Ocular surface assessment in patients with obstructive sleep apnea-hypopnea syndrome.
The aim of this study was to assess the correlation between ocular surface changes and disease severity in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Two hundred eighty patients with OSAHS were compared with respect to the presence of a floppy eyelid syndrome (FES), Ocular Surface Disease Index (OSDI) questionnaire, the corneal fluorescein staining stages, the Schirmer I test, and tear film break-up time (TBUT) values. Based on the apnea-hypopnea index, the presence of FES was detected at the following rates: 23.1 % in non-OSAHS group (A), 41.7 % in mild group (B), 66.7 % in moderate group (C), and 74.6 % in severe group (D); severe and moderate stage of FES was found in groups C and D and mild stage of FES in group B (p < 0.01). OSDI questionnaire values were as follows: group A, 12.57 ± 17.64; group B, 22.90 ± 16.78; group C, 45.94 ± 22.03; and group D, 56.68 ± 22.85(p < 0.01). Schirmer values were as follows: group A, 10.76 ± 3.58 mm; group B, 9.83 ± 2.53 mm; group C, 7.73 ± 2.42 mm; and group D, 6.97 ± 2.15 mm (p < 0.01). The TBUT values were as follows: group A, 10.53 ± 3.64 s; group B, 9.46 ± 2.40 s; group C, 7.29 ± 2.13 s; and group D, 6.82 ± 2.20 s (p < 0.01). Corneal staining scores are as follows: 0.26 ± 0.60 in group A, 0.40 ± 0.71 in group B, 0.98 ± 0.72 in group C, and 1.14 ± 0.90 in group D, and the differences were statistically significant among the groups(p < 0.01). OSAHS, particularly the moderate and severe forms, is associated with low Schirmer and TBUT values and high scores in OSDI questionnaire and corneal staining pattern stage. The presence of FES is observed as a practically constant finding in OSAHS. If complaints such as burning, stinging, and itching which can be commonly observed in middle-aged patients are accompanied by FES, the patient should be evaluated for sleep disorders. We speculate that appropriate treatment of OSAHS may result in better control of these symptoms.


Partial meniscectomy and anterior cruciate ligament rupture in soccer players. A study with a minimum 20-year followup.
A retrospective review of 77 soccer players with 91 affected knees that had undergone the same operation, a rim-preserving meniscectomy, was made with a minimum followup of 20 years and an average followup of 27 years. The patients were divided into groups based on the presence of an intact (Group 1) or ruptured (Group 2) anterior cruciate ligament. At 5 years after meniscectomy, 75% of Group 1 and 52% of Group 2 were still playing soccer, and 13% in Group 1 as opposed to 28% in Group 2 had given up sports. The sporting class assessment was good in 80% of the Group 1 knees and 62% in the Group 2 knees. By followup, 5% of Group 1 and 32% of Group 2 required further meniscectomies, and 2% of Group 1 and 16% of Group 2 required operations for osteoarthritis. Radiologically diagnosed osteoarthritis was present in 24% of Group 1 knees compared with 77% of Group 2. Functionally, 60% of the Group 1 knees were excellent at followup as opposed to 9% in Group 2 knees. In Group 1, 49% were still involved in sports compared with 22% in Group 2. However, 97% of Group 1 were satisfied with their knees compared with 74% of Group 2. All of these differences were statistically significant.


Thermoreversibly Cross-Linked EPM Rubber Nanocomposites with Carbon Nanotubes.
Conductive rubber nanocomposites were prepared by dispersing conductive nanotubes (CNT) in thermoreversibly cross-linked ethylene propylene rubbers grafted with furan groups (EPM-g-furan) rubbers. Their features were studied with a strong focus on conductive and mechanical properties relevant for strain-sensor applications. The Diels-Alder chemistry used for thermoreversible cross-linking allows for the preparation of fully recyclable, homogeneous, and conductive nanocomposites. CNT modified with compatible furan groups provided nanocomposites with a relatively large tensile strength and small elongation at break. High and low sensitivity deformation experiments of nanocomposites with 5 wt % CNT (at the percolation threshold) displayed an initially linear sensitivity to deformation. Notably, only fresh samples displayed a linear response of their electrical resistivity to deformations as the resistance variation collapsed already after one cycle of elongation. Notwithstanding this mediocre performance as a strain sensor, the advantages of using thermoreversible chemistry in a conductive rubber nanocomposite were highlighted by demonstrating crack-healing by welding due to the joule effect on the surface and the bulk of the material. This will open up new technological opportunities for the design of novel strain-sensors based on recyclable rubbers.


Pancreatic islet cell transplantation: a treatment strategy for type I diabetes mellitus.
Type I diabetes mellitus continues to be a serious disease with long-term morbidity from complications of the disease, despite better knowledge of physiology and better patient care. Pancreatic islet cell transplantation, still experimental, is gaining acceptance as a treatment strategy for individuals with type 1 diabetes who have poor glucose control and frequent hypoglycemic episodes despite maximal care. The procedure can improve glucose control, avoiding further hypoglycemic episodes, and can achieve insulin-independence at the expense of immunosuppression treatment. Islet cell transplantation does not correct all the metabolic abnormalities seen in type 1 diabetes, and glucose tolerance can remain abnormal. The dietary management of the patients still needs to be defined. Further research is focused at improvement in islet isolation and the refinement of immunosuppression strategies aiming toward immune tolerance, bringing hope for a cure of diabetes.


Synthesis of 3-arsonoalanine and its action on aspartate aminotransferase and aspartate ammonia-lyase. Comparison with arsenical analogues of malate and fumarate.
DL-3-Arsonoalanine has been synthesized by the Strecker synthesis from the unstable compound arsonoacetaldehyde. It inactivates pig heart cytosolic aspartate aminotransferase and inhibits aspartate ammonia-lyase by competing with aspartate (Ki/Km 0.23). The fumarate analogue (E)-3-arsonoacrylic acid and the malate analogue (RS)-3-arsonolactate also inhibit fumarate hydratase, competing with fumarate (Ki/Km 1.8) and malate (Ki/Km 1.6) respectively. Attempted non-enzymic transamination of 3-arsonoalanine gave elimination of arsenite, in contrast with the transamination of 3-phosphonoalanine, which is either successful or leads to loss of phosphate.


[Silicon of the medium in the postoperative maxillary cyst].
As part of a study on chronic inflammatory disease of the mucous membrane, silicon of the medium in postoperative maxillary cysts and in other cysts was measured, and following results were obtained. Silicon concentrations of the medium in the postoperative maxillary cysts and in the postoperative ethmoidal cysts were 34.5 ppm and 42.9 ppm (geometrical mean) respectively, and they were higher than in other primary cysts such as frontal cyst, nasal vestibular cyst, and dental cyst. The silicon content of the medium in the postoperative maxillary cyst varied with the water content of the medium; the lower the water content the higher was the silicon content and the relationship was expressed by the following equation. log S = 7.43 + 7.14 log d-6.14 log w, where S = Si (mcg), d = dry weight (g.) and w = wet weight (g.). The high concentration of silicon in the postoperative cyst was considered to be due to the large amount of silicon transudate from the surrounding fibrous tissue through a highly damaged or missing epithelial wall of the cyst.


In vitro and in vivo comparative studies on immunosuppressive properties of cyclosporines A, C, D and metabolites M1, M17 and M21.
Cyclosporine A (CsA) and its major metabolites: M1, M17 and M21 and two analogues: cyclosporines C (CsC) and D (CsD), were studied for their capacity to interfere with different in vitro activation pathways. Their inhibition potentials against the reaction of Graft-versus-Host (GvH) were also studied. The results showed: CsA, CsC and metabolite M17 were the most active compounds upon the inhibition of lymphocyte proliferation induced by different mitogens (ConA, PHA, PWM) and also on the proliferation of mixed lymphocyte cultures (MLC). The same results were observed concerning the direct activation by protein kinase C using a combined action of phorbol ester + calcium ionophore. In vivo using local GvH reaction, CsA and CsC proved more active than M17 in the two different combinations: H-2d --> (H-2b x H-2d)F1 and H-2k --> (H-2b x H-2k)F1 CsD and two metabolites M1 and M21 showed no or weak immunosuppressive effects. Overall, the immunosuppressive potency of six compounds could be schematized as: CsA > or = CsC > M17 > M1 > or = CsD > M21.


SELECTION ON A FLORAL COLOR POLYMORPHISM IN THE TALL MORNING GLORY (IPOMOEA PURPUREA): TRANSMISSION SUCCESS OF THE ALLELES THROUGH POLLEN.
The W locus, a codominant locus influencing floral pigment intensity in the tall morning glory, Ipomoea purpurea, is polymorphic throughout the southeastern United States. Previous studies suggest that this polymorphism is actively maintained by balancing selection, and that increased selfing accompanied by lack of pollen discounting ("Fisher effect") may act to protect the white allele when it is rare. Processes that act to protect the dark allele and thus stabilize the polymorphism in conjunction with the Fisher effect have not been previously detected. The goal of this study was to determine whether any of three such processes might operate in I. purpurea. Estimates of breeding system parameters in a large experimental population in which the white allele was in higher than normal frequency (0.5) provided little evidence that either dark- or light-flowered plants were more successful as pollen parents than white-flowered plants. In addition, no evidence was found for a transmission bias favoring the dark allele in the ovules produced by light heterozygotes. In contrast, a strong transmission bias favoring the dark allele in pollen of heterozygotes was observed. A simple model using parameter estimates derived from this and previous studies indicates that a balance between the Fisher effect and biased transmission in heterozygote pollen could account for many properties of the polymorphism.


"HLA-C: evolution, epigenetics, and pathological implications in the major histocompatibility complex".
HLA-C, a gene located within the major histocompatibility complex, has emerged as a prominent target in biomedical research due to its involvement in various diseases, including cancer and autoimmune disorders; even though its recent addition to the MHC, the interaction between HLA-C and KIR is crucial for immune responses, particularly in viral infections. This review provides an overview of the structure, origin, function, and pathological implications of HLA-C in the major histocompatibility complex. In the last decade, we systematically reviewed original publications from Pubmed, ScienceDirect, Scopus, and Google Scholar. Our findings reveal that genetic variations in HLA-C can determine susceptibility or resistance to certain diseases. However, the first four exons of HLA-C are particularly susceptible to epigenetic modifications, which can lead to gene silencing and alterations in immune function. These alterations can manifest in diseases such as alopecia areata and psoriasis and can also impact susceptibility to cancer and the effectiveness of cancer treatments. By comprehending the intricate interplay between genetic and epigenetic factors that regulate HLA-C expression, researchers may develop novel strategies for preventing and treating diseases associated with HLA-C dysregulation.


