Ketorolac May Increase Hematoma Risk in Reduction Mammaplasty: A Case-control Study.
Ketorolac is a potent nonsteroidal anti-inflammatory drug that has valuable analgesic properties but also a hypothetical risk of increased bleeding due to inhibition of platelet activation. The clinical significance of this risk, however, is unclear when it is used after reduction mammaplasty. Our study objective was to therefore examine the association between ketorolac exposure and hematoma occurrence after breast reduction surgery. We hypothesized that there was no association between ketorolac exposure and hematoma occurrence in breast reduction surgery. A case-control design was used. Data from charts of all reduction mammaplasties that developed hematomas requiring surgical evacuation (cases) at our university-based hospitals were retrieved and matched to data from charts of reduction mammaplasty patients who did not indicate this complication (controls). Matching occurred in a 1:1 ratio based on 4 criteria: age, body mass index, institution, and preexisting hypertension. Charts were reviewed for retrospective information on exposure to ketorolac. Odds ratio (OR) was calculated with an OR > 1 favoring an association. From 2002 to 2016, 40 cases of hematoma met inclusion criteria and were matched with 40 controls (N = 80). Cases had a significantly lower body mass index than controls; however, the other baseline patient demographics were similar between the 2 groups. There was an association between hematoma formation and exposure to ketorolac (OR, 2.4; 95% confidence interval, 0.8-7.4; P = 0.114) and a trend for greater risk of hematoma formation, although this was not statistically significant. Based on this level 3 evidence, there appears to be an association between perioperative ketorolac exposure and hematoma after breast reduction surgery, but it was not statistically significant. Although this study was adequately powered, the OR of 2.4 was associated with a wide confidence interval. A larger sample size may increase the precision of the results and may also make the association definitive.


Clinical trials in peripheral vascular disease: pipeline and trial designs: an evaluation of the ClinicalTrials.gov database.
Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease). We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD.


Energy expenditure in hospitalized patients: implications for nutritional support.
An understanding of energy expenditure in hospitalized patients is necessary to determine optimal energy supply in the care of individuals who require nutritional support. A review was conducted of 19 studies in which resting energy expenditure (REE) had been measured using indirect calorimetry and compared with estimated basal energy expenditure (BEE) from the Harris-Benedict equation. Studies of patients with burns, head injuries, and fever were excluded because REE is known to be increased in these conditions. The studies reported data on 1256 patients with the following diagnoses: postoperative (28%), trauma or sepsis (26%), cancer (18%), pulmonary disease (9%), cardiovascular disease (2%), miscellaneous (9%), and unspecified (6%). The average REE in the 19 studies was 113% of the BEE. The mean +/- SD REE/BEE ratio was higher in 11 studies in which the REE was measured during feeding than in 5 studies in which the measurement was made during fasting (117% +/- 3% vs 105% +/- 4%; P = .047). In those 11 studies, overfeeding may have contributed to higher REE values than otherwise would have been observed. Some evidence indicated that the REE/BEE ratio is higher in more severe illness, but results were inconsistent. Unfortunately, little information is available concerning total energy expenditure, which includes the contribution of physical activity. It appears that most patients can be fed adequately with energy equal to 100% to 120% of estimated BEE. Hypoenergetic feeding may be appropriate in some overweight and obese individuals. Additional research in hospitalized patients on total energy expenditure and on the relationship between severity of illness and energy expenditure is needed.


Coinage metal (4, 4) nanotubes, simulated by first-principles calculations.
The structural stability of coinage metal nanotubes with a square cross-section has been investigated by the first-principles numerical simulations. In addition to the reported (4, 4) silver tube, it is found that the hollow (4, 4) copper and gold nanotubes can also be formed by applying an appropriate stress to an 8(A)/8(B) fcc wire. The stability of these coinage metal (4, 4) nanotubes, formed by tip-stretching the wires, has been explained by a local minimum in the string tension variation with their tube lengths. Interestingly, we have explained why a low-stress stretching is needed to obtain the (4, 4) Cu tube in contrast to a higher one for both the (4, 4) Ag and Au tubes due to the larger stiffness coefficient of copper than those of silver and gold, which could be proved by future experiments.


Ultrasound Chemical Effects on Pure Organic Liquids.
Molecular fragmentation of organic liquids was produced by cavitation due to ultrasound waves, even in the absence of water. The sonolysis of acetonitrile under argon yielded N(2), CH(4), and H(2); but under oxygen the products were N(2), CO, CO(2), and H(2)O. Pure nonaqueous carbon tetrachloride also underwent sonolytic decomposition under either argon or oxygen, with the production of elemental chlorine.


Reliability and Validity of the Spanish Version of the Executive Function Performance Test (EFPT) in Assessing People in Treatment for Substance Addiction.
Assessing people's executive function (EF) during addiction treatment makes it possible to design individualized occupational goals. To determine the reliability and validity of the Spanish version of the Executive Function Performance Test (EFPT) in the occupational assessment of people being treated for substance addiction. Cross-sectional, observational study to determine the EFPT's internal consistency as well as its convergent and discriminant validity with complementary tests. A public, free addiction treatment center operated by Madrid Salud (Madrid City Council, Spain). Fifty-two people referred to an occupational therapy department for evaluation and intervention. Inclusion was based on Diagnostic and Statistical Manual of Mental Disorders (4th ed., text revision) criteria for substance abuse or dependence; the exclusion criterion consisted of any circumstances that made it difficult for a person to understand or perform the test. The EFPT, other occupational tests (Allen Cognitive Level Screen-5, Lowenstein Occupational Therapy Cognitive Assessment), and a battery of neuropsychological EF tests. The EFPT had an unequivocal unifactorial structure and showed strong correlations between its components and adequate consistency with the scales and the complete test. As expected, the EFPT correlated with the neuropsychological tests with a considerable effect size (-.40 < r < -.60). The EFPT's psychometric properties are adequate to assess the EF of people being treated for substance addiction from an occupational perspective using real activities of daily living (ADLs). The results show that the EFPT can be used to assess performance of ADLs without needing to use tests from disciplines other than occupational therapy. Further studies in different sociocultural settings are needed to generalize the results.


Spreading depolarization and angiographic spasm are separate mediators of delayed infarcts.
In DISCHARGE-1, a recent Phase III diagnostic trial in aneurysmal subarachnoid haemorrhage patients, spreading depolarization variables were found to be an independent real-time biomarker of delayed cerebral ischaemia. We here investigated based on prospectively collected data from DISCHARGE-1 whether delayed infarcts in the anterior, middle, or posterior cerebral artery territories correlate with (i) extravascular blood volumes; (ii) predefined spreading depolarization variables, or proximal vasospasm assessed by either (iii) digital subtraction angiography or (iv) transcranial Doppler-sonography; and whether spreading depolarizations and/or vasospasm are mediators between extravascular blood and delayed infarcts. Relationships between variable groups were analysed using Spearman correlations in 136 patients. Thereafter, principal component analyses were performed for each variable group. Obtained components were included in path models with a priori defined structure. In the first path model, we only included spreading depolarization variables, as our primary interest was to investigate spreading depolarizations. Standardised path coefficients were 0.22 for the path from extravascular bloodcomponent to depolarizationcomponent (P = 0.010); and 0.44 for the path from depolarizationcomponent to the first principal component of delayed infarct volume (P < 0.001); but only 0.07 for the direct path from bloodcomponent to delayed infarctcomponent (P = 0.36). Thus, the role of spreading depolarizations as a mediator between blood and delayed infarcts was confirmed. In the principal component analysis of extravascular blood volume, intraventricular haemorrhage was not represented in the first component. Therefore, based on the correlation analyses, we also constructed another path model with bloodcomponent without intraventricular haemorrhage as first and intraventricular haemorrhage as second extrinsic variable. We found two paths, one from (subarachnoid) bloodcomponent to delayed infarctcomponent with depolarizationcomponent as mediator (path coefficients from bloodcomponent to depolarizationcomponent = 0.23, P = 0.03; path coefficients from depolarizationcomponent to delayed infarctcomponent = 0.29, P = 0.002), and one from intraventricular haemorrhage to delayed infarctcomponent with angiographic vasospasmcomponent as mediator variable (path coefficients from intraventricular haemorrhage to vasospasmcomponent = 0.24, P = 0.03; path coefficients from vasospasmcomponent to delayed infarctcomponent = 0.35, P < 0.001). Human autopsy studies shaped the hypothesis that blood clots on the cortex surface suffice to cause delayed infarcts beneath the clots. Experimentally, clot-released factors induce cortical spreading depolarizations that trigger (i) neuronal cytotoxic oedema and (ii) spreading ischaemia. The statistical mediator role of spreading depolarization variables between subarachnoid blood volume and delayed infarct volume supports this pathogenetic concept. We did not find that angiographic vasospasm triggers spreading depolarizations, but angiographic vasospasm contributed to delayed infarct volume. This could possibly result from enhancement of spreading depolarization-induced spreading ischaemia by reduced upstream blood supply.


Recurrent Pain and Academic Achievement in School-Aged Children: A Systematic Review.
Recurrent pain and school failures are common problems in children visiting the school nurses office. The overall aim of the current study was to investigate the relationship between recurrent pain and academic achievement in school-aged children. Literature was searched in seven electronic databases and in relevant bibliographies. Study selection, data extraction, and study and evidence quality assessments were performed systematically with standardized tools. Twenty-one studies met the inclusion criteria and 13 verified an association between recurrent pain (headache, stomachache, and musculoskeletal pain) and negative academic achievement. Two longitudinal studies indicated a likely causal effect of pain on academic achievement. All studies had substantial methodological drawbacks and the overall quality of the evidence for the identified associations was low. Thus, children's lack of success in school may be partly attributed to recurrent pain problems. However, more high-quality studies are needed, including on the direction of the association and its moderators and mediators.


Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas.
In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish that 6/29 tumours possessed point mutations of the p53 gene. Using a monoclonal antibody that recognises the p53 protein in immunohistochemical staining experiments, we observed overexpression of the p53 protein in five of the six tumours containing point mutations in the p53 gene. Southern analysis of tumour DNA revealed that 2/29 tumours demonstrated amplification of the MDM2 gene. When considered together, these results indicate that alterations in both the p53 gene and MDM2 gene are important in the development of a significant minority of leiomyosarcomas. In addition, we have demonstrated a significant association between the presence of abnormalities of the p53 gene or MDM2 genes in leiomyosarcomas and a more advanced clinicopathological stage (P = 0.03). We have also examined the role of the DCC tumour-suppressor gene in the development of human soft-tissue tumours in a variety of histological types. Except for evidence of a rearrangement in a single leiomyosarcoma cell line, SK-UT-1, we have found no direct evidence to support a role for mutation of the gene in the development of human soft-tissue tumours.


Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. II. Biased T cell receptor V beta expression predominates in spinal cord infiltrating T cells.
The immune response of Lewis rat lymph node T cells to guinea pig myelin basic protein (GP-BP) in experimental allergic encephalomyelitis is directed primarily against a region of basic protein encompassed by residues 72-89. T cells that respond to this epitope are restricted by the RT1.B class II molecule of the MHC and use V beta 8.2 exclusively in their TCR. A second region of GP-BP, residues 87-99, also induces experimental allergic encephalomyelitis in Lewis rats but this response is restricted primarily by RT1.D. Elsewhere we describe the biologic characteristics of T cell clones responding to the synthetic peptide, s87-99, and to a related peptide, s85-99. We present a detailed analysis of TCR V beta gene expression among these clones, derived from the lymph node and spinal cord of immunized animals, and among spinal cord derived T cell clones reactive to GP-BP 72-89. We find that spinal cord-derived clones, reactive to s85-99 and to s87-99, use V beta 6 predominantly. In contrast, T cell clones derived from lymph nodes and reactive to the same peptides express multiple V beta genes including V beta 6. This difference in heterogeneity of V beta usage at the clonal level is also seen in T cell lines derived from spinal cord and immune lymph node. DNA sequence comparison of the CDR3 regions in V beta 6+ spinal cord clones revealed a conserved amino acid motif also found in the majority of V beta 6 sequences from the spinal cord anti-s85-99 line. Although V beta 6 was expressed in some lymph node-derived clones, only one contained a CDR3 region similar to that seen in spinal cord isolates. All spinal cord-derived T cell clones reactive to GP-BP 72-89 used V beta 8.2 and most (five of six) contained the AspSer residues in CDR3 previously shown to be associated with V beta 8.2 receptors expressed by the majority of lymph node T cells responding to GP-BP 72-89. These data indicate that TCR V beta usage in peripheral T cells responding to an autoantigen does not always predict the V beta usage among T cells at the site of an autoimmune attack. Possible explantations for the relative homogeneity in TCR V beta expression seen in T cell clones derived from the spinal cord are discussed.


THE PHYSIOLOGICAL BASIS OF MORPHOLOGICAL POLARITY IN REGENERATION. I.
1. In Bryophyllum calycinum two apical leaves suppress the shoot formation in all the dormant buds situated basally from the leaf; one apical leaf suppresses the shoot formation in the basal buds situated in the same half of the stem where the leaf is, and, if one-half of the petiole of such a leaf is removed, the growth of basal buds in one quadrant of the stem is suppressed. 2. This inhibitory influence of a leaf upon shoot formation in the basal part of a stem is diminished or disappears when the mass of the leaf is reduced below a certain limit. 3. The inhibitory influence of an apical leaf upon the growth of shoots in horizontally suspended stems is greater when the leaf is on the upper than when it is on the lower side of the stem. 4. All these facts suggest the possibility that the inhibitory influence of the leaf upon shoot formation is due to inhibitory substances secreted by the leaf and carried by the sap from the leaf towards the base of the stem. 5. An apical leaf accelerates root formation in the basal part of a stem and this accelerating effect increases with the mass of the leaf. 6. This inhibitory influence of a leaf upon shoot formation and the favoring influence upon root formation in the more basally situated parts of the stem is one of the factors determining the polar character of regeneration.


An attempt to estimate the global burden of disease due to fluoride in drinking water.
A study was conducted to examine the feasibility of estimating the global burden of disease due to fluoride in drinking water. Skeletal fluorosis is a serious and debilitating disease which, with the exception of one area in China, is overwhelmingly due to the presence of elevated fluoride levels in drinking water. The global burden of disease due to fluoride in drinking water was estimated by combining exposure-response curves for dental and skeletal fluorosis (derived from published data) with model-derived predicted drinking water fluoride concentrations and an estimate of the percentage population exposed. There are few data with which to validate the output but given the current uncertainties in the data used, both to form the exposure-response curves and those resulting from the prediction of fluoride concentrations, it is felt that the estimate is unlikely to be precise. However, the exercise has identified a number of data gaps and useful research avenues, especially in relation to determining exposure, which could contribute to future estimates of this problem.


Effects of rowing stroke rates on lower extremity intra-joint coordination variability in experienced young rowers.
The purpose of this study was to examine the effects of rowing stroke rates on lower extremity intra-joint coordination variability in professional rowers. Fifteen experienced young rowers volunteered to participate in this study. Kinematic data were recorded at different rowing speeds with seven Vicon cameras. The continuous relative phase (CRP) and CRP variability (CRPV) were used to calculate joint coordination and coordination variability, respectively, for the hip, knee, and ankle in the sagittal and horizontal planes, and a comparison was made among different rowing stroke rates. A vector analysis repeated measure ANOVA using statistical parametric mapping revealed that there were statistically significant differences in the hip-ankle, hip-knee, and knee-ankle CRPs for rowing at different stroke rates. Moreover, there was higher CRPV in the mid-drive and mid-recovery phases and less variability in the transition from the drive phase to the recovery phase. The results demonstrate the importance of knee joint in rowing tasks in experienced rowers during submaximal rowing stroke rate and the shift of movement to the hip at higher rowing stroke rate. Moreover, there was a smaller variability during drive-to-recovery transition, which may suggests an increased risk for overuse injuries.


Antibodies to hepatitis B surface antigen potentiate the response of human T lymphocyte clones to the same antigen.
Human t-helper lymphocyte clones specific for hepatitis B virus surface antigen (HBsAg) proliferate on stimulation with HBsAg in vitro. Antibodies specific for HBsAg, but no other antibodies, augment this proliferative response. In the presence of antibodies to HBsAg, the maximum response could be achieved at HBsAg concentrations that were 1 percent of those required in the absence of the antibodies. These findings suggest that antigen-specific antibodies exert regulatory controls on T cells that recognize the same antigens.


Wild orangutans can simultaneously use two independent vocal sound sources similarly to songbirds and human beatboxers.
Speech is among the most complex motoric tasks humans ever perform. Songbirds match this achievement during song production through the precise and simultaneous motor control of two sound sources in the syrinx. Integrated and intricate motor control has made songbirds comparative models par excellence for the evolution of speech, however, phylogenetic distance with humans prevents an improved understanding of the precursors that, within the human lineage, drove the emergence of advanced vocal motor control and speech. Here, we report two types of biphonic call combination in wild orangutans that articulatorily resemble human beatboxing and that result from the simultaneous exercise of two vocal sound sources: one unvoiced source achieved through articulatory maneuvering of the lips, tongue, and jaw as typically used for consonant-like call production, plus one voiced source achieved through laryngeal action and voice activation as typically used for vowel-like call production. Orangutan biphonic call combinations showcase unappreciated levels of, and distinct neuromotor channels for, vocal motor control in a wild great ape, providing a direct vocal motor analogy with birdsong based on the precise and simultaneous co-control of two sound sources. Findings suggest that speech and human vocal fluency likely built upon complex call combination, coordination and coarticulation capacities that involved vowel-like and consonant-like calls in an ancestral hominid.


Solid phase enzyme immunoassay of human interleukin 2 utilizing antibodies against synthetic IL-2 peptides.
In the present study, solid phase enzyme immunoassay utilizing antibodies against synthetic IL-2 peptides was used for quantitative measurements of human recombinant and lymphoid IL-2 preparations. The 27-peptide MCF-III-6 (Leu-Glu-His-Leu-Leu-Leu-Asp-Leu-Gln-Met-Ile-Leu-Asn-Gly-Ile-Asn-Asn-- Tyr-Lys-Asn-Pro-Lys-Leu-Thr-Arg-Met-Leu) that comprises the region 14-40 from the IL-2 amino acid sequence was synthesized and used for immunization of rabbits. Resulting anti-MCF-III-6 polyvalent rabbit antibodies reacted specifically in EIA up to dilution of 10(-7) with the MCF-III-6 peptide used for immunization as well as with 16-peptide I-16 (Cys-Nle-Gly-Ile-Asn-Asn-Tyr-Lys-Asn-Pro-Lys-Leu-Thr-Arg-Met-Leu) that comprises the region 27-40 from the IL-2 amino acid sequence. The anti-MCF-III-6 antibody reacted also with human recombinant IL-2 preparations obtained from three producers (Cetus, Riga and Amersham), to the concentration of 0.1 ng/ml, and with various human lymphoid IL-2 preparations. Direct correlation was observed between quantitative measurements of human lymphoid IL-2 by EIA and by CTLL bioassay. It can be concluded that utilization of synthetic IL-2 peptides provides a suitable and comparatively unexpensive immunogen for the production of IL-2 antibodies and that the solid phase EIA using such antibodies can be employed as a rapid, reproducible, and sensitive method for quantitative examination of both recombinant and lymphoid IL-2 preparations.


Inhibition of protein synthesis by the human immunodeficiency virus type 1 nef gene product.
During productive infection of human T lymphocytes in cell culture, the expression of human immunodeficiency virus type 1 is temporally regulated by virus-encoded regulatory proteins. Among these Nef, whose function has not been clearly elucidated, is thought to alter CD4+ T cells. We examined the possibility that the nef gene interferes with the translation process in a cell-free system. The results demonstrate that the nef gene product mediates an inhibitory effect on protein synthesis. Conversely, the use of antisense nef mRNA did not affect translation. Further observations suggest that this inhibitory effect is an inherent property of the nef gene product itself and not of its mRNA. The data show that the translational repression directed by Nef is a general phenomenon, acting on its own and on other messengers used as reporter mRNAs. We propose that, as a consequence, Nef can play an important role in the pathogenesis of AIDS.


