Ascorbic acid concentration and total antioxidant activity of human tear fluid measured using the FRASC assay.
To evaluate a novel method (FRASC) for total ferric reducing (antioxidant) activity and ascorbic acid concentration applied to human tears, to investigate the stability of ascorbic acid, and to determine the antioxidant status of human reflex tears. Linearity, sensitivity, and precision of FRASC and ascorbic acid loss during 7 days' storage were assessed; total antioxidant activity and ascorbic acid and uric acid concentrations of reflex tears from 47 healthy subjects were measured. FRASC has good precision, linearity, and sensitivity. Ascorbic acid is stable for at least 7 days at moderately acidic pH (pH 3.6) and low temperature. Total antioxidant activity and ascorbic acid and uric acid concentrations (mean +/- SD) in reflex tears were 409 +/- 162, 23 +/- 9.6, and 68 +/- 46 microM, respectively. Ascorbic acid and uric acid constituted around half the total antioxidant activity measured. There was a significant correlation between uric acid and total antioxidant activity (r = 0.754; P: < 0.0001). Men had significantly (P: = 0.0045) higher tear ascorbic acid concentrations than women. FRASC is suitable for measuring total antioxidant activity and ascorbic acid in human tears. Further clinical study is needed to investigate the male-female difference seen, to characterize the remaining 50% antioxidant activity, and to investigate the effects of environmental conditions, antioxidant supplementation, age, and ocular disease on tear antioxidant status.


[Infrared spectroscopy of the enamel in dental fluorosis].
Structural relationships in orthophosphate (PO4)3-, carbonate (CO3)2-, and hydroxyl (OH)- groups were studied in 2 teeth with grave fluorosis manifestations, removed for orthodontic indications, by infrared spectroscopy. Two intact teeth were examined for control. The findings evidence ar elevated protein level in fluorosis-involved dental enamel and impaired enamel microstructure; this may be explained by specific features of fluorosis clinical manifestation and by increased enamel permeability in grave fluorosis.


[Chronic radiation damage by uranium and plutonium nuclear fission products].
Chronical radiation sickness is a special form of the radiation damage. It occurs when doses of chronical irradiation exceed their values established for professionals. The sickness is well studied in clinical observations. It may take place also if uranium and plutonium nuclear fission products (NFP) enter the organism. In the last case the chronical radiation sickness practically is not investigated. In the article we present the results of the experimental studies on dogs of the damage caused by NFP.


[Study of the role of colicins in the formation of microbial association in experiments in chick embryos].
Experiments were conducted on chick embryos; conditions of formation of bacterial cenosis of Shigella sonnei and E. coli were reproduced. The role of colicinogenia in the formation of bacterial cenosis was demonstrated. An accumulation of colicines in high titres (1: 5120- 1:2560) in the chick embryonic cavity was noted in combined or separate cultivation of colicinogenic shigellae and E. coli. An intergenera transmission of the col-factor was traced in experiments on chick embryos. The data obtained served as foundation for recommendation of the accessible and economic model (chick embryos) for the in vivo study of colicinogenia of the enteric bacteria representatives.


[Cecílio Romaña, Romaña's sign and Chagas' disease].
Cecílio Romaña was an important Argentinean researcher dedicated to tropical diseases in the period 1930-1960, recently died in Barcelona. Working mainly on the epidemiological, clinical and pathological aspects of American trypanosomiasis, Romaña became very famous in 1935 when he accurately described the most typical portal recognized in all the endemic area with the cognomen of "Romaña sign". This description caused an enormous polemic with Romaña's then director, the great Salvador Mazza, who never accepted the specificity of the sign and, much less, its popular name (which was proposed by the Brazilian researchers Emmanuel Dias and Evandro Chagas). This history is briefly summarized in the present article, as well as the great impact of Romaña's discovery in the recognition of the acute Chagas' disease in all the endemic area.


Antimicrobial resistance: steps to reduce the problem with emphasis on antibiotic utilization the Rapid City experience.
In summary, as the SHEA/IDSA Joint Committee on Prevention of Antimicrobial Resistance suggested, it should be easier to prevent the acquisition of resistance than to respond after the problem is extensive. We have taken that approach in the measures undertaken and outlined above. Our lower rates of resistant microorganisms are, in part, due to this, but also due to the diligent use of antibiotics by the medical staff-largely in avoiding empiric broad-spectrum antibiotic therapy when not needed. Our formulary is not restrictive but new antibiotics are not added unless there is a proven niche. The most appropriate and effective antibiotic at our hospital for Streptococcus pneumoniae is penicillin, for Streptococcus pyogenes, penicillin, for Staphylococcus aureus, nafcillin, for a severe Escherichia Coli infection, gentamicin, and for Pseudomonas aeurginosa, gentamicin and ceftazidime. Our efforts are to maintain this favorable situation for our patients and clinicians. Additionally, we will continue to explore and implement new avenues of prevention, with an emphasis on optimal antibiotic utilization, toward the goal of protecting our patients and health care workers from resistant bacteria.


Distinct mechanisms of STAT phosphorylation via the interferon-alpha/beta receptor. Selective inhibition of STAT3 and STAT5 by piceatannol.
Interferon-alpha (IFNalpha) can activate several members of the signal transducers and activator of transcription (STAT) transcription factor family, a process that requires the tyrosine kinases Jak1 and Tyk2. Here we provide evidence that IFNalpha-mediated activation of various STAT proteins is regulated by distinct mechanisms. Piceatannol, previously reported as a Syk/ZAP70-specific kinase inhibitor, selectively inhibits the tyrosine phosphorylation of STAT3 and STAT5, but not of STAT1 and STAT2. This inhibition is paralleled by the loss of Jak1 and IFNAR1 tyrosine phosphorylation in response to IFNalpha, whereas Tyk2 and IFNAR2 tyrosine phosphorylation is unaffected. Last, the IFNalpha-induced serine phosphorylation of STAT1 and STAT3 is not inhibited by piceatannol but is sensitive to the Src kinase-specific inhibitor PP2. Thus, our results not only demonstrate that the IFNalpha/beta receptor utilizes distinct mechanisms to trigger the tyrosine phosphorylation of specific STAT proteins, but they also indicate a diverging pathway that leads to the serine phosphorylation of STAT1 and STAT3.


Antidiabetic and antioxidant effects of tannic acid and melatonin on streptozotocin induced diabetes in rats.
The present investigation aimed to study the possible antidiabetic and related antioxidant potentials of tannic acid and melatonin in streptozotocin (STZ) induced diabetes in rats. Four groups of rats received intraperitoneal one dose of 50mg/kg body weight STZ for the induction of diabetes. The first group served as diabetic control group and received the vehicle. Four days after induction of diabetes, the remaining three groups received glibenclamide (6mg/kg/day), tannic acid (1 g/kg/day) and melatonin (10 mg/kg/day) for two weeks. A fifth group served as vehicle control group. At the end of the experimental period, blood samples and liver samples were collected for the determination of diabetes correlated biomarkers. Treatment of diabetic rats with tannic acid or melatonin attenuated most of the changes associated with STZ induced diabetes. The present results evidenced the beneficial effects of tannic acid and melatonin in diabetes management.


Proliferative synergy of ANG II and EGF in porcine aortic vascular smooth muscle cells.
To test growth effects of angiotensin II (ANG II) in porcine vascular smooth muscle cells (VSMC) and potential ANG II synergy with epidermal growth factor (EGF), we exposed subconfluent, near-quiescent porcine aortic VSMC to ANG II, EGF, or ANG II + EGF (each 10(-9) M) in Dulbecco's modified Eagle's-Ham's F-12 medium with insulin + 0.4% fetal calf serum (FCS) selected for minimal ANG II-degrading capacity. Cell number and DNA and protein synthesis (by [3H]-thymidine and [35S]methionine incorporation, respectively) were determined serially over 1-6 days. ANG II alone induced an early 20% increase and then a plateau in cell number over the 0.4% FCS control (P < 0.01; n = 8), thus without sustained increase in proliferation rate. Yet ANG II alone did not increase fractional DNA or protein synthesis (each as cpm/10(3) cells) and, by flow cytometry, reduced S phase fraction without increase in cell size. EGF alone induced brisk DNA synthesis yet minimal cell division over days 0-4, thus late-cycle arrest. ANG II + EGF, despite no increase in fractional DNA or protein synthesis rates over EGF alone, induced significant indomethacin-resistant dose-dependent (P < 0.001) increase in cell proliferation rate over EGF alone with a median effective dose of 5 x 10(-10) M ANG II, thus proliferative synergy. We propose that 1) ANG II induces a subpopulation of cells arrested in or beyond S phase to proceed through mitosis but does not influence G1 traversal or S phase entry and 2) ANG II + EGF achieve proliferative synergy by complementary actions at sequential cell cycle loci, with EGF supporting progression from G0/G1 to S phase and ANG II inducing completion of mitosis by cells already in or beyond S phase ("late-cycle completion").


Medial peritalar dislocation-associated foot injuries and mechanism of injury.
1) Two cases of medial peritalar dislocation with accompanying foot injuries considerably altering prognosis are presented. 2) Although most cases of this uncommon injury respond well to treatment, a careful investigation for accompanying injuries should be performed. 3) The mechanism of injury is discussed.


Nutrient removal in wastewater treatment high rate algal ponds with carbon dioxide addition.
The influence of CO2 addition to high rate algal ponds (HRAPS) on nitrogen removal was investigated using two pilot-scale HRAPs operated with different hydraulic retention times (HRT: 4 and 8 days), and was compared to the nitrogen removal by the 8-day HRT pond before CO2 addition was installed. Nitrogen balances were calculated by partitioning total nitrogen into organic and inorganic nitrogen (NH4+-N and NO3--N), and by separation of the organic nitrogen into particulate (PON) and dissolved organic nitrogen (DON). PON was further divided into algal organic nitrogen (AON) and bacteria organic nitrogen (BON) to investigate nitrogen mass flow in the HRAPS. This research shows that the proportion of algae in the algal/bacterial biomass in the longer 8-day HRT HRAP8d (55.6%) was appreciably lower than that in the shorter 4-day HRT HRAP4d (80.5%) when CO2 was added to control the maximum pH to <8.0 during the summer. Higher bacterial biomass in the longer 8-day HRT HRAP corresponded with higher nitrification rates, indicating that the longer 8-day HRT in the summer was detrimental for two reasons: lower algal productivity and increased nitrogen loss through nitrification/denitrification. Overall nitrogen removal of approximately 60% in the HRAPS with CO2 addition was mainly achieved by algal assimilation followed by sedimentation in the settling unit.


