Effect of dihydroergocryptine and dihydroergocristine on cyclic AMP accumulation and prolactin release in vitro: evidence for a dopaminomimetic action.
Dihydroergocryptine and dihydroergocristine, two C-9, 10-hydrogenated ergot alkaloids, inhibited in a concentration-dependent manner prolactin release and cyclic AMP accumulation in cultured anterior pituitary cells. The inhibitory effect of dihydroergocryptine was more potent and started at lower concentrations than that of dihydroergocristine. Haloperidol and pimozide, two dopamine receptor antagonists, completely abolished the inhibitory activity of the ergot alkaloids. The involvement of the adenylate cyclase-cyclic AMP system in the inhibitory action of the two compounds was demonstrated by the antagonism by pertussis toxin of the reduction of both prolactin release and cyclic AMP accumulation produced by dihydroergocryptine and dihydroergocristine.


Population variability of nonacosan-10-ol and n-alkanes in needle cuticular waxes of Macedonian pine (Pinus peuce GRISEB.).
This is the first report on population variability of nonacosan-10-ol and n-alkanes in needle epicuticular waxes of Macedonian pine (Pinus peuce GRISEB.) Hexane extracts of needle samples, originating from two natural populations in Montenegro (Zeletin and Sjekirica) and from one population in Serbia (Mokra Gora) were analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The amount of nonacosan-10-ol varied individually from 41.3 to 72.31% (average 55.9%), with the Sjekirica population being statistically divergent (64.4% on average). The results showed n-alkanes in epicuticular waxes ranging from C₁₈ to C₃₃. The most abundant alkanes were C₂₉, C₂₅, C₂₇, and C₂₃ (15.5, 11.1, 10.6, and 10.5% on average, resp.). The carbon preference index of Pinus peuce ranged from 1.0 to 4.3 (1.9 on average). Average chain length ranged from 18.4 to 27.7 (average 25.7). A high level of inidividual quantitative variation in all of these hydrocarbon parameters was also detected. These results were compared with published data on other species from the Pinus genus.


Ultrafast conformational dynamics of pyranine during excited state proton transfer in aqueous solution revealed by femtosecond stimulated Raman spectroscopy.
Proton transfer reaction plays an essential role in a myriad of chemical and biological processes, and to reveal the choreography of the proton motion intra- and intermolecularly, a spectroscopic technique capable of capturing molecular structural snapshots on the intrinsic time scale of proton transfer motions is needed. The photoacid pyranine (8-hydroxypyrene-1,3,6-trisulfonic acid, HPTS) serves as a paradigm case to dissect excited state proton transfer (ESPT) events in aqueous solution, triggered precisely by photoexcitation. We have used femtosecond stimulated Raman spectroscopy (FSRS) to yield novel insights into the ultrafast conformational dynamics of photoexcited HPTS in complex with water and acetate molecules. Marker bands attributed to the deprotonated form of HPTS (1139 cm(-1), ∼220 fs rise) appear earlier and faster than the monomer acetic acid peak (864 cm(-1), ∼530 fs rise), indicating that water molecules actively participate in the ESPT chain. Several key low-frequency modes at 106, 150, 195, and 321 cm(-1) have been identified to facilitate ESPT at different stages from 300 fs, 1 ps, to 6 ps and beyond, having distinctive dynamics contributing through hydrogen bonds with 0, 1, and more intervening water molecules. The time-resolved FSRS spectroscopy renders a direct approach to observe the reactive coupling between the vibrational degrees of freedom of photoexcited HPTS in action, therefore revealing the anharmonicity matrix both within HPTS and between HPTS and the neighboring acceptor molecules. The observed excited state conformational dynamics are along the ESPT multidimensional reaction coordinate and are responsible for the photoacidity of HPTS in aqueous solution.


Dysgerminoma of the ovary.
Dysgerminomas of the ovary are rare germ cell tumors. They are more common at puberty. Surgery followed by irradiation has resulted in excellent cure rates in early stages of this disease. This paper is a review of six patients with a diagnosis of dysgerminoma who were treated at the Department of Radiation Oncology, University of Louisville. The controversy on the use of irradiation in Stage Ia tumor is discussed in detail. A review of the literature is also done in this paper.


Evaluation of MALDI-TOF mass spectrometry and MALDI BioTyper in comparison to 16S rDNA sequencing for the identification of bacteria isolated from Arctic sea water.
MALDI-TOF Mass Spectrometry in association with the MALDI BioTyper 3.1 software has been evaluated for the identification and classification of 45 Arctic bacteria isolated from Kandalaksha Bay (White Sea, Russia). The high reliability of this method has been already demonstrated, in clinical microbiology, by a number of studies showing high attribution concordance with other credited analyses. Recently, it has been employed also in other branches of microbiology with controversial performance. The phyloproteomic results reported in this study were validated with those obtained by the "gold standard" 16S rDNA analysis. Concordance between the two methods was 100% at the genus level, while at the species level it was 48%. These percentages appeared to be quite high compared with other studies regarding environmental bacteria. However, the performance of MALDI BioTyper changed in relation to the taxonomical group analyzed, reflecting known identification problems related to certain genera. In our case, attribution concordance for Pseudomonas species was rather low (29%), confirming the problematic taxonomy of this genus, whereas that of strains from other genera was quite high (> 60%). Among the isolates tested in this study, two strains (Exiguobacterium oxidotolerans and Pseudomonas costantinii) were misidentified by MALDI BioTyper due to absence of reference spectra in the database. Accordingly, missing spectra were acquired for the database implementation.


Primary structure and pathological study of phospholipase A2-I from Agkistrodon bilineatus (common cantil) venom.
Phospholipase A2-I (PLA2-I) was isolated from Agkistrodon bilineatus venom by Nikai (Nikai et al., 1993). The amino acid sequence of the phospholipase A2-I was determined by the Edman sequencing procedure of peptides derived from digests utilizing cyanogen bromide, clostripain, metalloendopeptidase, chymotrypsin, and Staphylococcus aureus V8 protease. In the reduced state, purified phospholipase A2's molecular weight was determined to be 14,000 as demonstrated by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Purified PLA2-I also contained 1 mol of Ca per mol of protein and consists of 123 amino acid residues resulting in a calculated molecular weight of 14,133. Both phospholipase and lethal activities were found to be inhibited by bromophenacyl bromide, suggesting that the histidine residue is involved in this activity. Also there was an increase in the creatine kinase activity of mice serum, which is an indicator that PLA2-I is involved in muscle damage.


Effects of habitual alcohol intake and cigarette smoking on the development of hepatocellular carcinoma.
To study the effects of habitual alcohol intake and cigarette smoking on the latency period for the development of hepatocellular carcinoma (HCC), 455 patients with HCC were analyzed with respect to age at diagnosis. They were divided into hepatitis B virus (HBV) positive and negative patients based on HbsAg and high titer anti-HBc in serum. HBV-positive and negative HCC patients were further subdivided into four subgroups based on the history of drinking more than one small bottle of Japanese "sake" or its equivalent per day for more than 10 yr and the history of smoking more than one cigarette per day for more than 10 yr. Among HBV-positive HCC patients, the average age of those with a drinking and a smoking habit (50 +/- 10 yr) was younger compared with that of patients with a drinking habit but without a smoking habit (56 +/- 14 yr, not significant, NS), of those who were smokers and nondrinkers (55 +/- 10 yr, NS) and of those who did not drink nor smoke (59 +/- 8 yr, p less than 0.005). Among HBV-negative HCC patients, patients with drinking and smoking habits (57 +/- 9 yr) were younger compared with those with a drinking habit without smoking (59 +/- 9 yr, NS), those who were smokers and nondrinkers (62 +/- 9 yr, p less than 0.005), and those who were nondrinkers and nonsmokers (63 +/- 12 yr, p less than 0.005). These data suggest that habitual alcohol intake may promote the development of HCC if the patients smoke cigarette regardless of the status of HBV seromakers.


Designing voice interfaces to support mindfulness-based pain management.
Chronic pain is a critical public health issue affecting approximately 20% of the adult population in the United States. Given the opioid crisis, there has been an urgent focus on non-addictive pain management methods including mindfulness-based stress reduction (MBSR). Prior work has successfully used MBSR for pain management. However, ensuring longitudinal engagement in MBSR practices remains a serious challenge. In this work, we explore the utility of a voice interface to support MBSR home practice. We interviewed 10 mindfulness program facilitators to understand how such a technology might fit in the context of the MBSR class and identify potential usability issues with our prototype. We then used directed content analysis to identify key themes and sub-themes within the interview data. Our findings show that facilitators supported the use of the voice interface for MBSR, particularly for individuals with limited motor function. Facilitators also highlighted the unique affordances of voice interfaces, including perceived social presence, to support sustained engagement. We demonstrate the acceptability of a voice interface to support home practice for MBSR participants among trained mindfulness facilitators. Based on our findings, we outline design recommendations for technologies aiming to provide longitudinal support for mindfulness-based interventions. Future work should further these efforts toward making non-addictive pain management interventions accessible and efficacious for a wide audience of users.


Lack of association of delta-aminolevulinic acid dehydratase genotype with cytogenetic damage in lead workers.
The objective of this study was to evaluate the correlations of genetic polymorphism of genotypes delta-aminolevulinic acid dehydratase (ALAD), blood lead levels (BLLs), zinc protoporphyrin (ZPP), sister chromatid exchanges (SCEs), and high SCE frequency cells (HFCs) in lead workers. Three groups of lead workers were included in the study: high lead exposure group (26 workers), low lead exposure group (31 workers) and control group (30 controls who lived in an area uncontaminated by lead). Blood samples were taken from all subjects and analyzed for lead levels, ALAD genotype and SCE levels. Occupationally exposed workers had significantly higher BLLs, ZPP and hemoglobin levels than the controls. There were no differences among the three groups regarding percentages of ALAD 1-1 and ALAD 1-2 genotypes, but the ALAD 2-2 genotype was not detected in any of the three groups. There were no significant differences among the three groups for BLLs, ZPP and hemoglobin levels based on ALAD 1-1 and ALAD 1-2. Average SCE values in the high lead exposure group were significantly greater than those in the control group (6.2 vs 5.2 SCEs/cell, P < 0.05). HFC analysis revealed a significantly higher HFC percentage (53.9%) in the high lead exposure group than in the low lead exposure group (16.1%) and the control group (10%). There appeared to be an interaction effect on HFC percentages between smoking and lead exposure. When multiple regression analysis was used, the factors that affected SCE levels were lead exposure and smoking, but ALAD genotypes did not have any significant effect. A significant association existed between both SCE and HFC levels and lead exposure. However, different ALAD genotypes were not found to be associated with levels of blood lead and ZPP in the three groups.