Post graduate clinical placements: evaluating benefits and challenges with a mixed methods cross sectional design.
Systematic evaluations of clinical placements are rare, especially when offered alongside academic postgraduate courses. An evidence-based approach is important to allow pedagogically-driven provision, rather than that solely governed by opinion or market demand. Our evaluation assessed a voluntary clinical placement scheme allied to a mental health course. Data were collected over academic years 2010/11- 2013/14, from participating students (n = 20 to 58) and clinician supervisors (n = 10-12), using a mixed-methods cross-sectional design. Quantitative evaluation captured information on uptake, dropout, resource use, attitudes and experience, using standardized (the Placement Evaluation Questionnaire; the Scale To Assess the Therapeutic Relationship - Clinical version and the University of Toronto Placement Supervisor Evaluation) and bespoke questionnaires and audit data. Qualitative evaluation comprised two focus groups (5 clinicians, 5 students), to investigate attitudes, experience, perceived benefits, disadvantages and desired future developments. Data were analysed using framework analysis to identify a priori and emergent themes. High uptake (around 70 placements per annum), low dropout (2-3 students per annum; 5 %) and positive focus group comments suggested placements successfully provided added value and catered sufficiently to student demand. Students' responses confirmed that placements met expectations and the perception of benefit remained after completion with 70 % (n = 14) reporting an overall positive experience, 75 % (n = 15) reporting a pleasant learning experience, 60 % (n = 12) feeling that their clinical skills were enhanced and 85 % (n = 17) believing that it would benefit other students. Placements contributed the equivalent of seven full time unskilled posts per annum to local health care services. While qualitative data revealed perceived 'mutual benefit' for both students and clinicians, this was qualified by the inherent limitations of students' time and expertise. Areas for development included fostering learning around professionalism and students' confidence on placement. The addition of healthcare placements to academic postgraduate taught courses can improve their attractiveness to applicants, benefit healthcare services and enhance students' perception of their learning experiences. Well-positioned and supported placement learning opportunities could become a key differentiator for academic courses, over potential competitors. However, the actual implications for student employability and achievement remain to be established.


Milk-substitute diet composition and abomasal secretion in the calf.
1. The effect of different protein sources in milk-substitute diets on abomasal acidity and proteolytic activity was studied in Friesian calves, aged 20-58 d (Expt 1). The diets contained 'mildly' preheated, spray-dried skim-milk powder (MHM), severely preheated, spray-dried skim-milk powder (SHM), fish-protein concentrate (FPC) or solvent-extracted soya-bean flour (SF) as the main protein source. 2. Gastric juice was collected from abomasal pouches before feeding and at 15 min intervals for 8 h after the morning feed. Samples of digesta were obtained from the abomasum at 1 h intervals during the same period. 3. Digesta pH was lower and titratable acidity higher 0-3 after giving the diet containing MHM than when any of the other three diets was given. 3. Acid secretion from the pouches for the different diets was in the order: FPC greater than MHM greater than SHM greater than or equal to SF. 5. Protease secretion from the pouches, assayed at pH 2-1, was in the order: MHM greater than SHM = FPC greater than SF. 6. The effect of dry matter (DM) intake and concentration on abomasal acidity was also studied in calves given diets which contained MHM (Expt 2). This diet was reconstituted at either 100 or 149 g DM/kg liquid diet and fed at either 32-5 or 49-0 g DM/kg live weight 0-75 per d. Samples of abomasal digesta were collected as in Expt 1. 7. A high intake of DM at a low DM concentration resulted in low acidity of the digesta in the first 3 h after feeding, which suggested a dilution effect. Comparison of two diets of different DM concentration, which were fed in the same volume of liquid, indicated that the greater the DM intake, the greater was the amount of acid secreted. 8. It is concluded that the protein sources varied in their ability to stimulate abomasal acid and protease secretion and it is suggested that this may relate to calf performance.


Crossing experiments detect partial reproductive isolation among populations of Triatoma longipennis (Hemiptera: Reduviidae: Triatominae).
Chagas disease is an important vector-borne disease endemic in Mexico. Of the 33 triatomine species found in Mexico, Triatoma longipennis (Usinger) is considered among the most important because of its infection indices, capacity for transmitting Trypanosoma cruzi (Chagas), and its distribution areas. Here, we describe the results of a reproductive isolation analysis among 5 populations of T. longipennis collected from representative areas of Mexico. Fertility and segregation of morphological characteristics were examined in two generations of hybrids. The percentage of pairs with (fertile) offspring varied from 30% to 100% in the parental crosses, while these values varied from 0 to 100% in the intersite crosses. Our results indicate partial reproductive isolation among these populations. These findings shed light on the potential presence of a cryptic species complex of T. longipennis in Mexico.


Usefulness of full-thickness skin grafting from the infraclavicular area for facial reconstruction.
Full-thickness skin grafts (FTSGs) have been widely used after facial skin cancer resection, for correcting defects that are too wide to be reconstructed using a local flap or if structural deformation is expected. The preauricular, posterior auricular, supraclavicular, conchal bowl, nasolabial fold, and upper eyelid skin areas are known as the main donor sites for facial FTSG. Herein, we aimed to describe the effectiveness of using infraclavicular skin as the donor site for specific cases. We performed FTSG using the infraclavicular skin as the donor site in older Asian adults following skin cancer resection. Outcomes were observed for > 6 months postoperatively. The Manchester Scar Scale was used for an objective evaluation of satisfaction following surgery and scarring. We analyzed the data of 17 patients. During follow-up, the donor and recipient sites of all patients healed without complications. Upon evaluation, the average Manchester Scar Scale scores for the recipient and donor sites were 7.4 points and 5.7 points, respectively. In general, conventional donor sites, such as the preauricular, posterior auricular, and supraclavicular sites, are widely used for facial FTSG because they achieve good cosmetic results. However, the infraclavicular skin may be a useful donor for facial FTSG in cases where the duration of time spent under anesthesia must be minimized due to a patient's advanced age or underlying health conditions, or when the recipient site is relatively thick area, such as the nose, forehead, or cheek.


Malignant mammary cells acquire independence from extracellular context for regulation of estrogen receptor alpha.
Interactions between luminal epithelial cells and their surrounding microenvironment govern the normal development and function of the mammary gland. Alterations of these interactions can induce abnormal intracellular signaling pathways that affect the development and progression of breast tumors. One critical component of mammary gland development, as well as breast cancer progression, is the expression of estrogen receptors. In a previous study using cultured nonmalignant mammary epithelial cells, we found that the basement membrane molecules, laminin-1 and collagen-IV, were involved in maintenance of estrogen receptor (ER) alpha expression, and that this response could be interfered with by disrupting cell-extracellular matrix adhesion. Here we use phenotypically normal mammary epithelial SCp2 cells to dissect the promoter region of the ERalpha that is involved in the selective response to basement membrane. We also analyze the alteration of this response in SCg6 cells, a malignant cell line that shares a common lineage with the SCp2 cells, to provide insight into the relative overexpression of ERalpha and the unresponsiveness to basement membrane regulation found in those malignant cells. Evidence is presented to show the relevance of the cross-talk between different signaling pathways in the constitution of a functional tissue organization and how this integration may be disrupted in the malignant phenotype.


SIRT4 prevents hypoxia-induced apoptosis in H9c2 cardiomyoblast cells.
Apoptosis plays a critical role in cardiomyocyte loss during ischaemic heart injury. A detailed understanding of the mechanism involved has a substantial impact on the optimization and development of treatment strategies. Here, we report that the expression of SIRT4, a mitochondrial sirtuin, is markedly down-regulated in hypoxia-induced apoptosis of H9c2 cardiomyoblast cells. SIRT4 interference significantly alters H9c2 cell viability, apoptotic cell number and caspase-3/7 activity. Furthermore, SIRT4 expression can affect the ratio of pro-caspase 9/caspase 9 or pro-caspase 3/caspase 3, an affect Bax translocation, which in turn alters the development of H9c2 cell apoptosis. These results suggest that SIRT4 is a key player in hypoxia-induced cardiomyocyte apoptosis, and that strategies based on its enhancement might be of benefit in the treatment of ischaemic heart disease.


The aryl hydrocarbon receptor at the forefront of host-microbe interactions in the skin: A perspective on current knowledge gaps and directions for future research and therapeutic applications.
The skin is home to a community of skin microbiota including bacteria, viruses and fungi, which are widely accepted to be of importance for skin homeostasis but also associated with skin diseases. Detailed knowledge on the skin microbiota composition and its changes in a number of skin diseases is available. Yet, specific interactions between microbes and the host skin cells or how they communicate with each other are less well understood. To identify, understand and eventually therapeutically exploit causal relationships of microbial dysbiosis with disease, studies are required that address the receptors and mediators involved in host-microbe interactions. In this perspective article, we provide an outlook on one of such receptors, namely the aryl hydrocarbon receptor (AHR). The AHR is well known for being a ligand-activated transcription factor regulating the proliferation, differentiation and function of many cell types present in the skin. Its targeting by anti-inflammatory therapeutics such as coal tar and Tapinarof is effective in atopic dermatitis and psoriasis. AHR signalling is activated upon binding of wide variety of small chemicals or ligands, including microbiota-derived metabolites. New evidence has emerged pointing towards a key role for epidermal AHR signalling through skin microbiota-derived metabolites. In response, AHR-driven expression of antimicrobial peptides and stratum corneum formation may alter the skin microbiota composition. This a self-perpetuating feedback loop calls for novel therapeutic intervention strategies for which we herein discuss the requirements in future mechanistic studies.