Cellular interactions in the proliferative response of human T and B lymphocytes to phytomitogens and allogeneic lymphocytes.
In vitro studies were performed to determine the proliferative responsiveness of human peripheral blood thymus-dependent (T) and thymus-independent (B) lymphocytes to phytomitogens and allogeneic lymphocytes. Recombination of T and B cells, with selective inhibition of proliferation of one of the two populations, was used to identify cellular interactions which may contribute to cell proliferation. The distinctive feature of human T lymphocytes to form rosettes with unsensitized sheep erythrocytes was utilized to separate human peripheral blood lymphocytes into highly purified resetting (T) and non-rosetting (B) cells. The proliferative response of these separated lymphocyte subpopulations to various stimulants was assessed from the uptake of tritiated thymidine into DNA. Phytohemagglutinin, concanavalin A, pokeweed mitogen, and allogeneic lymphocytes stimulated separated T cells, whereas no proliferation was observed with the T-cell-depleted B-cell population. This suggests that it is the human T cell which is activated directly by these stimulants. In the presence of T cells (proliferating or nonproliferating), B cells were capable of proliferation following stimulation with phytomitogens, but not in response to histocompatibility antigens. Thus, T-cell-mediated B-cell proliferation contributes to the overall lymphocyte response in phytomitogen-stimulated T + B cell mixtures, but not in human mixed leukocyte cultures. T-cell activation by allogeneic cells required the presence of monocytes; in contrast, the three tested phytomitogens stimulated T cells in the absence of monocytes. This indicates that direct interaction of mitogens with lymphocyte membrane receptors is sufficient to trigger T cells into proliferative response. However, monocytes considerably enhanced the proliferative response of T cells in a dose-dependent fashion; this monocyte-dependent mechanism of T-cell activation was predominant at lower concentrations of phytomitogens, and contributed relatively less at higher mitogen doses. Both, the direct, monocyte-independent, and the indirect, monocyte-dependent T-lymphocyte activation contribute to the total in vitro response of lymphocyte preparations to phytomitogens.


Distinct patterns of expression of interleukin-1 alpha and beta by normal and cancerous human ovarian tissues.
Immunohistochemical staining of normal and cancerous ovarian tissues has demonstrated that both IL-1 alpha and IL-1 beta are more strongly expressed in cancerous than in normal tissues and are secreted mainly by epithelial cells. We have shown by bioassay and immunoassay that cancerous, but not normal ovarian tissues constitutively secrete IL-1 in vitro. Activation of cancerous ovarian tissues by lipopolysaccharide (LPS) increased its capacity to secrete IL-1. Normal ovarian tissues secreted low amounts of IL-1 only after prolonged stimulation (72-96 h) by high doses of LPS (10-100 micrograms/ml). On the other hand, constitutive IL-1 was detected in homogenates of normal ovarian tissues and stimulation by LPS increased its capacity to produce IL-1. IL-1 beta was the main type of IL-1 secreted by cancerous ovarian tissues. IL-1 alpha was detected at lower levels. In contrast, in normal tissues similar amounts of both IL-1 alpha and IL-1 beta were detected in the supernatants. The levels of both types of IL-1, and also the bioactivity of IL-1 were significantly higher in cancerous than in normal ovarian tissues. Established primary cell lines from normal ovarian tissues did not secrete IL-1 into supernatants but did express it at very low levels. Stimulation with LPS did not affect the capacity of these cell lines to secrete IL-1 but it increased their capacity to express it. In contrast, primary established epithelial cell lines from cancerous ovarian tissues did secrete and express high levels of IL-1 and these levels were increased under stimulation with LPS. Cancerous ovarian tissues did not only secrete higher levels of both IL-1 alpha and beta than normal ovarian tissues, but also the mechanism controlling the secretion of these factors in cancerous ovarian tissues seemed to be different from that found in normal ovarian tissues. Our results suggest that paracrine/autocrine factors may be involved in the regulation of both types of IL-1 secreted by ovarian tissues. These cytokines may play a role in regulating the physiological, pathophysiological and oncogenic processes of the ovary.


Training Residents in Advance Care Planning: A Task-Based Needs Assessment Using the 4-Component Instructional Design.
Residents may learn how to perform advance care planning (ACP) through informal curriculum. Task-based instructional designs and recent international consensus statements for ACP provide opportunities to explicitly train residents, but residents' needs are poorly understood. We assessed residents' training needs in ACP at the Geneva University Hospitals in Geneva, Switzerland. Qualitative data were collected and analyzed iteratively between December 2017 and September 2019. Transcripts were coded using both a deductive content analysis based on the 4-Component Instructional Design (4C/ID) model and an inductive thematic analysis. Out of 55 individuals contacted by email, 49 (89%) participated in 7 focus groups and 10 individual interviews, including 19 residents, 18 fellows and attending physicians, 4 nurses, 1 psychologist, 1 medical ethics consultant, 3 researchers, and 3 patients. Participants identified 3 tasks expected of residents (preparing, discussing, and documenting ACP) and discussed why training residents in ACP is complex. Participants described knowledge (eg, prognosis), skills (eg, clinical and ethical reasoning), and attitudes (eg, reflexivity) that residents need to become competent in ACP and identified needs for future training. In terms of the 4C/ID, these needs revolved around: (1) learning tasks (eg, workplace practice, simulated scenarios); (2) supportive information (eg, videotaped worked examples, cognitive feedback); (3) procedural information (eg, ACP pocket-sized information sheet, corrective feedback); and (4) part-task practice (eg, rehearsal of communication skills, simulation). This study provides a comprehensive description of tasks and competencies to train residents in ACP.


Maternal factors in predicting low birth weight babies.
This study examines the association between maternal factors and low birth weight among newborns at a tertiary hospital in Malaysia. This was a cross-sectional study where mothers were followed through from first booking till delivery. There were 666 mothers who delivered from May 2007 to March 2008. Infants' birth weight were compared with maternal age, pre-pregnancy BMI, fathers BMI, parity, ethnicity, per capita monthly income, and maternal blood pressure during pregnancy. A multiple logistic regressions was used to determine the relationship of maternal factors and low birth weight, while the ROC curve was constructed to assess the sensitivity and specificity of the predictive model. Among the significant risk factors of low birth weight were older age (35 years and above), low pre-pregnancy BMI (<20 kg/m2), parity of 4 and above, Indian origin, economically under privileged, and low and high blood pressure. Blood pressure during pregnancy was an important risk factor for LBW, by using this parameter alone the risk of LBW could be predicted with a sensitivity rate of 70% and a specificity rate of 70%. The sensitivity and specificity was further improved to 80% and 75% percent respectively when other factors like maternal factors such as maternal age, pre-pregnancy BMI, ethnicity, and per capita monthly income were included in the analysis.


MicroRNA in Multiple Myeloma - A Role in Pathogenesis and Prognostic Significance.
Multiple myeloma (MM) is a common malignant hematological malignancy. Recently, interest has grown in the role of non-coding regions in disease pathogenesis. MicroRNAs (miRNAs) are small non-coding RNAs containing 19-25 bases that play a crucial role in messenger RNA silencing and post-transcriptional regulation of gene expression. Several miRNAs demonstrate markedly dysregulated expression in MM, suggesting that they may act as both tumor suppressors and oncogenes. microRNAs are also reportedly involved in the regulation of other epigenetic mechanisms of gene expression. Additionally, some miRNAs have been associated with drug resistance, and therefore a further exploration of their activity may lead to its reversal. Moreover, miRNA expression patterns in either MM cells or serum exosomes have been shown to be good prognostic markers. This review describes the roles of miRNAs in MM and examines their potential to predict MM prognosis and play a role in novel therapeutic strategies.


Iododerma complicating cardiovascular surgery.
A patient had cardiovascular surgery and received pericardial povidone-iodine irrigation along with extensive topical povidone-iodine. A postoperative febrile response occurred and persisted despite antibiotic therapy. Within 24 hours of the administration of oral potassium iodide, a pustular iododerma occurred. Discontinuation of oral and topical iodine resulted in defervescence of fever and resolution of the cutaneous eruption.


Circulating anti-filamin C autoantibody as a potential serum biomarker for low-grade gliomas.
Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable due to its invasive nature. Establishment of serum biomarkers for glioma would be beneficial both for early diagnosis and adequate therapeutic intervention. Filamins are an actin cross-linker and filamin C (FLNC), normally restricted in muscle tissues, offers many signaling molecules an essential communication fields. Recently, filamins have been considered important for tumorigenesis in cancers. We searched for novel glioma-associated antigens by serological identification of antigens utilizing recombinant cDNA expression cloning (SEREX), and found FLNC as a candidate protein. Tissue expressions of FLNC (both in normal and tumor tissues) were examined by immunohistochemistry and quantitative RT-PCR analyses. Serum anti-FLNC autoantibody level was measured by ELISA in normal volunteers and in the patients with various grade gliomas. FLNC was expressed in glioma tissues and its level got higher as tumor grade advanced. Anti-FLNC autoantibody was also detected in the serum of glioma patients, but its levels were inversely correlated with the tissue expression. Serum anti-FLNC autoantibody level was significantly higher in low-grade glioma patients than in high-grade glioma patients or in normal volunteers, which was confirmed in an independent validation set of patients' sera. The autoantibody levels in the patients with meningioma or cerebral infarction were at the same level of normal volunteers, and they were significantly lower than that of low-grade gliomas. Total IgG and anti-glutatione S-transferase (GST) antibody level were not altered among the patient groups, which suggest that the autoantibody response was specific for FLNC. The present results suggest that serum anti-FLNC autoantibody can be a potential serum biomarker for early diagnosis of low-grade gliomas while it needs a large-scale clinical study.


