver genes and clinicopathological features) affecting their prognosis. Ultimately, 759 patients with LUAD were enrolled, including 135, 130, and 494 cases of AIS, MIA, and IAC, respectively. EGFR mutations were identified in 359 (61.8%) patients, and with the transition from AIS to MIA, the frequency of EGFR mutations increased from 33.3% to 50.8%, p = 0.004, whereas the frequency of EGFR mutations was comparable for MIA and IAC (50.8% vs. 50.2%, p = 0.922). Moreover, ALK and ROS1 gene fusions were identified in 17 cases (2.2%) and 2 cases (3.0‰) respectively. For AIS, neither ALK gene nor ROS1 gene fusions were observed. When the tumour progressed to MIA, the ALK fusion frequency was 2.3% (3/130), which was basically consistent with the ALK fusion frequency of 2.8% in IAC, p = 0.143. For IAC, fusions of ROS1 fell into this category. In addition, we found that 40 patients (5.3%) developed metastasis/recurrence, and 14 patients (1.8%) died of cancer-specific related diseases. Notably, for AIS, there were no recurrences and no deaths, and for MIA, only 1 patient died with LUAD. Finally, survival analysis was performed in patients with stage IA invasive adenocarcinoma, and EGFR-mutant patients showed better DFS than EGFR-wild-type patients (p = 0.036). Conversely, patients with ALK fusions showed worse DFS than those with ALK wild-type (p = 0.004), and the same results were found in OS analysis. The accumulation of EGFR driver gene mutation frequencies mediates the progression of LUAD from AIS to MIA. When the tumour progresses to stage IA invasive adenocarcinoma, multivariate analysis based on driver gene status can be used as a pivotal prognostic factor.


Activity controlled cardiac pacemakers during stairwalking: a comparison of accelerometer with vibration guided devices and with sinus rate.
Activity controlled pacemakers are the most widely used rate adaptive systems. We studied second-generation activity controlled systems (accelerometer) in 21 patients with such an accelerometer controlled system implanted during walking level and stairs. We compared them to the rate of vibration controlled, first-generation activity pacemakers and to the sinus rate of a healthy control group. A metronome directed the speed during walking and climbing stairs at 92, 108, and 120 steps/min. At 92 steps/min, the new accelerometer controlled systems showed a significant (P < or = 0.001) pacing rate increase from 107 +/- 8 beats/min during walking level to 124 +/- 8 beats/min during climbing stairs, and a significant decrease to 105 +/- 12 beats/min during walking downstairs. In contrast, first-generation activity controlled pacemakers showed a less physiological rate behavior with higher pacing rate (113 +/- 7 beats/min) walking downstairs than walking upstairs (97 +/- 9). For everyday activities at normal walking speed, accelerometer controlled pacemakers show a more physiological rate behavior than first-generation pacemakers, but they lose this physiological response with faster walking.


Para-articular ossification in total hip replacement: an indication for irradiation therapy.
The results of postoperative irradiation therapy after total hip replacement or resection of para-articular ossification in 25 patients are reported. The patients were kept under radiological observation for an average period of 26 months and clinical observation for an average period of 31 months after surgery. There were only two clinically relevant recurrences of para-articular ossification. The earlier radiotherapy with a total dose of 2000 rads (2000 cGy) was begun, the better was the effect. In this small population sample statistical significance could not be calculated. No side effects were detected.


MiR-137 inhibits proliferation and angiogenesis of human glioblastoma cells by targeting EZH2.
It is suggested that microRNAs play important roles in the development of various cancers. Here, we showed that miR-137 is downregulated in glioblastoma (GBM) cell lines and that low levels of miR-137 are associated with a poor prognostic phenotype of GBM patients. Ectopic expression of miR-137 significantly inhibited GBM cell proliferation and angiogenesis. In addition, ectopic expression of miR-137 inhibited tumor growth and angiogenesis in a SCID mouse xenograft model. EZH2 was identified as a direct target of miR-137 by using luciferase reporter and Western blot assays, and EZH2 overexpression can rescue the inhibitory effect of miR-137 on cell proliferation and angiogenesis. Furthermore, tumor samples from GBM patients showed an inverse relationship between miR-137 and EZH2 levels. Our results suggest that miR-137 may serve as a biomarker in GBM, and the modulation of its activity may represent a novel therapeutic strategy for the treatment of GBM patients.


Impact of COVID-19 epidemic on port operations: Evidence from Asian ports.
The outbreak of COVID-19 has impacted the shipping industry while the extent of the impact is still not fully understood. To quantitatively investigate the relationship between pandemic-related factors and port operations, a panel regression analysis is conducted using data from three important Asian ports, Shenzhen, Hong Kong, and Singapore. Daily data from the Automatic Identification System (AIS), Oxford COVID-19 Government Response Tracker (OxCGRT) database, and port authorities from January 2020 to December 2021 are utilized. Local newly confirmed cases of ports tend to negatively impact cargo throughput, while worldwide newly confirmed cases outside of ports tend to positively impact cargo throughput. Overall, the policy implications are that ports with better control of COVID-19 reap the benefits of more cargo throughput. In addition, countermeasures against COVID-19 and other epidemics should be designed deliberately to minimize the side-effect on port operations and maritime transportation.


Anti-Müllerian hormone versus antral follicle count for defining the starting dose of FSH.
This pilot study compared the efficacy and safety of two simple dosing algorithms, one based on anti-Müllerian Hormone (AMH) and the other on the antral follicle count (AFC), to determine the starting dose of recombinant FSH (rFSH) for ovarian stimulation in 348 women. Patients were randomized to a predefined AMH- or AFC-based algorithm. The proportion of cycles with the desired response was similar when rFSH dose was determined using AMH or AFC (35.2% versus 28.4%). There was a significant difference between the groups in the proportion of cycles with a hyperresponse (8.6% and 17.4%, but the incidence of ovarian hyperstimulation syndrome was similar (1.1% and 4.6%). There were no significant differences between two groups in outcomes, including implantation (19.3% versus 19.0%), clinical pregnancy (38.0% versus 46.9%), multiple pregnancy (16.5% versus 15.2%) and miscarriage (7.0% versus 8.3%). However, statistically significant differences in ovarian response were evident among the AMH and AFC subgroups: for AMH, Desired and Hypo; for AFC, Hypo and Hyper. This pilot study provides information for developing protocols to further validate the use of either AMH or AFC to guide the starting dose of rFSH in ovarian stimulation. The ideal outcome for couples undergoing IVF treatment is the birth of a healthy baby. One factor that might influence this is retrieving an adequate number of eggs, which are obtained using various treatment protocols. A group of drugs called gonadotrophins have been used for more than 20years to stimulate the ovaries to produce eggs. However, the dose to start treatment has not been clearly defined. A few studies have looked at ways to use the best gonadotrophin dose for each woman, but to be useful in the clinic any approach needs to be simple and easy to use. This study compared the effectiveness and safety of two simple approaches to determining the starting dose of recombinant FSH (rFSH) for ovarian stimulation in women undergoing IVF. One was based on the concentration of a hormone secreted by developing eggs (anti-Müllerian hormone; AMH) and the other on the number of developing follicles (antral follicle count; AFC). The number of cycles achieving the desired response in terms of number of eggs was similar when rFSH dose was guided using AMH or AFC, and the incidence of ovarian hyperstimulation syndrome was also similar. In addition, rates of clinical pregnancy, multiple pregnancy and miscarriage did not differ between the two groups. However, patients with low AMH concentrations or low AFC had a poor response to ovarian stimulation. This pilot study provides useful information from which new studies can further assess these approaches to personalizing treatment during IVF.


Analysis of interstrain variation in a putative immediate-early region of human herpesvirus 6 DNA and definition of variant-specific sequences.
Sequences of a 2.6- to 2.9-kb open reading frame in a putative immediate-early region of the human herpesvirus 6 (HHV6) genome were determined and compared in three reference and six local isolates of HHV6. The sequences segregated into two variant groups (A and B) having only 75% nucleotide homology and 62% peptide homology, in part because of deletions in the variant A strains. Among the variant B isolates, further sequence grouping was evident; two clinical isolates segregated with reference strain Z29 into a cluster that had 96.6% nucleotide homology and 92.6% peptide homology when compared to a second variant B cluster of four isolates. Within each cluster of variant B isolates, nucleotide homology was 99.4% or more. Two pairs of isolates had identical sequences. The marked divergence of variants A and B permitted the design of variant-specific oligonucleotide primers that could detect in a single polymerase chain reaction the presence of either or both variant A and B HHV6 DNA. Variation in this gene region of HHV6 is more extensive than in the envelope glycoprotein (gB and gH) coding regions and could be related to known biological differences between variant groups.


