Somatic instability of CTG repeats in the cerebellum of myotonic dystrophy type 1.
We statistically analyzed somatic instability of the CTG expansion in the central nervous system and visceral organs in 7 patients with myotonic dystrophy type 1 and also report intracerebellar instability in 2 patients. CTG repeat expansion was estimated in the samples from autopsied brains and visceral organs by Southern blot analysis. Pathological study was performed. Samples were taken from several sites in the cerebellum to examine intracerebellar instability. The CTG repeat expansion was shortest in the cerebellar cortex among all tissues examined. With regard to the intracerebellar difference, the shortest expansion was seen in the cortices of the hemisphere and vermis, whereas it was moderate in the dentate nucleus and longest in the white matter of the hemisphere and middle cerebellar peduncle. The shortest expansion might be attributable to packed granule cells in the cerebellar cortex. Further analysis of cell-specific methylation states might elucidate the enigma of somatic instability.


Management of thromboembolic disease in pregnancy.
Venous thromboembolism (VTE) is the leading cause of maternal mortality and morbidity in developed countries including Singapore. The physiological changes of pregnancy and other factors, such as maternal age, parity, obesity, operative delivery, general anaesthesia and congenital and acquired thrombophilia, further increase the risk of VTE throughout all three trimesters of pregnancy, including the puerperium. VTE has a wide spectrum of clinical presentations and a high index of clinical suspicion is vital. Clinicians should not withhold the use of chest X-rays and ventilation-perfusion (V/Q) lung scans in pregnancy as the radiation emitted is well within the safety limits to the fetus. Most treatment guidelines are based on studies in non-pregnant populations. Heparin is the preferred anticoagulant as it does not cross the placenta and therefore carries no teratogenic risk to the fetus. There is increasing experience and confidence in the use of fixed dose subcutaneous low molecular weight heparin (LMWH) which removes the need for cumbersome monitoring, thereby allowing outpatient treatment. LMWH may also have a lower risk of osteopaenic complications compared to unfractionated heparin. With the exception of acute phase treatment of pulmonary embolism, LMWH is used in all other aspects of the treatment of VTE in pregnancy, including thromboprophylaxis. Risk stratification of women into high and low risk allows judicious use of anticoagulants for thromboprophylaxis. Antenatal thromboprophylaxis with LMWH is reserved for high-risk women, while low-risk women will only require such cover in the postpartum period.


Memantine inhibits efferent cholinergic transmission in the cochlea by blocking nicotinic acetylcholine receptors of outer hair cells.
Memantine is a blocker of Ca(2+)-permeable glutamate and nicotinic acetylcholine receptors (nAChR). We investigated the action of memantine on cholinergic synaptic transmission at cochlear outer hair cells (OHCs). At this inhibitory synapse, hyperpolarization of the postsynaptic cell results from opening of SK-type Ca(2+)-activated K(+) channels via a highly Ca(2+)-permeable nAChR containing the alpha 9 subunit. We show that inhibitory postsynaptic currents recorded from OHCs were reversibly blocked by memantine with an IC(50) value of 16 microM. RT-PCR revealed that a newly cloned nAChR subunit, alpha 10, is expressed in OHCs. In contrast to homomeric expression, coexpression of alpha 9 and alpha 10 subunits in Xenopus laevis oocytes resulted in robust acetylcholine-induced currents, indicating that the OHC nAChR may be an alpha 9/alpha 10 heteromer. Accordingly, nAChR currents evoked by application of the ligand to OHCs and currents through alpha 9/alpha 10 were blocked by memantine with a similar IC(50) value of about 1 microM. Memantine block of alpha 9/alpha 10 was moderately voltage dependent. The lower efficacy of memantine for inhibition of inhibitory postsynaptic currents (IPSCs) most probably results from a blocking rate that is slow with respect to the short open time of the receptor channels during an IPSC. Thus, synaptic transmission in OHCs is inhibited by memantine block of Ca(2+) influx through nAChRs. Importantly, prolonged receptor activation and consequently massive Ca(2+) influx, as might occur under pathological conditions, is blocked at low micromolar concentrations, whereas the fast IPSCs initiated by short receptor activation are only blocked at concentrations above 10 microM.


Cardiac Metastasis Caused Fatal Ventricular Arrhythmia in a Patient with a Rectal Neuroendocrine Tumor.
A 60-year-old man had received octreotide for a metastatic neuroendocrine tumor (NET) in the rectum. Computed tomography and ultrasonography revealed a cardiac tumor, diffuse thickness of the ventricular wall and pericardial effusion, which was diagnosed as cardiac metastasis. The metastatic lesions continued to grow despite the alteration of chemotherapy, and the patient complained of repeated syncope and was admitted to our hospital at 11 months after the diagnosis of cardiac metastasis. An electrocardiogram during syncope showed sustained ventricular tachycardia, which was considered to be caused by the cardiac metastasis. We herein report a case of NET with cardiac metastasis which caused lethal arrhythmia along with a review of the pertinent literature.


Genotype-Based Gene Expression in Colon Tissue-Prediction Accuracy and Relationship with the Prognosis of Colorectal Cancer Patients.
Colorectal cancer (CRC) survival has environmental and inherited components. The expression of specific genes can be inferred based on individual genotypes-so called expression quantitative trait loci. In this study, we used the PrediXcan method to predict gene expression in normal colon tissue using individual genotype data from 91 CRC patients and examined the correlation ρ between predicted and measured gene expression levels. Out of 5434 predicted genes, 58% showed a negative ρ value and only 16% presented a ρ higher than 0.10. We subsequently investigated the association between genotype-based gene expression in colon tissue for genes with ρ > 0.10 and survival of 4436 CRC patients. We identified an inverse association between the predicted expression of ARID3B and CRC-specific survival for patients with a body mass index greater than or equal to 30 kg/m2 (HR (hazard ratio) = 0.66 for an expression higher vs. lower than the median, p = 0.005). This association was validated using genotype and clinical data from the UK Biobank (HR = 0.74, p = 0.04). In addition to the identification of ARID3B expression in normal colon tissue as a candidate prognostic biomarker for obese CRC patients, our study illustrates the challenges of genotype-based prediction of gene expression, and the advantage of reassessing the prediction accuracy in a subset of the study population using measured gene expression data.


[The case of numerous foreign bodies in bronchial tree of both lungs and digestive tract].
The article shows the description of the seldom met case of simultaneous appearing of numerous foreign bodies situated both in air passages and in the alimentary canal at patient of mentally handicapped with the tendency to swallowing of small objects. After observing by guardians of the patients fact of swallowing metallic foreign bodies by him the specified research were made (X-ray pictures, computer tomography) and the presence in the bronchial tree of both lungs and in the upper and lower section of the alimentary canal were confirmed. Swallowed and aspirated objects did not cause no complaints at the patient. Revealed foreign bodies were removed from air passages by using of the bronchofiberoscopy method and the surgical treatment. Foreign bodies of the alimentary canal were voided by patient through natural tract.


Does a trade-off between growth plasticity and resource conservatism mediate post-fire shrubland responses to rainfall seasonality?
Growth plasticity may allow fire-prone species to maximize their recovery rates during temporary, sporadic periods of rainfall availability in the post-fire environment. However, moisture-driven growth plasticity could be maladaptive in nutrient-limited environments that require tighter control of growth and resource use. We investigated whether a trade-off between plasticity and conservatism mediates growth responses to altered rainfall seasonality in neighbouring shrubland communities that occupy different soils. We monitored post-fire vegetation regrowth in two structurally similar, Mediterranean-type shrublands for 3 years. We investigated the effects of experimentally altered rainfall seasonality on post-fire species' growth rates. We found that moisture-driven growth plasticity was higher among species occupying the fertile soils of the renosterveld site relative to those occupying the nutrient-poor soils of the fynbos site. This resulted in higher overall responsiveness of post-fire recovery patterns in renosterveld to experimental shifts in rainfall seasonality. In post-fire shrubland communities, the trade-off between moisture-dependent growth plasticity and resource conservatism could be mediated by soil nutrient availability. Therefore, edaphic differences between structurally similar shrublands could lead to differences in their sensitivity to post-fire rainfall seasonality.


Pregnancy and delivery after pelvic fracture in fertile-aged women: A nationwide population-based cohort study in Finland.
Only a few small studies have assessed the effects of pelvic fractures on pregnancies, deliveries, and rates of cesarean sections. We aimed to evaluate the effect of pelvic fractures on subsequent pregnancy and delivery in Finland. In this retrospective register-based nationwide cohort study, data on all fertile-aged (aged 15-49) women with a pelvic fracture during our study period (1998-2018) were retrieved from the Care Register for Health Care. The data were subsequently combined with data from the National Medical Birth Register. Women with pelvic fracture before pregnancy were compared with a no-fracture group consisting of 621 141 women who had had 1 156 723 singleton deliveries without a preceding pelvic fracture. We used logistic regression to analyze preterm deliveries, cesarean sections, and neonatal health. Results are reported as adjusted odds ratios (AOR) with 95% confidence intervals (CI). A total of 2 878 women with a previous pelvic fracture were identified. Of these, 596 women had 1024 singleton deliveries after pelvic fracture. In the no-fracture group, 621 141 women had 1 156 378 singleton deliveries. Compared to the no-fracture group, women with a previous pelvic fracture had higher rates of cesarean sections (22.6% vs 15.9%) (AOR 1.55 CI 1.32-1.80), higher rate of preterm deliveries (6.2% vs 4.6%) (1.32 CI 1.01-1.69), and a higher rate of neonates requiring intensive care unit treatment (13.5% vs 10.0%) (AOR 1.35 CI 1.13-1.62). Vaginal delivery was the primary mode of delivery despite the higher rate of cesarean section among women with a previous fracture of the pelvis. The rate for preterm deliveries and need for neonatal intensive care was also higher, but the clinical importance of these findings is unclear. Our results suggest that vaginal delivery after fractures of the pelvic circle is generally safe for both mother and neonate.


[Separation of gamma linolenic acid from evening primrose oil with urea inclusion--orthogonal experiment of optimizing technological parameters and observation of urea inclusion compound I].
The influence on the urea inclusion compound under different conditions (allocated proportion, time of inclusion, temperature of inclusion) were studied through the orthogonal test, and theoretical reference of urea inclusion process for further optimization wound be offered. The orthogonal experiment was adopted, and microscope was used to observe the shape, aperture size of the urea inclusion compound under different technological parameters, the GC was employed to inspect the purity of GLA. The results indicated that the ratio of fatty acids and urea, inclusion of temperature, time of inclusion had great effect on urea inclusion compound. The three factors and its interactions significantly affected the purity of GLA. The results also showed that the best process was that the ratio of fatty acids and urea was 1 : 3, temperature of inclusion was--15 degrees C, time of inclusion was 24 h. Under the best condition, the purity of GLA reach up to 95.575 9%; and it is feasible to observe the shape and the amount of the urea inclusion compound to reflect and guide the urea inclusion technology.