Dark chocolate reduces endothelial dysfunction after successive breath-hold dives in cool water.
The aim of this study is to observe the effects of dark chocolate on endothelial function after a series of successive apnea dives in non-thermoneutral water. Twenty breath-hold divers were divided into two groups: a control group (8 males and 2 females) and a chocolate group (9 males and 1 female). The control group was asked to perform a series of dives to 20 m adding up to 20 min in the quiet diving pool of Conflans-Ste-Honorine (Paris, France), water temperature was 27 °C. The chocolate group performed the dives 1 h after ingestion of 30 g of dark chocolate. Flow-mediated dilatation (FMD), digital photoplethysmography, nitric oxide (NO), and peroxynitrite ONOO−) levels were measured before and after each series of breath-hold dives. A significant decrease in FMD was observed in the control group after the dives (95.28 ± 2.9 % of pre-dive values, p < 0.001) while it was increased in the chocolate group (104.1 ± 2.9 % of pre-dive values, p < 0.01). A decrease in the NO level was observed in the control group (86.76 ± 15.57 %, p < 0.05) whereas no difference was shown in the chocolate group (98.44 ± 31.86 %, p > 0.05). No differences in digital photoplethysmography and peroxynitrites were observed between before and after the dives. Antioxidants contained in dark chocolate scavenge free radicals produced during breath-hold diving. Ingestion of 30 g of dark chocolate 1 h before the dive can thus prevent endothelial dysfunction which can be observed after a series of breath-hold dives.


Phenolic profiles and in vitro biochemical properties of Thai herb ingredients for chronic diseases prevention.
Traditional remedies using natural ingredients have been handed down over generations, providing collective information for the development of modern therapeutics. These natural products have a long history of safe consumption with curative effects but lack of scientific-based evidence hinders the mass production of new remedies containing active ingredients with particular medicinal properties. This research investigated the phenolic profiles and biochemical properties of 29 herbal ingredients identified in two traditional Thai remedies, Prasachandaeng (PSCD) and Chantaharuethai (CHRT), and their effectiveness in combating chronic diseases. These two traditional remedies are used to reduce fever but some ingredients have been previously reported to possess other health-related properties. Statistical analysis by TOPSIS indicated that Biancaea sappan (L.) Tod. extract exhibited the highest overall closeness coefficient (C) score analyzed from all variables including total phenolic contents, antioxidant potentials, and enzyme inhibitions. Bouea macrophylla Griff. extract showed potential as an effective agent against diabetes through inhibition of two carbohydrate degrading enzymes, α-glucosidase and α-amylase, while Dischidia major (Vahl) Merr. showed strong properties as an anti-angiotensin-converting enzyme, leading to the control of hypertension. Dracaena cochinchinensis (Lour.) S.C. Chen effectively controlled the progression of Alzheimer's disease through the inhibition of cholinergic and β-amyloid formation enzymes. These results can be used as preliminary data for the development of new remedies to prevent or treat particular chronic diseases.


Aromatase in the brain of teleost fish: expression, regulation and putative functions.
Unlike that of mammals, the brain of teleost fish exhibits an intense aromatase activity due to the strong expression of one of two aromatase genes (aromatase A or cyp19a1a and aromatase B or cyp19a1b) that arose from a gene duplication event. In situ hybridization, immunohistochemistry and expression of GFP (green fluorescent protein) in transgenic tg(cyp19a1b-GFP) fish demonstrate that aromatase B is only expressed in radial glial cells (RGC) of adult fish. These cells persist throughout life and act as progenitors in the brain of both developing and adult fish. Although aromatase B-positive radial glial cells are most abundant in the preoptic area and the hypothalamus, they are observed throughout the entire central nervous system and spinal cord. In agreement with the fact that brain aromatase activity is correlated to sex steroid levels, the high expression of cyp19a1b is due to an auto-regulatory loop through which estrogens and aromatizable androgens up-regulate aromatase expression. This mechanism involves estrogen receptor binding on an estrogen response element located on the cyp19a1b promoter. Cell specificity is achieved by a mandatory cooperation between estrogen receptors and unidentified glial factors. Given the emerging roles of estrogens in neurogenesis, the unique feature of the adult fish brain suggests that, in addition to classical functions on brain sexual differentiation and sexual behaviour, aromatase expression in radial glial cells could be part of the mechanisms authorizing the maintenance of a high proliferative activity in the brain of fish.


The renal-cardiac connection in subjects with preserved ejection fraction: a population based study.
Chronic kidney disease (CKD) is prevalent and is associated with increased cardiovascular morbidity and mortality. The interaction between diastolic dysfunction (DD) and CKD in subjects with preserved systolic function is not well defined. This study sought to determine the association between renal function and DD in subjects with preserved ejection fraction. Through the Rochester Epidemiology Project, subjects who underwent echocardiography over 2 years with EF ≥50% were identified and the clinical data were obtained. Glomerular filtration rate (GFR) was estimated using the modification of diet in renal disease equation. Linear regression was used to test for association of GFR and DD. DD was defined as follows: Grade 2 or pseudonormal pattern (0.75 < E/A ≤ 1.5, E/e' ≥ 10, DT > 140 ms, ΔE/A ≥ 0.5, and PV S < D) or Grade 3+ or restrictive pattern (E/A > 1.5, E/e' ≥ 10, DT < 140 ms, and PV S < D). Cox regression was used to assess correlation of GFR and DD with time-to-event outcomes. A total of 2056 patients were identified. There was significant correlation between worsening GFR and degree of DD assessed by echo Doppler E/e' ratio (P = 0.005), left ventricular mass index (P = 0.004), and right ventricular systolic pressure (P = 0.01). Worsening GFR was associated with increased mortality, development of heart failure, and hospitalization (P < 0.001). Within each GFR group, abnormal DD was associated with a higher risk of the clinical outcomes. No interaction between GFR and DD was noted, suggesting an increased risk of events associated with abnormal DD across ranges of GFR. Worsening GFR was associated with a greater degree of diastolic dysfunction and adverse clinical outcomes. Within each GFR group, the presence of DD was associated with increased morbidity and mortality. Further studies are warranted to determine if improving DD in patients with CKD will benefit clinical outcomes.


Financial Rx for physicians.
It's no secret that doctors are facing more financial struggles than ever before. Thanks to skyrocketing malpractice insurance premiums, slashed or stagnant reimbursement rates, and an aging population that will need more care, physicians across the country are struggling to stay financially solvent. This article outlines some simple steps that physicians can take to keep their personal and professional lives financially healthy. Not only will these suggestions help ease the difficulties of the present, but they will also help doctors plan for the future.


Outcome prediction in home- and community-based brain injury rehabilitation using the Mayo-Portland Adaptability Inventory.
The objective of the study was to develop statistical formulas to predict levels of community participation on discharge from post-hospital brain injury rehabilitation using retrospective data analysis. Data were collected from seven geographically distinct programmes in a home- and community-based brain injury rehabilitation provider network. Participants were 642 individuals with post-traumatic brain injury. Interventions consisted of home- and community-based brain injury rehabilitation. The main outcome measure was the Mayo-Portland Adaptability Inventory (MPAI-4) Participation Index. Linear discriminant models using admission MPAI-4 Participation Index score and log chronicity correctly predicted excellent (no to minimal participation limitations), very good (very mild participation limitations), good (mild participation limitations), and limited (significant participation limitations) outcome levels at discharge. Predicting broad outcome categories for post-hospital rehabilitation programmes based on admission assessment data appears feasible and valid. Equations to provide patients and families with probability statements on admission about expected levels of outcome are provided. It is unknown to what degree these prediction equations can be reliably applied and valid in other settings.


Unraveling the seasonal epidemiology of pneumococcus.
Infections caused by Streptococcus pneumoniae-including invasive pneumococcal diseases (IPDs)-remain a significant public health concern worldwide. The marked winter seasonality of IPDs is a striking, but still enigmatic aspect of pneumococcal epidemiology in nontropical climates. Here we confronted age-structured dynamic models of carriage transmission and disease with detailed IPD incidence data to test a range of hypotheses about the components and the mechanisms of pneumococcal seasonality. We find that seasonal variations in climate, influenza-like illnesses, and interindividual contacts jointly explain IPD seasonality. We show that both the carriage acquisition rate and the invasion rate vary seasonally, acting in concert to generate the marked seasonality typical of IPDs. We also find evidence that influenza-like illnesses increase the invasion rate in an age-specific manner, with a more pronounced effect in the elderly than in other demographics. Finally, we quantify the potential impact of seasonally timed interventions, a type of control measures that exploit pneumococcal seasonality to help reduce IPDs. Our findings shed light on the epidemiology of pneumococcus and may have notable implications for the control of pneumococcal infections.


Development of an Enzyme-Linked Immunosorbent Assay for the Detection of Metosulam.
A direct enzyme-linked immunosorbent assay (ELISA) was developed to quantitate the herbicide metosulam (N-(2,6-dichloro-3-methylphenyl)-5,7-dimethoxy-1,2,4-triazolo(1,5a)pyrimidine-2-sulfonamide) in soil and water. The ELISA had a detection limit of 0.3 ng.mL(-1), a linear working range of 0.5 ng.mL(-1) to 10 ng.mL(-1), and an IC(50) value of 2.8 ng.mL(-1). The metosulam antisera cross-reacted with 5-OH and 7-OH metosulam (N-(2,6-dichloro-3-methylphenyl)-5-hydroxy-7-methoxy-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide and N-(2,6-dichloro-3-methylphenyl)-5-methoxy-7-hydroxy-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonamide, respectively) and the manufacturing intermediate XDE-564 (N-(2,6-dichlorophenyl)-5-ethoxy-7-fluoro[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide). The assay was used to estimate, accurately and precisely, metosulam concentrations in soil and water samples. Water samples were analyzed directly while soil sample analysis required solvent extraction and dilution prior to analysis. Extraction efficiency was 95%. The ELISA estimations in water correlated well with those from HPLC analysis (r(2) = 0.99; slope = 0.99), making the ELISA a cheap and reliable alternative to conventional residue analysis techniques for quantification of metosulam.


[An auricular pseudocyst. A report of 4 cases].
The words pseudocyst of the pinna was suggested in 1966 by Engel for those intracartilaginous swellings of the auricula, presenting in young healthy males without traumatic precedents or previous manipulation. The AA. report 4 cases diagnosed and treated in their Hospital Department. A woman, 85, was one of them. Review of the subject's literature.