Mitochondrial myopathy and sensorineural hearing loss: case study.
Mitochondrial myopathy is caused by the absence and/or insufficiency of L-carnitine, a quaternary enzyme responsible for transporting free fatty acids into the mitochondria. The primary function of the mitochondria is to produce energy, contributing to proper cell functioning. Muscular lipidosis causes abnormalities in enzymes that metabolize fat, resulting in the accumulation of harmful amounts of fats in tissues. The aim of this study was to present the case study of patient B.D., a 37-year-old woman diagnosed with muscular lipidosis with L-carnitine deficiency at 6 years old, and describe the speech-language follow-up performed at a hearing care clinic. The first entry in the patient's medical chart was on 03/05/1989, with continuous use of 2g/day of L-carnitine prescribed by a neurologist. The mother reported that B.D. had difficulty hearing and was inattentive, which became more evident when she started school. In 1988 the patient was diagnosed with moderate bilateral sensorineural hearing loss and began using behind-the-ear (BTE) hearing aids in 1989, after which her academic performance and communication improved. In 1998 she switched to Completely in Canal (CIC) hearing aids, which are more discreet, provided better sound localization and greater high frequency gain, although her hearing thresholds worsened slightly. She completed her graduate studies and currently works at a large financial institution. It was concluded that early neurological diagnosis and speech-language intervention enabled adequate language development in the patient.


Novel non-contiguous exon duplication in choroideremia.
The importance of establishing a genetic diagnosis in patients with a choroideremia phenotype has been underscored by the advent of gene replacement therapy for this condition. Here, we describe a complex imbalance at the CHM locus in a male patient with classical disease. At the DNA level, this imbalance consists of 2 non-contiguous duplications (exons 1-2 and 9-12). Further characterization suggests the generation of 2 independent CHM transcriptional units, one of which may produce a deleted form of the Rab escort protein 1 protein. Expression of such a type of aberrant protein in photoreceptors may have important implications when considering gene therapy for this disorder.


Protective effect of mussel polysaccharide on cyclophosphamide-induced intestinal oxidative stress injury via Nrf2-Keap1 signaling pathway.
The hard-shelled mussel (Mytilus coruscus) has been used as a traditional Chinese medicine and health food in China for centuries. Polysaccharides from mussel has been reported to have multiple biological functions, however, it remains unclear whether mussel polysaccharide (MP) exerts protective effects in intestinal functions, and the underlying mechanisms of action remain unclear. The aim of this study was to investigate the protective effects and mechanism of MP on intestinal oxidative injury in mice. In this study, 40 male BALB/C mice were used, with 30 utilized to produce an animal model of intestinal oxidative injury with intraperitoneal injection of cyclophosphamide (Cy) for four consecutive days. The protective effects of two different doses of MP (300 and 600 mg/kg) were assessed by investigating the change in body weight, visceral index, and observing colon histomorphology. Moreover, the underlying molecular mechanisms were investigated by measuring the antioxidant enzymes and related signaling molecules through ELISA, real-time PCR, and western blot methods. The results showed that MP pretreatment effectively protected the intestinal from Cy-induced injury: improved the colon tissue morphology and villus structure, increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and reduced malondialdehyde (MDA) content in serum and colon tissues. Meanwhile, MP also significantly increased the expression levels of SOD, GSH-Px, heme oxygenase-1 (HO-1), and nuclear factor E2-related factor 2 (Nrf2) mRNA in colon tissues. Further, western blot results showed that the expression of Nrf2 protein was significantly upregulated while kelch-like ECH-associated protein 1 (Keap1) was significantly downregulated by MP in the colonic tissues. This study indicates that MP can ameliorate Cy-induced oxidative stress injury in mice, and Nrf2-Keap1 signaling pathway may mediate these protective effects.


Evidence that red blood cell protein p55 may participate in the skeleton-membrane linkage that involves protein 4.1 and glycophorin C.
Human erythrocyte p55 is a peripheral membrane protein that contains three distinct domains in its primary structure: an N-terminal domain, an SH3 motif, and a C-terminal guanylate kinase domain. We used naturally mutated red blood cells (RBCs) with primary genetic defects resulting in the absence of protein 4.1 (4.1[-] hereditary elliptocytosis) or glycophorin C (Leach elliptocytosis). The absence of either protein was associated with the absence of p55. On a stoichiometric basis, the reduction in glycophorin C (about 80%) was concomitant to the lack of p55 in RBCs devoid of protein 4.1. Similarly, the reduction of protein 4.1 (about 20%) was equivalent to the absence of p55 in RBCs devoid of glycophorin C. These correlations suggest that p55 is associated, in precise proportions, with the protein 4.1-glycophorin-C complex, linking the skeleton and the membrane. The protein 4.1-glycophorin-C cross-bridge is known to be critically important for the stability and mechanical properties of human RBC plasma membrane. Because isoforms of protein 4.1, glycophorin C, and p55 exist in many tissues, these results provide evidence of a linkage between the skeleton and the membrane that may have implications in many nonerythroid cells.


Bioactive peptides from selected latin american food crops - A nutraceutical and molecular approach.
This review reported an updated survey on the molecular functional properties of bioactive peptides derived from different Latin American ancient grains such as Maize, common Bean, Amaranth, Quinoa and Chia seeds. Seed storage proteins ecrypt in their sequences diverse peptides associated with a wide range of beneficial effects on the human health and the most studied are antihypertensive, anti-cholesterolemic, antioxidant, anti-inflammatory, anticancer, antimicrobial and immunomodulatory properties. Additionally, in the last decades molecular properties have been also used for their characterization to understand their activities and it makes them highly attractive to be incorporated into food formulations and to complement or replace some conventional cereal grains. Due to the nutraceutical effects, today, these seeds are one of the main gastronomic trends of consumption worldwide due to their nutritional benefits and are part of the shopping lists of many people, among them vegetarians, vegans, celiacs or lovers of raw food. These seeds are a legacy of pre-Columbian civilizations reason why in our time they are considered as "Superfoods of the Gods", "The pre-hispanic superfoods of the future" and "The new golden seeds of the XXI century".


Mutual recognition of sphingolipid molecular species in membranes.
In membranes liquid disordered (l(d)) and liquid ordered (l(o)) domains can exist that differ in fluidity and function. L(o) areas are predominantly composed of cholesterol and sphingomyelin (SM). Study of the formation of such domains is hampered by a lack of methods to analyze specific lipid-lipid interactions at low concentrations of individual molecular lipid species in membranes. Here, we developed a simple biophysical method to experimentally assess the affinity of various molecular species of SM for cholesterol, and for their endogenous counterparts (kin) at physiological concentrations. Fluorescent SM (flc SM) molecular species with a conjugated pentaene system in their fatty acids are employed to monitor their affinity to either cholesterol or their kin by fluorescence unquenching. With this novel method we show that specific interactions of individual SMs with cholesterol or their kin exist, indicating the presence of SM nano-domains in l(d)-phases, strictly based on kin/cholesterol recognition.


Femtosecond laser-assisted inverted mushroom keratoplasty.
To evaluate best-corrected visual acuity (BCVA), refractive outcome, corneal topography, optical coherence tomography, and endothelial cell density 12 months after femtosecond laser-assisted inverted mushroom keratoplasty. We performed a prospective study of a surgical case series of 5 patients undergoing femtosecond laser-assisted inverted mushroom keratoplasty for pseudophakic bullous keratopathy or pre-Descemet X-linked ichthyosis. The femtosecond laser was used to create a top-hat configuration in the donor cornea and recipient cornea. Laser parameters were as follows: energy, 4.0 (anterior inner vertical side cut and horizontal lamellar cut) and 7.0 microJ (posterior outer vertical side cut); spiral pattern with a firing rate of 15 kHz. The size of the anterior inner diameter was 7.4 mm in the donor cornea and 7.0 mm in the recipient cornea. The posterior outer diameter was 9.0 mm in all eyes. At 6 and 12 months after surgery, all corneal grafts were clear and showed an excellent adaptation of the lamellar donor and recipient wound surfaces. At 12 months postoperatively, BCVA averaged 20/32 (range, 20/60-20/20), refractive cylinder averaged -3.20 +/- 2.0 D, topographical cylinder averaged 3.26 +/- 2.1 D, and the mean endothelial cell density was 1793 +/- 491 cells/mm2 (range, 954-2237 cells/mm2). The mean central corneal thickness and thickness of the posterior shelf was 517 +/- 3 and 175 +/- 8 microm, respectively. The femtosecond laser-assisted inverted mushroom keratoplasty shows good promise in surgical treatment of corneal diseases. The multiplanar fit between the donor and recipient cornea allows early suture removal and visual rehabilitation.


Influencing factors of pneumothorax and parenchymal haemorrhage after CT-guided transthoracic needle biopsy: single-institution experience.
To evaluate the incidences and influencing factors of pneumothorax and parenchymal haemorrhage after computed tomography (CT)-guided transthoracic needle biopsy (TTNB). A retrospective analysis of 216 patients who underwent CT-guided TTNB was performed. The frequencies and risk factors of pneumothorax and parenchymal haemorrhage were determined. P values less than 0.05 were considered statistically significant. The incidences of pneumothorax and parenchymal haemorrhage were 23.1% and 45.4%, respectively. Twenty-two per cent of patients with pneumothorax needed percutaneous drainage, but all patients with parenchymal haemorrhage had clinical improvement after conservative treatment. No procedure-related mortality was detected. Univariate analysis showed that underlying pulmonary infection, lesion size of less than 1 cm, and lesion depth of more than 2 cm were significant influencing factors of pneumothorax. A significant relationship between the underlying chronic obstructive pulmonary disease (COPD) and the need for drainage catheter insertion was found. Pulmonary haemorrhage was more likely to occur in patients with underlying malignancy, solid pulmonary nodule, lesion size of 3 cm or less, and lesion depth of more than 3 cm. Consolidation was the protective factor for pulmonary haemorrhage. Sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV), and accuracy of CT-guided core needle biopsy (CNB) for the diagnosis of malignancy were 95.7%, 100%, 100%, 93.3%, and 97.3%, respectively. The rate of diagnostic failure was 10.2%. Pulmonary hemorrhage is the most common complication after CT-guided TTNB. Influencing factors for pneumothorax are underlying pulmonary infection, lesion size < 1 cm, and lesion depth > 2 cm. Underlying malignancy, solid pulmonary nodule, lesion size ≤ 3 cm, and lesion depth > 3 cm are associated with pulmonary haemorrhage.