[Tumour banks: a major stake for both patient care and research].
Tumour banks are created by pathology and haematology departments, using cell and tissue samples from patients, obtained for diagnostic purpose, and secondarily requalified for research. These banks are the most important source of human samples for research. It appears important to maintain research programs on human tissues and cells, since cell lines and animal models only partly reflect human lesions. Tumours banks are also important for patient care, since they allow patients to benefit from recent therapeutic advances. Indeed some drugs only kill some tumour cells, which can be identified from the initial tumour samples by means of specific markers. Moreover, tumours banks are the choice tool for transferring scientific discoveries to daily patients care in oncology.


Comparison of the TBARS assay and BODIPY C11 probes for assessing lipid peroxidation in red deer spermatozoa.
Several methods are used to measure lipid peroxidation (LPO) in spermatozoa. The objective of this study was comparing the thiobarbituric acid reactive species (TBARS) method and the BODIPY 581/591 C(11) (B581) and BODIPY 665/676 C(11) (B665) fluorescent probes to measure induced peroxidative damage in thawed epididymal spermatozoa from Iberian red deer. Samples from three males were thawed, pooled, diluted in PBS, incubated at room temperature and assessed at 0, 3, 6 and 24 h under different experimental conditions: Control, hydrogen peroxide (H(2)O(2) ) 0.1 mM or 1 mM, or tert-butyl hydroperoxide (TBH) 0.1 mM or 1 mM. LPO was assessed by the TBARS assay [malondialdehyde (MDA) detection] and by the fluorescence probes B581 and B665 (microplate fluorimeter and flow cytometry). Increasing MDA levels were only detectable at 1 mM of TBH or H(2)O(2). Both fluorescence probes, measured with fluorometer, detected significant increases of LPO with time in all treatments, except Control. Flow cytometry allowed for higher sensitivity, with both probes showing a significant linear relationship of increasing LPO with time for all oxidizing treatments (p < 0.001). All methods showed a good agreement, except TBARS, and flow cytometry showed the highest repeatability. Our results show that both B581 and B665 might be used for LPO analysis in Iberian red deer epididymal spermatozoa, together with fluorometry or flow cytometry. Yet, the TBARS method offered comparatively limited sensitivity, and further research must determine the source of that limitation.


Generation of diacylglycerol and ceramide during homologous complement activation.
Formation of sublytic terminal complement complexes (TCC) on nucleated cells produces transient increase in [Ca2+]i and activates protein kinase C. The present study is to evaluate whether TCC can generate endogenous signal messengers other than Ca2+ that regulate cell activities by measuring mass-levels of sn-1,2-diacylglycerol (DAG) and ceramide. As targets, lymphoblastoid human B cell lines JY25 and its mutant JY5 were used. JY5, cells deficient in glycosylphosphatidylinositol-anchored proteins with higher lytic susceptibility to human complement, are four times more efficient in forming C5b-9. When cells sensitized with limited anti-class II IgG were exposed to human serum to generate sublytic TCC, a sustained increase in DAG and ceramide was observed with a maximum 3.6-fold DAG increase over basal level in JY25 and 2.8-fold in JY5, and 6.3-fold ceramide increase in JY25 and 2.8-fold in JY5. The effect of TCC was evaluated with C7-deficient human serum (C7D) +/- C7 and also with C5b6, C7, C8, and C9 proteins. The DAG and ceramide increase by C7D + C7 over C7D control were 1.6- and 1.8-fold, respectively, in JY25, and 2.3-, and two-fold in JY5. TCC activation also induced an increased hydrolysis of sphyingomyelin and phosphatidylcholine. In addition, DAG increase by TCC was primarily achieved by C5b-7 and preincubation of cells with pertussis toxininhibited DAG increase, suggesting an involvement of a pertussis toxin-sensitive GTP-binding protein. As important signal transduction molecules, DAG and ceramide generated in response to TCC assembly, could participate in cell activation during inflammation and repair.


Effects on Gene Transcription Profile and Fatty Acid Composition by Genetic Modification of Mevalonate Diphosphate Decarboxylase MVD/Erg19 in Aspergillus Oryzae.
Mevalonate diphosphate decarboxylase MVD/Erg19 is required for ergosterol biosynthesis, growth, sporulation, and stress tolerance in Aspergillus oryzae. In this study, RNA-seq was used to analyze the gene transcription profile in AoErg19 overexpression (OE) and RNAi strains. There were 256 and 74 differentially expressed genes (DEGs) in AoErg19 OE and RNAi strains, respectively, compared with the control strain (CK). The most common DEGs were transport- and metabolism-related genes. Only 22 DEGs were obtained that were regulated in both OE and RNAi strains. The transcriptomic comparison between CK and AoErg19 overexpression strain (CK vs. OE), and between CK and AoErg19 RNAi strain (CK vs. RNAi) revealed that the greatest difference existed in the number of genes belonging to the cytochrome P450 family; 12 were found in CK vs. OE, whereas 1 was found in CK vs. RNAi. The expression patterns of lipid biosynthesis and metabolism related genes were altered in OE and RNAi strains, either by gene induction or suppression. Moreover, the total fatty acid content in the RNAi strain was 12.1% greater than the control strain, but no difference in total acid content was found between the overexpression strain and the control strain. Therefore, this study highlights the gene expression regulation within mevalonate (MVA), ergosterol biosynthesis, and fatty acid biosynthesis pathways.


Cefixime-induced oculogyric crisis.
Oculogyric crisis is a neurologic adverse event characterized by bilateral dystonic, usually upward, conjugate eye deviations. Cefixime is a third-generation cephalosporin and is widely used in clinical practice in childhood. Confusion, encephalopathy, coma, myoclonus, nonconvulsive status epilepticus, and seizures have been described with the use of cephalosporins. We presented a cefixime-induced oculogyric crisis in a 7-year-old boy during the treatment of urinary tract infection, and this is the first case of cefixime-induced oculogyric crisis whose ocular symptoms gradually disappeared within 48 hours after the drug was discontinued.


[A case of advanced gastric cancer with invasion of pancreas effectively treated by combined chemotherapy of TS-1 and paclitaxel (TXL)].
The patient was a 55-year-old woman who had unresectable advanced gastric cancer with celiac lymph node metastases and invasion of pancreas. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy consisting of TS-1 and low-dose CDDP, for a total of 3 courses of TS-1 (100 mg/day, 12 weeks) and 2 courses of low-dose CDDP (10 mg/day, 100 mg). The only side effect of this chemotherapy was light anorexia, and the patient maintained a good QOL. After chemotherapy, the tumor had decreased partially in size, but there was little change in the abdominal lymph node metastases. She was considered to have little response and underwent palliative distal gastrectomy, because of the incomplete dissection of abdominal lymph node metastases. After the operation, she was treated with 2 courses of TS-1 100 mg/day (3 weeks administration and 2 weeks rest) and CDDP 70 mg or 50 mg/body (day 8). She had grade 3 anorexia. After discharge, she was treated by combined therapy of TS-1 100 mg/day (2 weeks administration and 2 weeks rest) and TXL 60 mg/body (day 1, 8, 15). After 2 courses of TS-1/TXL therapy, the abdominal lymph node metastases had decreased in size and the tumor markers were reduced remarkably: CEA 146.1-->26.9 ng/ml, and CA19-9,351.5-->210.6 U/ml. The patient received 5 courses of TS-1/TXL therapy, and she had no trouble with side effects. She maintained a good QOL. TS-1/TXL therapy was associated with few adverse events in hospital visits, and thought to be an effective adjuvant chemotherapy against advanced gastric cancer.


Locus determining the human sperm-specific lactate dehydrogenase, LDHC, is syntenic with LDHA.
From the data presented in this report, the human LDHC gene locus is assigned to chromosome 11. Three genes determine lactate dehydrogenase (LDH) in man. LDHA and LDHB are expressed in most somatic tissues, while expression of LDHC is confined to the germinal epithelium of the testes. A human LDHC cDNA clone was used as a probe to analyze genomic DNA from rodent/human somatic cell hybrids. The pattern of bands with LDHC hybridization is easily distinguished from the pattern detected by LDHA hybridization, and the LDHC probe is specific for testis mRNA. The structural gene LDHA has been previously assigned to human chromosome 11, while LDHB maps to chromosome 12. Studies of pigeon LDH have shown tight linkage between LDHB and LDHC leading to the expectation that these genes would be syntenic in man. However, the data presented in this paper show conclusively that LDHC is syntenic with LDHA on human chromosome 11. The terminology for LDH genes LDHA, LDHB, and LDHC is equivalent to Ldh1, Ldh2, and Ldh3, respectively.


Effects of ciliary neurotrophic factor (CNTF) on protein turnover in cultured muscle cells.
The goal of the study was to evaluate the mechanism by which ciliary neurotrophic factor (CNTF) regulated protein metabolism in skeletal muscle. L8 myotubes were cultured and effects of various times and doses of CNTF on protein synthesis and degradation were evaluated. Effects of CNTF on turnover of specific pools of proteins (myofibrillar and non-myofibrillar) were also evaluated. Protein synthesis was assayed by incorporation of radioactive tyrosine into muscle proteins. Degradation was assessed by release of labelled tyrosine from pre-labelled myotubes. Effects of CNTF on protein turnover were found to be time- and dose-dependent. CNTF (1 and 10 ng/ml) increased myofibrillar protein synthesis after 12 h of exposure but had no effect on non-myofibrillar protein synthesis. Longer exposures of CNTF (24 h) reduced non-myofibrillar protein synthesis and had no effect on myofibrillar protein synthesis. High concentrations of CNTF (10 and 20 ng/ml) reduced myofibrillar protein degradation but had no effect on degradation of non-myofibrillar proteins. To evaluate the mechanism by which CNTF exerts control of protein turnover, we completed a Northern blot for CNTF receptor alpha-subunit (CNTFRalpha). This was non-detectable via conventional northern analysis. Use of RT-PCR, however, confirmed expression of CNTFRalpha, albeit at a low level compared to rat skeletal muscle. This low expression of the receptor in L8 myotubes may explain the limited effect of CNTF in vitro compared to the larger effects typically detected in vivo. CNTF regulated protein turnover through control of protein synthesis and degradation. Effects were dose and timedependent. These observations may explain ability of CNTF to exert both anabolic and catabolic actions in vivo.


