Absence of Residual Microcalcifications in Atypical Ductal Hyperplasia Diagnosed via Stereotactic Vacuum-Assisted Breast Biopsy: Is Surgical Excision Obviated?
The purpose of our study was to evaluate the underestimation rate of atypical ductal hyperplasia (ADH) on vacuum-assisted breast biopsy (VABB), and to examine the correlation between residual microcalcifications and the underestimation rate of ADH. A retrospective study was performed on 27 women (mean age, 49.2±9.2 years) who underwent additional excision for ADH via VABB for microcalcifications observed by using mammography. The mammographic findings, histopathologic diagnosis of all VABB and surgical specimens, and association of malignancy with residual microcalcifications were evaluated. The underestimation rate of ADH was also calculated. Of the 27 women with microcalcifications, nine were upgraded to ductal carcinoma in situ (DCIS); thus, the underestimation rate was 33.3% (9/27). There was no difference in age (p=0.40) and extent of microcalcifications (p=0.10) when comparing benign and malignant cases. Six of 17 patients (35.3%) with remaining calcifications after VABB were upgraded to DCIS, and three of 10 patients (30%) with no residual calcifications after VABB were upgraded (p=1.00). The underestimation rate of ADH on VABB was 33.3%. Furthermore, 30% of patients with no remaining calcifications were upgraded to DCIS. Therefore, we conclude that all ADH cases diagnosed via VABB should be excised regardless of the presence of residual microcalcifications.


Long-range interactions stabilize the fold of a non-natural oligomer.
Toward designing nonbiological polymers that fold into predictable tertiary structures, we report a "beta-oligomer" composed of beta-amino acids that adopts a cooperatively folded structure. We have computationally designed a C(2)-symmetrical pair of interacting 14-helical beta-oligomers stabilized via long-range interhelical interactions and stapled together by a disulfide bond. The reduced (BHBred) and oxidized (BHBox) forms of the synthetic beta-oligomer represent the individual isolated helices and the two-helix bundle, respectively. We also prepared a third monomeric synthetic beta-oligomer (BHBmon) to avoid inadvertent disulfide formation during characterization. Circular dichroism spectroscopy revealed that BHBox showed a 2-fold increase in secondary structure, relative to the monohelical controls, BHBred and BHBmon. Further, BHBox showed a sigmoidal thermal unfolding curve with a per-residue van't Hoff enthalpy of approximately 0.7 kcal/(mol.residue), analogous to folded proteins. In contrast, BHBmon shows a broad thermal transition, typical of multistate unfolding for monomeric helices. Also, analytical ultracentrifugation showed that BHBmon and BHBox were monomeric at concentrations < or =800 and 280 microM, respectively. Therefore, the enhanced helicity of BHBox could be attributed to intramolecular helix-helix interactions.


Faster identification of optimal contraction sequences for tensor networks.
The efficient evaluation of tensor expressions involving sums over multiple indices is of significant importance to many fields of research, including quantum many-body physics, loop quantum gravity, and quantum chemistry. The computational cost of evaluating an expression may depend strongly on the order in which the index sums are evaluated, and determination of the operation-minimizing contraction sequence for a single tensor network (single term, in quantum chemistry) is known to be NP-hard. The current preferred solution is an exhaustive search, using either an iterative depth-first approach with pruning or dynamic programming and memoization, but these approaches are impractical for many of the larger tensor network ansätze encountered in quantum many-body physics. We present a modified search algorithm with enhanced pruning which exhibits a performance increase of several orders of magnitude while still guaranteeing identification of an optimal operation-minimizing contraction sequence for a single tensor network. A reference implementation for matlab, compatible with the ncon() and multienv() network contractors of arXiv:1402.0939 and Evenbly and Pfeifer, Phys. Rev. B 89, 245118 (2014), respectively, is supplied.


Aldose reductase inhibitor prevents hyperproliferation and hypertrophy of cultured rat vascular smooth muscle cells induced by high glucose.
Vascular remodeling is a key process in the pathophysiology of atherosclerosis. Recent evidence suggests that high glucose levels may function as a vascular smooth muscle growth and proliferation-promoting substance. To explore the role of the polyol pathway in this process, we examined the effect of an aldose reductase inhibitor (ARI), epalrestat, on the growth characteristics of cultured rat vascular smooth muscle cells (VSMCs). Epalrestat (10 nmol/L, 1 mumol/L) significantly suppressed the high glucose-induced proliferative effect as measured by [3H]thymidine incorporation by 67% and 82% in cell number, suggesting ARI as an antimitogenic factor. In VSMCs, epalrestat (10 nmol/L, 1 mumol/L) significantly suppressed the high glucose-induced incorporation of [3H]leucine by 45% and 58% with the concomitant reduction of the cell size estimated by flowcytometry. Epalrestat (1 mumol/L) also suppressed high glucose-induced intracellular NADH/NAD+ increase and membrane-bound protein kinase C activation. These results indicate that this ARI possesses an antiproliferative and antihypertrophic action on VSMCs induced by high glucose possibly through protein kinase C suppression.


Effect of fasting on insulin-like growth factor (IGF)-IA and IGF-IB messenger ribonucleic acids and prehormones in rat liver.
The insulin-like growth factor I (IGF-I) gene generates by alternative splicing two IGF-I messenger RNAs (mRNAs) coding for IGF-I prehormones with different E domain sequences. In rats, these two mRNAs differ by the presence (IGF-IB) or absence (IGF-IA) of a 52-bp insert in the E domain coding region. The purpose of this study was to investigate the effect of nutritional perturbation on IGF-IA and -IB expression in rat liver. Northern blot analysis of liver mRNA revealed that the 1.5-1.9 kb and 0.9-1.2 kb IGF-I mRNA species were decreased in rats fasted for 48 h compared with either fasted-refed (48 h of each) or control-fed rats (each, P < 0.01), whereas the 7.5 kb IGF-I mRNA was decreased only when compared with the fasted-refed animals. Using semiquantitative RT-PCR, the IGF-IA transcript (114 bp amplicon) was not altered, whereas the IGF-IB transcript (166 bp amplicon) was decreased in fasted rats compared with the other two groups (both P < 0.01). We confirmed the RT-PCR results by RNase protection assay (RPA), observing that the IGF-IA (224 and 100 bases protected) was not decreased and that the IGF-IB transcript (376 bases protected), accounting for only 23% of the total IGF-I transcripts of control fed rats, was decreased by fasting. Because the results from RT-PCR and RPA do not necessarily predict full-length translatable mRNA, we subjected hepatic IGF-I transcripts to in vitro translation, and we immunoprecipitated IGF-IA and -IB prehormones. Both prehormones were translated principally from exon 1-containing mRNAs, with molecular weights of about 17K and 18K, representing 80% and 20% of the total IGF-I prehormones observed in control fed rats, respectively. Both peptides were reduced in fasted rats compared with controls (P < 0.01), and refeeding restored both. By immunoblotting of the protein extract from liver of fasted rats, IGF-IA was decreased by 77% compared with control-fed animals. Refeeding returned IGF-IA to normal. The lack of reduction of IGF-IA transcript at the alternative splice site suggests that posttranscriptional mechanisms are responsible for the reduction in steady-state IGF-I mRNAs that occurs during fasting. Additionally, we present evidence that biosynthesis of IGF-IA and -IB prehormones by liver is impaired at a posttranscriptional level.


[Role of lyrics and melody in song recognition: why is song recognition faster?].
Two experiments were conducted to identify the role of lyrics and melody in song recognition. Experiment 1 (N = 30) investigated the ratings of familiarity, age of acquisition, retrievability of lyrics or melody, and happiness for 100 Japanese children's songs. In Experiment 2 (N = 31), a familiarity-judgment task was conducted involving three stimulus types-sung lyrics (SONG), spoken lyrics (LYRICS), and sung melody using the syllable/la/ (MELODY)--for two excerpts (beginning and middle locations). The participants were instructed to judge whether an excerpt sounded familiar as quickly as possible. The more familiar the songs, the easier could they be identified from the three stimulus types. SONG-response time (RT) was shorter than MELODY-RT for both beginning and middle, and than LYRICS-RT for the middle. The location effect emerged most prominently for LYRICS-RT. Our results suggest that interactively connected information of lyrics and melody may facilitate song recognition. Lyrics in the beginning might be an index only for certain, very familiar songs, whereas melody may play a facilitative role for song recognition regardless of location.


Plateau iris syndrome associated with multiple ciliary body cysts. Report of three cases.
To describe plateau iris syndrome associated with multiple neuroepithelial cysts of the pars plicata. Case reports of 3 patients with plateau iris syndrome who were found to have multiple bilateral ciliary body cysts on ultrasound biomicroscopic examination. Ultrasound biomicroscopy revealed classic features of plateau iris syndrome in each patient but also showed multiple neuroepithelial cysts of the ciliary body in each eye. Plateau iris syndrome may be associated with multiple ciliary body cysts.


Primary carcinoma of the vagina. Case report.
An unusual case of Primary Carcinoma of the vagina was recently observed. The patient was treated surgically in 1981 for squamous cervical carcinoma in situ (CIN 3); eight years later the same patient was treated for squamous carcinoma of the vagina that involved the upper, median and lower tract. She was treated with radical colpectomy and VBP chemotherapy for three courses. The pathology, natural history and treatment are discussed.


Green synthesised iron and iron-based nanoparticle in environmental and biomedical application: - a review.
Owing to the development of nanotechnology and its influence in various fields, the development of efficient and environmental friendly technique for the synthesis of nanomaterials is important. Among the various traditional and conventional methods available for the synthesis, plant-mediated synthesis seems to be a very attractive and environmental friendly method, attributing to its simple methodology and eco-friendly approach. The synthesis rate and stability of the nanoparticle synthesised are good when compared to the other methods of synthesis and it is proved to be efficient in various fields of application. Hence, the present review article deals with furnishing information about the plant sources used so far and details about the environmental and biomedical applications of the synthesised nanoparticles.