Protein antigens of Mycobacterium leprae.
Protein antigens of Mycobacterium leprae have been identified by screening the lambda gt11, pYA626 and pHC79::M. leprae genomic libraries with pooled sera from leprosy patients and with antiserum to M. leprae cell wall protein (CWP) aggregate. Immunological screening of the lambda gt11 library with pooled sera from 21 lepromatous (LL) leprosy patients resulted in the identification of 19 antigens that are apparently different from previously identified M. leprae antigens. Five additional antigens were identified by screening the lambda gt11 library with pooled sera from 30 borderline tuberculoid or tuberculoid patients. Four other antigens were identified by screening the lambda gt11 library with anti-CWP. Two groups of recombinant cosmids were identified by screening the pHC79 library with LL patients' sera: one group specified proteins that reacted with monoclonal antibodies (mAb) against the 65-kDa protein and against the 18-kDa protein; the other group specified a 15-kDa protein that did not react with any of the mAb that were tested. One pYA626 clone also specified a 15-kDa protein that reacted with LL patients' sera, but did not react with any mAb. Genes specifying several of these antigens have been subcloned into the Asd+ plasmid vector pYA292 and have been introduced into a delta cya delta crp delta asd Salmonella typhimurium strain to evaluate the ability of individual M. leprae proteins to elicit immune responses against M. leprae infection.


Characterization of the nitrite production of mesophilic spore-forming bacteria during the handling of reconstituted infant formula.
The microbiological safety of reconstituted infant formula (RIF) has focused on infectious pathogens, whereas the risk of spore-forming bacteria (SFB) has been limited to spoilage and toxin production. This study suggests an underrecognized niche of SFB as nitrite producers during the handling of RIF. The production of nitrite along with the bacterial growth of 133 nitrite-producing SFB isolated from infant formula processing environments and end-products (70 mesophiles and 63 thermophiles) under RIF handling conditions were analysed. Most mesophiles (68 out of 70) and two thermophiles showed nitrite production during growth at 30 °C or 40 °C. Vigorous producers of nitrite [Bacillus sp. strains (FHS-PPBM449, 481, 236, 237)] showed a rapid onset of nitrite production (within 4 h). In particular, FHS-PPBM449 (2-3 log CFU/mL) exhibited the shortest onset time (210 min) and a nitrite production level up to 521 µM in RIF with 100 ppm nitrate at 40 °C. Overall, the results of the maximum level of nitrite produced by vigorous nitrite producers indicate that infants can consume more than seven times the acceptable daily intake of nitrite (0.74 mg for 12-month-old infants with an average body weight), even via a single feeding of RIF. An analysis of the relationship of the onset time of nitrite production with the bacterial concentration based on predictive models suggests that the growth of SFB up to 5-6 log CFU/mL is regarded as a prerequisite for nitrite production. This study revealed an underreported source of nitrite from RIF handling conditions, and the rapid onset of a high level of nitrite production from SFB should be the major target in the establishment of intervention strategies against nitrite as a microbial risk.


Are We on the Verge of a Major Transformation of the Global Economy?
The article contains an analysis of the events of world economic history related to the processes of globalization. The principles and nature of the functioning of international institutions that determine the world order in recent decades are described. In the context of significant changes taking place in the world in recent years, the question is raised of changing the balance of power in the world economy and the possibility of transition to its "deglobalization" is assessed.


Effectiveness of hard inserts in sports mouthguards: a systematic review.
Objectives To improve the protective capacity of conventional ethylene-vinyl acetate mouthguards, some authors have suggested reinforcement with a hard material to distribute impact energy more widely. The research question for this systematic review was: 'does the inclusion of a hard insert in mouthguards improve the protection of anterior teeth from a direct blow?'Data sources Three bibliographic databases (PubMed/Medline, Ovid/Embase and the Cochrane CENTRAL databases) were searched up to 20 February 2021. Additional searches included hand searching of key articles and journals.Data selection A systematic search of the literature included studies where the intervention was the incorporation of hard material into sports mouthguards and where the comparator was conventional mouthguard material. Eligibility required the use of anatomical specimens or anatomical analogues which included or represented anterior maxillary teeth. Twelve eligible publications were identified.Data extraction Data extraction was first carried out independently by two reviewers. Discrepancies were resolved by discussion.Data synthesis Results of individual studies were conflicting and methodological diversity created difficulty in making a synthesis of results. All studies employed low-energy impacts that did not represent the potentially high-energy impacts encountered in sport.Conclusion The efficacy of hard inserts in sports mouthguards has not been demonstrated.


Multimodal feature learning and fusion on B-mode ultrasonography and sonoelastography using point-wise gated deep networks for prostate cancer diagnosis.
B-mode ultrasonography and sonoelastography are used in the clinical diagnosis of prostate cancer (PCa). A combination of the two ultrasound (US) modalities using computer aid may be helpful for improving the diagnostic performance. A technique for computer-aided diagnosis (CAD) of PCa is presented based on multimodal US. Firstly, quantitative features are extracted from both B-mode US images and sonoelastograms, including intensity statistics, regional percentile features, gray-level co-occurrence matrix (GLCM) texture features and binary texture features. Secondly, a deep network named PGBM-RBM2 is proposed to learn and fuse multimodal features, which is composed of the point-wise gated Boltzmann machine (PGBM) and two layers of the restricted Boltzmann machines (RBMs). Finally, the support vector machine (SVM) is used for prostatic disease classification. Experimental evaluation was conducted on 313 multimodal US images of the prostate from 103 patients with prostatic diseases (47 malignant and 56 benign). Under five-fold cross-validation, the classification sensitivity, specificity, accuracy, Youden's index and area under the receiver operating characteristic (ROC) curve with the PGBM-RBM2 were 87.0%, 88.8%, 87.9%, 75.8% and 0.851, respectively. The results demonstrate that multimodal feature learning and fusion using the PGBM-RBM2 can assist in the diagnosis of PCa. This deep network is expected to be useful in the clinical diagnosis of PCa.


Prevalence and associated factors of undernutrition among pregnant women visiting ANC clinics in Silte zone, Southern Ethiopia.
Maternal undernutrition is highly prevalent in underdeveloped countries. Hence, this study was intended to determine the prevalence and associated factors of undernutrition among pregnant women visiting ANC clinics in Silte Zone. Facility-based cross-sectional study was conducted from July to January 2019. Systematic random sampling technique was used to select 422 study participants from 11 randomly selected health facilities. Data was collected by using a structured-interviewer administered questionnaire. Mid upper arm circumference (MUAC) was measured by standard non stretchable MUAC tape. Data was entered into a computer using Epi data 3.1 and edited, cleaned, and analyzed using SPSS version 20. Both bivariate and multiple logistic regression analyses were employed to identify factors associated with maternal undernutrition. In this study, the overall prevalence of undernutrition among study subjects was 21.8%. Age greater than 31 years of women (AOR = 0.15; 95% CI: 0.03, 0.93), Birth intervals > 2 years (AOR = 0.18; 95% CI: 0.04, 0.76), good nutritional knowledge (AOR = 0.34; 95% CI: 0.17, 0.67), and having no dietary change as a result of current pregnancy AOR = 6.02; 95% CI: 2.99, 12.14) were significantly associated with undernutrition. The prevalence of undernutrition among pregnant women was 21.8%. Current estimate is lower than previously reported in the study area but higher than reported in developed country. Age of women, Birth intervals, and Dietary change as a result of current pregnancy and Nutrition knowledge were important risk factors/ predictors of undernutrition (MUAC < 23 cm). Interventions targeting maternal nutrition education and child spacing with giving special emphasis to adolescent pregnant women are recommended.