Plantamajoside promotes metformin-induced apoptosis, autophagy and proliferation arrest of liver cancer cells via suppressing Akt/GSK3β signaling.
Metformin, a well-known antidiabetic drug, exhibits anticancer effect in a variety of cancers, including liver cancer. Plantamajoside (PMS), a phenylethanoid glycoside compound isolated from Plantago asiatica, is proved to possess anticancer effects, too. In our study, we hypothesized that PMS might promote metformin mediated anticancer effects on liver cancer. The half maximal inhibitory concentration (IC50) of metformin was evaluated by cell viability assay. The influence of PMS on proliferation, migration, invasion and apoptosis of metformin-treated cells was evaluated by BrdU incorporation assay, flow cytometry, western blot, wound scratch healing assay, transwell cell migration assay and immunofluorescence. A fasting/feeding mouse model was built to evaluate the influence of PMS on metformin sensitivity in vivo. PMS (2.5, 10 or 40 μg/mL) treatment reduced the IC50 of metformin under different glucose concentrations. PMS (10 μg/mL) promoted metformin (5 mm) induced apoptosis and autophagy, and inhibition on proliferation, migration and invasion of HepG2 and HuH-7 cells. In the fasting/feeding mouse model, PMS (50 mg/kg) promoted metformin (200 mg/kg) induced proliferation arrest and apoptosis in vivo. Meanwhile, PMS reduced the level of pAkt(ser473) and GSK3β(ser9) in HepG2 and HuH-7 cells. Restoration of Akt/GSK3β signaling by a constitutively activated myr-Akt1 abrogated the effects of PMS on metformin-treated liver cancer cells. Our results demonstrated that PMS promoted the anticancer effects of metformin on liver cancer in vitro and in vivo.


Iatrogenic Spinal Subdural Extra-Arachnoid Hygroma Following Uncomplicated Lumbar Decompression.
Intradural spinal arachnoid cysts (ISACs) have been reported in the current literature as either an idiopathic disease or exceedingly rare sequelae after lumbar puncture, spinal trauma, or meningitis. Other studies have more appropriately termed the iatrogenic pathology as a spinal subdural extra-arachnoid hygroma (SSEH), as there is not often a clear cyst wall as in a true arachnoid cyst. However, to the best of our knowledge, none of the previous studies described an SSEH following uncomplicated posterior lumbar surgery, as they have previously involved clear durotomies during the initial operation. Here, we report the case of a 53-year-old woman who presented to the emergency department with a persistent severe orthostatic headache and worsening leg pain, six days following an uneventful L5-S1 discectomy and left L4-5 laminoforaminotomy, without intraoperative durotomy. Lumbar magnetic resonance imaging (MRI) scan revealed a pseudomeningocele and an SSEH extending from the S1 up to the lower thoracic spine, compressing and displacing the cauda equina. Although the hygroma extended up to the lower thoracic spine, surgical exploration was performed only at the index surgical site with bilateral L5 laminectomy, wide durotomy, and wide fenestration of the arachnoid layer. Postoperatively, her headaches dissipated and her pain improved with complete radiographic resolution of the collection. Iatrogenic SSEH is an exceedingly rare complication of posterior lumbar decompression and can occur in the absence of a durotomy during the index surgery. Although these hygromas may span multiple levels, the initial surgical site or the site of known durotomy should be explored first. They can potentially be treated with only a limited durotomy and arachnoid fenestration at a single level rather than at a multilevel arachnoid fenestration.


Cytokine response to pulmonary thromboendarterectomy.
Pulmonary thromboendarterectomy (PTE) is an effective but challenging treatment for chronic thromboembolic pulmonary hypertension (CTEPH). PTE is associated with marked hemodynamic instability in the perioperative course, suggesting the involvement of circulating mediators. The aim of this study was to characterize the expression of proinflammatory and anti-inflammatory cytokines in patients undergoing PTE. Fourteen patients with CTEPH (mean [+/- SD] pulmonary vascular resistance, 1,056 +/- 399 dyne.s.cm(-5)) underwent PTE using cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Peripheral arterial blood samples were drawn prior to patients undergoing sternotomy, during CPB, before and after DHCA, and 0, 8, 16, 24, and 48 h after surgery. An enzyme-linked-immunosorbent assay was used to analyze the plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10. Seven patients undergoing aortic arch replacement (ARCH) in DHCA served as a control group. Prior to and during PTE, the CTEPH patients exhibited elevated TNF-alpha levels, which decreased within the first 24 postoperative hours (p = 0.02). There was no TNF-alpha release among patients in the ARCH group. IL-6 levels were similar in both groups throughout the perioperative course. A profound anti-inflammatory response was observed in the PTE group, which was reflected by elevated IL-10 levels prior to surgery and a marked peak level immediately after surgery. A positive correlation was found between maximum vasopressor support and peak levels of IL-6 (r = 0.82) in the PTE patients. Heart failure due to CTEPH appears to generate a pronounced inflammatory response with the release of proinflammatory and anti-inflammatory cytokines. PTE results in the rapid normalization of preoperatively elevated TNF-alpha levels. IL-6-mediated systemic inflammatory cascades may be involved in the regulation of peripheral vascular tone after PTE.


CTCF binding landscape in jawless fish with reference to Hox cluster evolution.
The nuclear protein CCCTC-binding factor (CTCF) contributes as an insulator to chromatin organization in animal genomes. Currently, our knowledge of its binding property is confined mainly to mammals. In this study, we identified CTCF homologs in extant jawless fishes and performed ChIP-seq for the CTCF protein in the Arctic lamprey. Our phylogenetic analysis suggests that the lamprey lineage experienced gene duplication that gave rise to its unique paralog, designated CTCF2, which is independent from the previously recognized duplication between CTCF and CTCFL. The ChIP-seq analysis detected comparable numbers of CTCF binding sites between lamprey, chicken, and human, and revealed that the lamprey CTCF protein binds to the two-part motif, consisting of core and upstream motifs previously reported for mammals. These findings suggest that this mode of CTCF binding was established in the last common ancestor of extant vertebrates (more than 500 million years ago). We analyzed CTCF binding inside Hox clusters, which revealed a reinforcement of CTCF binding in the region spanning Hox1-4 genes that is unique to lamprey. Our study provides not only biological insights into the antiquity of CTCF-based epigenomic regulation known in mammals but also a technical basis for comparative epigenomic studies encompassing the whole taxon Vertebrata.


Regulation of alpha-ketoisovalerate decarboxylase expression in Lactococcus lactis IFPL730.
The alpha-ketoisovalerate decarboxylase (Kivd) is a unique lactococcal key enzyme in the decarboxylation of branched-chain alpha-keto acids derived from branched-chain amino acids transamination into aldehydes. These products are important aroma compounds produced during cheese ripening. In this study, the Kivd expression of Lactococcus lactis IFPL730 growing either in nitrogen-rich media or in chemically defined media supplemented with different concentrations of branched-chain amino acids and casitone was analyzed. Isoleucine starvation increased 4-fold the Kivd activity of L. lactis IFPL730 compared to cells grown in chemically defined medium with casitone as nitrogen source. Regulation of expression was at the transcription level, probably mediated by CodY, for which a consensus CodY-box sequence was identified in the kivd promoter region.


Clinical Usefulness of Proteomics in Inflammatory Bowel Disease: A Comprehensive Review.
The protein domain is probably the most ubiquitously affected in disease, response and recovery, and therefore proteomics holds special promise for biomarker discovery in general, and particularly in inflammatory bowel disease [IBD], i.e. ulcerative colitis and Crohn's disease. Tremendous progress has been made over the past decade in the development and refinement of proteomics technologies. These advances provide opportunities for a long-anticipated personalized medicine approach to the treatment of IBD. The present review examines the current state of IBD proteomics research and its usefulness in clinical practice. We performed a systematic bibliographic search to identify studies investigating the use of proteomics in patients with IBD, and we then summarized the current 'state of the art' in the applications of proteomic technologies in the study of IBD. In particular, in the present review we provide: [1] a brief introduction to proteomics in health and disease; [2] a review of the different stages from biomarker discovery to clinical application; and [3] a comprehensive review of the clinical usefulness and application of proteomics in IBD, including: [a] screening to differentiate IBD from healthy controls; [b] differentiating Crohn's disease from ulcerative colitis; [c] prediction of the behaviour or the IBD course; [d] prediction of IBD response to biological treatment; and [e] monitoring response to treatment. We also review the importance of the type of sample-blood vs intestinal tissue-for the study of proteomics in IBD patients. Finally, we emphasize the current limitations of proteomic studies in IBD.


PM10, ozone, and hospital admissions for the elderly in Minneapolis-St. Paul, Minnesota.
Several recent studies have reported associations between airborne particles and/or ozone and hospital admissions for respiratory disease. PM10 has rarely been used as the particle exposure measure, however. This study examined whether such an association could be seen in Minneapolis-St. Paul, Minnesota, which has daily monitoring data for PM10. Data on hospital admissions in persons aged 65 y and older were obtained from Medicare records for the years 1986 through 1989. Daily counts of admissions, by admit date, were computed for pneumonia (ICD9 480-487) and chronic obstructive pulmonary disease (COPD) (ICD9 490-496). Classification was by discharge diagnosis. Daily air pollution data from all monitoring stations for ozone and PM10 in Minneapolis-St. Paul were obtained, and the daily average for each pollutant was computed. An average of approximately six pneumonia admissions and two admissions for chronic obstructive pulmonary disease occurred each day. Poisson regression analysis was used to control for time trends, seasonal fluctuations, and weather. PM10 was a risk factor for pneumonia admissions (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.33-1.02) and COPD admissions (RR = 1.57, 95% CI = 2.06-1.20). Ozone was also associated with pneumonia admissions (RR = 1.15, 95% CI = 1.36-0.97). The relative risks are for an increase of 100 micrograms/m3 in daily PM10 and 50 ppb in daily ozone concentration. Several alternative methods for controlling for seasonal patterns and weather were used, including nonparametric regression techniques. The results were not sensitive to the methods. When days exceeding the National Ambient Air Quality Standard for either pollutant were excluded, the association remained for both pneumonia (RR = 1.18, 95% CI = 1.34-1.03 for PM10, and RR = 1.18, 95% CI = 1.41-0.99 for ozone) and COPD (RR = 1.54, 95% CI = 2.06-1.16 for PM10).