[Evaluation of a modified exogenous creatinine clearance as a suitable renal function test for the small animal practice].
A suitable method in the routine veterinary practice for the quantitative determination of the glomerular filtration rate (GFR) in dogs and cats has not been available until to date. Therefore, we modified the known plasma clearance model (=P-CL). The resulting P-CLterminal was assessed concerning its diagnostic value. P-CL of exogenous creatinine (P-CLcrea) and of inulin were determined in dogs (n=12, Beagle, 6 months of age) and cats (n=11, Domestic Short Hair, 14 months of age). The marker substances were administered as a bolus injection. In fasted dogs, P-CLcrea was 84.3 +/- 14.85 ml/min/m2 after a creatinine dose of 2.4 g/m2. An electrolyte infusion during the clearance determination did not alter the resulting values (p>0.05). In fasted cats, P-CLcrea was 54.7 +/- 5.8 ml/min/m2 (creatinine dose 2.0 g/m2). The inulin clearance, determined at the same time, was 104.5 +/- 19.81 ml/min/m2. Feeding the cats just before and during the test increased P-CL of both markers significantly (p<0.05). In order to adapt the clearance method for diagnostic assessment of GFR in the small animal practice, we aimed at minimizing the number of required blood samples (3 instead of 7 or more) and introduced the modified exogenous creatinine clearance (P-CLterminal). These values determined were 108.4 +/- 20.81 ml/min/m2 in fasted dogs and 66.3 +/- 11.81 ml/min/m2 in fasted cats. An electrolyte infusion (dogs) and feeding (cats) had the same effect on P-CLterminal values as described above for P-CL. In conclusion,the modified exogenous creatinine clearance is a suitable renal function test for the early diagnosis of renal disease in dogs and cats presented in small animal practices.


Primary epithelioid angiosarcoma of the mediastinum, cytomorphologic features of a rare entity-A case report and literature review.
Epithelioid angiosarcoma (EA) is a highly aggressive vascular neoplasm. Primary mediastinal EA is extremely rare with only few cases reported in the English literature. We herein present a case of a 78-year-old patient, who was found to have a right superior mediastinal mass associated with mediastinal and hilar lymphadenopathy. Endobronchial ultrasound guided fine needle aspiration cytology of a station 4R lymph node revealed a cellular, discohesive malignant neoplasm displaying primarily epithelioid morphology with occasional spindled, plasmacytoid, and tumor giant cells. The tumor cells had ample eosinophilic cytoplasm with pleomorphic nuclei and prominent nucleoli. Vasoformative features were noted, exemplified by widespread cytoplasmic vacuoles containing neutrophils and rare red blood cells (hemophagocytosis) and vascular channels identified solely in the cell block. By immunohistochemistry, the tumor cells stained strongly positive for vimentin, positive for ERG, CD-31, FLI-1, and focally positive for pan-cytokeratin. The cytomorphological features and immunostaining patterns were diagnostic of EA. No history of malignancy was reported, and no other lesions were identified on imaging. The diagnosis of primary mediastinal EA on cytology and small biopsy specimens may be challenging due to the rarity of this tumor, limited diagnostic material, and overlapping morphologic features with other entities in the differential diagnosis. A high index of suspicion, especially in cases with vasoformative features, and utilization of ancillary studies can help establish the diagnosis.


Effects of temperature elevation on neuronal inhibition in hippocampal neurons of immature and mature rats.
Febrile seizures are the most common seizure type in children, and hyperthermia may contribute to seizure generation during fever. We have previously demonstrated that hyperthermia suppressed gamma-aminobutyric acid (GABA)-ergic synaptic transmission in CA1 neurons of immature rats. However, whether this suppression is age-dependent is unknown. Moreover, it is unclear whether hyperthermia has differential effects on neuronal inhibition in CA1 pyramidal cells (PCs) and dentate gyrus granule cells (GCs). In this study, we investigated the effects of hyperthermia on GABA(A) and GABA(B) receptor-mediated inhibitory postsynaptic currents (IPSCs) in CA1 and DG neurons from immature (11-17 days old) and mature (6-8 weeks old) rats using whole-cell recordings in vitro. In immature rats, hyperthermia decreased the peak amplitude of GABA(A) receptor-mediated IPSCs (GABA(A) IPSCs) in PCs but not in GCs. However, hyperthermia decreased the decay time constant of GABA(A) IPSCs to a similar extent in both PCs and GCs. In mature rats, hyperthermia decreased the peak amplitude but not the decay time constant of GABA(A) IPSCs in both PCs and GCs. Hyperthermia decreased charge transfer (area) of the GABA(A) IPSC of PCs more in immature than in mature rats. In contrast, hyperthermia decreased the GABA(B) receptor-mediated IPSCs to the same degree in immature and mature rats, for either CA1 or DG neurons. Because the hippocampus has been found to be involved in hyperthermia-induced behavioral seizures in immature rats, we suggest that the higher sensitivity of CA1 inhibitory synaptic function to hyperthermia in immature compared with mature rats might partially explain the higher susceptibility for febrile seizures in immature animals.


IgG antibodies that recognize epitope Gly40-Arg43 in domain I of beta 2-glycoprotein I cause LAC, and their presence correlates strongly with thrombosis.
Anti-beta(2)-glycoprotein I antibodies are known to have a heterogeneous reactivity against beta(2)-glycoprotein I. We performed this study to characterize the epitope on beta(2)-glycoprotein I to which pathologic anti-beta(2)-glycoprotein I antibodies are directed. Plasma samples from 198 patients with various systemic autoimmune diseases were tested for the presence of lupus anticoagulant and anti-beta(2)-glycoprotein I immunoglobulin G (IgG) antibodies. The reactivity of the anti-beta(2)-glycoprotein I-positive samples was further tested by coating recombinant full-length beta(2)-glycoprotein I and 8 deletion mutants of beta(2)-glycoprotein I onto hydrophilic and hydrophobic enzyme-linked immunosorbent assay (ELISA) plates. Full-length beta(2)-glycoprotein I with point mutations in domain I at positions 8, 40, and 43 were used in inhibition experiments. Fifty-two patients with anti-beta(2)-glycoprotein I IgG antibodies could be divided into 2 patterns. Type A antibodies only recognize domain I when coated onto hydrophobic plates; they do not recognize domain I coated onto hydrophilic plates. Type B antibodies have heterogeneous reactivity for all domains. Type A antibodies recognize the epitope around amino acids Gly40-Arg43 and cause lupus anticoagulant activity. In contrast to type B antibodies, those of type A strongly correlated with thrombosis. In conclusion, antibodies directed at domain I (epitope comprising Gly40 and Arg43) have lupus anticoagulant activity and strongly associate with thrombosis.


Primary structure and functional expression of rat and human stem cell factor DNAs.
Partial cDNA and genomic clones of rat stem cell factor (SCF) have been isolated. Using probes based on the rat sequence, partial and full-length cDNA and genomic clones of human SCF have been isolated. Based on the primary structure of the 164 amino acid protein purified from BRL-3A cells, truncated forms of the rat and human proteins have been expressed in E. coli and mammalian cells and have been shown to possess biological activity. SCF is able to augment the proliferation of both myeloid and lymphoid hematopoietic progenitors in bone marrow cultures. SCF exhibits potent synergistic activities in conjunction with colony-stimulating factors, resulting in increased colony numbers and colony size.


Evidence on sociodemographic and clinical correlates of antidepressant combination or augmentation with second-generation antipsychotics in major depressive disorder.
About two thirds of the patients with major depressive disorder (MDD) do not sufficiently respond to monotherapy with antidepressants (ADs) which makes them reliant on further treatment approaches. Hereby, combination of different ADs and augmentation with second-generation antipsychotics (SGAs) are widely used and recommended psychopharmacotherapeutic strategies. The present secondary analyses are based on an international, naturalistic, cross-sectional multicenter study conducted by the European Group for the Study of Resistant Depression. Comparing socio-demographic and clinical characteristics of 436 adult MDD patients receiving either SGAs (N = 191, 43.8%) or ADs (N = 245, 56.2%), that were additionally administered to their first-line AD psychopharmacotherapy, we aimed to identify possible trajectories of decision-making for clinicians regarding which treatment option to prefer in individual patients. Our most robust findings represent an association of SGA augmentation with the presence of psychotic symptoms, longer mean duration of lifetime psychiatric hospitalizations, employment of further augmentation strategies with mood-stabilizers and benzodiazepines, and a trend towards higher mean daily dosages of their first-line ADs and current suicidal risk. Treatment outcome was not significantly different between patients receiving either SGA augmentation or AD combination. Being aware of limitations inherent to the cross-sectional study design and the lack of randomization, more severe and rather chronic conditions in MDD seemed to encourage clinicians to choose SGA augmentation over AD combination. The fact that mood-stabilizers and/or benzodiazepines were more frequently co-administered with SGAs may represent a requirement of an overall refined psychopharmacotherapy including additional fast-acting agents with potent AD, tranquilizing and anti-suicidal effects in MDD patients experiencing challenging clinical manifestations. New glutamatergic substances seem to be promising in this regard.


IGF-1 is not related to long-term outcome in hyperglycemic acute coronary syndrome patients.
Insulin-like growth factor-1 (IGF-1) has been associated with both protective and detrimental effects on the development of ischemic heart disease. The relationship between IGF-1 levels and major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients remains unclear. This study aimed to investigate the relationship between IGF-1 admission levels in hyperglycemic ACS patients and: (1) MACE over a 5 years follow-up, (2) type 2 diabetes at discharge, and (3) post-ACS myocardial infarct size and dysfunction. This was a post hoc analysis of the BIOMArCS-2 randomized controlled trial. From July 2008 to February 2012, 276 ACS patients with admission plasma glucose level between 140 and 288 mg/dL were included. Records of the composite of all-cause mortality and recurrent non-fatal myocardial infarction were obtained during 5 years follow-up. Venous blood samples were collected on admission. IGF-1 was measured batchwise after study completion. Oral glucose tolerance test was performed to diagnose type 2 diabetes, whereas infarct size and left ventricular function were assessed by myocardial perfusion scintigraphy (MPS) imaging, 6 weeks post-ACS. Cumulative incidence of MACE was 24% at 5 years follow-up. IGF-1 was not independently associated with MACE (HR:1.00 (95%CI:0.99-1.00), p = 0.29). Seventy-eight patients (28%) had type 2 diabetes at discharge, and the highest quartile of IGF-1 levels was associated with the lowest incidence of diabetes (HR:0.40 (95%CI:0.17-0.95), p = 0.037). IGF-1 levels were not associated with post-ACS myocardial infarct size and dysfunction. IGF-1 carries potential for predicting type 2 diabetes, rather than long-term cardiovascular outcomes and post-ACS myocardial infarct size and dysfunction, in hyperglycemic ACS patients.