Endocytic membrane traffic to the Golgi apparatus in a regulated secretory cell line.
We have established a ricin-resistant glycosylation-defective PC12 pheochromocytoma cell line to study biochemically glycoprotein traffic from the cell surface to the Golgi apparatus in regulated secretory cells. The strategy employed in this study is a modification of that used previously (Duncan, J. R., and Kornfeld, S. (1988) J. Cell Biol. 106, 617-628) to demonstrate transport of the cation-independent and -dependent mannose 6-phosphate receptors from the cell surface to the trans-Golgi network in nonsecretory cell types. In ricin-resistant PC12 cells, radiolabeled galactose was incorporated enzymatically into surface glycoconjugates, primarily glycoproteins. Resistance to beta-galactosidase was acquired upon reculture at 37 degrees C due to further terminal glycosylation of the galactose residues. Treatment of N-linked oligosaccharides isolated from recultured cells with a variety of glycosidases in conjunction with beta-galactosidase demonstrated the addition of sialic acid N-acetylglucosamine and fucose residues to the galactose residues in recultured cells. Resistance to beta-galactosidase was not acquired in cells recultured at 19 degrees C, indicating that subsequent glycosylation of galactose residues did not occur at the cell surface or in endosomes. While glycosylation of galactose incorporated into asparagine oligosaccharides in Chinese hamster ovary clone 13 cells was not significant (less than 1%) after 6 h of reculture, approximately 10% of the galactose incorporated into surface oligosaccharides was further glycosylated in PC12 cells in this time. Analysis of total labeled versus beta-galactosidase-resistant proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that endocytic traffic to the site of glycosylation activity in mutant PC12 cells was highly selective, but included a much greater number of proteins than were detected in Chinese hamster ovary clone 13 fibroblasts.


Free radical yields from the homolysis of peroxynitrous acid.
A recent study reports discordant results for maximal free-radical yields from the decomposition of peroxynitrous acid using different assay reagents and a puzzling decrease (to zero) of the radical yields with increasing pH. An assay method using 2,2,'azino-bis(3-ethyl-benzthiazoline sulphonate) (ABTS) has been tested using stopped-flow kinetic studies, and the results imply that the assay is satisfactory when [HOONO] much greater than [-OONO] but that reactions involving peroxynitrite anion interfere at higher pH. Evidence is presented that peroxynitrite was an interfering species in the earlier studies.


Riparin II potentials the effect of ephedrine on inflammation and remodelling in the airway of rats suffering from asthma by regulating transforming growth factor-β/Smad3 signalling pathway.
Asthma is a chronic obstructive lung disorder involving hyperresponsive lung tissue. This study evaluated the protective effects of riparin II against asthma and determined the synergistic effects of riparin II with ephedrine in treatment of asthma. Asthma was induced by intraperitoneal injection of Al(OH)3 (100 mg) with ovalbumin 1 mg/kg and subsequent exposure to 2% ovalbumin aerosol for 1 week. All animals were treated with riparin II 50 mg/kg and ephedrine 25 mg/kg alone and in combination for the duration of the study. Interleukin levels were assessed in the serum and bronchoalveolar lavage fluid (BALF) of asthmatic rats, while inflammatory cell infiltration was determined in the lungs. Airway remodelling was determined by assessing the lung tissue expression levels of transforming growth factor beta 1 (TGF-β1), Smad, and collagen I in asthmatic rats. There were lower levels of cytokines in the serum and BALF in riparin II-treated rats than in negative control rats. Moreover, inflammatory cell and IgE levels were reduced while interferon level was enhanced in the lungs of riparin II-treated rats, compared to negative control rats. These data reveal that treatment with riparin II ameliorates the altered expression of TGF-β1, Smad, and collagen I in lung tissue of asthmatic rats. In conclusion, riparin II treatment alone and in combination with ephedrine ameliorated the hyperresponsiveness of lung tissue due to reductions in airway remodelling and inflammation in asthmatic rats.


National outbreaks of Salmonella infection in the UK, 2000-2011.
Over a 12-year period, the Health Protection Agency's (now Public Health England's) Department of Gastrointestinal and Emerging Infections (GEZI) investigated over 100 potential national outbreaks of Salmonella enterica. These ranged from a cluster of cases requiring data interrogation and monitoring of the situation, to full blown case-control studies involving hundreds of interviews, many staff, multi-agency collaboration and the media. Vehicles of infection ranged from the usual suspects of chicken and eggs, to the less frequently implicated snake feed and chocolate. This has forced us to alter our preconceptions of disease transmission. The way in which GEZI investigate outbreaks and conduct case-control studies is constantly evolving as we learn and adapt to the changing aetiology of S. enterica. We present the findings and lessons learned during the last 12 years of investigating S. enterica outbreaks in England and Wales.


Clinical illustrations of the sexual misuse of girls.
The sexual misuse of girls, usually incestuous, often results in profound psychological impairment, sometimes transmitted to the next generation.


[Intravital study of the hematocrit value in the microcirculatory system before and after polyglucin administration].
The hematocrit index in the microvessels of the rat mesentery was studied in vivo before and after intravenous injection of polyglucin. It was maximal in arterio-venular anastomoses (44%) and minimal (11%) in the capillaries. Polyglucin reduced the hematocrit value in all the microvessels and to a greater degree in the arterio-venular anastomoses and capillaries.


Kinetic properties and inactivation of the gating currents of sodium channels in squid axon.
Associated with the opening and closing of the sodium channels of nerve membrane is a small component of capacitative current, the gating current. After termination of a depolarizing step the gating current and sodium current decay with similar time courses. Both currents decay more rapidly at relatively negative membrane voltages than at positive ones. The gating current that flows during a depolarizing step is diminished by a pre-pulse that inactivates the sodium permeability. A pre-pulse has no effect after inactivation has been destroyed by internal perfusion with the proteolytic enzyme pronase. Gating charge (considered as positive charge) moves outward during a positive voltage step, with voltage dependent kinetics. The time constant of the outward gating current is a maximum at about minus 10 mV, and has a smaller value at voltages either more positive or negative than this value.


Comparison of cataract surgery outcomes between a secondary and a tertiary eye hospital in Tamil Nadu, India.
To examine the difference in post-operative visual outcomes of cataract surgeries between a tertiary and secondary centre at Aravind Eye Hospitals in Tamil Nadu, India. Our retrospective cross-sectional study analysed cataract surgeries at a secondary centre and its associated tertiary centre in 2021. Our main outcome measures were postoperative best corrected visual acuity (BCVA), spherical equivalent, and intraoperative and postoperative complications. Two-sample proportion tests and logistic regression analyses were performed. The analysis of 32,302 cataract surgeries in 2021 of which 4357 were performed at the secondary centre and 27,945 were performed at the tertiary centre showed that the tertiary centre operated on more advanced cataract condition (p < 0.001). Intraoperative (p < 0.001) and post-operative complication rates (p < 0.001) were higher in the tertiary centre. The odds of effective outcomes (BCVA > = 6/12) controlling for all covariates are poorer (p < 0.0001) in the tertiary centre for both phacoemulsification (phaco) and manual small incision cataract surgeries (MSICS). World Health Organization recommendations for the effective outcome of cataract surgery are met by both the tertiary and secondary centres, but the odds of effective outcomes in the tertiary centre was lower after adjusting for all known factors. Further investigations of the causes of poor vision in both phaco and MSICS in the tertiary centre are needed to improve the situation.


Twenty-Nail-Dystrophy / Trachyonychia: a case report in a five year old girl seen at the Paediatric Out-patient Department of a Tertiary Hospital in Lafia North-Central Nigeria.
Twenty-Nail-Dystrophy (TND) also referred to as Trachyonychia is a disorder of the nails. It can affect all the nails hence the name. Trachyonychia is characterized by nail roughness, longitudinal ridging, fragility and hyper-pigmentation. It can occur in all ages and respond poorly to treatment. With this background, we report the case of a five year old girl with this disorder.


Jargonagraphia: clinical and neuropsychological correlates.
Jargonagraphia (i.e., fluent, unintelligible writing with abundant paragraphias and preserved mechanics of writing) is considered to be an infrequent symptom of Wernicke's aphasia. Six cases fulfilling the definition of jargonagraphia were found in a retrospective series of 1076 consecutive aphasics and the neuropyschological and clinical correlates of this phenomenon were analysed. Jargonagraphia was not qualitatively uniform, and its appearance seems to be conditioned by the interaction of an increased "impulse to write" with disrupted language mechanisms.