Emergency presentations of head and neck cancer: a modern perspective.
Head and neck cancer emergency presentations are uncommon but persistent. However, there is little published literature on this aspect of cancer and patient demographics. This study aimed to assess the incidence, patient profile, tumour site and stage of emergency cancer presentations in our region. Retrospective review of regional cancer database over a five-year period. Emergency presentations accounted for 7 per cent of all cases. There was no difference in patient age and risk factors between the emergency and non-emergency presentations. The emergency presentation group showed a greater proportion of female patients compared to the non-emergency presentation group (30 vs 15 per cent). In all emergency presentations, the cancer was at advanced stages. Oropharyngeal cancer was the commonest emergency presentation of cancer, but the third commonest in the non-emergency group. Emergency presentations are increasing annually. Female patients and oropharyngeal cancer showed greater representation compared to male patients and laryngeal cancer.


Effect of posterior subtenon injection of 40 mg of triamcinolone acetonide on glycemic control and serum cortisol and adrenocorticotropic hormone in diabetic patients.
To evaluate the influence of posterior subtenon injection of 40 mg of triamcinolone acetonide (TA) on blood glucose, cortisol and adrenocorticotrophic hormone (ACTH) in patients with clinically significant diabetic macular oedema. This prospective clinical study included 33 type 2 diabetic patients assigned to receive subtenon injection of 40 mg of TA (study group: 20 patients, 9 women and 11 men, mean age 60.8 ± 10.1 years) or subtenon injection of 1 ml of saline solution (control group: 13 patients, 7 women and 6 men, mean age 57.9 ± 7.5 years) as an adjunct to focal/grid laser therapy. Pre-injection laboratory tests consisted of fasting blood glucose (FBG), glicolised hemoglobin (HbA1c), fructosamine, ACTH and cortisol. Post-injection measurements were performed in a following schedule: FBG in day 1; FBG, ACTH and cortisol at week 1; FBG, fructosamine, ACTH and cortisol at month 1, 2 and 3. HbA1c was also measured at 3 months. The mean ± SD values of groups at each visit were compared. The time-related changes in the parameters in each group were also analyzed using SPSS (Statistical Package for Social Sciences) for Windows 15.0 software. Pre-injection FBG, HbA1c, fructosamine, ACTH and cortisol were similar in both groups (p > 0.05 for all). Pre-injection and final HbA1c values were similar in the study (8.6% ± 1.9 and 8.7% ± 1.8, respectively) and control groups (8.6% ± 1.7 and 8.5% ± 1.8, respectively) (p > 0.05 for all). None of the patients had a decrease in plasma cortisol that decreased below normal values at either time point. There was no statistically significant difference between groups and between each visit in groups according to FBG levels, blood fructosamine, ACTH and cortisol levels (p > 0.05 for all). No adverse event was observed. Subtenon injection of 40 mg of TA does not increase blood sugar levels significantly, and it does not suppress blood cortisol or ACTH levels at 1 week or later in patients with diabetes mellitus. Subtenon injection of 40 mg TA seems to be safe in respect to elevation of blood sugar levels or systemic corticosteroid pathways.


Injury characteristics and circumstances of firearm trauma: Assessing suicide survivors and decedents.
Despite representing fewer than 5% of suicide attempts, firearms account for over half of deaths. Yet there is little clinical information regarding firearm attempts, particularly survivors. We assessed clinical factors differentiating firearm suicide survivors from decedents, firearm attempters from other methods, and firearm attempters from similarly injured trauma patients. We used clinical data from the National Trauma Data Bank (2017) to assess firearm suicide attempts using cross-sectional and case-control designs. We used logistic and multinomial regression to compare groups and assess firearm type and discharge destination. Older age, being uninsured, and injury location were associated with increased mortality among firearm attempters. Older age, White race, male sex, and being uninsured were associated with firearm attempts. Major psychiatric disorders were associated with firearm attempts and using a rifle or shotgun. Major psychiatric disorders, female sex, and smoking were associated with psychiatric discharge. Black and other race were associated with law enforcement discharge, and Black race was associated with lower odds of psychiatric discharge. Uninsured patients had lower odds of discharge to long-term care, psychiatric, or rehabilitation facilities. This study identifies factors associated with firearm suicide and includes indicators of disparities in health services for patients at high risk of suicide death.


Beam transmission characteristics of a collinear polarization rotator.
Beam transmission characteristics of a collinear prismatic polarization rotator are given. It is found that a TMoo laser beam is transmitted with good fidelity at an efficiency of 94.7%.


Individualized transscleral cyclophotocoagulation as the initial surgical intervention for medically uncontrolled glaucoma after blunt trauma.
To investigate the safety and feasibility of individualized transscleral cyclophotocoagulation (TSCPC) as the initial non-incisional surgical intervention for medically uncontrolled glaucoma after blunt trauma. The therapy records were reviewed of medically uncontrolled traumatic glaucoma after blunt trauma treated with TSCPC in a single hospital between January 2014 and December 2018. Thirty-one patients (31 eyes) received individualized TSCPC after ultrasound biomicroscopy and gonioscopy examination to localize and quantify the injured quadrants of the anterior chamber angle. In addition to the number of IOP lowing drugs, visual acuity (VA), IOP, inflammation and hemorrhage in the anterior chamber were analyzed at 1 day, 3 weeks and 3 months after operation, respectively. Success was defined as the IOP was not more than 21 mmHg. Compared with the data of pre-operation, constituent ratio of VA had no significant difference at 3 weeks (χ2 = 0.56, p > 0.75). At 3 months the average IOP was 22.2 ± 6.8 mmHg, which was significantly lower than that of pre-operation (46.6 ± 5.6 mmHg) (t = 19.818, p < 0.001). No IOP lowing drug was needed in 12 eyes, and more than three kinds of drugs were still needed in five eyes. The average number of medications decreased to 1.2 ± 1.2 (χ2 = 93.496, p < 0.001). The complete success rate was 38.7% and the relative success rate (combined with no more than two kinds of drugs) was 83.9% at 3 months. Individualized TSCPC could be applied as an initial non-incisional surgical intervention to treat traumatic glaucoma refractory to the medicine therapy.


Dysplasia in ulcerative colitis: is radiography adequate for diagnosis?
To determine to usefulness of barium enema examination in detecting dysplasia in patients with ulcerative colitis. Radiographic findings of 22 areas of dysplasia in 10 patients (seven men, three women; aged 34-81 years at diagnosis) were reviewed. Serial changes in radiographic features of four areas of dysplasia in three patients were retrospectively investigated. Fourteen of 22 areas of dysplasia were shown on radiographs. Dysplasia in the rectum or sigmoid colon was depicted less frequently than that in other segments of the colon. Radiographic features were classified as obvious nodular protrusions (seven lesions), irregular mucosa (five lesions), or nodular protrusions with irregular mucosa (two lesions). Six of the seven areas of dysplasia shown as irregular mucosa were accompanied by minute spiculations in the margin of the colonic lumen. There was no correlation between radiologic features and histologic grade of dysplasia. Barium enema examination may be used as a complementary method of cancer surveillance with endoscopy. These methods show about two-thirds of lesions associated with dysplasia.


Silencing LncRNA PVT1 Reverses High Glucose-Induced Regulation of the High Expression of PVT1 in HRMECs by Targeting miR-128-3p.
This paper aims to discuss the possibility of lncRNA PVT1 as a diagnostic biomarker for diabetic retinopathy (DR) and explore the underlying mechanism. Real-time quantitative polymerase chain reaction (RT-qPCR) was selected to determine the expression level of lncRNA PVT1 in the serum of all subjects. The receiver operating characteristic (ROC) curve reflected the diagnostic significance of PVT1 for DR patients. The Cell Counting Kit-8 (CCK-8) and Transwell assays were used to evaluate the effect of PVT1 expression on the proliferation and migration of human retinal microvascular endothelial cells (HRMECs). The luciferase reporter gene was selected to verify the interaction between PVT1 and miR-128-3p. The relative expression level of PVT1 in serum was higher in both the DB and DR group than in the healthy controls group (HC), and it was highest in the DR group. ROC curve indicated that serum PVT1 could distinguish between HC and DB patients, DB patients and DR patients, respectively. In vitro, high glucose induction significantly increased the proliferation and migration capabilities of HRMECs, but silencing PVT1 (si-PVT1) downregulated the proliferation and migration capabilities of HRMECs. The detection of luciferase reporter gene showed that lncRNA PVT1 targeted miR-128-3p, and there was a negative correlation in the serum of DR patients. In conclusion, this study confirmed that lncRNA PVT1 might regulate the process of DR by targeting miR-128-3p, and has the potential as a biomarker for the diagnosis of DR.


Volcano explosion in the eye: Expulsive choroidal haemorrhage.
This video shows the dreaded complication of expulsive suprachoroidal haemorrhage in a penetrating keratoplasty . It teaches the various measures that help in preventing and managing the challenge peri-operatively. This video is intended to sensitize the corneal surgeons about this rare complication using real-time surgical video and prepare them to face this challenge by demonstrating the preventive and mitigating strategies. A patient who was suitably taken up for an autokeratoplasty had expulsive choroidal haemorrhage in the non-seeing eye. This complication was managed using glycerin-preserved donor corneal button. Further, the video discusses various pre-operative and intra-operative optimizations to avoid such a complication and mitigate the damage caused by it, should it ever happen during a surgery. Expulsive choroidal haemorrhage can be a traumatizing event and one must be mentally prepared to manage it. Pre-operative high-risk factors should always be managed and intra-operative maneuvers performed to prevent the complication, as shown in the video. https://youtu.be/s_ImBugPELw.


Radiation oncology residents' computer workstation.
We are investigating the feasibility of using the Macintosh computer as a workstation platform for radiation oncology residents because of its ease of use, graphics capability, and low cost. Hypercard was chosen as the programming environment because it easily mixes graphics, text, and control functions in an integrated screen display. Furthermore, it results in a system that can be relatively easily extended and customized by individual users with varying degrees of computer skills. We have developed several software modules in order to test the ability of this environment to support the demands of such a workstation. Modules created thus far include various clinical physics aids and tutorials, treatment planning guides, oncology databases, and others. The software runs on all Macintosh configurations, but calculation speeds are improved when a 68020 or greater processor is used. In general, we have been pleased with the implementation thus far. Graphics display capability is good, but design and entry of graphics have proved labor-intensive. Searching is fast and text is easily entered and manipulated. Finished modules can be customized with minimal computer training, but implementing complex new functions requires familiarity with Hypercard's programming language. New modules, once developed, are easily integrated into the workstation universe, suggesting that cooperative development of the workstation by multiple contributors is realistically achievable.