[Cellular responses to vibration during dental drilling with belt drive motor engine (in vitro) (author's transl)].
There have been many reports on the pulpal reaction caused by vibration during high speed dental drilling with air turbine hand-piece. It is, however, not clear pulpal responses to vibration of low speed drilling with 7 000 rpm of belt drive motor engine which produces a fundamental vibration of about 170 cps having most unpleasant sensation at vestibular apparatus. Here, cellular responses of L strain cells to vibration derived from 7 000 rpm and 15 000 rpm of belt drive motor engine were observed in vitro system. There is no difference between the both cellular responses to the vibration of 7 000 rpm and 15 000 rpm. Suspended free cells were easily influenced and degenerated by the vibration, and remarkably checked in their cell-multiplication. On the contrary, in the cells adhered to the substratum of glassware, no degeneration and no inhibitory effect were observed. And the cells showed reversible response of cytoplasmic shrinkage only.


Separation of two major chalcones from Angelica keiskei by high-speed counter-current chromatography.
Angelica keiskei (Shin-sun cho) is an edible higher plant with the beneficial preventive effects on cancer, hypertension, and coronary heart disease. Two bioactive chalcones of Shin-sun cho, xanthoangelol (1) and 4-hydroxyderricin (2), were separated simultaneously by using high-speed counter-current chromatography with a two-phase solvent system composed of n-hexane-EtOAc-MeOH-H2O (9:5:9:4). Only nonconsuming processes, solvent fractionations and Sephadex LH-20 column chromatography, were conducted as presteps. Xanthoangelol (1, 35.9 mg, 99.9 % purity at 254 and 365 nm) and 4-hydroxyderricin (2, 4.4 mg, 98.7 % purity at 254 nm and 98.8 % purity at 365 nm) were successfully purified from 70 mg of the processed extract from A. keiskei. The structures of two compounds were confirmed by (1)H- and (13)C-NMR analysis.


Health care utilization in patients with gout: a prospective multicenter cohort study.
All published studies of health care utilization in gout have been cross-sectional to date, and most used a patient-reported diagnosis of gout. Our objective was to assess health care utilization and its predictors in patients with physician-confirmed gout in a prospective cohort study. In a multi-center prospective cohort study of U.S. veterans with rheumatologist-confirmed gout (N = 186; two centers), we assessed patient self-reported overall and gout-specific health care utilization with the Gout Assessment Questionnaire (GAQ) every 3-months for a 9-month period. Comparisons were made using the student's t test or the chi-square, Wilcoxon rank sum test or Fisher exact test, as appropriate. Mixed effects Poisson regression was used to assess potential correlates of gout-related health care utilization. Mean age was 64.6 years, 98% were men, 13% Hispanic or Latino, 32% were African-American, 6% did not graduate high school, mean serum urate was 8.3 and mean Deyo-Charlson score was 3.1. During the past year, mean gout-related visits were as follows: rheumatologist, 1.5; primary care physician, 2 visits; ≥1 inpatient visits, 7%; ≥1 ER visits, 26%; and urgent care/walk-in visit, 33%. In longitudinal analyses, African-American race and gout flares in the last 3 months were associated with significantly higher rate ratio of gout-related outpatient visits. African-American race and lack of college education were associated with significantly higher rate ratio for gout-related urgent visits and overnight stays. African-American race and recent gout flares were associated with higher outpatient utilization and African-American race and no college education with higher urgent or inpatient utilization. Future studies should examine whether modifiable predictors of utilization can be targeted to reduce healthcare utilization in patients with gout.


The 8-bromobaicalein alleviated chikungunya-induced musculoskeletal inflammation and reduced the viral load in healthy adult mice.
Chikungunya virus is a re-emerging arbovirus that has caused epidemic outbreaks in recent decades. Patients in older age groups with high viral load and severe immunologic response during acute infection are likely to develop chronic arthritis and severe joint pain. Currently, no antiviral drug is available. Previous studies suggested that a flavone derivative, 8-bromobaicalein, was a potential dengue and Zika replication inhibitor in a cell-based system targeting flaviviral polymerase. Here we characterized that 8-bromobaicalein inhibited chikungunya virus replication with EC50 of 0.49 ± 0.11 µM in Vero cells. The molecular target predicted at viral nsP1 methyltransferase using molecular binding and fragment molecular orbital calculation. Additionally, oral administration of 250 mg/kg twice daily treatment alleviated chikungunya-induced musculoskeletal inflammation and reduced viral load in healthy adult mice. Pharmacokinetic analysis indicated that the 250 mg/kg administration maintained the compound level above EC99.9 for 12 h. Therefore, 8-bromobaicalein should be a potential candidate for further development as a pan-arboviral drug.


Design strengths and issues of SAMHSA's Women, Co-occurring Disorders, and Violence Study.
In 1998 the Substance Abuse and Mental Health Services Administration launched the Women, Co-occurring Disorders, and Violence Study (WCDVS). The WCDVS developed, implemented, and evaluated the outcomes and costs of comprehensive, trauma-informed treatment programs for women with a history of violence and trauma who have substance use and mental health disorders. This article discusses the overall design features of the study, issues related to such a design, results of the outcomes and cost evaluations, and suggestions for future research. The nine WCDVS sites were located across the continental United States, with six sites on the East Coast, two on the West Coast, and one in Colorado. A total of 2,729 women (1,415 in the intervention condition and 1,314 in the comparison condition) were enrolled over the 13.5-month baseline accrual period (January 2001 through February 2002). Follow-up interviews were conducted with all participants at three, six, nine and 12 months post-baseline. Women in the intervention and the comparison groups showed improvement in outcomes in four areas: alcohol use, drug use, mental health, and trauma. At six months women in the intervention group scored modestly better than women in the usual-care group for outcome measures for drug use, trauma, and mental health. At 12 months women in the intervention group maintained their improvement in drug use outcomes and continued to improve in mental health and trauma outcomes. After a start-up period, costs for services were not significantly different between the intervention and comparison groups at both follow-up points. Despite their very modest nature, the WCDVS results are promising.


Prostate cancer. Promising advances that may alter survival rates.
Recent advances in the diagnosis and treatment of patients with prostate cancer have altered clinical management of the disease. Although direct rectal examination remains the standard clinical tool for staging prostate cancer, transrectal ultrasound appears to be about twice as sensitive for detection. Prostate-specific antigen (PSA) has replaced prostate-specific acid phosphatase as a serum tumor marker for prostate cancer. When used in conjunction with measurement of prostate volume by transrectal ultrasound, PSA values may identify patients at increased risk for occult cancer. Use of transrectal ultrasound and PSA values has also improved the accuracy of clinical staging. Modifications in the technique of radical prostatectomy have minimized the morbidity associated with this procedure, making it a more attractive therapeutic option in patients with localized prostate cancer. In patients with metastatic disease, total androgen blockade is an option that appears superior to standard hormonal therapy.


Female victims of rape and their genital injuries.
A minority (some report < 10%) of women report sexual assault. Of those that negotiate the police process, only a minority will come to a court hearing. It is thought that the courts still rely upon medical evidence, in particular evidence of genital injury to 'prove' the rape. This study aimed to ascertain the incidence of genital injury in victims of alleged rape. Retrospective review of case records of women who reported they had had been raped, provided by women doctors on the Northumbrian Police Doctors scheme. Case records from Newcastle, North and South Tyneside, Sunderland and Northumbria. Analysis of records in the standardised booklet used by police surgeons to examine women reporting rape. Presence of genital injury, presence of other physical injuries. A minority of women had genital injuries (22/83); the majority had some form of physical injury (68/83), although most of these were minor. The study shows that only a minority of women examined by specifically trained police doctors show evidence of genital injury. The absence of genital injury does not exclude rape.


Muscle strength and its development. New perspectives.
Skeletal muscle undergoes substantial adaptation when it is subjected to a strength training regimen. At one extreme, these effects are manifested as profound morphological changes, such as those exemplified by bodybuilders. However, it is possible to increase strength without any change in muscle size. This dissociation underscores the notion that strength is not solely a property of muscle but rather it is a property of the motor system. The nervous system seems to be of paramount importance for the expression and development of strength. Indeed, it is probable that increases in strength can be achieved without morphological changes in muscle but not without neural adaptations. This review focuses on the role of the nervous system in the development of strength. In the strength literature, 3 topics exemplify the importance of the nervous system in strength development. These 3 topics are considered in detail in the review: electromyostimulation, cross-training effects, and EMG-force relationships. Evidence is presented from several different paradigms emphasising the significant contribution of neural mechanisms to the gains in strength with short term training. Although little is known about the specific neural mechanisms associated with strength training adaptations, the literature emphasises that the measure of human performance known as strength can be influenced by a variety of neurophysiological processes.