Glucocorticoid inhibition of neurohypophysial vasopressin secretion.
Several lines of evidence have suggested that neurohypophysial vasopressin secretion is under the influence of glucocorticoid negative feedback. Studies in clinical and experimental adrenal insufficiency have suggested that the impaired water excretion accompanying that syndrome may be due to elevated vasopressin levels. Furthermore, both the impaired water excretion and elevated vasopressin levels observed in adrenal insufficiency may be normalized by glucocorticoid treatment. This topic remains controversial, with a considerable body of evidence suggesting that vasopressin is elevated during adrenal insufficiency not because of a loss of central steroid negative feedback but because of alterations in plasma volume osmolality (renal mechanisms). Vasopressin responses to a variety of stimuli (hemorrhage, hypoxia, hypertonic saline) in normal humans and animals appear to be attenuated or eliminated by pretreatment with glucocorticoids. However, the vasopressinergic system appears to be considerably less sensitive to negative feedback than the corticotropin-releasing factor-adrenocorticotropic hormone (ACTH) system. There is evidence that the locus for this inhibitory effect is both directly at the posterior pituitary and within the hypothalamus. It is unlikely that corticosteroid negative feedback closes a direct hypothalamo-neurohypophysial-adrenocortical feedback loop. Since neurohypophysial vasopressin is involved in the control of ACTH secretion, it is more likely that the modulation of neurohypophysial vasopressin by glucocorticoid is an integral part of the overall negative-feedback control of ACTH secretion. The physiological role of glucocorticoid inhibition of vasopressin secretion remains speculative.


Hypothermia, immune suppression and SDD: can we have our cake and eat it?
In vitro studies and clinical observations suggest that both accidental and controlled/therapeutic hypothermia have a strong immunosuppressive effect, and that hypothermia increases the risk of infections, especially wound infections and pneumonia. In the previous issue of Critical Care, Kamps and colleagues report that when hypothermia was used for prolonged periods in patients with severe traumatic brain injury in conjunction with selective decontamination of the digestive tract, the risks of infection were the same or lower in patients treated with therapeutic cooling. The risk of infection is widely regarded as the most important danger of therapeutic cooling. The findings of Kamps and colleagues need to be verified in prospective trials and in higher-resistance environments, but raise the possibility of cooling for prolonged periods with greatly reduced risk. We may be able to have our cake and eat it.


An international survey of surveillance schemes for unaffected BRCA1 and BRCA2 mutation carriers.
Female BRCA1/BRCA2 mutation carriers are at substantially increased risk for developing breast and/or ovarian cancer, and are offered enhanced surveillance including screening from a young age and risk-reducing surgery (RRS)-mastectomy (RRM) and/or salpingo-oophorectomy (RRSO). While there are established guidelines for early detection of breast cancer in high-risk women who have not undergone RRM, there are less developed guidelines after RRM. We evaluated the schemes offered before and after RRS in internationally diverse high-risk clinics. An e-mailed survey was distributed to high-risk clinics affiliated with CIMBA. Overall, 22 centers from 16 countries responded. Pre RRS surveillance schemes overwhelmingly included breast imaging (primarily MRI) from 18 to 30 years and clinical breast exam (CBE) at 6-12 month intervals. For ovarian cancer, all but 6 centers offered semiannual/annual gynecological exam, transvaginal ultrasound, and CA 125 measurements. Post RRM, most centers offered only annual CBE while 4 centers offered annual MRI, primarily for substantial residual breast tissue. After RRSO only 4 centers offered specific gynecological surveillance. Existing guidelines for breast/ovarian cancer detection in BRCA carriers are being applied pre RRS but are not globally harmonized, and most centers offer no specific surveillance post RRS. From this comprehensive multinational study it is clear that evidence-based, long-term prospective data on the most effective scheme for BRCA carriers post RRS is needed.


A historical analysis of the relationship between encephalitis lethargica and postencephalitic parkinsonism: a complex rather than a direct relationship.
Postencephalitic parkinsonism has been considered unique among disorders with parkinsonian features because it is believed to have a unitary etiology associated with the virus that presumably caused encephalitis lethargica. Careful analysis of the historical record, however, suggests that this relationship is more complex than commonly perceived. In most cases, the diagnosis of acute encephalitis lethargica was made post hoc, and virtually any catarrh-like illness was considered to have represented encephalitis lethargica, often after an oral history-taking that was undoubtedly subject to patient recall and physician bias. Also, postencephalitic parkinsonism and oculogyric crises were not recognized as sequelae to encephalitis lethargica until well after other sequelae such as movement disorders and mental disturbances had been identified (see previous paper). We suggest here that the relationship between encephalitis lethargica and postencephalitic parkinsonism is not simplistic, i.e., encephalitis lethargica was not solely responsible for the etiology of postencephalitic parkinsonism, thus aligning the latter with most other parkinsonian disorders that are now believed to have multiple causes.


Trans-anethole protects cortical neuronal cells against oxygen-glucose deprivation/reoxygenation.
Trans-anethole has been studied on pharmacological properties such as anti-inflammation, anti-oxidative stress, antifungal and anticancer. However, to date, the anti-ischemic effects of trans-anethole have not been assessed. Therefore, we investigated the neuroprotection of trans-anethole against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cortical neuronal cell injury, an in vitro model of ischemia. The abilities of trans-anethole to block excitotoxicity, oxidative stress and mitochondrial dysfunction were evaluated in OGD/R-induced neurons. Trans-anethole significantly ameliorated OGD/R-induced neuronal cell injury by attenuating the intracellular calcium overload via the activation of NMDA receptors. Trans-anethole also inhibited OGD/R-induced reactive oxygen species overproduction, which may be derived from the scavenging activity in peroxyl radicals, assessed in an oxygen radical absorbance capacity assay. Furthermore, trans-anethole was shown to attenuate the depolarization of mitochondrial transmembrane. These results indicated that the neuroprotective effect of trans-anethole on OGD/R-induced neuronal injury might be due to its ability to inhibit excitotoxicity, oxidative stress and mitochondrial dysfunction. Considering these multiple pathways causing ischemic neuronal damage, the multi-functional effect of trans-anethole suggested that it may be effective in treating ischemic stroke.


High frequency of memory and effector gag specific cytotoxic T lymphocytes in HIV seropositive individuals.
Human immunodeficiency virus type 1 (HIV-1) specific cytotoxic T lymphocytes (CTL) have been detected in most patients following infection. It has also been suggested that the specific CTL response, which may play an important role in delaying disease in infected humans, may decline during the course of disease progression. We have measured HIV peptide specific CTL precursor frequency by limiting dilution analysis in two healthy seropositive patients whose fresh peripheral blood mononuclear cells (PBM) specifically lysed MHC matched target cells (restricted by HLA B27 and B8 respectively). The frequency of HIV peptide specific CTL precursors is high (3 x 10(-3)-10(-4], but lower than estimates of circulating CTL with the same specific cytotoxic activity present directly in peripheral blood using the same sample (10(-2)-10(-3]. We suggest that this difference may result from terminal effector CTL differentiation in the T cell lineage. This implies that only a subset of CTL effectors have growth potential, whereas relatively higher levels of CTL with lytic activity can be detected in PBM of healthy HIV seropositive patients.


Photothermal analysis of individual nanoparticulate samples using micromechanical resonators.
The ability to detect and analyze single sample entities such as single nanoparticles, viruses, spores, or molecules is of fundamental interest. This can provide insight into the individual specific properties which may differ from the statistical sample average. Here we introduce resonant photothermal spectroscopy, a novel method that enables the analysis of individual nanoparticulate samples. Absorption of light by an individual sample placed on a microstring resonator results in local heating of the string, which is reflected in its resonance frequency. The working principle of the spectrometer is demonstrated by analyzing the optical absorption of different micro- and nanoparticles on a microstring. We present the measurement of a simple absorption spectrum of multiple polystyrene microparticles illuminated with an unfocused LED light source. Using a diode laser, single 170 nm polystyrene nanoparticles are detected. With the current setup, nanoparticulate samples with a mass of ~40 ag are detectable. By using nanostrings, visible and infrared photothermal spectroscopy in the subattogram mass regime is possible and single molecule detection is within reach.


Cavernous malformations of the basal ganglia in children.
Cavernous malformations (CMs) of the basal ganglia are relatively rare lesions that can lead to considerable neurological impairment because of their eloquent location. The authors reviewed the clinical course and surgical outcome of a series of children with basal ganglia CMs. The authors retrospectively reviewed the operative experience of the senior author (R.M.S.) and the 1997-2011 database of Boston Children's Hospital for children with CM of the basal ganglia (which includes CM of the caudate and/or lentiform nucleus and excludes CM of the thalamus). They evaluated baseline demographics, presenting signs, operative outcomes, and condition at long-term follow-up visits and compared these characteristics among patients who underwent surgery and those who were observed. Of 180 children with a diagnosis of CM, 11 (6%) had CM of the basal ganglia. The mean age at diagnosis was 9.3 years, and the male/female ratio was 1.8:1. Presenting signs were as follows: hemorrhage (8 children), incidental lesions (2), and seizures (1); 2 children had choreiform movement disorders. Treatment was observation or surgery. Observation was chosen for 5 children either because the lesions were asymptomatic (2 children) or because the risk for neurological dysfunction after attempted excision was believed to be high (3 children). These 5 children were observed over a combined total of 30.4 patient-years; none experienced neurological deterioration or symptomatic hemorrhage from their lesions. The other 6 children underwent microsurgical resection of the lesion because they were symptomatic from hemorrhage or increasing mass effect. All 6 of these children had hemorrhagic lesions, of which the smallest dimension was at least 1.5 cm. Of these 6 lesions, 5 were excised completely, and over a combined total of 46 patient-years of follow-up, no rebleeding or late neurological deterioration after surgery was reported. In this patient population, the natural history of small and asymptomatic CMs of the basal ganglia was benign. The children with large (> 1.5 cm) symptomatic lesions underwent excision; neurological impairment was apparently minimal, and no hemorrhage or neurological deterioration occurred later.


Lateral superresolution using a posteriori phase shift estimation for a moving object: experimental results.
Structured illumination imaging uses multiple images of an object having different phase shifts in the sinusoidally patterned illumination to obtain lateral superresolution in stationary specimens in microscopy. In our recent work we have discussed a method to estimate these phase shifts a posteriori, allowing us to apply this technique to non-stationary objects such as in vivo tissue. Here we show experimental verification of our earlier simulations for phase shift estimation a posteriori. We estimated phase shifts in fluorescence microscopy images for an object having unknown, random translational motion and used them to obtain an artifact-free reconstruction having the expected superresolution.