Characterization of cultured tobacco cell lines resistant to ethionine, a methionine analog.
Two cultured tobacco cell lines (Nicotiana tabacum L. cv Xanthi) were selected for resistance to growth inhibition by the methionine analog ethionine. Comparison of the free amino acid pool levels in these lines with those of the ethionine-sensitive parental line showed substantial accumulation of methionine (110x), threonine (18x), and lysine (5x). In vitro enzymic analysis of lysine-sensitive aspartate kinase activity showed the resistant lines to contain 16 times that found in the sensitive line. The lysine-sensitive enzymes from both resistant and sensitive lines coeluted from DEAE-cellulose and exhibited similar K(m) values. Both showed identical lysine plus S-adenosylmethionine inhibition profiles suggesting that the elevated activity in the resistant lines is not due to a structural change in the lysine-sensitive enzyme but possibly to the level of its expression.


Evaluation of swabs, transport media, and specimen transport conditions for optimal detection of viruses by PCR.
Depletion of swabs and viral transport medium during epidemics may prompt the use of unvalidated alternatives. Swabs collected and transported dry or in saline were compared to commercially available swab/medium combinations for PCR detection of influenza, enterovirus, herpes simplex virus, and adenovirus. Each was detected at an ambient temperature (22°C) and 4°C for 7 days. Detection of influenza on dry or saline swabs is important because of its capacity to cause outbreaks involving large numbers of cases.


Anisotropic deformation of NiO nanoparticles embedded in silica under swift heavy ion irradiation.
We report on the ion-induced anisotropic deformation in nickel oxide nanoparticles prepared by conventional sol-gel technique. Colloidal-like NiO nanoparticles with an average diameter of about 40-50 nm embedded in a SiO2 layer change their shape dramatically under swift heavy ion irradiation with 32 MeV Cu+5 ions at room temperature and normal incidence. Transmission electron microscopy analysis show irradiation induced shape transformation from nearly spherical nanoparticles into oblate nanorods at a rate that increases with ion fluence. For low nanoparticle density, the apparent nanoparticle size aspect ratio increases gradually with increasing irradiation fluence to 5 × 1014 ions cm-2 while no significant volume change is observed upon irradiation. For higher density of the nanoparticles, Rutherford backscattering spectrometry analysis indicates collective growth of nanoparticles under irradiation with fluence above 5 × 1014 ions cm-2. Magnetization experiments of the NiO nanoparticles show that the film consisting the pristine NiO nanoaprticles has a small magnetic anisotropy with axis in the direction parallel to ion beam. However, after 32 MeV Cu+5 ion irradiation, the change in magnetic anisotropy is much larger, which can be correlated with the elongation of nanoparticles in the beam direction. Furthermore, a threshold fluence, under which no deformation takes place is observed.


Stability across cohorts in divorce risk factors.
Over the past quarter-century, many covariates of divorce have been identified. However, the extent to which the effects of these covariates remain constant across time is not known. In this article, I examine the stability of the effects of a wide range of divorce covariates using a pooled sample of data taken from five rounds of the National Survey of Family Growth. This sample includes consistent measures of important predictors of divorce, covers marriages formed over 35 years (1950-1984), and spans substantial historical variation in the overall risk of marital dissolution. For the most part, the effects of the major sociodemographic predictors of divorce do not vary by historical period. The one exception is race. These results suggest that the effects associated with historical period have been pervasive, simultaneously altering the risk of divorce for most marriages.


Hologram recording by a pulsed method on phase-change media.
We present a novel real-time hologram-recording method and derive a formula for calculating the diffraction efficiency of gratings recorded in phase-change media. The formula gives media parameters for high diffraction efficiency. In addition, a two-dimensional character pattern is successfully reconstructed by using a GeTe alloy film.


Comparison of the enzyme-linked immunosorbant assay III, recombinant immunoblot third generation assay, and polymerase chain reaction method in the detection of hepatitis C virus infection in haemodialysis patients.
Hepatitis C virus (HCV) serotyping assays have evolved from simple antibody screening tests to complex RNA-based qualitative and quantitative methods. The objective of this study was to compare the HCV screening results from 161 patients in long-term maintenance haemodialysis (HD) as assessed by the recently developed Enzyme Linked ImmunosorbantAssay III (ELISA III), confirmed by the Recombinant Immunoblot 3rd generation assay (RIBA 3rd) and determined by the qualitative HCV reverse transcription polymerase chain reaction (RT-PCR) method. One hundred sixty-one HD patients were tested for the presence of anti-HCV antibodies by the ELISA III and confirmed by the RIBA 3rd. HCV RNA was determined by an HCV RT-PCR method. All reported results that were designated as discrepant, anti-HCV (+) and/or HCV RNA (+) were further investigated by means of a quantitative HCV RT-PCR assay. Reported results obtained from ELISA III and qualitative RT-PCR assays were HCV positive for 16/161 patients (9,93%) and these were designated as anti-HCV (+)/HCV RNA (+). Subsequently, these 16 anti-HCV positive/161 HD patients were confirmed by the RIBA 3rd. Three individuals anti-HCV (-)/RIBA (+)/HCV RNA (-)], the viral load that was reported from the quantitative RT-PCR was less than the assay detection level (< 2,000 viral copies/ml). In view of previous observations, our findings suggest that ELISA III remains still a highly reliable and valuable assay. However, despite the cost, the combination of both ELISA III and qualitative RT-PCR allows a definitive classification on HCV diagnosis.


Low number of functionally active B lymphocytes in the peripheral blood of HIV-1-seropositive individuals with low p24-specific serum antibody titers.
The in vitro synthesis of HIV-1, p24-, reverse transcriptase (RT)- and gp120-specific immunoglobulin (Ig) G by unstimulated peripheral blood mononuclear cells (PBMC) from 38 asymptomatic and 10 symptomatic HIV-1-seropositive individuals was analysed. In the majority of these individuals, spontaneous production of HIV-1- and gp120-specific IgG from PBMC cultures was demonstrated. In addition, in the majority of the PBMC cultures from individuals with high serum antibody titers to p24, spontaneous production of p24-specific IgG was shown. In contrast, no p24-specific IgG production was detected in PBMC cultures from seropositive individuals with low or no serum antibody titers to p24. A similar relationship between low or absent RT-specific serum antibody titers and the absence of in vitro RT-specific IgG synthesis was not demonstrated. Furthermore, it was shown that the number of p24-specific B lymphocytes in circulation, as calculated by a spot enzyme-linked immunosorbent assay, were significantly lower in individuals with low serum antibody titers to p24. These results suggest that the decline in p24-specific serum antibodies observed during progression towards AIDS is not merely a reflection of the clearance via immune complexes, but may also be attributable, at least in part, to a reduction of p24-specific antibody-producing active B lymphocytes.


Is the Mayo model for predicting survival useful after the introduction of ursodeoxycholic acid treatment for primary biliary cirrhosis?
Treatment of patients with primary biliary cirrhosis (PBC) using ursodeoxycholic acid (UDCA) leads to a reduction in serum bilirubin. The first objective of this study was to assess the performance of certain prognostic indicators for PBC after the introduction of treatment with UDCA. Serum bilirubin is an important prognostic indicator for PBC and an important component of the Mayo model for grading patients into risk categories. In an analysis of patients enrolled in the Canadian multicenter trial, the Mayo score was calculated before and after treatment with UDCA. After treatment, the Mayo score continued to divide patients with PBC into groups with varying risk. In addition, the serum bilirubin alone was shown to do the same even after the introduction of treatment with UDCA. A second objective was to establish whether UDCA had an effect on long-term (2- to 6-year) survival in patients with PBC.


[Changes of edema associated with I-125 prostate brachytherapy].
We have been performing TRUS-guided transperineal prostate brachytherapy with I-125 for prostate-confined adenocarcinoma since October 2003. We examined prostate volume using CT scanning on Day 1, Day 15, and Day 30 in the initial 15 patients, and investigated time-dependent changes of edema associated with I-125 prostate brachytherapy. Prostate volume had increased to 173% of the average on the first day after implantation. Improvements in the swelling of the prostate showed decreases in 30% in the first 2 weeks (Days 1-15) and 12% in the second 2 weeks (Days 15-30). V100 and D 90% showed statistically significant increases of 5.5% and 8.4% in the first 2 weeks after implantation and 2.3% and 5.2% in the second 2 weeks (Days 15-30). We considered one month a suitable time at which to calculate post-planning because V100 and D 90% changed little statistically.


Effect of Pain Education and Exercise on Pain and Function in Chronic Achilles Tendinopathy: Protocol for a Double-Blind, Placebo-Controlled Randomized Trial.
Achilles tendinopathy (AT) rehabilitation traditionally includes progressive tendon loading exercises. Recent evidence suggests a biopsychosocial approach that incorporates patient education on psychosocial factors and mechanisms of pain can reduce pain and disability in individuals with chronic pain. This is yet to be examined in individuals with AT. This study aims to compare the effects on movement-evoked pain and self-reported function of pain education as part of a biopsychosocial approach with pathoanatomical education for people with AT when combined with a progressive tendon loading exercise program. A single-site, randomized, double-blind, placebo-controlled clinical trial will be conducted in a university-based hospital in a laboratory setting and/or by telehealth. A total of 66 participants with chronic (>3 months) midportion or insertional AT will be randomized for the Tendinopathy Education of the Achilles (TEAch) study. All participants will complete progressive Achilles tendon loading exercises over 12 weeks and will be encouraged to continue with self-selected exercises as tolerated. All participants will complete 6-7 one-to-one sessions with a physical therapist to progress exercises in a standardized manner over 8 weeks. During the last 4 weeks of the intervention, participants will be encouraged to maintain their home exercise program. Participants will be randomized to 1 of 2 types of education (pain education or pathoanatomic), in addition to exercise. Pain education will focus on the biological and psychological mechanisms of pain within a biopsychosocial framing of AT. Pathoanatomic education will focus on biological processes within a more traditional biomedical framework of AT. Evaluation sessions will be completed at baseline and 8-week follow-up, and self-reported outcome measures will be completed at the 12-week follow-up. Both groups will complete progressive Achilles loading exercises in 4 phases throughout the 12 weeks and will be encouraged to continue with self-selected exercises as tolerated. Primary outcomes are movement-evoked pain during heel raises and self-reported function (patient-reported outcome measure information system-Physical Function). Secondary outcomes assess central nervous system nociceptive processing, psychological factors, motor function, and feasibility. Institutional review board approval was obtained on April 15, 2019, and study funding began in July 2019. As of March 2020, we randomized 23 out of 66 participants. In September 2020, we screened 267 individuals, consented 68 participants, and randomized 51 participants. We anticipate completing the primary data analysis by March 2022. The TEAch study will evaluate the utility of pain education for those with AT and the effects of improved patient knowledge on pain, physical function, and clinical outcomes. DERR1-10.2196/19111.