The burden of child and maternal malnutrition and trends in its indicators in the states of India: the Global Burden of Disease Study 1990-2017.
Malnutrition is a major contributor to disease burden in India. To inform subnational action, we aimed to assess the disease burden due to malnutrition and the trends in its indicators in every state of India in relation to Indian and global nutrition targets. We analysed the disease burden attributable to child and maternal malnutrition, and the trends in the malnutrition indicators from 1990 to 2017 in every state of India using all accessible data from multiple sources, as part of Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. The states were categorised into three groups using their Socio-demographic Index (SDI) calculated by GBD on the basis of per capita income, mean education, and fertility rate in women younger than 25 years. We projected the prevalence of malnutrition indicators for the states of India up to 2030 on the basis of the 1990-2017 trends for comparison with India National Nutrition Mission (NNM) 2022 and WHO and UNICEF 2030 targets. Malnutrition was the predominant risk factor for death in children younger than 5 years of age in every state of India in 2017, accounting for 68·2% (95% UI 65·8-70·7) of the total under-5 deaths, and the leading risk factor for health loss for all ages, responsible for 17·3% (16·3-18·2) of the total disability-adjusted life years (DALYs). The malnutrition DALY rate was much higher in the low SDI than in the middle SDI and high SDI state groups. This rate varied 6·8 times between the states in 2017, and was highest in the states of Uttar Pradesh, Bihar, Assam, and Rajasthan. The prevalence of low birthweight in India in 2017 was 21·4% (20·8-21·9), child stunting 39·3% (38·7-40·1), child wasting 15·7% (15·6-15·9), child underweight 32·7% (32·3-33·1), anaemia in children 59·7% (56·2-63·8), anaemia in women 15-49 years of age 54·4% (53·7-55·2), exclusive breastfeeding 53·3% (51·5-54·9), and child overweight 11·5% (8·5-14·9). If the trends estimated up to 2017 for the indicators in the NNM 2022 continue in India, there would be 8·9% excess prevalence for low birthweight, 9·6% for stunting, 4·8% for underweight, 11·7% for anaemia in children, and 13·8% for anaemia in women relative to the 2022 targets. For the additional indicators in the WHO and UNICEF 2030 targets, the trends up to 2017 would lead to 10·4% excess prevalence for wasting, 14·5% excess prevalence for overweight, and 10·7% less exclusive breastfeeding in 2030. The prevalence of malnutrition indicators, their rates of improvement, and the gaps between projected prevalence and targets vary substantially between the states. Malnutrition continues to be the leading risk factor for disease burden in India. It is encouraging that India has set ambitious targets to reduce malnutrition through NNM. The trends up to 2017 indicate that substantially higher rates of improvement will be needed for all malnutrition indicators in most states to achieve the Indian 2022 and the global 2030 targets. The state-specific findings in this report indicate the effort needed in each state, which will be useful in tracking and motivating further progress. Similar subnational analyses might be useful for other low-income and middle-income countries. Bill & Melinda Gates Foundation; Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India.


Blood pressure regulation on low and high sodium diets in normotensive members of normotensive or hypertensive families.
In members of hypertensive families a high sodium intake may have a pressor effect. The mechanism mediating the sodium sensitivity is unclear. Blood pressure, exchangeable sodium, plasma levels of norepinephrine, epinephrine, renin and aldosterone, the pressor response to infused norepinephrine or angiotensin II and the urinary excretion of prostaglandin (PG) E2 and F2 alpha were measured after 7 days of low sodium diet (urinary sodium 13 +/- 10 s.d. mmol/24 h) and 7 days of high sodium intake (urinary sodium 268 +/- 97 mmol/24 h) in 10 normotensive men without and 13 men with family history of essential hypertension. After the low sodium phase, blood pressure, heart rate, exchangeable sodium, plasma levels of norepinephrine, epinephrine, renin and aldosterone, pressor doses of norepinephrine or angiotensin II and the urinary excretion of PGE2 or PGF2 alpha did not differ between the two groups. After the high sodium phase, blood pressure increased only in subjects with positive (P less than 0.05) but not in those with negative family history. In the two groups exchangeable sodium increased (P less than 0.05) and plasma levels of NE (-33% versus -32%), renin (-31% versus -27%) or aldosterone (-74% versus -61%) and pressor doses of NE (-55% versus -54%) or ANG II (-72% versus -44%) decreased by a comparable extent. Urinary PGE2 or PGF2 alpha were unchanged. These findings suggest that a high dietary sodium intake exerts a pressor effect in subjects with familial predisposition to essential hypertension. This pressor effect is not explained by an abnormal adaptation of body sodium, sympathetic activity, renin-angiotensin-aldosterone axis, cardiovascular pressor responsiveness and renal prostaglandin excretion to a high sodium diet.


Metacognition as a Mediating Variable Between Neurocognition and Functional Outcome in First Episode Psychosis.
Neurocognitive and functional outcome deficits have long been acknowledged in schizophrenia and neurocognition has been found to account for functional disability to a greater extent than psychopathology. Much of the variance in functional outcome however still remains unexplained and metacognition may mediate the relationship between neurocognition, functional capacity, and self-reported social and occupational function. Eighty first episode psychosis participants were recruited and completed measures of neurocognition (memory, executive function, and intelligence quotient), metacognition (Beck Cognitive Insight Scale, Metacognitive Awareness Interview), psychopathology (PANSS), and both functional capacity (UPSA) and real-life social and occupational function (The Time Use Survey). Path analyses investigated the relationships between variables through structural equation modeling. A series of path models demonstrated that metacognition partially mediates the relationship between neurocognition and functional capacity, and fully mediates the relationship between functional capacity and social and occupational function. The present study findings identify that metacognition may be critical to translating cognitive and functional skills into real-world contexts, and this relationship is found at early stages of illness. Understanding how individuals translate cognitive and functional skills into the real-world (the competence-performance gap) may offer valuable guidance to intervention programs. This finding is important to models of recovery as it suggests that intervention programs that focus on enhancing metacognition abilities may have a greater impact than traditional rehabilitation programs focusing on cognitive abilities, on social and occupational outcomes.


Correlating Lithium Hydroxyl Accumulation with Capacity Retention in V2O5 Aerogel Cathodes.
V2O5 aerogels are capable of reversibly intercalating more than 5 Li(+)/V2O5 but suffer from lifetime issues due to their poor capacity retention upon cycling. We employed a range of material characterization and electrochemical techniques along with atomic pair distribution function, X-ray photoelectron spectroscopy, and density functional theory to determine the origin of the capacity fading in V2O5 aerogel cathodes. In addition to the expected vanadium redox due to intercalation, we observed LiOH species that formed upon discharge and were only partially removed after charging, resulting in an accumulation of electrochemically inactive LiOH over each cycle. Our results indicate that the tightly bound water that is necessary for maintaining the aerogel structure is also inherently responsible for the capacity fade.


Guidance or Gatekeeping: An Audit Examination of Racial Discrimination in Leading STEM High Schools: Systems that Marginalize BIPOC Youth Special Issue: Dismantling Oppression Series: Systems that Marginalize BIPOC Youth Special Issue: Dismantling Oppression Series.
Racial discrimination remains a mechanism by which ethnic-racial minorities are restricted from power. We examined whether racial discrimination restricts ethnic-racial minority access to high-achieving STEM schools. We conducted an audit correspondence experiment to investigate racial discrimination in guidance counselor responsiveness to 976 emails from fictitious Asian, Black, Latina, and White mothers inquiring about school enrollment. Moderation analyses revealed that guidance counselors restricted access from Asian mothers at schools characterized as rural, lower socioeconomic status, and higher STEM prestige-evidence of gatekeeping points to the restriction of Asian students from advanced STEM opportunities. Results are situated within educational audit experiments to objectively document how racism from multiple facets of the education system intersect to inhibit ethnic-racial minority youth.


Inhibition of autophagy may suppress the development of hepatoblastoma.
Hepatoblastoma (HB) is a rare cancer but represents the most common liver malignancy in children under 3 years of age. Nevertheless, a clear understanding of the pathogenesis is lacking. Although the treatment of HB has been dramatically improved by combining chemotherapy regimens with surgery, its fatal outcome of fast development and recurrence makes new treatment strategies for HB, based on an improved understanding of the pathogenesis, essential. Autophagy is believed to be important in the progression of cancers. However, the role of autophagy in HB remains to be elucidated. Here, we show that autophagy is activated in HB tissues and cells under the conditions of starvation or chemotherapy, coupled with the over-expression of autophagic-related genes BECN1 and ATG5. Suppression of autophagy with pharmacological agents and small interfering RNAs significantly increased cell apoptosis and retarded proliferation in response to nutrition deprivation and treatment with chemotherapeutics. Our data demonstrate that the BECN1 and ATG5-dependent phosphoinositide 3-kinase (PI3K) signaling pathway is essential for the survival of HB cells and their tolerance to chemotherapy and starvation-induced death, and suggests that modifying such autophagic genes may suppress the development of HB, thus offering a therapeutic potential for patients with HB.


Cardiac electrophysiological and hemodynamic effects of beta-adrenoceptor blockade and thoracic epidural analgesia in the dog.
To investigate whether thoracic epidural analgesia (TEA) has additional cardiac electrophysiological and hemodynamic effects when induced after beta-adrenergic blockade, bupivacaine (0.7-1.2 mg/kg) was injected into the epidural space at T2-3 after intravenous injection of atenolol (1.0 mg/kg) in anesthetized dogs. Cardiac electrophysiology was studied by His bundle electrography, programmed electrical stimulation, and monophasic action potential recordings. Atenolol reduced heart rate, prolonged atrio-ventricular (AV) nodal impulse conduction time and refractoriness, prolonged ventricular refractoriness and action potential duration, and decreased left ventricular (LV) dP/dt max. Addition of TEA further reduced heart rate, prolonged AV nodal conduction time and refractoriness, decreased LV dP/dt max and arterial blood pressure, but had no effect on atrial and ventricular electrophysiology. Induction of TEA during beta-blockade may thus have additive depressive effects on sinoatrial and AV nodal functions, as well as on left ventricular inotropy. The study indicates that the cardiac electrophysiological effects induced by TEA are mainly caused by decreased beta-receptor stimulation, but increased vagal activity may also contribute.