Pesticide residue profiles in bee bread and pollen samples and the survival of honeybee colonies-a case study from Luxembourg.
Pesticide residues (112 compounds) were quantified by GC-MS/MS or LC-MS/MS in 85 bee bread samples and 154 pollen samples obtained from five apiaries each with three or four colonies (genotype Buckfast) in Luxembourg over the period 2011-2013. Thiacloprid, chlorfenvinphos, tebuconazole, and methiocarb were found most frequently in bee bread while thiacloprid, permethrin-cis, and permethrin-trans were detected most frequently in the pollen samples. Three neonicotinoid insecticides (clothianidin, imidacloprid, and thiamethoxam) that were restricted by an EU regulation in 2013 after our sampling campaign was finished were each found in less than 8% of the pollen or bee bread samples. The maximum concentrations of thiacloprid, metazachlor, and methiocarb measured in the pollen collected by a group of honeybee colonies (n = 5) without survivors within the 3-year period of observation were 86.20 ± 10.74 ng/g, 2.80 ± 1.26 ng/g, and below the limit of quantification, respectively. The maximum concentrations of the same compounds measured in the pollen collected by a group of honeybee colonies with significantly (P = 0.02) more survivors (7 out of 9) than expected, if the survivors had been distributed randomly among the groups of colonies, were 11.98 ± 2.28 ng/g, 0.44 ± 0.29 ng/g, and 8.49 ± 4.13 ng/g, respectively. No honeybee colony that gathered pollen containing more than 23 ng/g thiacloprid survived the 3-year project period. There was no statistically significant association between pesticide residues in the bee bread and the survival of the colonies. Actions already taken or planned and potential further actions to protect bees from exposure to pesticides are discussed.


Fibronectin is an estrogen-repressed protein in RUCA-I rat endometrial adenocarcinoma cells.
We recently established and characterized two rat endometrial adenocarcinoma cell lines which we called RUCA-I and RUCA-II. Despite high estrogen receptor levels neither cell line responded to estradiol in conventional cell culture conditions on plastic and in the presence of charcoal stripped fetal calf serum. We further demonstrated that culturing of these cells on a reconstituted basement membrane induced the estrogen responsiveness for both proliferation and gene expression. Particularly, the expression of components of the complement C3 system, which represent major estradiol inducible proteins in the rat uterus in vivo, were found to be under the control of estrogens and antiestrogens. In this paper the search for estrogen repressed proteins is reported. For this purpose secretory proteins of RUCA-I cells were metabolically labelled with 35S-methionine and tested for the presence of estrogen-repressed, antiestrogen-inducible protein species. Analyzing cell culture supernatants of RUCA-I cells by polyacrylamide gel electrophoresis under reducing conditions a protein with an apparent size of approx. 250-270 kDa became conspicuous. The formation and secretion of this protein was suppressed by estradiol and induced by the antiestrogen ICI 164384. Gel electrophoresis performed under non-reducing conditions and hyaluronidase digestion showed that this estrogen-repressed protein represents a dimeric glycoprotein. By immunoprecipitation this glycoprotein was identified as fibronectin. Investigations of steady state mRNA levels of fibronectin by rtPCR suggested a post-transcriptional regulation of this molecule by estradiol. This is the first report on repression of components of the extracellular matrix by estradiol and induction by the complete antiestrogen ICI 164384. The consequences of this finding in regard to growth and invasion of endometrial tumors are discussed.


Diagnosis and classification of chronic low back pain disorders: maladaptive movement and motor control impairments as underlying mechanism.
Low back pain (LBP) is a very common but largely self-limiting condition. The problem arises however, when LBP disorders do not resolve beyond normal expected tissue healing time and become chronic. Eighty five percent of chronic low back pain (CLBP) disorders have no known diagnosis leading to a classification of 'non-specific CLBP' that leaves a diagnostic and management vacuum. Even when a specific radiological diagnosis is reached the underlying pain mechanism cannot always be assumed. It is now widely accepted that CLBP disorders are multi-factorial in nature. However the presence and dominance of the patho-anatomical, physical, neuro-physiological, psychological and social factors that can influence the disorder is different for each individual. Classification of CLBP pain disorders into sub-groups, based on the mechanism underlying the disorder, is considered critical to ensure appropriate management. It is proposed that three broad sub-groups of CLBP disorders exist. The first group of disorders present where underlying pathological processes drive the pain, and the patients' motor responses in the disorder are adaptive. A second group of disorders present where psychological and/or social factors represent the primary mechanism underlying the disorder that centrally drives pain, and where the patient's coping and motor control strategies are mal-adaptive in nature. Finally it is proposed that there is a large group of CLBP disorders where patients present with either movement impairments (characterized by pain avoidance behaviour) or control impairments (characterized by pain provocation behaviour). These pain disorders are predominantly mechanically induced and patients typically present with mal-adaptive primary physical and secondary cognitive compensations for their disorders that become a mechanism for ongoing pain. These subjects present either with an excess or deficit in spinal stability, which underlies their pain disorder. For this group, physiotherapy interventions that are specifically directed and classification based, have the potential to impact on both the physical and cognitive drivers of pain leading to resolution of the disorder. Two case studies highlight the different mechanisms involved in patients with movement and control impairment disorder outlining distinct treatment approaches involved for management. Although growing evidence exists to support this approach, further research is required to fully validate it.


Assessment of trace pollutants in Korean coastal sediments using the triad approach: a review.
Here we summarize and review the previous efforts on sediment assessment together with major scientific findings that were conducted in the Korean coastal waters since late 1990s. Towards integrated triad analysis, sediment data (>1700 samples) reported from the Korean coasts were collected and reviewed of which data collectively includes three components of chemical, toxicological, and ecological measures. First, the chemistry data suggested widespread and historic distribution of sedimentary pollutants along the Korean coasts. Spatial distributions suggested that their sources were independent of each other, while some localized areas (highlighted for Lake Shihwa, Masan Bay, and Ulsan Bay) and zones with extremely high pressures of certain pollutants were also identified. The mass balance analyses and/or direct correlations linking triad components reflected a general agreement between endpoints. The benthic community responses given by species occurrence and diversity also reflected the type and degree of sediment contamination, however, could not be fully explained by the known target chemicals. Overall, the triad assessment of trace pollutants in Korean coastal sediments seemed to be useful and much powerful when all the components are fully addressed.


Humanized Mouse Model of HIV Infection.
The development of new drugs for the treatment of HIV infection requires testing of their efficacy in a relevant animal model, such as humanized mice, which, unfortunately, are not yet available in Russia. In the present study, we have developed conditions for the humanization of immunodeficient NSG mice with human hematopoietic stem cells. Humanized animals generated during the study showed a high degree of chimerism and harbored repopulation of the entire range of human lymphocytes required for HIV replication in the blood and organs. Inoculation of these mice with HIV-1 virus led to stable viremia, which was confirmed by the presence of viral RNA in blood plasma throughout the entire period of observation and proviral DNA in the organs of animals 4 weeks after HIV infection.


NAD+-dependent synthesis of a 5'-phospho-ADP-ribosylated RNA/DNA cap by RNA 2'-phosphotransferase Tpt1.
RNA 2'-phosphotransferase Tpt1 converts an internal RNA 2'-monophosphate to a 2'-OH via a two-step NAD+-dependent mechanism in which: (i) the 2'-phosphate attacks the C1″ of NAD+ to expel nicotinamide and form a 2'-phospho-ADP-ribosylated RNA intermediate; and (ii) the ADP-ribose O2″ attacks the phosphate of the RNA 2'-phospho-ADPR intermediate to expel the RNA 2'-OH and generate ADP-ribose 1″-2″ cyclic phosphate. Tpt1 is an essential component of the fungal tRNA splicing pathway that generates a unique 2'-PO4, 3'-5' phosphodiester splice junction during tRNA ligation. The wide distribution of Tpt1 enzymes in taxa that have no fungal-type RNA ligase raises the prospect that Tpt1 might catalyze reactions other than RNA 2'-phosphate removal. A survey of Tpt1 enzymes from diverse sources reveals that whereas all of the Tpt1 enzymes are capable of NAD+-dependent conversion of an internal RNA 2'-PO4 to a 2'-OH (the canonical Tpt1 reaction), a subset of Tpt1 enzymes also catalyzed NAD+-dependent ADP-ribosylation of an RNA or DNA 5'-monophosphate terminus. Aeropyrum pernix Tpt1 (ApeTpt1) is particularly adept in this respect. One-step synthesis of a 5'-phospho-ADP-ribosylated cap structure by ApeTpt1 (with no subsequent 5'-phosphotransferase step) extends the repertoire of the Tpt1 enzyme family and the catalogue of ADP-ribosylation reactions involving nucleic acid acceptors.