Development of Nitrogen Assimilation Enzymes during Photoautotrophic Growth of Chenopodium rubrum Suspension Cultures.
Chenopodium rubrum cells were grown in suspension as a photoautotrophic culture with a 16 hour day. Cell growth had three phases: a 3-day lag, a 3-week logarithmic phase, and a 10-day stationary phase. Chlorophyll content increased steadily during log phase and reached a level of 0.5 to 0.6 mg Chl g(-1) fresh weight. Soluble protein of the cells increased more rapidly from day 4 to day 12 than during midlog phase. Initially, ammonium was taken up in preference to nitrate. However, during the second two weeks of growth, ammonium and nitrate were taken up simultaneously; this period of growth was the time of highest rates of N uptake by the cultured cells. Glutamine synthetase had a high specific activity (17 mumol.hour(-1) mg(-1) protein) in day 1 cells, and this level was sustained until midlog phase when it increased by 20%. Methyl viologen-dependent glutamate synthase specific activity increased rapidly in lag phase cells (day 4 = 10 mumol.hour(-1) mg(-1) protein), but decreased by day 9 to about 50% of the peak and remained constant. NADH:nitrate reductase specific activity increased rapidly in lag phase cells and reached a plateau that lasted from day 4 to 14 (1 mumol.hour(-1) mg(-1) protein). Methyl viologen-dependent nitrite reductase specific activity was high when assayed on day 5 and increased to a maximum on day 15 to 16 (12 mumol.hour(-1) mg(-1) protein). NADPH- and NADH-dependent glutamate dehydrogenase specific activities remained rather constant throughout the growth cycle. The cells appeared to have developed photosynthetic competence and to have leaf-like activities of nitrogen assimilation enzymes.


Effects of Let-7c on the processing of hepatitis B virus associated liver diseases.
The most common type of cancer of the digestive system is hepatocellular carcinoma. In China, many patients harbour HBV. The lin28B/Let-7c/MYC axis is associated with the occurrence of many cancers. Therefore, we aimed to illuminate the function of the lin28B/Let-7c/MYC axis in hepatocellular carcinoma. We aimed to evaluate the critical involvement of lin28B and Let-7c in the carcinogenesis of human hepatocellular carcinoma (B-HCC). Data from the GEO database were used to analyse differentially expressed genes and IRGs. A protein - protein interaction (PPI) network and Venn diagram were generated to analyse relationships. Real-time RT-PCR, Western blotting, and cell counting kit-8 assays were used to examine the association of lin28B, Let-7c, and MYC with cell proliferation. A total of 2552 functionally annotated differentially expressed RNAs were analysed in HBV patients from the GSE135860 database. In addition, 46 let-7c target genes were screened in HBV patients, and the interactions were analysed through PPI network analysis. The results confirmed that Let-7c and its target genes play a key role in HBV-related diseases. Next, we discovered a gradual decrease in Let-7c expression during the progression from HBV-associated chronic hepatitis (B-CH) and HBV-associated liver cirrhosis (B-LC) to B-HCC. We found evidence for a negative association between lin28B expression and Let-7c expression. The expression of MYC was obviously upregulated when Let-7c was inhibited. Our results highlight that Let-7c and lin28B participate in the carcinogenesis of HBV-associated diseases through the lin28B/Let-7c/MYC axis.


Photodermatitis from ketoprofen with cross-reactivity to fenofibrate and benzophenones.
The aim of this study was to evaluate the possibility of cross-reactivity between ketoprofen, fenofibrate and benzophenones because of their structural similarities. Seven patients presenting photodermatitis from ketoprofen underwent patch and photopatch tests. Ketoprofen, fenofibrate, benzophenone 3, benzophenone 10, benzophenone 4, personal medications and topical creams were tested. All patients had positive patch or photopatch tests to ketoprofen and fenofibrate, four patients had positive UVA photopatch tests to benzophenone 3, and two to benzophenone 10. Patients presenting photosensitization to ketoprofen may also have cross-reactivity to fenofibrate and some benzophenones.


Chemical modification of ovatodiolide revealed a promising amino-prodrug with improved pharmacokinetic profile.
Stepwise modification of ovatodiolide revealed a prodrug, NMP-diepoxyovatodiolide, which can provide sustained release of an active compound, substantial metabolic stability and a unique accumulation profile in the liver. Besides, NMP-diepoxyovatodiolide demonstrated therapeutic benefits in an acute autoimmune hepatitis mouse model and a broad safety window. Therefore, NMP-diepoxyovatodiolide is a very promising candidate for further development of liver-related drugs.


Prelicensure Simulation-Enhanced Interprofessional Education: A Critical Review of the Research Literature.
This review explores the state of prelicensure interprofessional education (IPE) using simulation-based education (SBE) by examining studies that use SBE for prelicensure IPE through a critical review of the research literature. We focus particularly on studies that included experiential SBE with reported measures and formal IPE with prelicensure participants from at least 2 health care professions. Fifty-four studies met criteria. We explore these studies, providing a compilation of information (e.g., educational, simulation, and research methods used; outcome measures reported; and demographics of learner groups), identifying themes that may affect learning, as well as surfacing challenges and gaps in the field. The quality and rigor of the existing literature is inadequate to confidently determine factors that affect learning through simulation-enhanced IPE. We suggest that more rigorous research criteria be included in future studies and a list of reporting items be provided, where future publications can enhance knowledge to guide best practice in simulation-enhanced IPE.


Effectiveness of a new cervical pillow on pain and sleep quality in recreational athletes with chronic mechanical neck pain: a preliminary comparative study.
The aim of this intervention study was to determine the effects of a new experimental cervical pillow, on symptomatic adults affected by chronic mechanical neck pain. Twelve recreational athletes of both sexes (mean age 40.5 years; range 35-55), affected by grade II chronic mechanical neck pain, were evaluated with a daily diary type of self-report questionnaire, which incorporated an 11-point Numerical Rating Pain Scale, to collect the primary outcome measures of pre- and post-sleep neck pain and with the Neck Pain Disability Scale. Tympanic temperature, heart rate (HR) variability continuous monitoring during sleep, overnight pillow comfort and sleep quality were assessed. Average weekly scores in overall questionnaires, tympanic temperature and the HR low frequency (LF) / high frequency (HF) ratio were significantly lower (P<0.05) after the use of the DM2 pillow than the own pillow. The 80% of participants considered the DM2 "perfectly comfortable" and reported a "good" quality of sleep lying over it. The use of an appropriate pillow is a determinant factor in relieving neck pain, improving LF/HF ratio and enhancing-vagal activity, promoting deeper stages during the sleep. The shape of this pillow maintains an appropriate cervical curvature, reduces intra-disc pressure allowing a better distribution of loads between cervical discs. The round shaped portion of the pillow, facilitates breathing and avoids the narrowing of the airway due to the incorrect position during the sleep. The peculiar material of the DM2 pillow, contributed to lower brain temperature promoting dry heat loss from the head to the pillow, reducing sweating.


Bi-allelic LETM1 variants perturb mitochondrial ion homeostasis leading to a clinical spectrum with predominant nervous system involvement.
Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) encodes an inner mitochondrial membrane protein with an osmoregulatory function controlling mitochondrial volume and ion homeostasis. The putative association of LETM1 with a human disease was initially suggested in Wolf-Hirschhorn syndrome, a disorder that results from de novo monoallelic deletion of chromosome 4p16.3, a region encompassing LETM1. Utilizing exome sequencing and international gene-matching efforts, we have identified 18 affected individuals from 11 unrelated families harboring ultra-rare bi-allelic missense and loss-of-function LETM1 variants and clinical presentations highly suggestive of mitochondrial disease. These manifested as a spectrum of predominantly infantile-onset (14/18, 78%) and variably progressive neurological, metabolic, and dysmorphic symptoms, plus multiple organ dysfunction associated with neurodegeneration. The common features included respiratory chain complex deficiencies (100%), global developmental delay (94%), optic atrophy (83%), sensorineural hearing loss (78%), and cerebellar ataxia (78%) followed by epilepsy (67%), spasticity (53%), and myopathy (50%). Other features included bilateral cataracts (42%), cardiomyopathy (36%), and diabetes (27%). To better understand the pathogenic mechanism of the identified LETM1 variants, we performed biochemical and morphological studies on mitochondrial K+/H+ exchange activity, proteins, and shape in proband-derived fibroblasts and muscles and in Saccharomyces cerevisiae, which is an important model organism for mitochondrial osmotic regulation. Our results demonstrate that bi-allelic LETM1 variants are associated with defective mitochondrial K+ efflux, swollen mitochondrial matrix structures, and loss of important mitochondrial oxidative phosphorylation protein components, thus highlighting the implication of perturbed mitochondrial osmoregulation caused by LETM1 variants in neurological and mitochondrial pathologies.


Agarose as crystallisation media for proteins II: trapping of gel fibres into the crystals.
The crystallisation pressure exerted by protein crystals growing in agarose gel does not disrupt the gel network. However, protein crystals trap agarose fibres when they grow in agarose gels. The fibres of agarose are distributed randomly in the crystals explaining why they do not appreciably affect the diffraction quality of the crystal


Innovative Ingredients and Emerging Technologies for Controlling Ice Recrystallization, Texture, and Structure Stability in Frozen Dairy Desserts: A Review.
Over the past decade, ice cream manufacturers have developed a strong understanding of the functionality of key ingredients and processing, developing effective explanations for the link between structure forming agents, stability mechanisms, and perceived quality. Increasing demand for products perceived as healthier/more natural with minimal processing has identified a number of new tools to improve quality and storage stability of frozen dairy desserts. Ingredients such as dietary fiber, polysaccharides, prebiotics, alternate sweeteners, fat sources rich in unsaturated fatty acids and ice strucsturing proteins (ISP) have been successfully applied as cryoprotective, texturizing, and structuring agents. Emerging minimal processing technologies including hydrostatic pressure processing, ultrasonic or high pressure assisted freezing, low temperature extrusion and enzymatically induced biopolymers crosslinking have been evaluated for their ability to improve colloidal stability, texture and sensory quality. It is therefore timely for a comprehensive review.


Unexpected enantioseparation of mandelic acids and their derivatives on 1,2,3-triazolo-linked quinine tert-butyl carbamate anion exchange-type chiral stationary phase.
Replacement of the flexible thioether linker for the novel, rigid 1,2,3-triazole spacer group in the course of immobilization of quinine tert-butyl carbamate onto a silica surface led to a chiral stationary phase (CSP) with enhanced enantioselectivity for the resolution of mandelic acid and derivatives thereof. These new CSPs allowed efficient resolution of a wide set of mandelic acids with α-values between 1.08 and 1.68. The high loadability of these chiral ion exchange type CSPs allows preparative separation in the milligram range on an analytical column of 100×4 mm id in a single run as it was demonstrated for 4-trifluoromethylmandelic, 2-naphthylglycolic and 3,4-methylenedioxymandelic acids. The chiral recognition process has been studied using a library of 25 diverse racemic probes. A tentative model suggests that the rigid 1,2,3-triazole group takes part in the formation of an enantioselective-binding pocket of the entire and immobilized selector moiety of the CSP. The primary interaction site is given by the ionizable quinuclidine group of the Cinchona alkaloid supported by possible π-π stabilization effects within the selector-selectand complex.