Reduced Concentrations of NSE, S100β, Aβ, and Proinflammatory Cytokines in Elderly Patients Receiving Ultrasound-Guided Combined Lumbar Plexus-Sciatic Nerve Block during Hip Replacement.
The increase of hip fractures is related to the aging of the population, which has caused a huge medical burden in many countries. Hip replacement has been approved as a highly successful surgical intervention for the patients with hip fractures. Different anesthesia choices in the surgical intervention are associated with the prognosis of patients. This study focused on investigating the application of ultrasound-guided combined lumbar plexus-sciatic nerve block in elderly patients with hip fractures. In this retrospective study, 62 elderly patients received combined spinal-epidural anesthesia and 58 elderly patients underwent ultrasound-guided combined lumbar plexus-sciatic nerve block during the surgery. Hemodynamic monitoring including pulse oxygen saturation (SpO2), heart rate and blood pressure, the assessment of pain intensity using Visual Analogue Scale (VAS), cognitive function assessment through Montreal Cognitive Assessment (MoCA) and biomarkers consisting of serum levels of neuron specific-enolase (NSE), S100 beta protein (S100-β), and amyloid beta protein (Aβ), as well as immune function by interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP) were detected in this study. Furthermore, length of hospital stay (LOS) and adverse reactions including hematoma, hypotension, nausea, and vomit were analyzed. The findings indicated that comparing with the patients receiving combined spinal-epidural anesthesia, those undergoing ultrasound-guided combined lumbar plexus-sciatic nerve block showed significantly lower level of heart rate, higher level of SpO2, and lower level of diastolic pressure and systolic pressure at 5 minutes and 30 minutes after anesthesia and after surgery (P < 0.05), indicated obviously lower VAS score at 12, 24, and 48 hours after surgery (P < 0.05), and revealed higher MoCA score at 12 days after surgery (P < 0.05). A significantly higher level of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP was revealed in the two groups receiving different anesthesia methods at 10 days after surgery compared with that before surgery (P < 0.05). However, the patients receiving ultrasound-guided combined lumbar plexus-sciatic nerve block had obviously lower expression of NSE, S100β, Aβ, IL-6, IL-1β, TNF-α, and hs-CRP compared with the group accepting combined spinal-epidural anesthesia (P < 0.05). The two groups indicated no significant difference in incidence of hypotension and vomit, etc. (P < 0.05), but showed remarkable difference referring to total incidence of adverse reactions and LOS (P < 0.05). The application of ultrasound-guided combined lumbar plexus-sciatic nerve block in hip replacement contributes to the stability of hemodynamics and alleviation of postoperative pain intensity. It can reduce cognitive and immune impairment of the elderly patients with hip fractures.


Effect of Selected Luminescent Layers on CCT, CRI, and Response Times.
Phosphors have been used as wavelength converters in illumination for many years. When it is excited with blue light, the frequently used yttrium aluminium garnet doped with cerium (YAG:Ce) phosphor converts a part of blue light to a wideband yellow light, resulting in the generated light having a white color. By combining an appropriate concentration of the YAG:Ce phosphor and blue excitant light, white light of a desired correlated color temperature (CCT) can be obtained. However, this type of illumination has a lower color rendering index value (CRI). In an attempt to improve the CRI value, we mixed the YAG:Ce phosphor with europium-doped calcium sulfide phosphor (CaS:Eu), which resulted in a considerably increased CRI value. This article examines an experiment with luminescent layers consisting of a mixture of selected phosphors and polydimethylsiloxane (PDMS). Different thicknesses in these layers were achieved by changing the speed of rotation during their accumulation onto laboratory glass using the method of spin coating. The spectral characteristics of these luminescent layers as they were excited with blue light emitting diode (LED) and laser diode (LD) were then determined. A suitable combination of the YAG:Ce phosphor with a phosphor containing europium, as it was excited with a blue LED, yielded a source of white light with a CRI value of greater than 85. The response time in the tested luminescent layers to a rectangular excitant impulse (generated by a signal generator and transmitted by LD) was also measured in order to examine their potential use in visible light communications (VLC).


Subjective Cognitive Complaints in Parkinson Disease Without Dementia: A Preliminary Study.
Little is known about the subjective cognitive complaints of individuals with Parkinson disease (PD). Such complaints have become a topic of interest recently as they play a role in the diagnosis of neurocognitive disorders. The aim of this preliminary study was to determine whether a sample of nondemented individuals with PD reported significantly more difficulties with multiple elements of cognition than a control sample and to assess the relation between their ratings and demographics, motor symptom severity, neuropsychological test performance, and measures of depression and anxiety. Forty nondemented individuals with PD and 27 healthy individuals completed a questionnaire assessing everyday cognitive difficulties. Independent t tests indicated that individuals with PD reported significantly more cognitive complaints in general and in specific tasks involving complex attention, executive function, processing speed, and verbal fluency but not memory. Questionnaire ratings significantly correlated with measures assessing anxiety, verbal memory, processing speed, and verbal fluency. Results suggest that it is important to ask individuals with PD about cognitive complaints across several cognitive domains and also inquire about symptoms of anxiety, which may be related to their self-reported cognitive difficulties.


Pharmacological treatment for premature ejaculation.
Premature ejaculation is a common male sexual dysfunction. Treatment modalities as recommended by the British Association of Sexual Health and HIV include behavioural therapy, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and local anaesthetic creams. We audited the clinical cohort from our dedicated sexual dysfunction clinic to determine the success of prescribed treatment and co-existing prostatitis/male pelvic pain, erectile dysfunction, phosphodiesterase-5 (PDE5) inhibitor use and anxiety. The use of SSRIs was successful in the treatment of premature ejaculation with or without the use of local anaesthetic cream. Co-existing prostatitis/male pelvic pain, erectile dysfunction, PDE5 inhibitor use and anxiety were high.


[Sclerosing of the parotid gland using a protein solution for instillation in the excretory ducts. Long-term results of animal experiments].
The histological changes of the parotid gland after instillation of a resorbable protein solution into the excretory ducts were investigated by animal experiments. The glands of eleven rabbits were examined twelve months or more after occlusion of the duct system. Atrophy of parenchyma, fibrosis of interstitial tissue and recanalisation of the ducts was found. The epithelial lining of the excretory ducts showed metaplasia, and sometimes even dysplasia. This histological feature is also seen in "necrotizing sialometaplasia" but has no tendency to undergo malignant transformation. The aim of the method described is elimination of secretory parenchyma. It depends on three mechanisms: suppression of secretion, chemical influence of the solution on tissue, and diminution of acinar blood supply. Complications such as abscesses or fistula occurred after paraductal instillation of the solution, or when the recanalization of the ducts was disturbed. Compared to ligation of Stensen's duct this method has some advantages in the treatment of chronic recurrent parotitis, sialadenosis, salivary fistulae or sialorrhea.


Generation and functional characterization of anti-human and anti-mouse IL-36R antagonist monoclonal antibodies.
Deficiency of interleukin (IL)-36 receptor antagonist (DITRA) syndrome is a rare autosomal recessive disease caused by mutations in IL36RN. IL-36R is a cell surface receptor and a member of the IL1R family that is involved in inflammatory responses triggered in skin and other epithelial tissues. Accumulating evidence suggests that IL-36R signaling may play a role in the pathogenesis of psoriasis. Therapeutic intervention of IL-36R signaling offers an innovative treatment paradigm for targeting epithelial cell-mediated inflammatory diseases such as the life-threatening psoriasis variant called generalized pustular psoriasis (GPP). We report the discovery and characterization of MAB92, a potent, high affinity anti-human IL-36 receptor antagonistic antibody that blocks human IL-36 ligand (α, β and γ)-mediated signaling. In vitro treatment with MAB92 directly inhibits human IL-36R-mediated signaling and inflammatory cytokine production in primary human keratinocytes and dermal fibroblasts. MAB92 shows exquisite species specificity toward human IL-36R and does not cross react to murine IL-36R. To enable in vivo pharmacology studies, we developed a mouse cross-reactive antibody, MAB04, which exhibits overlapping binding and pharmacological activity as MAB92. Epitope mapping indicates that MAB92 and MAB04 bind primarily to domain-2 of the human and mouse IL-36R proteins, respectively. Treatment with MAB04 abrogates imiquimod and IL-36-mediated skin inflammation in the mouse, further supporting an important role for IL-36R signaling in epithelial cell-mediated inflammation.


The potential clinical relevance of serum vascular endothelial growth factor (VEGF) and VEGF-C in recurrent papillary thyroid carcinoma.
Vascular endothelial growth factor (VEGF) promotes tumor angioinvasion while VEGF-C is a potent lymphangiogenic factor. This study aims at evaluating serum VEGF (sVEGF) and sVEGF-C levels in recurrent papillary thyroid carcinoma (PTC) patients. Serum samples were collected preoperatively from 85 patients with primary PTC, 44 with benign thyroid diseases, and 19 with recurrent PTC. sVEGF and sVEGF-C levels were measured by enzyme-linked immunosorbent assay. Twelve patients had locoregional recurrence only while 7 patients had distant metastases, including 6 with concomitant or history of locoregional recurrence. Patients with recurrent PTC had significantly higher sVEGF (432 vs 263 pg/mL, P = .004) and sVEGF-C (6,433 vs 5,289 pg/mL, P = .006) levels than benign controls. sVEGF level was significantly elevated in patients with distant metastases compared with those of local recurrences only (580 vs 345 pg/mL, P = .037) while there was no significant difference of sVEGF-C level in both subgroup of patients. sVEGF, but not VEGF-C, showed a linear correlation with thyroglobulin levels in recurrent PTC patients. Both sVEGF and sVEGF-C levels are elevated in patients with recurrent PTC, and sVEGF distinguishes the presence of distant metastasis. Angiogenic markers should be further evaluated for their clinical relevance in monitoring and predicting the type of recurrence.


Adrenal Insufficiency in Children With Nephrotic Syndrome on Corticosteroid Treatment.
Background: Adrenal insufficiency can result from impaired functions at all levels of hypothalamic-pituitary-adrenal (HPA) axis. We here studied risk factors associated with adrenal insufficiency in children receiving prolonged exogenous steroid treatment for nephrotic syndrome. Method:We performed low-dose Synacthen tests (LDSTs, 0.5 μg/m2) in children with steroid-sensitive nephrotic syndrome 4-6 weeks after discontinuation of the corticosteroid therapy. We measured early morning serum cortisol levels at baseline and at intervals of 10, 20, 30, and 60 min following the stimulation test. We defined normal HPA axis stimulation responses as those with peak cortisol cut-off values >550 nmol/L. Result:We enrolled 37 children for this study research. All children enrolled had normal early morning cortisol levels. However, 13 (35.1%) demonstrated HPA axis suppression (by LDST) 4-+6 weeks after discontinuation of oral prednisolone. Nephrotic syndrome diagnosed before 5 years of age (OR, 0.75; 95% CI, 0.57-0.99; p = 0.043), and steroid-dependence [OR, 5.58; 95% confidence interval (CI), 1.06-29.34; p = 0.042] were associated with increased risk of developing adrenal suppression after steroid discontinuation. Conclusion:HPA axis suppression, may go unnoticed without proper screening. A normal early morning cortisol level (275-555 nmol/L) does not exclude adrenal insufficiency in children with steroid-sensitive nephrotic syndrome. Further screening with LDSTs, particularly in children younger than 5 years at diagnosis, may be warranted.