Association of vitamin D receptor gene polymorphism with urolithiasis.
Recent studies suggest that allelic variations of the vitamin D receptor (VDR) gene can influence calcium absorption and excretion. Therefore, we studied the association of VDR gene polymorphism with urolithiasis. We studied 83 patients with urinary stones and 83 controls. Patients were scored for certain clinical characteristics, including long axis diameter of the largest stone (1 point-less than 10 mm. and 2-10 mm. or greater), number of stones (1 point-1 and 2-multiple) and history of calcium stone disease (1 point-absent and 2-present). They were classified into 3 groups according to the total score, including low-3, intermediate-4 or 5 and high-6 points. The 2 VDR gene polymorphisms TaqI and ApaI were detected by polymerase chain reaction-restriction fragment length polymorphism and their relationships with the urinary calcium level were examined. The incidence of TaqI Tt and tt genotypes was significantly higher in the high score group than in controls. The TaqI t allele was associated with a 5.2-fold increase in the risk of severe stone disease. The urinary calcium level in patients with the Tt and tt genotypes was also higher than in those with the TT genotype. The rate of the ApaI genotype was not different in the high score group and controls. The TaqI t allele of the VDR gene may be a risk factor for severe stone disease and recurrent stones.


Bone disease in anorexia nervosa.
Anorexia nervosa is a serious psychiatric disorder accompanied by high morbidity and mortality. It is characterized by emaciation due to self-starvation and displays a unique hormonal profile. Alterations in gonadal axis, growth hormone resistance with low insulin-like growth factor I levels, hypercortisolemia and low triiodothyronine levels are almost universally present and constitute an adaptive response to malnutrition. Bone metabolism is likewise affected resulting in low bone mineral density, reduced bone accrual and increased fracture risk. Skeletal deficits often persist even after recovery from the disease with serious implications for future skeletal health. The pathogenetic mechanisms underlying bone disease are quite complicated and treatment is a particularly challenging task.


Role of mammary casein kinase in the phosphorylation of milk proteins.
Casein kinase from lactating bovine mammary gland catalyses the transfer of the terminal phosphoryl group of ATP to specific serine residues in dephosphorylated caseins. Best substrates for casein kinase are the dephosphorylated proteins (bovine alpha S1- and beta-caseins and pepsin), unphosphorylated human beta-casein and the dephosphorylated peptide (residues 1-25) from bovine beta-casein. Results obtained with bovine and human beta-caseins indicate that the two serines underlined in the cluster Ser-Leu-Ser-Ser-Ser are particularly susceptible to the action of casein kinase. Since a similar sequence is found in dephosphorylated alpha S1-casein, it is probable that serines in this region of alpha S1-casein are also phosphorylated. The results support the concept that certain serines in casein are particularly susceptible to phosphorylation by casein kinase.


Application of a multi-method approach in characterization of natural aquatic colloids from different sources along Huangpu River in Shanghai, China.
Natural colloid properties and the impact of human activities on these properties are important considerations for studies seeking to understand the fate and transport of pollutants. In this study, the relationship between size and fluorescence properties of natural colloids from 4 different sources were quantified using a multi-method analytical approach including UV-visible and fluorescence spectroscopy, flow field flow fractionation (FlFFF) coupled online to fluorescence spectrometer, and atomic force microscopy (AFM). Results indicate that colloids from pristine natural river water have higher aromaticity and humification, higher fluorescent intensity, and smaller size compared to those from the rivers impacted by livestock. The majority of colloids are smaller than 10nm in size as measured by AFM and FlFFF. Colloid size measured by FlFFF coupled to fluorescence spectroscopy increases in the order peak C (Ex/Em at 300-340/400-460 nm)<peak D (Ex/Em at 210-230/340-360 nm)<peak T (Ex/Em at 270-280/330-370 nm)<peak A (Ex/Em at 210-250/400-460 nm), revealing that optical properties such as fluorescence are correlated with size. This trend is confirmed by the principal component analysis, which demonstrates that the first principal component (PC1) reflecting colloid optical properties decrease with the increase in PC3 which is correlated to the colloid size.


Development of natural killer cells: comparison of the maturation rates in different lymphoid compartments.
By means of semisyngeneic bone marrow transplantation, the appearance of donor-type natural killer (NK) cells in different organs (spleen, blood, lungs) of the recipients was studied. Seven days after the transplantation the first donor-type NK cells appeared in all these organs, and adult NK levels were reached simultaneously within a couple of days. The first NK cells to appear in every organ divided rapidly (sensitive to hydroxyurea) and contained a high proportion of Thy-1+ cells. These data suggest that NK cell precursors mature locally and simultaneously in different organs.


Complications after 90Y microsphere radioembolization for unresectable hepatic tumors: An evaluation of 112 patients.
The aim of this study was to estimate the incidence of complications after (90)Y microsphere radioembolization for unresectable hepatic tumors and evaluate risk factors for late complications. A cohort of 112 consecutive patients from two institutions underwent (90)Y microsphere radioembolization for unresectable hepatic tumors. Complications were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Symptoms secondary to postradioembolization syndrome occurring within 30 days were recorded as early complications, and all other complications were considered late complications. Seventy-eight patients (70%) experienced postradioembolization syndrome, including fatigue, abdominal pain, nausea, vomiting, anorexia, or fever. Three patients (3%) experienced a Grade 3 early complication; no Grade 4 or 5 early toxicity occurred. Two patients (2%) experienced clinically significant liver dysfunction; 13 patients (12%), 27 patients (24%), and 9 patients (8%) had an elevation of bilirubin, aspartate aminotransferase, and alanine aminotransferase, respectively. Eleven patients (10%) experienced gastrointestinal ulceration, including two Grade 3 complications and one Grade 4 complication. Cholecystitis occurred in 7 patients (6%), including two Grade 3 complications. Grade 2 pancreatitis occurred in 1 patient (1%). No radiation pneumonitis was observed. The cumulative incidence of late Grade 3 or 4 complications at 12 months after radioembolization was 8%. No Grade 5 toxicity occurred. (90)Y microsphere radioembolization is a well-tolerated treatment for unresectable hepatic tumors with a low risk of Grade 3 or higher early or late toxicity.


GALPROP cosmic-ray propagation code: recent results and updates.
Information on cosmic-ray (CR) composition comes from direct CR measurements while their distribution in the Galaxy is evaluated from observations of their associated diffuse emission in the range from radio to gamma rays. Even though the main interaction processes are identified, more and more precise observations provide an opportunity to study more subtle effects and pose a challenge to the propagation models. GALPROP is a sophisticated CR propagation code that is being developed for about 20 years. It provides a unified framework for interpretations of data from many different types of experiments. It is used for a description of direct CR measurements and associated interstellar emissions (radio to gamma rays), thereby providing important information about CR injection and propagation in the interstellar medium. By accounting for all relevant observables at a time, the GALPROP code brings together theoretical predictions, interpretation of the most recent observations, and helps to reveal the signatures of new phenomena. In this paper we review latest applications of GALPROP and address ongoing and near future improvements. We are discussing effects of different propagation models, and of the transition from cylindrically symmetrical models to a proper 3D description of the components of the interstellar medium and the source distribution.