Video-EEG monitoring differences in children with frontal and temporal onset seizures.
The objective of this study was to explore the clinical manifestations and electroencephalogram (EEG) features in children with frontal and temporal onset seizures. The method used was video-EEG monitoring that was conducted for 24 h in children with seizure disorders. The results were as follows: There were fewer children with temporal EEG onset seizure (TOS) than with frontal EEG onset seizure (FOS) (p = 0.132). Within the TOS category, PTOS was most frequent, and ATOS was rare (p = 0.001). The mean duration of ATOS was longer than that of TOS and PTOS (p < 0.05). There were no significant differences in seizure frequency and nocturnal attacks between children with TOS and children with FOS. Furthermore, we observed the interictal EEG from three aspects: the background, the location of discharges, and the time of discharges. The frequency of the multi-focal and bilateral discharges of FOS was higher than that of TOS (p < 0.01). The FOS discharged easily and quickly spread to the bilateral hemisphere and formed secondary bilateral synchrony. Focal discharges predominated in TOS, and rarely showed the paroxysm of bilateral synchronous rhythm. Bursts of fast rhythms predominated in the onset of TOS. In contrast, there were a variety of ictal EEG in FOS. Finally, it was concluded that in the group of children studied, the clinical and EEG characteristics of TOS were different from those of FOS.


Cross Talk between Mitochondria and Other Targets in Alzheimer's Disease.
Among the neurodegenerative diseases, Alzheimer's disease (AD) is a predominant public health issue, affecting 16 million people around the world. It is clinically manifested by the presence of amyloid plaques (Aβ) and neurofibrillary tangles (NFT) within the brain. Due to intraneuronal processing, Aβ interacts with cellular targets such as mitochondria, ER, and Golgi apparatus and hampers their normal functions. Alteration in the mitochondrial function, closely related to the production of reactive oxygen species (ROS), Ca+2 overload, and apoptosis in the brain, is one of the key pathological events studied in AD pathogenesis. It is also an important pivot for the intracellular interaction with ER and Golgi through signal transduction and membrane contact to regulate cell survival and death mechanism. Alteration in mitochondrial function is intimately connected with abnormal ER or Golgi function. Stimuli that enhance perturbation in the normal ER or Golgi organelles function can involve mitochondria mediated apoptotic cell death. In this review, we address the importance of the mitochondria and their cross talk with ER and Golgi in AD pathogenesis and animal models with a therapeutic strategy to improve the mitochondrial functions.


Noggin induces human bone marrow-derived mesenchymal stem cells to differentiate into neural and photoreceptor cells.
The present study was undertaken to explore the effect of noggin on neuronal differentiating potential of human bone marrow-derived mesenchymal stem cells (hBMMSCs) in vitro so as to provide a means of alleviate retinal degeneration. A green fluorescent protein-tagged noggin gene was transferred into adult hBMMSCs or induce hBMMSCs with classical inducer, epidermal growth factor(EGF). Neurons were observed as early as 48 h after transduction of hBMMSCs with a noggin adenoviral vector. Differentiation peaked by 10 days in culture, and these differentiated cells expressed multiple markers including rhodopsin (18.4 +/- 1.5% of cells), chx10 (4.8 +/- 0.6%), nestin (4.2 +/- 0.8%), and Nrl (3.7 +/- 0.4%), as verified by immunofluorescence staining. Noggin-transduced cells produced more photoreceptor cells than non-transduced cells, suggesting that noggin has the ability to induce hBMMSCs to trans-differentiate into photoreceptor cells. In contrast, induction with EGF for 10 days led to lower levels of rhodopsin and chx10, and undetectable levels of Nrl and Nestin. These findings suggested noggin-transduced hBMMSCs produced more photoreceptor cells than EGF-induced cells. It is suggested that the present protocol has application in cell replacement therapy for patients suffering from photoreceptor cell loss.


EGF induces epithelial-mesenchymal transition through phospho-Smad2/3-Snail signaling pathway in breast cancer cells.
Epithelial-mesenchymal transition (EMT) can contribute to tumor invasion, metastasis, and resistance to chemotherapy or hormone therapy. EMT may be induced by a variety of growth factors, such as epidermal growth factor (EGF). Most studies regarding EMT have focused on TGF-β-Smads signaling. The mechanism of EGF-induced EMT via activation of the Smad2/3 in breast cancer cells, MCF-7 and MDA-MB-231, remains unclear. The expression levels of Snail, vimentin, and fibronectin were increased by EGF treatment in a time-dependent manner, while the expression level of E-cadherin was decreased. EGF-induced nuclear co-localization of phospho-Smad2/3 and Snail and cancer cell migration were inhibited by pretreatment with an ERK1/2 inhibitor, PD98059 and a phospho-Smad2 inhibitor, SB203580. Knockdown of Smad2/3 expression suppressed EGF-induced expressions of Snail, vimentin, fibronectin, and cancer cell invasion, suggesting an acquisition of the mesenchymal and migratory phenotype in less aggressive MCF-7 cells. Moreover, MDA-MB-231 cells were shown that EGF-induced EMT, and cell invasion through ERK1/2-phospho-Smad2/3-Snail signaling pathway. We have discovered that EGF-stimulated activation of Smad2/3 upregulated several key EMT markers, inhibited E-cadherin expression, promoted EMT, enhanced migration and invasion in MCF-7 and MDA-MB-231 breast cancer cells. Identification of this molecular mechanism may provide new molecular targets for the development of therapies for metastatic breast cancer.


Electrons transfer determined greenhouse gas emissions in enhanced nitrogen-removal constructed wetlands with different carbon sources and carbon-to-nitrogen ratios.
A constructed wetland (CW) was established to explore the influence of carbon addition (glucose or sodium acetate) on nitrogen removal and greenhouse gas (GHG) emissions at chemical oxygen demand to nitrogen ratios (COD/Ns) of 0, 4, 7. Results showed that the type of carbon source and COD/N significantly influenced the CW performance, in which the electrons transfer determined the regulation of denitrification, methanogenesis and respiration. Higher N2O emissions were consistent with higher nitrite accumulation at low COD/N because of electrons competition. The residual carbon source after near-complete denitrification could be further utilized by methanogenesis. Sodium acetate was superior to glucose in promoting denitrification and reducing global warming potential (GWP). In addition, bacteria sequencing and functional genes confirmed the important role of the type of carbon source on controlling nitrogen removal, carbon consumption and GHG emissions in microbial communities.


Incident-to Billing for Pharmacists.
The inclusion of pharmacists on care teams has been shown to improve clinical and economic health outcomes. However, a significant barrier to the widespread incorporation of pharmacists into care teams is the ability to financially support the salary of the pharmacist. A mechanism to improve the ability of pharmacists to generate clinical revenue already exists in the form of incident-to billing, although there remains considerable uncertainty regarding the criteria for incident-to billing and specifically how pharmacists can use this model to capture revenue for clinical services. In this article, we discuss incident-to billing criteria as it pertains to outpatient clinics, common misconceptions related to incident-to billing, and how clinical pharmacists may use this mechanism to generate revenue for the clinical services they provide. DISCLOSURES: This work was not supported by any funding source. The authors have no relevant conflicts of interest to disclose.


The piglet can be used to study the effects of parenteral and enteral nutrition on body composition.
Measurement of body composition provides insight into the regulation of normal development as well as the interactions among nutritional, physiological, and biochemical functions. Studies of body composition require an animal model in which body composition at birth and postnatal changes are comparable to those in human infants. Essential to studies of body composition is an animal model that can be fed under various conditions (parenteral and enteral) and can undergo various measurements (whole body and cellular level). The piglet meets these requirements. The postnatal changes in the body composition of infants and piglets are reviewed, and various studies are discussed to show the effect of parenteral and enteral nutrition on piglet body composition. Confirmation of physiological and biochemical similarities in the regulation of body composition in human infants and piglets awaits further study.


A poly(D,L-lactide) resin for the preparation of tissue engineering scaffolds by stereolithography.
Porous polylactide constructs were prepared by stereolithography, for the first time without the use of reactive diluents. Star-shaped poly(D,L-lactide) oligomers with 2, 3 and 6 arms were synthesised, end-functionalised with methacryloyl chloride and photo-crosslinked in the presence of ethyl lactate as a non-reactive diluent. The molecular weights of the arms of the macromers were 0.2, 0.6, 1.1 and 5 kg/mol, allowing variation of the crosslink density of the resulting networks. Networks prepared from macromers of which the molecular weight per arm was 0.6 kg/mol or higher had good mechanical properties, similar to linear high-molecular weight poly(D,L-lactide). A resin based on a 2-armed poly(D,L-lactide) macromer with a molecular weight of 0.6 kg/mol per arm (75 wt%), ethyl lactate (19 wt%), photo-initiator (6 wt%), inhibitor and dye was prepared. Using this resin, films and computer-designed porous constructs were accurately fabricated by stereolithography. Pre-osteoblasts showed good adherence to these photo-crosslinked networks. The proliferation rate on these materials was comparable to that on high-molecular weight poly(D,L-lactide) and tissue culture polystyrene.


DNA Antenna Tile-Associated Deoxyribozyme Sensor with Improved Sensitivity.
Some natural enzymes increase the rate of diffusion-limited reactions by facilitating substrate flow to their active sites. Inspired by this natural phenomenon, we developed a strategy for efficient substrate delivery to a deoxyribozyme (DZ) catalytic sensor. This resulted in a three- to fourfold increase in sensitivity and up to a ninefold improvement in the detection limit. The reported strategy can be used to enhance catalytic efficiency of diffusion-limited enzymes and to improve sensitivity of enzyme-based biosensors.


Tracheobronchitis as an extraintestinal manifestation of ulcerative colitis.
Respiratory involvement is a rare extraintestinal manifestation of ulcerative colitis (UC). It commonly presents as bronchiectasis and rarely as tracheobronchitis. It can occur before or after the presentation of gastrointestinal symptoms. Only rarely does it occur after the patient undergoes colectomy. Diagnosis should be considered in any patient with UC who presents with unexplained upper respiratory symptoms and a negative work up for infectious aetiologies. It responds well to immunosuppressive therapy. We present a case of a 21-year-old woman who underwent colectomy for ulcerative colitis and later presented with new onset severe reversible inflammation of the upper respiratory tract.