Autogenous bone block in the treatment of teeth with hopeless prognosis.
Autogenous bone graft, although considered as a gold standard, has been relegated to background because of limited quantity and donor site morbidity. Revival of interest in its use has been reflected by its tremendous capacity for regeneration in less than ideal situation. Bone blocks have been used for implant site augmentation, with varied success. Aim of the study was to evaluate the efficacy of autogenous bone block in the regeneration of bone, for saving teeth with a hopeless prognosis. A total of six patients and 12 sites with grade II and III mobile teeth were treated with autogenous bone blocks and fiber splinting. Attachment loss, probing depths, and radiographic bone loss were recorded at baseline and at 12 months interval. The Student paired t test was used for evaluation of the changes from baseline to 12 months. At 12 months post-operatively, there was a highly significant amount of bone gain as compared to the baseline. The mean amount of bone loss reduced from 9.41 ± 1.16 to 5.41 ± 1.01. The clinical attachment loss reduced from 7.37 ± 1.24 mm to 3.79 ± 0.89 mm and probing depth reduced from 7 ± 1.67 mm to 5.5 ± 0.63 mm. The grafted bone was observed to have been incorporated with the host bone in most of the sites as evidenced by radiographs. For teeth with hopeless prognosis, this method can be considered to be a very viable alternative to extraction and replacement by costly implants.


Treatment of diabetes in the elderly--an analysis of 885 cases.
Besides treating elderly diabetics basically for the disease, the author treated the patients by traditional Chinese medicine based on an overall analysis of their symptoms and signs, dividing the course of the disease into 5 stages comprising 16 syndromes types. He evaluated the quality of their survival according to an the health rating of Karnofsky, and advised them on the amount of work or other activity appropriate in each case in order to relieve the symptoms, retard the disease process, and improve the quality of survival.


Nutrition Classification Schemes for Informing Nutrition Policy in Australia: Nutrient-Based, Food-Based, or Dietary-Based?
Policy makers are increasingly using nutrition classification schemes (NCSs) to assess a food's health potential for informing nutrition policy actions. However, there is wide variability among the NCSs implemented and no standard benchmark against which their contrasting assessments can be validated. This study aimed to compare the agreement of nutrient-, food-, and dietary-based NCSs in their assessment of a food's health potential within the Australian food supply, and examine the conceptual underpinnings and technical characteristics that explain differences in performance. A dataset combining food compositional data from the Mintel Global New Products Database and the Australian Food Composition Database (AUSNUT 2011-2012) (n = 7322) was assembled. Products were classified by 7 prominent NCSs that were selected as representative of one or other of 1) nutrient-based NCSs [the Chilean nutrient profile model (NPM), Health Star Rating (HSR), Nutri-Score, the WHO European Region's NPM (WHO-Euro NPM), and the Pan American Health Organization's (PAHO) NPM]; 2) food-based NCS (NOVA), and 3) dietary-based NCS [Australian Dietary Guidelines (ADGs)]. The PAHO NPM classified the lowest proportion (22%) of products as "healthy", and the HSR the highest (63%). The PAHO NPM, NOVA, WHO-Euro NPM, and the Chilean NPM classified >50% of products as "unhealthy," and the ADGs, HSR, and Nutri-Score classified <50% of products as "unhealthy." The HSR and Nutri-Score had the highest pairwise agreement (κ = 0.7809, 89.70%), and the PAHO NPM and HSR the lowest (κ = 0.1793, 53.22%). Characteristics of NCSs that more effectively identified ultraprocessed and discretionary foods were: category-specific assessment, the classification of categories as always "healthy" or "unhealthy," consideration of level of food processing, thresholds for "risk" nutrients that do not penalize whole foods; and no allowance for the substitution of ingredients. Wide variation was observed in agreement of the assessment of a food's health potential among the NCSs analyzed due to differing conceptual underpinnings and technical characteristics.


1-Acyldihydroxyacetone-phosphate reductase (Ayr1p) of the yeast Saccharomyces cerevisiae encoded by the open reading frame YIL124w is a major component of lipid particles.
Biosynthesis of phosphatidic acid through the dihydroxyacetone phosphate pathway requires NADPH-dependent reduction of the intermediate 1-acyldihydroxyacetone phosphate before the second step of acylation. Studies with isolated subcellular fractions of the yeast Saccharomyces cerevisiae revealed that lipid particles and the endoplasmic reticulum harbor 1-acyldihydroxyacetone-phosphate reductase (ADR) activity. Deletion of the open reading frame YIL124w (in the following named AYR1) abolished reduction of 1-acyldihydroxyacetone phosphate in lipid particles, whereas ADR activity in microsomes of the deletion strain was decreased approximately 3-fold as compared with the wild-type level. This result indicates that (i) both lipid particles and microsomes harbor Ayr1p, which was confirmed by immunological detection of the protein in these two cellular compartments, and (ii) microsomes contain at least one additional ADR activity. As a consequence of this redundancy, deletion of AYR1 neither results in an obvious growth phenotype nor affects the lipid composition of a haploid deletion strain. When a heterozygous AYR1(+)/ayr1(-) diploid strain was subjected to sporulation; however, spores bearing the ayr1 defect failed to germinate, suggesting that Ayr1p plays an essential role at this stage. Overexpression of Ayr1p at a 5- to 10-fold level of wild type caused growth arrest. Heterologous expression of Ayr1p in Escherichia coli resulted in gain of ADR activity in the prokaryote, confirming that YIL124w is the structural gene of the enzyme and does not encode a regulatory or auxiliary component required for reduction of 1-acyldihydroxyacetone phosphate. Taken together, these results identified Ayr1p of the yeast as the first ADR from any organism at the molecular level.


The Effect of Stimulus Choice on an EEG-Based Objective Measure of Speech Intelligibility.
Recently, an objective measure of speech intelligibility (SI), based on brain responses derived from the electroencephalogram (EEG), has been developed using isolated Matrix sentences as a stimulus. We investigated whether this objective measure of SI can also be used with natural speech as a stimulus, as this would be beneficial for clinical applications. We recorded the EEG in 19 normal-hearing participants while they listened to two types of stimuli: Matrix sentences and a natural story. Each stimulus was presented at different levels of SI by adding speech weighted noise. SI was assessed in two ways for both stimuli: (1) behaviorally and (2) objectively by reconstructing the speech envelope from the EEG using a linear decoder and correlating it with the acoustic envelope. We also calculated temporal response functions (TRFs) to investigate the temporal characteristics of the brain responses in the EEG channels covering different brain areas. For both stimulus types, the correlation between the speech envelope and the reconstructed envelope increased with increasing SI. In addition, correlations were higher for the natural story than for the Matrix sentences. Similar to the linear decoder analysis, TRF amplitudes increased with increasing SI for both stimuli. Remarkable is that although SI remained unchanged under the no-noise and +2.5 dB SNR conditions, neural speech processing was affected by the addition of this small amount of noise: TRF amplitudes across the entire scalp decreased between 0 and 150 ms, while amplitudes between 150 and 200 ms increased in the presence of noise. TRF latency changes in function of SI appeared to be stimulus specific: the latency of the prominent negative peak in the early responses (50 to 300 ms) increased with increasing SI for the Matrix sentences, but remained unchanged for the natural story. These results show (1) the feasibility of natural speech as a stimulus for the objective measure of SI; (2) that neural tracking of speech is enhanced using a natural story compared to Matrix sentences; and (3) that noise and the stimulus type can change the temporal characteristics of the brain responses. These results might reflect the integration of incoming acoustic features and top-down information, suggesting that the choice of the stimulus has to be considered based on the intended purpose of the measurement.


Interactions of the antimicrobial peptides temporins with model biomembranes. Comparison of temporins B and L.
Temporins are short (10-13 amino acids) and linear antimicrobial peptides first isolated from the skin of the European red frog, Rana temporaria, and are effective against Gram-positive bacteria and Candida albicans. To get insight into their mechanism(s) of action, we compared the effects on model membranes exerted by two members of this family, viz., temporin B (LLPIVGNLLKSLL-NH(2)) and temporin L (FVQWFSKFLGRIL-NH(2)). More specifically, we measured their insertion into lipid monolayers as well as their effects on the structural dynamics of liposomal bilayers as revealed by diphenylhexatriene (DPH)- and pyrene-labeled phospholipids. We also observed the impact of these peptides on the topology of giant vesicles. Both temporins readily penetrate into lipid monolayers, their intercalation being enhanced in the presence of the common bacterial negatively charged phospholipid phosphatidylglycerol. Instead, the eukaryotic lipid cholesterol did to some extent counteract their penetration into the lipid films. Both temporin B and temporin L caused an enrichment of phospholipids in the bilayers, and in the presence of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), these peptides increased acyl chain order. Temporin B had practically no effect on giant liposomes composed of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), whereas rapid vesiculation was observed when POPG was present. In contrast, temporin L induced vesiculation of both SOPC and SOPC/POPG giant vesicles while the presence of cholesterol in SOPC giant vesicles attenuated this effect.


Quality of life in Ethiopia's street youth at a rehabilitation center and the association with trauma.
Quality of life (QOL) tends to be lower among the homeless than the general population, and traumatic events experienced on the streets have a negative impact on QOL. Low-income countries face a high number of street youth, yet little research has been performed so far on QOL, trauma, and posttraumatic stress disorder (PTSD) among this group. This study aimed at examining the QOL of a sample of Ethiopian street youth within a rehabilitation program and at exploring whether the street youth have experienced traumatic events and show posttraumatic stress symptoms. We interviewed 84 street youths with the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) and the Diagnostic Interview for Children and Adolescents (DICA). Mean QOL scores differed significantly between the groups assessed at the beginning and at the end of the program (Cohen's d = 0.48). Eighty-three percent of the Ethiopian street youths had experienced traumatic events, and 25.0% met criteria for PTSD according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. QOL did not differ between those with and without PTSD symptoms. These findings show the high rate of traumatic events among Ethiopian street youth and the importance for rehabilitation programs that focus on improving QOL. The results of the study may have cultural limitations.