Death of a parent and the children's experience: don't ignore the elephant in the room.
This paper explores two interlinked components of practitioner's support to children when a parent or carer is at the end of life or has died. The primary issue relates to communication and the competence and confidence of practitioners when working with this community of children. The paper suggests that related to this is the lack of training practitioners receive, both as students and through continual professional development, within the fields of social care and health. The metaphor of the elephant in the room is used to delineate how practitioners avoid such discussions and thereby miss opportunities to support children experiencing potentially the most traumatic life event they have faced. Drawing on current research and the author's experience and reflections as a researcher and practitioner the paper suggests that children experiencing the death of a parent or carer are not being recognized as children in need but rather requiring interventions from specialist services.


Histological examination of the liver after experimental administration of MK-801 and dexamethasone.
The aim of the research was histological assessment of the influence of MK-801 (NMDA receptor antagonist) and dexamethasone on the liver. The experiment was carried out on adult Albino-Swiss mouse males. MK-801 was administered in the dose of 0.3 mg/kg/24 h for 8 days, dexamethasone--in the toxic dose of 120 mg/kg/24 h. Liver slices stained with hematoxylin and eosin were examined with light microscope. The performed experiments revealed that MK-801 can cause morphological changes of the liver in the shape of increased transparence of hepatocyte cytoplasm and narrowing of the liver sinusoids. MK-801 intensifies liver damage induced by toxic doses of dexamethasone leading to focal necrosis of hepatocytes.


[Guidelines for diagnosis and management of cirrhotic ascites and its complications. The Israeli Association for the Study of the Liver].
Ascites is the most common manifestation of decompensated liver cirrhosis. The life expectancy of cirrhotic patients developing uncomplicated ascites is 50% for 3 years. Refractory ascites, electrolyte imbalance, hepato-renal syndrome and spontaneous bacterial peritonitis may develop. Successful treatment can improve symptoms and outcomes. This article summarizes the Israeli Association for the Study of the Liver guidelines for diagnosis and management of cirrhotic ascites and its complications.


Quality of life related to visual function in three young adults with mucopolysaccharidoses.
The systemic mucopolysaccharidoses are complex syndromes, which may include corneal clouding as a mechanism leading to decreased vision and hence decreased quality of life. This study presents three young adult patients with mucopolysaccharidoses in order to compare their visual status through retrospective chart review, including patient and guardian interview, history, and examination, including a modified form of the VF-14 questionnaire (visual function with 14 questions). When the visual acuity and VF-14 results of the three patients were compared, the results of the VF-14 correlated with the patients" visual acuity status. The two patients who retained clear corneas or underwent penetrating keratoplasty had a wider range of social and physical activities, and an overall better quality of life than did the patient with decreased vision due to opacified corneas. We conclude that close monitoring of the ocular health of patients with storage syndromes that may compromise visual acuity must be stressed, and intervention to insure good vision is of the utmost importance to maintaining a good quality of life for these patients, especially as new therapies assist these patients to achieve increased longevity with better health.


Pulsed field gel electrophoresis identifies a high degree of variability in the number of tandem 21-hydroxylase and complement C4 gene repeats in 21-hydroxylase deficiency haplotypes.
The human steroid 21-hydroxylase gene, CYP21B, and its closely homologous pseudogene, CYP21A, are each normally located centromeric to a complement C4 gene C4B and C4A respectively, in an organization suggesting tandem duplication of a CYP21 + C4 unit. Such an organization has been considered to facilitate gene deletion and addition events by unequal crossover between the tandem repeats. However, the large size (approximately 30 kb) of the individual CYP21 + C4 repeat units together with the difficulty in identifying reliable CYP21A- and CYP21B-specific markers has prevented direct monitoring of gene organization on individual haplotypes by conventional Southern analyses. In the present investigation we have sought to clarify the CYP21 and C4 gene organization in members of 32 British 21-hydroxylase deficiency families by employing additional experimental approaches, notably a long-range restriction mapping approach, which permits assessment through a VNTR type of analysis, of the number of CYP21 and C4 units on individual haplotypes. Our results show that there is a very high frequency (33%) of 21-hydroxylase deficiency haplotypes where functional CYP21B gene sequence has been removed as a consequence of CYP21 + C4 gene deletion while several haplotypes show evidence of gene addition. In each case that we have investigated the gene deletion and gene addition haplotypes differ in length from conventional haplotypes by integral multiples of approximately 30 kb, which strongly supports the involvement of unequal crossover mechanisms. Additionally, the comparatively frequent occurrence of CYP21 fusion genes which contain both CYP21A- and CYP21B-associated markers is suggested by the combined data from Southern analyses, long-range restriction mapping and characterization of selected regions of CYP21 genes which have been amplified in vitro.


Aberrant expression of long noncoding RNAs in chronic thromboembolic pulmonary hypertension.
Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the primary causes of severe pulmonary hypertension. In order to identify long noncoding RNAs (lncRNAs) that may be involved in the development of CTEPH, comprehensive lncRNA and messenger RNA (mRNA) profiling of endothelial tissues from the pulmonary arteries of CTEPH patients was conducted with microarray analysis. Differential expression of 185 lncRNAs was observed in the CTEPH tissues compared with healthy control tissues. Further analysis identified 464 regulated enhancer‑like lncRNAs and overlapping, antisense or nearby mRNA pairs. Coexpression networks were subsequently constructed and investigated. The expression levels of the lncRNAs, NR_036693, NR_027783, NR_033766 and NR_001284, were significantly altered. Gene ontology and pathway analysis demonstrated the potential role of lncRNAs in the regulation of central process, including inflammatory response, response to endogenous stimulus and antigen processing and presentation. The use of bioinformatics may help to uncover and analyze large quantities of data identified by microarray analyses, through rigorous experimental planning, statistical analysis and the collection of more comprehensive data regarding CTEPH. The results of the present study provided evidence which may be helpful in future studies on the diagnosis and management of CTEPH.


A Case of Solitary Lung Metastasis of Breast Cancer Successfully Treated with Stereotactic Body Radiotherapy after Chemotherapy.
A 62-year-old woman with triple-negative breast cancer underwent breast-conserving surgery followed by adjuvant chemotherapy and radiotherapy to the breast. The patient developed a solitary lung metastasis at the left hilum 44 months after the operation. The lung metastasis responded partially to capecitabine chemotherapy, but showed regrowth in 7 months. The patient received second-line oral cyclophosphamide (CPA) chemotherapy, resulting in marked tumor regression without new lesions for 10 months. To further control the lung metastasis, stereotactic body radiotherapy (SBRT; 5.1 Gy ×10 fractions) under breath holding without a localization device was given to the regressed lung metastasis after CPA therapy. Positron emission tomography at 24 months after the completion of SBRT did not show any recurrences, and the patient has been well for 100 months without any recurrences. Breast oncologist should take SBRT into consideration to treat lung oligometastasis of breast cancer especially locating at the lung hilum with curative intent.


Effects of Mikania glomerata Spreng. and Mikania laevigata Schultz Bip. ex Baker (Asteraceae) extracts on pulmonary inflammation and oxidative stress caused by acute coal dust exposure.
Several studies have reported biological effects of Mikania glomerata and Mikania laevigata, used in Brazilian folk medicine for respiratory diseases. Pneumoconiosis is characterized by pulmonary inflammation caused by coal dust exposure. In this work, we evaluated the effect of pretreatment with M. glomerata and M. laevigata extracts (MGE and MLE, respectively) (100 mg/kg, s.c.) on inflammatory and oxidative stress parameters in lung of rats subjected to a single coal dust intratracheal instillation. Rats were pretreated for 2 weeks with saline solution, MGE, or MLE. On day 15, the animals were anesthetized, and gross mineral coal dust or saline solutions were administered directly in the lung by intratracheal instillation. Fifteen days after coal dust instillation, the animals were killed. Bronchoalveolar lavage (BAL) was obtained; total cell count and lactate dehydrogenase (LDH) activity were determined. In the lung, myeloperoxidase activity, thiobarbituric acid-reactive substances (TBARS) level, and protein carbonyl and sulfhydryl contents were evaluated. In BAL of treated animals, we verified an increased total cell count and LDH activity. MGE and MLE prevented the increase in cell count, but only MLE prevented the increase in LDH. Myeloperoxidase and TBARS levels were not affected, protein carbonylation was increased, and the protein thiol levels were decreased by acute coal dust intratracheal administration. The findings also suggest that both extracts present an important protective effect on the oxidation of thiol groups. Moreover, pretreatment with MGE and MLE also diminished lung inflammatory infiltration induced by coal dust, as assessed by histopathologic analyses. The present study indicates that M. glomerata and M. laevigata might become good candidates for the prevention of lung oxidative injury caused by coal dust exposure.


Structure-activity relationships in further series of amino-halogen substituted phenyl-aminoethanols.
Series of 1-(4-amino-phenyl)-2-aminoethanol derivatives having different substituents in the phenyl nucleus were compared with 1-(4-amino-3,5-dichloro-phenyl)-2-tert.-butylamino-ethanol (clenbuterol) with regard to their action on the adrenergic beta-receptors of guinea pigs, cats and rats. The exchange of the two chlorine atoms of clenbuterol led to substances with a potent beta 2-mimetic activity, surpassing that of clenbuterol, in the bronchial muscles and/or to a beta 1-blocking action in the heart with a relatively low beta 1-intrinsic activity. The strongest action was found with the chloro-cyano, fluoro-cyano and mono-cyano substituted compounds. The chloro-fluoro, bromo-fluoro, mono-fluoro and chloro-trifluoromethyl substituted compounds showed a good oral absorption, comparable to that of clenbuterol. Because of a particularly low beta 1-intrinsic activity in the heart with a long-lasting beta 2-mimetic action on the bronchial muscles also after oral administration, the 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol) must come of all the structures investigated particularly into consideration as broncholytic agent for therapeutic use.