Adult height in women with early-treated congenital adrenal hyperplasia (21-hydroxylase type): relation to body mass index in earlier childhood.
To investigate if obesity, as judged by increased body mass index (BMI), during childhood is associated with impaired adult stature in patients with 21-hydroxylase-type congenital adrenal hyperplasia (CAH), a retrospective analysis was carried out on outpatient records of 30 girls with CAH who had reached adult height. Height SD score for age (HtSDS(ca)), HtSDS for bone age (HtSDS(ba)), BMI and steroid dosage in early childhood (3.2-4.6 years) and later childhood (7.2-9.1 years), were compared with adult HtSDS (HtSDS(adlt)), adult HtSDS less mid-parental HtSDS (HtSDS(adlt)-HtSDS(mp)), predicted adult height SDS (HtSDS(pdct)), adult height SDS less predicted adult HtSDS (HtSDS(adlt)-HtSDS(pdct)) and age at menarche. Mean (SD) for HtSDS(adlt) was -1.13 (1.05), mean HtSDS(pdct) -0.12 (0.9) and mean age at menarche 13.5 (1.9) years. BMI in childhood was not correlated with HtSDS(adlt) but showed negative correlations with HtSDS(adlt)-HtSDS(mp) (r = -0.43; p < 0.02) and HtSDS(adlt)-HtSDS(pdct) (r-0.45; p < 0.02). BMI in later childhood showed negative correlations with HtSDS(adlt)-HtSDS(pdct) (r = -0.61; p < 0.001) and age at menarche (r = -0.63; p < 0.001). We conclude that in girls with early-treated CAH, a high BMI during early childhood is associated with loss of genetic height potential, and in later childhood with over-prediction of adult height and early menarche.


Leading tip drives soma translocation via forward F-actin flow during neuronal migration.
Neuronal migration involves coordinated extension of the leading process and translocation of the soma, but the relative contribution of different subcellular regions, including the leading process and cell rear, in driving soma translocation remains unclear. By local manipulation of cytoskeletal components in restricted regions of cultured neurons, we examined the molecular machinery underlying the generation of traction force for soma translocation during neuronal migration. In actively migrating cerebellar granule cells in culture, a growth cone (GC)-like structure at the leading tip exhibits high dynamics, and severing the tip or disrupting its dynamics suppressed soma translocation within minutes. Soma translocation was also suppressed by local disruption of F-actin along the leading process but not at the soma, whereas disrupting microtubules along the leading process or at the soma accelerated soma translocation. Fluorescent speckle microscopy using GFP-alpha-actinin showed that a forward F-actin flow along the leading process correlated with and was required for soma translocation, and such F-actin flow depended on myosin II activity. In migrating neurons, myosin II activity was high at the leading tip but low at the soma, and increasing or decreasing this front-to-rear difference accelerated or impeded soma advance. Thus, the tip of the leading process actively pulls the soma forward during neuronal migration through a myosin II-dependent forward F-actin flow along the leading process.


Release of soluble tumor necrosis factor receptor 1 from corneal epithelium by TNF-alpha-converting enzyme-dependent ectodomain shedding.
An involvement of tumor necrosis factor-alpha-converting enzyme (TACE)-dependent ectodomain shedding in the release of soluble tumor necrosis factor receptor 1 (sTNFR1) from corneal epithelium was evaluated. In vitro experiments were performed using the human SV40-transformed human corneal epithelial cell (HCEC) line. Ectodomain shedding was stimulated by phorbol myristate acetate (PMA, 3 microM) or peptidoglycan (PGN, 100 microg/mL), with or without TACE inhibition, using TNF-alpha processing inhibitor-1 (TAPI-1, 250 microg/mL) or tissue inhibitor of metalloproteinase-3 (TIMP-3, 2 microg/mL) by addition to the HCEC culture medium. The concentrations of sTNFR1 in culture medium were analyzed by enzyme-linked immunosorbent assay. To induce an inflammatory response in the ocular surface, corneal alkali burn of BALB/c mice was made from a filter paper dipped in 1 N NaOH solution. TNFR1 expression in corneal and conjunctival epithelia was evaluated by immunohistochemistry 28 days after wounding. In HCEC culture medium, sTNFR1 release was significantly increased by the addition of PMA (t-test, P < 0.01) or PGN (P < 0.01). The increased release of sTNFR1 was significantly inhibited by the addition of TAPI-1 or TIMP-3, indicating the possibility of TACE-dependent ectodomain shedding of TNFR1. In the corneal alkali burn model, TNFR1 was expressed in corneal and conjunctival epithelia. TACE-dependent ectodomain shedding of sTNFR1 was recognized in corneal epithelium. In the inflamed ocular surface, TNFR1 was expressed in the corneal and conjunctival epithelia after alkali burn treatment. sTNFR1, released from the ocular surface, may play an anti-inflammatory role in the inflammatory condition.


Analysis of barriers and facilitators to early hearing detection and intervention in KwaZulu-Natal, South Africa.
There is slow progress in early hearing detection and intervention (EHDI) services within South Africa. Audiologists are EHDI gatekeepers and can provide valuable insights into the barriers and facilitators that can progressively move EHDI towards best practice in South Africa. The study aimed to determine the barriers and facilitators to EHDI in KwaZulu-Natal as reported by audiologists/speech therapists and audiologists (A/STAs). A descriptive qualitative approach was used. Telephonic interviews were conducted with 12 A/STAs working in public and private healthcare facilities, using the strengths, weaknesses, opportunities, threats (SWOT) conceptual framework. Data was analysed using thematic analysis in conjunction with NVivo software. One of the main barriers perceived by A/STAs, affecting EHDI was the lack of resources in healthcare facilities. The participants indicated that although there was a guideline in place to guide practice, it may be more suited to an urban area versus a rural area. Poor knowledge and awareness of EHDI was also identified as a barrier. Information provided from A/STAs at grassroots level, in the various provinces, may benefit in developing a more contextually relevant and practical guideline. Facilitators included; development of task teams specifically for EHDI programmes, creation of improved communication networks for collaboration and communication, training of healthcare professionals and improving data management systems. Strategies such as an increase in resources, further education and training, development of contextually relevant, culturally, and linguistically diverse practices and protocols need to be in place to improve EHDI implementation. Further research, clinical implications and limitations are provided emanating from the study.


Diagnosis of Upper Quadrant Lymphedema Secondary to Cancer: Clinical Practice Guideline From the Oncology Section of the American Physical Therapy Association.
The Oncology Section of the American Physical Therapy Association (APTA) developed a clinical practice guideline to aid the clinician in diagnosing secondary upper quadrant cancer-related lymphedema. Following a systematic review of published studies and a structured appraisal process, recommendations were written to guide the physical therapist and other health care clinicians in the diagnostic process. Overall clinical practice recommendations were formulated based on the evidence for each diagnostic method and were assigned a grade based on the strength of the evidence for different patient presentations and clinical utility. In an effort to maximize clinical applicability, recommendations were based on the characteristics as to the location and stage of a patient's upper quadrant lymphedema.


Surface disinfection by exposure to germicidal UV light.
The present study was aimed to design a simple model to check efficacy of germicidal UV tube, to standardise the position, distance and time for UV light and also to find out its efficacy against medically important bacteria, the bacterial spores and fungi. The microbial cultures tested included gram positive and gram negative bacteria, bacterial spores and fungal spores. The microbes streaked on solid media were exposed to UV light. The inactivation of the order of four logs was observed for bacteria. UV light can have efficient inactivation of bacteria up to a distance of eight feet on either side and exposure time of 30 minutes is adequate.


Modifications of Sulfhydryl Groups on Phytochrome and Their Influence on Physicochemical Differences between the Red- and Far-Red-Absorbing Forms.
Phytochrome extracted from shoots of dark-grown rye (Secale cereale cv Rymin) and oat (Avena sativa cv Garry) as the far-red-form (Pfr) and/or under conditions conducive to oxidation exhibited a blue shift in the visible absorption maximum of its red-light-absorbing form (Pr) relative to that measured in vivo. This spectral alteration could not be reversed but could be prevented by inclusion of 10 millimolar diethyldithiocarbamate and 140 millimolar 2-mercaptoethanol in homogenization buffers. Similar blue shifts were induced in purified rye phytochrome by addition of the sulfhydryl-modifying reagent, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). In spectrally normal phytochrome (i.e., no detectable blue shift), Pfr had three to four more sulfhydryls available for rapid reaction with DTNB than did Pr. This difference was maintained over a 2.5-hour time course. Phytochrome purified under conditions resulting in a blue-shifted Pr absorption maximum exhibited a decreased short-term reactivity of Pfr to DTNB. Comparison of the binding and elution of altered and unaltered phytochrome from agarose-immobilized Cibacron blue 3GA confirmed that the Pfr form of spectrally normal phytochrome had a greater affinity for the dye than did the Pr form but that spectral alteration of phytochrome was accompanied by a loss of this difference as evidenced by an increased binding of Pr to the dye. It was concluded that phytochrome has highly reactive sulfhydryl residues located on the portion of the protein that undergoes conformational changes on interconversion of Pr and Pfr and that these residues require rigorous protection in order to extract the native form of the protein from plant tissue.


Sarcomas in north west England: I. Histopathological peer review.
A total of 468 cases of bone, soft tissue and visceral sarcomas (and certain other tumours) diagnosed during the years 1982-84 in North West England were entered in a study of histopathological peer review, incidence and survival. This paper describes the effects of peer review. Material was reviewed by a panel of five pathologists for 413 of the 450 cases originally registered as sarcomas with the Regional Cancer Registry. The diagnosis of sarcomas was confirmed in 76% cases and and there was agreement on sub-type for 53% cases. Measures of agreement were lowest for the two sub-types most commonly diagnosed i.e. malignant fibrous histiocytoma and leiomyosarcoma. Degree of agreement between individual pathologists and final panel diagnosis was also very variable but never less than 65%. It is concluded that second opinion is essential in cases of presumed sarcomas for studies of incidence and aetiology and to ensure that appropriate treatment is selected.