Improving therapeutic properties of protein drugs through alteration of intracellular trafficking pathways.
Although intracellular trafficking processes can play a central role in the physiological function of a protein, these same processes can also limit the benefit of the protein when it is taken out of its physiological context and used as a protein drug. Therefore, the properties of certain protein drugs may be improved by manipulating their trafficking pathways to suit their therapeutic function. A detailed consideration of the factors that govern how protein traffic is routed among different cellular destinations can be used to ascertain molecular design criteria for engineering a protein drug so as to alter its trafficking pathway in a beneficial manner. In this review, we summarize studies that have applied this approach to achieve the following three improvements in protein drug function: (1) half-life extension of the Fc fragment of IgG, (2) half-life extension of granulocyte colony-stimulating factor, and (3) increase in cellular association of transferrin.


The macrocyclic peptide natural product CJ-15,208 is orally active and prevents reinstatement of extinguished cocaine-seeking behavior.
The macrocyclic tetrapeptide natural product CJ-15,208 (cyclo[Phe-d-Pro-Phe-Trp]) exhibited both dose-dependent antinociception and kappa opioid receptor (KOR) antagonist activity after oral administration. CJ-15,208 antagonized a centrally administered KOR selective agonist, providing strong evidence it crosses the blood-brain barrier to reach KOR in the CNS. Orally administered CJ-15,208 also prevented both cocaine- and stress-induced reinstatement of extinguished cocaine-seeking behavior in the conditioned place preference assay in a time- and dose-dependent manner. Thus, CJ-15,208 is a promising lead compound with a unique activity profile for potential development, particularly as a therapeutic to prevent relapse to drug-seeking behavior in abstinent subjects.


Humoral immune response against BNT162b2 mRNA COVID-19 vaccine in patients with rheumatic disease undergoing immunosuppressive therapy: A Japanese monocentric study.
We investigated serum total antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain after BNT162b2 mRNA vaccination against coronavirus disease 2019 (COVID-19) in Japanese patients taking various immunosuppressive medications for rheumatic disease. In 212 outpatients with rheumatic diseases at Kagawa University Hospital and 43 healthy volunteers (controls), all of whom had received 2 doses of BNT162b2 vaccine, serum antibody titers of SARS-CoV-2 spike protein were analyzed at least 14 days after the second dose. Many of the patients were taking immunosuppressive agents to manage their rheumatic disease. The antibody titers against SARS-CoV-2 spike protein in these patients were significantly lower than those in controls. The analysis of therapeutic agents revealed that the antibody titers in patients treated with rituximab were much lower than those in controls. In patients treated with tacrolimus, baricitinib, azathioprine, mycophenolate mofetil, abatacept, tumor necrosis factor inhibitors, cyclosporine, interleukin-6 inhibitors, methotrexate, or glucocorticoids, antibody titers were moderately lower than those of controls. Interleukin-17 and interleukin-23 inhibitors did not impair the humoral response. In addition, the combination of methotrexate with various immunosuppressive agents reduced titers, although not significantly. In Japanese patients with rheumatic disease, many immunosuppressants impaired the immune response to the BNT162b2 vaccine. The degree of decline in antibody titers differed according to immunosuppressant. When used concomitantly with other immunosuppressants, methotrexate may impair the immune response to the BNT162b2 vaccine. However, immunomodulatory treatments such as interleukin-17 and -23 inhibitors may not attenuate this response in patients with rheumatic disease.


Benign teratoma of the thyroid gland.
Although pathology reports of thyroid tissue in ovarian teratomas are abundant, benign teratomas of the thyroid are extremely rare in adolescents and adults. Therefore, their clinical characteristics are still not well characterized. We report a case of a 54-year-old woman with a growing mass in her neck. Left lobectomy of the thyroid revealed it to be a benign thyroid teratoma composed of tissues from all three germ layers. Preoperative evaluations included thyroid ultrasonography (US), ultrasound-guided fine needle aspiration cytology (FNAC), and computed tomography (CT) of the neck. A 4.7-cm, well defined, predominantly hypoechoic mass intermingled with hyperechoic internal lesions, was observed in the inferior portion of the left thyroid lobe with substernal extension on US. The posterior extent of the nodule was not visualized due to deep attenuation of the echo. US-guided FNAC failed to reveal any thyroid follicular cells, but suggested a benign cystic tumor. Neck CT hinted at the diagnosis of teratoma because the mass contained large amounts of fat, and the margin was well defined. Extrathyroidal extension and cervical lymphadenopathy were not seen. She underwent left thyroid lobectomy, and histologic examination confirmed benign thyroid teratoma. To the best of our knowledge, this is the first case report of benign thyroid teratoma in Korea.


Measuring fluctuating asymmetry in fattening rabbits: a valid indicator of performance and housing quality?
Fluctuating asymmetry (FA) has been advocated as the preferred measure of developmental instability and a reliable indicator of the quality of an animal (performance/fitness) and of its environment during its growing life. Empirical studies, however, are too scant or equivocal to consider this assumption adequately validated, which is partly due to the lack of a robust methodological framework for collecting and analyzing FA data. Therefore, we conducted an experiment in which 306 weaned rabbits were housed either in welfare-friendly pens (n = 6) or barren pens (n = 6). The size of both types of pen was similar (1.91 m2), but the welfare-friendly pens were equipped with suitable enrichment material (gnawing stick, elevated platform, and hiding box) and were stocked with one-half of the number of rabbits compared with the barren pens (17 vs. 34 rabbits per pen). Performance data (BW gain, ADFI, and G:F) were collected every 14 d. After slaughter (d 63 to 72), we measured twice the left- and right-hand side of 11 presumed bilateral traits on intact carcasses and 50 traits on fleshed bones. Using a stringent decision process, an optimal combination of morphological traits for estimating FA in fattening rabbits was determined. This combination consisted of five traits (fleshed bones) that showed no directional asymmetry or antisymmetry and showed a high level of FA relative to the measurement error; also, these traits were not correlated in their signed FA values. Measurements on intact carcasses seemed inappropriate for estimating FA. Using this robust FA measuring protocol, rabbits housed in the welfare-friendly pens were less asymmetric than were rabbits from the barren pens. Except for a greater daily BW gain in the welfare-friendly pens during the first 14 d after weaning, there were no effects of housing conditions on performance traits. The FA was negatively correlated with BW gain in rabbits from the barren pens, whereas in the welfare-friendly pens, there was no correlation. These results support the application of FA as an indicator of animal welfare and performance; however, FA seems to be a more reliable estimator of the underlying developmental instability when living conditions are suboptimal.


Sexual violence victimization among American college students studying abroad.
Objective: Research has just begun to identify American college students who study abroad as a group at-risk for sexual violence victimization. The purpose of the current study was to examine the context of these incidents. Participants: We utilized a large longitudinal sample of 2,428 United States college students studying abroad for between 4 and 21 weeks in 12 different foreign countries. Methods: We estimated descriptive statistics and logistic regression models to assess prevalence and correlates of sexual victimization abroad, as well as effect size comparisons to quantify changes in drinking abroad. Results: Over one-fifth of students experienced sexual violence while abroad, including sexual assault and verbal coercion. Women, younger students, those who experienced sexual violence prior, and heavier drinkers had the greatest odds of sexual violence victimization abroad. Conclusions: Findings point to the need for evidence-based programming to reduce sexual violence risk among American college students studying in foreign countries.


Clinical manifestations and epigenetic mechanisms of gastric mucosa associated lymphoid tissue lymphoma and long-term follow-up following Helicobacter pylori eradication.
The current study aimed to summarize the clinical manifestations and identify the epigenetic mechanisms of gastric mucosa associated lymphoid tissue (MALT) lymphoma, as well as evaluate the long-term effects of Helicobacter pylori (H. pylori) eradication. A total of 122 patients with marginal zone B-cell lymphoma of primary gastric MALT lymphoma were enrolled in the present study. The clinical manifestations of gastric MALT lymphoma, including symptoms, H. pylori state and endoscopic type, were summarized. The response to therapy was evaluated in patients that underwent H. pylori eradication. Survival analysis was estimated using the Kaplan-Meier method. The expression of microRNA-383 (miR-383) in tumor tissues and cell lines was determined using reverse transcription quantitative polymerase chain reaction. Furthermore, bioinformatic analyses, luciferase reporter assays. and western blot analysis identified zinc finger E-box binding homeobox 2 (ZEB2) as a direct target gene of miR-383. An MTT assay was used to examine the function of miR-383 and ZEB2 in MALT lymphoma. The clinical symptoms of patients with gastric MALT lymphoma were non-specific and included epigastric pain, abdominal discomfort and bleeding. The majority of endoscopic types were classified as ulcer, erosion and mucosa edema. The H. pylori infection rate was 79.5% (97/122) and a total of 47 patients underwent eradication therapy. Lymphoma remission was achieved in 93.6% (44/47) of patients and complete remission (CR) was achieved in 74.4% (35/47). The median follow-up time was 38 months (range, 10-132 months) and the median time taken to achieve CR was 4 months (range, 3-7 months). The estimated 3-year survival rate was 90.3% and the 5-year survival rate was 76.2%. Therefore, it was determined that patients with stage I or II gastric MALT lymphoma are able to undergo H. pylori eradication as a first-line treatment and that the survival rate of patients undergoing this treatment is high. Furthermore, it was determined that the mechanism by which miR-383 and ZEB2 contribute to MALT lymphoma progression is by the targeting of ZEB2 by miR-383, which inhibits the proliferation of cancer cells.


The first detection of Toxoplasma gondii DNA in environmental air samples using gelatine filters, real-time PCR and loop-mediated isothermal (LAMP) assays: qualitative and quantitative analysis.
Toxoplasma gondii infections are acquired through the ingestion of oocysts present in the environment. However, there is no data about their occurrence in the air or about airborne transmission of these infections. In the present paper, we report on the identification of T. gondii using rapid molecular detection methods, supported by microscopic analysis, in environmental air samples. A total of 71 samples were collected, using gelatine filters, from kitchen gardens, recreational areas and sandpits located in northern and north-eastern Poland. Material recovered from the filters was analysed using real-time PCR and loop-mediated isothermal assays targeting the T. gondii B1 gene. Toxoplasma gondii DNA was found in two samples, as confirmed by both molecular assays. Genotyping at the SAG2 locus showed Toxoplasma SAG2 type I. Moreover, the presence of T. gondii oocysts was confirmed in one of the positive samples with the use of microscopy. The results showed that T. gondii may be present in environmental air samples and that respiratory tract infections may play a role in the high prevalence of toxoplasmosis in humans and animals. To the best of our knowledge, this is the first epidemiological evidence that oro-fecal and foodborne toxoplasmosis may be traceable to an airborne respiratory origin and that this may represent a new, previously unknown transmission route for this disease.