Effect of dimethylglycine on gastric ulcers in rats.
Dimethylglycine is an anti-stress nutrient with antioxidant properties. Recently, studies have implicated the generation of oxygen-derived free radicals and lipid peroxidation as one of the mechanisms in the pathogenesis of gastric ulcer. Hence, we evaluated the antiulcer activity of dimethylglycine in various rat models of ulcer and also investigated the probable antioxidant mechanism of the anti-ulcer effect. Dimethylglycine at a dose of 25 and 35 mg kg(-1) significantly reduced ulcer number, ulcer size and ulcer index in pyloric-ligation-, ibuprofen- and stress-induced ulcers. The 35 mg kg(-1) dose was more effective than 25 mg kg(-1) and was comparable to famotidine. Dimethylglycine did not produce any significant change in acid secretion, unlike famotidine. There was a significant increase in plasma and tissue malondialdehyde levels in pyloric-ligated rats but these levels fell following dimethylglycine treatment. Also, there was a significant reduction in glutathione levels after dimethylglycine treatment. The results suggest that the gastroprotective effect of dimethylglycine could be mediated by its free radical scavenging activity and cytoprotection of gastric mucosa.


Isolated Distal Interphalangeal Joint Flexion Contracture of the Ring Finger due to Dupuytren Disease: A Case Report.
Dupuytren disease is a common benign fibromatosis of the palmar and finger fascia caused by pathological cord formation. As both the retrovascular and lateral cords are jointly responsible for the flexion contracture of the distal interphalangeal (DIP) joint, isolated DIP joint contracture caused by Dupuytren disease is rare. We present a 34-year-old right-hand-dominant male patient with a 6-month history of an isolated DIP joint flexion contracture in the right ring finger due to Dupuytren disease. Surgical fasciotomy of the retrovascular cord improved the contracture without adverse events. It is important to pay attention to the anatomical relationships between the pathological cord and neurovascular bundle to avoid neurovascular injury during fasciotomy in patients with Dupuytren disease, especially in isolated DIP joint contracture cases. Level of Evidence: Level V (Therapeutic).


Physical activity and mortality among Norwegian women - the Norwegian Women and Cancer Study.
Physical activity (PA) and its relationship with all-cause mortality suggest a strong and consistent inverse association. This study prospectively investigated the association between PA level and mortality among participants of the Norwegian Women and Cancer (NOWAC) Study. A total of 66,136 NOWAC participants were followed-up until December 31st 2008. PA level and possible confounding factors were obtained through a self-administered questionnaire at enrolment. Cox proportional hazards regression was used to calculate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD) and cancer mortality and PA levels defined from 1 to 10 on a global scale. PA levels 1-4 were associated with a significantly increased risk of all-cause mortality (level 1 RR = 2.35; 95% CI: 1.94-2.84, level 2 RR = 1.71; 95% CI: 1.45-2.00, level 3 RR = 1.30; 95% CI: 1.14-1.49, level 4 RR = 1.07; 95% CI: 0.95-1.22), compared with PA level 5. CVD mortality risk increased in PA levels 1-3 (level 1 RR = 3.50; 95% CI: 2.41-5.10, level 2 RR = 1.50; 95% CI: 0.99-2.25, level 3 RR = 1.12; 95% CI: 0.79-1.60) as did cancer mortality risk (RR = 1.32; 95% CI: 0.96-1.81, RR = 1.48; 95% CI: 1.19-1.84, RR = 1.26; 95% CI: 1.06-1.50, respectively). The magnitude of the associations was consistent across strata of age, smoking, and body mass index. The population attributable fractions for PA levels 1-4 were: all-cause mortality, 11.5%; CVD mortality, 11.3%; cancer mortality, 7.8%. There is a significant trend of increased risk of all-cause, CVD and cancer mortality in relation to low PA levels among Norwegian women.


Restoration of CREB function is linked to completion and stabilization of adaptive cardiac hypertrophy in response to exercise.
Potential regulation of two factors linked to physiological outcomes with left ventricular (LV) hypertrophy, resistance to apoptosis, and matching of metabolic capacity, by the transcription factor cyclic-nucleotide regulatory element binding protein (CREB), was examined in the two models of physiological LV hypertrophy: involuntary treadmill running of female Sprague-Dawley rats and voluntary exercise wheel running in female C57Bl/6 mice. Comparative studies were performed in the models of pathological LV hypertrophy and failure: the spontaneously hypertension heart failure (SHHF) rat and the hypertrophic cardiomyopathy (HCM) transgenic mouse, a model of familial idiopathic cardiomyopathy. Activating CREB serine-133 phosphorylation was decreased early in remodeling in response to both physiological (decreased 50-80%) and pathological (decreased 60-80%) hypertrophic stimuli. Restoration of LV CREB phosphorylation occurred concurrent with completion of physiological hypertrophy (94% of sedentary control), but remained decreased (by 90%) during pathological hypertrophy. In all models of hypertrophy, CREB phosphorylation/activation demonstrated strong positive correlations with 1) expression of the anti-apoptotic protein bcl-2 (a CREB-dependent gene) and subsequent reductions in the activation of caspase 9 and caspase 3; 2) expression of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1; a major regulator of mitochondrial content and respiratory capacity), and 3) LV mitochondrial respiratory rates and mitochondrial protein content. Exercise-induced increases in LV mitochondrial respiratory capacity were commensurate with increases observed in LV mass, as previously reported in the literature. Exercise training of SHHF rats and HCM mice in LV failure improved cardiac phenotype, increased CREB activation (31 and 118%, respectively), increased bcl-2 content, improved apoptotic status, and enhanced PGC-1 content and mitochondrial gene expression. Adenovirus-mediated expression of constitutively active CREB in neonatal rat cardiac recapitulated exercise-induced upregulation of PGC-1 content and mitochondrial oxidative gene expression. These data support a model wherein CREB contributes to physiological hypertrophy by enhancing expression of genes important for efficient oxidative capacity and resistance to apoptosis.


Predicting crystal structures ab initio: group 14 nitrides and phosphides.
Crystal structures are predicted for a range of group 14 nitrides and phosphides with 1 : 1 stoichiometry, following our method of starting from the known structures for a range of binary compounds and looking for trends in the preferred local bonding environments in the optimised structures. We have previously applied this method to predict the structures of carbon nitride and phosphorus carbide. Here, we use a similar approach to predict the structures of silicon and germanium nitrides and phosphides with 1 : 1 stoichiometry. We find that the local bonding environments in the preferred structures for the nitrides are the same as those for the 3 : 4 stoichiometry. For the phosphides, we have found several possible structures with similar energies. Structures containing hypervalent phosphorus must be considered as these are often low in energy, particularly for GeP; these have not been included in previous work. The greater tendency to form hypervalent phosphorus in GeP than SiP can be rationalised by considering the bond enthalpies for the two compositions.


CLCA2 as a p53-inducible senescence mediator.
p53 is a tumor suppressor gene that is frequently mutated in multiple cancer tissues. Activated p53 protein regulates its downstream genes and subsequently inhibits malignant transformation by inducing cell cycle arrest, apoptosis, DNA repair, and senescence. However, genes involved in the p53-mediated senescence pathway are not yet fully elucidated. Through the screening of two genome-wide expression profile data sets, one for cells in which exogenous p53 was introduced and the other for senescent fibroblasts, we have identified chloride channel accessory 2 (CLCA2) as a p53-inducible senescence-associated gene. CLCA2 was remarkably induced by replicative senescence as well as oxidative stress in a p53-dependent manner. We also found that ectopically expressed CLCA2 induced cellular senescence, and the down-regulation of CLCA2 by small interfering RNA caused inhibition of oxidative stress-induced senescence. Interestingly, the reduced expression of CLCA2 was frequently observed in various kinds of cancers including prostate cancer, whereas its expression was not affected in precancerous prostatic intraepithelial neoplasia. Thus, our findings suggest a crucial role of p53/CLCA2-mediated senescence induction as a barrier for malignant transformation.


[Protein and amino acid metabolism in the digestive tract growing young bulls. 1. Flow of bacterial raw protein in the duodenum determined by 2,6-diaminopimelic acid as a marker].
The influence of the composition of the rations on the content of diamino pimelic acid (DAP) and N in the bacteria dry matter and on the flow of bacteria crude protein into the duodenum, determined with DAP as marker, was determined on the basis of experimental investigations with young bulls provided with duodenal cannulae and with 28 different rations whose details are described. At a production level corresponding to dry matter intake and a variation range of the crude fibre content of between 11.3 and 29.1% in the DM, a content of N-free extractives between 50.9 and 77.4% in the DM, a content of soluble carbohydrates ibetween 5.3 and 6.4% in the DM, a crude protein content of between 6.4 and 17.1% in the DM and a pure protein content of between 4.9 and 15.5% in the DM, the DAP content of the bacteria DM amounts the 0.350 g 100 g DM +/- 0.090 the N-content of the bacteria DM amounts to 7.37 +/- 1.08 g/100 g DM, there are no relations between DAP- and N-content in the bacteria DM and the content of the individual carbohydrate fractions of the ration, there are positive relations between DAP- and N-content of the bacteria DM, the flow of bacterial crude protein into the duodenum amounts to 133 +/- 14 g/kg truly fermentable organic matter or 130 +/- 14 g/kg apparently digestible organic matter, there is a negative relation between bacteria crude protein at the duodenum (BCPD)/kg truly fermentable organic matter and the crude fibre content of the ration, there is a positive relation between BCPD/kg truly fermentable organic matter and N-free extractives and soluble carbohydrate content as well as the digestibility of the organic matter of the ration, there is no specific influence of the flow rate (kg digesta/kg intake of org. matter) or the dilution rate (g bacteriafree org. matter D/kg LW075/b) on BCPD/kg truly fermentable org. matter, there is a dependence of BCPD/kg truly fermentable org. matter on crude protein concentration in the ration in the concentration range of 6.4-9.0% crude protein in the ration (provided endogenous CP equivalents are used).


Impact of Human Immunodeficiency Virus Drug Resistance on Treatment of Human Immunodeficiency Virus Infection in Children in Low- and Middle-Income Countries.
Children living with human immunodeficiency virus (HIV) in low- and middle-income countries (LMICs) experience higher rates of virologic failure than adults. Human immunodeficiency virus drug resistance (HIVDR) plays a major role in pediatric HIV treatment failure because nonsuppressive maternal antiretroviral therapy (ART) during pregnancy and breastfeeding as well as infant antiretroviral prophylaxis lead to high rates of pretreatment drug resistance to regimens most commonly used in children living with HIV. Lack of availability of durable, potent drugs in child-friendly formulations in LMICs and adherence difficulties contribute to acquired drug resistance during treatment. Optimizing drugs available for treating children living with HIV in LMICs, providing robust adherence support, and ensuring virologic monitoring for children receiving ART are essential for reducing HIVDR and improving treatment outcomes for children living with HIV in LMICs.