Anxiety disorders and disability secondary to urinary incontinence among adults over age 50.
No previous research has investigated whether there is an association between anxiety disorders and urinary incontinence. We hypothesized that anxiety disorders would be associated with increased urinary incontinence related disability. Continuing participants who were aged 50 years and older in a longitudinal study of community-dwelling adults who were initially living in East Baltimore in 1981 (n = 787). Participants were classified as incontinent if any uncontrolled urine loss within the 12 months prior to the interview was reported. Urinary incontinence related functional loss was further assessed based on a series of questions relating directly to participants' inability to engage in certain activities due to their urinary incontinence. Anxiety disorders were assessed with standardized interviews. Persons meeting criteria for an anxiety disorder were no more likely to have urinary incontinence than were persons without anxiety disorders (unadjusted odds ratio (OR) = 1.36,95 percent confidence interval (CI) [0.96, 1.93]). Among people with urinary incontinence (n = 159), persons meeting criteria for anxiety disorders in 1981 and in 1994 were much more likely to report urinary incontinence relatedfunctional impairment in 1994(adjusted OR = 6.51, 95 percent CI [1.42, 29.86]). Individuals with changes in day-to-day routines or activities secondary to urinary incontinence were more likely to meet criteria for an anxiety disorder than were other older adults. Further studies must tease out the temporal relationship and whether early detection of urinary incontinence and associated anxiety improves quality of life and functioning.


Nanostructured 3D electrode architectures for high-rate Li-ion batteries.
By initially depositing a sub-10 nm-thick SnO2 film, the microstructural evolution that is often considered problematic can be utilized to form Sn nanoparticles on the surface of a 3D current collector for enhanced cycling stability. The work described here highlights a novel approach for the uniform deposition of Sn nanoparticles, which can be used to design electrodes with high capacities and high-rate capabilities.


Masquerade scleritis.
To report two cases in which malignancy masqueraded as scleritis, delaying the diagnosis. Two patients initially diagnosed and treated for unilateral scleritis were referred for management of persistent inflammation. Additional evaluation uncovered underlying malignant processes. The first patient presented with scleritis initially responsive to systemic corticosteroids, with relapse one month later. Upon referral, peripheral fundus examination revealed elevated lesions. Additional studies confirmed the diagnosis of choroidal melanoma. The patient was treated with proton-beam irradiation. The second patient developed necrotizing scleritis unresponsive to systemic steroids, methotrexate, and cyclophosphamide. A scleral biopsy disclosed an undifferentiated high-grade carcinoma, likely metastatic. Exenteration was performed. Scleritis can present a diagnostic challenge. It is often the sole initial manifestation of an occult systemic problem. Treatment-resistant scleritis should raise the suspicion of an infectious or malignant masquerade.


Expression and characterization of recombinant murine factor VIII.
Hemophilia A is the inherited bleeding disorder that results from mutation of blood coagulation factor VIII (fVIII). Described here is the generation of a regulated expression system producing recombinant murine fVIII. Murine B-domainless fVIII was expressed at a peak level of 4 units/106 cells/24 h in serum-free media. Subsequently, a two-step purification procedure resulted in 5,300-fold enrichment and a 70% yield. Highly purified recombinant murine fVIII had a specific coagulant activity of 660 units per nanomole. It underwent proteolytic processing by thrombin to yield an activated heterotrimer that demonstrated significantly greater stability than activated human fVIII. Recombinant murine fVIII was utilized to generate an anti-fVIII polyclonal antibody. Intravenous injection of recombinant murine fVIII into hemophilia A mice failed to induce a significant anti-fVIII immune response using a schedule that yielded high titer inhibitory antibodies to human fVIII. This may provide an important model for the study of immune tolerance to fVIII.


ATP-independent control of autotransporter virulence protein transport via the folding properties of the secreted protein.
Autotransporter (AT) proteins are the largest class of extracellular virulence proteins secreted from Gram-negative bacteria. The mechanism by which AT proteins cross the bacterial outer membrane (OM), in the absence of ATP or another external energy source, is unknown. Here we demonstrate a linear correlation between localized regions of stability (ΔG(folding)) in the mature virulence protein (the AT "passenger") and OM secretion efficiency. Destabilizing the C-terminal β-helical domain of a passenger reduced secretion efficiency. In contrast, destabilizing the globular N-terminal domain of a passenger produced a linearly correlated increase in secretion efficiency. Thus, C-terminal passenger stability facilitates OM secretion, whereas N-terminal stability hinders it. The contributions of regional passenger stability to OM secretion demonstrate a crucial role for the passenger itself in directing its secretion, suggesting a novel type of ATP-independent, folding-driven transporter.


Mast cell activation in human synovium explants by calcium ionophore A23187, compound 48/80, and rabbit IgG anti-human IgE, but not morphine sulfate.
To investigate human synovial mast cell physiology, we developed a model in which mast cells in human synovial explant cultures were activated by immunologic or non-immunologic mechanisms. Small (3 mm) cubes of synovial membrane were incubated with or without secretagogue for 30, 45 or 60 min, and supernatant histamine concentrations were quantified. We measured significant histamine release with compound 48/80 at concentrations > or = 1 mg/ml, and with calcium ionophore A23187 at > or = 5 micrograms/ml. Rabbit IgG anti-human IgE induced significant histamine release at all concentrations tested, maximum at 78 micrograms/ml. Morphine sulfate produced no histamine release from synovial explants, in contrast to its significant stimulation of histamine release from neonatal foreskin explants in our explant system. We confirmed synovial mast cell degranulation by electron microscopy, and showed that it corresponded with measurable histamine release. Furthermore, histamine release was not due to secretagogue-induced cytotoxicity, as assessed by supernatant lactate dehydrogenase levels and by ultrastructural analysis. Since morphine sulfate induces mast cell degranulation and histamine release in adult and neonatal human skin, our data show that although synovial and dermal mast cells have a similar granule enzyme profile and electron microscopic morphology, they differ in functional responses. These observations support recent data that among similar human mast cell subtypes there are physiologic differences. Finally, our explant model will be useful in studies of mast cell involvement in arthritis.


Intranasal application of vasopressin fails to elicit changes in brain immediate early gene expression, neural activity and behavioural performance of rats.
Intranasal administration has been widely used to investigate the effects of the neuropeptides vasopressin and oxytocin on human behaviour and neurological disorders, although exactly what happens when these neuropeptides are administered intranasally is far from clear. In particular, it is not clear whether a physiological significant amount of peptide enters the brain to account for the observed effects. In the present study, we investigated whether the intranasal administration of vasopressin and oxytocin to rats induces the expression of the immediate-early gene product Fos in brain areas that are sensitive to centrally-administered peptide, whether it alters neuronal activity in the way that centrally-administered peptide does, and whether it affects behaviour in the ways that are expected from studies of centrally-administered peptide. We found that, whereas i.c.v. injection of very low doses of vasopressin or oxytocin increased Fos expression in several distinct brain regions, intranasal administration of large doses of the peptides had no significant effect. By contrast to the effects of vasopressin applied topically to the main olfactory bulb, we saw no changes in the electrical activity of olfactory bulb mitral cells after intranasal vasopressin administration. In addition, vasopressin given intranasally had no significant effects on social recognition or short-term recognition memory. Finally, intranasal infusions of vasopressin had no significant effects on the parameters monitored on the elevated plus maze, a rodent model of anxiety. Our data obtained in rats suggest that, after intranasal administration, significant amounts of vasopressin and oxytocin do not reach areas in the brain at levels sufficient to change immediate early gene expression, neural activity or behaviour in the ways described for central administration of the peptides.


Staphylococcal Scalded Skin Syndrome and Bullous Impetigo.
Staphylococcal scalded skin syndrome (SSSS) and bullous impetigo are infections caused by Staphylococcus aureus. The pathogenesis of both conditions centers around exotoxin mediated cleavage of desmoglein-1, which results in intraepidermal desquamation. Bullous impetigo is due to the local release of these toxins and thus, often presents with localized skin findings, whereas SSSS is from the systemic spread of these toxins, resulting in a more generalized rash and severe presentation. Both conditions are treated with antibiotics that target S. aureus. These conditions can sometimes be confused with other conditions that result in superficial blistering; the distinguishing features are outlined below.


Treatment with an antisense oligodeoxynucleotide to the GABAA receptor gamma 2 subunit increases convulsive threshold for beta-CCM, a benzodiazepine "inverse agonist', in rats.
The gamma 2 subunit of the gamma-aminobutyric acid type-A (GABAA) receptor is associated with the actions of benzodiazepines and related drugs. A phosphorothioate-modified antisense oligodeoxynucleotide directed against the gamma 2 subunit was given by i.c.v. injection (18 micrograms in 2 microliters saline) to male Sprague-Dawley rats every 12 h for 3 days. Controls received the corresponding sense oligodeoxynucleotide. 4-6 h after the last i.c.v. treatment, rats were given methyl-beta-carboline-3-carboxylate (beta-CCM), a benzodiazepine "inverse agonist', by slow i.v. infusion. Compared to naive rats, the beta-CCM threshold dose was not affected by the sense oligodeoxynucleotide, but was increased 87% in antisense oligodeoxynucleotide-treated rats. The treatment had no effect on the seizure threshold for picrotoxin. Both antisense and sense oligodeoxynucleotide treatments slightly increased the threshold for strychnine seizures. The results suggest that antisense oligodeoxynucleotide treatment altered GABAA receptor composition and interfered with the actions of a benzodiazepine receptor ligand in vivo, and may provide a tool for studying regulation of receptor structure and function.


N-Glycosylation Fingerprinting of Viral Glycoproteins by xCGE-LIF.
The ongoing threat of pathogens, increasing resistance against antibiotics, and the risk of fast spreading of infectious diseases in a global community resulted in an intensified development of vaccines. Antigens used for vaccination comprise a wide variety of macromolecules including glycoproteins, lipopolysaccharides, and complex carbohydrates. For all of these antigens the sugar composition plays a crucial role for immunogenicity and protective efficacy of the vaccine. Here, we provide a protocol for N-glycosylation fingerprinting utilizing high performance multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (xCGE-LIF) technology. The method described, enables to analyze the N-glycosylation of specific proteins out of a complex sample or even the total of all N-glycans contained in such a sample. The protocol is exemplarily demonstrated for N-glycosylation fingerprinting of cell culture-derived influenza A and B viruses and their major antigens, the membrane glycoproteins hemagglutinin and neuraminidase.