Hard-rock mining exposures affect smokers and nonsmokers differently. Results of a community prevalence study.
The physiologic consequences of occupational dust exposure, their relation to smoking, and their reversibility with cessation of exposure remain controversial. To address these questions, we studied a random sample of male residents of Leadville, Colorado when the major employer, a hard-rock mine, had been closed for 5 to 11 months. Subjects were interviewed for respiratory symptoms and occupational history, underwent plethysmographic measurements of lung volume and airflow, and performed a single breath diffusing capacity procedure. Dyspnea was the only respiratory symptom exacerbated by mining exposures. Cumulative dust exposure, estimated with historic respirable dust measurements for mining job titles and weighted by time at the job, was associated with decreases in maximal expiratory flow rates when controlled for smoking, age, and height. However, determinations of plethysmographic lung volume that allowed calculation of flow rates at equivalent absolute lung volume indicated that dust effects differed in never-smokers and smokers. In never-smokers, dust exposure was associated with decreased lung volume, increased flow rates, and increased DLCO/VA. In smokers, dust exposure was associated with increased lung volume, lower flow rates, and lower DLCO/VA than that accounted for by smoking. We suggest that hard-rock mining exposures result in irreversible pulmonary function changes of airflow limitation in smokers and of a restrictive nature in never-smokers.


Observations of bacterial diseases of captive snakes in Finland.
Eighteen captive, nonpoisonous snakes which suffered from bacterial infections were studied. The most usual bacteria found were gram-negative rods; especially Pseudomonas aeruginosa, Aeromonas hydrophila and Proteus spp. The most common disorders caused by them were stomatitis, septicaemia, bronchopneumonia and abscesses. The sensitivities of ten isolated bacteria to antimicrobial drugs were tested. Neomycin and gentamicin seemed to be effective, especially against P. aeruginosa.


Five analytic challenges in working with electronic health records data to support clinical trials with some solutions.
Electronic health records data are becoming a key data resource in clinical research. Owing to issues of data efficiency, electronic health records data are being used for clinical trials. This includes both large-scale pragmatic trails and smaller-more focused-point-of-care trials. While electronic health records data open up a number of scientific opportunities, they also present a number of analytic challenges. This article discusses five particular challenges related to organizing electronic health records data for analytic purposes. These are as follows: (1) data are not organized for research purposes, (2) data are both densely and irregularly observed, (3) we don't have all data elements we may want or need, (4) data are both cross-sectional and longitudinal, and (5) data may be informatively observed. While laying out these challenges, the article notes how many of these challenges can be addressed by careful and thoughtful study design as well as by integration of clinicians and informaticians into the analytic team.


Encephalopathy with status epilepticus during sleep (ESES) induced by oxcarbazepine in idiopathic focal epilepsy in childhood.
Encephalopathy with status epilepticus during sleep (ESES) is an age-related disorder characterized by neuropsychological regression, epilepsy and a typical EEG pattern of continuous epileptiform activity (> 85%) during NREM sleep. Cases of worsening or induction of ESES with phenytoin, carbamazepine and phenobarbital have been reported. We describe a child with benign epilepsy with centrotemporal spikes (BECTS) in whom treatment with oxcarbazepine (OXC) induced ESES. The patient was studied through repeated clinical-neuropsychological evaluations and 24-hour EEG recordings. He was treated with OXC two months after epilepsy onset. One month after starting OXC, he developed an abrupt and severe cognitive deterioration. A 24-hour EEG and neuropsychological tests showed an electroclinical picture compatible with ESES. Withdrawal of OXC and introduction of other drugs were followed by a prompt improvement. Five months after ESES onset, a 24-hour EEG was normal. Our report indicates that OXC can induce ESES in BECTS.


Epidemiological profile of tinea capitis in São Paulo City.
Tinea capitis is the most common fungal infection in children. The identification of the etiologic agent helps clinicians make their therapeutic choice. Studies conducted in different countries show a changing pattern of the main etiological agents according to their regions. We performed a retrospective study in the tertiary public service in São Paulo, analyzing the isolated etiological agents in patients with tinea capitis from March 2013 to May 2015. Microsporum canis was the main agent (56.6%), followed by Trichophyton tonsurans (36.6%). Despite recent migratory movements in the city, we observed no change in the causative agent of tinea capitis.


Problem gambling severity and the incidence of Axis I psychopathology among older adults in the general population.
To examine the longitudinal relationship between past-year problem-gambling severity and incident Axis I psychopathology among older adults (aged 55-90), analyses were conducted on data from the National Epidemiologic Study of Alcohol and Related Conditions (NESARC). This nationally-representative population-based survey was conducted in two waves (Wave 1, 2000-2001; and Wave 2, 2004-2005). Past-year problem-gambling severity at Wave 1 and incident Axis I psychopathology at Wave 2 were evaluated with the Alcohol Use Disorder and Associated Disabilities Interview Schedule-Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. Multivariate logistic regression modeling was conducted on groups categorized into low-frequency gambling/non-gambling (LFG/NG), low-risk gambling (LRG), and at-risk/problem/pathological gambling (ARPG) based on DSM-IV criteria for pathological gambling. Relative to LFG/NG, ARPG at Wave 1 was positively associated with the incidence of generalized anxiety disorder (OR = 2.51; p = .011) and any substance use disorder (OR = 2.61; p = .0036); LRG was negatively associated with the incidence of hypomania (OR = 0.33; p = .017). Models were adjusted for demographic characteristics, psychiatric comorbidity, health behaviors, physical health, and stressful life events assessed at baseline. While gambling may represent a positive activity for some older adults, data suggest that risky/problematic gambling behavior may be associated with the development of psychiatric problems in this population. Older-adult gamblers, as well as their clinicians, friends, and family, should be aware of potential risks associated with gambling, adopt strategies to prevent the onset of secondary disorders, and monitor themselves and others for signs of problems.


Low-level prenatal lead exposure and infant sensory function.
Lead is a pervasive neurotoxicant that has been associated with poorer cognitive, behavioral, and motor outcomes in children. The effects of lead on sensory function have not been well characterized. The aim of this study was to assess the effects of prenatal lead exposure on infant sensory function, as measured by auditory brainstem response (ABR) and grating visual acuity (VA). Lead was measured in maternal blood in mid- and late-pregnancy (mean gestational age = 15.5 and 39.0 weeks, respectively) and umbilical cord blood in a cohort of full-term infants in rural northeastern China. ABR latencies (peaks I, III, V) were measured in newborns during unsedated sleep (n = 315). The ABR central-to-peripheral (C-P) ratio was calculated as the ratio between the III-V and I-III interpeak intervals. VA was measured in 6-week-olds using Teller Acuity Cards (n = 1019) and assigned as the narrowest grid the infant fixated on. Multivariate linear regression was used to evaluate relationships between tertiles of mid-pregnancy, late-pregnancy, or cord lead and newborn ABR or 6-week VA. Higher late-pregnancy lead levels were associated with higher ABR C-P ratios and lower VA. In covariate-adjusted analyses, mean C-P ratios were 4.6 and 3.2 % higher in infants whose mothers had lead > 3.8 μg/dL and lead = 2-3.8 μg/dL, respectively, than for infants whose mothers had lead < 2 μg/dL (p-trend =0.002). In adjusted analyses for VA, mean scores were 8.5 and 7.2 % lower for maternal lead > 3.8 μg/dL and lead = 2-3.8 μg/dL, respectively, compared to lead < 2 μg/dL (p-trend =0.009). Auditory and visual systems maturation appears delayed in infants with higher prenatal lead exposure during late-pregnancy, even at relatively low levels. Both systems start myelinating in late gestation and mature rapidly in infancy. Higher ABR C-P ratio and lower grating VA scores suggest effects of low-level lead exposure on sensory system myelination.


[Efficacy of cereton in acute ischemic stroke: results of the trial SOLNTSE].
We studied 95 patients with acute (no later than 24h after onset) carotid ischemic stroke. Patients of the main group (50 patients) received cereton in dose 4 ml (1000 mg) intravenously during 10 days in the combination with traditional treatment; 45 patients of the control group received only traditional treatment. Neurological deficit on NIHSS and vigilance on The Glasgow Coma Scale were assessed at baseline and in 5th, 7th and 19-21th days. The Barthel index was used to measure functional independence of the patient at the discharge from a hospital (21th day). The "cost-effectiveness" ratio, the cost of one score on the NIHSS and Barthel scales were calculated. The reduction in neurological deficit (p<0.05) and higher extent of functional independence were seen in the main group compared to the controls. Based on the "cost-effectiveness" analysis, the use of cereton was shown to be more effective for treatment of patients with acute ischemic stroke: the cost of the achievement of positive effect in patients of the control group receiving only traditional treatment was significantly higher (p<0.05).


Anxiolytic-Like Effects and Increase in Locomotor Activity Induced by Infusions of NMDA into the Ventral Hippocampus in Rat: Interaction with GABAergic System.
In this study, we investigated the role of N-Methyl-D-Aspartate (NMDA) receptors in the ventral hippocampus (VH) and their possible interactions with GABAA system on anxiety-like behaviors. We used an elevated-plus maze test (EPM) to assess anxiety-like behaviors and locomotor activity in male Wistar rats. The results showed that intra-VH infusions of different doses of NMDA (0.25 and 0.5 μg/rat) increased locomotor activity, and also induced anxiolytic-like behaviors, as revealed by a tendency to increase percentage of open arm time (%OAT), and a significant increase in percentage of open arm entries (%OAE). The results also showed that intra-VH infusions of muscimol (0.5 and 1 μg/rat) or bicuculline (0.5 and 1 μg/rat) did not significantly affect anxiety-like behaviors, but bicuculline at dose of 1 μg/rat increased locomotor activity. Intra-VH co-infusions of muscimol (0.5 μg/rat) along with low doses of NMDA (0.0625 and 0.125 μg/rat) showed a tendency to increase %OAT, %OAE and locomotor activity; however, no interaction was observed between the drugs. Interestingly, intra-VH co-infusions of bicuculline (0.5 μg/rat) along with effective doses of NMDA (0.25 and 0.5 μg/rat) decreased %OAT, %OAE and locomotor activity, and a significant interaction between two drugs was observed. It can be concluded that GABAergic system may mediate the anxiolytic-like effects and increase in locomotor activity induced by NMDA in the VH.