Molecularly imprinted adsorbents for selective separation and/or concentration of environmental pollutants.
This review describes the development of molecularly imprinted materials for selective separation and/or concentration of environmental pollutants, the quantitative concentration of which is usually difficult to determine because of their low level of concentration and existence of a large number of contaminants in environmental water. The fragment imprinting technique allowed for the selective separation of endocrine disrupters and halogenated aromatic compounds, including bisphenol A, and chlorinated/brominated aromatic compounds by the specific structural recognition based on the breeds, position, and number of the substituents. Also, the interval immobilization technique provided the specific materials enabling selective concentration based on the interval recognition of ionic functional groups in the targeting compounds, so that the effective determinations were achieved for natural toxins and pharmaceuticals in environmental water. Additionally, a selective photodegradation of toxins and a stimulus responsible hydrogel by the similar molecular recognition ability were successfully carried out. We have summarized these techniques including our recent studies.


Debate: the argument against. Should all pregnant women be offered type-specific serological screening for HSV infection?
The first goal in minimizing herpes simplex virus (HSV) mortality and morbidity in infants is to reduce the risk of acquisition of new infections during pregnancy, especially in late gestation. Antenatal testing does not necessarily predict the risk of transmission to the newborn infant, since this risk is variable. In order to identify newly acquired infection in women who are HSV-seronegative, repeat testing in late pregnancy would need to be offered. In those who are HSV-seropositive, concern for transmission to the infant is likely to result in administration of antiviral drugs to the mother or in Caesarean delivery. The potential consequence is medical intervention for many pregnancies that would not have been complicated by perinatal HSV transmission. Risk - and cost-benefit analyses are needed to assess HSV type-specific serological screening of pregnant women. Practical benefit can be achieved by counselling all pregnant women against oral or unprotected sexual contact during pregnancy.


The motion-induced contour revisited: Observations on 3-D structure and illusory contour formation in moving stimuli.
The motion-induced contour (MIC) was first described by Victor Klymenko and Naomi Weisstein in a series of papers in the 1980s. The effect is created by rotating the outline of a tilted cube in depth. When one of the vertical edges is removed, an illusory contour can be seen in its place. In four experiments, we explored which stimulus features influence perceived illusory contour strength. Participants provided subjective ratings of illusory contour strength as a function of orientation of the stimulus, separation between inducing edges, and the length of inducing edges. We found that the angle of tilt of the object in depth had the largest impact on perceived illusory contour strength with tilt angles of 20° and 30° producing the strongest percepts. Tilt angle is an unexplored feature of structure-from-motion displays. In addition, we found that once the depth structure of the object was extracted, other features of the display, such as the distance spanned by the illusory contour, could also influence its strength, similar to the notion of support ratio for 2-D illusory contours. Illusory contour strength was better predicted by the length of the contour in 3-D rather than in 2-D, suggesting that MICs are constructed by a 3-D process that takes as input initially recovered contour orientation and position information in depth and only then forms interpolations between them.


[Indications for laparoscopic colorectal resections--also for cancers?].
In the last decade, laparoscopy has dramatically changed colonic surgery. Laparoscopic procedures are applied to the treatment of almost all colonic diseases, including both benign and malignant lesions. Significant benefits can be expected with a laparoscopic approach relative to decreased pain, ileus, length of hospital stay, disability, and possibly, adhesion formation and subsequent bowel obstruction, and improved cosmesis. However, all those benefits are secondary in the treatment of cancer; tumor-free survival must be the primary goal. Early comparative studies have shown that laparoscopic colectomy for cancer is safe, feasible, and an oncologic adequate resection can be performed with acceptable operative times and conversion rates. The most recent results of prospective randomized trials are now showing similar survival and cure rates after laparoscopic colectomy. There is evidence that laparoscopic colectomy for curable cancer results in equivalent cancer related survival compared to open colectomy when performed by experienced surgeons. The surgical techniques are demanding and require a level of standardization to achieve success. Laparoscopic colorectal surgery for cancer will have a definite role in the future.


Early experience with laparoscopic splenectomy.
Laparoscopic splenectomy is an example of the recent continued advancement in laparoscopic surgery as techniques are adapted for procedures previously done only via a laparotomy. We analyzed our initial experience with laparoscopic splenectomy for details of the operative procedure and the clinical outcome including length of stay and complication rates. Two surgeons performed 11 laparoscopic splenectomies for cancer or hematologic disorders. In two instances (18%) conversion to open splenectomy was necessary due to bleeding at the splenic hilum. There were no mortalities. Two patients developed pancreatic fluid collections that were successfully drained percutaneously. The seven patients who had an uncomplicated course resumed eating a regular diet in 2.0 +/- 0.6 days (mu +/- SD) and had a hospital stay of 2.7 +/- 1.1 days. Hospital stay was significantly longer for the patients who had complications 9.7 +/- 7.2 days (p < 0.05) and for the 11 patients undergoing on elective uncomplicated open splenectomy during the same time period, 6.5 +/- 2.0 days (p < 0.05). For the 9 patients who had a completed laparoscopic splenectomy, the mean operative blood loss was 263.9 +/- 241.4 cc. The mean operative time was 293.3 +/- 91.4 minutes. The spleens removed laparoscopically weighed an average of 390 grams (range 17 to 1584 grams). Laparoscopic splenectomy can be performed safely and is associated with a rapid resumption of oral alimentation and shortened hospital stay compared to open splenectomy. Complications experienced in our early experience included conversion to open splenectomy and fluid collections from pancreatic leakage.


Cholinergic-dopaminergic interactions in cognitive performance.
Both acetylcholinergic (ACh) and dopaminergic (DA) systems have been found to be crucial for the maintenance of accurate cognitive performance. In a series of studies examining those aspects of cognitive function revealed by the radial-arm maze, we have found that these two neurotransmitter systems interact in a complex fashion. Choice accuracy deficits in the radial-arm maze can be induced by blockade of either muscarinic- or nicotinic-ACh receptors. The choice accuracy deficit induced by blockade of muscarinic receptors with scopolamine can be reversed by the DA receptor blocker, haloperidol. The specific DA D1 blocker SCH 23390 also has this effect, whereas the specific D2 blocker raclopride does not, implying that it is D1 blockade that is critical for reversing the scopolamine effect. On the other hand, the choice accuracy deficit induced by nicotinic blockade with mecamylamine is potentiated by haloperidol. This effect is also seen with the D2 antagonist raclopride, but not with the D1 antagonist SCH 23390, implying that it is the D2 receptor which is important for the potentiation of the mecamylamine effect. The relevance of the D2 receptor for nicotinic actions on cognitive function is emphasized by the finding that the selective D2 agonist LY 171555 reverses the choice accuracy deficit caused by mecamylamine. Nicotinic and muscarinic blockade are synergistic in the deficit they produce. Antagonist doses subthreshold when given alone produce a pronounced impairment when given together. This latter deficit can be reversed by the D2 agonist LY 171555. These studies have outlined the complex nature of ACh-DA interactions with regard to cognitive function. Possible neural circuits for these interactions are discussed. The effectiveness of these selective DA treatments in reversing cognitive deficits due to ACh underactivation suggests a novel approach to treating cognitive dysfunction in syndromes such as Alzheimer's disease.


The impact of body mass index and physical disability on home-based anal self-sampling.
Self-sampling is increasingly being used in screening programs, yet no studies to date have examined the impact of bodily characteristics on self-sampling experiences. Our objective was to assess whether body mass index (BMI) and physical disability were associated with anal self-sampling difficulty. We recruited sexual minority men (SMM) and trans persons in Milwaukee, Wisconsin to participate in an anal cancer screening study. Between January 2020 and August 2022, 240 participants were randomized to a home (n = 120) or clinic (n = 120) screening arm. Home participants received a mailed at-home anal self-sampling kit and were asked to attend a baseline clinic visit where biometric measurements were collected. Participants were asked to complete a survey about their experience with the kit. This research utilized data from participants who used the at-home kit and completed a baseline clinic visit and post-swab survey (n = 82). We assessed the impact of BMI and physical disability on reported body or swab positioning difficulty. Most participants reported no or little difficulty with body positioning (90.3%) or swab positioning (82.9%). Higher BMI was significantly associated with greater reported difficulty with body positioning (aOR = 1.10, 95% CI 1.003-1.20, p = 0.04) and swab positioning (aOR = 1.11, 95% CI 1.02-1.20, p = 0.01). Although not significant, participants who said body positioning was difficult had 2.79 higher odds of having a physical disability. Specimen adequacy did not differ by BMI category (p = 0.76) or physical disability (p = 0.88). Anal self-sampling may be a viable option to reach obese persons who may be more likely to avoid screening due to weight-related barriers.


Immune responses of sheep to louping-ill virus vaccine.
The immune responses of sheep to single and double doses of commercially available louping-ill virus vaccine were examined. The susceptibility to challenge of sheep which had been vaccinated but showed a poor response was also investigated. Two injections of vaccine were required to provoke an adequate antibody response and maximum titres were obtained when there was an interval of two to eight weeks between injections. After challenge, viraemia could not be detected in animals with an antibody titre of 20 although increase in the concentration of humoral antibodies indicated that infection had occurred. Vaccinated but seronegative sheep and vaccinated animals with an antibody titre of 10 were also clinically resistant to the challenge, although circulation of virus was demonstrated. That vaccination had sensitised those animals to viral antigen was evident from the reduced viraemias, the early rise in humoral antibody titres and subsequent protection afforded compared to unvaccinated control animals. Thus, animals with minimal antibody titres after vaccination are protected, but it is recommended that vaccines eliciting the highest possible antibody responses will be the most useful under field conditions.