N-Propargyl Caffeamide Skews Macrophages Towards a Resolving M2-Like Phenotype Against Myocardial Ischemic Injury via Activating Nrf2/HO-1 Pathway and Inhibiting NF-ĸB Pathway.
Macrophages exhibit dynamic pro-inflammatory and resolving activities in myocardial infarction. The present study investigated whether caffeic acid derivatives could induce macrophage polarization towards a resolving M2 phenotype against myocardial infarction injury. Western blotting, RT-PCR and flow cytometry techniques are used to evaluate macrophage biomarkers expression and specific proteins in the related signaling pathways. Ligation of the left anterior descending artery induced rat model of myocardial infarction, TTC staining and immunohistochemical staining are used to examine cardioprotective effect in vivo. We initially evaluated the anti-inflammatory activity of four caffeic acid derivatives including n-propargyl caffeamide (PACA) in RAW264.7 macrophages. As result, PACA selectively suppressed the up-regulation of inducible nitric oxide synthase (iNOS) over cyclooxygenase-2 (COX-2) in lipopolysaccharides (LPS)-stimulated cells. We subsequently examined the effects of PACA on macrophage polarization by determining macrophage biomarkers. PACA down-regulated M1 biomarkers (e.g., iNOS, tumor necrosis factor-α (TNF-α), C-X-C motif chemokine 10 (CXCL10) and CD80) but up-regulated M2 biomarkers (e.g., Ym-1 and arginase-1). On the other hand, PACA suppressed macrophage chemotaxis while enhanced macrophage phagocytosis. We further examined the in vivo cardioprotective activity of PACA in a rat model of myocardial infarction. Following ligation of the left anterior descending artery, PACA treatment effectively reduced myocardial infarct size and promoted macrophage M2 polarization. We finally explored the underlying mechanisms. We found that PACA attenuated LPS-induced NF-ĸB activation while activated Nrf2/HO-1 pathway. HO-1 inhibitor SnPP attenuated the effects of PACA on iNOS expression in LPS-challenged macrophages, possibly by regulating the cross-talk between HO-1 and NF-ĸB pathways. The key finding from the present study was that PACA promoted timely switch of macrophage phenotypes from pro-inflammatory M1 to resolving M2. We anticipate that PACA is a potential drug candidate for the resolution of inflammation and cardiac repair after myocardial infarction.


[Decentralized high-dose cytostatic treatment with autologous stem cell support].
In the past high-dose chemotherapy with autologous stem cell support in the treatment of certain types of cancer, was centralized to two hospitals in Norway. Almost three years ago it was decided that the treatment should be offered by all five university hospitals. In the northernmost university hospital of Norway, Tromsø, peripheral stem cells were harvested from 29 patients after successful mobilization with chemotherapy and granulocyte colony-stimulating factor (G-CSF). After high-dose chemotherapy, more than 2 x 10(6) CD34-positive stem cells/kg were transplanted in 24 patients and a sign of reconstitution of bone marrow function was achieved with mean time for neutrophils > 0.5x10(9)/l, 9.8 days and for platelets > 20x10(9)/l, 10.8 days. No treatment-related deaths have occurred. Transplantation of selected CD34-positive stem cells has been performed in one patient. Recovery was comparable to the recovery of patients who had undergone transplantation with unselected products. This indicates that even small centres performing as few as ten procedures per year may offer high-dose chemotherapy with autologous stem cell support safely and successfully.


Pulmonary MicroRNA Changes Alter Angiogenesis in Chronic Obstructive Pulmonary Disease and Lung Cancer.
The pulmonary endothelium is dysfunctional in chronic obstructive pulmonary disease (COPD), a known risk factor for lung cancer. The pulmonary endothelium is altered in emphysema, which is disproportionately affected by cancers. Gene and microRNA expression differs between COPD and non-COPD lung. We hypothesised that the alteration in microRNA expression in the pulmonary endothelium contributes to its dysfunction. A total of 28 patients undergoing pulmonary resection were recruited and endothelial cells were isolated from healthy lung and tumour. MicroRNA expression was compared between COPD and non-COPD patients. Positive findings were confirmed by quantitative polymerase chain reaction (qPCR). Assays assessing angiogenesis and cellular migration were conducted in Human Umbilical Vein Endothelial Cells (n = 3-4) transfected with microRNA mimics and compared to cells transfected with negative control RNA. Expression of miR-181b-3p, miR-429 and miR-23c (all p < 0.05) was increased in COPD. Over-expression of miR-181b-3p was associated with reduced endothelial sprouting (p < 0.05). miR-429 was overexpressed in lung cancer as well and exhibited a reduction in tubular formation. MicroRNA-driven changes in the pulmonary endothelium thus represent a novel mechanism driving emphysema. These processes warrant further study to determine if they may be therapeutic targets in COPD and lung cancer.


Eosinophilic esophagitis.
Eosinophilic esophagitis (EoE) is an atopic disease in which eosinophils infiltrate the esophageal mucosa and may result in a variety of upper gastrointestinal symptoms. Chief among these are dysphagia, heartburn, and food bolus obstruction in adults whereas children often present with abdominal pain or vomiting. Eosinophilic esophagitis is a chronic condition that if not detected and left untreated could lead to the development of subepithelial fibrosis and esophageal stenosis. The diagnosis of EoE is confirmed in a patient presenting with characteristic EoE symptoms, classic signs on endoscopy, and biopsy results showing >15 eosinophils/hpf. A number of useful treatments against EoE are currently available with new therapeutics on the horizon. The former include PPIs, topical steroids, and elimination diet; the latter comprise novel biologics including the monoclonal antibody dupilumab. All these treatments can improve symptoms and reduce esophageal eosinophil count. This brief introductory review describes the detection, diagnosis, and management of EoE.


RNA polymerase alpha subunit binding site in positively controlled promoters: a new model for RNA polymerase-promoter interaction and transcriptional activation in the Escherichia coli ada and aidB genes.
The ada and aidB genes are part of the adaptive response to DNA methylation damage in Escherichia coli. Transcription of the ada and the aidB genes is triggered by binding of the methylated Ada protein (meAda) to a specific sequence located 40-60 base pairs upstream of the transcriptional start, which is internal to an A/T-rich region. In this report we demonstrate that the Ada binding site is also a binding site for RNA polymerase. RNA polymerase is able to bind the -40 to -60 region of the ada and the aidB promoters in the absence of meAda, and its binding is mediated by the alpha subunit. This region resembles the UP element of the rrnB P1 promoter in location, sequence and mechanism of interaction with RNA polymerase. We discuss the function of UP-like elements in positively controlled promoters and provide evidence that Ada does not act by enhancing RNA polymerase binding affinity to the promoter region. Instead, Ada stimulates transcription by modifying the nature of the RNA polymerase-promoter interaction, allowing RNA polymerase to recognize the core promoter -35 and -10 elements in addition to the UP-like element.


Surgical Site Infections Following Bimaxillary Orthognathic, Osseous Genioplasty, and Intranasal Surgery: A Retrospective Cohort Study.
Frequency estimates of surgical site infection (SSI) after orthognathic surgery vary considerably. The purpose of this study was to determine the incidence and site of SSIs and associated risk factors after bimaxillary orthognathic, osseous genioplasty, and intranasal surgery. The authors executed a retrospective cohort study of patients with a bimaxillary developmental dentofacial deformity (DFD) and symptomatic chronic obstructive nasal breathing. All patients underwent at a minimum Le Fort I osteotomy, bilateral sagittal ramus osteotomies (SROs), septoplasty, inferior turbinate reduction, and osseous genioplasty. The primary outcome variable studied was the incidence and site of SSI. Predictor variables were type and extent of prophylactic antibiotic used, demographic (age and gender), and anatomic (pattern of DFD, surgical site, and presence of third molar). Two hundred sixty-two patients met the inclusion criteria. Their average age at surgery was 25 years (range, 13 to 63 yr) and there were 134 female patients (51%). The major presenting patterns of DFD included long face (30%) and maxillary deficiency (25%). Forty percent of patients undergoing an SRO and 47% of those undergoing a Le Fort I osteotomy underwent simultaneous removal of a third molar. Ninety percent of patients received cefazolin or cephalexin antibiotics. Overall, 5 of 1,048 (0.5%) osteotomy sites sustained an infection, including 1 chin and 4 ramus SSIs. There were no delays in bone healing. Fixation hardware removal was not required in any patient who developed an infection. Two of the 25 patients (8%) given clindamycin prophylaxis developed an SSI, whereas 3 of 237 patients (1%) receiving cefazolin did. Three of the 4 patients who developed an SRO SSI underwent simultaneous removal of an erupted or partially erupted mandibular third molar (P < .05). In this study, the incidence of SSI was limited to 1% of patients who were given cefazolin or cephalexin extended for 5 days. The removal of an erupted or partially erupted mandibular third molar in conjunction with an SRO was associated with risk of SSI, but the incidence remains low.


Fournier's gangrene - challenge for surgeon.
Fournier gangrene (FG) is life - threatening condition, defined as the necrotizing fascitis of perineum and can spread to the adjacent areas. It is rare disease and infection is caused by mixed bacterial flora, seldom by fungal infection. Risk factors are: male sex, diabetes, hypertension, malignant neoplasms, alcoholism, immunospression. The analysis of four group patients treateted for Fournier gangrene was made about diagnostic and therapeutic process, assessment of prognosis based on Fournier's Gangrene Severity Index). All patients were males. Average age at the moment of diagnosis was 60 years. All of them had comorbidities resulting with the higher risk of susceptibility to FG. Morbitity was 50%, despite of all of patients had less than 9 points in FGSI. The FG, despite of better diagnostic tools and technological progres remaines the significant clinical issue because of the mortality - 80%. "The golden standard" is surgical excision of necrotic tissues, antibiotics support, equation of fluid, electrolytes and base - acid balance, level of glycemia is very important. The treating results were assessed on the base of FGSI. The significance has the moment of performing the surgical intervention - it is proven, that should be carried out during 24 hours. The hyperbaric oxygen therapy is controversial. Seem to be appropriate if the infection is caused by anaerobic bacteria. Fournier syndrome is significant clinical issue. Its treatment requires early surgical approach with exicision of necrotic tissues, antibiotics support and treatment of hyperbaric oxygen in some cases.