Unsteady motion of receding contact lines of surfactant solutions: the role of surfactant re-self-assembly.
Re-self-assembly of surfactant molecules must occur at moving contact lines of soluble surfactant solutions. Molecules are transported into and out of the contact line region from four sources: the three interfaces meeting at the contact line and the fluid confined between the solid-liquid and liquid-vapor interfaces. As molecules move among these sources at the contact line, they must rearrange. The dynamics of this re-self-assembly has been shown to have a dominating effect on the structure of advancing contact lines, causing unsteady motion and complex structure of the contact line. It might be assumed that the re-self-assembly for receding contact lines leads to more steady contact line movement. However, in this article we show that for a wide variety of systems this is not true. Quasi-static distortions of the contact line occur as it retreats because of the inability of the surfactant to completely re-self-assemble at localized positions along the contact line.


Lower uterine artery blood flow and higher endothelin relative to nitric oxide metabolite levels are associated with reductions in birth weight at high altitude.
Reduced uteroplacental blood flow is hypothesized to play a key role in altitude-associated fetal growth restriction. It is unknown whether reduced blood flow is a cause or consequence of reduced fetal size. We asked whether determinants of uteroplacental blood flow were altered prior to reduced fetal growth and whether vasoactive and/or angiogenic factors were involved. Women residing at low (LA; 1,600 m, n = 18) or high altitude (HA; 3,100 m, n = 25) were studied during pregnancy (20, 30, and 36 wk) and 4 mo postpartum (PP) using Doppler ultrasound. In each study, endothelin (ET-1), nitric oxide metabolites (NO(x)), soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PlGF) levels were quantified. At HA, birth weights were lower (P < 0.01) and small-for-gestational age was more common (P < 0.05) compared with LA. HA was associated with lower uterine artery (UA) diameter (P < 0.01) and blood flow (P < 0.05). Altitude did not affect ET-1, sFlt-1 or PlGF; however, ET-1/NO(x) was greater and NO(x) lower during pregnancy and PP at HA vs. LA. ET-1/NO(x) was negatively associated with birth weight (20 wk, P < 0.01; 36 wk, P = 0.05) at LA and HA combined. At HA, UA blood flow (30 wk) was positively associated with birth weight (dagger). UA blood flow and ET-1/NO(x) levels accounted for 45% (20 wk) and 32% (30 wk) of birth weight variation at LA and HA combined, primarily attributed to effects at HA. We concluded that elevated ET-1/NO(x) and altered determinants of uteroplacental blood flow occur prior to altitude-associated reductions in fetal growth, and therefore, they are likely a cause rather than a consequence of smaller fetal size.


Quantitative measurement of renal perfusion following transplant surgery.
We developed an easily implemented clinical procedure for quantitative perfusion measurements in transplanted kidneys using intravenously administered [99mTc]DTPA and the tracer fractionation technique. F = Ak(T)/0 integral of T [Aa(t)/Va] dt, where F = renal blood flow, Ak(T) = DTPA activity in kidney at time = T, Va = ultrasonographically measured femoral artery segment volume, T = time postinjection of F determination, and Aa(t) = time course of DTPA activity in femoral artery segment. The technique was applied to a group of 80 studies in 35 patients in whom an independent clinical determination of transplant function was available. Blood flow (units of ml/min) measured 439 +/- 83 in normally functioning transplants, 248 +/- 63 in transplants with acute tubular necrosis, 128 +/- 62 in transplants with rejection, and 284 +/- 97 in transplants with cyclosporine toxicity. These preliminary results indicate potential usefulness of this method in the evaluation of renal function following transplant surgery.


Bootstrap approach for constructing confidence intervals for population pharmacokinetic parameters. II: A bootstrap modification of standard two-stage (STS) method for phase I trial.
For population pharmacokinetics in phase I trials, the standard two-stage (STS) method is quite appealing, especially to non-statisticians, because the method is theoretically and computationally simple. The method, however, does not take into account the uncertainty in estimating individual-specific parameters and gives biased estimates for population variances of pharmacokinetic parameters. This is one of the main reasons why the STS method is not generally recommended. This paper proposes a simple bootstrap modification of the STS method for estimating confidence intervals of population means and standard deviations of pharmacokinetic parameters in phase I trials. The proposed approach adopts a bootstrap bias correction in estimating population variances of pharmacokinetic parameters. Applications are given to a simulated data set and an actual phase I trial to show how the proposed approach works in practice.


Determination of firefighter exposure to polycyclic aromatic hydrocarbons and benzene during fire fighting using measurement of biological indicators.
In accomplishing their duties, firefighters are potentially exposed to a vast array of toxic combustion and pyrolysis products such as benzene, carbon monoxide, acrolein, nitrogen dioxide, and polycyclic aromatic hydrocarbons. Exposure to PAH and benzene was assessed by means of urinary measurements of 1-hydroxypyrene and t,t-muconic acid, respectively. All urine samples were collected from 43 firefighters during a period extending for 20 h following the end of exposure during a fire. A control sample was also obtained from each participant after at least four days without involvement in fire fighting activities. Only one control 1-hydroxypyrene measurement exceeded the value of 0.32 micromol/mol creatinine considered as the 95th percentile of a normal reference population in this study. Following exposure, 38 percent of the maximum values of all samples collected from each firefighter exceeded this reference value. The highest single value observed in this study was 3.6 micromol/mol creatinine. None of the control samples had a t,t-muconic acid concentration above the limit of detection. A large number (81%) of post-fire samples also had nonquantifiable concentrations of this metabolite. Among 43 firefighters in this study, 17 had measurable excretion of this metabolite in any of the urine samples after fire fighting and, of the latter group, only 6 had t,t-muconic acid concentrations exceeding 1.1 mmol/mol creatinine, a value considered to correspond to a benzene-air concentration of approximately 1 ppm according to the literature. There is clear evidence that fire fighting activities are associated with exposure to PAH above environmental background, as assessed by 1-hydroxypyrene measurements, despite the use of protective equipment. However, in comparison with observations made in other cohorts of industrial workers with known polycyclic aromatic hydrocarbons exposure, firefighters' exposure in this study was low. Similarly, based on t,t-muconic acid determinations, exposure to benzene was rather low in this study. For both contaminants, observation of low exposure could be due to either low concentrations of the contaminant during fire fighting or to the efficiency of protective equipment worn.


The caveolin scaffolding domain modifies 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor binding properties by inhibiting phospholipase A2 activity.
Activation of the enzyme phospholipase (PLA 2) has been proposed to be part of the molecular mechanism involved in the alteration of 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) glutamate receptor responsiveness during long term changes in synaptic plasticity (long term potentiation). This study assesses the effect of the caveolin-1 scaffolding domain (CSD) on the activity of the regulatory enzyme PLA2. Caveolin-1 is a 22-kDa cholesterol-binding membrane protein known to inhibit the activity of most of its interacting partners. Our results show that the calcium-dependent cytosolic form of PLA2 (cPLA2) and caveolin-1 co-localized in mouse primary hippocampal neuron cultures and that they were co-immunoprecipitated from mouse hippocampal homogenates. A peptide corresponding to the scaffolding domain of caveolin-1 (Cav-(82-101)) dramatically inhibited cPLA2 activity in purified hippocampal synaptoneurosomes. Activation of endogenous PLA2 activity with KCl or melittin increased the binding of [3H]AMPA to its receptor. This effect was almost completely abolished by the addition of the CSD peptide to these preparations. Moreover, we demonstrated that the inhibitory action of the CSD peptide on AMPA receptor binding properties is specific (because a scrambled version of this peptide failed to have any effect) and that it is mediated by an inhibition of PLA2 enzymatic activity (because the CSD peptide failed to have an effect in membrane preparations lacking endogenous PLA2 activity). These results raised the possibility that caveolin-1, via the inhibition of cPLA2 enzymatic activity, may interfere with synaptic facilitation and long term potentiation formation in the hippocampus.


Descemet Stripping Automated Endothelial Keratoplasty: Our Experience at King Hussein Medical Center.
In this study, we report our experience at King Hussein Medical Center with Descemet stripping automated endothelial keratoplasty. This study was conducted at King Hussein Medical Center of the Royal Medical Services during the period between January 2015 and January 2016. Patients who underwent Descemet stripping automated endothelial keratoplasty were enrolled in the study. We performed a comprehensive overview of the advantages of the surgery and analyzed the donor tissue selection criteria, indications, detailed surgical techniques of the procedure, and surgical outcomes. Our cohort included 13 patients. We had successful results for all of our patients, with final visual acuity of more than 6/12. The 2 indications for surgery were pseudophakic bullous keratopathy and Fuchs endothelial dystrophy. Descemet stripping automated endothelial keratoplasty is becoming a revolutionary procedure in corneal surgery and replacing penetrating keratoplasty in many clinical situations.


Primary mandibular bone xanthoma. A case report.
We describe a case of a xanthoma located in the mandible of an 11-year-old boy. The lesion, apparently benign, did not produce pain. It did, however, produce mandibular expansion by infiltration. In jaws, xanthoma has been very rare; in order to diagnose primary xanthoma, it was necessary to discount other histological entities or the association of hyperlipoproteinemia. Treatment was the total excision of the lesion.


Current status of endoluminal grafting for exclusion of abdominal aortic aneurysms. The beauty and the beast.
The exclusion of abdominal aortic aneurysms with endoluminal grafts has generated a great deal of interest since the early 1990s, and many centers are currently evaluating the procedure and comparing it to classic surgical exclusion. Although endoluminal grafting procedures show promise, development and clinical testing of devices is a time-consuming process that is influenced greatly by the regulatory climate in the country where the clinical trials take place. Nevertheless, a number of devices are currently under study, and the advantages of 2nd- and 3rd-generation technology are reflected in reduced rates of complications such as endoleaks and thrombosis. Further study will be required to perfect these devices and observe their long-term success in the exclusion of abdominal aortic aneurysms.