ADAMTS13 activity and the presence of acquired inhibitors in human immunodeficiency virus-related thrombotic thrombocytopenic purpura.
Little is known about the pathophysiology of human immunodeficiency virus (HIV)-related thrombotic thrombocytopenic purpura (TTP). It is generally assumed that acquired ADAMTS13 deficiency is due to the presence of autoantibody inhibitors, but limited data are available regarding ADAMTS13 activity and inhibitors in such patients. By use of a collagen-binding assay, ADAMTS13 activity was analyzed at presentation in 20 patients with HIV-related TTP. The presence of inhibitors in patients with reduced ADAMTS13 activity was assessed with mixing studies. The correlation between ADAMTS13 activity and inhibitors and other laboratory and clinical parameters was assessed. The patients fell clearly into two groups with regard to ADAMTS13 activity. Six patients (30%) had activity within the normal range, whereas the remaining 14 patients had severely reduced levels. Of the patients with reduced activity, only 5 patients had a detectable inhibitor whereas 8 showed no evidence of an inhibitor. There was significant correlation between normal ADAMTS13 activity and lower CD4 counts (p = 0.049). von Willebrand factor (VWF) antigen levels were significantly higher in patients with reduced ADAMTS13 activity (p = 0.03). Low activity in the absence of a detectable inhibitor was associated with significantly higher D-dimer levels (p = 0.01) and worse clinical outcome. The heterogeneity with regard to ADAMTS13 activity and the absence of inhibitors in the majority of patients indicate that other factors are important in the pathogenesis of HIV-related TTP. VWF release and localized coagulation activation due to direct viral or cytokine-mediated endothelial cell injury is likely to be playing a major role.


[Antibiotic resistance and virulence factors in clinical Salmonella enterica isolates].
The increase of Salmonella enterica isolates multi-resistant to different antibiotics, including β-lactams and fluoroquinolones, is a problem of clinical importance. The dissemination of Salmonella Typhimurium resistant to ampicillin (AMP)-chloramphenicol (CHL)-streptomycin (STR)-sulphonamides and (SUL)-tetracycline (TET), that harbour the Salmonella Genomic Island type 1 (SGI1), and the acquisition of transferable genetic material have favoured the multi-resistance in this genus. A total of 114 clinical S.enterica isolates were studied (period 2009-2010). The susceptibility to 20 antibiotics was determined by disc diffusion and microdilution. The antimicrobial resistance mechanisms and the integrons were analysed by PCR, and sequencing in the AMP(R) isolates. In all the blaPSE-1-positive isolates, the clonal relationship was determined by PFGE, as well as the presence of SGI1 and 29 virulence genes by PCR. Eighteen different serotypes were found among the 114 isolates studied, Typhimurium (61%) and Enteritidis (16%) being the most prevalent. High percentages of resistance to SUL (68%), TET (58%), AMP (55%) and STR (46%) were observed. The great majority (92%) of 63 AMP(R) isolates were multi-resistant, with the AMP-STR-TET-SUL phenotype (19 isolates) being the most frequent one and associated with the blaTEM-1b+strA-strB+tet(B)+sul2 genotype. Class 1 integrons (7 different structures) were observed in 48% AMP(R) isolates, highlighting the blaOXA-1+aadA1 structure (8 isolates), one empty integron and non-classical integrons (5 isolates). The blaPSE-1 gene was detected inside the classical SGI1 structure in 13 clonally-related isolates that showed the same virulence profile. The high percentage of multi-resistant S.enterica isolates, especially associated to S.Typhimurium, to the AMP, STR, TET and SUL phenotype, and to the blaTEM-1b+strA-strB+tet(B)+sul2 genotype, shows an important risk of possible failures in the treatment of serious infections caused by this serotype.


Effect of gammahydroxybutyric acid on serotonin synthesis, concentration and metabolism in the developing rat brain.
5-HT synthesis, levels and degradation were investigated in the whole brain and regional brain areas in 4, 14, and 28 days old rats after administration of gammahydroxybutyric acid (GHBA). 5-HT synthesis was investigated by means of 5-HTP accumulation after decarboxylase inhibition by NSD 1015. 5-HTP accumulation increased in the 14 and 28 days old rats but decreased in the 4 days old animals 90 min after GHBA, 750 mg/kg. In the 28 days old rats a corresponding increase was also noted in the precursor amino acid tryptophan. Regional and whole brain 5-HT levels were not altered by GHBA treatment. Regional as well as whole brain levels of 5-HIAA increased in the 14 and 28 days old rats after GHBA administration. In conclusion, the present data indicate that GHBA increases the synthesis and degradation of 5-HT in adolescent rats. These effects of GHBA were not seen in the neonatal animals.


SUPFUNSIM: Spatial Filtering Toolbox for EEG.
Brain activity pattern recognition from EEG or MEG signal analysis is one of the most important method in cognitive neuroscience. The SUPFUNSIM library is a new MATLAB toolbox which generates accurate EEG forward model and implements a collection of spatial filters for EEG source reconstruction, including the linearly constrained minimum-variance (LCMV), eigenspace LCMV, nulling (NL), and minimum-variance pseudo-unbiased reduced-rank (MV-PURE) filters in various versions. It also enables source-level directed connectivity analysis using partial directed coherence (PDC) measure. The SUPFUNSIM library is based on the well-known FIELDTRIP toolbox for EEG and MEG analysis and is written using object-oriented programming paradigm. The resulting modularity of the toolbox enables its simple extensibility. This paper gives a complete overview of the toolbox from both developer and end-user perspectives, including description of the installation process and use cases.


[The Effect in Extraction of Different Ratio of Dahuang-Taoren for Ten Kinds of Chemical Constituents from Rhizoma Rhei].
To investigate the effect of Dahuang-Taoren with different proportion of extraction amount changes of ten kinds of chemical constituents in Rhizoma Rhei. Uniform method to set different ratio( 1∶ 5,2∶ 5,2∶ 3,1∶ 1,3∶ 2,5∶ 2,5∶ 1),and set the control group ( Dahuang-Taoren( 1 ∶ 0). HPLC was used to determine the content of ten constituents as gallic acid,( +)-catechin,sennoside B,anthraquinones( aloe-emodin,rhein,emodin,chrysophanol,physcion,chrysophanol-1-O-glucoside,emodin major grape glycoside) in different ratio of drug. Different proportions of Dahuang-Taoren on the extraction amount of ten chemical components in Rhizoma Rhei changes were analyzed. . Compared to the control group, Dahuang-Taoren with different ratio( 5∶ 1,5∶ 2,3∶ 2) in a sample with increasing proportion of Taoren,the extraction amount of ten kinds of constituents of Rhizoma Rhei gradually decreased;Dahuang-Taoren with ratio of 1∶ 1,ten kinds of constituents in extraction of total amount arrived minimum value. Dahuang-Taoren with different ratio( 2∶ 3,2∶ 5,1∶ 5) in a sample with increasing proportion of Taoren,the extraction amount of gallic acid,( +) catechin,chrysophanol of Rhizoma Rhei increased significantly. There is obvious change in chemical constituents of the extraction amount of Rhizoma Rhei with the change of the ratio in Dahuang-Taoren, and Dahuang-Taoren with the ratio( 2∶ 3,2∶ 5,1∶ 5),the extraction amount of gallic acid,( +)-catechin,sennoside B,aloe-emodin,emodin,chrysophanol,physcion,chrysophanol-1-O-glucoside are significantly higher than control group.


Anticipating antiport in P-type ATPases.
Cation-transporting P-type ATPases show a high degree of structural and functional homology. Nevertheless, for many members of this large family, the molecular mechanism of transport is unclear; namely, whether transport is electrogenic or not and if countertransport is involved remains to be established. In a few well-studied cases such as the Na(+)-K(+)-ATPase, plasma membrane Ca(2+) ATPase (PMCA) and sarcoplasmic reticulum Ca(2+) ATPase (SERCA) countertransport has been clearly demonstrated. New data based on the crystal structure of SERCA now strongly indicate that countertransport could be mandatory for all P-type ATPases. This concept should be verified for other known and for all newly characterized P-type ATPases.


A ratiometric fluorescence-scattered light strategy based on MoS2 quantum dots/CoOOH nanoflakes system for ascorbic acid detection.
A facile ratiometric fluorescence method for ascorbic acid (AA) detection was established by combining the fluorescence of MoS2 quantum dots (QDs) with second-order scattering (SOS) of CoOOH. In MoS2 QDs/CoOOH nanohybrid system, the fluorescence of MoS2 QDs was quenched by CoOOH whereas the intensity of SOS was relatively close to the fluorescence due to the intrinsic high scattering ability of large size CoOOH nanoflakes. With the addition of AA, CoOOH nanoflakes were reduced to Co2+ accompanied the size decline and the disappearance of characteristic absorption in UV-vis spectrum, resulting in the fluorescence recovery and SOS fading. Thus, the ratiometric detection of AA was obtained through the opposite changes of fluorescence and SOS. Under optimized conditions, the detection limit of AA was 0.21 μmol L-1 with a linear range from 0.80 to 32.0 μmol L-1. Furthermore, the MoS2 QDs/CoOOH nanohybrid system was applied to the detection of AA in human serum samples and vitamin C tablets with satisfactory results.