Uncovering the Principles of Genome Folding by 3D Chromatin Modeling.
Our understanding of how genomic DNA is tightly packed inside the nucleus, yet is still accessible for vital cellular processes, has grown dramatically over recent years with advances in microscopy and genomics technologies. Computational methods have played a pivotal role in the structural interpretation of experimental data, which helped unravel some organizational principles of genome folding. Here, we give an overview of current computational efforts in mechanistic and data-driven 3D chromatin structure modeling. We discuss strengths and limitations of different methods and evaluate the added value and benefits of computational approaches to infer the 3D structural and dynamic properties of the genome and its underlying mechanisms at different scales and resolution, ranging from the dynamic formation of chromatin loops and topological associated domains to nuclear compartmentalization of chromatin and nuclear bodies.


[Studies on the novel association of human herpesvirus-7 with skin diseases].
Human herpesvirus 7 in pityriasis rosea, this and other viruses in papular-purpuric gloves-and-socks syndrome have been implicated, but their primary or recurrent infections are still in question. In one available blood sample, therefore, IgM, IgG and its high avidity fraction characteristic for recurrent infections were quantitated by indirect immunofluorescence. Peripheral lymphocytes were subjected to nested polymerase chain reaction to detect viral DNA, or cocultivated with several cell cultures. One third of 33 pityriasis rosea patients had elevated IgM, another third had elevated IgG without high avidity molecules to human herpesvirus 7 suggesting primary infection. Thirty percent of controls, more than half of the patients had virtual DNA in their lymphocytes, but only one in 5 skin biopsy specimens were PCR positive. All three co-cultivation attempts yielded viruses extremely rapidly, verified by electron microscopy, polymerase chain reaction and monoclonal antibodies as human herpesvirus 7. These are the first isolates in the geographical regions of Hungary. These data suggest that pityriasis rosea is the consequence of a primary human herpesvirus 7 infection in seronegative adults, and only occasionally is due to virus reactivation. One patient with gloves-and-socks syndrome had an acute, another patient had a persistent coinfection with human herpesvirus 7 and parvovirus B19, two others had a primary herpesvirus 7 infection. Interestingly, this disease might be elicited by both viruses individually or in synergism. Neither human herpesvirus 7 nor parvovirus B19 infect skin cells, but both can be detected in the infiltrating lymphocytes of skin eruptions, in which they induce an altered mediator production, that might be responsible for the general and local symptoms.


Novel therapies for myelodysplastic syndromes.
The assessment of patients with myelodysplastic syndromes (MDS) and the choice of therapies remain challenging. New therapies are now emerging after the identification of molecular targets that result in improvement of hematologic parameters and may hold promise for the prevention of disease progression. A review of the English literature was performed that included original articles and related reviews from MEDLINE (PubMed) and abstracts based on published meeting material. MDS is a heterogeneous group of disorders. Although current classification and prognostic schemes have proven valid to define subgroups, they are insufficient to take into consideration the significant biologic diversity of MDS. New molecular targets are identified as the mosaic of pathophysiologic pathways in MDS is being unraveled. Novel and targeted therapeutic agents, such as the inhibition of farnesyl transferases and receptor tyrosine kinases, more potent thalidomide analogs, and arsenic trioxide, have shown encouraging results and may offer durable benefit to patients with MDS. Although progress has been made in the understanding of clinical manifestations and some of the molecular pathways underlying ineffective hematopoiesis and leukemic transformation in MDS, intensive clinical and laboratory research continues to 1) identify further relevant pathophysiologic pathways, 2) better define MDS subgroups, and 3) develop new drugs based on a clearer understanding of disease biology.


A hospital archives ... what's it all about?
Establishing a hospital archives can be a daunting, though exciting project, with many positive outcomes. The description of archives, in general, and the distinctions of a hospital archives, specifically, are presented. The initial steps which need to be considered when developing a hospital archives are detailed using the Maine Medical Center Archives as an example.


Distinguishing Admissions Specifically for COVID-19 from Incidental SARS-CoV-2 Admissions: A National EHR Research Consortium Study.
Admissions are generally classified as COVID-19 hospitalizations if the patient has a positive SARS-CoV-2 polymerase chain reaction (PCR) test. However, because 35% of SARS-CoV-2 infections are asymptomatic, patients admitted for unrelated indications with an incidentally positive test could be misclassified as a COVID-19 hospitalization. EHR-based studies have been unable to distinguish between a hospitalization specifically for COVID-19 versus an incidental SARS-CoV-2 hospitalization. From a retrospective EHR-based cohort in four US healthcare systems, a random sample of 1,123 SARS-CoV-2 PCR-positive patients hospitalized between 3/2020â€"8/2021 was manually chart-reviewed and classified as admitted-with-COVID-19 (incidental) vs. specifically admitted for COVID-19 (for-COVID-19). EHR-based phenotyped feature sets filtered out incidental admissions, which occurred in 26%. The top site-specific feature sets had 79-99% specificity with 62-75% sensitivity, while the best performing across-site feature set had 71-94% specificity with 69-81% sensitivity. A large proportion of SARS-CoV-2 PCR-positive admissions were incidental. Straightforward EHR-based phenotypes differentiated admissions, which is important to assure accurate public health reporting and research.


Enhancement of in vitro cell motility and invasiveness of human malignant pleural mesothelioma cells through the HIF-1α-MUC1 pathway.
In this study, we examined the effects of hypoxia on the malignancy of human malignant pleural mesothelioma (MPM) cell lines, and found (1) hypoxia enhanced motility and invasiveness of human malignant pleural mesothelioma (MPM) cells; (2) this phenomenon resulted from increased expression of sialylated MUC1 through the activation of HIF-1 pathway; (3) two HIF-binding sites located in the promoter region of MUC1 were important for MUC1 transactivation under hypoxia. These findings are useful for better understanding molecular mechanisms of aggressive behavior of MPM cells and for targeting them in the clinical therapies for MPM patients.


The induction of tolerance of renal allografts by adoptive transfer in miniature swine.
Our previous in vitro data have demonstrated that regulatory mechanisms are involved in tolerance of class I-mismatched renal allografts in miniature swine treated with 12 days of high dose Cyclsporin A. In this study, we attempted to induce tolerance of class I-mismatched kidneys by adoptive transfer of cells and/or kidneys from long-term tolerant animals. Fifteen SLA(dd) miniature swine received 1.5 Gy whole body irradiation and class I-mismatched (SLA(gg) ) kidneys from naïve pigs with or without cotransplanted kidneys and/or adoptively transferred cells from long-term tolerant (LTT) SLA(dd) recipients of SLA(gg) grafts. In addition, three SLA(dd) miniature swine received class I mismatched kidney with adoptively transferred cells from LTT SLA(dd) recipients. Naïve kidneys transplanted without a LTT kidney were rejected within 9 days. All recipients of naive kidneys along with cells and kidney grafts from LTT animals showed markedly prolonged survival of the naive renal grafts (day 28, >150 and >150 days). These studies suggest that (1) tolerated kidneys have potent regulatory effects and (2) cells from LTT animals infused in conjunction with kidney grafts augment these regulatory effects. To our knowledge, these studies represent the first demonstration of successful adoptive transfer of tolerance in large animals.


Combined captopril treatment in severe and moderately severe hypertension resistant to therapy.
Combined Captopril treatment was applied in 61 patients with severe or moderately severe hypertension in patients insufficiently or not reacting to the usual combined antihypertensive therapy (3-7 kinds of drug). The combination included diuretics, beta-blockers, alpha-blockers, vasodilators, Ca-antagonists and centrally acting agents. Diuretics were used in all cases. Average duration of treatment was 8.2 months (i.e. 2-40 months). Mean systolic pressure prior to Captopril treatment was 202.4 mm Hg (S.D. +/- 27.6), while the diastolic 122.0 mm Hg (S.D. +/- 11.3). During combined Captopril treatment the average values were 154.2 mm Hg (S.D. +/- 18.8) and 97.6 mm Hg diastolic pressures (S.D. +/- 10.7), the difference being significant (p less than 0.001). Refractory hypertension occurred in three middle-aged female patients in response to combined Captopril treatments. Captopril treatment had to be discontinued for the appearance of side-effects (severe skin symptoms) only in a single case. A minor deterioration of renal functions was observed in three patients (in one bilateral renovascular, and in two essential hypertension). Serum creatinine value and renal functions of four patients showed significant improvement as a result of combined Captopril treatment. During combined Captopril treatments (also with a diuretic) two patients had so severe hypokalaemia that they needed potassium substitution or administration of a potassium-saving diuretic.


miRNA‑mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin‑induced acute kidney injury identifies roles for miR‑210/Serpine1 and miR‑378/Fos in regulating inflammation.
The present study aimed to identify microRNAs (miRNAs) that may be crucial for the mechanism of mesenchymal stem cell (MSC) treatment in cisplatin‑induced acute kidney injury (AKI) and to investigate other potential drugs that may have a similar function. Transcriptomics (GSE85957) and miRNA expression (GSE66761) datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified using the linear models for microarray data method and mRNA targets of DEMs were predicted using the miRWalk2.0 database. The crucial DEGs were screened by constructing a protein‑protein interaction (PPI) network and module analysis. Functions of target genes were analyzed using the database for annotation, visualization and integrated discovery. Small molecule drugs were predicted using the connectivity map database. As a result, 5 DEMs were identified to be shared and oppositely expressed in comparisons between AKI model and control groups, and between MSC treatment and AKI model groups. The 103 DEGs were overlapped with the target genes of 5 common DEMs, and the resulting list was used for constructing the miRNA‑mRNA regulatory network, including rno‑miR‑210/Serpine1 and rno‑miR‑378/Fos. Serpine1 (degree=17) and Fos (degree=42) were predicted to be hub genes according to the topological characteristic of degree in the PPI network. Function analysis indicated Serpine1 and Fos may be inflammation‑related. Furthermore, gliclazide was suggested to be a potential drug for the treatment of AKI because the enrichment score was the closest to ‑1 (‑0.9). In conclusion, it can be speculated that gliclazide may have a similar mechanism to MSC as a potential therapeutic agent for cisplatin‑induced AKI, by regulating miR‑210/Serpine1 and miR‑378‑/Fos‑mediated inflammation and cell apoptosis.


Ribosomal binding site of release factors RF1 and RF2. A new translational termination assay in vitro.
We have established a new in vitro assay for translational termination. It consists of 70 S ribosomes bound to a synthetic RNA minimessenger via interaction with P-site binding fMet-tRNAfMet. If the A-site codon is a stop signal, release activity can be measured by quantifying hydrolyzed formylmethionine. Characteristics of this assay in terms of reaction time, ion concentration, release factor RF1 and RF2 concentration, and competition with A-site-decoding tRNA are discussed. The new assay shows that polypeptide chain release activity is directly dependent on the presence of a stop codon in the ribosomal A-site.