Effects of High Salt-Low Potassium Diet on Blood Pressure and Vascular Reactivity in Male Sprague Dawley Rats.
Sodium (Na) intake increases vascular reactivity. Whether low potassium (K) intake affects vascular reactivity-associated blood pressure (BP) changes is uncertain. This study aimed to determine whether Na-induced increases in BP and vascular reactivity are altered by low K intake. Male Sprague Dawley rats were assigned to 3 dietary groups for 6 weeks: a standard Na-K diet (control, n = 12), a high Na-normal K diet (HS-NormK, n = 12), and a high Na-low K diet (HS-LowK, n = 12). BP was measured at baseline and after the dietary intervention. Na and K excretions and vascular reactivity were measured after the dietary intervention. The Na/K ratio was significantly higher in the HS-LowK compared with the other groups. Systolic and diastolic BPs increased significantly in the HS-NormK and HS-LowK groups. In mesenteric arteries, the dose-response curves for phenylephrine-induced contractions shifted to the left and the EC50 (mean ± SD) was significantly lower in the HS-NormK (0.51 ± 0.17 μM, P = 0.003) and HS-LowK (0.69 ± 0.14 μM, P = 0.005) groups compared with the control (3.24 ± 0.79 μM). Systolic (r = -0.58 P = 0.002) and diastolic (r = -0.61 P = 0.001) BPs were associated with the EC50 of phenylephrine-induced contraction in mesenteric arteries. High Na intake induces increased alpha-1 receptor responsiveness in mesenteric arteries, which may be responsible for the increase in BP and is not affected by low dietary K intake.


Serial nerve conduction and electromyographic studies in experimental allergic neuritis.
Experimental allergic neuritis (EAN) was produced in ten guinea pigs by intradermal injection of peripheral nerve antigen and complete Freund's adjuvant. Six additional animals were injected with adjuvant only, and three control animals received saline. Slowing of motor nerve conduction velocity occurred in all animals ijected with antigen. Velocities progressively decreased through the first six weeks, at which time they started increasing, returning to the normal range in the third month. Six of the animals--generally those having received the greatest amount of antigen and adjuvant--developed severe encephalomyelitis and died early in the study. These animals also developed more severe peripheral nerve involvement, and conduction velocities decreased more than in mildly affected animals. Abnormal electromyographic findings were observed in all EAN animals surviving through the third week. Two of the six animals injected with complete adjuvant without antigen showed some minimal electromyographic changes. Several developed slight slowing of nerve conduction velocity during the first few weeks. Saline control animals had normal nerve conductions and electromyographic studies throughout the course of observation.


Updated perspectives on emerging vibrios associated with human infections.
This review describes the ecological, clinical and epidemiological features of emerging vibrios and discusses what laboratory methods are being used for the detection of pathogenic vibrios in clinical, environmental and food samples. After selecting articles illustrative of the current scientific research on pathogenic vibrios, the review focuses on the need for better insight into the risk factors of emerging infections to establish adequate prevention procedures.


Re(I) derivatives functionalised with thioether crowns containing the 1,10-phenanthroline subunit as a new class of chemosensors.
A series of luminescent fac-[Re(CO)3(L)(NN)](+) complexes, where L is a pyridine or an imidazole and NN is the 1,10-phenanthroline subunit of mixed donor pentadentate thioether crowns have been synthesised and their luminescence properties have been analysed. Then, heterometallic Re(i)/Au(i) complexes, with the Au(i) fragment bonded directly to the imidazole ligand, and heterometallic Re(i)/Ag(i) complexes, with the silver fragment coordinating the S-donor thioether linker of the rings have also been prepared. Analysis of their luminescence properties showed a considerable blue shift of the emission maxima for the Re(i)/Ag(i) derivatives, upon coordination of the silver centre to the S-donor atoms of the aliphatic chain of the macrocyclic units.


Novel method for estimating viable Salmonella cell counts using real-time PCR.
A novel method for estimating viable Salmonella Enteritidis cell counts with 5'-nuclease real-time PCR was developed in this study. Our method was based on the increase kinetics of the target DNA region (invA) of the microorganism growing in a food/clinical sample in a culture medium during incubation. The index of increase in the target DNA region studied here was threshold cycle, CT. A test Salmonella strain was grown in buffered peptone water at the optimal temperature (39 degrees C). As Salmonella cells were grown, the value of CT decreased with time, generating a downward sigmoidal curve. The slope of the curve was constant at various initial cell concentrations. With higher initial cell concentration, the CT value evaluated from the slope at a given time was lower. With this relationship, a novel method for estimating the initial viable cell concentration of a sample was developed. Dead Salmonella cells or bacteria other than the target cell caused deviation in the CT curve. Incubation in a selective media suppressed the deviation caused by other bacterial cells. We think that this method could be applied to many other microorganisms cultivable in a suitable medium.


Biomagnetic Monitoring of Atmospheric Pollution: A Review of Magnetic Signatures from Biological Sensors.
Biomagnetic monitoring of atmospheric pollution is a growing application in the field of environmental magnetism. Particulate matter (PM) in atmospheric pollution contains readily measurable concentrations of magnetic minerals. Biological surfaces, exposed to atmospheric pollution, accumulate magnetic particles over time, providing a record of location-specific, time-integrated air quality information. This review summarizes current knowledge of biological material ("sensors") used for biomagnetic monitoring purposes. Our work addresses the following: the range of magnetic properties reported for lichens, mosses, leaves, bark, trunk wood, insects, crustaceans, mammal and human tissues; their associations with atmospheric pollutant species (PM, NOx, trace elements, PAHs); the pros and cons of biomagnetic monitoring of atmospheric pollution; current challenges for large-scale implementation of biomagnetic monitoring; and future perspectives. A summary table is presented, with the aim of aiding researchers and policy makers in selecting the most suitable biological sensor for their intended biomagnetic monitoring purpose.


Occlusal migration of the maxillary first primary molars subsequent to the loss of antagonists.
The purpose of this study was to observe the vertical changes in unopposed maxillary first primary molars longitudinally. The subjects of this study were 17 children whose lower first primary molars had to be extracted. Space closure were prevented by crown-loop space maintainers for all these children. Plaster casts were made every 4 months for 16 to 24 months after the extraction. These series of casts were standardized, and vertical changes of the maxillary first primary molars against the occlusal plane were measured using a micro-reader. The mean changes indicated that maxillary first primary molars without intercuspidation tend to drift toward the extraction space. On the control side with antagonists, the maxillary first molars seemed to move reversed to apical throughout the observation period. Accordingly, the results of this study showed new trends after the premature loss of primary molars. The vertical changes toward extraction space varied from -0.40 mm to 1.43 mm at the 16 months after extraction. Mean changes were small, but there were some individual differences in reaction, giving negative values. However, we should always be concerned about loss of arch length and also occlusal drift of unopposed teeth, because the vertical changes were greater than 1 mm at 16 months after extraction in some cases.


Diaphragm dysfunction and peripheral muscle wasting in septic shock patients: Exploring their relationship over time using ultrasound technology (the MUSiShock protocol).
Intensive Care Unit (ICU) patients are known to lose muscle mass and function during ICU stay. Ultrasonography (US) application for the assessment of the skeletal muscle is a promising tool and might help detecting muscle changes and thus several dysfunctions during early stages of ICU stay. MUSiShock is a research project aiming to investigate structure and function of diaphragm and peripheral muscles using ultrasound techniques in septic shock patients, and to assess their relevance in several clinical outcomes such as the weaning process. This is a research protocol from an observational prospective cohort study. We plan to assess eighty-four septic shock patients during their ICU stay at the following time-points: at 24 hours of ICU admission, then daily until day 5, then weekly, at extubation time and at ICU discharge. At each time-point, we will measure the quadriceps rectus femoris and diaphragm muscles, using innovative US muscle markers such as Shear-Wave Elastography (SWE). In parallel, the Medical Research Council (MRC) sum score for muscle testing and the Airway occlusion pressure (P0.1) will also be collected. We will describe the association between SWE assessment and other US markers for each muscle. The association between the changes in both diaphragm and rectus femoris US markers over time will be explored as well; finally, the analysis of a combined model of one diaphragm US marker and one limb muscle US marker to predict weaning success/failure will be tested. By using muscle ultrasound at both diaphragm and limb levels, MUSiShock aims to improve knowledge in the early detection of muscle dysfunction and weakness, and their relationship with muscle strength and MV weaning, in critically ill patients. A better anticipation of these short-term muscle structure and function outcomes may allow clinicians to rapidly implement measures to counteract it. ClinicalTrials.gov, NCT04550143. Registered on 16 September 2020.


[History of orthopedic surgery in Belgrade--100 years of orthopedics in Serbia (1905-2005)].
The history of orthopedics in Serbia is related to a hand x-ray made in 1905 by dr. Nikola Krstić. The first orthopedic word was founded in 1919, to be enlarged into a full-fledged orthopedic surgical ward of the General State Hospital in 1932. Until 1941, the ward headed by Dr. Nikola Krstić. The Orthopedics course was headed by Dr. Borivoje Gradojević, who also wrote the first textbook in our country in 1934. In 1947, the ward became the Clinic for Orthopedic Surgery and Traumatology in Belgrade which is the orthopedic basis of Serbia, together with the Special Orthopedic Surgery Hospital Banjica, even today.


CLINICALLY INVISIBLE RETINOBLASTOMA RECURRENCE IN AN INFANT.
To report a case of clinically invisible retinoblastoma recurrence detected only on spectral-domain optical coherence tomography. Case report. A 3-week-old girl with bilateral familial retinoblastoma underwent six cycles of intravenous chemoreduction. Both eyes showed tumor regression. After 6 cycles of chemoreduction, the tumor in the right eye appeared with clinical regression; however, by spectral-domain optical coherence tomography, there was 40 μm increase in thickness and 290 μm increase in basal diameter. Due to tumor proximity of 1.85 mm to the foveola, the recurrence was treated via intraarterial chemotherapy with two cycles of Melphalan 3 mg. After treatment, spectral-domain optical coherence tomography showed complete regression of the recurrent tumor to a flat scar with intact fovea. Precise submillimeter imaging with spectral-domain optical coherence tomography for monitoring retinoblastoma is important and can allow detection of early recurrences that might be clinically invisible otherwise, as well as surveillance of the fovea.