WHO DOES WHAT IN HUMAN FACTORS/ERGONOMICS IN MALAYSIA?
Individuals' expertise in human factors and ergonomics in Malaysia was studied with a view to aiding in gauging the confusion and conjectures of the expertise in this area. The choices and preferences of individuals in dealing with the current issues of human factors and ergonomics were examined. The authors suggest the ways to meet ethical challenges in their work and professions.


Extension of the substrate spectrum by an amino acid substitution at residue 219 in the Citrobacter freundii cephalosporinase.
The cephalosporinase of Citrobacter freundii GN346 is a class C beta-lactamase, consisting of 361 amino acids and exhibiting the substrate profile of a typical cephalosporinase. On the conversion of a conserved glutamic acid at residue 219 to lysine, the substrate spectrum of the cephalosporinase was extended to oxyimino cephalosporins, aztreonam and carbenicillin, which are essentially undesirable substrates for the enzyme. Escherichia coli cells carrying the mutant gene showed higher resistance levels to cefuroxime, aztreonam, and carbenicillin, but a lower resistance level to cefoxitin, than cells carrying the wild gene. The kcat values of the purified mutant enzyme for ceftazidime, cefuroxime, and cefmenoxime were 77,100, and 300 times those of the wild enzyme, respectively. The relative Vmax values of the mutant enzyme for aztreonam and carbenicillin were determined to be 11 and 23 times those of the wild enzyme, respectively, but the value of the mutant enzyme for cefoxitin was only one-third that of the wild enzyme.


Temperature adaptation of fish hemoglobins reflected in rates of autoxidation.
Observation of rapid autoxidation of oxyhemoglobin (HbO2) from a deep-sea fish (Co-ryphaenoides acrolepis) prompted a survey of rates of autoxidation of HbO2 to methemoglobin in vitro from fishes inhabiting vastly different depths (1 to 3800 m) in order to discover any relationship between autoxidation rates and different environmental temperatures and pressures to which hemoglobins may be adapted. The rate of autoxidation was found to be sensitive to temperature in both deep- and shallow-living fishes. Hemoglobin appears to be thermally adapted since autoxidation was 10 times faster at all temperatures tested with HbO2 obtained from a cold-adapted fish (Coryphaenoides armatus variabilis) than from a comparatively warm-adapted one (Paralabrax nebulifer). High hydrostatic pressure does not affect autoxidation rates in either deep- or shallow-dwelling species. Rates of autoxidation may be intimately related to hemoglobin function thus providing a means for studying hemoglobin adaptation in poikilothermic vertebrates, especially among cold-adapted species.


[Local staging of prostate carcinoma with phased array MR imaging: prospective study over 5 years].
To assess by MRI, using a pelvic phased array coil, the accuracy for staging prostate carcinoma and to correlate the results with the rate of positive surgical margins. Between January 1995 and December 1999, 176 patients with localized prostate carcinoma underwent a preoperative MRI examination using a pelvic phased-array coil (1 Tesla). MRI and histological results were compared in a prospective study. 131 were classified T2 and 45 were classified T3 at MRI. Pathologic findings showed 103 pT2 and 73 pT3. The accuracy of MRI (extra capsular or vesicle extension) was 75%. The risk for a patient labelled T2 or T3 at MRI to have a positive surgical margin was respectively 13.7% and 31%. This study shows that the phased-array coil has a low sensitivity but a good specificity to distinguish between organ-confined cancer or not. It shows that the risk of positive surgical margins is higher for T3 lesions at MRI. The low sensitivity should be improved by using a multi coil phased array.


Characterization of tau protein present in microtubules and paired helical filaments of Alzheimer's disease patient's brain.
Two proteins immunologically related to porcine tau protein are found in the brain of Alzheimer's disease patients. One is bound to microtubules and, after isolation by co-polymerization with tubulin, shows a size and tryptic peptide map, similar to the microtubule-associated tau protein, present in the brain of non-demented patients. The other tau-related protein is present as the major protein of a purified fraction of paired helical filaments. The paired helical filament-associated protein shows smaller molecular weight (33,000) than microtubule-associated tau; however, this 33,000 mol. wt protein reacts with a monospecific anti-tau antibody and with an antibody to a 19-amino acid peptide corresponding to amino acids 228-246 of human tau. Furthermore, the 33,000 mol. wt protein and the tau protein have similar tryptic peptide maps. These results suggest that the paired helical filament protein is a modified form of the microtubule-associated tau protein.


Identification of candidate ATP-binding cassette transporter gene family members in Diaphorina citri (Hemiptera: Psyllidae) via adult tissues transcriptome analysis.
The ATP-binding cassette (ABC) transporters exist in all living organisms and play major roles in various biological functions by transporting a wide variety of substrates across membranes. The functions of ABC transporters in drug resistance have been extensively studied in vertebrates; however, they are rarely characterized in agricultural pests. The Asian citrus psyllid, Diaphorina citri, is one of the most damaging pests of the Citrus genus because of its transmission of Huanglongbing, also known as Yellow Dragon disease. In this study, the next-generation sequencing technique was applied to research the ABC transporters of D. citri. Fifty-three ABC transporter genes were found in the RNA-Seq data, and among these ABC transporters, 4, 4, 5, 2, 1, 4, 18 and 15 ABC proteins belonged to the ABCA-ABCH subfamilies, respectively. Different expression profiles of 52 genes between imidacloprid-resistant and imidacloprid-susceptible strains were studied by qRT-PCR; 5 ABCGs and 4 ABCHs were significantly upregulated in the imidacloprid-resistant strain. In addition, five of the nine upregulated genes were widely expressed in adult tissues in spatial expression analysis. The results suggest that these genes may play key roles in this phenotype. In general, this study contributed to our current understanding of D. citri resistance to insecticides.


Structure determination of inactive-state GPCRs with a universal nanobody.
Cryogenic electron microscopy (cryo-EM) has widened the field of structure-based drug discovery by allowing for routine determination of membrane protein structures previously intractable. Despite representing one of the largest classes of therapeutic targets, most inactive-state G protein-coupled receptors (GPCRs) have remained inaccessible for cryo-EM because their small size and membrane-embedded nature impedes projection alignment for high-resolution map reconstructions. Here we demonstrate that the same single-chain camelid antibody (nanobody) recognizing a grafted intracellular loop can be used to obtain cryo-EM structures of inactive-state GPCRs at resolutions comparable or better than those obtained by X-ray crystallography. Using this approach, we obtained structures of neurotensin 1 receptor bound to antagonist SR48692, μ-opioid receptor bound to alvimopan, apo somatostatin receptor 2 and histamine receptor 2 bound to famotidine. We expect this rapid, straightforward approach to facilitate the broad exploration of GPCR inactive states without the need for extensive engineering and crystallization.


Gene expression profile and histopathology of experimental bronchopulmonary dysplasia induced by prolonged oxidative stress.
Oxidative stress is an important factor in the pathogenesis of bronchopulmonary dysplasia (BPD), a chronic lung disease of premature infants characterized by arrested alveolar and vascular development of the immature lung. We investigated differential gene expression with DNA microarray analysis in premature rat lungs exposed to prolonged hyperoxia during the saccular stage of development, which closely resembles the development of the lungs of premature infants receiving neonatal intensive care. Expression profiles were largely confirmed by real-time RT-PCR (27 genes) and in line with histopathology and fibrin deposition studied by Western blotting. Oxidative stress affected a complex orchestra of genes involved in inflammation, coagulation, fibrinolysis, extracellular matrix turnover, cell cycle, signal transduction, and alveolar enlargement and explains, at least in part, the pathological alterations that occur in lungs developing BPD. Exciting findings were the magnitude of fibrin deposition; the upregulation of chemokine-induced neutrophilic chemoattractant-1 (CINC-1), monocyte chemoattractant protein-1 (MCP-1), amphiregulin, plasminogen activator inhibitor-1 (PAI-1), secretory leukocyte proteinase inhibitor (SLPI), matrix metalloproteinase-12 (MMP12), p21, metallothionein, and heme oxygenase (HO); and the downregulation of fibroblast growth factor receptor-4 (FGFR4) and vascular endothelial growth factor (VEGF) receptor-2 (Flk-1). These findings are not only of fundamental importance in the understanding of the pathophysiology of BPD, but also essential for the development of new therapeutic strategies.