Analysis of flow disturbance in a stenosed carotid artery bifurcation using two-equation transitional and turbulence models.
In this study, newly developed two-equation turbulence models and transitional variants are employed for the prediction of blood flow patterns in a diseased carotid artery where the growth, progression, and structure of the plaque at rupture are closely linked to low and oscillating wall shear stresses. Moreover, the laminar-turbulent transition in the poststenotic zone can alter the separation zone length, wall shear stress, and pressure distribution over the plaque, with potential implications for stresses within the plaque. Following the validation with well established experimental measurements and numerical studies, a magnetic-resonance (MR) image-based model of the carotid bifurcation with 70% stenosis was reconstructed and simulated using realistic patient-specific conditions. Laminar flow, a correlation-based transitional version of Menter's hybrid k-epsilon/k-omega shear stress transport (SST) model and its "scale adaptive simulation" (SAS) variant were implemented in pulsatile simulations from which analyses of velocity profiles, wall shear stress, and turbulence intensity were conducted. In general, the transitional version of SST and its SAS variant are shown to give a better overall agreement than their standard counterparts with experimental data for pulsatile flow in an axisymmetric stenosed tube. For the patient-specific case reported, the wall shear stress analysis showed discernable differences between the laminar flow and SST transitional models but virtually no difference between the SST transitional model and its SAS variant.


Effect of lymphoplasmapheresis on clinical indices and T cell subsets in rheumatoid arthritis. A double-blind controlled study.
The effects of lymphoplasmapheresis on immunologic indices, including T cell subsets, and on clinical parameters of rheumatoid arthritis were evaluated in a controlled double-blind trial. Twenty patients were randomized to receive either 6 lymphoplasmapheresis sessions or a seemingly identical control procedure over a 3-week period. Lymphoplasmapheresis produced significant reduction in serum levels of total lymphocytes, erythrocyte sedimentation rate, C-reactive protein, and IgG. These serologic measures returned to baseline 5 weeks after lymphoplasmapheresis. No change in the imbalance of T cell subsets (increased helper/suppressor ratio) was observed. No changes in the serologic measures, except IgA, were observed in the control group. An improvement in some of the clinical parameters was observed in both the lymphoplasmapheresis and control groups. A rebound above baseline values for several parameters was observed in both the lymphoplasmapheresis and the sham apheresis groups.


Single-trial log transformation is optimal in frequency analysis of resting EEG alpha.
The appropriate definition and scaling of the magnitude of electroencephalogram (EEG) oscillations is an underdeveloped area. The aim of this study was to optimize the analysis of resting EEG alpha magnitude, focusing on alpha peak frequency and nonlinear transformation of alpha power. A family of nonlinear transforms, Box-Cox transforms, were applied to find the transform that (a) maximized a non-disputed effect: the increase in alpha magnitude when the eyes are closed (Berger effect), and (b) made the distribution of alpha magnitude closest to normal across epochs within each participant, or across participants. The transformations were performed either at the single epoch level or at the epoch-average level. Alpha peak frequency showed large individual differences, yet good correspondence between various ways to estimate it in 2 min of eyes-closed and 2 min of eyes-open resting EEG data. Both alpha magnitude and the Berger effect were larger for individual alpha than for a generic (8-12 Hz) alpha band. The log-transform on single epochs (a) maximized the t-value of the contrast between the eyes-open and eyes-closed conditions when tested within each participant, and (b) rendered near-normally distributed alpha power across epochs and participants, thereby making further transformation of epoch averages superfluous. The results suggest that the log-normal distribution is a fundamental property of variations in alpha power across time in the order of seconds. Moreover, effects on alpha power appear to be multiplicative rather than additive. These findings support the use of the log-transform on single epochs to achieve appropriate scaling of alpha magnitude.


Arthrogryposis as neonatal presentation of Loeys-Dietz syndrome due to a novel TGFBR2 mutation.
Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized mainly by cardiovascular, craniofacial and skeletal features. We report on a patient with LDS, whose prenatal examination was compatible with the diagnosis of arthrogryposis multiplex congenita. Neonatal assessment showed craniofacial and cardiovascular findings suggestive of LDS whose diagnosis was confirmed by the detection of a novel mutation (HGVN: NM_003242.5 (TGFBR2): c.1381T > C (p.(Cys461Arg))) in the TGFBR2 gene. Few prenatal and neonatal cases of LDS have been reported in the literature. We reviewed all cases reported to date with perinatal onset to delineate the clinical manifestations that allow us to prompt diagnosis of this syndrome at an early stage to prevent fatal cardiovascular complications. Furthermore we discuss the multidisciplinary follow up required in these patients.


In Vitro Evaluation of the Antiamoebic Activity of Kaempferol against Trophozoites of Entamoeba histolytica and in the Interactions of Amoebae with Hamster Neutrophils.
Entamoeba histolytica (E. histolytica) is a parasite in humans that provokes amoebiasis. The most employed drug is metronidazole (MTZ); however, some studies have reported that this drug induces genotoxic effects. Therefore, it is necessary to explore new compounds without toxicity that can eliminate E. histolytica. Flavonoids are polyphenolic compounds that have demonstrated inhibition of growth and dysregulation of amoebic proteins. Despite the knowledge acquired to date, action mechanisms are not completely understood. The present work evaluates the effect of kaempferol against E. histolytica trophozoites and in the interactions with neutrophils from hamster, which is a susceptibility model. Our study demonstrated a significant reduction in the amoebic viability of trophozoites incubated with kaempferol at 150 μM for 90 min. The gene expression analysis showed a significant downregulation of Pr (peroxiredoxin), Rr (rubrerythrin), and TrxR (thioredoxin reductase). In interactions with amoebae and neutrophils for short times, we observed a reduction in ROS (reactive oxygen species), NO (nitric oxide), and MPO (myeloperoxidase) neutrophil activities. In conclusion, we confirmed that kaempferol is an effective drug against E. histolytica through the decrease in E. histolytica antioxidant enzyme expression and a regulator of several neutrophil mechanisms, such as MPO activity and the regulation of ROS and NO.


Violent and Nonviolent Youth Offenders: Preliminary Evidence on Group Subtypes.
Youth violence is a costly social problem. This study compared the risk and needs of nonviolent youth offenders, with those who had committed violent offenses only (violent only) and those who had committed violent and nonviolent offenses (violent plus) to determine whether violent youth were a different "type" from nonviolent youth. The case files of 3,744 youth offenders (3,327 males and 417 females, between 12 and 18 years old) were retrospectively coded, before official recidivism records were obtained. Multivariate analysis of variance (MANOVA), χ2, and Cox regressions were conducted. Violent-plus youth were younger; higher in their total risk and all criminogenic needs; more likely to have several noncriminogenic needs; and at higher risk of any reoffending, violent reoffending, and nonviolent reoffending than nonviolent youth. Violent-only youth had the same total risk and risk of general and violent recidivism as nonviolent offenders but presented different criminogenic and noncriminogenic needs and risk of nonviolent recidivism. Compared to violent-only youth, violent-plus youth were younger, had higher total risk and criminogenic needs on five domains, were more likely to have several noncriminogenic needs, and were at higher risk of all types of reoffending (except sexual reoffending), suggesting subtypes of violent youth offenders. The implication is that nonviolent and violent youth offenders require different dosage and types of intervention.


Generic decoding of seen and imagined objects using hierarchical visual features.
Object recognition is a key function in both human and machine vision. While brain decoding of seen and imagined objects has been achieved, the prediction is limited to training examples. We present a decoding approach for arbitrary objects using the machine vision principle that an object category is represented by a set of features rendered invariant through hierarchical processing. We show that visual features, including those derived from a deep convolutional neural network, can be predicted from fMRI patterns, and that greater accuracy is achieved for low-/high-level features with lower-/higher-level visual areas, respectively. Predicted features are used to identify seen/imagined object categories (extending beyond decoder training) from a set of computed features for numerous object images. Furthermore, decoding of imagined objects reveals progressive recruitment of higher-to-lower visual representations. Our results demonstrate a homology between human and machine vision and its utility for brain-based information retrieval.


[Diagnostic and therapeutic management of breast cysts].
In a study of 144 patients with cystic dysplasia of the breast diagnostic and therapeutic accuracy of palpation, mammography, aspiration cytology and pneumocystography was investigated. Only in 9.7% of the cases a surgical biopsy was necessary. In more than 90% of the cases biopsy was not performed; instead of this follow up with palpation, mammography and aspiration cytology up to 11 months was done. No breast cancer was overlooked, three of four proliferating dysplasias were detected. In 21% a local cystic recidive occurred which again was punctured. In contrary to surgical biopsy follow up of cystic dysplasias is not complicated by scars and their diagnostic problems. No complications were seen.


Chrysophanol suppresses pro-inflammatory response in microglia via regulation of Drp1-dependent mitochondrial fission.
Chrysophanol, also called chrysophanic acid, is a natural anthraquinone compound found in Rheum palmatum. R. palmatum has been used in oriental medicine in ancient East Asia. Microglial cells represent not only the forefront immune defense in the central nervous system but also the most reactive sensors to various threats. However, activated microglia can exert neurotoxic effects via excessive production of cytotoxic molecules and proinflammatory cytokines. Therefore, modulation of microglial cell activation is important for maintaining neuronal function. Pretreatment of chrysophanol in BV-2 murein microglial cells was carried out for 1 hour, followed by stimulation with 1 μg/mL LPS. Level of proteins and RNAs were detected by western blotting and Reverse Transcriptase PCR. DsRed2-Mito-expressing cells were used for detecting mitochondrial morphology. In this study, we determined the effects of chrysophanol on lipopolysaccharide (LPS)-induced microglial activation. Chrysophanol inhibited the LPS-induced production of proinflammatory mediators and cytokines via suppression of mitogen-activated protein kinase/nuclear factor kappa-B activation and reactive oxygen species generation. In addition, chrysophanol downregulated LPS-induced mitochondrial fission by diminishing dynamin-related protein 1 (Drp1) dephosphorylation. Taken together, chrysophanol suppressed the proinflammatory response of activated microglia via inhibition of Drp1-dependent mitochondrial fission. Our findings can provide the basis for the use of chrysophanol in microglial inflammatory response-mediated neurodegenerative diseases. Furthermore, our study can contribute to the production of new drugs for inflammatory response-mediated neurodegenerative diseases by purification of chrysophanol.