BMP is an important regulator of proepicardial identity in the chick embryo.
The proepicardium (PE) is a transient structure formed by pericardial coelomic mesothelium at the venous pole of the embryonic heart and gives rise to several cell types of the mature heart. In order to study PE development in chick embryos, we have analyzed the expression pattern of the marker genes Tbx18, Wt1, and Cfc. During PE induction, the three marker genes displayed a left-right asymmetric expression pattern. In each case, expression on the right side was stronger than on the left side. The left-right asymmetric gene expression observed here is in accord with the asymmetric formation of the proepicardium in the chick embryo. While initially the marker genes were expressed in the primitive sinus horn, subsequently, expression became confined to the PE mesothelium. In order to search for signaling factors involved in PE development, we studied Bmp2 and Bmp4 expression. Bmp2 was bilaterally expressed in the sinus venosus. In contrast, Bmp4 expression was initially expressed unilaterally in the right sinus horn and subsequently in the PE. In order to assess its functional role, BMP signaling was experimentally modulated by supplying exogenous BMP2 and by inhibiting endogenous BMP signaling through the addition of Noggin. Both supplying BMP and blocking BMP signaling resulted in a loss of PE marker gene expression. Surprisingly, both experimental situations lead to cardiac myocyte formation in the PE cultures. Careful titration experiments with exogenously added BMP2 or Noggin revealed that PE-specific marker gene expression depends on a low level of BMP signaling. Implantation of BMP2-secreting cells or beads filled with Noggin protein into the right sinus horn of HH stage 11 embryos resulted in downregulation of Tbx18 expression, corresponding to the results of the explant assay. Thus, a distinct level of BMP signaling is required for PE formation in the chick embryo.


Treatment of acute myeloid leukaemia in a renal allograft recipient: implications of cyclosporin immunosuppressive treatment.
The clinical effects of cyclosporin were evaluated during cytotoxic treatment in a 61 year old man with acute myeloid leukaemia. He had required a renal transplant 18 months before presenting with acute myeloid leukaemia (FAB subtype M4). He had received cyclosporin 3.5-4.0 mg/kg daily to maintain a plasma cyclosporin concentration of 75-150 ng/ml. Cyclosporin was continued during induction chemotherapy with daunorubicin, cytarabine, and 6-thioguanine (DAT). He had fever and oropharyngeal candidiasis that was unresponsive to anti-bacterial drugs but responsive to systemic amphotericin. Bone marrow examination 14 days after chemotherapy showed complete haematological remission. Subsequently he tolerated consolidation treatment with DAT with no serious complications. Unfortunately he developed fatal septicaemia following a second consolidation with mitozantrone and cytarabine. Inhibition of P-glycoprotein activity by cyclosporin may not significantly increase the toxicity of aggressive chemotherapeutic regimens, and as benefit may be achieved by this approach further clinical evaluation is justified.


Combined modalities for the prevention of ovarian hyperstimulation syndrome following an excessive response to stimulation.
Although the classification and management of ovarian hyperstimulation syndrome (OHSS) are well described in the literature, little attention has been given to modalities that aim to prevent its occurrence. In this retrospective study, we sought to investigate whether a combination of modalities in addition to GnRH agonist triggering in GnRH antagonist cycles could result in better prevention of OHSS. The study included 170 hyperresponder patients who were stimulated with GnRH antagonist protocol and were triggered with GnRH agonist for final oocyte maturation. Freeze all embryos was performed in all patients. The intervention group included treatment with dopamine agonist and restarting the GnRH antagonist. Of the 170 patients included, 63 were included in the intervention group. Compared to no intervention, women in the intervention group were more likely to have: menses within 7 days of the oocyte retrieval, smaller ovarian diameter, the absence of free pelvic fluid, less hemoconcentration and higher serum sodium levels. It can be concluded that combining other modalities in addition to triggering with GnRH agonist in GnRH antagonist cycles, results in targeting several pathways that lead to OHSS and result in rapid resolution of signs of ovarian hyperstimulation.


Rearranged Diels-Alder Adducts and Prenylated Flavonoids as Potential PTP1B Inhibitors from Morus nigra.
Two novel rearranged Diels-Alder adducts, morunigrines A (1) and B (2), and four new prenylated flavonoids, morunigrols A-D (3-6), were isolated from the twigs of Morus nigra, together with four known prenylated phenolic compounds, including two flavonoids (7 and 8) and two 2-arylbenzofurans (9 and 10). Morunigrines A (1) and B (2) are a novel class of Diels-Alder adducts with unprecedented carbon skeletons featuring a rearranged chalcone-stilbene/2-arylbenzofuran core decorated with a unique methylbiphenyl moiety. The structures of the new compounds were assigned by analysis of spectroscopic data. The absolute configuration of compound 6 was determined by the measurement of specific rotation. A plausible biogenetic pathway for 1 and 2 is also proposed. Compounds 1 and 2 exhibited more potent protein tyrosine phosphatase 1B inhibitory activity with IC50 values of 1.8 ± 0.2 and 1.3 ± 0.3 μM, respectively, than that of the positive control oleanolic acid (IC50, 2.5 ± 0.1 μM).


Chemical signaling in ciliates.
For long, our knowledge of the biology of ciliate pheromones has long relied solely upon the study of the two structurally unrelated "gamones" identified in culture filtrates of a Blepharisma species. However, the characterization of a number of polypeptide pheromones secreted by Euplotes raikovi and E. octocarinatus has now established that structural relationships of homology usually link these molecules, which is consistent with the genetic basis of the mating type systems evolved by these species. In this context, our growing appreciation of the conserved and variable elements of the pheromone architecture should foster progress in the understanding of pheromone-receptor interactions and thus, provide important clues into pheromone mechanisms of action.


A food chain model to predict the levels of lipophilic organic contaminants in humans.
A fugacity-based, nonsteady state, mechanistic model called ACC-HUMAN was developed to describe bioaccumulation of lipophilic organic pollutants from air, water, and soil to humans. The physical environment was linked via a marine and an agricultural food chain model to a human bioaccumulation model. Contaminant uptake via the primary dietary sources of persistent lipophilic contaminants in industrialized countries was addressed, namely fish, dairy products, and beef. In addition, uptake from air and water was considered, allowing the model also to treat less lipophilic compounds. To evaluate the model, the food chain characteristics were parameterized for southern Sweden and historical scenarios of polychlorinated biphenyl (PCB) concentrations in air, water, and soil in this region were constructed from published data. The resulting model predictions of PCB concentrations in fish, milk, beef, and human tissue agreed well with measured concentrations from Swedish monitoring programs. This suggests that ACC-HUMAN is a useful tool for predicting human exposure to bioaccumulative organic compounds. It can be linked easily to existing multimedia fate and transport models.


Numerical Analysis and Simulation for a Generalized Planar Ginzburg-Landau Equation in a Circular Geometry.
In this paper, a numerical scheme for a generalized planar Ginzburg-Landau energy in a circular geometry is studied. A spectral-Galerkin method is utilized, and a stability analysis and an error estimate for the scheme are presented. It is shown that the scheme is unconditionally stable. We present numerical simulation results that have been obtained by using the scheme with various sets of boundary data, including those the form u(θ) = exp(idθ), where the integer d denotes the topological degree of the solution. These numerical results are in good agreement with the experimental and analytical results. Results include the computation of bifurcations from pure bend or splay patterns to spiral patterns for d = 1, and computations of metastable or unstable higher-energy solutions as well as the lowest energy ground state solutions for values of d ranging from two to five.


Evolving trends in pancreatic cancer therapeutic development.
Despite advances in translational research, the overall 5-year survival for pancreatic cancer remains dismal and with rising incidence pancreatic cancer is predicted to be the second leading cause of cancer death for many developed countries. Surgical intervention followed by cytotoxic chemotherapy are currently the best options for treatment, but disease recurrence is very common. Efforts to develop new therapeutic agents and delivery systems are necessary to achieve better clinical efficacy with less toxicity. Promising prospects are arising with new preclinical and clinical therapeutic strategies using small molecule targeted therapies, RNAi, stromal therapies, and immunotherapies. With a better understanding of the biology to aid target selection and discovery of biomarkers to aid precision medicine, better opportunities will evolve to shape the therapeutic landscape, enhance patient quality of life and increase overall survival.


Intracranial administration of vaccinia virus complement control protein in Mo/Hu APPswe PS1dE9 transgenic mice at an early age shows enhanced performance at a later age using a cheese board maze test.
One of the key pro-inflammatory mediators activated by amyloid protein in neurodegenerative disorders of the brain, such as Alzheimer's disease is the complement system. Vaccinia virus complement control protein secreted by vaccinia virus, commonly known as VCP, was found to inhibit amyloid protein mediated up-regulation of complement system in vitro. In the current research investigation, VCP was administered twice (First dose at 3 weeks and the second dose at 6-7 months) intracranially into the parietal cortical area of Mo/Hu APPswe transgenic mice. At the age of 2 years or more, the same mice were subjected to cued-learning, spatial learning, probe and reverse probe trial paradigms of cheese board maze tasks for cognitive assessment. A significant difference was observed between VCP treated mice and the transgenic controls on days two and three of the cued trials and probe trials. The VCP treated group showed a similar trend as revealed during the spatial learning trial and reverse probe trial. A differential pattern of thioflavine S staining was observed in the VCP treated group. These results suggest that administration of VCP at an early age in transgenic mice may be effective in regulating the progression to the familial form of Alzheimer's disease at a later age.


Carotenoid Composition of the Fruit of Red Mamey (Pouteria sapota).
The detailed carotenoid analysis of red mamey (Pouteria sapota) was achieved by HPLC-DAD-MS, chemical tests, and cochromatography with authentic samples. Altogether 47 components were detected and 34 identified from the total extract or after fractionation with column chromatography. The main carotenoids were cryptocapsin, sapotexanthin, and capsanthin 5,6-epoxide. Some further minor components containing the κ-end group with or without a hydroxy group and their 5,6-epoxy precursors were identified. Some comments are made about the biosynthesis of κ-carotenoids in red mamey.


Understanding exposures and latent disease risk within the National Institute of Environmental Health Sciences Superfund Research Program.
Understanding the health effects of exposures when there is a lag between exposure and the onset of disease is an important and challenging topic in environmental health research. The National Institute of Environmental Health Sciences (NIEHS) Superfund Basic Research and Training Program (SRP) is a National Institutes of Health (NIH) grant program that uses a multidisciplinary approach to support biomedical and environmental science and engineering research. Because of the multidisciplinary nature of the program, SRP grantees are well-positioned to study exposure and latent disease risk across humans, animal models, and various life stages. SRP-funded scientists are working to address the challenge of connecting exposures that occur early in life and prior to conception with diseases that manifest much later, including developing new tools and approaches to predict how chemicals may affect long-term health. Here, we highlight research from the SRP focused on understanding the health effects of exposures with a lag between exposure and the onset of the disease as well as provide future directions for addressing knowledge gaps for this highly complex and challenging topic. Advancing the knowledge of latency to disease will require a multidisciplinary approach to research, the need for data sharing and integration, and new tools and computation approaches to make better predications about the timing of disease onset. A better understanding of exposures that may contribute to later-life diseases is essential to supporting the implementation of prevention and intervention strategies to reduce or modulate exposures to reduce disease burden.