A Comparative Analysis Between Antibiotic- and Nonantibiotic-Associated Delayed Cutaneous Adverse Drug Reactions.
The difference in clinical presentation, causality assessments, and outcomes of patients with delayed antibiotic-associated cutaneous adverse drug reactions (AA-cADR) and nonantibiotic-associated (NA)-cADR is ill defined. We examined the etiology of AA-cADR, with regard to the type of antibiotic exposure, allergy labeling, and patient outcomes, in comparison with NA-cADR. A retrospective observational inpatient cohort study of cADR was performed from January 2004 to August 2014. Patients were divided into AA-cADR and NA-cADR groups for analysis. cADR was defined as erythema multiforme, fixed drug eruption, acute generalized erythematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), drug-associated linear IgA disease, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Of the 84 patients with cADR, 48% were AA-cADR. Male sex (60% vs 32%, P = .004), median length of stay (14.5 vs 11 days, P = .05), median Charlson comorbidity index (3 vs 1, P = .03), and inpatient mortality (20% vs 5%, P = .04) were higher in AA-cADR compared with NA-cADR. The median drug latency was lower in AA-cADR (6 vs 20 days, P = .001). Sulfonamide antibiotics and glycopeptides were implicated in 20% of AA-cADR. DRESS was more frequently reported in AA-cADR. After cADR diagnosis, further antibiotic therapy was administered in 64% of patients, higher in AA-cADR (75%, 30 of 40) compared with NA-cADR (55%, 24 of 44) (P = .06). Fluoroquinolones (53% vs 21%, P = .02), glycopeptides (vancomycin and teicoplanin; 70% vs 38%, P = .05), and carbapenems (33% vs 13%, P = .11) were used more commonly in AA-cADR. Antibiotics were the cause of cADR requiring hospital admission in 48% of episodes, and were associated with longer length of stay, higher age-adjusted Charlson comorbidity index, shorter drug latency, and mortality. In AA-cADR, glycopeptide and sulfonamide antibiotic exposure predominated.


Complications following parametrial radiogold treatment for cervical carcinoma.
Between January 1950 and March 1965, 382 patients with carcinoma of the uterine cervix were treated with parametrial radiogold injections. One hundred and ninety-two patients are known to have survived 5 or more years after the treatment without evidence of recurrence. Major complications with significant morbidity requiring hospitalization or additional surgery was observed in 9.4% of the patients. Parametrial radiogold injection is associated with a high incidence of major lower urinary tract complications, including an increased incidence of ureteral obstruction as a result of radiation fibrosis, Heterogenous distribution of radioactive material with localized areas of heavy irradiation is probably responsible for the development of late major complications.


Prognostic significance of macrophage invasion in hilar cholangiocarcinoma.
Tumor-associated macrophages (TAMs) promote tumor progression and have an effect on survival in human cancer. However, little is known regarding their influence on tumor progression and prognosis in human hilar cholangiocarcinoma. We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution and localization of TAMs, as defined by expression of CD68. Abundance of TAMs was correlated with clinicopathologic characteristics, tumor recurrence and patients' survival. Statistical analysis was performed using SPSS software. Patients with high density of TAMs in tumor invasive front (TIF) showed significantly higher local and overall tumor recurrence (both ρ < 0.05). Furthermore, high density of TAMs was associated with decreased overall (one-year 83.6% vs. 75.1%; three-year 61.3% vs. 42.4%; both ρ < 0.05) and recurrence-free survival (one-year 93.9% vs. 57.4%; three-year 59.8% vs. 26.2%; both ρ < 0.05). TAMs in TIF and tumor recurrence, were confirmed as the only independent prognostic variables in the multivariate survival analysis (all ρ < 0.05). Overall survival and recurrence free survival of patients with hilar cholangiocarcinoma significantly improved in patients with low levels of TAMs in the area of TIF, when compared to those with a high density of TAMs. These observations suggest their utilization as valuable prognostic markers in routine histopathologic evaluation, and might indicate future therapeutic approaches by targeting TAMs.


Massive hiatal hernia in children.
Ten children had massive hiatal hernias repaired between January 1982 and February 1991. Their clinical presentation, association with other congenital abnormalities, and postoperative complications were different from those seen in adults. Vomiting (n = 7) and anaemia (n = 7) were the most common symptoms, followed by respiratory distress (n = 5), cough (n = 3), and regurgitation (n = 3). Abdominal pain was uncommon. The clinical diagnosis was confirmed in seven cases by barium meal examination. The most common operation was Nissen's fundoplication (n = 7); the hiatus alone was repaired in the remainder. Five patients developed postoperative complications and two died probably as a result of delay in diagnosis and associated malformations.


Oral immunotherapy against a pollen allergy using a seed-based peptide vaccine.
Peptide immunotherapy using dominant T-cell epitopes is safer and more effective than conventional immunotherapy for the treatment of immunoglobulin E (IgE)-mediated allergic diseases. When allergenic T-cell epitope peptides are expressed in the edible part of transgenic plants, successful mucosal immune tolerance to these allergens may be attainable by the consumption of these plants. In this study, we generated transgenic rice seed that accumulated high concentrations (about 60 microg per grain) of polypeptide consisting of seven dominant human T-cell epitopes derived from the Japanese cedar pollen allergens, Cry j 1 and Cry j 2, in the endosperm. Oral administration of these transgenic rice seeds to B10.S mice before or after they were immunized with Cry j 1 holoprotein reduced not only their T-cell proliferative response to Cry j 1, but also their serum IgE levels, proving the efficacy of oral immunotherapy for the treatment of pollinosis.


Cyclostationarity-based joint monitoring of symbol-rate, frequency offset, CD and OSNR for Nyquist WDM superchannels.
Software-defined transceivers can be reconfigured based on demand and existing channel impairments, and as such, monitoring of both signal and channel parameters is necessary. We demonstrate a novel joint estimation method suitable for spectrally efficient Nyquist wavelength-division multiplexing (WDM), based on the cyclostationary property of linearly modulated signals, exploited both in the frequency and time domains. Using a Nyquist superchannel composed of three 10 GBaud channels, we experimentally demonstrate the simultaneous monitoring of symbol-rate with 100% accuracy, roll-off, frequency offset (FO), chromatic dispersion (CD) and optical signal-to-noise ratio (OSNR) with root-mean-square errors (RMSE) of 20%, 4 MHz, 200 ps/nm and 1.5 dB respectively, when the roll-off factor is larger than 0.06 for DP-QPSK and 0.3 for DP-16QAM.


The effect of therapeutic agents on cartilage degradation in-vivo.
Implantation of minced autologous cartilage into inflamed air pouches in mice allows the study of therapeutic agents on both the inflammatory process and cartilage degradation. Non-steroidal anti-inflammatory agents were found to reduce cell accumulation in response to carrageenan, but were unable to prevent proteoglycan loss from cartilage. In contrast, D-penicillamine had no effect on the inflammatory process but significantly reduced proteoglycan loss. Our findings suggest that the autologous cartilage transplantation model in the mouse may be useful for studying novel anti-arthritic agents.


BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3.
Pre-B-cell leukemia spontaneously develops in BLNK-deficient mice, and pre-B-cell acute lymphoblastic leukemia cells in children often lack BLNK protein expression, demonstrating that BLNK functions as a tumor suppressor. However, the mechanism by which BLNK suppresses pre-B-cell leukemia, as well as the identification of other genetic alterations that collaborate with BLNK deficiency to cause leukemogenesis, are still unknown. Here, we demonstrate that the JAK3/STAT5 signaling pathway is constitutively activated in pre-B leukemia cells derived from BLNK(-/-) mice, mostly due to autocrine production of IL-7. Inhibition of IL-7R signaling or JAK3/STAT5 activity resulted in the induction of p27(kip1) expression and cell-cycle arrest, accompanied by apoptosis in the leukemia cells. Transgene-derived constitutively active STAT5 (STAT5b-CA) strongly synergized with the loss of BLNK to initiate leukemia in vivo. In the leukemia cells, exogenously expressed BLNK inhibited autocrine JAK3/STAT5 signaling, resulting in p27(kip1) induction, cell-cycle arrest, and apoptosis. BLNK-inhibition of JAK3 was dependent on the binding of BLNK to JAK3. These data indicate that BLNK normally regulates IL-7-dependent proliferation and survival of pre-B cells through direct inhibition of JAK3. Thus, somatic loss of BLNK and concomitant mutations leading to constitutive activation of Jak/STAT5 pathway result in the generation of pre-B-cell leukemia.


Fusion of Ultraviolet-Visible and Infrared Transient Absorption Spectroscopy Data to Model Ultrafast Photoisomerization.
Ultrafast photoisomerization reactions generally start at a higher excited state with excess of internal vibrational energy and occur via conical intersections. This leads to ultrafast dynamics which are difficult to investigate with a single transient absorption spectroscopy technique, be it in the ultraviolet-visible (UV-vis) or infrared (IR) domain. On one hand, the information available in the UV-vis domain is limited as only slight spectral changes are observed for different isomers. On the other hand, the interpretation of vibrational spectra is strongly hindered by intramolecular relaxation and vibrational cooling. These limitations can be circumvented by fusing UV-vis and IR transient absorption spectroscopy data in a multiset multivariate curve resolution analysis. We apply this approach to describe the spectrodynamics of the ultrafast cis-trans photoisomerization around the C-N double bond observed for aromatic Schiff bases. Twisted intermediate states could be elucidated, and isomerization was shown to occur through a continuous complete rotation. More broadly, data fusion can be used to rationalize a vast range of ultrafast photoisomerization processes of interest in photochemistry.


Drug exposure opportunities and use patterns among college students: results of a longitudinal prospective cohort study.
Underage drinking and drug use among college students are major public health concerns, yet few studies have examined these behaviors and their associated risk factors and consequences prospectively. This paper describes the sampling and recruitment methods of a longitudinal study of 1253 college students at a large, mid-Atlantic university. Incoming first-year students were screened during the unique window between high school and college in order to oversample drug users for longitudinal follow-up. Intensive recruitment strategies yielded a 95% cumulative response rate in annual interviews and semiannual surveys. The authors report preliminary results on exposure opportunity, lifetime prevalence, initiation, continuation, and cessation of substance use for alcohol, tobacco, and 10 illicit and prescription drugs during the first 2 years of college. Findings suggest that although some substance use represents a continuation of patterns initiated in high school, exposure opportunity and initiation of substance use frequently occur in college. Implications for prevention and early intervention are discussed.