The effects of recombinant human interferon-gamma on a panel of human bladder cancer cell lines.
We have examined the Major Histocompatibility Complex class II antigen inducing capabilities of recombinant human interferon-gamma, on a panel of human transitional cell carcinoma lines which have been raised from original tumours of varying histological grades: RT4 (grade 1), RT112 (grade 2) and MGH-U1 (grade 3). Cells were examined for class II antigens using an indirect immunofluorescent staining method and analysed on a fluorescence activated cell sorter. Twenty percent of RT4 cells constitutively expressed class II antigen. Both RT112 and MGH-U1 were repeatedly found to be negative for this antigen prior to treatment with interferon-gamma. Following treatment with interferon-gamma all three lines showed an increase in class II antigen expression, which was consistently dependent on both the length of incubation and concentration of interferon-gamma. A differential susceptibility was found amongst the three cell lines which may relate to the histological grade of the parent tumor.


[A case of fulminant acute poststreptococcal glomerulonephritis showing mesangiolysis and crescent formation preceded by erysipelas].
A 66-year-old man with erysipelas was admitted with complaints of oliguria and massive proteinuria/hematuria. He was diagnosed as having acute poststreptococcal glomerulonephritis(APSGN) due to erysipelas infected by group A streptococcus pyogenes. On admission, his white cell count increased to 31,000, and CRP was 27.3 mg/dl. Serum urea nitrogen and creatinine were increased to 90.1 mg/dl and 4.5 mg/dl, respectively. He had diabetes mellitus(HbA1c 7.9%) and liver dysfunction(total bilirubin 3.5 mg/dl, AST 76 IU, ALT 41 IU) caused by alcoholic liver cirrhosis. Hypocomplementemia was found in addition to ASO 216 U/ml and ASK 10,240 x. After antibiotics treatment was initiated, inflammation of the erysipelas began to improve. Disseminated intravascular coagulation syndrome, probably due to sepsis, occurred on the 5th hospital day. He died of gastrointestinal bleeding on the 18th hospital day. Renal autopsy revealed 37% formation of fibrocellular crescents, and marked mesangiolysis was noted by light microscopy. Granular deposition of C3 and IgG was seen along the capillary walls on immunofluorescence study. Intramembranous deposits were scattered on electron microscopy. This case illustrates a fulminant type of APSGN, which was in part attributed to the presence of diabetes and alcoholic liver cirrhosis. Histological findings of crescent formation and marked mesangiolysis may account for the fulminant clinical course.


CORRELATION BETWEEN INNER-RETINAL CHANGES AND OUTER-RETINAL DAMAGE IN PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANE.
To investigate correlations between the inner-retinal irregularity index and interdigitation zone (IZ) defects preidiopathic and postidiopathic epiretinal membrane (ERM) surgery. The authors retrospectively assessed ophthalmic parameters in 89 eyes of 89 patients with ERM. They divided patients into the no-IZ defect (51, 57%) and IZ defect (38, 43%) groups. The IZ defect group was subdivided into recovered (22, 58%) and remaining IZ defect (16, 42%) subgroups, according to IZ recovery status at final examination. The inner-retinal irregularity index of each group was measured before and 1-, 3-, and 6-month postsurgery. Clinical characteristics were similar in both groups. The IZ defect group had a statistically significant higher inner-retinal irregularity index than the no-IZ defect group before (P = 0.023), but not after ERM surgery. The inner-retinal irregularity index of the recovered and remaining IZ defect subgroups was similar before surgery, but differed markedly 6 months after surgery (P = 0.048). Changes in the inner-retinal irregularity index quantitatively correlated with IZ defect size before and after ERM surgery (P < 0.001). The inner-retinal irregularity index differed significantly according to the IZ status and also correlated with the IZ defect before and after ERM surgery. The inner-retinal irregularity index may reflect the outer-retinal damage in ERM.


Intracranial hypertension in siblings with infantile hypercalcemia.
Idiopathic intracranial hypertension is a clinical condition with elevated intracranial pressure of uncertain etiology. Although various underlying causes are suspected and familial occurrence has also been reported, however, it still remains an unexplained phenomenon. We report the case of dizygotic siblings with a known CYP24A1 mutation resulting in chronic hypercalcemia and impairment of kidney function. At the same point in time both of them developed intracranial hypertension resistant to conservative therapy necessitating therefore ventriculoperitoneal shunt implantation. In both children magnetic resonance imaging showed slightly hypoplastic sinus transversus as the potential underlying cause. The simultaneous clinical presentation could be due to a genetic factor or might be a component of the underlying disease or the consequence of its treatment. Further cases and clinical experience are needed to clarify this issue.


External quality assessment for arbovirus diagnostics in the World Health Organization Western Pacific Region, 2013-2016: improving laboratory quality over the years.
Arboviruses continue to pose serious public health threats in the World Health Organization (WHO) Western Pacific Region. As such, laboratories need to be equipped for their accurate detection. In 2011, to ensure test proficiency, the WHO Regional Office for the Western Pacific piloted an external quality assessment (EQA) programme for arbovirus diagnostics. By 2016, it had grown into a global programme with participation of 96 laboratories worldwide, including 25 laboratories from 19 countries, territories and areas in the Region. The test performance of the 25 laboratories in the Region in 2016 was high with 23 (92%) reporting correct results in all specimens for dengue and chikungunya viruses. For Zika virus, 18 (72%) of the 25 laboratories reported correct results in all specimens, while seven (28%) demonstrated at least one error. When comparing iterations of this EQA programme in the Region between 2013 and 2016, the number of participating laboratories increased from 18 to 25. The first round only included dengue virus, while the latest round additionally included chikungunya, Zika and yellow fever viruses. Proficiency for molecular detection of dengue virus remained high (83-94%) over the four-year period. The observed proficiency for arbovirus diagnostics between 2013 and 2016 is an indicator of laboratory quality improvement in the Region.


Ab initio QM/MM dynamics simulation of the tetrahedral intermediate of serine proteases: insights into the active site hydrogen-bonding network.
Ab initio QM/MM dynamics simulation is employed to examine the stability of the tetrahedral intermediate during the deacylation step in elastase-catalyzed hydrolysis of a simple peptide. An extended quantum region includes the catalytic triad, the tetrahedral structure, and the oxyanion hole. The calculations indicate that the tetrahedral intermediate of serine proteases is a stable species on the picosecond time scale. On the basis of geometrical and dynamical properties, and in agreement with many experimental and theoretical studies, it is suggested that the crucial hydrogen bonds involved in stabilizing this intermediate are between Asp-102 and His-57 and between the charged oxygen of the intermediate and the backbone N-H group of Gly-193 in the oxyanion hole. The mobility of the imidazolium ring between O(w) and O(gamma), two of the oxygens of the tetrahedral structure, shows how the intermediate could proceed toward the product state without a "ring-flip mechanism", proposed earlier on the basis of NMR data. In addition to the proposed C(epsilon)(1)-H.O hydrogen bond between the imidazolium ring and the backbone carbonyl of Ser-214, we observe an alternative C(epsilon)(1)-H.O hydrogen bond with the backbone carbonyl of Thr-213, that can stabilize the intermediate during the imidazolium movement. Proton hopping occurs between Asp-102 and His-57 during the simulation. The proton is, however, largely localized on the nitrogen, and hence it does not participate in a low-barrier hydrogen bond. The study also suggests factors that may be implicated in product release: breaking the hydrogen bond of the charged oxygen with the backbone of Ser-195 in the oxyanion hole and a loop opening between residues 216-225 that enables the breaking of a hydrogen bond in subsite S(3).


Mycobacteriophage D29 Lysin B exhibits promising anti-mycobacterial activity against drug-resistant Mycobacterium tuberculosis.
To combat the rapidly emerging drug-resistant M. tuberculosis, it is now essential to look for alternative therapeutics. Mycobacteriophages can be considered as efficient therapeutics due to their natural ability to infect and kill mycobacteria including M. tuberculosis. Here, we have exploited the mycolyl-arabinogalactan esterase property of LysB encoded from mycobacteriophage D29. This study is novel in terms of targeting a multi-drug-resistant pathogenic strain of M. tuberculosis with LysB and also examining the combination of anti-TB drugs and LysB. All the experiments include external administration of LysB. Therefore, the remarkable lytic activity of LysB overcomes the difficulty to enter the complex cell envelope of mycobacteria. Targeting the intracellularly located M. tuberculosis by LysB and non-toxicity to macrophages take the process of the development of LysB as a drug one step ahead, and also, the interaction studies with rifampicin and isoniazid will help to form a new treatment regimen against tuberculosis.


Dual ETA/ETB blockade with macitentan improves both vascular remodeling and angiogenesis in pulmonary arterial hypertension.
Dysregulated metabolism and rarefaction of the capillary network play a critical role in pulmonary arterial hypertension (PAH) etiology. They are associated with a decrease in perfusion of the lungs, skeletal muscles, and right ventricle (RV). Previous studies suggested that endothelin-1 (ET-1) modulates both metabolism and angiogenesis. We hypothesized that dual ETA/ETB receptors blockade improves PAH by improving cell metabolism and promoting angiogenesis. Five weeks after disease induction, Sugen/hypoxic rats presented severe PAH with pulmonary artery (PA) remodeling, RV hypertrophy and capillary rarefaction in the lungs, RV, and skeletal muscles (microCT angiogram, lectin perfusion, CD31 staining). Two-week treatment with dual ETA/ETB receptors antagonist macitentan (30 mg/kg/d) significantly improved pulmonary hemodynamics, PA vascular remodeling, and RV function and hypertrophy compared to vehicle-treated animals (all P = 0.05). Moreover, macitentan markedly increased lung, RV and quadriceps perfusion, and microvascular density (all P = 0.05). In vitro, these effects were associated with increases in oxidative phosphorylation (oxPhox) and markedly reduced cell proliferation of PAH-PA smooth muscle cells (PASMCs) treated with macitentan without affecting apoptosis. While macitentan did not affect oxPhox, proliferation, and apoptosis of PAH-PA endothelial cells (PAECs), it significantly improved their angiogenic capacity (tube formation assay). Exposure of control PASMC and PAEC to ET-1 fully mimicked the PAH cells phenotype, thus confirming that ET-1 is implicated in both metabolism and angiogenesis abnormalities in PAH. Dual ETA/ETB receptor blockade improved the metabolic changes involved in PAH-PASMCs' proliferation and the angiogenic capacity of PAH-PAEC leading to an increased capillary density in lungs, RV, and skeletal muscles.