The effect of pre-analytical handling on the stability of fractalkine, monocyte chemoattractant protein 1 (MCP1), interleukin 6 and interleukin 8 in samples of human cerebrospinal fluid.
Cytokine networks in cerebrospinal fluid (CSF) are important to our understanding of several neuroinflammatory diseases. Knowledge about optimal handling of samples is limited but important to minimize bias and reduce costs in CSF biomarker studies. The aim of this study was to examine the effect of storage temperature and time delay from CSF sample collection until freezing on the concentration of 11 different cytokines thought to be associated with chronic pain. CSF samples from 21 individuals undergoing hip or knee arthroplasty under spinal anesthesia were divided between two tubes. One tube was stored and centrifuged (within 30 min) at room temperature, and one tube was stored in ice water and centrifuged (within 30 min) at 4 °C. Each tube was split into six vials that were frozen at -80 °C, 0.5, 1, 2, 3, 4, or 5 h after collection. Cytokines were analyzed using a multiplex panel. A random effect panel data regression was conducted for each biomarker including the variables of storage temperature until freezing and time delay. Four cytokines had detectable levels: Fractalkine, monocyte chemoattractant protein 1(MCP-1), interleukine 6 (IL-6), and interleukine 8 (IL-8). There was no significant effect of storage temperature and time delay on MCP-1, IL-6, or IL-8 concentrations. Fractalkine concentration showed no clear trend. No concentration differences were observed between samples kept in ice water and those at room temperature except at the 3-h time point, and there was no overall significant effect of time delay on fractalkine concentration. We found no clear effect of storage temperature and time delay up to five hours from sample collection until freezing on the CSF concentrations of fractalkine, MCP-1, IL-6, or IL-8.


Structure and development of the glomerular capillary wall and basement membrane.
The renal glomerular epithelium, Bowman's capsule, and tubule originate from a condensate of mesenchymal cells induced to undergo epithelial differentiation by a branch of the uretic bud. These nephrogenic cells aggregate and begin synthesizing the basement membrane molecules collagen type IV, heparan sulfate proteoglycans, and laminin as shown by immunofluorescence microscopy. Soon, the primitive nephron is invaginated by mesenchymal cells that establish the glomerular endothelium. Electron microscopy, metabolic labeling, and immunocytochemical techniques show that the endothelium and epithelium of early stage glomeruli each synthesize a basement membrane that appears to fuse, giving rise to the glomerular basement membrane (GBM). As development progresses, however, bulk GBM biosynthesis by the endothelium greatly diminishes or ceases. In contrast, GBM assembly by the epithelial podocytes continues and segments of new GBM appear beneath developing foot processes. In vivo labeling experiments with anti-laminin antibodies have shown that this new GBM derived from podocytes is subsequently spliced into existing GBM as capillary loop diameters expand. Molecular mechanisms for basement membrane fusion or splicing are not presently known but may involve partial enzymatic digestion and specific binding interactions among GBM components. The developing glomerular capillary wall, which filters plasma from very early stages, becomes decreasingly permeable to perfused macromolecules such as ferritin or immunoglobulin as the glomerulus matures. Evidence from immunolabeling studies showing that some monoclonal IgGs bind to the GBM only at specific developmental stages also indicates that temporal biochemical changes take place during GBM assembly. Such changes could include molecular rearrangement during basement membrane fusion and splicing and/or enzymatic and compositional modifications during maturation of the filtration barrier.


Analysis of prothrombotic mutations and polymorphisms in children who developed thrombosis in the perioperative period of congenital cardiac surgery.
In this study, we investigated some of the prothrombothic mutations and polymorphisms in 15 children with congenital cardiac malformations who developed severe thrombosis in the perioperative period following surgical repair. The mutations and polymorphisms included in the study were Factor V Leiden, prothrombin G20210A, methylentetrahydrofolate reductase C677T, endothelial nitric oxide synthase intron 4 VNTR, alpha-fibrinogen Thr312Ala, Factor XIII Val34Leu, and insertion or deletion of angiotensin 1 converting enzyme. Compared to the healthy Turkish subjects, our patients had a similar rate of mutation of Factor V Leiden, Factor XIII Val34Leu, and endothelial nitric oxide synthase a/b polymorphisms, but higher frequency of the prothrombotic angiotensin 1 converting enzyme deletion/deletion genotype, and lower frequency of the antithrombotic alpha fibrinogen Thr/Thr genotype. None of the patients exhibited mutations involving prothrombin G20210A or methylentetrahydrofolate reductase C677T. The results of our study suggest that, in addition to prothrombotic mutations such as Factor V Leiden, single-nucleotide polymorphisms should be considered in all children with congenital cardiac malformations who develop thrombosis. Malformations of the heart are the most common of all serious lesions that are present at birth, with an incidence of 4 to 8 cases per 1,000 live births. If needed, corrective surgery is usually the optimal treatment for these anomalies, but perioperative morbidity and mortality still remain high due to several factors. Arterial or venous thrombosis, or both varieties of thrombosis, is among these factors. Prior to surgery, the most frequent time at which these children develop thrombosis is during cardiac catheterization. Postoperative thrombosis in this group of patients is a more complex disorder, which can affect both small and large vessels, and is associated with a high morbidity and mortality. Recent studies indicate that both point mutations and single-nucleotide polymorphisms of genes that encode proteins involved in the coagulative and anticoagulative cascades are important risk factors for development of thrombosis. Patients with these risk factors are most likely to develop thrombosis when triggering elements, such as placement of catheters, prolonged immobilization, or surgery, are also present. In this study, we investigated some of the above-mentioned mutations and polymorphisms in children who developed thrombosis in the perioperative period after correction of congenital cardiac malformations.


Botulinum toxin in the treatment of adductor spasmodic dysphonia.
Spasmodic dysphonia (SD) is a voice disorder that causes marked disability in the affected individual because of the severe disruption of normal communication that the disorder creates. Of the two distinct types, adductor and abductor SD, the adductor type is the most common and the most amenable to treatment. It is felt to be a neurological problem, but the specific lesion has not been found. The best treatment for adductor SD is injection of botulinum toxin into the thyroarytenoid muscles of the larynx.


Robust and censored modeling and prediction of progression in glaucomatous visual fields.
Classic regression is based on certain assumptions that conflict with visual field (VF) data. We investigate and evaluate different regression models and their assumptions in order to determine point-wise VF progression in glaucoma and to better predict future field loss for personalised clinical glaucoma management. Standard automated visual fields of 130 patients with primary glaucoma with a minimum of 6 years of follow-up were included. Sensitivity estimates at each VF location were regressed on time with classical linear and exponential regression models, as well as different variants of these models that take into account censoring and allow for robust fits. These models were compared for the best fit and for their predictive ability. The prediction was evaluated at six measurements (approximately 3 years) ahead using varying numbers of measurements. For fitting the data, the classical uncensored linear regression model had the lowest root mean square error and 95th percentile of the absolute errors. These errors were reduced in all models when increasing the number of measurements used for the prediction of future measurements, with the classical uncensored linear regression model having the lowest values for these errors irrespective of how many measurements were included. All models performed similarly. Despite violation of its assumptions, the classical uncensored linear regression model appeared to provide the best fit for our data. In addition, this model appeared to perform the best when predicting future VFs. However, more advanced regression models exploring any temporal-spatial relationships of glaucomatous progression are needed to reduce prediction errors to clinically meaningful levels.


Recent Abacavir Use Increases Risk of Type 1 and Type 2 Myocardial Infarctions Among Adults With HIV.
There is persistent confusion as to whether abacavir (ABC) increases the risk of myocardial infarction (MI), and whether such risk differs by type 1 (T1MI) or 2 (T2MI) MI in adults with HIV. Incident MIs in North American Cohort Collaboration on Research and Design participants were identified from 2001 to 2013. Discrete time marginal structural models addressed channeling biases and time-dependent confounding to estimate crude hazard ratio (HR) and adjusted hazard ratio (aHR) and 95% confidence intervals; analyses were performed for T1MI and T2MI separately. A sensitivity analysis evaluated whether Framingham risk score (FRS) modified the effect of ABC on MI occurrence. Eight thousand two hundred sixty-five adults who initiated antiretroviral therapy contributed 29,077 person-years and 123 MI events (65 T1MI and 58 T2MI). Median follow-up time was 2.9 (interquartile range 1.4-5.1) years. ABC initiators were more likely to have a history of injection drug use, hepatitis C virus infection, hypertension, diabetes, impaired kidney function, hyperlipidemia, low (<200 cells/mm) CD4 counts, and a history of AIDS. The risk of the combined MI outcome was greater for persons who used ABC in the previous 6 months [aHR = 1.84 (1.17-2.91)]; and persisted for T1MI (aHR = 1.62 [1.01]) and T2MI [aHR = 2.11 (1.08-4.29)]. FRS did not modify the effect of ABC on MI (P = 0.14) and inclusion of FRS in the MSM did not diminish the effect of recent ABC use on the combined outcome. Recent ABC use was associated with MI after adjustment for known risk factors and for FRS. However, screening for T1MI risks may not identify all or even most persons at risk of ABC use-associated MIs.


Fibromuscular Dysplasia: A Rare Case with Multiple Vascular Beds Involvement.
Fibromuscular dysplasia (FMD) is an idiopathic, noninflammatory, and nonatherosclerotic vascular disease of small to medium-sized arteries. It can occur in almost all arteries and most commonly involving the cervicocranial and renal arteries. FMD is commonly presents as renovascular hypertension and affects mostly young ladies. However, this case demonstrates a casuistically rare form of multiple arterial beds involvement at different sites, that is, vertebral, coronary, hepatic, and lumbar arteries, with the conjunction of both bilateral renal and cervicocranial arteries.


One-pot mild and efficient synthesis of [1,3]thiazino[3,2-a]indol-4-ones and their anti-proliferative activity.
A base mediated environmentally benign one-pot efficient methodology has been developed for the synthesis of [1,3]thiazino[3,2-a]indol-4-ones using indoline-2-thiones and propiolate esters in aqueous medium. The conjugate addition of thiones first results in ethyl (3-(indol-2-yl)thio)acrylates in situ, which subsequently undergoes intramolecular cyclization to produce indole-fused thiazin-4-ones in good to excellent yields. The cytotoxic screening of the synthesized compounds using MTT assay revealed the anti-proliferative nature of these frameworks against triple negative breast cancer cell lines with the highest activity emanating from 4H-[1,3]thiazino[3,2-a]indol-4-one and 8-methyl-2-propyl-4H-[1,3]thiazino[3,2-a]indol-4-one compounds.