Measuring body mass index (BMI) in nursing home residents: the usefulness of measurement of arm span.
To study whether arm span can be used as substitute for measurement of height in nursing home patients for calculating body mass index (BMI). Explanatory observational study. Assessment of 35 nursing home residents admitted to long-term stay in a nursing home. Correlation between measured height and arm span and of BMI based on both measures. Measured height and arm span, and BMI calculated from either measure were significantly correlated, r(s)=0.75, p <0.001 and r(s)=0.89, p <0.001, respectively. The ratios of measured height and arm span and between BMIs based on height or arm span are close to 1, but the dispersion is rather large. Arm span is a reliable substitute for measurement of height in nursing home patients. In persons with severe height reduction, arm-span-based BMI is probably more accurate than conventional height-based BMI.


Fulvimarina manganoxydans sp. nov., isolated from a deep-sea hydrothermal plume in the south-west Indian Ocean.
An aerobic, Mn(II)-oxidizing, Gram-negative bacterium, strain 8047(T), was isolated from a deep-sea hydrothermal vent plume in the south-west Indian Ocean. The strain was rod-shaped and motile with a terminal flagellum, and formed yellowish colonies. It produced catalase and oxidase, hydrolysed gelatin and reduced nitrate. 16S rRNA gene sequence analysis showed that strain 8047(T) belonged to the order Rhizobiales of the class Alphaproteobacteria, and was phylogenetically most closely related to the genus Fulvimarina, sharing 94.4% sequence identity with the type strain of the type species. The taxonomic affiliation of strain 8047(T) was supported by phylogenetic analysis of four additional housekeeping genes, gyrB, recA, rpoC and rpoB. The predominant respiratory lipoquinone of strain 8047(T) was Q-10, the major fatty acid was C(18 : 1)ω7c and the DNA G+C content was 61.7 mol%. On the basis of the phenotypic and genotypic characteristics determined in this study, strain 8047(T) represents a novel species within the genus Fulvimarina, for which the name Fulvimarina manganoxydans sp. nov. is proposed. The type strain is strain 8047(T) ( = CGMCC1.10972(T) = JCM 18890(T)).


Sensitivity of coefficients for converting entrance surface dose and kerma-area product to effective dose and energy imparted to the patient.
We investigate the sensitivity of the conversions from entrance surface dose (ESD) or kerma-area product (KAP) to effective dose (E) or to energy imparted to the patient (epsilon) to the likely variations in tube potential, field size, patient size and sex which occur in clinical work. As part of a factorial design study for chest and lumbar spine examinations, the tube potentials were varied to be +/-10% of the typical values for the examinations while field sizes and the positions of the field centres were varied to be representative of values drawn from measurements on patient images. Variation over sex and patient size was based on anthropomorphic phantoms representing males and females of ages 15 years (small adult) and 21 years (reference adult). All the conversion coefficients were estimated using a mathematical phantom programmed with the Monte Carlo code EGS4 for all factor combinations and analysed statistically to derive factor effects. In general, the factors studied behaved independently in the sense that interaction of the physical factors generally gave no more than a 5% variation in a conversion coefficient. Taken together, variation of patient size, sex, field size and field position can lead to significant variation of E/KAP by up to a factor of 2, of E/ESD by up to a factor of 3, of epsilon/KAP by a factor of 1.3 and of epsilon/ESD by up to a factor of 2. While KAP is preferred to determine epsilon, the results show no strong preference of KAP over ESD in determining E. The mean absorbed dose D in the patient obtained by dividing epsilon (determined using KAP) by the patient's mass was found to be the most robust measure of E.


Protein Phosphatase 1 inactivates Mps1 to ensure efficient Spindle Assembly Checkpoint silencing.
Faithfull genome partitioning during cell division relies on the Spindle Assembly Checkpoint (SAC), a conserved signaling pathway that delays anaphase onset until all chromosomes are attached to spindle microtubules. Mps1 kinase is an upstream SAC regulator that promotes the assembly of an anaphase inhibitor through a sequential multi-target phosphorylation cascade. Thus, the SAC is highly responsive to Mps1, whose activity peaks in early mitosis as a result of its T-loop autophosphorylation. However, the mechanism controlling Mps1 inactivation once kinetochores attach to microtubules and the SAC is satisfied remains unknown. Here we show in vitro and in Drosophila that Protein Phosphatase 1 (PP1) inactivates Mps1 by dephosphorylating its T-loop. PP1-mediated dephosphorylation of Mps1 occurs at kinetochores and in the cytosol, and inactivation of both pools of Mps1 during metaphase is essential to ensure prompt and efficient SAC silencing. Overall, our findings uncover a mechanism of SAC inactivation required for timely mitotic exit.


Mutated influenza A virus exhibiting reduced susceptibility to baloxavir marboxil from an experimentally infected horse.
Baloxavir marboxil (BXM), an inhibitor of the cap-dependent endonuclease of the influenza virus polymerase acidic protein (PA), exerts an antiviral effect against influenza A virus. It has been available in Japan since March 2018. This study evaluated the antiviral efficacy of BXM against equine influenza A virus (EIV) by an experimental challenge study using horses. Six horses were experimentally inoculated with EIV, and BXM was administered to the three horses at 2 days post inoculation. Horses treated with BXM showed milder clinical signs than horses without treatment and shed less virus. These results suggest that BXM is effective against EIV. The PA gene of viruses present in the nasopharyngeal swabs collected from horses treated with BXM was sequenced. Two mutations have been detected in viruses recovered from horses treated with BXM. These mutations were the substitution of isoleucine with threonine at position 38 (PA-I38T) and that of asparagine with aspartic acid at position 675 in PA (PA-N675D). A mutated virus with PA-I38T was less susceptible to BXM than viruses with PA-N675D or without mutation. A PA-I38T mutation has also been detected in viruses recovered from humans treated with BXM and is responsible for the reduction in susceptibility to BXM. This suggests that we should not unthinkingly use BXM for the treatment of EI. BXM is likely to easily induce resistance in influenza A viruses, not only in humans but also in horses.


[Infection with high-risk human papillomavirus and prognosis of cervical carcinoma].
Real-time polymerase chain reaction procedure was used to evaluate bioptic tumor samples from patients suffering cervical carcinoma (CC) stages I-IV. Out of 110 patients, high-risk human papillomavirus (HPV) infection was identified in 98 (89.1%), HPV type 16--63, HPV type 18--10 and HPV type 45--5. One of genotypes 31.33, 35, 39, 52, 58, 59 was established in 8 and a combination of several genotypes of the virus--12 patients. Frequency of remission in CC patients associated with HPV type 16 who had survived 3 years was significantly higher than in the same category associated with HPV type 18 (p=0.03). Relapse frequency and mortality rates in patients with tumors associated with one of viruses 31.33, 35, 39, 52, 58 or 59 were higher as compared with HPV type 16--associated cases 2 years (p=0.03) or 3 years on (p=0.11), respectively. A similar trend was established for squamous-cell tumors stages 1 and 2 (p=0.07) (p=0.12), respectively. No difference was observed in efficacy of therapy for infection with one or a combination of several genotypes of high-risk HPV. Hence, the genotype of virus is believed to be a factor of prognosis in CC early cancers. However, a definitive conclusion cannot be reached until results of a larger body of evidence and longer follow-up are available.


Drugs Dosing in Geriatric Patients Depending on Kidney Function Estimated by MDRD and Cockroft-Gault Formulas.
According to the current data, regardless of the method used to estimate GFR, the differences between the obtained results should be insignificant and do not imply therapeutic decisions. The aim of this study was to analyze and compare the eGFR results with the estimated creatinine clearance score calculated according to the Cockroft-Gault equation, and to assess the significance of the difference between these two results. A study group was constituted of 115 patients, of whom 76 were women and 39 men at the age range of 55-93 years, with a median of 79 years. The study analyzed differences in the assessment of kidney function by comparing the results of eGFR assessed by MDRD method obtained from the laboratory with the calculated values of creatinine clearance using the Cockroft-Gault formula, and examining the correlation between the difference D = eGFR -eClCr and BMI and body surface. In the entire group of patients (N = 115), the significant statistical difference was found between eGFR and eClCr. In the subgroup of patients (N = 45) with the lower baseline eGFR <60, there was no significant difference between eGFR and eClCr, while in the subgroup of patients with baseline eGFR ≥60 (N = 75), there was a significant difference between eGFR and eClCr. The study showed that based on the estimated GFR using both methods (C-G and MDRD), 29.2% and 32.4% of patients, respectively, were incorrectly assigned to given stage of chronic kidney disease. Proper assessment of kidney function is very important in order to properly drugs dosing, especially to adjust the doses of drugs metabolized by the kidneys in order to avoid or minimize their nephrotoxic effects.


Atypical chemokine receptors: from silence to sound.
ACRs (atypical chemokine receptors) were initially referred to as 'silent' receptors on the basis of a lack of signalling and functional activities that are typically observed with conventional chemokine receptors. Although ACRs do not directly induce cell migration, they indirectly control leucocyte recruitment by shaping chemokine gradients in tissues through degradation, transcytosis or local concentration of their cognate ligands. Recent evidence also suggests that these biological activities are supported by G-protein-independent, β-arrestin-dependent signalling events. In the present article, we review current knowledge on structural and signalling properties of ACRs that are changing our view on this entire class of receptors from silent to endogenous β-arrestin-biased signalling receptors.


Bioinformatic methods for finding differentially expressed genes in cDNA libraries, applied to the identification of tumour vascular targets.
The aim of this method is to guide a bench scientist to maximise cDNA library analyses to predict biologically relevant genes to pursue in the laboratory. Many groups have successfully utilised cDNA libraries to discover novel and/or differentially expressed genes in pathologies of interest. This is despite the high cost of cDNA library production using the Sanger method of sequencing, which produces modest numbers of expressed sequences compared to the total transcriptome. Both public and propriety cDNA libraries can be utilised in this way, and combining biologically relevant data can reveal biologically interesting genes. Pivotal to the quality of target identification are the selection of biologically relevant libraries, the accuracy of Expressed Sequence Tag to gene assignment, and the statistics used. The key steps, methods, and tools used to this end will be described using vascular targeting as an example. With the advent of next-generation sequencing, these or similar methods can be applied to find novel genes with this new source of data.


Micro-emultocrit technique: a valuable tool for determination of critical HLB value of emulsions.
The aim of this work was to develop a methodology for rapid determination of the critical hydrophilic-lipophilic balance (HLB) value of lipophilic fractions of emulsions. The emulsions were prepared by the spontaneous emulsification process with HLB value from 4.3 to 16.7. The preparations were stored at 2 different temperatures (25 degrees C and 4 degrees C) and their physicochemical behavior was evaluated by the micro-emultocrit technique and the long-term stability study. The experimental data show a reverse relationship between HLB values of the surfactant mixtures and emulsion stability. A close correlation between the results for both stability procedures was observed, suggesting the use of micro-emultocrit to predict stabilities of such systems. In addition, it was found that the critical HLB of the Mygliol 812 was 15.367.