MiR-485-3p modulates neural stem cell differentiation and proliferation via regulating TRIP6 expression.
Recent references have showed crucial roles of several miRNAs in neural stem cell differentiation and proliferation. However, the expression and role of miR-485-3p remains unknown. In our reference, we indicated that miR-485-3p expression was down-regulated during NSCs differentiation to neural and astrocytes cell. In addition, the TRIP6 expression was up-regulated during NSCs differentiation to neural and astrocytes cell. We carried out the dual-luciferase reporter and found that overexpression of miR-485-3p decreased the luciferase activity of pmirGLO-TRIP6-wt but not the pmirGLO-TRIP6-mut. Ectopic expression of miR-485-3p decreased the expression of TRIP6 in NSC. Ectopic miR-485-3p expression suppressed the cell growth of NSCs and inhibited nestin expression of NSCs. Moreover, elevated expression of miR-485-3p decreased the ki-67 and cyclin D1 expression in NSCs. Furthermore, we indicated that miR-485-3p reduced proliferation and induced differentiation of NSCs via targeting TRIP6 expression. These data suggested that a crucial role of miR-485-3p in self-proliferation and differentiation of NSCs. Thus, altering miR-485-3p and TRIP6 modulation may be one promising therapy for treating with neurodegenerative and neurogenesis diseases.


Guided versus unguided mandibular movement for duplicating intraoral eccentric tooth contacts in the articulator.
The extent to which intraoral excursive tooth contacts are duplicated correctly in the articulator is constantly being investigated. This study evaluated whether data from unguided or guided hinge axis movement are superior in duplicating excursive tooth contacts. Intraoral records of tooth contacts from intercuspal position to 4 mm protrusion and laterotrusion were obtained from 50 subjects by using occlusogram wax. These movements were simulated in a SAM2 "P" articulator using horizontal condylar inclination and Bennett angle from recorded guided and unguided mandibular movements. Occlusograms were compared with contacts generated by the articulator. On average, the articulator duplicated approximately 73% of intraoral protrusive and 81% of intraoral laterotrusive contacts for up to 4 mm of movement, using either data from unguided or guided movements. Both movements yielded identical means and no significant difference of duplicated contacts. However, individual differences scattered within approximately +/-32%. Exclusive recommendation of guided movement can be questioned for accurate imitation of dynamic tooth contacts. In addition to the type of movement, other factors must be detected to enhance articulator adjustment and workings.


Management of pulmonary tuberculosis suspects with negative sputum smears and normal or minimally abnormal chest radiographs in resource-poor settings.
Queen Elizabeth Central Hospital, Blantyre, Malawi. 1) To determine the proportion of pulmonary tuberculosis (PTB) suspects with negative sputum smears and a normal/minimally abnormal chest radiograph (CXR) who are culture-positive for Mycobacterium tuberculosis, and 2) to determine how many develop smear or radiographic evidence of PTB (TB CXR) during follow-up. PTB suspects with negative sputum smears and a normal/minimally abnormal CXR were given a second course of antibiotics and followed up at 3-week intervals over 3 months with repeat sputum smears and chest radiography. Of 79 patients (38 men and 41 women, mean age 33 years) with negative smears and a normal/minimally abnormal CXR, 16 (21%) were culture-positive for M. tuberculosis. Of 15 culture-positive patients who were alive and attended follow-up, seven (47%) developed a TB-CXR by 3 months. Of 41 culture-negative patients who were alive and attended follow-up, 13 (32%) developed a TB-CXR, including one patient who became sputum smear-positive. TB-CXRs were found only in patients with a cough. TB suspects with negative smears and normal/minimally abnormal CXRs in high human immunodeficiency virus (HIV) prevalent countries should be given a second course of antibiotics. If cough improves, patients can be advised not to return for further follow-up. If cough continues, patients should return for further follow-up with sputum smear examination and chest radiography. Approximately 50% of those who have culture-positive PTB will develop a TB-CXR by 3 months and can be identified if radiographic facilities are available.


Radiation dose reduction in direct digital panoramic radiography.
(a) To measure the absorbed radiation doses at 16 anatomical sites of a Rando phantom and (b) to calculate the effective doses including and excluding the salivary gland doses in panoramic radiography using a conventional and a digital panoramic device. Thermoluminescent dosimeters (TLD-100) were placed at 16 sites in a Rando phantom, using a conventional, Planmeca Promax and a digital, Planmeca PM2002CC Proline 2000 (Planmeca Oy, 00880 Helsinki, Finland) panoramic device for panoramic radiography. During conventional radiography the selected exposure settings were 66 kVp, 6 mA and 16s, while during digital radiography two combinations were selected 60 kVp, 4 mA, 18 s and 66 kVp, 8 mA, 18s with and without image processing function. The dosimeters were annealed in a PTW-TLDO Harshaw oven. TLD energy response was studied using RQN beam narrow series at GAEC's Secondary Standard Calibration Laboratory. The reader used was a Harshaw, 4500. Effective dose was estimated according to ICRP(60) report (E(ICRP60)). An additional estimation of the effective dose was accomplished including the doses of the salivary glands (E(SAL)). A Wilcoxon signed ranks test was used for statistical analysis. The effective dose, according to ICRP report (E(ICRP60)) in conventional panoramic radiography was 17 microSv and E(SAL) was 26 microSv. The respective values in digital panoramic radiography were E(ICRP60)=23 microSv and E(SAL)=38 microSv; while using the lowest possible radiographic settings E(ICRP60) was 8 microSv and E(SAL) was 12 microSv. The effective dose reduction in digital panoramic radiography can be achieved, if the lowest possible radiographic settings are used.


Decreasing the ceiling effect in assessing meeting quality at an academic professional meeting.
The psychometric properties of evaluations at academic meetings have not been well studied. To explore the ceiling effect in the evaluation of quality of a professional meeting and whether a change in the scale labels would decrease the ceiling effect. Cross-sectional study at two national meetings (2009-2010), attendees completed the evaluation on paper forms or online (5-point Likert scale). Of 1,064 evaluations, the mean session ratings was higher among respondents to the paper version in 2009 (4.2; 95% confidence interval [CI], 4.1 to 4.3) as compared to online responders in 2009 (3.0; 95% CI, 2.9 to 3.1) or online responders in 2010 (3.0; 95% CI, 2.9 to 3.1)(p < 0.001). A ceiling effect was present in the evaluation of an academic meeting. A change in the evaluation scale labels decreased the ceiling effect and increased evaluation variability.


Association of the 2012 American Urological Association Vasectomy Guidelines with National Trends in Vasectomy Followup in the United States.
The American Urological Association Vasectomy Guidelines published in 2012 defined vasectomy success as either azoospermia or rare nonmotile sperm (≤100,000 nonmotile sperm/ml). We sought to characterize nationwide practice patterns surrounding vasectomy followup before and after publication of the guidelines. Data were collected using the MarketScan® database. We identified men 18 to 64 years old undergoing vasectomy between 2007 and 2015 with at least 12 months of followup to track post-vasectomy semen analysis claims. Demographic data including age, vasectomy provider type and regionality were also queried. We compared the likelihood of men obtaining multiple post-vasectomy semen analyses before vs after the guidelines release with multivariate logistic regression. Linear regression was used examine time to first post-vasectomy semen analysis association with observed post-vasectomy semen analysis frequency trends. We identified a total of 87,201 patients who underwent vasectomy between 2007 and 2015 and had at least 1 post-vasectomy semen analysis claim. Men undergoing vasectomy in the post-guideline years of 2013 to 2015 were at lower risk for requiring any repeat post-vasectomy semen analysis (OR 0.68, 95% CI 0.66-0.71) and less likely to have had ≥3 post-vasectomy semen analyses (OR 0.82, 95% CI 0.77-0.88) than those in the pre-guideline (2007 to 2012) cohort. Mean time to first post-vasectomy semen analysis was shorter in men who submitted multiple analyses (p <0.001). Within a nationally representative patient cohort, men required fewer repeat post-vasectomy semen analyses after publication of the 2012 guidelines. Further research on patient and provider characteristics affecting variations in vasectomy followup patterns and guideline adherence is needed.