Blood Stream Infections and Antibiotic Utilization in Pediatric Leukemia Patients With Febrile Neutropenia.
Frequent surveillance of bacterial pathogens responsible for microbiologically defined-blood stream infections (MD-BSI), and their respective antibiotic susceptibilities is central to tailoring empiric antibiotic therapy in febrile neutropenia (FN) episodes in pediatric patients with leukemia. The safety of deescalating antibiotic therapy in pediatric patients with leukemia and neutropenia is incompletely understood. A retrospective chart review of 194 FN episodes occurred between the years of 2013 and 2016 in 67 patients with leukemia. Clinical and microbiologic data were recorded. MD-BSI occurred in 36 of 194 (18%) of FN episodes. Deescalation of empiric antibiotic therapy based on antibiotic susceptibilities was possible in 25 of 36 (69.4%) episodes. In those 25 episodes, where there was an opportunity to deescalate the antibiotic spectrum, it was clinically appropriate to do so in 19. Deescalation occurred in 9 (47.4%) of these episodes without complication. The remaining 10 patients received a median of 20 additional days of broad-spectrum antibiotic therapy (range, 12 to 30 d). In our small cohort of patients, deescalation of antibiotic therapy based on antimicrobial susceptibilities did not result in complication. Larger prospective studies are needed to address the safety of deescalating antibiotic therapy in this population.


Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct Cells.
Extracellular vesicles (ECVs) facilitate intercellular communication along the nephron, with the potential to change the function of the recipient cell. However, it is not known whether this is a regulated process analogous to other signaling systems. We investigated the potential hormonal regulation of ECV transfer and report that desmopressin, a vasopressin analogue, stimulated the uptake of fluorescently loaded ECVs into a kidney collecting duct cell line (mCCDC11) and into primary cells. Exposure of mCCDC11 cells to ECVs isolated from cells overexpressing microRNA-503 led to downregulated expression of microRNA-503 target genes, but only in the presence of desmopressin. Mechanistically, ECV entry into mCCDC11 cells required cAMP production, was reduced by inhibiting dynamin, and was selective for ECVs from kidney tubular cells. In vivo, we measured the urinary excretion and tissue uptake of fluorescently loaded ECVs delivered systemically to mice before and after administration of the vasopressin V2 receptor antagonist tolvaptan. In control-treated mice, we recovered 2.5% of administered ECVs in the urine; tolvaptan increased recovery five-fold and reduced ECV deposition in kidney tissue. Furthermore, in a patient with central diabetes insipidus, desmopressin reduced the excretion of ECVs derived from glomerular and proximal tubular cells. These data are consistent with vasopressin-regulated uptake of ECVs in vivo We conclude that ECV uptake is a specific and regulated process. Physiologically, ECVs are a new mechanism of intercellular communication; therapeutically, ECVs may be a vehicle by which RNA therapy could be targeted to specific cells for the treatment of kidney disease.


Transmission of severe acute respiratory syndrome coronavirus 2 from humans to animals: is there a risk of novel reservoirs?
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic virus able to infect humans and multiple nonhuman animal species. Most natural infections in companion, captive zoo, livestock, and wildlife species have been related to a reverse transmission, raising concern about potential generation of animal reservoirs due to human-animal interactions. To date, American mink and white-tailed deer are the only species that led to extensive intraspecies transmission of SARS-CoV-2 after reverse zoonosis, leading to an efficient spread of the virus and subsequent animal-to-human transmission. Viral host adaptations increase the probability of new SARS-CoV-2 variants' emergence that could cause a major global health impact. Therefore, applying the One Health approach is crucial to prevent and overcome future threats for human, animal, and environmental fields.


Exploring potential explanations for the increase in antidepressant prescribing in Scotland using secondary analyses of routine data.
Antidepressant prescribing in general practice has dramatically increased since the beginning of the last decade. To determine if the increase in antidepressants prescribed in Scotland between 1995 and 2001 was due to increase in incidence, prevalence, care-seeking behaviour by patients, or identification by GPs of depression. Secondary analysis of routine data. Prescribing information was obtained from Information and Statistics Division Scotland, psychosocial morbidity from the Scottish Health Surveys of 1995 and 1998 and GP consultations from the continuous morbidity recording (CMR) dataset. Annual trends in antidepressant prescribing for prescriptions, gross ingredient cost and defined daily doses (DDDs) were examined for all Scottish Practices and 54 stable CMR practices (175 955 patients). Prevalence of psychological morbidity in responders with a General Health Questionnaire score > or = 4, their contact probability and contact frequency was compared in the 1995 and 1998 Scottish Health Surveys. Changes in diagnostic and GP consultation patterns in CMR practices were compared. Total prescriptions for antidepressants increased from 1.5 million in 1995-1996 to 2.8. million in 2000-2001. The gross ingredient cost increased from pounds 20 to pounds 44 million and total DDDs from 44.5 to 93.2 million. Prescription trends in CMR practices were similar. Overall prevalence of psychological morbidity was the same in the 1995 and 1998 Scottish Health Surveys. Percentage of consultations in CMR practices for new diagnoses of depression decreased from 1.7 to 1.3%, the depression-related contact rate decreased and annual prevalence rates for depressive illness were stable between 1998-1999 and 2000-2001. There is no evidence of an increase in incidence, prevalence, care-seeking behaviour or identification of depression during the period of a sharp increase in antidepressant prescribing. Further work is required to explain the increase.


The Russia-Ukraine Conflict: Its Implications for the Global Food Supply Chains.
Food is one of the most traded goods, and the conflict in Ukraine, one of the European breadbaskets, has triggered a significant additional disruption in the global food supply chains after the COVID-19 impact. The disruption to food output, supply chains, availability, and affordability could have a long-standing impact. As a result, the availability and supply of a wide range of food raw materials and finished food products are under threat, and global markets have seen recent increases in food prices. Furthermore, the Russian-Ukrainian conflict has adversely affected food supply chains, with significant effects on production, sourcing, manufacturing, processing, logistics, and significant shifts in demand between nations reliant on imports from Ukraine. This paper aims to analyze the impacts of the conflict between Russia and Ukraine on the effectiveness and responsiveness of the global food supply chains. A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach, including grey literature, was deployed to investigate six key areas of the food supply chains that would be impacted most due to the ongoing war. Findings include solutions and strategies to mitigate supply chain impacts such as alternative food raw materials, suppliers and supply chain partners supported by technological innovations to ensure food safety and quality in warlike situations.


Potential for immunotherapy in the treatment of herpesvirus infections.
The concept of using immunotherapy to treat recurrent herpesvirus infections dates back to the 1930s, although many of the initial studies were seriously flawed. Since the late-1980s, however, the use of the guinea pig model of genital herpes has allowed investigators to evaluate carefully several vaccine and immunomodulatory strategies for the control of recurrent herpesvirus infections. These investigations have clearly shown that both approaches can significantly decrease recurrence rates of genital herpes, and the most effective routes, adjuvants and treatment regimens have been identified. Similar strategies have also been shown to decrease herpes simplex virus (HSV)-1 recurrences in animal models of ocular infection. To date, only moderate success has been reported for human trials, although the optimum strategies that were identified in the animal models have not yet been evaluated.


Testing relationships between DSM-5 Section III maladaptive traits and measures of self and interpersonal impairment in Italian community dwelling adults.
In order to study the relationships between DSM-5 Section III maladaptive personality traits and personality dysfunction, 312 Italian community dwelling adults completed the Italian translations of the Personality Inventory for DSM-5 (PID-5) and the Measure of Disordered Personality Functioning Scale (MDPF); participants were also administered the Iowa Personality Disorder Screen (IPDS). Consistent with previous findings, 22 (88.0%) PID-5 maladaptive trait scales showed moderate and significant correlations with MDPF Non Coping (median r value = .32), and Non Cooperativeness, (median r value = .24) scales. Regression analyses showed that PID-5 trait scales explained roughly 59% and 35% of the variance in MDPF Non Coping and Non Cooperativeness scales, respectively. PID-5 traits were significantly associated also with the IPDS total score, adjusted R2 = .45, p < .001. As a whole, our data seemed to indicate that the wide majority of the PID-5 scales showed significant relationships of at least moderate size with a self-report measure of personality dysfunction, lending further support to the criterion validity of the PID-5. (PsycINFO Database Record


A Model of Genome Size Evolution for Prokaryotes in Stable and Fluctuating Environments.
Temporal variability in ecosystems significantly impacts species diversity and ecosystem productivity and therefore the evolution of organisms. Different levels of environmental perturbations such as seasonal fluctuations, natural disasters, and global change have different impacts on organisms and therefore their ability to acclimatize and adapt. Thus, to understand how organisms evolve under different perturbations is a key for predicting how environmental change will impact species diversity and ecosystem productivity. Here, we developed a computer simulation utilizing the individual-based model approach to investigate genome size evolution of a haploid, clonal and free-living prokaryotic population across different levels of environmental perturbations. Our results show that a greater variability of the environment resulted in genomes with a larger number of genes. Environmental perturbations were more effectively buffered by populations of individuals with relatively large genomes. Unpredictable changes of the environment led to a series of population bottlenecks followed by adaptive radiations. Our model shows that the evolution of genome size is indirectly driven by the temporal variability of the environment. This complements the effects of natural selection directly acting on genome optimization. Furthermore, species that have evolved in relatively stable environments may face the greatest risk of extinction under global change as genome streamlining genetically constrains their ability to acclimatize to the new environmental conditions, unless mechanisms of genetic diversification such as horizontal gene transfer will enrich their gene pool and therefore their potential to adapt.


Scleroderma-like changes in insulin-dependent diabetes mellitus: clinical and biochemical studies.
Children with insulin-dependent diabetes mellitus (IDDM) were examined for scleroderma-like changes of digital sclerosis and joint contractures. Of the 104 patients, 19 (18%) demonstrated these features; five patients had both multiple joint involvement and skin changes; three were studied in detail. All three had restrictive pulmonary disease. Histopathology of skin in these three patients demonstrated increased accumulation of collagen in the lower dermis. In two of the patients, the extractability of collagen in 0.5 N acetic acid was decreased by about 50% as compared with normal controls, which suggests increased cross-linkage of collagen. In addition, the mean nonenzymatic glycosylation of collagen in these three patients was 13 times that of controls. The results indicate that distinct histopathologic and biochemical changes can be detected in the skin of these patients. The results further support the hypothesis that nonenzymatic glycosylation may alter the turnover of collagen, thus contributing to the development of a scleroderma-like syndrome with skin, joint, and pulmonary findings in patients with IDDM.