Comparison of nocturnal and diurnal metabolomes of rose flowers and leaves.
Roses are one of the most essential ornamental flowers and are commonly used in perfumery, cosmetics, and food. They are rich in bioactive compounds, which are of interest for therapeutic effects. The objective of this study was to understand the kinds of changes that occur between the nocturnal and diurnal metabolism of rose and to suggest hypotheses. Reversed-phase ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry or triple quadrupole mass spectrometry (TQ MS/MS) was used for nontargeted metabolomics and hormonal profiling respectively. For metabolite annotation, accurate mass spectra were compared with those in databases. The hormonal profile of flowers showed an increase in jasmonate at night, while that of leaves indicated an increase in the salicylic acid pathway. Nontargeted analyses of the flower revealed a switch in the plant's defense mechanisms from glycosylated metabolites during the day to acid metabolites at night. In leaves, a significant decrease in flavonoids was observed at night in favor of acid metabolism to maintain a level of protection. Moreover, it might be possible to place back some of the annotated molecules on the shikimate pathway. The influence of day and night on the metabolome of rose flowers and leaves has been clearly demonstrated. The hormonal modulations occurring during the night and at day are consistent with the plant circadian cycle. A proposed management of the sesquiterpenoid and triterpenoid biosynthetic pathway may explain these changes in the flower. In leaves, the metabolic differences may reflect night-time regulation in favor of the salicylic acid pathway.


The structure of suspended graphene sheets.
The recent discovery of graphene has sparked much interest, thus far focused on the peculiar electronic structure of this material, in which charge carriers mimic massless relativistic particles. However, the physical structure of graphene--a single layer of carbon atoms densely packed in a honeycomb crystal lattice--is also puzzling. On the one hand, graphene appears to be a strictly two-dimensional material, exhibiting such a high crystal quality that electrons can travel submicrometre distances without scattering. On the other hand, perfect two-dimensional crystals cannot exist in the free state, according to both theory and experiment. This incompatibility can be avoided by arguing that all the graphene structures studied so far were an integral part of larger three-dimensional structures, either supported by a bulk substrate or embedded in a three-dimensional matrix. Here we report on individual graphene sheets freely suspended on a microfabricated scaffold in vacuum or air. These membranes are only one atom thick, yet they still display long-range crystalline order. However, our studies by transmission electron microscopy also reveal that these suspended graphene sheets are not perfectly flat: they exhibit intrinsic microscopic roughening such that the surface normal varies by several degrees and out-of-plane deformations reach 1 nm. The atomically thin single-crystal membranes offer ample scope for fundamental research and new technologies, whereas the observed corrugations in the third dimension may provide subtle reasons for the stability of two-dimensional crystals.


Impaired muscle force production and higher fatigability in a mouse model of sickle cell disease.
Skeletal muscle function has been scarcely investigated in sickle cell disease (SCD) so that the corresponding impact of sickle hemoglobin is still a matter of debate. The purpose of this study was to investigate muscle force production and fatigability in SCD and to identify whether exercise intensity could have a modulatory effect. Ten homozygous sickle cell (HbSS), ten control (HbAA) and ten heterozygous (HbAS) mice were submitted to two stimulation protocols (moderate and intense) to assess force production and fatigability. We showed that specific maximal tetanic force was lower in HbSS mice as compared to other groups. At the onset of the stimulation period, peak force was reduced in HbSS and HbAS mice as compared to HbAA mice. Contrary to the moderate protocol, the intense stimulation protocol was associated with a larger decrease in peak force and rate of force development in HbSS mice as compared to HbAA and HbAS mice. These findings provide in vivo evidence of impaired muscle force production and resistance to fatigue in SCD. These changes are independent of muscle mass. Moreover, SCD is associated with muscle fatigability when exercise intensity is high.


The non-peptidic part determines the internalization mechanism and intracellular trafficking of peptide amphiphiles.
Peptide amphiphiles (PAs) are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications. PAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol) to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time. Control over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems.


Review: Hippocampal sclerosis in epilepsy: a neuropathology review.
Hippocampal sclerosis (HS) is a common pathology encountered in mesial temporal lobe epilepsy (MTLE) as well as other epilepsy syndromes and in both surgical and post-mortem practice. The 2013 International League Against Epilepsy (ILAE) classification segregates HS into typical (type 1) and atypical (type 2 and 3) groups, based on the histological patterns of subfield neuronal loss and gliosis. In addition, granule cell reorganization and alterations of interneuronal populations, neuropeptide fibre networks and mossy fibre sprouting are distinctive features of HS associated with epilepsies; they can be useful diagnostic aids to discriminate from other causes of HS, as well as highlighting potential mechanisms of hippocampal epileptogenesis. The cause of HS remains elusive and may be multifactorial; the contribution of febrile seizures, genetic susceptibility, inflammatory and neurodevelopmental factors are discussed. Post-mortem based research in HS, as an addition to studies on surgical samples, has the added advantage of enabling the study of the wider network changes associated with HS, the long-term effects of epilepsy on the pathology and associated comorbidities. It is likely that HS is heterogeneous in aspects of its cause, epileptogenetic mechanisms, network alterations and response to medical and surgical treatments. Future neuropathological studies will contribute to better recognition and understanding of these clinical and patho-aetiological subtypes of HS.


Association of Post-discharge Service Types and Timing with 30-Day Readmissions, Length of Stay, and Costs.
Although early follow-up after discharge from an index admission (IA) has been postulated to reduce 30-day readmission, some researchers have questioned its efficacy, which may depend upon the likelihood of readmission at a given time and the health conditions contributing to readmissions. To investigate the relationship between post-discharge services utilization of different types and at different timepoints and unplanned 30-day readmission, length of stay (LOS), and inpatient costs. The study sample included 583,199 all-cause IAs among 2014 Medicare fee-for-service beneficiaries that met IA inclusion criteria. The outcomes were probability of 30-day readmission, average readmission LOS per IA discharge, and average readmission inpatient cost per IA discharge. The primary independent variables were 7 post-discharge health services (institutional outpatient, primary care physician, specialist, non-physician provider, emergency department (ED), home health care, skilled nursing facility) utilized within 7 days, 14 days, and 30 days of IA discharge. To examine the association with post-discharge services utilization, we employed multivariable logistic regressions for 30-day readmissions and two-part models for LOS and inpatient costs. Among all IA discharges, the probability of unplanned 30-day readmission was 0.1176, the average readmission LOS per discharge was 0.67 days, and the average inpatient cost per discharge was $5648. Institutional outpatient, home health care, and primary care physician visits at all timepoints were associated with decreased readmission and resource utilization. Conversely, 7-day and 14-day specialist visits were positively associated with all three outcomes, while 30-day visits were negatively associated. ED visits were strongly associated with increases in all three outcomes at all timepoints. Post-discharge services of different types and at different timepoints have varying impacts on 30-day readmission, LOS, and costs. These impacts should be considered when coordinating post-discharge follow-up, and their drivers should be further explored to reduce readmission throughout the health care system.


Cost-Effectiveness Analysis of Supervised Exercise Training in Men with Prostate Cancer Previously Treated with Radiation Therapy and Androgen-Deprivation Therapy.
Exercise for prostate cancer (PCa) survivors has been shown to be effective in addressing metabolic function and associated co-morbidities, as well as sarcopenia and significant functional impairment resulting from long-term androgen deprivation. Evidence on the cost-effectiveness of exercise interventions for PCa, however, is lacking, thus the aim of this study was to determine the cost-effectiveness of a supervised exercise intervention for long-term PCa survivors who previously received radiation therapy and androgen-deprivation therapy. Cost-effectiveness analysis from an Australian healthcare-payer perspective was conducted using patient-level data from a multicentre randomised controlled trial (RCT) of supervised exercise training (resistance and aerobic) compared to receiving printed exercise material and a recommendation to exercise in long-term PCa survivors (> 5 years post-diagnosis). Analysis was undertaken for the 6-month supervised exercise portion of the intervention, which involved 100 men aged between 62 and 85 years, 50 in each arm. The primary outcome was cost per quality-adjusted life-years (QALYs). A 6-month supervised exercise intervention for PCa survivors resulted in an incremental cost-effectiveness ratio of AU$64,235 (2018 AUD) at an incremental cost of AU$546 per person and a QALY gain of 0.0085. At a willingness-to-pay of AU$50,000, the probability that the intervention is cost-effective was 41%. Sensitivity analysis showed that maintenance of benefits via a 6-month home-based intervention, immediately following the supervised intervention, lowered the cost per QALY gained to AU$32,051. This is the first cost-effectiveness analysis of exercise for PCa survivors. The intervention was effective, but unlikely to be cost-effective at the generally accepted willingness-to-pay of AU$50,000 per QALY. It is likely that evidence to support cost savings from post-intervention outcomes would reveal greater benefits and contribute to a more comprehensive cost-effectiveness analysis. Future RCTs should incorporate longer follow-up durations and collection of data to support modelling to capture future health benefits. Measures of quality of life or utility more sensitive to the impact of physical activity would also improve future economic evaluations.


Peptic ulcer disease in early infancy: clinical presentation and roentgenographic features.
Sixteen infants under 11 weeks of age developed documented peptic ulcer disease involving the stomach, duodenum or pylorus during an eight-year period in a Newborn Intensive Care Unit. The precipitous onset of gastrointestinal bleeding and/or perforation commonly associated with ulcer disease in early infancy was present in only seven (44%) of the 16 patients. The remaining nine infants (56%) presented with recurrent emesis, a presentation of peptic ulcer disease rarely described in the first weeks of life. Contrast radiography was used to demonstrate a definite ulcer crate in 13 of these patients. Two had their ulcers diagnosed at surgery and one by endoscopy. Radiographic demonstration of pylorospasm and/or gastric retention was often associated with ulcer craters located in the pyloric channel or gastric antrum. Only two patients required surgery for massive bleeding and perforation. The remainder were successfully managed medically using orogastric suction antacids and gradual resumption of milk feedings. There were no deaths within our population attributable to peptic ulcer disease.