Comparison of saphenous vein graft versus right gastroepiploic artery to revascularize the right coronary artery: a prospective randomized clinical, functional, and angiographic midterm evaluation.
Despite its theoretic advantage over saphenous vein grafts, the right gastroepiploic artery graft has not been accepted as the ideal conduit to revascularize the right coronary artery. We therefore prospectively randomized these 2 grafts types to compare their clinical, functional, and angiographic evolution at 6 months and 3 years. From 2003 to 2006, 1397 consecutive patients underwent isolated revascularization at the University of Louvain Medical School. Of this group, 370 patients met the inclusion criteria for randomization and 66% of those were randomized. The right coronary artery was revascularized with saphenous vein grafts in 116 patients and with right gastroepiploic arteries in 122 patients. All patients underwent angiographic control 6 months postoperatively. The end points were major adverse cerebrocardiovascular events and proportion of grafts patent or functional at follow-up angiography. There were no significant differences between the 2 groups in terms of hospital events. At follow-up there was no significant difference in major adverse cerebrocardiovascular events between the 2 groups. At the 6-month angiographic follow-up, 91% of the anastomoses in the right gastroepiploic artery group and 95% of the anastomoses in the saphenous vein graft group were controlled patent (P = .92). In nonoccluded right coronary arteries, the proportion of patent grafts was significantly lower and the proportion of nonfunctioning grafts was significantly higher in the right gastroepiploic artery group than in the saphenous vein graft group. There were no significant patency or major adverse cerebrocardiovascular events rate differences between the 2 groups; however, the number of functional grafts was significantly higher in the saphenous vein graft group. Careful selection of the coronary target is mandatory to obtain good results in gastroepiploic artery grafting.


[Effect of triamcinolone acetonide, montelukast, nedocromil sodium and formoterol on eosinophil blood counts, ECP serum levels and clinical progression of asthma in children].
Eosinophil-mediated damage to the respiratory epithelium is a major pathogenetic mechanism in asthma. Glucocorticoids have confirmed antiinflammatory properties and effect of formoterol, montelukast and nedocromil on markers of inflammation has been studied. Eosinophil blood counts and eosinophil cation protein (ECP) serum level are often use as markers of clinical monitoring of the disease activity. To evaluate the effect of treatment on allergic inflammation, we measured eosinophil blood counts and ECP serum level, and clinical parameters before and after 4 weeks treatment with triamcinolon, montelukast, nedocromil, formoterol. It was 8 week, placebo-controlled and randomized, double blind trial of 154 children with moderate atopic asthma. Patients were randomly allocated to receive 400 mg triamcinolon (n = 28), 5 or 10 mg (according to age) montelukast (n = 27), 16 mg nedocromil (n = 26), 24 micrograms formoterol (n = 28) or placebo (n = 45). 140 children completed the study. After treatment with triamcinolon and montelukast eosinophil blood counts significantly decreased, after treatment with triamcinolon, montelukast and nedocromil ECP serum level significantly decreased; all clinical parameters improved after treatment with each drug; treatment with triamcinolon had the strongest effect on most parameters (except of FEV1). Mean eosinophil blood counts before and after treatment with triamcinolon were 277.4 and 187.2 cells/mm3 respectively (p < 0.001); with montelukast were 279.6 and 250.7 cells/mm3 respectively (p = 0.002); with nedocromil were 181.7 and 170.1 cells/mm3 respectively (p < 0.183); with formoterol were 276.4 and 264.1 cells/mm3 respectively (p = 0.2). Mean ECP serum levels before and after treatment with triamcinolon were 94.3 and 63.5 micrograms/l respectively (p < 0.001); with montelukast were 85.1 micrograms/l and 71.2 micrograms/l respectively (p < 0.001); with nedocromil were 92.6 and 80.1 micrograms/l respectively (p < 0.001); with formoterol were 95.9 micrograms/l and 87.8 micrograms/l (p = 0.05). We found significant correlation between ECP and hyperresponsiveness after treatment with triamcinolon, montelukast. This study shows that triamcinolon, montelukast contribute to inhibition of allergic inflammation by decreasing eosinophil blood counts and ECP. The serum level of ECP seems to be a good clinical marker of monitoring the disease.


Trends in the susceptibility of U.S. Acinetobacter baumannii-calcoaceticus species complex and Stenotrophomonas maltophilia isolates to minocycline, 2014-2021.
Acinetobacter baumannii-calcoaceticus species complex and Stenotrophomonas maltophilia are opportunistic, non-fermentative Gram-negative organisms that can cause serious hospital-acquired infections in immunocompromised patients. These pathogens are inherently resistant to several common drug classes and often acquire other resistance mechanisms, making them difficult to treat. In this study, we analyzed the trends of susceptibility of over 2,500 U.S. bacterial isolates collected from hospitalized patients over an 8-year period to minocycline, which is used to treat infections caused by these pathogens. These in vitro data suggest that minocycline is a useful treatment option for infections caused by Acinetobacter baumannii-calcoaceticus species complex or Stenotrophomonas maltophilia.


Brucellosis in Qatar: A retrospective cohort study.
We conducted a retrospective cohort study to evaluate the clinical manifestations, laboratory findings, complications and treatment of brucellosis in the State of Qatar. The medical records of patients in Hamad Medical Corporation, Doha, Qatar were reviewed from January 2000 to December 2006. History, various socio-demographic features, clinical and biochemical parameters, therapeutic features, and complications were retrospectively collected from the patient database. Around three quarters of the study population were males. History of raw milk consumption and animal contact were seen in 41.7% and 12.5% respectively. The main presenting features of our cohort were fever, chills and sweating (93.1%, 62.5% and 58.3% respectively). Positive antibody titre (>1:160) was detected in 95.8% and positive blood culture was reported in 63.9% of the cohort. Splenomegaly was observed in 19.4%, hepatomegaly in 15.3% and lymphadenopathy in 9.7% of the cases. Approximately half of our patients were treated with a combination of doxycycline and streptomycine and nearly one quarter received doxycycline and rifampicine combination therapy. Brucellosis is an important public health problem worldwide. It is associated with significant morbidity and mortality. It may affect any organ system and can present with a variety of clinical features. Diagnosis of brucellosis requires serological tests with or without blood culture. Treatment with at least two antibiotics for six weeks or more appears to be effective.


Cutting edge: Sympathetic nervous system increases proinflammatory cytokines and exacerbates influenza A virus pathogenesis.
Although the sympathetic nervous system innervates the lung, little is known about its participation in host immunity to pulmonary pathogens. In this study, we show that peripheral sympathectomy reduces mouse morbidity and mortality from influenza A virus-induced pneumonia due to reduced inflammatory influx of monocytes, neutrophils, and NK cells. Mortality was also delayed by treating mice with an alpha-adrenergic antagonist. Sympathectomy diminished the immediate innate cytokine responses, particularly IL-1, which was profoundly reduced. These findings demonstrate an unexpected role for the sympathetic nervous system in innate antiviral immunity and in exacerbating the pathology of a virus of great significance to human and animal health.


[Studies on immunization strategy against hepatitis A in a highly prevalent area].
To explore a strategy for immunization against hepatitis A (HA) in highly prevalent areas. Maternal antibodies against hepatitis A virus (anti-HAV) were detected for newly born infants and infection rate of HAV was monitored for children at various stages of epidemic of HA. Proportions of positive maternal anti-HAV in newly born infants decreased from 97.4% to 5.0% during their first 13 months of life in a logistic curve pattern. HAV infection increased with age after one and a half years old during non-epidemic period, and kept in less than 10% before two years old. The age of the increase in HAV infection shifted to an earlier dates and the rate of infection speeded up more for children during an epidemic period. The "window" phase converting maternal anti-HAV to natural infection for infants in the highly prevalent areas was in 12 to 24 months after birth, because the age starting to increase HA infection lagged behind that of infection. Based on the prevalence of HA and economic situation, the appropriate time for children's HAV immunization is 12 to 24 months of age.


Evaluation of the ASTRA o-cresolphthalein complexone calcium method.
An automated calcium method based on o-cresolphthalein complexone chemistry and designed to be used in conjunction with the Beckman ASTRA systems (Beckman Instruments, Inc., Brea, CA) was evaluated. Day-to-day reproducibility studies yielded coefficients of variation ranging from 1.2 to 3.1%. Linearity was 5.0-15.5 mg/dL, and recovery of calcium averaged 98%. Bilirubin, creatinine, hemoglobin, and turbidity did not cause significant interference while there was a positive interference due to magnesium. The throughput is 70 samples per hour, and a single stat result can be obtained in 9 minutes from the standby mode. Very little sample (12 microL) or reagent (150 microL) is required. There was excellent correlation between the ASTRA calcium method and atomic absorption spectrophotometry (Y = 1.047x - 0.39, r = 0.9941). Analytic performance was judged acceptable according to Westgard's medical usefulness criteria of the observed total analytic errors being less than the limit of allowable error.


Correlation of Ambient Temperature With Feedlot Cattle Morbidity and Mortality in the Texas Panhandle.
Anecdotal data would suggest that weather patterns influence beef cattle health in feedyards, and cattle producers often associate the seasonality of some illnesses with changes in environmental temperatures. However, to our knowledge, there is little information from large-scale feeding operations and precision weather stations that establishes a link or lack thereof between weather patterns and cattle health. Additionally, we are unaware of any studies correlating other weather parameters with animal health data. Therefore, the objective of this study was to test for associations between monthly temperature variation and animal morbidity/mortality in feedlots in the Texas Panhandle. Weather data was collected from a Texas Tech University Mesonet weather station in close proximity to 19 beef cattle feedyards in the Texas Panhandle. Additionally, near real-time morbidity and mortality data was collected from those yards from 2015 to 2018. These data document a seasonal pattern relative to cattle morbidity and mortality with most health events occurring from November to January. This pattern is differentiated when comparing morbidity and mortality by listed causation (e.g., respiratory, digestive, other), and the majority of deaths over the entire time course were attributed to respiratory disease. Most cattle morbidity was documented in the winter months, most of which were classified as respiratory disorders. Additionally, an increase in health events was observed as the population of the feedyard increased. However, the overall effects of ambient temperature on cattle health were minimal and the two may not be causally linked. The initial overview of the relationships documented in this manuscript may warrant further stratification and exploration.