High rates of tuberculin skin test positivity due to methotrexate therapy: False positive results?
The tuberculin skin test (TST) and interferon ? release assays (IGRAs) are commonly used for latent tuberculosis infection (LTBI) screening. Unexpectedly high TST positivity rates have been reported in patients with rheumatic diseases, and methotrexate is frequently used in this population. We hypothesized that methotrexate use could be associated with false-positive TST results. To investigate whether treatment with methotrexate and other factors are associated with false-positive TST results in patients with rheumatic diseases. Prospective single-center study conducted between April 2013 and March 2016. Adult patients with rheumatic diseases were evaluated with a TST and two IGRAs for LTBI screening. We compared TST and IGRA results in patients treated and not treated with methotrexate and analyzed for factors associated with positive TST results. Our data suggest false-positive TST results associated with methotrexate therapy. Thus, we recommend against using the TST for LTBI screening in patients receiving methotrexate and the preferential use of IGRAs in such patients. We studied 393 patients with rheumatic diseases, including ankylosing spondylitis (ASP, n = 90), rheumatoid arthritis (RA; n = 120), psoriatic arthritis (PA, n = 126), and other disorders (n = 57). The rate of TST positivity varied across the groups: ASP 22.2%, RA 25%, PA 35.7%, and other disorders (22.8%). Positivity rates were lower with IGRAs. Methotrexate use was associated with a statistically significant two-fold increase in the risk of a positive TST and a dose\x96 response relationship was observed. We found no statistically significant associations between methotrexate use and IGRA test positivity.


Increased sodium pump activity following repetitive stimulation of rat soleus muscles.
1. Soleus muscles of anaesthetized rats were stimulated tetanically (4 s at 20 Hz every 5 s for 5 min), following which the resting and action potentials were measured in surface fibres. 2. At the end of the stimulation period, the mean resting potential was found to have increased from a control value of -79.5 +/- 4.8 mV (mean +/- S.D.) to -90.5 +/- 6.3 mV. The hyperpolarization started to decline after 9 min but was still present at 15 min. 3. Associated with the membrane hyperpolarization was an increase in the mean amplitude of the muscle fibre action potential, from 82.2 +/- 10.8 to 96.8 +/- 10.0 mV. 4. Both the hyperpolarization and the enlargement of the muscle fibre action potential were abolished by 1.25 X 10(-4) M-ouabain, cooling the bathing fluid to 19 degrees C or removing K+ from the bathing fluid. 5. The results are explained in terms of an increase in electrogenic sodium pump activity resulting from tetanic stimulation. When the bathing fluid contained 20 mM-K+, the mean resting potential of stimulated fibres was approximately -30 mV greater than that calculated from the Goldman-Hodgkin-Katz equation. 6. The increase in sodium pumping not only acts to restore the concentrations of Na+ and K+ on either side of the muscle fibre membrane, but, through its electrogenic effect, enables fibres to remain excitable during continuous contractile activity.


Cutaneous cancers in the Mosan region and Ardennes of Belgium.
The ratios of basal cell carcinomas (BBC) to squamous cell carcinomas (SCC) and to malignant melanomas (MM) have changed over time in the white population throughout the world. To evaluate the incidence of skin cancers in the Mosan region and the Belgian Ardennes over the past 6 years. In contrast with epidemiological data reported by the Belgian National Cancer Registry, cutaneous cancers are the commonest malignancies occurring in humans. At the present time, the ratio BCC:SCC roughly equals 4 to 1. When combined, the incidence of BCC and SCC is about 10 times greater than that of MM. The rate of detection of skin cancers does not always correlate with the rate of notification of a national registry.


Quantitative evaluation of retinal response to laser photocoagulation using dual-wavelength fundus autofluorescence imaging in a small animal model.
To demonstrate the usefulness of dual-wavelength fundus autofluorescence (FAF) imaging for noninvasive, quantitative monitoring of dynamic changes associated with healing of retinal photocoagulation lesions in a small animal model. Brown Norway rats, exhibiting substantial age-dependent lipofuscin autofluorescence, were used to characterize the kinetics of FAF recovery after retinal photocoagulation. An argon laser with a beam diameter of 100 μm, exposure duration of 0.1 seconds, and a range of laser powers (8-22 mW) were used to create subthreshold, threshold, and suprathreshold lesions. A modified retinal angiograph was used to obtain dual-wavelength FAF images at 488 and 514 nm to quantify and monitor changes in retinal fluorescence up to 6 months. Compared to white light funduscopy, the FAF images exhibited heightened definition and clarity of lesion boundaries immediately after laser exposure. No significant reduction in FAF was measured at or below laser powers of 8 mW. Furthermore, a linear, dose-dependent decrease in FAF (R(2) = 0.9605) was observed immediately after laser exposures of 13 to 22 mW. Complete recovery of baseline FAF was observed for 13.5 and 16 mW exposures at 3 weeks and 4 months, respectively. However, retinal damage was still evident at 6 months after suprathreshold exposure induced using 22 mW laser power. The accumulation of lipofuscin in the aged Brown Norway rat makes it a suitable small animal model for the characterization of laser-induced injury in the retina based on FAF. Dual-wavelength FAF measurements provide a sensitive, quantitative, noninvasive means of monitoring recovery of laser-induced retinal injury.


Evaluation of DBM/AM composite as a graft substitute for posterolateral lumbar fusion.
Demineralized bone matrix (DBM) has been investigated as a bone graft substitute for spinal fusion with less morbidity. Various carriers have been added to DBM to enhance its handling characteristics. This study investigates the spinal fusion induced by a composite of DBM and acellular dermal matrix (AM) in comparison with autologous bone in an athymic rat spinal fusion model. Single-level intertransverse process fusions were performed in 60 athymic nude rats grafted with 2 mL/kg of DBM/AM composite, AM alone, or autologous bone. Fusion was assessed at 6 weeks by radiography, manual palpation, and histology. At 6 weeks, 70% of the animals from the DBM/AM composite group exhibited complete spine fusion, whereas 35% from the autologous bone group and 20% from AM group showed bridging with some gaps. The DBM/AM composite induced a significantly higher fusion rate than both the autologous bone and AM groups (p < 0.001) in all measured parameters. The current study demonstrated that using DBM/AM composite can have more robust fusion than autologous bone at 6 weeks in an athymic rat spinal fusion model.


Cure of metastatic uterine carcinosarcoma to lungs: a case report.
Most patients with advanced or recurrent uterine sarcoma experience disease progression and ultimately die. We present a case of uterine sarcoma with lung metastasis treated with systemic chemotherapy and with no evidence of disease for more than 5 years. A 77-year-old woman underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy for carcinosarcoma of the uterus followed by external pelvic radiotherapy. Ten months later, the tumor recurred in the apex of the vagina and was treated with brachytherapy. After 6 months of remission, she presented with pulmonary metastasis. After four cycles of systemic chemotherapy with cisplatin and ifosfamide, the pulmonary nodules completely disappeared. Currently she is still in complete remission after more than 5 years, but unfortunately she has developed myelodysplastic syndrome. This is the first reported case in the literature of cured metastatic uterine carcinosarcoma to lungs, with long-term survival of 5 years.


Large-area nanoimprinting on various substrates by reconfigurable maskless laser direct writing.
Laser-assisted, one-step direct nanoimprinting of metal and semiconductor nanoparticles (NPs) was investigated to fabricate submicron structures including mesh, line, nanopillar and nanowire arrays. Master molds were fabricated with high-speed (200 mm s(-1)) laser direct writing (LDW) of negative or positive photoresists on Si wafers. The fabrication was completely free of lift-off or reactive ion etching processes. Polydimethylsiloxane (PDMS) stamps fabricated from master molds replicated nanoscale structures (down to 200 nm) with no or negligible residual layers on various substrates. The low temperature and pressure used for nanoimprinting enabled direct nanofabrication on flexible substrates. With the aid of high-speed LDW, wafer scale 4 inch direct nanoimprinting was demonstrated.


Movento influences development of granulosa cells and ovarian follicles and FoxO1 and Vnn1 gene expression in BALB/c mice.
Pesticides has wide range of infertility in female reproductive. This study was done to evaluate the effect of movento pesticide on development of granulosa cells and ovarian follicles and FoxO1 and Vnn1 gene expression in BALB/c mice. In this study 40 healthy BALB/c mice 5-6 weeks age were used. Animals were randomly allocated into four groups. Control (without any intervention), three experimental groups received 25, 50 and 100 mg/kg movento dissolved in PBS by gavage for 21 days. Animals scarified after three weeks. For determining the effects of movento on granulosa cells in culture, treatments were conducted to movento (125, 250, 500 μg/ml) for 24 hr. We surveyed the expression of the FoxO1 and Vnn1 in granulosa cells in vitro, and its relation to cell death by flowcytometer and DAPI. Levels of FoxO1 and Vnn1 were analyzed by real-time PCR. Exposure to movento significantly decreased ovarian weight and the number of primary, secondary and antral follicles. Further, treatment with different concentration of movento induced apoptosis on granulosa cells. Gene expression analysis showed the transcriptional expression of FoxO1 and vnn1 in granulosa cells. Level of Vnn1 mRNA in granulosa cells was decreased in granulosa cells and expression of FoxO1 significantly increased in treated groups in compare to controls (P-value <0.05). Exposure to movento significantly reduced the number of follicles and increased apoptosis of granulosa cells leading disruption of the reproductive system. Also movento reduced expression of Vnn1 and increased FoxO1 genes in a dose dependent manner.