Assessment of cancellous bone quality in severe osteoarthrosis: bone mineral density, mechanics, and microdamage.
The role of bone microdamage (microscopic cracks or microcracks and ultrastructural collagen matrix and bone mineral damage) in diseases such as osteoarthrosis and osteoporosis is poorly understood. Microdamage accumulation in vivo is influenced by age and cyclic loading, therefore, it would be useful if the burden of microdamage in bone could be assessed by noninvasive measures such as the radiological measurement of bone mineral density (BMD). The aim of this study was to investigate the relationship between BMD, compressive strength and stiffness, and microdamage in the cancellous bone of the proximal femur in patients with severe osteoarthrosis. Trabecular bone core samples, from the intertrochanteric region of the femur, were obtained from 34 patients, with a mean age of 70.3 +/- 11.1 years, undergoing total hip arthroplasty for osteoarthrosis. Cores selected from contact X-ray images were used for BMD measurement, compressive mechanical testing or left untested (uncrushed), en bloc staining for microdamage, and bone histomorphometry. The study shows a strong dependence of both the elastic modulus and ultimate failure stress of the bone samples on BMD and a significant relationship between the elastic modulus and trabecular anisotropy (Tr. An). In multiple linear regression, BMD and Tr. An together account for about 70% of the variance in the elastic modulus. Then including microcrack crack density (Cr.Dn) and damage volume fraction (DxV/BV) variables, Tr. An alone accounts for a relatively small amount of the variation (8.5%) in ultimate failure stress and elastic modulus. The Cr.Dn accounts for more of the variation in the ultimate failure stress than in the elastic modulus (50% vs. 7%). In this experiment, data for Cr.Dn provide a measure of damage associated with the ultimate failure of cancellous bone. In specimens that were not mechanically tested, in vivo microcrack accumulation increases exponentially with age. In conclusion, data from this study suggest that BMD and Cr.Dn are the major determinants of cancellous bone strength, whereas BMD and Tr. An are major determinants of cancellous bone stiffness. In bone specimens subjected to compressive testing there was no relationship between microdamage and BMD, suggesting that BMD cannot be used to monitor changes in the mechanical properties of bone due to microdamage accumulation.


Pharyngolaryngo-esophagectomy with laparoscopic gastric pull-up: a reappraisal for the pharyngoesophageal junction cancer.
Surgical treatment of advanced hypopharyngeal tumors is still a surgical challenge. We report a case of a hypopharyngeal tumor treated with a pharyngolaryngo-esophagectomy (PLE) and laparoscopic gastric tubulization and interposition. A 56-year-old man presented with a relapsing hypopharynx carcinoma, after primary chemoradiation therapy. Preoperative workup showed a stage IV cancer with esophageal invasion and multiple cervical lymph node metastases. Surgical treatment consisted of a cervical phase, with larynx, pharynx, and esophagus dissection, radical lymph node dissection, homolateral hemithyroidectomy and definitive tracheostomy, and an abdominal phase with a 4-trocar laparoscopy. The gastrocolic ligament was opened, and short gastric and left gastric vessels were divided preserving an accessory left hepatic artery. Gastric tailoring was carried out with 45-mm linear staplers. The hiatus was opened and the esophagus dissected free with Ultracision (Ethicon Endo-Surgery, Cincinnati, OH) to the tracheal bifurcation. The upper esophagus was bluntly mobilized by finger and sponge stick dissection. The gastric tube was pulled up, and the anastomosis between the stomach and the tongue base was performed with a 2-layer interrupted hand-sewn technique. Total operative time was 390 min (abdominal time 180 min). Estimated blood loss was 400 cc. The number of dissected cervical lymph nodes was 32. Oral feeding was started after 10 days, and the patient was discharged after 14 days. Stage of disease was pT4N1M0 G3 R0. Laparoscopic surgery allows a minimally invasive gastric tailoring and tubulization and transhiatal esophageal dissection and represents a valuable alternative for intestinal reconstruction after PLE. CT scan showing a large hypopharynx carcinoma involving cervical lymph nodes and cervical esophagus.


The Current State and Legal Issues of Online Crimes Related to Children and Adolescents.
There are two categories of online crimes related to children and adolescents: those committed by adolescents and those committed against children and adolescents. While recent trends in criminal law show consensus on strengthening punishment in cases of crimes against children and adolescents, there are mixed stances in cases of juvenile delinquency. One perspective emphasizes strict punishment, whereas the other emphasizes dispositions aligned with human rights. While various forms of online crime share the commonality in that the main part of the criminal act occurs online, they can be categorized into three types: those seeking financial gain, those driven by sexual motives, and those engaged in bullying. Among these, crimes driven by sexual motives are the most serious. Second-hand trading fraud and conditional (sexual) meeting fraud fall under the category of seeking financial gain and occur frequently. Crimes driven by sexual motives include obscenity via telecommunication, filming with discrete cameras, child and adolescent sexual exploitation material, fake video distribution, and blackmail/coercion using intimate images/videos ("sextortion"). These crimes lead to various legal issues such as whether to view vulgar acronyms or body cams that teenagers frequently use as simple subcultures or crimes, what criteria should be applied to judge whether a recorded material induces sexual desire or shame, and at what stage sexual grooming becomes punishable. For example, sniping posts, KakaoTalk prisons, and chat room explosions are tricky issues, as they may or may not be punished depending on the case. Particular caution should be exercised against the indiscriminate application of a strict punishment-oriented approach to the juvenile justice system, which is being discussed in relation to online sexual offenses. In the punishment case of online crime, juvenile offenders with a high potential for future improvement and reform must be treated with special consideration.


Angioleiomyoma: magnetic resonance imaging features in ten cases.
Angioleiomyoma is a rare, benign smooth muscle tumour arising from the tunica media of small veins and arteries and can occur anywhere in the body. The histological appearances are well documented, but there are relatively few descriptions of the magnetic resonance imaging (MRI) findings. A retrospective study of the clinical presentation, MRI appearances and histological findings of ten angioleiomyomas presenting as extremity soft tissue masses. MRI typically demonstrated a well-defined, oval mass located superficial to the fascia with the commonest sites being the hand (three cases) and ankle/foot (five cases). The lesion was isointense to muscle on T1-weighted spin echo images with heterogeneous increased internal T2W/short tau inversion recovery (STIR) signal intensity, which commonly appeared as multiple linear or branching areas of hyperintensity. Enhancement after IV gadolinium ranged from diffuse to heterogeneous. In a single case, central fat signal intensity was seen, while a further case showed marked T2W/STIR hypointensity due to diffuse hyalinisation within the lesion. This is the largest reported MRI series of extremity musculoskeletal angioleiomyoma. Angioleiomyoma should be considered in the differential diagnosis of a superficial mass in the hand or foot, particularly when characteristic linear or branching hyperintensity is seen on T2W or STIR images.


Water availability predicts forest canopy height at the global scale.
The tendency of trees to grow taller with increasing water availability is common knowledge. Yet a robust, universal relationship between the spatial distribution of water availability and forest canopy height (H) is lacking. Here, we created a global water availability map by calculating an annual budget as the difference between precipitation (P) and potential evapotranspiration (PET) at a 1-km spatial resolution, and in turn correlated it with a global H map of the same resolution. Across forested areas over the globe, Hmean increased with P-PET, roughly: Hmean (m) = 19.3 + 0.077*(P-PET). Maximum forest canopy height also increased gradually from ~ 5 to ~ 50 m, saturating at ~ 45 m for P-PET > 500 mm. Forests were far from their maximum height potential in cold, boreal regions and in disturbed areas. The strong association between forest height and P-PET provides a useful tool when studying future forest dynamics under climate change, and in quantifying anthropogenic forest disturbance.


[Low-risk thyroid carcinoma--therapy, follow-up and prognosis].
A retrospective study was performed to determine the frequency of local recurrences and distant metastases as well as potential risk factors in patients with low-risk differentiated thyroid carcinoma. In addition, the efficiency of our follow-up programme and the diagnostic value of the procedures administered was to be evaluated. 41/740 (8%) patients developed 62 recurrences at a mean 4.7 years after the onset of the disease. In 14 cases the tumor marker thyroglobulin was the first diagnostic sign. 13 recurrences were diagnosed by chest x-ray and/or CT. In 12 cases recurrences/metastases were detected by iodine-131 whole body scan, and 8 cases by ultrasound of the neck. A good prognosis was found if patients were under 45 years of age when the tumor was first diagnosed, and if the tumor did not exceed 20 mm in diameter. The prognosis was not statistically significant influenced by histology, gender and surgical methods. The 10-year survival rate for papillary carcinomas was 91% and for follicular carcinomas 84%. We recommend yearly follow-up examinations with selective use of other diagnostic methods in order to provide best patient care.


A mild thermomechanical process for the enzymatic conversion of radiata pine into fermentable sugars and lignin.
Conversion of softwoods into sustainable fuels and chemicals is important for parts of the world where softwoods are the dominant forest species. While they have high theoretical sugar yields, softwoods are amongst the most recalcitrant feedstocks for enzymatic processes, typically requiring both more severe pretreatment conditions and higher enzyme doses than needed for other lignocellulosic feedstocks. Although a number of processes have been proposed for converting softwoods into sugars suitable for fuel and chemical production, there is still a need for a high-yielding, industrially scalable and cost-effective conversion route. We summarise work leading to the development of an efficient process for the enzymatic conversion of radiata pine (Pinus radiata) into wood sugars. The process involves initial pressurised steaming of wood chips under relatively mild conditions (173 °C for 3-72 min) without added acid catalyst. The steamed chips then pass through a compression screw to squeeze out a pressate rich in solubilised hemicelluloses. The pressed chips are disc-refined and wet ball-milled to produce a substrate which is rapidly saccharified using commercially available enzyme cocktails. Adding 0.1% polyethylene glycol during saccharification was found to be particularly effective with these substrates, reducing enzyme usage to acceptable levels, e.g. 5 FPU/g OD substrate. The pressate is separately hydrolysed using acid, providing additional hemicellulose-derived sugars, for an overall sugar yield of 535 kg/ODT chips (76% of theoretical). The total pretreatment energy input is comparable to other processes, with the additional energy for attrition being balanced by a lower thermal energy requirement. This pretreatment strategy produces substrates with low levels of fermentation inhibitors, so the glucose-rich mainline and pressate syrups can be fermented to ethanol without detoxification. The lignin from the process remains comparatively unmodified, as evident from the level of retained β-ether interunit linkages, providing an opportunity for conversion into saleable co-products. This process is an efficient route for the enzymatic conversion of radiata pine, and potentially other softwoods, into a sugar syrup suitable for conversion into fuels and chemicals. Furthermore, the process uses standard equipment that is largely proven at commercial scale, de-risking process scale-up.


Analyzing the Performance of the Population Health Environment on the Promotion of Provincial Governors in China.
China's economy has achieved rapid growth, but the change has also brought about serious environmental degradation, which is the main factor endangering human health. This study empirically investigates the impact of the population health environmental index on the promotion of provincial governors using an ordered probit model. The sample of the study consists of regions where provincial governors, municipal mayors, and autonomous region chairmen were stationed from 1995 to 2015. The results show that the population health environmental index had a significant and positive impact on governors' promotions, especially in the eastern region. The reformation of the population health environmental index assessment system for government officials was the initial factor that brought about these effects.