MRI of the Achilles tendon: a comprehensive review of the anatomy, biomechanics, and imaging of overuse tendinopathies.
The Achilles tendon is the largest tendon in the body; it plays an important role in the biomechanics of the lower extremity. It can withstand great forces, especially during sporting exercises and pivoting. The pathologies related to the Achilles tendon are diverse and many carry undesirable consequences. We retrospectively analyzed the images of patients who underwent examinations of the ankle/foot region to review the anatomy of the Achilles tendon and its surroundings and to search for pathologies consistent with overuse injuries. The anatomy of the tendon is described from origin to insertion. The imaging characteristics of the Achilles tendon including pitfalls are reviewed. We also describe the Achilles overuse injuries: paratenonitis, tendinosis, tendon tear, atypical tear, tendon re-tear, retrocalcaneal bursitis, retro-Achilles bursitis, Haglund's deformity, and tendon calcification. We present other entities like tendon ossification and failed transplanted Achilles tendon, with emphasis on MRI.


[A Case of Late Recurrence of Breast Cancer Causing Multiple Organ Metastases 27 Years Postoperatively].
The patient was a 77-year-old female with a history of treatment for cancer of the right breast 27 years earlier, who presented with a chief complaint of a subcutaneous mass in the left lower quadrant of her abdomen. A thorough examination revealed high breast cancer-related tumor marker values, and based on a computed tomography(CT)examination, a tentative diagnosis of multiple lung, liver, retroperitoneal, and abdominal wall metastases was made. Although there were multiple organ metastases, in view of the long interval before the recurrence, absence of any symptoms, and the patient's age, we initiated treatment by weekly administration of an aromatase inhibitor and trastuzumab. The treatment was effective; the multiple metastases regressed, and the tumor marker levels decreased. One year after the start of treatment, the patient had a rebound in the tumor marker levels, and an increase in the size of the liver metastases was observed in diagnostic images. The aromatase inhibitor was discontinued and replaced with high-dose toremifene citrate, and trastuzumab was administered every other week. This regimen achieved efficacy, and the liver metastases regressed. As of 2years since the start of the initial treatment, no progression of the metastases has been observed, and the patient continues to be treated with the same regimen.


[Detection of the pericardial branch of the phrenic nerve by silver impregnation method].
The pericardial branch (R. pericardiacus) of the phrenic nerve (N. phrenicus) was examined in 14 pericardia of 8 male and 6 female adult Japanese cadavers. Specimens were impregnated with silver nitrate, and cleared and mounted in lactic acid. A pericardial branch was detected in the right side of one specimen (No. 273, male). This branch arose from the phrenic nerve at approximately the same level as the root of lung. The branch ran from the cervical plexus together with the proper phrenic nerve. The distribution of this branch to the pericardium could not be determined as the branch was accidentally cut near the above mentioned arising point during the anatomical practice. Even by this impregnation method, the pericardial branch of the phrenic nerve could not be detected in any other specimens.


Compact all-fiber thermo-optic modulator based on a Michelson interferometer coated with NaNdF4 nanoparticles.
We propose and investigate an all-fiber thermo-optic modulator based on a side-polished twin-core fiber (TCF) Michelson interferometer (MI) coated with NaNdF4 nanoparticles. The MI was fabricated by tapering the splicing point between the TCF and a single mode fiber (SMF). A short suspended core fiber (SCF) is spliced to one core of the TCF to introduce a fixed optical phase difference (OPD). The side-polished core is coated with photo-thermal material NaNdF4. Owing to the ohmic heating of NaNdF4 nanoparticles under 808 nm pump laser, the effective refractive index of the polished core is changed, resulting in a phase shift of the MI. The MI has a significant modulation phase shift with 2.9 π near the wavelength of 1260 nm and can obtain an optical switching with a rise (fall) time of 152 (50) ms. The proposed device will have a great application potential in optical modulators due to compact structure and strong robustness.


Climate variability and migration in the Philippines.
This study investigates the effects of climatic variations and extremes captured by variability in temperature, precipitation, and incidents of typhoons on aggregate inter-provincial migration within the Philippines using panel data. Our results indicate that a rise in temperature and to some extent increased typhoon activity increase outmigration, while precipitation does not have a consistent, significant effect. We also find that temperature and typhoons have significant negative effects on rice yields, a proxy for agricultural productivity, and generate more outmigration from provinces that are more agriculturally dependent and have a larger share of rural population. Finally, migration decisions of males, younger individuals, and those with higher levels of education are more sensitive to rising temperature and typhoons. We conclude that temperature increase and to some extent typhoon activities promote migration, potentially through their negative effect on crop yields. The migration responses of males, more educated, and younger individuals are more sensitive to these climatic impacts.


Effects of increasing co-product inclusion and reducing dietary protein on growth performance, carcass characteristics, and jowl fatty acid profile of growing-finishing pigs.
Dietary inclusion of co-products (Co-P) provides opportunities for diversifying the feedstuff matrix by using local feedstuffs, reducing feed costs, and producing value-added pork. In 2 studies, we determined effects of Co-P (canola meal, distillers dried grains with solubles, and co-extruded oil seed and field pea) inclusion level and reduced dietary CP concentration on growth performance, carcass characteristics, and jowl fatty acid profiles of growing-finishing pigs. Pigs were fed isoenergetic and isolysinic diets over 4 growth phases with 8 pen observations per dietary regimen. At slaughter, carcasses were characterized for all pigs and jowl fat was collected from 2 pigs per pen. In Exp. 1, 1,056 pigs (initial BW, 35.3 ± 0.4 kg) were fed 3 levels of dietary Co-P (low, mid, and high) and 2 CP concentrations (low and normal). Overall (d 0 to 86), increasing Co-P inclusion from low to mid or high decreased (P < 0.001) ADFI and ADG of pigs. Low CP concentration increased (P < 0.05) ADFI and ADG compared with normal CP concentration. An interaction (P = 0.026) occurred between dietary Co-P inclusion and CP concentration for G:F; low CP reduced (P < 0.05) G:F compared with normal CP for pig fed low Co-P, but G:F did not differ between CP concentrations for pigs fed mid and high Co-P. Increasing dietary Co-P inclusion from low to high increased (P < 0.001) α-linolenic acid (ALA) in jowl fat but decreased (P < 0.001) carcass weight and loin depth. In Exp. 2, 1,008 pigs (initial BW, 30.3 ± 0.4 kg) were assigned to 5 dietary regimens with Co-P increasing from 2.0 to 50.0% or a sixth regimen with 10% extra supplemental AA for the 37.5% Co-P diet. Overall (d 0 to 97), increasing Co-P inclusion did not affect ADFI, ADG, and G:F. Increasing dietary Co-P inclusion linearly decreased (P < 0.01) carcass weight, dressing percentage, backfat thickness, and loin depth but linearly increased (P < 0.001) jowl ALA. Supplementing 10% extra AA to the 37.5% Co-P diet did not affect growth performance or dressing percentage but increased (P = 0.014) carcass leanness and decreased (P = 0.023) backfat thickness compared with the 37.5% Co-P diet, indicating that dietary AA supply did not limit BW gain. In conclusion, Co-P can be included by up to 50% in diets for growing-finishing pigs without affecting G:F. However, increasing dietary Co-P may reduce ADG, ADFI, and carcass weight even if diets are balanced for dietary NE and standardized ileal digestible AA content.


5'-O-phosphonomethyl-2',3'-dideoxynucleosides: synthesis and anti-HIV activity.
5'-O-Phosphonomethylation of different pyrimidine 2',3'-dideoxynucleosides was accomplished by reaction of the latter with diethyl [(p-toylsulfonyl)oxy]methanephosphonate (1) in the presence of sodium hydride. The base-phosphonomethylated (15-19) and sugar-phosphonomethylated (8-12) derivatives could be readily distinguished by 1H and 13C NMR and MS analysis. Protection of the uracil or thymine residue with a N3-benzoyl group failed to prevent base modification. However, O4-methyl-protected 2',3'-dideoxyuridine readily afforded the 5'-O-phosphonomethylated derivative 12, which was converted to both the 2',3'-didoxyuridine analogue 27 and the 2',3'-dideoxycytidine counterpart 29. The 5'-O-phosphonomethyl derivatives of 3'-deoxythymidine (23), 2',3'-dideoxyuridine, (27), 2',3'-dideoxycytidine (29), 3'-O-methylthymidine (26), and 3'-amino-3'-deoxythymidine (28) did not show an appreciable anti-HIV activity in MT-4 cells. In contrast, the 5'-O-phosphonomethyl derivatives of 3'-deoxy-3'-fluorothymidine (24) and 3'-azido-3'-deoxythymidine (25) inhibited HIV-1 cytopathogenicity by 50% at a concentration of approximately 1 microM.


DYNAMIC AND GENETIC CONSEQUENCES OF VARIATION IN HORIZONTAL TRANSMISSION FOR A MICROPARASITIC INFECTION.
Transmission to a new host is a critical step in the life cycle of a parasite. Variation in the characteristics of the transmission process, for example, due to host demography, is assumed to select for different variants of the parasite. We have experimentally tested how variation in the time to transmission (early or late after infection) and exposure to adverse conditions outside the host (immediate or delayed contact with new host) interact to determine the success of the infection in the next host, using the trypanosome Crithidia bombi infecting its bumblebee host, Bombus terrestris. These two experimentally manageable steps mimic the processes of within- and among-host selection for the parasite. We found that early transmission led to higher infection success in the next host as did immediate contact with the new host. However, there was no interaction between the two parameters as would be expected if early-transmitted variants, resulting from rapid multiplication within the host, would be less adapted to the conditions encountered during the between-host transfer or infection of the next host. Furthermore, typing the genetic variability of the parasites with microsatellites showed that the four different transmission routes of our experiment selected for different degrees of allelic diversity of the infecting parasite populations. The results support the idea that variation in the transmission process selects for different genotypic variants of the parasite. At the same time, the relationship of allelic diversity with infection intensity suggested that the coinfection model of May and Nowak (1995) may be appropriate, where each parasite is able to infect and multiply independent of others within the same host.