Molecular surveillance of piroplasms in ticks from small and medium-sized urban and peri-urban mammals in Australia.
Natural landscape alterations as a consequence of urbanisation are one of the main drivers in the movements of wildlife into metropolitan and peri-urban areas. Worldwide, these wildlife species are highly adaptable and may be responsible for the transmission of tick-borne pathogens including piroplasms (Babesia, Theileria and Cytauxzoon spp.) that cause piroplasmosis in animals and occasionally in humans. Little is known about piroplasms in the ticks of urban wildlife in Australia. Ticks from long-nosed bandicoots (Perameles nasuta; n = 71), eastern-barred bandicoots (Perameles gunnii; n = 41), northern-brown bandicoots (Isoodon macrourus; n = 19), southern-brown bandicoots (Isoodon obesulus; n = 4), bandicoot sp. (n = 2), flying foxes (Pteropus sp.; n = 3), black rats (Rattus rattus; n = 7), bush rats (Rattus fuscipes; n = 4), brushtail possums (Trichosurus vulpecula; n = 19), ringtail possums (Pseudocheirus peregrinus; n = 12), short-eared possums (Trichosurus caninus; n = 6), possum sp. (Trichosurus sp.; n = 8), and red foxes (Vulpes vulpes; n = 12) were analysed using piroplasm-specific 18S primers and Sanger sequencing. Seven Ixodes tasmani ticks from long-nosed bandicoots and bandicoots sp., three I. tasmani ticks and one Ixodes holocyclus tick from brushtail possums, and one Haemaphysalis longicornis tick from a red fox were positive for piroplasms. New genotypes, with sequences sharing 98% nucleotide similarities with Theileria sp. K1 detected in a burrowing bettong (Bettongia lesueur), were identified from bandicoot ticks. New genotypes were detected in ticks from brushtail possums, which shared 98% similarity with a Babesia sp. (JQ682877) previously identified in marsupials. Theileria orientalis was identified in the H. longicornis tick from the red fox. Babesia and Theileria spp. in the ticks parasitizing bandicoots and brushtail possums clustered closely with respective Babesia and Theileria clades derived from Australian marsupials. This represents the first detection of piroplasms in ticks parasitizing brushtail possums and a red fox in Australia.


Association between Neu5Gc carbohydrate and serum antibodies against it provides the molecular link to cancer: French NutriNet-Santé study.
High consumption of red and processed meat is commonly associated with increased cancer risk, particularly colorectal cancer. Antibodies against the red meat-derived carbohydrate N-glycolylneuraminic acid (Neu5Gc) exacerbate cancer in "human-like" mice. Human anti-Neu5Gc IgG and red meat are both independently proposed to increase cancer risk, yet how diet affects these antibodies is largely unknown. We used world global data to demonstrate that colorectal cancer incidence and mortality are associated with increased national meat consumption. In a well-defined large cohort, we used glycomics to measure daily Neu5Gc intake from red meat and dairy, and investigated serum as well as affinity-purified anti-Neu5Gc antibodies. Based on 24-h dietary records, daily Neu5Gc intake was calculated for 19,621 subjects aged ≥ 18 years of the NutriNet-Santé study. Serum and affinity-purified anti-Neu5Gc antibodies were evaluated by ELISA and glycan microarrays in representative 120 individuals, each with at least eighteen 24-h dietary records (aged 45-60, Q1-Q4; aged > 60, Q1 and Q4; 10 men/women per quartile). We found that high-Neu5Gc diet, gender, and age affect the specificity, levels, and repertoires of anti-Neu5Gc IgG immune responses, but not their affinity. Men consumed more Neu5Gc than women, mostly from red meat (p = 0.0015), and exhibited higher overall serum anti-Neu5Gc IgG levels by ELISA (3.94 ng/μl versus 2.22 ng/μl, respectively; p = 0.039). Detailed glycan microarray analysis against 56 different glycans revealed high Neu5Gc-specificity with increased anti-Neu5Gc IgG and altered repertoires, associated with higher consumption of Neu5Gc from red meat and cow dairy. Affinity purification of serum anti-Neu5Gc antibodies revealed increased levels and biased array repertoire patterns, without an increase in antibody affinity, in individuals consuming higher Neu5Gc levels. Furthermore, in a high-meat diet, antibody diversity patterns on glycan microarrays shifted towards Neu5Gcα3-linked glycans, increasing the α3/α6-glycans ratio score. We found a clear link between the levels and repertoire of serum anti-Neu5Gc IgG and Neu5Gc intake from red meat and dairy. These precise rational methodologies allowed to develop a Gcemic index to simplify the assessment of Neu5Gc in foods that could potentially be adapted for dietary recommendations to reduce cancer risk.


Contemporary management of preterm premature rupture of membranes (PPROM): a survey of maternal-fetal medicine providers.
This study was undertaken to characterize variations in the management for women with preterm premature rupture of membranes (PPROM) among maternal-fetal medicine (MFM) specialists in the context of current recommendations for clinical practice and evidenced-based practice. We performed a Web-based survey of 1375 MFM providers. Participants were queried on practice characteristics and management issues including use of tocolytics, antibiotics, steroids, and timing of delivery. A total of 508 providers (37%), representing all 50 states and 13 countries, responded to the survey. Only 30% reported a formal departmental protocol for managing women with PPROM. Consistent use of steroids (99.4%) and antibiotics (99.6%) were reported. Administration of steroids was confined to < or =32 weeks by 37%, and < or =34 weeks by 51% of practitioners. Repeated dosing of steroids was uncommon (16%). The antibiotics use and rationale for use varied among respondents. Tocolytics were used by 73% of respondents with magnesium sulfate the main agent used (98%). Use of tocolytics was generally used for 48 hours or less to attain steroid benefit (88%). Amniocentesis was used by 66% of practitioners in the acute evaluation of PPROM. Fetal lung maturity testing was reported by 78% with variability noted with respect to the test used. Outpatient management of women with PPROM after viability was noted by 43% of respondents. Gestational age at which expectant management is abandoned in women with PPROM varied significantly between respondents: > or =34 weeks by 56%, > pr =35 weeks by 26%, > or =36 weeks by 12%, and > or =37 weeks by 4.0%. Although many management practices for women with PPROM are consistent with currently available evidence and practice recommendations, substantial variations still exist among MFM providers.


A qualitative analysis of the nurturing care environment of families participating in Brazil's Criança Feliz early childhood program.
Investing in early childhood programs such as Brazil's Criança Feliz Program (PCF) to support low-income families in providing a nurturing care environment is critical to ensure that children reach their full developmental potential. We aimed to analyze the influence of the PCF on the nurturing care environment provided by families enrolled in the program in the Federal District, Brazil. A qualitative case study was conducted based on in-depth interviews with a purposive sampling of 22 caregivers enrolled in the PCF for at least six months. Eighteen subthemes emerged from the thematic analysis following the five components of the Nurturing Care Framework (i.e., good health, adequate nutrition, responsive care, early learning, and security and safety). Caregivers recognized the benefits of the PCF on children's mental health (good health) and reported challenges in providing adequate nutrition due to food insecurity (adequate nutrition). A bond between the home visitor and families was identified as critical to promote responsive parenting practices (responsive care). Caregivers appreciated the early stimulation activities provided during PCF home visits (opportunities for early learning). Access to social welfare programs, such as conditional cash transfer and food assistance, were facilitated through PCF multisectoral actions (safety and security). On the other hand, families reported not receiving support from PCF for issues such as breastfeeding, maternal mental health, and disciplinary practices. In summary, PCF enhanced the components of the nurturing care environment provided by families. However, their vulnerabilities and contextual implementation barriers may prevent families from fully benefiting from PCF activities.


Paradox lost on the U.S.-Mexico border: U.S. Latinas and cesarean rates.
We apply Intersectional Theory to examine how compounded disadvantage affects the odds of women having a cesarean in U.S.-Mexico border hospitals and in non-border hospitals. We define U.S. Latinas with compounded disadvantage as those who have neither a college education nor private health insurance. Analyzing quantitative and qualitative data from Childbirth Connection's Listening to Mothers III Survey, we find that, consistent with the notion of the Latinx Health Paradox, compounded disadvantage serves as a protective buffer and decreases the odds of cesarean among women in non-border hospitals. However, the Latinx Health Paradox is absent on the border. Our data show that women with compounded disadvantage who give birth on the border have significantly higher odds of a cesarean compared to women without such disadvantage. Further, women with compounded disadvantage who give birth in border hospitals report receiving insufficient prenatal, pregnancy, and postpartum information, providing a direction for future research to explain the border disparity in cesareans.


Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials.
The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference -0·91 (95% CI -1·65, -0·17) kg, 1415 patients), TAG (weighted mean difference -0·18 (95% CI -0·27, -0·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference -1·43 (95% CI -2·49, -0·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.


Genetically distant American Canine distemper virus lineages have recently caused epizootics with somewhat different characteristics in raccoons living around a large suburban zoo in the USA.
Mortality rates have differed during distemper outbreaks among free-ranging raccoons (Procyon lotor) living around a large Chicago-area zoo, and appeared higher in year 2001 than in 1998 and 2000. We hypothesized that a more lethal variant of the local Canine distemper virus (CDV) lineage had emerged in 2001, and sought the genetic basis that led to increased virulence. However, a more complex model surfaced during preliminary analyses of CDV genomic sequences in infected tissues and of virus isolated in vitro from the raccoons. Phylogenetic analyses of subgenomic CDV fusion (F) -, phosphoprotein (P) -, and complete hemagglutinin (H) - gene sequences indicated that distinct American CDV lineages caused the distemper epizootics. The 1998 outbreak was caused by viruses that are likely from an old CDV lineage that includes CDV Snyder Hill and Lederle, which are CDV strains from the early 1950's. The 2000 and 2001 viruses appear to stem from the lineage of CDV A75/17, which was isolated in the mid 1970's. Only the 2001 viruses formed large syncytia in brain and/or lung tissue, and during primary isolation in-vitro in Vero cells, demonstrating at least one phenotypic property by which they differed from the other viruses. Two different American CDV lineages caused the raccoon distemper outbreaks. The 1998 viruses are genetically distant to the 2000/2001 viruses. Since CDV does not cause persistent infections, the cycling of different CDV lineages within the same locale suggests multiple reintroductions of the virus to area raccoons. Our findings establish a precedent for determining whether the perceived differences in mortality rates are actual and attributable in part to inherent differences between CDV strains arising from different CDV lineages.