Learning versus habit formation: Optimal timing of lockdown for disease containment.
We analyze a model where the government has to decide whether to impose a lockdown in a country to prevent the spread of a possibly virulent disease. If the government decides to impose a lockdown, it has to determine its intensity, timing and duration. We find that there are two competing effects that push the decision in opposite directions. An early lockdown is beneficial not only to slow down the spread of the disease, but creates beneficial habit formation (such as social distancing, developing hygienic habits) that persists even after the lockdown is lifted. Against this benefit of an early lockdown, there is a cost from loss of information about the virulence and spread of the disease in the population in addition to a direct cost to the economy. Based on the prior probability of the disease being virulent, we characterize the timing, intensity and duration of a lockdown with the above mentioned tradeoffs. Specifically, we show that as the precision of learning goes up, a government tends to delay the imposition of lockdown. Conversely, if the habit formation parameter is very strong, a government is likely to impose an early lockdown.


[Normalization of acupuncture anesthesia used in operation of neoplasm in functional area or deep site of brain].
From October 1990 to December 1995, the national cooperative neurosurgical acupuncture research group had already accumulated 100 clinical cases, consisting of 20 cases in deep site of brain, 80 cases in the functional region. By the same manipulative procedures and scaling criteria, the indication, choice of acupoints, stimulus parameters and adjuvants were studied. Practically, the results was not only reliable, but repetitive highly, 98% the cases belonged to grade I (success). We suggest that acupuncture anesthesia should be used as one of the usual methods of anesthesia. In this paper, the relative specification of acupuncture, the mechanism of methods for operation were discussed. In the meantime, the advantages and the remaining problems of acupuncture anesthesia in craniocerebral operations were also mentioned.


Dopaminergic contributions to distance estimation in Parkinson's disease: a sensory-perceptual deficit?
Recent research has found that perceptual deficits exist in Parkinson's disease (PD), yet the link between perception and movement impairments is not well understood. Inaccurate estimation of distance has the potential to be an underlying cause of movement impairments. Alternatively, those with PD may not be able to perceive their own movements accurately. The main objectives of these studies were to evaluate (1) whether distance estimation is influenced by static perception compared to perception during movement in PD, (2) how visual motion processing contributes to distance estimation during movement, and (3) how dopaminergic medication contributes to these distance estimation deficits. Thirty-seven participants (19 individuals with PD, 18 age-matched healthy control (HC) participants) estimated distance to a remembered target in a total of 48 trials, in 4 randomized blocks. Estimation conditions included: (i) static perception (laser): participants pointed with a laser, (ii) active dynamic perception (walk): participants walked to the estimated position, (iii) passive dynamic perception (wheelchair): participants were pushed in a wheelchair while they gave their estimate. PD patients completed this protocol twice; once OFF and once ON dopaminergic medication. Participants with PD and HC did not differ in judgment accuracy during the static perception (laser) condition. However, those with PD had greater amounts of error compared to HC participants while estimating distance during active dynamic perception (walk). Interestingly, those with PD significantly underestimated the target position compared to healthy control participants across all conditions. Individuals with PD also demonstrated greater variability in their judgments overall. There was no significant influence of dopaminergic medication in any of the conditions. Individuals with PD demonstrated distance estimation deficits only when required to actively move through their environment. In contrast to estimations made with movement, neither static perception (laser) nor passive dynamic perceptions (wheelchair) revealed significant differences in the magnitude of error between the two groups. Thus perceptual estimation deficits appear to be amplified during movement, which may be suggestive of an underlying sensory processing deficit which leads to a problem integrating vision and self-motion information.


Estimation of age from the teeth of unidentified corpses using the amino acid racemization method with reference to actual cases.
We report the results of a study for estimating the age of unidentified corpses from teeth using the amino acid racemization method. By calculating the ratio of D-aspartic acid to L-aspartic acid (referred to as the D/L ratio), we studied samples from 24 corpses of known identity. The results showed that the approach yielded satisfactory age estimates with an accuracy of +/- 3 years. Detailed examination of these results indicated that powdered dentin produced more favorable results than fragmented dentin. No differences in the estimated age related to cause of death were noted. However, better results were obtained with a larger number of control teeth and a higher correlation coefficient between the D/L ratio and the actual age of the control teeth. In terms of age and estimation accuracy, corpses of individuals > 40 years of age generally gave more satisfactory results than those of younger individuals. It was also reconfirmed that preparation of control teeth is required each time an age estimate is performed.


The role of pathologists in recognition of morphologic and biologic features of genetically mutated breast cancer.
The recent introduction of genomic medicine and emphasis on optimizing breast cancer risk reduction mortalities has provided opportunities for pathologists to partner with clinicians in advancing the diagnosis and management of breast cancer patients. The discovery of breast cancer genes BRCA1, BRCA2, and other breast cancer genes is considered a major breakthrough in the understanding of hereditary breast cancer. These discoveries have contributed to investigate the nature of tumorigenesis and the genetic and molecular pathology in multistep tumor development, as well as their relationship to endocrine and environmental factors. The recognition of unique morphologic and biological features associated with genetically mutated breast cancer by pathologists may have an impact on appropriate follow-up management of breast cancer patients.


CpABC, a Cryptosporidium parvum ATP-binding cassette protein at the host-parasite boundary in intracellular stages.
The intracellular parasite Cryptosporidium parvum develops inside a vacuole at the apex of its epithelial host cell. The developing parasite is separated from the host cell cytoplasm by a zone of attachment that consists of an extensively folded membranous structure known as the feeder organelle. It has been proposed that the feeder organelle is the site of regulation of transport of nutrients and drugs into the parasite. In this report, we localize an approximately 200-kDa integral membrane protein, CpABC, from Cryptosporidium parvum to the host-parasite boundary, possibly the feeder organelle. The predicted amino acid sequence of CpABC has significant structural similarity with the cystic fibrosis conductance regulator and the multidrug resistance protein subfamily of ATP-binding cassette proteins. This is an example of a parasite-encoded transport protein localized at the parasite-host interface of an intracellular protozoan.


Cetacean Acoustic Welfare in Wild and Managed-Care Settings: Gaps and Opportunities.
Cetaceans are potentially at risk of poor welfare due to the animals' natural reliance on sound and the persistent nature of anthropogenic noise, especially in the wild. Industrial, commercial, and recreational human activity has expanded across the seas, resulting in a propagation of sound with varying frequency characteristics. In many countries, current regulations are based on the potential to induce hearing loss; however, a more nuanced approach is needed when shaping regulations, due to other non-hearing loss effects including activation of the stress response, acoustic masking, frequency shifts, alterations in behavior, and decreased foraging. Cetaceans in managed-care settings share the same acoustic characteristics as their wild counterparts, but face different environmental parameters. There have been steps to integrate work on welfare in the wild and in managed-care contexts, and the domain of acoustics offers the opportunity to inform and connect information from both managed-care settings and the wild. Studies of subjects in managed-care give controls not available to wild studies, yet because of the conservation implications, wild studies on welfare impacts of the acoustic environment on cetaceans have largely been the focus, rather than those in captive settings. A deep integration of wild and managed-care-based acoustic welfare research can complement discovery in both domains, as captive studies can provide greater experimental control, while the more comprehensive domain of wild noise studies can help determine the gaps in managed-care based acoustic welfare science. We advocate for a new paradigm in anthropogenic noise research, recognizing the value that both wild and managed-care research plays in illustrating how noise pollution affects welfare including physiology, behavior, and cognition.


The association of dipyridamole side effects with hemodynamic parameters, ECG findings, and scintigraphy outcomes.
Dipyridamole has extensively been administered as a substitute for physical activity in cardiovascular assessment. The aim of this study was to evaluate the association of dipyridamole side effects with hemodynamic oscillations, scanning results, and electrocardiography (ECG) findings. Overall, 590 patients referred to the nuclear medicine center for myocardial perfusion imaging were evaluated for adverse dipyridamole effects concurrent with a low level of exercise. Before and during dipyridamole infusion, the patients' vital signs, electrocardiogram, heart rate, systolic blood pressure, and diastolic blood pressure were monitored; all patients underwent stress-rest (99m)Tc-sestamibi gated SPECT using a 2-d protocol. Eighty-eight patients (14.9%) experienced at least one side effect during dipyridamole infusion, and abnormal ECG and scan results were observed in 32.4% and 48.6% of patients, respectively. We observed a positive correlation between a higher incidence of chest discomfort, headache, and dyspnea and abnormalities on ECG and myocardial perfusion imaging. In addition, these 3 side effects were also associated with a higher postinfusion heart rate, lower preinfusion systolic blood pressure, and lower postinfusion diastolic blood pressure. There were significant differences between pre- and postinfusion heart rate, preinfusion systolic blood pressure, and postinfusion diastolic blood pressure among patients with or without side effects, whereas no significant difference was observed in any of the hemodynamic parameters between patients with normal and abnormal ECG results or myocardial perfusion imaging results. This study demonstrated a correlation between hemodynamic variables and side effects but not with imaging findings or ECG findings.


Few-Layer Thin-Film Metallic Glass-Enhanced Optical Properties of ZnO Nanostructures.
A few layers of Cu-based (Cu47Zr42Al7Ti4) thin-film metallic glasses (TFMGs) were sputtered on hydrothermally synthesized ZnO nanowires/glass and ZnO nanotubes/glass to fabricate UV photodetectors. The few layers of Cu-based TFMG are ultrathin at ∼0.98 nm and have a noncrystalline metal structure according to X-ray diffraction, Raman, photoluminescence, and high-temperature transmission electron microscopy verification. The photoresponse performance of the coated few-layers Cu-TFMG samples was enhanced 1680-7700% compared with the noncoated sample. The few-layers Cu-TFMG has high transmittance ∼90% in the visible band and creates a large capacitor to absorb UV photocurrent and release dark current.


Characterization of the peptide-binding specificity of HLA-B*7301.
Previous studies showed the human MHC class I heavy chain HLA-B*7301 has a sequence very divergent from other class I alleles. Despite the unusual sequence, we predicted B*7301 would retain the peptide-binding function typical of other HLA-A, B and C glycoproteins, and sequence similarity to B*2705 in a region of the peptide-binding site known as the B pocket suggested B*7301 would bind peptides with Arg at position 2. To test this hypothesis, the peptide-binding specificity of B*7301 was investigated. Sequence analysis of peptides bound endogenously by B*7301 indeed found selectivity for nonamer peptides possessing Arg at position 2 and a preference for small nonpolar residues such as Pro or Ala at the C terminus was also revealed. B*7301 therefore possesses the potential to function as a conventional antigen presenting class I glycoprotein. Functional similarities between B*7301 and B*2705 are discussed in the context of the association of B*27 subtypes with susceptibility to ankylosing sponylitis and arthritic diseases.